Ad Majorem Dei Gloriam

THE SEC-C GUIDE TO

INFECTIOUS DISEASES
AND
RHEUMATOLOGY

Prepared By C-Medicine 2019

Contributors: ​Kathleen Monfort, JC Moreno, Neri Natata, Jolo Leachon, Bea Naidas, Joice Rañoa, Ayen Javiniar, Maika Manicad,
Marvin Marasigan, Abbey Matibag, Cedy Lo, Camille Icaro, Nikol Hilario, Jermine Muarip, Sharmaine Lee, Diane Lusaya, Johanne
Morales, Val Natividad, Patrick Jacinto, Erika Mantilla, John Kelly Parangat, Wedcell Hernandez, Apollo Manuel, Mark Martinez,
Kevin Magadia, Joseph Manuel, Aiyah Magsalin, Corina Manalang, Bianca Maranan, Grazielli Millare, Denny Horneja, Anna Jimenez,
Ciara Morales, Chrisztine Lim, Sharmaine Lozano, Patricia Moran, Michiko Kimura, Cyra Mina, Katherine Manuel, Carissa Lim,
Angelo Navarro, Mike Lazatin, Beteena Muñoz, Savannah Johnson, Jude Mascariñas, Juaymah Leynes, Joyce Hernandez, Jo-lo
Lopez, Johnson Idanan, Remar Hapan, Michelle Morco, Carlo Manugas, Danica Martin, Denise Ibay, Rhett Monville, Fatima Jusay,
Catherine Marang, Beatrice Mendoza, Matt Jocson, Claire Monzon, Alee Macarubbo, William Mendoza, Charlene Mondelo, Florence
Maramba, Joseph Pamatian, Divina Jose, Alyanna Mañego, Lois Lapitan, Zaren Mabanta, Rainier Ples, Ella Mendoza ​Edited by:
Abbey Matibag and Redd Mapalo
 THE SEC-C GUIDE TO
INFECTIOUS DISEASES AND RHEUMATOLOGY
ID-ICD TOPICS

1. Tetanus (MONFORT, MORENO)

Case: 42/M farmer, inability to open jaw, intermittent toothache
● Etiology
○ Clostridium tetani - ​anaerobic, gram-positive, spore-forming rod whose spores are highly
resilient and can survive readily in the environment
○ The spores or bacteria enter the body through abrasions, wounds, or (in the case of
neonates) the umbilical stump. Once in a suitable anaerobic environment, the organisms
grow, multiply, and release ​tetanus toxin​, an ​exotoxin that enters the nervous system
and causes disease. Very low concentrations of this highly potent toxin can result in
tetanus (minimum lethal human dose, 2.5 ng/kg).
● Clinical Manifestations
○ Synaptobrevin - responsible for
docking the inhibitory
neurotransmitters to its receptor sites
○ Tetanospasmin ​- ​cleaves
synaptobrevin → (-) release of
inhibitory neurotransmitters
○ Uninhibited firing of excitatory
neurotransmitters (tetany)
○ Trismus happens after cleaving the
light chains
○ Unregulated activity of the motor system → uncontrolled spasms
○ Unregulated autonomic dysfunction → labile blood pressure (hypotension/hypertension),
hypothermia/hyperthermia, respiratory failure, tachyarrhythmia/bradyarrhythmia

Classification of Ablett for the Clinical Severity of Tetanus

*​A subclinical (asymptomatic) infection could be graded as Grade 0.

*Marked autonomic disturbances in Grade IV may include severe hypertension and tachycardia alternating
with hypotension and bradycardia.

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Cole Staging

● Diagnosis
○ Based on clinical manifestations
○ Q: Why not culture?
■ Not all ​Clostridium tetani ​can produce the toxin; you may yield a positive culture,
but it doesn’t necessarily mean the species isolated can produce the toxin
■ You may have a positive culture, but the patient had a previous tetanus toxoid
immunization
■ The etiology is the toxin, not the organism itself
○ Spatula Test: (+) bite, (-) gag reflex
● Treatment
○ Decrease bacterial burden
■ Clean​ the wound
■ Metronidazole​: Given per IV then shift to rectal or oral administration, 7-10 days
■ Don’t give penicillin because it inhibits GABA (leading to increased spasms)
○ Neutralize the unbound toxin
■ TIG 3000-5000 IU single IM​ (for board exams)
■ TIG 500 IU single IM​ (if in the quiz there is “in the local setting”)
○ To control the spasm
■ Admit the patient in an environment with less stimulus: dark and quiet room
■ SA Benzodiazepine: GABA agonist; sedative
● DOC: ​midazolam
● Diazepam causes lactic acidosis when given in drip/in high doses due to
the propylene glycol content
■ When the spasm is so severe that it cannot be controlled by BZD, give:
● Phenobarbital​ (first-line)
● Magnesium sulfate – aside from the spasm, CV instability is also
controlled
● Propofol
● Non-depolarizing NM blocking agent – anesthetize the patient but will
paralyze the diaphragm; make sure to give the patient a sedation holiday
○ Pancuronium
○ Rocuronium

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 ● When removing the drugs, remove the last drug added then work your
way back
● Titrate very slowly when removing the BZD or the patient might have
rebound spasm
○ Prevent the complication
■ Stabilize the cardiovascular system: ​magnesium sulfate
■ if the patient develops hypertension, give:
● short acting beta-blocker and CCB IV (IV in order to titrate the drug easily,
because the patient has labile autonomic system)
○ Nicardipine​, ​Esmolol
● When the patient suddenly develops hypotension, turn off the drip then
give fluids; if no response, give vasopressors (Dopamine, NE)
■ If the patient has moderate to severe tetanus, do tracheostomy upon admission.
(the shorter IP, the greater the spasm is)
○ Immunize the patient (post-exposure prophylaxis)
■ Needed because the ​disease is ​weakly immunogenic, therefore the antibodies
produced from the disease is not enough to protect us from future infection
■ Active immunization: ​Tetanus toxoid given at 0 (upon admission), 1, 6 months
after the first dose 0.5mL IM, separate deltoid
■ Patient should have completed 2 doses of vaccine before discharge
■ Booster every 10 years
■ Passive immunization: ​TIG 250mL single IM​ - only for dirty, unimmunized wound
○ Pre-exposure prophylaxis:
■ If no previous vaccination: Tetanus toxoid 0,1,6 mos
■ If completely immunized, last dose was within the last 10 years: no vaccination
■ If completely immunized, last dose was >10 years: Tetanus toxoid booster

2. Rabies (MONFORT, NATATA, LEACHON)

Case: 29/M, petshop owner, paresthesia on L hand
● Etiology: Rabies Virus (Family- ​Rhabdoviridae​; Genera- ​Lyssavirus​)
○ Possible sources of Rabies: Cat scratch, inhalation of the rabies in a close cave (Palawan
not included), terrestrial mammals
○ House rats, rabbits are not rabid in the Philippines, instead, give tetanus vaccine.
○ Non-bite transmission is possible - Bats in caves, human to human corneal transplant
○ Routes of infection: Animal bite, mucosal, or respiratory
● Clinical Manifestations
○ Dumb rabies is more difficult to diagnose because they do not show more bizarre behavior
○ No one survives once in acute neurologic disease already, expect them to die within 7-10
days
○ In rabies, emphasis must be on PEP initiated before any signs and symptoms develop
○ Post exposure prophylaxis (PEP) is only effective in incubation period (around 3 months)
○ Rabies should usually be suspected on the basis of the clinical presentation
○ Bite → multiply in the muscle to bind to nicotinic acetylcholine receptors on postsynaptic
membranes at NMJ ​(incubation period) ​→ centripetally via retrograde axonal transport, it
goes to the peripheral nerves ​(prodrome period) ​→ infection of brain neurons with
neuronal dysfunction ​(acute neurologic phase) → centrifugal spread along the nerves to
salivary glands, skin, cornea, etc.
○ Usually presents as atypical encephalitis with relative preservation of consciousness
○ Rabies encephalitis is distinguished by ​early brainstem involvement, which results in the
classic features of hydrophobia and aerophobia
○ Late complications:
■ cardiac - arrhythmias may be due to dysfunction affecting vital centers in the
brainstem or to myocarditis
■ respiratory failure - noncardiogenic pulmonary edema
■ Endocrine - disturbances of water balance (SIADH or DI)
■ GI - hemorrhage

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● Diagnosis
○ History of exposure to the saliva of rabid animals (clinically)
○ Rabies testing is only done to the patient who are highly suspected to acquire the rabies.
○ Laboratory tests:
■ Saliva, CSF, urine of the human ​(although lower yield if saliva because of
intermittent production of rabies in saliva)
■ Brain biopsy of the animal – DFAT, histopath
■ Skin biopsy of the human – skin of the nape with 10 follicles 1x1cm – DFAT
■ Blood exam is not helpful
■ DFAT – Gold standard
■ Upon observation of the animal within 10-14 days, suspect it is rabid if there is
change in behavior: bites unprovoked, howling, mutilates itself (biting itself, etc),
blank stare, hypersalivation, snaps at imaginary objects, at everything.
● Treatment
○ Post-exposure Prophylaxis:
■ Given during incubation period
■ PEP includes local wound care and both active and passive immunization
■ In the Philippines, you start the post-exposure prophylaxis at the day of
presentation sa clinic/upon consult.
○ Passive Immunization: Rabies IG: 1 dose
■ Human IG: 20 IU/kg infiltrated around the wound.
● If the volume is in excess, administer at a distant site and change the
needle
● If the amount is too small, dilute it to cover the whole area.
● Replace any amount that has been lost if spillage occurs
■ Equine IG: 40 IU/kg

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 ● Contraindications: Hypersensitivity, giving it to special population
(pregnant, newborn, HIV patient, renal transplant patient, etc)
○ Active Immunization: Inactivated Rabies Vaccine: 1 mL/dose 4 doses at days 0, 3, 7, 14
■ In the Philippines, post-exposure prophylaxis will have already been finished once
you finish observing the animal
■ Purified Vero cell Rabies Vaccine (PVRV): 0.5mL/dose at day 0,3,7,14
■ Purified Chick embryonal cell Rabies Vaccine (PCECV): 1mL/dose IM at day
0,3,7,14
■ Intradermal route: 0.1mL at 2 sides/dose at day 0,3,7,14
■ Do not use in special population
■ Pregnancy and lactation are not contraindicated in vaccination.
○ If unrecalled vaccination, consider the patient unimmunized
○ If the patient presents to you and claimed to have been bitten by a dog:
■ First, categorize the wound
■ Clean the wound
■ Give Vaccine at day 0,3,7,14 IM
■ Give Immunoglobulin in the face, if sobra, at a distant area other side that of the
vaccine. If kulang, dilute it.
■ Give Tetanus toxoid in the anterolateral thigh and Immunoglobulin on the other
side
■ Give antibiotic
■ Pre-exposure Vaccination
● Vaccine 1 mL/dose IM at day 0, 7, 21 or 28
● If the patient with pre-exposure vaccination was bitten, give Booster at
day 0, 3
○ Without pre-exposure prophylaxis:
■ Post-exposure prophylaxis category II: active immunization 4 doses at day 0, 3, 7,
14
■ Post-exposure prophylaxis category III: active immunization 4 doses at day 0, 3,
7, 14 + Immunoglobulin
○ With pre-exposure prophylaxis:
■ active immunization (booster) at day 0,3

3. Leptospirosis (LOZANO)
Case: 45/F, market vendor, fever, chills, headache for 10 days
● Differential Diagnosis
○ Viral Hepatitis
■ Look at the temporal relationship of the fever and jaundice
■ Viral Hepa: fever then after lysis is jaundice
■ Patient in the case: fever and jaundice occurs simultaneously
■ Choledocholithiasis/Cholangitis: jaundice then fever (due to obstruction of biliary
tree + stasis of bile + contamination of the bile) *​stasis of the bile first before
having fever
○ Malaria
■ Jaundice and fever can also occur

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 ■ Rule out because no history of travel to endemic area
○ Leptospirosis
■ Fever and jaundice occurring simultaneously
■ Caused by the spirochete ​Leptospira interrogans
● Clinical Manifestations
○ Acute Leptospiremic Phase
■ Bacteria is in the blood stream
■ Use blood if you want to diagnose – culture/PCR
■ Blood culture – Ellinghausen - McCullough - Johnson - Harris (EMJH) / Fletcher’s
medium (Not advised due to long time of culture [several days], risk of biohazard)
■ PCR
● detects the antigen, also detects the strains
● Not advisable - expensive
■ Best time also to give antibiotics
■ 10 days – should diagnose early because you have only 10 days to intervene
■ Beyond 10 days – not in the leptospiremic phase anymore and antibiotic may no
longer be effective
○ Leptospiruric Phase
■ Present in the urine
■ vasculitis – immune reaction
■ the problem is no longer the bacteria but our own immune system reacting to the
pathogen
■ immune phase – antibody develops
■ antibiotic is not effective anymore and patient may not survive unless you do
dialysis
■ bacteria is not in the blood but it is found in other organs like lungs, liver, cns and
urine
■ contributory factor of jaundice in leptospirosis: cholestasis (bile canaliculi is
plugged)
■ Excessive urination leading to too much potassium excretion → early part of renal
failure/acute phase of kidney injury: nonoliguric hypokalemia
■ if not treated, pt will develop acute tubular necrosis → Potassium is not excreted
leading to accumulation → oliguric hyperkalemia
■ Weakness, calf muscle tenderness – can be associated; due to electrolyte
imbalance
● Diagnosis
○ Microscopic Agglutination Test (MAT)
■ Gold standard
■ Useless in leptospiremic phase because it detects antibody
■ cannot give the diagnosis using a single elevation of MAT titer
■ example: 1:32 – probable only because mat tells us that the patient has antibody
to lepto
■ antibody takes time to develop, it also takes time to wane
■ If antibodies are already present at the time of analysis, it may be that the patient
already had leptospirosis several months ago and the fever the patient is
presenting with is only due to flu
■ so if you have single elevation of titer, it might only offer a probable diagnosis
■ to get a definitive diagnosis, get a paired serum sample because we have to
compare the levels of the titers – 4 fold increase or seroconversion (zero titer and
then becomes positive
● During acute – Ex. 1:2 (2 x 2 x 2 x 2)
● During convalescent – Ex. 1:16
● Treatment
○ Mild
■ oral (doxycycline – not given to pregnant patients; amoxicillin/ampicillin for
pregnant) – 7 days
○ Mod/severe

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 ■ Weil’s syndrome – high creatinine (>3), ph (<7.2), oliguric (< 5cc/hr), altered
sensorium, excessive vomiting
■ DOC: Aqueous IV Penicillin G (1.5 mg ) for 7 days
■ Alternative: ceftriaxone/cefotaxime
■ Don’t give doxycycline because it can further promote AZOTEMIA, and it is only
bacteriostatic
■ Even if the creatinine is very high, you do not adjust the dose of penicillin anymore
because that dose is very very low already
○ Chemoprophylaxis
■ Low risk: once within the first 72 hours – doxycycline 200 mg (but not available so
prescribe 100 mg, 2 capsules to be taken once) ; with exposure but without wound
■ Moderate risk: single exposure with wound; within 72 hours- same dose but give
for 3-5 days)
■ High risk: once a week
■ if chemoprophylaxis is already taken but fever persists after, leptospirosis cannot
be ruled out bec no prophylaxis is 100% effective
■ Pregnant – azithromycin prophylaxis
○ Indications to perform dialysis
■ Oliguric
■ creatinine is increased
■ increased acidity in the body – very low ph

4. Cholera (LOZANO)
Case: 32/M, tricycle driver, 15 episodes of watery, non-bloody, non-mucoid stools
● Clinical Assessment
○ First focus: duration of fever
○ Diarrhea: check the characteristic – watery, mucoid, bloody – can already eliminate other
differentials
○ Patient: non mucoid, non bloody, watery; have already signs of severe dehydration
(hypotensive)
● Differential Diagnosis and Clinical Manifestations
○ Non-inflammatory diarrhea
■ Usually due to a toxin
■ If it is toxin – doesn’t do much damage in the intestinal mucosa; you just secrete a
lot
■ proximal intestine is affected – responsible for the absorption of solute and water
therefore expect a voluminous, watery diarrhea
■ toxin mediated – no mucus/blood
■ fecalysis – no wbc, rbc
■ Vibrio cholerae​, ​Bacillus cereus​, ​Staphylococcus aureus​, ETEC (enterotoxigenic
E. coli​), norovirus, some parasite
○ Inflammatory
■ distal small bowel and colon are affected – no absorption of fluid and electrolytes
(because there are functions of the proximal si); therefore, scanty diarrhea
■ mucosa is invaded – observe bloody, mucoid stool aka dysentery
■ fecalysis – pmns, mucus, rbcs
■ Shigella​, some ​Salmonella​, amoebiasis (​Entamoeba histolytica​), EHEC
(enterohemorrhagic ​E. coli​), EIEC (enteroinvasive ​E. coli​), ​Clostridium difficile​,
Campylobacter
○ Penetrating
■ does not manifest much with diarrhea – because salmonella has the capacity to
just penetrate/ traverse the intestinal lining without causing inflammation – stealth
phenomenon
■ if with diarrhea, sometimes bloody
■ fecalysis: can have blood, mucus; mononuclear cells like macrophage
■ the presentation is enteric fever
■ hallmark of typhoid/enteric fever: prolonged fever and abdominal pain
■ Salmonella, Yersinia enterocolitica

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 ○ Pathophysiology
■ Adenylyl cyclase is stimulated → CAMP is increased
■ Chloride is released in the lumen and sodium’s absorption is inhibited → becomes
salt and where salt is, water follows
○ Isotonic diarrhea – classic diarrhea of cholera, because salt and water are excreted at the
same time, voluminous; therefore the treatment is also isotonic fluids like ORS
● Diagnosis
○ Culture medium – TCBS (Thiosulfate Citrate Bile Salt Sucrose) Agar
○ When is stool culture requested?
■ bloody diarrhea
■ watery diarrhea if you are entertaining cholera
■ most of non inflammatory diarrhea are toxin mediated therefore the primary
treatment is hydration – even if you have isolated the organism it doesn’t matter,
you just have to hydrate the pt UNLESS if it is cholera -if mild, hydrate; if severe,
give antibiotics
■ dysentery – there is invasion of mucosa so the treatment will depend on the
culture
○ amoebiasis – even if it is an inflammatory diarrhea, you do not culture parasites; do wet
mount- look for trophozoites
● Treatment
○ Hydration
■ iv ors or isotonic fluids
■ hypotensive, vomiting severely dehydrated - don’t aggravate the vomiting by
giving oral, give it iv
■ you have to correct the deficit very very fast otherwise the pt will develop acute
tubular necrosis because of persistent hypotension
■ factors to consider when computing for the deficit: maintenance losses like sweat,
stool, ongoing losses
● deficit – past; lost stools the previous days
● ongoing losses – present
● maintenance – future
○ no need to give antibiotics, mainstay tx is hydration but you can give antibiotics
■ erythromycin – least to give; can further promote diarrhea (prokinetic)
■ Azithromycin
○ Vaccine-preventable:
■ Rotavirus - live
■ Cholera - live
■ Typhoid (Salmonella) – live/inactivated
○ don’t give live vaccines to immunocompromised
○ don’t give antibiotics because vaccine will die - can be given in inactivated salmonella
○ paratyphoid fever – vaccine can’t protect you from typhoid fever 100% because of this
○ no vaccine available
■ Norovirus
■ Shigella
○ ciprofloxacin – shigella

5. Dengue (LOZANO)
Case: 19/F student, high fever, headache, severe myalgia for 4 days
● Differential diagnosis for acute onset fever ​(first consideration: duration of fever)​:
○ Shigella​ (dysentery)
○ Chikungunya
■ considered due to high grade fever and myalgia
■ Joint pains/arthritis – can be debilitating and may last up to months or sometimes
up to years
■ Rash during the fever
■ High grade fever, shorter duration compared to dengue (3-5 days)
■ Normal wbc or slight leukocytosis, normal or mild thrombocytopenia (not expect
bleeding), normal hct (unless dehydrated) – no hemoconcentration

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 ■ Serum transaminases may be elevated
■ Clinical picture: fever begins and spikes up then lyses; when the fever subsides,
thrombocytopenia and hemoconcentration are not expected; what is expected
would be prominent peripheral joint pains (mimicking RA)
○ Dengue
■ considered because the patient presented with thrombocytopenia and
hemoconcentration at the time when the fever lysed
■ Herman’s rash in the recovery phase
■ Fever – usually 3-7 days
■ Leukopenic, thrombocytopenic, inc hematocrit (hemoconcentration)
■ Higher serum transaminases compared to chikungunya because the dengue
virus is hepatotropic – Dengue hepatitis
■ Clinical Picture: fever may last from 3 to 7 days; when the fever lyses,
thrombocytopenia and hemoconcentration become apparent; the liver may
become inflamed and lead to dengue hepatitis (compared to chikungunya which
does not lead to much hepatitis)
■ Joint pains may also occur especially at the joints of the back
○ Influenza
■ Considered due to fever and myalgia
■ Fever is high grade – very acute (usually after 24 hours the patient will recover, or
will feel under the weather for 2-3 days, but once the fever lyses, the patient feels
better)
■ Upper respiratory tract symptoms – cough, sore throat (​not ​usually ​seen in
dengue; but some dengue virus infections can manifest with sore throat)
■ May have thrombocytopenia but mild
■ Hemoconcentration seen when dehydrated only
■ Slight elevation of transaminases but not as severe as seen in dengue
○ Hepatitis A
■ Also present with fever, myalgia
■ Does not present with thrombocytopenia and hemoconcentration
■ More than 100; usually more than 1000 serum transaminases
■ Fever precedes jaundice – fever lyses then jaundice sets in; di sila pwede
magsabay
○ Enteric Fever
■ Should not be included in the differentials because this presents with prolonged
fever
■ Stepladder Fever – starts with a low-grade fever which increases in temperature
as time passes
● Other clinical manifestations:
○ liver bone marrow, endothelial cells
○ Thrombasthenia – platelet dysfunction
○ Factors leading to Thrombocytopenia:
■ BM suppression (patient may also become leukopenic)
■ Liver – brought about by coagulopathy (fibrinolytic system is activated due to the
toxin brought about by the infection; platelets are consumed in the process) and
decreased thrombopoietin (produced in the liver; will stimulate the BM LESS to
produce platelet)
○ Hemoconcentration – fluid from the vascular system goes out due to plasma leakage
(spaces between the endothelial cells widen because of the infection)
● Course of illness:
○ Febrile Period
■ Viremic
■ Test for antigen only (no antibodies present yet): viral (blood) culture or antigen
testing by PCR or NS1 (direct antigen testing)
■ RT-PCR: not practical in our setting
■ Culture is also not practical because it will take a long time to get the results
■ NS1 (Non structural protein 1) – more practical; not confirmatory because it can
be falsely positive with other Flaviviruses like Yellow fever

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 ■ Patient: 4​th day of illness (on admission), still with fever but not yet on the critical
period (still not thrombocytopenia and hemoconcentration): request CBC and NS1
○ Critical Period
■ Primary Dengue: no fever but decreasing platelet count and increasing hematocrit
■ Secondary Dengue: fever, decreasing platelet count, increasing hematocrit →
worse presentation
■ Do not wait for fever to subside to declare patient on critical period; observe PC &
Hct
■ Request for Dengue IgM or IgG
■ IgM > IgG because IgM develops earlier than IgG; day 5 and beyond, testing for
NS1 cannot be done anymore (NS1 is usually elevated in the first to the fourth day
of the infection so measuring it on the fifth day and beyond will only reveal a
reduced titer)
■ Will a single elevation of IgM give you a definitive diagnosis of dengue? NO. This
will only give you a probable diagnosis of dengue. IgM doesn’t disappear
instantaneously and this may just be a result of a previous dengue infection in the
last month.
■ IgM Definitive Dx: Paired serum sample in the acute and convalescent phase
■ (+) Seroconversion – previously negative becomes positive (means recent
infection)
■ IgG: Paired Serum from acute and convalescent
■ Primary Dengue: (+) seroconversion
■ Secondary Dengue: 4 fold increase in rise in titer (Ex: 1:2 [acute] to 1:16
[convalescent])
○ Recovery Period
■ 3-5 days
■ Herman’s rash: “white islands in a sea of red”; sign of recovery
● Warning signs:
○ thrombocytopenia and hemoconcentration (must occur together) – admit
○ Mucosal bleeding
○ Persistent vomiting
○ Severe abdominal Pain
○ Fluid accumulation
○ Lethargy
○ Hepatomegaly (>2 cm increase)
● Severe dengue:
○ bad prognosis
○ Severe bleeding
○ Severe fluid accumulation – manifested by respiratory distress (due to massive pleural
effusion)
○ Severe organ impairment – coma, hepatitis
● Patients that need admission even if without warning signs:
○ Pregnant
○ Patients who live alone
○ With comorbid conditions
○ People living in mountainous areas wherein the travel to hospital is long
● Patient classification:
○ Group A – without warning signs
○ Group B – with warning signs (patient)
○ Group C – with signs of hypovolemic shock
● Treatment:
○ IV fluids – start kahit wala pang cbc; isotonic fluids like plain NSS
○ Case Scenario:
■ Plt 75 000, Hct 60
● Low hct: Maintain or Increase the rate (because of hemoconcentration)
● Low plt: observe, don’t transfuse because the infection is self-limiting and
transfusion of platelets will promote production of antibodies and these
will destroy your own platelets eventually; there can be negative feedback

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 (transfusion of platelets will cause the liver to lessen its production of
thrombopoietin)
■ Plt 5000, Hct 45
● From 60 naging 45: means that you hydrated the patient; another reason
is there can be bleeding (resulting in a reduced plt count); do not
decrease fluids immediately, check if the patient is bleeding before doing
so, stopping fluids abruptly in a bleeding patient will cause the patient to
go into hypovolemic shock
● If with bleeding: Increase the fluid and transfuse blood (packed RBC)
● Suspect significant bleeding:
○ Check vital signs: hypotensive, tachycardia
○ Mucosal petechiae
○ Pale
○ GI (melena, hematochezia, hematemesis)
○ Menorrhagia
○ Hematuria
● If without bleeding: decrease the fluid; no need for transfusion
■ Plt 100 000, Hct 40
● Recovery Phase – function is restored; capillary leakage is diminished
(fluid from interstitial fluid will go back to intravascular space); best thing
to do is discontinue the IV fluids
● Decrease the rate because if not, you may over hydrate the patient
● Dengue vaccine:
○ Efficacy: 60% effective
○ Receiving the vaccine does not mean that the patient will not contract dengue anymore
○ Dengue Shock Syndrome may occur if the patient develops Dengue 5 and 6 because of
Antibody Dependent Enhancement/Cell Cytotoxicity (ADCC)
○ ADCC explains why the 2​nd to 4​th dengue are more dangerous than the 1​st because you
have the memory cells for the 1​st​; the antibody you’re producing will protect you from that
strain but it can cross react with other dengue virus strains (they all have the same Fc
receptors) and because of the cross reaction, the body’s response to the dengue virus is
prematurely stimulated however, the antibody you are producing is not neutralized in
dengue 2, 3, and 4. You are continuously producing antibodies to dengue 1. The body
then realizes too late that the antibodies it is producing isn’t capable of neutralizing
dengue strains 2-4 after having produced too much antibodies for dengue strain 1 causing
an overwhelming immune response leading to massive capillary leak due to inflammation.
○ ADCC is the reason why some doctors don’t recommend the dengue vaccine. The
vaccine allows antibodies to be produced against the four strains of dengue, so when a
fifth dengue strain infects the patient, shock occurs.

6. Malaria (LOZANO)
Case: 34/M news correspondent from Palawan, fever, chills, headache for 2 weeks
● Differential diagnosis:
○ Hepatitis
■ not all patients will present with lethargy
■ Hepatic encephalopathy – seen in fulminant hepatitis; lethargy
○ Enteric/Typhoid Fever
■ Abdominal pain: even though this is a hallmark, it doesn’t mean that if this is
absent typhoid is not considered anymore
■ Hallmark: prolonged fever and abdominal pain will make you highly suspect
typhoid but it cannot be ruled out in the absence of these
■ If this will be included in the DDx, look for risk factors but for this patient there is
none so we should not consider it anymore
○ Malaria
■ Intermittent Fever
● P. falciparum​ - Malignant Tertian
● P. vivax/ovale​ - Benign Tertian
● P. malariae​ - Benign Quartan

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 ● P. knowlesi​ - Quotidian
● Life cycle:
○ Schizogony and merogony – twice (when it invades the rbc and when it is in the
hepatocyte
○ Once the parasite invades the hepatocyte, it will undergo schizogony and release
merozoites then the merozoite will attack an rbc or it will become dormant in the liver to
produce a hypnozoite. WHen the merozoite invades the RBC, it will undergo schizogony
again and release merozoites to invade more RBCs.
○ Hypoglycemia – due to decreased gluconeogenesis and increased glucose consumption
of the host and the parasite
○ Splenic clearance is augmented because of ​less deformable rbc membrane​. This will
contribute to anemia and to jaundice. The liver then becomes overwhelmed in trying to
conjugate the excess bilirubin. The increased unconjugated bilirubin will now deposit in
soft tissues.
○ Cytoadherence, rosetting and agglutination will result to disruption of microcirculatory
blood flow. ​P. falciparum can do this that’s why it’s the only specie that can produce
severe malaria which can lead to cerebral malaria. There is hypoxia and there is a shift in
anaerobic glycolysis leading to acidosis. In kidneys, it will result to renal failure.
● Diagnosis
○ Thick blood smear ​– for detection, more parasites acquired; monitor response to
treatment because it can quantify the parasite count
○ Thin blood smear ​– for speciation; necessary because different species have different
management and treatment
○ PfHRP2 ​disadvantages:
■ detect ​P. falciparum only because Histidine Rich Protein is specific for ​P.
falciparum
■ Cannot monitor response to treatment because you cannot quantify – as long as
there are live parasites, a positive result will be seen; sometimes even if they are
dead it can still be positive because you still have HSP
■ May be used in endemic or hyperendemic area – people are expected to have low
level parasitemia but it doesn’t necessarily mean that they have malaria, they will
be (+) but without any manifestations. Their bodies have grown accustomed to the
level of parasitaemia.
■ Ex. In manila – if (+), it will be significant
○ LDH
■ can detect all species
■ P. falciparum has the highest parasite burden because of ​cytoadherence​; they
stick to the blood vessel walls that’s why the can’t be cleared by the spleen; they
have the higher tendency to be detected by LDH because of higher level of
parasitemia
■ P. vivax, ovale, malariae – they are cleared by the spleen; pwede pa rin
madetect ng LDH pero lower level; so most of the time their diagnosis is missed
by LDH
○ PCR
■ also capable of speciating the parasite especially between malaria and knowlesi
(they look the same on smear); knowlesi – mukhang [Link] pero yung patient
is toxic-looking
○ Philippines: ​vivax, falciparum
○ There can be mixed infection
● Treatment:
○ Severe falciparum malaria
■ DOC - Artesunate IV
■ Alternative: Quinine and Quinidine
■ Side effect for Quinine
● Hypoglycemia – due to hyperinsulinism
● Cinchonism
● Arrhythmia
○ Uncomplicated Malaria

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 ■P. falciparum
● DOC: Co-Artem (Artemether – Lumefantrine)
● MOA: prevents conversion of heme to hemozoin; heme is toxic to the
parasite; same MOA for chloroquine
● Not effective for gametocyte because it kills the parasite inside the RBC
● Day 0, 1, 2 followed by Primaquine for 1 day (Purpose: not for radical cure
because not after the hypnozoites. Used as gametocidal; it kills the
parasite outside the RBC)
■ P. vivax and ovale
● DOC: Chloroquine
● Day 0, 1, 2 followed by Primaquine for 14 days (we are after the
anti-hypnozoite effect)
■ P. malariae
● DOC: Chloroquine
● Day 0, 1, 2 then Primaquine for 1 day only (we are no longer after the
anti-hypnozoite effect)
○ If we do not know if the parasite is sensitive to the drug, always treat it as severe malaria
● Chemoprophylaxis:
○ Doxycycline
■ Daily, 2 days before up to 4 weeks after travel to an endemic area
○ Mefloquine
■ Once weekly, 1-2 weeks before up to 4 weeks after travel to an endemic area

7. Schistosomiasis (MONZON, MENDOZA ELLA)

Case: 39/M copra farmer from Samar, intermittent throbbing bitemporal headache for 6 months
● Epidemiology
○ Five Schistosomal species (​S. mansoni, S. japonicum, S. mekongi, S. Intercalatum​): infect
200-300 million individuals in South America, Africa, Caribbean, Middle East, Southeast
Asia
○ 440 million: over-all affected by Schistosomes
○ Most affected: children and young adults
○ Parasite-related disease persists even after resolution of active disease → health burden
among adult population
○ Prevalence in endemic areas
■ 3-4 y/o:​ prevalence starts to be appreciable
■ 12-20 y/o:​ maximum prevalence
■ Older age group (>40 y/o):​ stabilized or decline
○ Intensity (egg count in feces or urine): correlated with adult worm burdens
■ 12-20 y/o: increased
■ Older age group: decline
■ Reflects acquisition of resistance to schistosoma or changes in water contact
exposure (less exposure among older age group)
○ Overdispersed pattern: Most individuals infected with schistosoma have low worm burden
while small percentage of those infected have high worm burden (heavily
infected/high-intensity infection)
■ Due to:
● Differences in worm infectivity
● Genetic susceptibility
■ Heavily infected: more prone to disease sequelae and become reservoir of the
infection in endemic areas
○ Most disease syndromes/symptoms related to:
■ presence of one or more parasitic stages of the schistosome present in the host
■ Intensity and duration of infection
■ Age
■ Genetic susceptibility
○ Intestinal schistosomes: rarely manifest with severe Schistosoma-specific disease
○ Urogenital Schistosoma (​S. haematobium​): mostly manifest with clinical symptoms

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 ○ All forms of Schistosoma: manifest with subclinical systemic morbidities that affect
physical and cognitive performance
○ Schistosomiasis: co-factor in the spread of HIV/AIDS in areas where they are both
endemic
● Etiology
○ Human infections caused by 5 species:
■ S. mansoni
■ S. japonicum​ - Intestinal Schistosoma
■ S. mekongi
■ S. intercalatum​ - Intestinal and hepatic schistosomiasis
■ S. haematobium​ - Urogenital schistosomiasis
○ infection may cause considerable morbidity in the intestines, liver or urinary tract
○ small portion of affected individuals die
○ Avian species of Schistosoma: self-limited cutaneous manifestations
■ invade the skin but die in the subcutaneous tissues
● Pathophysiology
○ Penetration of intact skin with cercariae​: initiates human infection
○ Schistosomula: main adaptive mechanism of schistosoma for survival within definitive
host
■ transformation form of the cercariae once it enters the subcutaneous tissue
○ (+) Heptalaminal outer membrane: from a trilaminar membrane
○ Schistosomula migration: within 2-4 days via the lymphatic or venous vessels
■ leads to eosinophilia
■ Travels via the lymphatic or venous vessels then to the lungs and finally to
the liver parenchyma
○ Sexually mature worms
■ Descend to the venous system at specific anatomic sites
■ What guides adult schistosomes to these anatomic sites are still unknown
■ Intestinal veins (superior and inferior mesenteric veins; ​S. mansoni, S. japonicum,
S. mekongi, S. intercalatum​)
■ Pelvic veins (​S. haematobium​)
■ Inhibit coagulation cascade and evade effector arms of host immune system by
still undetermined mechanisms
■ Small tributaries: where adult gravid females will travel to deposit their ova
intravascularly after mating
■ Note: they travel against the venous blood flow after mating to reach tributaries
(endurance!)
○ Ova: moves through the venous wall with the help of enzymes secreted in the minipores of
their eggshells to reach the lumen of intestinal and urinary tracts
■ Voided via urine or stools
■ 50%: retained in host tissues locally (urinary or intestinal tract) or carried by
venous blood flow to the liver and other organs
■ Reach freshwater and hatch to miracidia
○ Miracidae: infective to freshwater snails
○ Cercariae: developed in and released by snails
○ Metacercariae: infective to humans
○ Curative treatment of infected population in endemic areas is followed by differentiation in
reinfection patterns
○ Chromosome 5: related to the intensity of schistosomal infection
○ No vaccine to date
○ S. japonicum produces 10 times more egg than S. mansoni but difference in eggs produce
does not cause difference in severity of disease manifestation in host
● Clinical Manifestations
○ Dermatitis (swimmer’s itch)​: cercarial invasion
■ Arises from dermal and subdermal inflammatory responses
■ Involves humoral and cell-mediated immunity
■ S​. japonicum ​and​ ​S​. mansoni
■ Manifests 2-3 days after infection

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 ■ Itchy maculopapular rash on affected area of the skin
■ Self-limiting (except if AVIAN SCHISTOSOMES)
○ Katayama fever (or acute schistosomiasis)​: occurs as worm maturity occurs in the liver
of the host and as oviposition commences
■ Due to tissue deposition of soluble immune complexes formed die to excessive
antigen
■ Occurs 4-8 weeks after skin invasion
■ Occurs during worm maturation and beginning of oviposition
■ Parasite-specific antibodies may be detected before schistosomal eggs are
excreted in excreta
■ Manifestations:
● High degree of peripheral-blood eosinophilia
● Serum sickness-like syndrome with fever
● Generalized lymphadenopathy
● Hepatosplenomegaly
■ Exposure while wading or swimming in freshwater
○ Chronic schistosomiasis:
■ caused by egg retention in host tissues
■ Involves:
● (+) granuloma formation - cell-mediated
● Begins with inflammatory cell recruitment in response to antigen
secreted by organism within ova
■ Initial: phagocytes, antigen-specific T-cells, eosinophil
■ Later: B-cells, fibroblasts, giant cells
■ Fibrosis sets in after
■ Organomegaly and obstruction: cumulative lesions brought about by cell mediated
response
■ Kidney disease: deposition of antigen-antibody complexes in renal glomeruli
■ Immunomodulation ​or ​downregulation ​of host responses: limits extent of
granulomatous lesions
■ manifestations are species-dependent
■ S. haematobium​ infection occur early and involve high percentage of individuals
■ Intestinal species may cause intestinal and hepatosplenic disease, and portal
hypertension
■ severity of intestinal schistosomiasis = intensity of worm burden
■ LUNGS, CNS, SKIN, GENITAL ORGANS: may also be affected
○ Liver schistosomiasis​: involves granuloma formation, fibrosis
■ Schistosomal hepatomegaly
● Occurs due to granulomatous formation
● Differential diagnosis:
○ Viral hepatitis of all etiologies
○ Miliary TB
○ Malaria
○ Visceral Leishmaniasis
○ Ethanol abuse
○ Other causes of hepatic and portal vein obstruction
● Presinusoidal sites​: where ova carried by portal blood embolize to the
liver lodge in
○ also where granuloma formation occurs
○ Granuloma, HLA 1&2: related to schistosomal hepatomegaly
○ PRESINUSOIDAL PORTAL BLOCKAGE: leads to hemodynamic
changes (e.g. portal hypertension, formation of portosystemic
collaterals at esophagogastric junction)
○ Breakage of esophageal varices: HEMATEMESIS
○ COMPENSATORY ARTERIALIZATION: due to slow changes in
hepatic portal blood flow
○ may lead to:
■ Metabolic side effects

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 ■ Maintenance of normal liver function for years
● Periportal (Symmer’s clay pipe-stem) fibrosis
○ Seen in areas of egg deposition, granuloma formation and distal
tracts (portal tracts)
○ Schistosomiasis results in pure fibrotic lesions in the liver
■ Deposition of fibrotic tissue in the ECM results from:
interaction of T-cells with fibroblast cells
■ Fibrogenesis stimulated by: cytokines (IL-1,IL-2, IL-4,
Transforming growth factor β)
■ Suppressed by: IL-10, IL-12, Interferon ɣ
○ Cirrhosis: only occurs when other toxic factors or infectious
agents (e.g. hep B & C) are involved
○ Urogenital schistosomiasis​ - involves granuloma formation and fibrosis; S.
haematobium
■ Differential diagnosis:
● Bacterial cystitis
● TB
● Urinary stones
● Malignancy
■ Granuloma formation occurs at:
● Lower end of the ureters - ​causes urinary flow obstruction with
subsequent development of hydroureter and hydronephrosis
● Urinary bladder - ​lead to ulceration and bleeding
■ Chronic stage of infection​: associated with scarring and calcium deposition in
the bladder wall
■ Involvement of birth canal can cause:
● cervical or vaginal wall polyps: friability
could cause contact bleeding
● increased risk for hiv transmission
■ Female genital schistosomiasis: involves the uterus, fallopian tube and ovaries
■ May lead to secondary infertility and subfecundity
■ S. haematobium in men: result in prostatic and testicular lesions with
hematospermia
■ Perineal superficial cutaneous lesion may also occur in both sexes
○ Intestinal schistosomes (​S. mansoni, S. japonicum, S. mekongi, S. intercalatum​)
■ Intestinal phase
● Begins few months after infection
● May last for years
● Runs a chronic course
● May result in colonic polyposis
● Manifestations:
○ colicky abdominal pain
○ bloody diarrhea
○ anemia
● Patients may also report: fatigue, inability to perform daily function, growth
retardation
■ Hepatosplenic phase
● Manifests early (during the first year of infection)
● (+) hepatomegaly: due to granulomatous lesions
● Correlates to intensity of worm burden, HLA, HLA-2, age (children)
● ↑ presinusoidal blockade → portal hypertension & splenomegaly→
varices at the lower end of the esophagus
● Esophageal varices​: first clinical manifestation of hepatosplenic phase
● Liver schistosomiasis: may present with right upper quadrant dragging
pain that may move to the left upper quadrant
● Adequate total hepatic blood flow: allows normal liver function despite
repeated bleeding due to varices
■ Late-stage disease

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 ● Fibrotic changes
● Liver function deterioration
● Onset of ascites
● Hypoalbuminemia
● Coagulation defects
● Acceleration of deterioration of hepatic function:
● Intercurrent liver disease (Hep B & C) → CIRRHOSIS
● Toxic insults (excessive ethanol, organic poison exposure, aflatoxin
exposure)
● Nutritional deficiencies
○ UROGENITAL SCHISTOSOMIASIS ​(​S. haematobium​)
■ Manifestations:
● Dysuria
● Frequency
● Hematuria: occur at the end of voiding
■ Urine examination: (+) blood, (+) albumin, (+) high frequency of bacterial UTI, (+)
high urinary sediment cellular metaplasia
● Correlate with intensity of infection, granulomas, ulcerations
■ granuloma: obstruction at the lower end of the ureter → hydroureter &
hydronephrosis
■ cystoscopy: (+) sandy patches due to fibrosis of granuloma
■ endemic areas: there is an association between squamous cell carcinoma of
bladder and s. haematobium
● younger age group
○ pulmonary schistosomiasis
■ small arterioles: where embolized eggs lodge
● produce acute necrotizing arteriolitis & granuloma formation
● s. mansoni​ and ​s. japonicum:​ reach lungs via portosystemic collaterals
● s. haematobium: reach lungs directly via vesical and systemic circulation
● fibrous tissue deposition → endarteritis obliterans, pulmonary
hypertension, cor pulmonale
● cor pulmonale: (+) prominence of right side of the heart, (+) pulmonary
artery dilatation
● most common symptoms:
○ cough
○ fever
○ dyspnea
○ cns schistosomiasis​: ​s. japonicum, s. mansoni, s. haematobium
■ migratory worms deposit eggs in the brain → granulomatous response
■ Philippines (2-4%)
■ S. japonicum​: 2​nd​ most common cause of jacksonian epilepsy in the philippines
■ S. mansoni​ and ​s. haematobium​: transverse myelitis
● eggs are along the granulomatous or necrotic lesions
● due to eggs traveling to the venous plexus around the spinal cord
● S. mansoni​: seen in chronic stage after development of portal
hypertension & portosystemic shunts
● S. haematobium​: ​visceral & systemic veins​; spinal cord disease
detectable at any stage of infection
■ common manifestations:
● acute or rapidly progressing lower leg weakness accompanied by
sphincter dysfunction
● Diagnosis
○ based on detection of parasite in excreta, sputum, tissue samples (rare) or on sensitive
and specific serologic tests
○ diagnosed by combination of geographic history, clinical presentation, and presence of
ova in excreta
○ HISTORY: history of travel, details of geographic history, exposure to freshwater,
indulgence in local eating habits,

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 ○Traveler usually returns with signs and symptoms of acute schistosomiasis: cercarial
dermatitis or katayama syndrome
■ Katayama syndrome: Prompt diagnosis is essential, based on clinical
presentation, peripheral blood eosinophilia, (+) serologic assay for schistosomal
antibodies
○ Differential diagnosis:
● Dengue fever
● Enteric fever
● Leptospirosis
● Rickettsia
● Malaria
○ FAST-ELISA
○ Enzyme-linked immunoelectrotransfer blot (EITB): confirmatory
○ Kato thick smear: identifies heavy infection but does not identify those with light infection;
stool examination
○ Point-of-care test: detect parasite circulating cathodic antigen in urine
■ S. mansoni
■ Monitoring of infection of clearance after treatment
○ Microscopy of sediment: ​S. haematobium
■ Testing for parasite DNA in urine sediment: increases sensitivity
○ Nuclepore filtration: ​S. haematobium​; quantitative data on intensity of infection
○ Biopsy
■ Rectal biopsy: typically used
○ Liver biopsy: not necessary
● TREATMENT
○ depends on stage of infection and clinical presentation
○ Cercarial Dermatitis
■ topical dermatological relief for itch
■ No specific treatment
○ Acute Schistosomiasis/Katayama Disease
■ DOC: Praziquantel
■ Needs to be adjusted for each case
■ antischistosomal chemotherapy: does not have a significant impact on maturing
worms
■ severe acute schistosomiasis
● Glucocorticoid: reduce inflammation
○ Praziquantel
■ Administered PO
■ 40-60 mg/kg per day divided into 2-3 doses
■ Lower efficacy rate in children <5 years old → more likely to need retreatment to
effect a cure
■ Parasitic cure in 85% of cases
■ Reduces egg count by >90%
○ After chemotherapy
■ Early hepatomegaly and bladder lesions: resolve after chemotherapy
■ Late manifestation symptoms (e.g. fibrosis): do not resolve
■ Additional management modalities: hepatocellular failure, recurrent hematemesis
○ Prevention and control
■ Avoid contact/exposure to freshwater bodies
■ Follow-up visit with healthcare provider if exposure occurs
■ Application of molluscicides, sanitary water and sewage provision, chemotherapy,
health education
■ Praziquantel: antischistosomal chemotherapy agent; most successful in reducing
intensity and reversing disease

8. Meningitis (MUARIP, LEE, NAIDAS)

Case: 38/M microbiology laboratory technician, stuffy nose & productive cough for the past 2 days, high
fever, chills, severe headache unrelieved by medication

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● Etiology of acute bacterial meningitis:
○ Streptococcus pneumoniae​ (~50%), ​Neisseria meningitidis​ (~25%), group B
streptococci (~15%), ​Listeria monocytogenes​ (~10%), ​Haemophilus influenzae​ type b
(<10%)
● Clinical Manifestations:
○ Triad of meningitis: headache, fever, nuchal rigidity
○ Since most common etiologic agent is ​S.​ ​pneumoniae​, most important risk factor is
pneumococcal pneumonia
○ Does not usually present with symptoms of upper respiratory tract infections (e.g. stuffy
nose) but may present as the bacteria spreads via the hematogenous route hence the
consideration of an invasive pneumococcal disease
● Differential diagnosis:
○ Meningococcal - R/O due to (-) rash (purpura fulminans)
○ Encephalitis - R/O due to (+) nuchal rigidity
○ TB and Fungal meningitis - R/O due to acute presentation
○ Pneumococcal
● Diagnosis:
○ CNS Evaluation - important 1st step
■ To know if CT scan/MRI is needed prior to LP (Avoid uncal herniation)
● Immunocompromised (HIV, post transplant patients, post chemotherapy
patients)
● Hx of head trauma (stroke, malignancy)
● Hx of neurologic injury or disease
● Altered level on consciousness
● Neurologic deficit
● Papilledema
○ CSF Examination - 2nd step is LP (Cerebral herniation may happen if not properly
executed)
■ Hypoglycorrhachia - ​csf/serum glucose ratio: <0.4​ (bacteria eats glucose)
■ Protein: >0.45 g/L
○ PCR – if treatment has been given
○ Gram stain – FAST but G(-) does not R/O bacterial cause
■ S. pneumoniae​: G(+) bacilli
■ E. coli​: G(-) bacilli
■ N. meningitidis​: G(-) intracellular diplococci
■ H. influenzae​ B: G(-) coccobacilli; rare in adults due to vaccination
○ Sensitivity of Gram stain: >60%; culture: >80%
○ CBC to know bacterial vs viral
○ Blood culture - hematogenous spread
○ Immune system intact -> Release cytokines in CNS -> Manifestations
○ If immunocompromised -> No manifestations → need high index of suspicion
● Treatment:
○ Antibiotics can cause altered CSF results BUT do not wait for culture results when you
give antibiotics, do not delay antibiotics in these patients
○ DOC: Cefotaxime / ceftriaxone / rifampin + vancomycin
○ Neisserial/Streptococcal ​meningitis
■ 3rd/ 4th gen cephalosporin (ceftriaxone/ cefotaxime)
■ S. pneumoniae​: 2 weeks
■ N. meningitidis​: 7 days
■ ceftriaxone alone is used as empiric treatment in our local setting
■ international recommendations are to use ceftriaxone + vancomycin due to
increased emergence of resistance
■ vaccines are not recommended for n. meningitides in the philippines
○ Pneumococcal​ meningitis
■ High dose Penicillin G
■ Pneumococcal vaccine
● conjugated - better because it stimulates cell-mediated immunity
● polysaccharide - just humoral immunity

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 ● PCV13 (protein conjugate vaccine) - more immunologic so need 8 weeks
before giving PPSV23
● PPSV23 (capsular polysaccharide vaccine) - give pcv 1 year later
○ Neonatal​ sepsis/ ​group b​ strep - ampicillin + gentamicin
○ Listeria​ - ampicillin
○ Pseudomonas​ - ​quinolone(​slowly bactericidal) + ​beta-lactam (​rapidly bactericidal​)

9. Unarmored Crusade (LUSAYA, MORALES JOHANNE)

27/F with NHL, CC: fever, pain on port-A-cath site, painless to slightly tender necrotic lesion with eschar on
the dorsum of the left hand and abdomen
● NHL Chemotherapy: R-CHOP (Rituximab, Cyclophosphamide, Doxorubicin, Vincristine,
Prednisone)
○ Both humoral and cell-mediated immunity are affected
■ Humoral - targets ​extracellular​ o ​ rganisms (Ex: ​S. pneumoniae​)
■ Cytotoxic / cell-mediated - targets ​intracellular ​organisms (Ex: ​Salmonella,
Chlamydia​, Tuberculosis)
● Etiology​:
○ Px has erythematous & tender port-A-cath site and is immunocompromised (consider
gram positive organisms)
■ Possible etiologic agents: ​S. epidermidis, E. coli, S. aureus
○ Most common organism in ecthyma gangrenosum: ​Pseudomonas
● Febrile Neutropenia Differentials:
○ NORMAL FLORA
■ Can cause infections in
neutropenic/granulocytopenic
patients especially with the use
of catheters
■ Most common pathogen:
Staphylococcus aureus
● Increased rate of
colonization in
immunosuppressed
● Direct personal contact,
inhalation of infected
droplets
○ PNEUMOCYSTIS JIROVECI
■ Due to glucocorticoid
(Prednisone) use
■ Proliferation of normal flora in
lungs
■ Airborne transmission, human
transmission
○ E. COLI
■ GI epithelium is denuded with
chemotherapy so there will be
altered normal flora and
proliferation of commensal
strains
■ From the gut to port-A-cath site
via hematogenous route
(TRANSLOCATION)
○ PSEUDOMONAS AERUGINOSA
■ Not part of the normal flora of the
body; often seen in the
environment
● Clinical​ ​Manifestations
○ Patients with NHL will usually present with B symptoms:
■ Fever (which can come and go over several days or weeks) without an infection

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 ■ Night sweats
■ Weight loss (at least 10% of body weight over 6 months
○ Ecthyma Gangrenosum
■ A cutaneous lesion seen almost exclusively in markedly neutropenic patients and
patients with AIDS
■ Often caused by P. aeruginosa in bacteremia
■ A bullous lesion surrounded by edema that undergoes central hemorrhage and
necrosis
■ These small or large, painful, reddish, maculopapular lesions have a geographic
margin; they are initially pink, then darkens to purple, and finally becomes black
and necrotic
■ Histopathologic studies indicate that the lesions are due to vascular invasion and
are teeming with bacteria in and around the wall of a small vessel, with little or no
neutrophilic response
■ Similar lesions may occur in aspergillosis and mucormycosis
○ Rituximab - anti-CD20; inactivates B cells leading to a decreased antibody production
○ R-CHOP: decline in absolute neutrophil count (determines severity of neutropenia)
■ Severe neutropenia: <500
● Diagnosis
○ CBC
○ Biopsy
○ Blood culture (Obtain from peripheral site and central line)
● Treatment
○ Debridement of the necrotic tissues with eschar
○ If neutropenia >7 days (prolonged): include Ceftazidime or Cefepime,
Piperacillin-Tazobactam, Imipenem or Meropenem
■ These can cover for Pseudomonas
■ Broad spectrum
■ Bactericidal
■ Must consider first patient’s recent drug use before giving (if used Ceftazidime
only recently then can not use again within 3 months due to possible resistance)
○ Vancomycin
■ not all neutropenic patients
should be given Vancomycin
■ Given as empiric therapy when
there is skin & soft tissue
infections
○ DOC: Carbapenems
■ Ertapenem​: ​has no activity
against Pseudomonas
■ Imipenem​:
● Combined with
cilastatin, ​a
mammalian renal
dipeptidase inhibitor
(as anhydrous
imipenem)
● 1-2 g daily in divided
doses every 6-8 hr (IV
infusion)
● Doses 250 or 500 mg
are infused over 20-30
min
● Doses of 750 mg or 1 g over 40-60 min
● Max: 4 g/day or 50 mg/kg
■ Meropenem​: 0.5-1 g q8 IV injection over 3-5 mins. or infusion over 15-30 mins.
○ Other Alternatives:

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 ■ According to Dra. Bergantin, Tigecycline & Fosfomycin are not used even in the
presence of ESBL [Link] because we are dealing with a neutropenic patient and
we need bactericidal drugs
○ Based on MASSC scoring
■ Only used when there is an inapparent focus of infection
■ Score >21 means that patient is ​low risk ​= step down to ​oral antibiotics
■ However, in the case, there is already an apparent source of infection (the eschar)
= patient is ​high risk​; give I​ V antibiotics
○ For bacteremia:​ at least 10-14 days of IV antibiotics (count from the time the repeat
culture of this patient is negative)
○ Dra. Bergantin: in neutropenic patients with pneumonia, possible to not see any infiltrates
on chest x-ray (because neutrophils initially go to site of inflammation)
○ Presence of mucositis
■ Give antifungal therapy
■ Not confined to the mouth; entire GI tract may be affected

10. Syphilis and Urethritis (NATIVIDAD, JACINTO)

● Differential diagnosis for genital lesion/ulcer:
○ Treponema pallidum​ (syphilis)
○ Chlamydia trachomatis​ (lymphogranuloma venereum)
○ Haemophilus ducreyi​ (chancroid)
○ Klebsiella granulomatis​ (donovanosis)
○ Herpes Simplex Virus​ 2

● Differential diagnosis for genital discharge:

○ Neisseria gonorrhoeae ​(purulent, urethral discharge)
○ Chlamydia trachomatis
○ Mycoplasma genitalium
○ Trichomonas vaginalis
● Clinical manifestations of syphilis:
○ Primary syphilis
■ Typical primary chancre
● Painless papule → indurated, painless ulcer
● Heterosexual men - chancre usually on penis
● MSM - may be found in the anal canal or rectum, mouth or external
genitalia
● Women - cervix and labia
■ Usually solitary (multiple primary lesions are seen in a minority of patients)
■ Regional inguinal lymphadenopathy - within 1 week of lesion onset; firm,
non-suppurative, bilateral, painless
■ Chancre generally heals in 4-6 weeks, lymphadenopathy may persist for months
○ Secondary syphilis
■ Mucocutaneous lesions, generalized non-tender lymphadenopathy
■ Healing chancre still present in 15% of cases (overlapping stages common in
HIV-infected)

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 ■ Constitutional signs and symptoms may accompany or precede secondary
syphilis
■ Skin rash - maculopapular, papular, papulosquamous, pustular; more than one
form
■ Skin Lesions
● Initial - pale red/pink, nonpruritic discrete macules; trunk and extremities
● Macules → papular lesions; widely distributed, frequently palms and soles
● Lues maligna - severe necrotic lesions; commonly seen in HIV-infected
individuals
■ Involvement of hair follicles = patchy alopecia
■ Condyloma lata - enlarged papules producing broad, highly infectious lesions in
warm, moist, intertriginous areas (perianal, vulva, scrotum)
■ Mucous patches - superficial mucosal erosions; painless silver-gray erosion
surrounded by red periphery; commonly oral or genital mucosa
■ Hepatic involvement - common but asymptomatic
■ Renal involvement - immune complex deposition → acute nephrotic syndrome
(proteinuria)
■ Ocular abnormalities - anterior uveitis; considered in patients that fail to respond
to steroid therapy
■ Less common complications - hepatitis, nephropathy, Gi involvement, arthritis
■ Secondary stage resolves spontaneously within 1-6 months
○ Latent
■ Positive serologic test, normal CSF, no clinical manifestations
■ Early latent = limited to the first year of infection; recall when genital lesion first
appeared
■ Late latent = > 1 year duration
■ Pregnant women may still infect fetus in utero (seed bloodstream), may still be
transmitted thru blood transfusion or organ donation
■ Occurrence of spontaneous cure in doubt
○ Neurosyphilis (involvement of the CNS)
■ not a “late manifestation”, is a continuum
■ Asymptomatic neurosyphilis
● absence of neurologic symptoms but shows CSF abnormalities
(mononuclear pleocytosis, inc. protein, CSF reactivity in VDRL)
● Even though asymptomatic, should be treated for neurosyphilis.
■ Symptomatic neurosyphilis - ​major categories = meningeal, meningovascular,
parenchymatous (paresis, tabes); frequent presentation if with HIV co-infection
● Onset
○ Meningeal - <1yr after infection
○ Meningovascular - up to 10yrs after infection
○ General paresis - ~20 years
○ Tabes dorsalis - 25-30 years
● Meningeal - ​headache, nausea, vomiting, neck stiffness, CN palsies,
seizures, changes in mental status, uveitis, iritis, hearing loss; ​“presents
like meningitis”
● Meningovascular ​- meningitis + vasculitis of small, medium, large vessels;
most common presentation = stroke syndrome involving the MCA in a
relatively young adult; ​“presents like stroke” (vs usual stroke of sudden
onset, meningovascular syphilis manifest after subacute encephalitic
prodrome, gradually progressive)
● Parenchymatous ​“presents as paralysis”
○ General PARESIS
■ P​ersonality, ​A​ffect, ​R​eflexes (hyper), ​E​ye (Argyll
Robertson pupils), ​Se ​ nsorium (illusions, delusion,
hallucinations), ​I​ntellect (decreased capacity), ​S​peech
○ Tabes dorsalis - a late manifestation; presents as symptoms and
signs of demyelination; ataxia, foot drop, paresthesias, bladder
disturbances, Argyll Robertson pupils, optic atrophy

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● Other manifestations:
○ Cardiovascular
■ 10-40 yrs after infection
■ Due to endarteritis obliterans of vasa vasorum
■ Aortitis, aortic regurgitation, saccular aneurysm (ascending aorta), coronary ostial
stenosis; linear calcifications of the ascending aorta may be seen in x-ray
○ Late benign​ (​ Gumma)
■ Usually solitary lesions
■ Common sites = skeletal system, skin
○ Congenital
■ Transmission occurs at any stage
■ Fetal damage - does not occur until after the 4th mos AOG (fetal immunologic
competence develops)
■ Adequate tx of the woman before the 16th week of pregnancy = prevent fetal
damage
■ Adequate tx before 3rd tri = treats infected fetus
■ Early manifestations - within the first 2 years of life (often 2-10wks age); infectious,
resemble secondary syphilis
■ Late manifestations - > 2 yrs., non-infectious; include = interstitial keratitis, 8th
nerve deafness, recurrent arthropathy, bilateral knee joint effusions (Clutton’s
joints). gummatous periostitis → destructive lesions of the palate and nasal
septum
■ Classic residual stigmata- Hutchinson’s teeth (centrally notched, widely spaced,
peg-shaped upper central incisor; mulberry molars, saddle nose deformity, saber
shins
■ Neonatal death - pulmonary hemorrhage, secondary bacterial infection, severe
hepatitis.
● Clinical manifestations of urethritis:
○ Urethral discharge, dysuria or both
○ Without inc frequency in urination.
○ Urethritis and urethral syndrome (in women)
■ C, trachomatis, N. gonorrhoeae, HSV
■ Internal dysuria, without urinary urgency( or frequency), pyuria, absence of E coli
and other uropathogens in urine (at >10​2​/ml)
● Diagnosis of syphilis:
○ Non-treponemal tests: for screening & monitoring
■ Rapid Plasma Reagin (RPR)
■ Venereal Disease Research Laboratory (VDRL)
○ Treponemal tests: confirmatory; persists for life
■ Fluorescent treponemal antibody absorption (FTA-ABS)
■ Treponema pallidum​ Particle Agglutination (TPPA) assay
■ Treponema pallidum​ Hemagglutination (TPHA) assay
○ For monitoring response - use Non-treponemal tests (cause titers will decrease after
treatment vs Treponemal test where titers will not disappear with treatment, remains with
patient for life)
○ For Neurosyphilis - use CSF-VDRL
● Diagnosis of urethritis:
○ For N. gonorrhea - Modified Thayer Martin culture: G(-) intracellular diplococci
● Treatment for syphilis:
○ Early latent: benzathine penicillin G 2.4 mIU IM single dose
■ <1 year; asymptomatic but with active bacterial replication
○ Late latent: benzathine penicillin G 2.4 mIU IM weekly for 3 weeks
○ Neurosyphilis: aqueous crystalline penicillin G 18-24 mIU/day, as 3-4 mIU q4 or
continuous infusion, for 10-14 days
○ Allergic to Penicillin
■ Desensitize - gradual increase in dose
■ If developed anaphylaxis after - don’t reattempt
■ Contraindications to desensitization - previous episode of anaphylaxis

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 ■ Alternative: Tetracycline or Doxycycline
● Treatment for urethritis:
○ Ceftriaxone 250 mg IM single dose + azithromycin 500 mg 2 tabs PO single dose
○ Treat sexual partner even without diagnosis

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 ID-BGD

1. HIV with Atypical Pneumonia (MATIBAG, PARANGAT, HERNANDEZ WEDCELL, RAÑOA)

● Must-knows:
○ Most common manifestation of pulmonary disease in HIV: ​pneumonia
○ 3 of the 10 most common AIDS-defining illnesses: ​recurrent bacterial pneumonia​,
tuberculosis​, ​Pneumocystis jiroveci​ pneumonia (PCP)
○ Common causes of atypical pneumonia: ​Mycoplasma pneumoniae​, ​Chlamydophila
pneumoniae​, L​ egionella pneumophila
● Mycobacterium tuberculosis
○ Associated with approximately ⅓ of all AIDS-related deaths worldwide
○ Primary cause of death for 10-15% of HIV patients
○ Active TB is most common in: 25-44 years old, African Americans and Hispanics, living in
NYC and Miami, in developing countries
○ Often develops relatively early in the course of HIV infection and may be an early clinical
sign
○ Does not respect CD4+ T cell count
○ Clinical manifestations:
■ In relatively high CD4 counts: typical pattern of pulmonary reactivation - fever,
cough, dyspnea on exertion, weight loss, night sweats, chest x-ray with cavitary
apical disease of the upper lobes
■ In lower CD4 counts: disseminated disease more common, chest x-ray with
diffuse or lower-lobe bilateral reticulonodular infiltrates consistent with miliary
spread, pleural effusions, hilar and/or mediastinal adenopathy
■ May be present in bone, brain, meninges, GI tract, lymph nodes, viscera
■ Advanced HIV: may have no symptoms
○ Diagnosis:
■ TB culture + Gene Xpert
● Culture will tell you if you are susceptible/resistant to HRZE
● Gene Xpert yields more rapid results
○ Treatment:
■ Do ​NOT​ delay cART therapy regardless of CD4 count EXCEPT in cases of TB
meningitis
■ Treatment regimen for TB is the ​same​ for HIV and non-HIV patients

● Primary prophylaxis:
○ Patient is (+) IGRA or PPD
○ Household contacts of persons with active TB
○ Isoniazid + pyridoxine for 9 months
● Immune Reconstitution Inflammatory Syndrome (IRIS)
○ Associated with initiation of cART and/or anti-TB therapy
○ Most common in patients initiating both treatments at the same time
○ May occur as early as 1 week after initiation of cART therapy
○ Seen more frequently in patients with advanced HIV disease

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● Pneumocystis jiroveci
○ Single most common cause of pneumonia in patients with HIV infection in the US
○ Likely etiologic agent in 25% of cases of pneumonia in HIV patients
○ Approximately 50% of cases of HIV-associated PCP occur in patients who are unaware of
their HIV status
○ High risk: ​CD4+ T cell count <200/uL​, ​experienced a previous bout of PCP
○ Associated symptoms: recurrent fever, night sweats, thrush, unexplained weight loss
○ Clinical presentation:
■ Fever
■ Cough, usually non-productive or productive of only scant amounts of white
sputum
■ Sharp or burning retrosternal chest pain that is worse on inspiration
■ Oral thrush
○ Laboratory findings:
■ Most common chest x-ray finding: normal or a faint ​bilateral interstitial infiltrate
■ Thin-section CT: patchy ground-glass appearance
■ Mild leukocytosis and ​elevated LDH​ are common
■ ABG: ​hypoxemia - decline in PaO2 and increase in arterial-alveolar (a-A)
gradient; ​sign of severe PCP
○ Definitive diagnosis:
■ Demonstration of the organism in samples obtained from induced sputum,
bronchoalveolar lavage, transbronchial biopsy, open-lung biopsy
■ Sputum sample in methenamine-silver stain
○ Extrapulmonary manifestations:
■ Primary infection - polypoid mass involving the external auditory canal
■ Ophthalmic lesions of the choroid
■ Necrotizing vasculitis that resembles Burger’s diseases
■ Bone marrow hypoplasia
■ Intestinal obstruction
○ Treatment:
■ Trimethoprim/sulfamethoxazole
(TMP/SMX) aka co-trimoxazole
(high-dose)
■ 160/800 mg 2 tabs q8 PO for
21 days
■ (14 days for PCP in non-HIV
patients)
■ Adjunct glucocorticoid therapy
for ​severe PCP only​:
● PaO2 <70 mmHg or
arterial-alveolar (a-A)
gradient >35 mmHg
● To reduce
overwhelming
inflammation in the
lungs
■ 21-day regimen is followed by
secondary prophylaxis​:
● Co-trimoxazole
(low-dose): 160/800 mg 1 tab daily
● Also provides protection against ​toxoplasmosis
● Stop prophylaxis if CD4+ T cell count >200/uL for 3 or more mos.
○ Primary prophylaxis:

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 ● Mycobacterium avium intracellulare
○ Most common atypical mycobacterial infection
○ Prior infection with Mtb decreases risk of MAC infection
○ Portals of entry: respiratory and GI tracts
○ Late complication of HIV infection; occurs predominantly in patients with CD4 <50/uL
○ Clinical presentation:
■ Most common presentation: disseminated disease with fever, weight loss, night
sweats
■ At least 85% of patients with MAC infection are mycobacteremic → demonstrated
on bone marrow biopsy
■ Chest x-ray: abnormal in 25% of patients; most common pattern is bilateral,
lower-lobe infiltrate suggestive of miliary spread
■ Endobronchial lesions, abdominal pain, diarrhea, lymphadenopathy
■ Anemia and elevated ALP are common
○ Diagnosis:
■ Culture of blood or involved tissue
■ Finding of 2 consecutive sputum samples positive for MAC is highly suggestive
○ Treatment:
■ Clarithromycin + rifampicin + ethambutol
■ Discontinue therapy for MAC in patients in whom cART induces a sustained
suppression of HIV replication and increase in CD4 count to >100/uL for 3-6
months
○ Primary prophylaxis:

■ For HIV patients with CD4 <50/uL

■ Discontinue in patients in whom cART induces a sustained suppression of HIV
replication and increase in CD4 count to >100/uL for 3-6 months
● More info for the case:
○ Patient has possible chronic HBV due to reactive anti-HBc total
○ Treatment for HIV + HBV: must be active for both viruses
■ Tenofovir + lamivudine
■ Tenofovir + emtricitabine

2. HIV with Opportunistic Infections

● Neurologic (MANUEL APOLLO, MARTINEZ, MAGADIA, MANUEL JOSEPH, MAGSALIN,
JAVINIAR)
○ Cryptococcal Meningitis
■ Cryptococcus ​is the leading cause of meningitis among ​AIDS​ patients

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 ■ Vast majority - due to ​neoformans​, 12% due to ​[Link]
■ Generally occurs in patients with CD4+ T cell count ​<100/uL
■ Presentation​: subacute meningoencephalitis w/ fever, nausea, vomiting, altered
mental status, headache & meningeal signs.
■ CSF profile: normal or slight elevation in WBC or protein levels and decrease in
glucose
■ Prostate gland may serve as reservoir
■ Diagnosis​: India Ink exam, detection of cryptococcal antigen
■ CNS cryptococcoma: Dx thru biopsy
■ Blood culture positive for fungus
■ Prevention: ​ for C ​ . neoformans -​ indicated prior to documented disease
● DOC: ​Fluconazole​ 200 mg/d PO
● Alternative: Itraconazole 200 mg/d PO
■ Treatment:
● IV amphotericin ​B 0.7 mg/kg daily, or ​liposomal amphotericin
4-6 mg/kg daily, with ​flucytosine 25 mg/kg QID for at least 2
weeks.
● Continue amphotericin alone until CSF turns negative
● Followed by: Fluconazole 400 mg/d PO (8 weeks) then
Fluconazole 200 mg/d until CD4+ count increase to >200/uL
○ TB Meningitis
■ ~5% of extrapulmonary cases in the US
■ most often in young children but also develops in adults, especially those
infected with HIV
■ results from:
● hematogenous spread of primary or post-primary pulmonary TB
● rupture of a subependymal tubercle into the subarachnoid space
■ chest radiography reveals evidence of old pulmonary lesions or miliary pattern
■ Presentation: headache and slight mental changes after a prodrome of weeks of
low-grade fever, malaise, anorexia, and irritability
■ tuberculous meningitis may evolve acutely with severe headache, confusion,
lethargy, altered sensorium, and neck rigidity
■ disease evolves over 1–2 weeks
● longer than bacterial meningitis
■ meningeal involvement is pronounced at the base of the brain
■ paresis of cranial nerves (ocular nerves)
■ involvement of cerebral arteries may produce focal ischemia
■ ultimate evolution is toward coma, with hydrocephalus and intracranial
hypertension
■ Lumbar puncture ​is the cornerstone of diagnosis
● examination of cerebrospinal fluid (CSF) reveals a high leukocyte count
(up to 1000/μL) predominance of lymphocytes
● sometimes with a predominance of neutrophils in the early stage
● protein content of 1–8 g/L (100–800 mg/dL)
● low glucose concentration
● NB: any of these three parameters can be within the normal range
■ Culture of CSF ​is diagnostic in up to 80% of cases and remains the gold
standard
■ Real- time automated nucleic acid amplification
● has a sensitivity of up to 80% and is the preferred initial diagnostic option
● Treatment should be initiated immediately upon a positive result
● negative result does not exclude a diagnosis of TB
■ CT/MRI: may show hydrocephalus and abnormal enhancement of basal cisterns
or ependymal
■ If unrecognized, tuberculous meningitis is uniformly fatal
■ responds to chemotherapy
● adjunctive glucocorticoids faster resolution of CSF abnormalities and
elevated CSF pressure
● adjunctive IV dexamethasone significantly enhances chances of survival
among persons >14 years of age
■ Tuberculoma: uncommon manifestation of CNS TB

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 ● presents as one or more space-occupying lesions
● causes seizures and focal signs
■ CT or MRI reveals contrast-enhanced ring lesions
■ biopsy is necessary to establish the diagnosis
○ Toxoplasmosis
■ is generally a late complication of HIV infection
■ occurs in patients with CD4+ T cell counts ​<200/μL
■ Cerebral toxoplasmosis
● reactivation of latent tissue cysts
● 10 times more common in patients with antibodies to the organism than in
patients who are seronegative
■ Patients diagnosed with HIV infection should be screened for IgG antibodies to T.
gondii
● If seronegative = counseled about ways to minimize the risk of primary
infection
● avoiding the consumption of undercooked meat and careful hand washing
after contact with soil or changing the cat litter box
■ Clinical presentation​ of cerebral toxoplasmosis:
● Fever
● Headache
● Focal neurologic deficits (seizure, hemiparesis, or aphasia)
● or confusion, dementia, and lethargy, which can progress to coma d/t
cerebral edema
■ Diagnosis
● MRI = multiple lesions in multiple locations (in some cases = single lesion)
● exhibit inflammation and central necrosis and, as a result, demonstrate
ring enhancement on contrast MRI
● Don't do lumbar puncture since there is a mass, possible uncal herniation
as complication.
● Definitive diagnostic procedure​: BRAIN BIOPSY - reserved for the
patient who failed 2–4 weeks of empiric therapy for toxoplasmosis.
- If seronegative for T. gondii, the likelihood that a mass lesion is
due to toxoplasmosis is <10% = perform a brain biopsy sooner
■ Differential diagnosis of single or multiple enhancing mass lesions in the
HIV-infected patient includes:
● Toxoplasmosis
● primary CNS lymphoma
● TB or fungal or bacterial abscesses (Less common)
■ Standard treatment
● Sulfadiazine and pyrimethamine with leucovorin (4–6 weeks) ​Leucovorin
for folate deficiency
● Local setting: ​TMP-SMX
■ Primary prophylaxis:
● CD4+ T cell counts <100/μL AND IgG antibody to Toxoplasma
● same with prophylaxis used for PCP: 1DS tab TMP/SMX qd PO
■ Secondary prophylaxis/maintenance therapy​:
● for patients with history of prior toxoplasmic encephalitis
● sulfadiazine, pyrimethamine, and leucovorin as long as their CD4+ T cell
counts remain <200 cells/μL
● discontinued if effective cART and CD4+ T cell counts to >200/μL for 6
months
■ Monitor using neuroimaging (if the lesions decreased in size) and if there are
diminishing signs of focal neurological deficit
○ Neurosyphilis (martinez)
● 3 Categories: Meningeal (Meningitis), Meningovascular (Vasculitis),
Parenchymatous (Paresis) syphilis

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○ Primary CNS Lymphoma
■ 20% of lymphoma in HIV patients, no age predilection
■ Most common extranodal type of lymphoma
■ Common in deep white matter of the brain
■ Commonly present at later stage of HIV (poor prognosis)
■ Usually ​positive for EBV​ (unlike Burkitt’s)
■ CD4+ cell count at diagnosis= ​50 cells per microliter
■ CLINICAL MANIFESTATIONS​:
● Focal neurologic deficits (cranial nerve findings, headaches and seizures)
● MRI/CT: app 3 to 5 lesions
■ TREATMENT
● Palliative measures such as radiation therapy for relief
■ PROGNOSIS​ is poor (2-year survival of 19%)
○ HAND ​HIV-associated Neurocognitive Disorders
■ Ranges from asymptomatic neurocognitive Impairment (ANI) to minor
neurocognitive disorder (MND) to clinically severe dementia
■ MOST SEVERE: ​HAD (HIV-associated Dementia) = ​AIDS-defining illness in
~3% of HIV patients, seen in px with CD4+ T cell counts ​>350 cells/uL
● Also referred to as AIDS Dementia complex or HIV encephalopathy
■ Damage to CNS
● Direct result of viral infection of the CNS macrophages or glial cells
● Secondary to the release of neurotoxins and potentially toxic cytokines
IL-1β, TNF⍺, IL6, and TGFβ
■ Individuals with ​E4 allele for apoE = increased risk for AIDS encephalopathy and
peripheral neuropathy
■ Neuro function of an HIV infected individual should be considered normal unless
clinical signs and symptoms suggests otherwise
■ HAD
● Major feature: development of dementia - decline in cognitive ability from
a previous level
● Aphasia and agnosia are UNCOMMON (unlike in Alzheimer’s = “cortical”
dementia)
● HAD = SUBCORTICAL dementia
○ Defects in short term memory and executive function
○ May also have motor and behavioral abnormalities
○ Late stages - bowel and/or bladder incontinence
○ No significant changes in alertness, unlike in somnolence present
in px with dementia due to toxic/metabolic abnormalities
○ CT or MRI = cerebral atrophy
○ No correlation between the presence of HIV in the CSF and the
presence of HIV encephalopathy

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 ○ Elevated levels of macrophage chemoattractant protein (MCP-1),
β2-microglobulin, neopterin, and quinolinic acid = in CSF of
patients with HIV encephalopathy

● DIAGNOSIS: MMSE
● DOC: cART

● Oropharyngeal and Gastrointestinal (MANALANG, MARANAN, MILLARE, HORNEJA,

JIMENEZ, MANICAD)
○ Oral Candidiasis (Manicad)
■ Thrush due to ​Candida ​infection
■ Generally occur in patients with CD4+ T cell count of​ < 300/uL
■ White cheesy exudate; often on an erythematous mucosa in the posterior
Oropharynx
■ Most commonly seen on ​soft palate
■ Early lesions on ​gingival border
■ Diagnosis:
● Direct examination of scraping for pseudohyphal elements
● Culture of NO DIAGNOSTIC VALUE (patients w/ HIV infection may have
(+) throat culture for Candida in absence of thrush)
■ Treatment:
● Oral fluconazole at 100 mg once a day ​for 1-2 weeks is considered the
drug of choice to treat oropharyngeal candidiasis except during pregnancy
(AI)
○ Cryptosporidiosis (___ and Millare)
■ Etiologic agent:​ Cryptosporidium hominis, Cryptosporidium parvum
■ MOT: Consumption of oocysts through direct contact with infected human and
animal feces, drinking of contaminated water, and eating raw shellfish
■ Clinical manifestations:
● Non-inflammatory diarrhea
○ Early stages of HIV infection - self-limited or intermittent diarrheal
illness
○ Severely immunodeficient - severe, life-threatening diarrhea
● Crampy abdominal pain (75%)
● Nausea and vomiting (25%)
● Biliary tract disease
○ Cholecystitis with or without accompanying cholangitis
○ Pancreatitis secondary to papillary stenosis
■ Diagnosis:
● Stool examination
● Biopsy of the small intestine with acid fast staining or direct
immunofluorescence or enzyme immunoassays
○ Characteristic finding: presence of oocysts
■ Treatment:
● Predominantly supportive, and marked improvements have been reported
in the setting of effective cART.
● Nitazoxanide (NTZ) 2000 mg/d: associated with improvement in
symptoms or a decrease in shedding of organisms in about half of
patients.

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 ● Symptomatic treatment of diarrhea with anti-motility agents
● Oral and/or IV rehydration and replacement of electrolyte loss
○ Microsporidiosis - ​Jimenez
■ Small, unicellular, obligate, spore-forming, Gram (+), intracellular parasite
● Resides in the cytoplasm of enteric cells
■ Etiologic agent: ​Enterocytozoon bieneusi
● Clinical manifestations: abdominal pain, malabsorption, diarrhea,
cholangitis
■ Other pathogens (acc. to Chapter 254)
● Encephalitozoon (Septata​ former name​) intestinalis:
○ Causes: fever,diarrhea, sinusitis, cholangitis, bronchitis
● Encephalitozoon hellem
○ Superficial keratoconjunctivitis, sinusitis, respiratory tract disease,
disseminated infection
■ Diagnosis:
● Difficult to detect due to small size
● Definitive findings: visualization of intracellular spores
● Via light microscopy:
○ In tissues: Hematoxylin-Eosin, Giemsa, Gram stain
○ In GI: Chromotrope-based stained (Modified Trichrome/
Chromotrope 2R-based stain) stool samples
● Via electron microscopy: (definitive diagnosis)
○ Specimens: stool, intestinal aspirate, intestinal biopsy
■ DDX: compared to Cryptosporidia, Microsporidiosis has...
● Variety of extraintestinal locations (eye, brain, sinuses, muscle, liver)
● Associated conjunctivitis and hepatitis
■ Treatment:
● Restore immune system with cART (most effective way)
○ Albendazole (400 mg BID): reported to benefit some patients
● Other Treatments: (acc. to Chapter 254)
○ E. hellem: topical Fumagillin suspension for keratoconjunctivitis
○ E. intestinalis: Albendazole for enteric infection
○ Isosporiasis - ​Manalang
■ ETIOLOGIC AGENT: ​Cystoisospora belli​ - C ​ occidian parasite
■ Most commonly found as a cause of diarrhea in patients from tropical and
subtropical regions.
■ Clinical syndromes of Isospora infection are identical to those caused by
cryptosporidia- ​watery diarrhea​.
■ DIAGNOSIS: ​Acid-fast staining of oocysts​ in stool sample
■ TREATMENT: ​Trimethoprim-sulfamethoxazole (TMP/SMX) ​is given QID for 10
days then TID for 3 weeks
■ Relapses are common, a ​thrice-weekly regimen of TMP/SMX appears
adequate to prevent recurrence​.
○ CMV Colitis - Horneja
■ β-herpesvirus, has double-stranded DNA, four species of mRNA, a protein capsid,
and a lipoprotein envelope.
■ Icosahedral symmetry, replicates in cell nucleus & can cause either a lytic and
productive or a latent infection.
■ Viral replication is associated with the production of large intranuclear inclusions
and smaller cytoplasmic inclusions.
■ EPIDEMIOLOGY: ​CMV - worldwide distribution
● CMV may be present in breast milk, saliva, feces, and urine.
● CMV is not readily spread by casual contact but requires
repeated/prolonged intimate exposure for transmission.
● Late adolescence and young adulthood and = CMV is transmitted
sexually, & asymptomatic carriage in semen or cervical secretions is
common.
● Once infected, an individual carries CMV for life.

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 ● Infection usually remains silent. CMV reactivation syndromes develop
more frequently.
■ PATHOLOGY: ​Cytomegalic cells in vivo are 2 - 4 times larger than surrounding
cells, contain 8-10μm intranuclear inclusion that is eccentrically place and
surrounded by clear halo = ​“OWL’S EYE” appearance.
■ CLINICAL MANIFESTATIONS:
● CMV Mononucleosis: ​Heterophile antibody – negative mononucleosis
syndrome = most common clinical manifestation of CMV infection in
immunocompetent hosts beyond neonatal period; most often involves
● CMV Infection in the Immunocompromised Host: ​CMV can cause
retinitis or disseminated disease in patients with advanced HIV infection,
especially when ​CD4+ T cell count fall below 50-100 ​μ​L. ​Early lesions
consist of small, opaque, white areas of granular retinal necrosis that
spread in a centrifugal manner & later accompanied by hemorrhages,
vessel sheathing, and retinal edema. ​Advise patient to have eyes checked
every 3-6 months.
● GI CMV involvement = ​Colitis is the most common clinical manifestation
in organ transplant recipients. Ulcers of the esophagus, stomach, small
intestine, or colon may result in bleeding or perforation.
■ DIAGNOSIS: CMV infection ​= QNAT for CMV by PCR
● CMV colitis ​= Endoscopy / Biopsy
■ TREATMENT: ​Ganciclovir or Valganciclovir for 14-21 day induction course (5
mg/kg IV twice daily for ganciclovir or 900 mg PO twice daily for valganciclovir),
sometimes followed by maintenance therapy (e.g., valganciclovir, 900 mg/d)
● Antiretroviral Therapy (MOA, Adverse Effects, Clinical Use, Availability in the Philippines)
(MORALES CIARA, LIM CHRISZTINE, MORAN, KIMURA, MARASIGAN)

○ Nucleoside Reverse Transcriptase Inhibitors

■ MOA: inhibit the HIV RT by competing with normal nucleoside triphosphates for
incorporation into the growing proviral DNA chain → Viral DNA chain elongation
terminated as absence of 3’-OH group on sugar moiety prevents addition of
another nucleotide → Viral replication ceases

Dose in
Drug Combinatio Adverse Events
n

200 mg q8h
Zidovudine Nail pigmentation, Hypertrichosis, Neutropenia, Anemia
or 300 mg
(Retrovir) N.B Prevention of maternal-fetal HIV transmission
bid

Lamivudine 150 mg bid Paronychia, Flare of hepatitis in HBV-coinfected patients who

(Epivir) 300 mg qd discontinue the drug

Emtricitabine
200 mg qd Skin discoloration
(Emtriva)

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 Hypersensitivity reaction in HLA-B5 701+ individuals (can be
Abacavir
300 mg bid fatal); fever, rash, nausea, vomiting, malaise or fatigue and loss
(Ziagen)
of appetite

Tenofovir Renal failure and electrolyte imbalance, osteomalacia, flare of

300 mg qd
(Viread) hepatitis in HBV-coinfected patients who discontinue the drug

○ Difference between NRTI and NNRTI:

■ NRTI needs phosphorylation to be active (NNRTI: the parent molecules are the
active moieties so they are immediately active once they enter the cell)
■ NRTI active against both HIV 1 and 2 (NNRTI only active against HIV-1)
■ Minimal drug interaction occur (A major issue with NNRTIs is the potential for drug
interactions)
■ NRTI less potent than NNRTIs
○ Non-nucleoside Reverse Transcriptase Inhibitors
■ Bind to a site on reverse transcriptase different from the binding site of NRTIs.
Non-nucleoside drugs do not require phosphorylation to be active and do not
compete with nucleoside triphosphates. There is no cross-resistance with NRTIs.
■ Only Nevirapine & Efavirenz are available in the Philippines
■ Nevirapine
● Good oral bioavailability with half life of more than 24h
● Penetrates most tissues including CNS
● Used in combination regimens and effective in preventing HIV vertical
transmission when given as single doses to mothers at the onset of labor
and to the neonate
● May have hypersensitivity reaction: rash, SJS-TEN
● Blood levels
○ increased by cimetidine and macrolide antibiotics
○ Decreased by enzyme inducers (rifampicin)
■ Efavirenz
● Only given once daily (long half life)
● Bioavailability is increased by fatty food
● Many drug interactions
● Toxicity: CNS dysfunction, sin rash, and elevations of plasma cholesterol
● Not used in pregnancy (specially first trimester) because of fetal
abnormalities
■ Delavirdine
● Major problem: many drug interactions
● Toxicity: rash, teratogenic (not used in pregnancy)
● Blood levels
○ Increased by azole antifungals and macrolide antibiotics
○ decreased by antacids, phenytoin, rifampicin, and nelfinavir
■ Etravirine
● NEWEST NNRTI approved for HIV patients
● May be effective against HIV strains resistant to other drugs in the group
● Adverse effect: rash, nausea, diarrhea, and elevations in serum
cholesterol, triglyceride, and transaminase
■ Rilpivirine
○ Protease Inhibitors
■ Combination with NRTIs: suppress HIV replication to <50 copies/ml
■ ALWAYS used in combination; NEVER monotherapy due to increased risk of
resistance
■ Side effects: usually ENDOCRINOLOGIC
■ Ritonavir (only protease inhibitor available in the Philippines)
● Philippines: Ritonavir-Lopinavir
● Poorly tolerated at full doses
● low doses: 100-200 mg once/2x a day
● Side effects: Hyperlipidemia, Fat redistribution, Circumoral Paresthesia

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 ■ Atazanavir
● Azapeptide inhibitor of HIV-1 protease
● Advantages:
○ Total cholesterol and TAGs do not increase as much than other
protease inhibitors
○ Once-daily schedule
● Side effects: increased serum bilirubin, renal stones, prolongation of PR
interval in ECG
● Requires acidic pH for absorption (that’s why PPI use is contraindicated)
■ Darunavir
● Nonpeptidic HIV protease inhibitor
● Co-administered with Ritonavir
● Side Effects: Skin rash, GI Intolerance, Headache
○ Integrase Inhibitors
■ Integrase is a viral enzyme that inserts the viral genome into the ​DNA of the host
cell.
■ MOA: act by blocking the action of the HIV integrase enzyme and thus preventing
integration of the HIV provirus into the host cell genome.
■ most potent and safest of the antiretroviral drugs and frequently part of initial
combination regimens

Drug MOA Dose in Combination Adverse Effects

Nausea, headache,
Acts by interfering with the binding diarrhea, CPK
Raltegravir
of the preintegration complex to 400 mg bid elevation, muscle
host DNA weakness,
rhabdomyolysis

Inhibits integrase thus preventing

the integration of HIV-1 DNA into
host genomic DNA, blocking the
Diarrhea, nausea,
Elvitegravir formation of the HIV-1 provirus and
1 tablet daily upper respiratory
propagation of the viral infection
infections, headache
I​nhibits CYP3A

50 mg daily for
treatment-naïve patient
Inhibits HIV integrase by binding to Insomnia, headache,
50 mg twice daily for
Dolutegravir the active site and blocking the hypersensitivity
treatment- experienced
strand transfer step of retroviral reactions,
patients or those also
DNA integration in the host cell. hepatotoxicity
receiving efavirenz or
rifampin

○ Entry Inhibitors
■ Maraviroc
● CCR5 antagonist that interferes with HIV binding at the stage of
co-receptor engagement.
● Indication: Used in combination with other antiretroviral agents in
adults infected with ONLY CCR5-tropic HIV 1
● Toxicity: Hepatotoxicity, dizziness due to postural hypotension
nasopharyngitis, fever, cough, rash, abdominal pain,
musculoskeletal symptoms
● Add:Co-receptor tropism assay, ensures that the potential patient
only has R5 virus.

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 ● Dose: 300 mg twice daily in combination with nucleoside analogs,
Tipranavir, Ritonavir, Enfuvirtide, Nevirapine; 600 mg twice daily
in the presence of CYP3A inducers (Efavirenz).
Treatment Hubs in the Philippines

NCR VISAYAS
● San Lazaro Hospital ● Western Visayas Medical Center (Iloilo
● Philippine General Hospital City)
● Research Institute for Tropical ● Corazon Locsin Montelibano Memorial
Medicine Regional Hospital (Bacolod)
● Makati Medical Center ● Vicente Sotto Sr. Memorial Medical
Center (Cebu)

LUZON MINDANAO
● Ilocos Training and Regional Medical ● Zamboanga City Medical Center
Center (La Union) ● Davao Medical Center
● Cagayan Valley Medical Center
(Tuguegarao)
● Baguio General Hospital and Medical
Center
● Jose B. Lingad Memorial Medical Center
(Pampanga)
● Bicol Regional Training and Teaching
Hospital (Legazpi City)
RH-ICD TOPICS

1. Osteoarthritis and Osteoporosis (MINA, MANUEL KATHERINE)

● Osteoarthritis
○ The most common type of arthritis
○ The most common cause of chronic knee pain in persons >45 years old
○ Commonly affected joints:
■ Cervical
■ Lumbosacral spine
■ Hip
■ Knee
■ 1st MTP
■ DIP, PIP
■ Base of the thumb
○ Definition: A concert of changes leading to joint failure, ​namely hyaline articular cartilage
loss accompanied by: an increasing thickness and sclerosis of the subchondral bony
plate, ​osteophyte ​formation, stretching of the articular capsule, mild synovitis, and
weakness of the muscles bridging the joint.

○ Clinical Manifestations

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 ■ Pain is ​activity related​, during or just after joint use then gradually resolves
■ Early in disease: episodic; triggered by a day or two overactive use of joint
■ On progression, becomes more continuous and even more bothersome at night.
With brief morning stiffness (<30 minutes).
■ Knees: buckling, catching, or locking. Pain comes from knee flexion (emanates
from: patellofemoral compartment of the knee)
■ Bursitis occurs commonly around the knees and hips. Anserine bursitis, especially
is a common cause of knee pain
■ Signs of Inflammatory arthritis - even though OA is classified as non-inflammatory,
these signs of
inflammation are
secondary to the
pathologic events from
articular cartilage loss.
○ Diagnosis
■ Physical Examination
● Tenderness over
the joint line or
outside of it
● Prominent
nocturnal pain
● Loss of internal
rotation on
passive
movement, in hip
pain
■ Blood tests not usually
warranted unless signs of
inflammatory arthritis are
suspected
■ Synovial Fluid
Examination
● WBC count
>1000/ul -
inflammatory

■ Radiographic findings correlate poorly with presence and severity of pain

○ Treatment
■ Treatment goals: alleviate pain and minimize loss of physical function (from the
consequences of inflammation, weakness of the structures around the joint and
joint instability)
■ Non-Pharmacotherapy:
● Lessen focal load
○ Avoid activities that overload the joint
○ Improve strength and conditioning of muscles
○ Unloading joint by redistributing load.
● The simplest effect treatment: avoid activities that precipitate pain
● Weight loss
● For hand joint, splinting by limiting motion
● Using a cane, crutches or walkers to reduce load on weight bearing joints
● Exercise​: mostly aerobic (low impact, such as water aerobics) and
resistance training to help strengthen the joints.
● Correction of malalignment [varus (bow-legged) and valgus (knock-knees)
deformity types]: Fitted brace, orthotics footwear, Neoprene sleeves
■ Pharmacotherapy:
● NSAIDS and COX-2 Inhibitors
○ Paracetamol initial analgesic of choice. DoseL 1g / 3x a day
● Table 394-1, summarizes pharmacologic treatment for osteoarthritis

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● Osteoporosis
○ Definition: a condition characterized
by a decrease in bone strength,
prevalent in postmenopausal women.
The loss of bone tissue is associated
with deterioration in skeletal
microarchitecture
○ WHO Definition of Osteoporosis: a
bone density that falls 2.5 SD below
the mean for young healthy adults of
the same sex. Also referred to as
T-score: -2.5 (in the lumbar spine,
femoral neck, or hip)​.
○ Chief Clinical manifestation: Increase risk for fractures (vertebral and hip)
○ Pathophysiology
■ Deformities in bone remodeling → Increased bone loss
■ Low peak bone bass:
● Inadequate calcium intake (along with other nutritional factors) →
secondary hyperparathyroidism and increase rate of bone remodeling →
Increased risk of osteoporosis
■ Vitamin D deficiency
● Rickets in children; Osteomalacia in adults
■ Estrogen deficiency
● Activation of new bone remodeling sites
● Exaggeration of the imbalance between bone formation and resorption
■ Prolonged inactivity
■ Chronic disease (refer to Table 425-1, if you’d want to even bother to know them).
■ Medications
● Glucocorticoids
○ Risk of fracture increases within 3 months; hence, it is
important to evaluate status of skeleton when receiving
long-term therapy (>3 months)
○ Prevention: using the lowest dose, topical and inhaled
preparations are preferred when appropriate. Adequate
calcium and vitamin D intake.
○ Treatment: Bisphosphonates, Teriparatide
● Excessive doses of thyroid hormone
● Patients undergoing transplantation
● Aromatase Inhibitors
● Some implicated drugs: SSRI, PPI, thiazolidinediones
■ Cigarette smoking
○ Bone Density Imaging

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 ■ Techniques: Dual-energy X-ray Absorptiometry (DXA), Single energy x-ray
absorptiometry (SXA), quantitative CT, and ultrasound
■ When to measure BMD?

● A height loss of >2.5-3.8 cm (>1-1.5 in) is an indication for VFA (vertebral

fracture assessment) by DXA or radiography, even in the absence of
specific risk factors.

○ Diagnosis
■ Routine Laboratory Evaluation: CBC, serum and 24-hr urine calcium, renal and
hepatic function tests, and a 25(OH)D level → helpful for the identification of
secondary causes of low bone mass.
● Secondary causes like: Cushing’s Syndrome, Hyperthyroid,
Malabsorption, Celiac Disease, etc.
● ↑ Serum Ca = Hyperparathyroidism or malignancy
○ ↑PTH = HyperPTH; ↓ PTH= malignancy
● ↓ Serum Ca = Malnutrition or osteomalacia
● ↓ Urine Ca (<50 mg/24 hr) = osteomalacia, malnutrition, malabsorption
● ↑ Urine Ca = Hypercalciuria
○ Renal calcium leak (males with osteoporosis)
○ Absorptive Hypercalciuria ( ↑ 1,25(OH)2D in granulomatous
disease)
○ Malignancies (e.g. Paget’s disease)
● TSH levels to evaluate Hyperthyroidism
● Myeloma can masquerade as generalised osteoporosis
○ Myeloma in radiography presents with “punched-out lesions”
○ Bone pain
○ Serum and urine electrophoresis and or Serum light chains are
required to exclude the diagnosis, also a bone marrow biopsy.
■ Bone Biopsy: Tetracycline labelling of the skeleton to determine rate of
remodeling.
■ Biochemical Markers, those of which related to bone formation or resorption,
testing out the overall state of bone remodeling in a single point in time. The
primary use of markers is to monitor the response to treatment.
● CTX (C-telopeptide) - preferred marker for the measurement of bone
resorption before initiating therapy, and 3-6 months after starting therapy
provide an earlier estimate of patient response.
● Bone turnover markers for monitoring osteoanabolic agents (e.g
teriparatide).
○ Treatment
■ Management of patients with fractures

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 ● Hip fractures - surgical repair, depending on extent and location of
disease the following may be done: open reduction, internal fixation with
pins and plates , hemiarthroplasties, and total arthroplasties. These
regiments are followed by intense rehabilitation.
● Long bone fractures (e.g. wrist) requires external or internal fixation.
● Other fractures (vertebral, rib, pelvic) managed by supportive care
● Symptomatic fracture: treat with analgesics including, NSAIDs, sometimes
a narcotic agent maybe used (codeine or oxycodone).
● Percutaneous injection of artificial cement (polymethylmethacrylate) into
vertebral body may provide pain relief for acute or subacute vertebral
fracture.
● Bed rest.
● Severe pain usually resolves in 6-10 weeks, any longer than that might
suggest multiple myeloma or metastatic disease.
○ Still requires analgesics and/or narcotics
○ Rest and exercises are beneficial
○ Heat treatment
○ US and transcutaneous nerve stimulation
● Risk factor reduction through the FRAX tool. In the US, it is cost-effective
to treat if 10 year major fracture risk is >/=20%, and hip fracture risk
>/=3%.
■ Nutritional requirements for Calcium

■ Exercise, especially weight bearing ones help prevent bone loss. A walking
program, and other light exercises such as dancing, racquet sports, skiing or the
use of gym equipment is also recommended.
■ Nonpharmacologic approaches
● Protective pads ​could ​help with hip fractures
● Kyphoplasty and vertebroplasty for vertebral fractures
■ Treatment monitoring
● BMD monitoring: changes must exceed ~4% in the spine, ^% in the hip
are considered significant, and would require a modification treatment.
● Biochemical markers, a change of 30-40% lower than the baseline is
needed for it to be significant. A positive change marks good treatment.
■ Pharmacological Therapy (Table taken from Katzung)
● Estrogen
○ Esterified estrogens 0.3 mg/d
○ Conjugated equine estrogen 0.625 mg/d
○ Ethinyl estradiol 5 ug/d
● Progestins
○ Daily progestins at least 12 days per month, prescribed together
with estrogens to reduce the risk of uterine cancer.
○ Medroxyprogesterone acetate and norethindrone acetate.
● SERMS
○ Raloxifene
○ Tamoxifen

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2. Gouty Arthritis (LIM CARISSA, NAVARRO)
● Affects middle aged to elderly men and postmenopausal women
● Results from an increased body pool of urate with hyperuricemia
● Characterized by episodic acute or chronic arthritis caused by deposition of monosodium urate
(MSU) crystals in joints and connective tissue tophi
● Risk of deposition in kidney interstitium or uric acid nephrolithiasis
● Clinical Manifestations:
○ Acute arthritis is the most common early clinical manifestation of gout → initially one joint
but polyarticular gout can occur in subsequent episodes
■ Metatarsophalangeal joint of the first toe is often involved
■ Tarsal joints, ankles, and knees are affected commonly
■ Elderly or advanced disease → finger joints may be involved
○ Inflamed Heberden's or Bouchard’s nodes may be the first manifestation of gouty arthritis
○ First episode of acute gouty arthritis frequently begins at night with dramatic joint pain and
swelling
■ Joints become rapidly warm, red, or tender with a clinical appearance that often
mimics that of cellulitis
■ Early attacks subside within 3-10 days
■ Most: intervals of varying length with no residual symptoms until the next episode
■ What may precipitate an acute attack: dietary excess, trauma, surgery, excessive
ethanol ingestion, hypouricemic therapy, and serious medical illness (e.g. MI and
stroke)
○ After many acute mono or oligoarticular attacks, some may present with chronic
non-symmetric synovitis (maybe confused with rheumatoid arthritis)
■ Less common: present only with chronic gouty arthritis
■ Rare: manifest as periarticular tophaceous deposits in the absence of synovitis
○ Women: 5-20% of all patients with gout
■ Postmenopausal and elderly, have osteoarthritis and arterial hypertension that
causes mild renal insufficiency, and are usually receiving diuretics
● Diagnosis

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 ○ Presumptive diagnosis ideally confirmed by needle aspiration of acutely or chronically
involved joints or tophaceous deposits
○ During acute gouty attacks, needle shaped MSU crystals are typically seen both
intracellularly or extracellularly
■ Brightly birefringent with negative elongation
○ Synovial fluid leukocyte counts are elevated from 2000 to 6000/𝞵L → effusions appear
cloudy
■ Large amount of crystals occasionally produce a thick pasty or chalky joint fluid
■ Bacterial infection can also coexist with urate crystals in synovial fluid
○ Suspicion of septic arthritis → culture joint fluid
○ MSU crystals can often be demonstrated in the first metatarsophalangeal joint and in
knees not acutely involved in gout → Arthrocentesis to establish diagnosis of gout
between attacks
○ Serum uric acid levels: normal or low during an acute attack
■ inflammatory cytokines can be uricosuric and initiation of hypouricemic therapy
can initiate attacks → Limits usefulness in diagnosis of gout
■ Always elevated at some time and is important to follow the course of
hypouricemic therapy
■ 24 hour collection for uric acid can be useful in assessing the risk of stone or
deciding when it may be appropriate to use uricosuric therapy
● >800mg or uric acid per 24 hours on a regular diet: consider causes of
overproduction of purine
○ Urinalysis, serum creatinine, hemoglobin, WBC count, liver function tests, and serum lipids
→ for possible sequelae of gout and other diseases; give baseline levels because of
possible adverse effects of gout treatment
○ Radiographic features
■ Crystal changes, well-defined erosions with sclerotic margins (often with
overhanging bony ridges) and soft tissue masses → characteristic for advanced
tophaceous gout
■ UTZ: double contour sign overlying articular cartilage
■ Dual energy CT: establish presence of urate crystals
● Treatment
○ Acute Gouty Arthritis
■ Mainstay during acute attack: giving anti-inflammatory drugs like NSAIDs,
colchicine, or glucocorticoids
● NSAID: without complaining comorbid conditions
● Colchicine and NSAIDs may be poorly tolerated in elderly; those with
renal insufficiency; and GI disorders
■ Ice pack applications to rest of joints may be helpful
■ Colchicine given orally is a traditional and effective treatment if used early in an
attack
● One 0.6mg tablet every 8 hours with subsequent tapering or 1.2mg
followed by 0.6mg in 1 hour with subsequent day dosing depending on
response
● Temporarily discontinue at first sign of loose stools and treat the diarrhea
■ NSAIDs in full inflammatory doses are effective in ~90% of patients and resolution
of signs and symptoms occurs in 5-8 days
● Most effective: short half life
● Indomethacin 25-50 mg tid; Naproxen 50-0 mg bid; Ibuprofen 800 mg tid;
Diclofenac 50 mg tid; and celecoxib 800 mg followed by 400 mg 12 hours
later, then 400 mg bid
■ Glucocorticoids given IM or orally can be effective in polyarticular gout
● Prednisone 30-50mg/d as initial dose and gradually tapered with the
resolution of attack
● Single or few involved joints: intraarticular triamcinolone acetonide 20-40
mg methylprednisolone 25-50mg → effective and well tolerated
○ Hyperuricemic therapy

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 ■ Ultimate control of gout: correction of hyperuricemia → normalize to <300-360
umol/L (5.0-6.0 mg/dL) to prevent recurrent gout attacks and eliminate
tophaceous deposits
■ Consider when the hyperuricemia cannot be corrected by simple means (e.g.
control body weight, low purine diet, increase in fluid intake, limitation of ethanol
use, decreased use of fructose containing foods and beverages, and avoidance of
diuretics)
■ Initiate in any patient who already has tophi or chronic gouty arthritis
■ Uricosuric agents like probenecid can be used in patients with good renal function
who underexcrete uric acid with <600mg in 24 hour urine sample
● Urine volume should be maintained by ingestion of 1500 mL of water
everyday
● Start probenecid at dose of 250 mg twice daily and increase gradually as
needed up to 3g per day to achieve and maintain a serum uric acid level
of less than 6 mg/dL
○ Generally not effective in patient with serum creatinine levels
>177 umol/L (2 mg/dL) → give allopurinol or benzbromarone
○ Benzbromarone: effective in patients with chronic kidney disease
■ Allopurinol (xanthine oxidase inhibitor): most commonly used hypouricemic agent
and is the best drug to lower serum urate in overproducers, urate stone formers,
and patients with renal disease
● Single morning doe usually 100 mg initially and increasing up to 800 mg if
needed
● In chronic kidney disease: initial allopurinol dose should be lower and
adjusted depending on the serum creatinine concentration
○ Creatinine clearance of 10 mL/min: 100 mg every other day
○ Doses can be increased gradually to reach the target urate level
of less than 6 mg/dL
● Allopurinol toxicity can be seen in patients who use thiazide diuretics, in
patients allergic to penicillin and ampicillin, and in Asians expressing
HLA-B*5801
● Most serious SE: life threatening toxic epidermal necrolysis, systemic
vasculitis, bone marrow suppression, granulomatous hepatitis, and renal
failure
● If patients have mild cutaneous reaction: use another uricosuric agent,
undergo attempt at desensitization, or take febuxostat (40-80mg once a
day and does not require dose adjustment in mild to moderate disease)
■ Pegloticase (pegylated uricase): for patients who do not tolerate or fail full doses
of other treatments (IV usually at 8 mg every 2 weeks)
■ Urate lowering drugs are generally not initiated during acute attacks but after
patient is stable and low dose colchicine has been initiated to decrease the risk of
flares that often occur during urate lowering
● Colchicine anti-inflammatory prophylaxis in doses of 0.6 mg one to two
times daily should be given along with hypouricemic therapy until patient
is normouricemic and without gouty attacks for 6 months or as long as
tophi are present
● Do not use colchicine in patients undergoing dialysis
● Low dose colchicine in patients with renal disease or with P glycoprotein
of CYP3A4 inhibitors (e.g. clarithromycin) that can increase the toxicity

3. Rheumatoid Arthritis (LAZATIN, MUÑOZ, LO)

● Clinical Manifestations:
○ Symmetrical polyarthritis, chronic (>6 weeks)
○ Chronic hand deformities
○ Subluxation
○ Z deformity (common)
○ Boutonniere (common)
○ Swan neck (very common)

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 ○ Ulnar deviation (very common)
○ Muscle atrophy X-ray
○ Bony erosion (juxtaarticular osteopenia)
○ Symmetrical Rheumatoid factor
○ Against Fc receptor
○ Prognostic factor
○ Not specic Anti-CCP
○ Against deaminated peptides
○ Initial evaluation of unexplained joint inammation Criteria
○ 7 categories (4 of 7)
○ Criteria 1-4: >6 weeks 2010 Criteria
○ More than or equal to 6
● Pathologic Hallmark:
○ Synovial inflammation and proliferation
○ Focal bone erosions
○ Thinning of articular cartilage
● Most common systemic & Extraarticular Features:
○ Constitutional signs and symptoms
○ Subcutaneous nodules: firm, ​nontender
○ Secondary Sjogren's Syndrome: keratoconjunctivitis sicca (dry eyes) + xerostomia (dry
mouth)
○ Pulmonary- most common: pleuritis
○ Cardiac - most frequent site: pericardium, most common valvular abnormality: mitral
regurgitation
○ Vasculitis- Long standing active disease, Positive high titer RF, ​Hypo​complementemia
○ Hematologic- most common: normochromic normocytic anemia, uncommon: leukopenia
○ Felty’s syndrome triad: neutropenia, splenomegaly, nodular RA
○ Lymphoma- most common: Diffuse large B cell lymphoma
● Associated Conditions:
○ Cardiovascular Disease: most common cause of death
○ Osteoporosis due to the chronic inflammation with sustained ​osteoclastic​ activity
○ Hypoandrogenism
● Environmental Factors: cigarette smoking, EBV
● Diagnosis
○ Rheumatoid factor
■ Not specific
■ Should be within the context of clinical manifestations
■ Diagnostic and prognostic factor
■ Antibody against Fc receptor (Ab vs Ab)
■ High titer, more severe
■ Can be detected in normal individuals
○ Anti-cyclic citrullinated Peptides (Anti-CCP)
■ Antibody against deaminated peptides
■ Initial evaluation of unexplained joint inflammation
■ Present in more aggressive disease

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 ■ Higher specificity than RF but same sensitivity
○ Criteria
■ You need 6 points to diagnose RA early for early treatment!
■ The new criteria focuses on identifying patients with early disease who may
benefit from early DMARD therapy or entry into clinical trials of promising new
agents that halt the development of persistent, disabling erosive disease
○ Synovial Fluid Analysis: Neutrophil- overwhelming cell type in RA
■ WBC count= 5,000-50,000 (Osteoarthritis= <2,000)
○ Joint Imaging: Plain X-ray- most common imaging modality
■ Periarticular Osteopenia- initial radiographic finding
■ Subchondral erosions- wrist and hand (MCPs and PIPS), feet (MTPs)
● Treatment:
○ NSAIDS
○ Glucocorticoids
○ DMARDs
■ Methotrexate (DMARD of choice)
■ Once a week
■ Folic acid
■ No alcohol
○ Biologics
■ Individualised

Rheumatoid Arthritis Psoriatic Arthritis Reactive Arthritis Ankylosing Spondylitis

More
Asymmetric
More symmetrical polyarthritis asymmetrical;
Oligoarthritis
25%symmetrical

Boutonniere and swan neck

Bamboo spine deformity
deformity GUT and GIT
Pencil in cup sign (bridging
(+) RF, anti-CCP infections
syndesmophytes
No DIP involvement

Skin and nail TRIAD: arthritis,

changes (pitting), conjunctivitis, HLA-B27
dactylitis urethritis

Inc ESR Inc ESR Inc ESR

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 More spine
involvement
No axial involvement; No sacroiliitis
May have Mainly spine involvement
asymmetrical
sacroiliitis

4. Psoriatic Arthritis (JOHNSON, MASCARIÑAS)

● Inflammatory musculoskeletal disease
● Autoimmune and autoinflammatory features
● Characteristically occurring in patients with psoriasis
● Clinical Manifestations
○ Usually, psoriasis precedes joint disease
○ Frequency in men and women almost equal
○ Typically begins in the fourth or fifth decade, average age of 37 years
○ Wright and Moll Classification Scheme
■ Arthritis of the DIP joints
■ Asymmetric Oligoarthritis
■ Symmetric polyarthritis similar to RA
■ Axial Involvement (spine and sacroiliac joints)
■ Arthritis Mutilans - highly destructive
● Widespread shortening of digits (“telescoping”)
○ Simpler scheme: oligoarthritis, polyarthritis, axial arthritis
○ Nail changes almost always present
■ Pitting
■ Horizontal ridging
■ Onycholysis
■ Yellowish discoloration of the nail margins
■ Dystrophic hyperkeratosis
■ Combination of all
○ Pustular psoriasis associated with more severe arthritis
○ Hallmark features: Dactylitis and Enthesitis
○ Characteristic: Shortening of digits because of underlying osteolysis
○ Tendency for fibrous and bony ankylosis of small joints
○ Extraarticular involvement
■ Eye: conjunctivitis, uveitis (bilateral, chronic, posterior)
■ Aortic Valve insufficiency
○ Psoriasis and arthropathy in HIV
■ Severe
■ Severe enthesopathy, dactylitis and rapidly progressive joint destruction
■ Axial involvement is rare
■ Responds to antiretroviral therapy
● Diagnosis
○ No laboratory tests diagnostic of Psoriatic arthritis
■ ESR and CRP : elevated
■ Uric acid: elevated (extensive psoriasis)
■ HLA B27 found in 50-70% with axial involvement but only 20% in peripheral joint
involvement
○ Radiographic features
■ Peripheral and axial arthropathies
● DIP involvement with classic “pencil in cup” deformity
● Marginal erosions with adjacent bony proliferation (“whiskering”)
● Small joint ankylosis
● Osteolysis of phalangeal and metacarpal bone with telescoping of digits
● Periostitis and proliferative new bone at sites of enthesitis
■ Axial PsA
● Asymmetric sacroiliitis
● Less zygapophyseal joint arthritis

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 ● Bulky “comma-shaped” syndesmophytes fewer and less symmetric than
in AS
● Fluffy hyperperiostosis on anterior vertebral bodies
● Severe cervical spine involvement with tendency of atlantoaxial
subluxation, sparing of thoracolumbar spine
● Paravertebral ossification
○ Ultrasound and MRI - Enthesitis and tendon sheath effusions
○ Classification Criteria for PsA [CASPAR] - useful for Early diagnosis *Table 384-2*
■ Examination of Psoriasiform lesions in the scalp, ears, umbilicus and gluteal folds
in addition to more accessible sites
■ History of trauma to an affected joint preceding the onset of arthritis is said to
occur more frequently in PsA perhaps reflecting the Koebner phenomenon in
which psoriatic skin lesions arise at sites of skin trauma.
● Treatment
○ No steroids -may produce rebound flare of psoriatic lesions
○ NSAIDs
○ DMARDs -
■ Methotrexate (once a week, add folic acid)
■ Sulfasalazine - for peripheral involvement and not spine and sacroiliac
involvement
○ Anti TNF-a
■ Etanercept, Infliximab, Adalimumab and Golimumab
■ Clinical response
■ Delay in disease progression
■ Trigger exacerbation or de novo appearance of psoriasis, typically the
palmoplantar pustular type
○ Ustekinumab
■ Monoclonal antibody to IL23/IL12p40
○ Other newer drugs
■ Secukinumab and Brodalumab: anti-IL-17
■ Apremilast: Oral phosphodiesterase 4 inhibitor
■ Tofacitinib: oral Jak inhibitor
■ Cyclosporine, retinoic acid derivatives
■ Psoralens plus ultraviolet A light (PUVA)
○ All treatment require careful monitoring
○ Immunosuppressive therapy may be used cautiously in HIV-associated PsA if the infection
is well controlled.

5. Systemic Lupus Erythematosus (LEYNES, HERNANDEZ CHRISTINE, MATIBAG)

● Clinical Manifestations
○ Musculoskeletal Manifestations
■ Intermittent polyarthritis
● Varying from mild to disabling
● Characterized by soft tissue swelling and tenderness in joints and/or
tendons, most commonly in hands, wrists, and knees.
■ Joint deformities
● Develop in only 10% (hands and feet)
● Erosions on joint x-rays are rare but can be identified by ultrasound.
■ “Rhupus”
● Rheumatoid-like arthritis with erosions and fulfill criteria for both RA and
SLE
■ Ischemic necrosis of the bone
● Considered if there are no other manifestations of active SLE
● Prevalence is increased in SLE, especially in patients treated with
systemic glucocorticoids
● Pain that persists in a single joint, such as knee, shoulder, or hip
■ Myositis

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 ● Present along with muscle weakness, elevated creatine kinase levels,
positive MRI scan, and muscle necrosis and inflammation on biopsy
● Most patients have myalgia without frank myositis
○ Cutaneous Manifestations
■ Lupus dermatitis can be classified as acute, subacute or chronic.
■ Acute SLE rash
● photosensitive, slightly raised erythema, occasionally scaly, on the face
(particularly the cheeks and nose-the “butterfly” rash), ears, chin, V region
of the neck and chest, upper back, and, extensor surfaces of the arms
● Worsening of this rash often accompanies flare of systemic disease
■ Subacute cutaneous lupus erythematosus (SCLE)
● Scaly red patches similar to psoriasis, or circular flat red-rimmed lesions
● Patients with these manifestations are exquisitely photosensitive; most
have antibodies to Ro (SS-A)
■ Discoid lupus erythematosus (DLE)
● Most common chronic dermatitis in lupus
● 20% of patients with SLE have DLE
● Lesions are roughly circular with slightly raised, scaly hyperpigmented
erythematous rims and depigmented, atrophic centers in which all dermal
appendages are permanently destroyed
● Lesions can be disfiguring, particularly on the face and scalp
● Tx: Topical or locally injected glucocorticoids; Systemic antimalarials
■ Oral or nasal ulcers: resemble aphthous ulcers
■ Other rashes include: recurring urticaria, lichen planus-like dermatitis, bullae, and
panniculitis (“lupus profundus”
○ Renal Manifestations
■ Nephritis
● Most serious manifestation of SLE
● One of the leading causes of mortality in the first decade of disease
● Usually asymptomatic
● Dx: Urinalysis, Renal Biopsy
● Patients with dangerous proliferative forms of glomerular damage (ISN III
and IV) present with hematuria and proteinuria (>500 mg/24 h); develop
nephrotic syndrome and hypertension.
● * For most people with lupus nephritis, accelerated atherosclerosis
becomes important after several of disease; attention must be given to
control of systemic inflammation, blood pressure, hyperlipidemia, and
hyperglycemia.
■ End-stage Renal Disease
● Develop within 2 years of diagnosis if diffuse proliferative
glomerulonephritis (DPGN) is inadequately treated
● Aggressive immunosuppression is indicated (usually ​systemic
glucocorticoids+cytotoxic drug​), unless damage is irreversible.
○ Nervous System Manifestations
■ * ​First, ask whether the symptoms result from SLE or another condition (such as
infection in immunosuppressed individuals or side effects of therapies).
■ * If sx are r/t SLE, determine whether they are caused by a ​diffused process
(requiring ​immunosuppression​) or ​vascular occlusive disease (requiring
anticoagulation​)
■ Cognitive dysfunction
● Most common manifestation of diffuse CNS lupus
● Difficulties with memory and reasoning
■ Headache
■ Seizures
● Tx: Anti-seizures and immunosuppressive therapy
■ Psychosis
● Must be distinguished from glucocorticoid-induced psychosis which
usually occurs in the first weeks of glucocorticoid therapy, at daily doses

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 of ≥40 mg of prednisone or equivalent; resolves over several days after
glucocorticoids are decreased or stopped.
■ Myelopathy: standard of care includes high-dose glucocorticoids
○ Vascular Occlusions
■ Increased prevalence of transient ischemic attacks, strokes, and myocardial
infarctions (especially those SLE patients with antiphospholipid antibodies which
is associated with hypercoagulability and acute thrombotic events)
■ Chronic SLE with or without antiphospholipid antibodies is associated with
accelerated atherosclerosis.
● Brain ischemia
○ Caused by focal occlusion (either non-inflammatory or associated
with vasculitis) or by embolization from carotid artery plaque or
from fibrinous vegetations of Libmann-Sacks endocarditis.
● Myocardial infarction
■ Increased risk for vascular events is three-to tenfold overall, and is highest in
woman <49 years old.
■ Characteristics associated with increased risk for atherosclerosis include older
age, hypertension, dyslipidemia, dysfunctional proinflammatory high-density
lipoproteins, repeated high scores for disease activity, high cumulative or daily
doses of glucocorticoids, and high levels of homocysteine.
■ Tx: Anticoagulation; anticoagulation+immunosuppression (for vasculitis plus bland
vascular occlusions); Statins (reduce levels of LDL)
○ Pulmonary Manifestations
■ Pleuritis
● Can occur with or without pleural effusion
● Most common pulmonary manifestation of SLE
● Tx: NSAIDS (mild); Glucocorticoid (severe)
■ Pulmonary infiltrates
● Manifestation of active SLE
● Difficult to distinguish from infection on imaging studies
■ Life-threatening pulmonary manifestations: interstitial inflammation leading to
fibrosis, shrinking lung syndrome, and intra-alveolar hemorrhage
● Tx: Aggressive immunosuppressive therapy
○ Cardiac Manifestations
■ Pericarditis
● Most frequent cardiac manifestation
● Usually responds to anti-inflammatory therapy
● Infrequently responds to tamponade
■ Serious cardiac manifestations
● Myocarditis
● Fibrinous endocarditis of Libman-Sacks
○ Leads to valvular insufficiencies (commonly mitral or aortic
valves) or embolic events
○ Hematologic Manifestations
■ Anemia: normocytic, normochromic reflecting chronic illness
■ Hemolysis: can be rapid in onset and severe, requiring high-dose glucocorticoid
therapy
■ Leukopenia: usually lymphopenia
■ Thrombocytopenia
● If >40,000/µL and abnormal bleeding is absent: therapy not required
● High-dose glucocorticoid therapy (for severe thrombocytopenia)
○ Gastrointestinal Manifestations
■ Nausea
■ Vomiting
■ Diarrhea
■ Diffuse abdominal pain: caused by autoimmune peritonitis and/or intestinal
vasculitis
■ Increased AST and ALT

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 ■ Vasculitis
● Involving the intestine may be life-threatening
● Complications: perforation, ischemia, bleeding, sepsis
● Tx: Aggressive immunosuppressive therapy with high-dose
glucocorticoids for short-term control
■ *Improve promptly during systemic glucocorticoid therapy
○ Ocular Manifestations
■ Sicca syndrome
■ Nonspecific conjunctivitis
■ Retinal vasculitis and optic neuritis: serious manifestations blindness can develop
over days to weeks
■ Complications of systemic and glucocorticoid therapy
● Cataracts (common)
● Glaucoma
● Diagnosis:
○ SYSTEMIC LUPUS INTERNATIONAL COLLABORATING CLINIC CRITERIA FOR
CLASSIFICATION OF SYSTEMIC LUPUS ERYTHEMATOSUS
■ CLINICAL MANIFESTATIONS
● Skin
○ Acute, subacute cutaneous LE
○ Chronic cutaneous
● Oral ulcers
● Alopecia
● Synovitis
● Renal
○ Protein/Creatinine ≥0.5
○ RBC casts
○ Biopsy (Renal biopsy read as systemic lupus qualifies for
classification as SLE even if none of the other above features are
present)
● Neurologic
○ Seizures, psychosis, mononeuritis,myelitis, peripheral or cranial
neuropathies, acute confusional state
● Hemolytic anemia
● Leukopenia (<4000) or Lymphopenia (<1000)
● Thrombocytopenia (<100, 000)
■ IMMUNOLOGIC MANIFESTATIONS
● ANA > reference negative value
● Anti-dsDNA
● Anti-Sm
● Antiphospholipid
● Low serum complement
● Positive direct Coombs test
○ Based on characteristic clinical features and autoantibodies
○ 4 or more criteria with at least 1 in the clinical and 1 in the immunologic category, well
documented at any time (sensitivity: 92%, specificity: 93%)
○ Antinuclear antibodies (ANA) are positive in >98% of patients during the course of disease
○ anti-dsDNA and anti-Sm are both specific for SLE

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● Treatment:
○ No cure for SLE; complete sustained remissions are rare
○ Goals of management:
■ Induce remissions of acute flares
■ Maintain improvements with strategies that suppress symptoms to an acceptable
level and prevent organ damage
○ Therapeutic choices depend on:
■ Whether disease manifestations are life-threatening or likely to cause organ
damage, justifying aggressive therapies
■ Whether manifestations are potentially reversible
■ The best approaches to preventing complications of disease and its treatments
○ Conservative Therapies for Management of Non-Life Threatening Disease
■ Analgesics (NSAIDs) and Antimalarials - mainstays of treatment
● 2 major issues in using NSAIDs: (1) SLE patients are at increased risk for
NSAID-induced aseptic meningitis, elevated serum transaminases,
hypertension, and renal dysfunction. (2)All NSAIDs, particularly those that
inhibit cyclooxygenase-2 specifically, may increase risk for myocardial
infarction.
○ Life-Threatening: Proliferative Forms of Lupus Nephritis
■ Systemic Glucocorticoids
● mainstay of treatment
● 0.5–1 mg/kg per day PO or 500–1000 mg of methylprednisolone sodium
succinate IV daily for 3 days followed by 0.5–1 mg/kg of daily prednisone
or equivalent
■ Cytotoxic/immunosuppressive agents
● added to glucocorticoids to treat serious SLE
● Cyclophosphamide (an alkylating agent)

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 ● Mycophenolate mofetil (a relatively lymphocyte-specific inhibitor of inosine
monophosphatase and therefore of purine synthesis)
● Azathioprine (a purine analogue and cycle-specific antimetabolite) - may
be effective but is slower to influence response and associated with more
flares.
● Mycophenolate and Azathioprine are safer than Cyclophosphamide
○ Special Conditions in SLE that may require additional or different therapies
■ Crescentic Lupus Nephritis
● Cellular or fibrotic crescents in glomeruli with proliferative
glomerulonephritis indicates a worse prognosis
● High-dose Cyclophosphamide is the induction therapy of choice, in
addition to high-dose glucocorticoids.
■ Membranous Lupus Nephritis (INS-V)
● Do not recommend immunosuppression unless proteinuria is in the
nephrotic range (although treatment with angiotensin-converting enzyme
inhibitors or angiotensin II receptor blockers is recommended).
● Alternate-day glucocorticoids plus cyclophosphamide or mycophenolate
mofetil or cyclosporine are all effective in reducing proteinuria
■ Pregnancy and lupus
● Systemic Glucocorticoids
○ 11-β-dehydrogenase 2 - placental enzyme that deactivates
glucocorticoids; it is more effective in deactivating prednisone and
prednisolone than the fluorinated glucocorticoids dexamethasone
and betamethasone.
○ Category A (no evidence of teratogenicity in human studies)
● Cyclosporine, tacrolimus, and rituximab
○ Category C (may be teratogenic in animals but no good evidence
in humans)
● Azathioprine, Hydroxychloroquine, Mycophenolate mofetil, and
Cyclophosphamide
○ Category D (there is evidence of teratogenicity in humans, but
benefits might outweigh risks in certain situations)
○ Cyclophosphamide and Mycophenolate mofetil are potentially
teratogenic; patients should be off either medication for at least 3
months before attempting to conceive.
○ Azathioprine may be used in SLE in patients who are pregnants.
Patients may be prescreened for homozygous deficiency of the
TPMT enzyme (which is required to metabolize the
6-mercaptopurine product of azathioprine) because they are at
higher risk for bone marrow suppression
● Methotrexate
○ Category X (risks outweigh benefits)
● Patients should consider not breastfeeding if they need therapy for SLE
■ Lupus and Antiphospholipid Syndrome
● Long term anticoagulation
● A target INR of 2.0–2.5 is recommended for patients with one episode of
venous clotting
● An INR of 3.0–3.5 is recommended for patients with recurrent clots or
arterial clotting, particularly in the CNS.
■ Microvascular Thrombotic Crisis (Thrombotic Thrombocytopenic Purpura,
Hemolytic-Uremic Syndrome)
● TRIAD: hemolysis, thrombocytopenia, microvascular thrombosis in
kidneys, brain, and other tissues
● Most useful laboratory tests: (1) identification of schistocytes on peripheral
blood smears, (2) elevated serum levels of lactate dehydrogenase, (3)
and antibodies to ADAMTS13.
● Plasma exchange or extensive plasmapheresis is usually life-saving; most
authorities recommend concomitant glucocorticoid therapy;

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 ■ Lupus Dermatitis
● Minimize exposure to UV light, using appropriate clothing and sun
screens with a sun protection factor of at least 30.
● Topical glucocorticoids and antimalarials (such as hydroxychloroquine)
are effective in reducing lesion severity in most patients and are relatively
safe.
● Retinoic acid - used in patients with inadequate improvement on topical
glucocorticoids and antimalarials
● In therapy-resistant lupus dermatitis: topical tacrolimus (possible
increased risk for malignancies), systemic dapsone or thalidomide (the
extreme danger of fetal deformities)
● SLE: Unfortunate Cascade of Events (November 27, 2017)
○ 32 y/o F, S/sx: Prolonged fever, malar rash, alopecia, arthritis (non-erosive, non-deforming
arthritis which involves the hands, wrists and knees)-MTX: given once a week for
Jaccoud’s arthropathy
○ Lab exams:
■ CBC: Thrombocytopenia, Leukopenia, Lymphopenia
■ Urinalysis: Proteinuria (due to nephritis)= decrease oncotic pressure= edema
(Nephrotic syndrome)
■ Low C3 (consumed in active disease and deposited in organs)
■ High ANA
■ High dsDNA (specific for SLE)
■ SLE Cell prep: macrophage-like (engulfs antibodies) will be stained and observed
under microscope; not done anymore
○ Non-life threatening manifestations:
■ Constitutional sx
■ Arthritis
■ Mucocutaneous manifestations
○ Life-threatening manifestations:
■ Proliferative Lupus Nephritis
■ CNS Lupus
■ Pulmonary Hemorrhage
○ Optic Neuropathy
■ Tx: Steroid and Cyclophosphamide pulses (minimal improvement only)
■ Hydroxychloroquine: Toll-like receptor (TLR) inhibitor; monitoring involves
ophthalmologic exam at least once a year
○ Transverse myelitis
■ Paraplegia, urinary retention, recurrent UTI
■ Tx: High-dose steroids
○ Interstitial Lung Disease
■ Dry cough, progressive SOB
■ Remember: Side effects and adverse effects of STEROIDS
○ Osteonecrosis/Avascular necrosis
■ Cellular death of bone components due to interruption of blood supply
■ Involves single terminal blood supply (femoral head, carpal tunnel)
■ Radiographic finding: Crescent sign (earliest radiographic finding)

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 RH-BGD TOPICS

1. Septic Arthritis (LOPEZ, IDANAN, HILARIO)

Case: Acute painful knee swelling (monoarthritis, infectious arthritis)
● Clinical Manifestations of Acute Bacterial Arthritis
○ Some 90% of patients present with o involvement of a ​single joint​. Most common:
​ ​knee​ > hip > shoulder, wrist, or elbow
○ After direct inoculation or a bite
■ Small joints of the hands and feet
○ Among IV drug users
■ infections of the spine, sacroiliac joints, and sternoclavicular joints, infections of
the appendicular skeleton
○ In patients with Rheumatoid arthritis
■ Polyarticular infection
■ may resemble a flare of the underlying disease
○ Usual presentation
■ moderate to severe pain, uniform around the joint,
■ effusion
■ muscle spasm
■ decreased range of motion
■ Fever in the range of 38.3–38.9°C (101–102°F)
● sometimes higher is common
● may not be present in persons with rheumatoid arthritis, renal or hepatic
insufficiency, or conditions requiring immunosuppressive therapy.
■ Extraarticular infection: a boil or pneumonia
■ peripheral-blood leukocytosis with a left shift
■ elevation of the erythrocyte sedimentation rate or C-reactive protein level
■ inflamed, swollen joint
● except in the case of a deeply situated joint such as the hip, shoulder, or
sacroiliac joint
● Diagnosis
○ Aspiration of synovial Fluid
■ Ultrasound-guided
■ Fluoroscopy-guided
■ Synovial fluid
● Normal
○ <180 cells/​µ​L
○ predominantly mononuclear cells
● Acute Bacterial Infections
○ 25,000-250,000/​µ​L
○ >90% neutrophils
● Crystal-induced, Non-infectious Inflammatory Arthritides
○ <30,000-50,000 cells/​µL ​
● Fungal and Mycobacterial
○ 10,000-30,000 cells/​µ​L
○ 50-70% neutrophils remaining are lymphocytes
○ Definitive Diagnosis
■ Identification of pathogen in stained smears of synovial fluid
■ Isolation of pathogen from cultures of synovial fluid and blood
■ Detection of microbial nucleic acid and proteins by nucleic acid amplification
(NAA)-based assays and immunologic techniques
● Nongonococcal Bacterial Arthritis
○ Blood culture (less frequently positive)
○ Synovial Fluid Analysis
■ Turbid, serosanguinous, or frankly purulent
■ In gram stain- neutrophilic predominance
■ Elevated total protein and lactate dehydrogenase
■ Low levels of glucose

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 ■ (+) in culture of synovial fluid
○ NAA-based assays for bacterial DNA
■ For partially treated or culture negative bacterial arthritis
● Gonococcal Arthritis
○ Disseminated Gonococcal Infection
■ Blood culture (positive in 45% of patients)
■ Synovial Fluid Analysis
● Culture (negative)
● 10,000-20,000 leukocytes/​µ​L
○ True Gonococcal Septic Arthritis
■ Blood culture almost always negative
■ Synovial Fluid Analysis
● Culture (<40% of patients)
● >50,000 leukocytes/​µ​L
● Gram Stain (less frequent)
● *Cultures placed on ​Thayer-Martin agar
■ NAA-based assays (extremely sensitive)Lyme Arthritis
○ Serologic tests for IgG antibodies to ​B. burgdorferi
○ NAA-based assays
● Syphilitic Arthritis
○ Synovial Fluid Analysis
■ Mixed mononuclear and neutrophilic pleocytosis (5,000-15,000/​µ​L)
● Mycobacterial Arthritis
○ Synovial Fluid Analysis
■ Cell count (20,000/​µ​L with 50% neutrophils)
■ Acid-fast staining (<⅓ of cases)
■ Culture (positive in 80%)
■ NAA-based assays
■ Radiographic findings
● Peripheral erosions ar points of synovial attachment
● Periarticular osteopenia
● Joint-space narrowing
● Fungal Arthritis
○ Synovial Fluid Analysis
■ 10,000-4000 cells/​µ​L with 70% neutrophils
■ Culture
● Viral Arthritis
○ Synovial Fluid Analysis
● Treatment (1234)
○ Nongonococcal Bacterial Arthritis
■ Prompt administration of IV bactericidal empiric antibiotics
● Community-acquired infections, negative smears
○ 3rd gen cephalosporins ie:
■ Cefotaxime (1g every 8 h)
■ Ceftriaxone (1-2 g every 24 h)
● G+ cocci on smears
○ IV vancomycin (ig every 12 h)
● MSSA
○ Oxacillin or nafcillin (2g every 4 h)
● IV drug users and ​P. aeruginosa
○ Aminoglycoside
○ 3rd gen cephalosporins
■ Definitive therapy
● Staphylococci
○ Oxacillin, nafcillin, or vancomycin for 4 weeks
● Pneumococcal and streptococcal infections due to
penicillin-susceptible organisms
○ Pen G (2 million units IV every 4 h for 2 wks)

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 ● H. influenzae​, and penicillin-resistant strains of ​Streptococcus
pneumoniae
○ Cefotaxime or ceftriaxone for 2 wks
● Enteric G-
○ IV 2nd or 3rd gen cephalosporins for 3-4 wks
○ Fluoroquinolone (levofloxacin 500 mg IV or PO every 24h)
● P. aeruginosa
○ Aminoglycoside + extended-spectrum penicillin (mezlocillin 3g IV
every 4 h) or antipseudomonal cephalosporin (ceftazidime 1g IV
every 8h) for 2 wks
■ Drainage of pus and necrotic debris
● Needle aspiration (e.g. knee)
● Arthroscopic drainage and lavage
○ If repeated needle aspiration fails to relieve symptoms, decrease
the volume of the effusion and the synovial white cell count, and
clear bacteria from smears and cultures
● Arthrotomy
○ Septic arthritis of the hip (young children)
○ Gonococcal Arthritis
■ Initial treatment
● Cover possible Penicillin-resistant organisms
○ Ceftriaxone (1g IV or IM every 24 h)
● Penicillin-susceptible
○ Oral fluoroquinolone (i.e. Ciprofloxacin 500 mg BID)
■ Suppurative arthritis
● Needle aspiration of involved joint
● 7-14 days antibiotic treatment
■ Arthroscopic lavage or arthrotomy
● Rarely required
■ Px with DGI (disseminated gonococcal infection)
● Treated for ​Chlamydia trachomatis​ infection
○ Unless ruled out
■ Responds to IV penicillin
● Meningococcemia - arthritis symptoms similar in DGI
● Dermatitis-arthritis syndrome
● Purulent monoarthritis
● Reactive polyarthritis
○ Lyme Arthritis
■ Responds well to therapy
● Oral doxycycline; or
○ 100 mg BID for 30 days
● Oral amoxicillin; or
○ 500 mg 4x daily for 30 days
● Parenteral ceftriaxone
○ 2g/d for 2-4 wks
■ No response to 2 mos. oral therapy or 1 mo. parenteral therapy
● Unlikely to benefit from additional antibiotic therapy
● Tx: anti-inflammatory agents or synovectomy
■ Failure of therapy
● Associated with:
○ human leukocyte antigen DR4 (HLA-DR4) genotype
○ persistent reactivity to OspA (outer surface protein A)
○ presence of hLFA-1 (human leukocyte function–associated
antigen 1 - Cross reacts with OspA
○ Prosthetic Joint Infections
■ Surgery
■ High doses of parenteral antibiotics
● 4-6 wks - bone usually involved

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 ● Replace prosthesis to cure infection
● Implantation of new prosthesis delayed for several weeks or mos.
○ Relapses commonly occur at this time frame
■ Reimplantation not possible
● Px must manage without a joint, fused joint, or amputation
■ Due to streptococci or pneumococci
● Lack radiologic evidence of loosening of prosthesis
○ Possible cure of infection without removal of prosthesis
○ Antibiotic therapy initiated within several days of onset
○ Vigorous drainage of joint
■ Open arthrotomy
■ Arthroscopically
■ Px who prefer to avoid the high morbidity rate associated with joint removal and
reimplantation
● Goal: Suppress infection with antibiotics
● Short duration staphylococcal prosthetic joint infection
○ Oral rifampin and ciprofloxacin 3-6 mos.

2. Rheumatoid Arthritis, anti-TNF Therapy, and Tuberculosis (HAPAN, MORCO, MANUGAS,

ICARO)
Case: Fever, pericardial effusion, lung infiltrates post TNF therapy for RA
● Clinical Manifestations (focus on adverse effects of anti-TNF therapy)
○ Presenting symptoms of RA typically result from inflammation of the joints, tendons, and
bursae
○ Early morning joint stiffness lasting more than 1 h that eases with physical activity
○ Small joints of the hands and feet- earliest involved joints
○ Initial pattern may be:
■ Monoarticular
■ Oligoarticular(</= 4)
■ Polyarticular (>5)
○ Symmetric distribution
○ Most frequently involved joints:
■ Wrists
■ MCP
■ PIP
○ DIP- usually manifestation of
coexistent osteoarthritis
○ Flexor tendon tenosynovitis
■ Is a frequent hallmark of RA
■ Leads to decreased range
of motion, reduced grip
strength, and “trigger”
fingers
○ Ulnar deviation
■ Subluxation of MCP joints
■ Subluxation of the proximal
phalanx to the volar side
○ Swan neck deformity
■ Hyperextension of PIP
■ Flexion of DIP
○ Boutonniere deformity
■ Flexion of PIP
■ Hyperextension of DIP
○ Z-line deformity
■ Subluxation of the 1st MCP
■ Hyperextension of the 1st IP
○ Piano key movement

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 ■ Inflammation about the ulnar styloid and tenosynovitis of the extensor carpi ulnaris
may cause subluxation of the distal ulna
○ Pes planovalgus (Flat feet)
○ Atlantoaxial involvement of the cervical spine
■ May cause compressive myelopathy and neurologic dysfunction
○ Most frequently observed extra articular manifestations
■ Subcutaneous nodules
■ Secondary Sjögren’s syndrome
■ Pulmonary nodules
■ Anemia
● Anti-TNF therapy
○ Should be avoided in patients with:
■ active infection
■ history of hypersensitivity to these agents
■ chronic hepatitis B infection
■ class III/IV congestive heart failure
○ major concern is the increased risk for infection
○ PPD- screening for latent TB
○ If patient is on anti-TNF therapy for over a year, repeat CXR and IGRA, if possible, to see
if patient developed TB

● Diagnosis
○ Clinical diagnosis largely based on signs of a chronic inflammatory arthritis

● Laboratory Features

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 ○ Elevated non-specific inflammatory markers
○ ANA positivity: does not translate to an infection, can be positive in anti-TNF therapy
○ RF (diagnostically non-specific), anti-CCP
■ anti-CCP shows the most value for predicting worse outcomes
○ Synovial fluid analysis
○ Generally, range is between 5,000 and 50,000 WBC/uL compared to <2000 uL for a
non-inflammatory condition
○ Neutrophil predominant
○ Analysis is most useful for confirming
○ Joint imaging
○ Plain x-ray is the most common imaging modality
○ MS US with power Doppler is increasingly used for detecting synovitis and bone erosion
○ Ultrasound
■ With Doppler
■ Has the ability to detect more erosions than plain radiograph
■ Can detect synovitis and increased joint vascularity
○ MRI
■ Offers the greatest sensitivity for detecting synovitis and joint effusions as well as
early bone and BM changes
■ Presence of bone marrow edema- early sign of inflammatory joint disease and
can predict the development of subsequent erosion
○ Plain radiography
■ Initial radiographic finding is periarticular osteopenia
■ In the feet, the lateral aspect of the 5th MTP is often targeted first
○ Cannot rule out SLE just by normal serum C3 alone
■ Check for serum complement level to check if SLE is active
■ C4 should also be measured
■ Patient might have SLE but is not active (based on C3 and TST) so the pericardial
effusion is probably caused by disseminated TB, not SLE
○ How to confirm TB in this patient
■ Pericardial biopsy vs pericardiocentesis
■ GU TB: urine AFB

● Treatment
○ ACR Improvement - commonly used in clinical trials as endpoint for comparing the
responders between treatment group
○ Continuous measures of disease activity:
■ Disease Activity Score (DAS)
■ Simplified Disease Activity Index (SDAI)
■ Clinical Disease Activity Index (CAI)
○ Developments in therapeutic landscape of RA:
■ emergence of methotrexate as DMARD of first choice for the treatment of early
RA
■ development of novel highly efficacious biologicals that can be used alone or
in combination with methotrexate
■ proven superiority of combination DMARD regimen than methotrexate alone
○ NSAIDS
■ Non-selective inhibitor of COX1 and COX2
■ Has both analgesic and anti-inflammatory properties
■ Adjunctive therapy for management of symptoms
■ Adverse effects: gastritis, PUD, renal impairment
○ GLUCOCORTICOIDS
■ Controls disease activity
■ Low to moderate doses → to achieve rapid disease control before onset of fully
effective DMARD therapy which often take several weeks to months
■ 1-2 wks burst of glucocorticoids → for management of acute flares
■ Chronic low dose prednisone administration → to control disease activity in those
w/ inadequate response to DMARD therapy

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 ■ High dose glucocorticoids - for treatment of severe extraarticular manifestations
■ Adverse effect: increases risk of PUD
■ Long term complication (chronic use): osteoporosis
■ Bisphosphonates - for primary prevention of glucocorticoid-induced osteoporosis
in patients receiving prednisone 5 mg/d or more for >3 months
○ DMARDS
■ Ability to prevent or to slow structural progression of RA
■ Methotrexate - DMARD of choice for treatment of RA and anchor drug for most
combination therapies (dose: 10-25 mg/wk)
■ Methotrexate has been shown to stimulate adenosine release of cells →
anti-inflammatory effect
■ Leflunomide - pyrimidine synthesis inhibitor; effective as monotherapy or in
combination w/ methotrexate
■ Hydroxychloroquine - for treatment of early or mild disease or as adjunctive
therapy
○ BIOLOGICALS - targets cytokines and cell surface molecules
■ Anti-TNF
● Infliximab - monoclonal antibody
● Adalimumab and Golimumab -​humanized​ monoclonal antibody
● Certolizumab - pegylated Fc-free fragment of humanized monoclonal
antibody with binding specificity of TNFa
● Etanercept - soluble fusion protein comprising TNF receptor 2 in covalent
linkage of Fc portion of IgG1
● anti-TNFs are typically used in combination with methotrexate
● Contraindications of anti-TNF agents:
○ Patients w/ active infection
○ History of hypersensitivity to these agents
○ Chronic hep B infection
○ Class III/IV CHF
● Major concerns: risk of infections (bacterial, fungal opportunistic) and
reactivation of latent TB
■ Anakinra
● Recombinant form of the naturally occuring IL-1 receptor antagonist
● Effective therapy of some rare inherited syndromes dependent on IL-1
production:
○ Muckle-wells syndrome
○ Familial cold urticaria
○ Systemic juvenile onset inflammatory arthritis
○ Adult onset Still’s disease
● Anakinra ​SHOULD NOT be combined with methotrexate due to high rate
of serious infections
■ Abatacept
● Soluble fusion protein consisting of extracellular domain of human
CTLA-4 linked to modified production of human IgG
● Inhibits co-stimulation of T-cells by blocking CD28-CD80/86 interactions
● May also inhibit the function of APCs by reverse signaling through CD80
& CD86
● Associated with increased risk of infection
● Many patients receive abatacept in combi with methotrexate or another
DMARD such as leflunomide
■ Rituximab
● Chimeric monoclonal antibody directed against CD20
● Depletes B-cells leading to reduction in the inflamm response by unknown
mechanisms
○ These mechanisms may include: reduction in autoantibodies,
inhibition of T cell activation and alteration of cytokine production
● Approved for treatment of refractory RA in combi with methotrexate (more
effective for patients with ​seropositive​ ​than seronegative disease)

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 ●Adverse effects: mild to moderate infusion reaction, increased risk for
infection
■ Tocilizumab
● anti-IL6
● Humanized monoclonal antibody directed against membrane and soluble
forms of IL-6 receptor
● IL-6 - proinflammatory cytokine implicated in pathogenesis of RA
● Adverse effects: increased risk of infection, neutropenia,
thrombocytopenia
● Hematologic abnormalities are reversible upon stopping the drug
● Has been shown to increase LD
○ SMALL MOLECULE INHIBITORS
■ Tofacitinib
● Inhibits JAK1 and JAK3 which mediate signaling of the receptors for the
common γ-chain-related cytokines IL-2, -4, -7, -9, -15, and -21 as well as
IFN-γ and IL-6
● Oral agent
● Can be used as monotherapy or in combi with methotrexate
● Adverse events: elevated serum transaminases(liver injury), neutropenia,
increased cholesterol levels, elevation in serum creatinine, increased risk
of infection

3. Pott’s Disease (MARTIN, IBAY)

● Clinical Manifestations
○ Most common manifestation of skeletal TB
○ Lower thoracic and upper lumber in adults; 2 adjacent vertebral bodies
○ Kyphosis (gibbus)
■ Destruction of intervertebral disc space and adjacent vertebral bodies
■ Collapse of spinal elements
■ Anterior wedging manifested as kyphosis
■ Loss of disc height
■ Osseous destruction
■ Soft tissue abscess
○ Paravertebral abscess
○ Soft tissue mass in lower spine
○ Fever
○ Weight loss
○ Catastrophic complication: Paraplegia
● Diagnosis (IBAY)
○ X-ray
■ Cornerstone of spinal imaging in resource-poor countries
■ Described changes consistent with spinal TB in 99% of cases
■ For SCREENING
■ Earliest findings:
● Radiolucencies and loss of definition of the plate margins
■ Characteristic findings:
● Rarefaction of vertebral end plates
● Loss of disc height
● Osseous destruction/osteolysis
● New-bone formation
● Soft tissue abscess
■ Tuberculous Cold Abscess
● Soft tissue shadows adjacent to the spine
○ CT Scan
■ Demonstrates abnormalities earlier than x-ray
■ Ideal for guiding percutaneous diagnostic needle for obtaining sample
■ DETECTS PATTERN OF BONE DESTRUCTION
○ MRI

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 ■ Neuroimaging of choice in spinal TB
■ More sensitive than x-ray
■ More specific than CT scan
■ Determines EARLY CHANGES and EXTENT OF SPREAD
■ GOLD STANDARD
● Treatment
○ Skeletal TB responds to chemotherapy, but severe cases may require surgery.

4. Dermatomyositis (and other Inflammatory Myopathies) (MONVILLE, JUSAY, MARANG)

● Clinical Manifestations
○ Progressive and symmetric muscle weakness of proximal muscles
○ Also affects ​distal muscles early in IBM​ but ​late in DM and PM
○ Ocular muscles are spared
○ Involvement of pharyngeal and neck muscles → dysphagia and head drop
○ Progression:
■ PM and DM - subacutely (weeks ot month), rarely acutely
■ IBM - very slowly (years)
○ Polymyositis​:
■ Diagnosis by exclusion
■ An adult who ​do not have​:
● Rash
● Extraocular or facial muscle involvement and muscle dystrophy
● Family history of neuromuscular disease
● Exposure to myotoxic drugs or toxins
● Endocrine or Neurogenic disorders
● Deficient muscle enzymes
● IBM (as excluded by muscle biopsy)
○ Dermatomyositis:
■ Heliotrope rash (blue-purple discoloration on the upper eyelids with edema)
■ Gottron’s sign (erythema on the knuckles with a raised violaceous scaly eruption)
■ Rash can occur on knees, elbows, malleoli, neck and anterior chest (V sign), or
back and shoulders (shawl sign)
■ Rash​ is accompanied with or preceded by muscle weakness
■ Dilated capillary loops at the base of the fingernails
■ Irregular, thickened, and distorted cuticles
■ Lateral and palmar areas may become rough and cracked (mechanic’s hand)
■ Usually occurs alone but may overlap with scleroderma and mixed CT disease
○ Inclusion Body Myositis
■ Most common inflammatory myopathy in patients ​>​50 y/o
■ Weakness and atrophy of the distal muscles, especially foot extensors and deep
finger flexors

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 ■ May resemble a lower motor neuron disease (weakness and atrophy involving the
quadriceps, iliopsoas, triceps, biceps, and finger flexors)
■ Dysphagia​ is common (60%)
■ Disease progression is slow but steady
■ 20% associated with systemic autoimmune or CT diseases
● Diagnosis
○ Most sensitive enzyme is CK​, can be elevated as much as 50-fold
○ EMG findings are not diagnostic of an inflammatory myopath​y but are useful to identify the
presence of active or chronic myopathy and to exclude neurogenic disorders
○ Muscle biops​y is the most sensitive and specific test for establishing the diagnosis
○ Inflammation​ is the histologic hallmark for these disorders
○ In PM, the inflammatory is PRIMARY (inflammation is not reactive and T cell infiltrates
surround individual, healthy muscle fibers and result in phagocytosis and necrosis)
○ In DM, the presence of ​perifascicular atrophy is diagnostic, even in the absence of
inflammation

● Treatment
○ Goal is to improve muscle strength, thereby improving function, and ameliorate
extramuscular manifestations
○ Glucocorticoids
■ Oral prednisone
● Effectiveness determined by increase in muscle strength by the third
month of therapy
■ If not responsive to prednisone after 3 months, tapering should be accelerated
while the next-in-line immunosuppressive drug is started
■ Long-term use may lead to steroid myopathy
○ Immunosuppressive drugs
■ Azathioprine
■ Methotrexate
■ Mycophenolate mofetil
■ Rituximab
■ Cyclosporine
■ Cyclophosphamide
■ Tacrolimus
○ Immunomodulation
■ In a controlled trial of patients with refractory DM, IVIg improved not only strength
and rash but also the underlying immunopathology
■ Benefit is short-lived
■ Repeated infusions every 6-8 weeks to maintain improvement
■ 2 g/kg divided over 2-5 days

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CCC CASES

● SLE patient with recurrent diarrhea, electrolyte imbalance, massive GI bleeding, sepsis, and
renal failure (MENDOZA BEA, JOCSON)
Case: 49/F with SLE, abdominal pain, constipation, diarrhea
● Differential diagnosis:
○ IBM
○ IBD
○ Malignancy
● Most informative tool: colonoscopy
● Clinical manifestations of SLE GI Vasculitis
○ Occurs in 1-2% of SLE patients with abdominal pain
○ Presents as:
■ Abdominal distention
■ Abdominal tenderness
■ Diarrhea
■ Nausea and Vomiting
■ CT scan: Double-halo or target sign -​ ​submucosal edema due to inflammation
○ CNS lupus vs electrolyte imbalance as a cause of seizure
Hypomagnesemia and Hypocalcemia CNS Lupus

Magnesium
● Membrane-stabilizing effects
● Interacts with NMDA glutamate receptors
● Immune complex deposition →
● Acts as a voltage dependent calcium
inflammation → perisulcal atrophy →
channel antagonist→ prevent membrane
seizures
depolarization
● Inflammation + corticosteroids → atrophy
→ seizures
Calcium
● Increase neuromuscular excitability and
tetany

● Diagnostic consideration for patients presenting with seizures:

○ SLE-induced seizures
■ Diffuse SLE
■ Vascular occlusive disease
○ Infection-induced seizures
○ Metabolic Abnormality
■ Electrolyte imbalance (hypocalcemia, hypomagnesemia)

Predisposing factors and susceptibility to infection in patients with SLE

Breakdown of epithelial barriers Abnormal T-cell mediated cytotoxicity

Impaired chemotaxis and phagocytosis of

macrophages and PMNs (impaired IL-8 and Complement deficiency
IL-12 for PMN function)

Dec. expression of cellular complement receptors

Mannose-binding lectin deficiency
(CR1, CR2, CR3)

Reduced CD4+ T cells (due to disease and/or

Low levels of soluble Fc-gamma receptor III
to corticosteroids)

Reduced CD25+ regulatory cells Chronic inflammation and tissue damage

● Sepsis
○ Annual number of cases >750,000 (~3 per 1000 population)
○ ~⅔ occur in patients with significant underlying illness

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 ○ Incidence increase with widespread use of immunosuppressive drugs, indwelling
catheters, and mechanical devices
○ Case-fatality rate: infected (33%), uninfected (15%)
○ New meaning: Life-threatening organ dysfunction due to a dysregulated host response to
infection
○ SOFA Score: ​S​epsis-related ​O​rgan ​F​ailure ​A​ssessment
■ Score >2 = mortality of 10%
■ Hypotension
■ Systolic BP <100
■ Altered mental state
■ Tachypnea RR >22
■ Septic shock - Subset of sepsis where underlying circulatory and
cellular/metabolic abnormalities are profound enough to substantially increase
mortality
○ Needing vasopressors for a MAP of 65 mmHg (septic shock)
■ Increase in lactate >2 mmol/L despite adequate fluid resuscitation
■ Treatment: within 30 minutes, give:
● Broad-spectrum antibiotics
● Fluid resuscitation
○ Steps:
■ 1st - SIRS
● Temp: >38 or <36 C
● RR: >24 cpm
● HR: >90 bpm
● WBC: >12,000/µL, <4000/µL, or >10% bands
■ 2nd - Sepsis
● 2 sirs + Confirmed or suspected infection
■ 3rd - Severe sepsis
● Sepsis + Signs of end organ damage + Hypotension (SBP <90mmHg)
● Lactate >4 mmol
■ 4th - Septic shock
● Severe sepsis with persistent hypotension
● Signs of end organ damage
● Lactate >4 mmol

Patient’s
Usual Signs and
Organ involvement Manifestation (CCC Rationale
Symptoms
case)

ARDS, Elevated
PCWP, Sepsis-induced Generalized
hypotension, maldistribution of blood
dehydration, Hypotension responsive flow and volume
Cardiopulmonary
Normal/increased CO + to fluid resuscitation Diffuse capillary
decreased SVR, leakage of intravascular
Increased EDV, fluid
Decreased EF

Dec. ECV
Palpable distended Inc. Renal
Oliguria, Azotemia, bladder, Urine catheter Vasoconstriction
Proteinuria initially yielded 1.8L of Inc. cytokines
Renal
↑ Creatinine >0.5 mg/dL urine, Serum creatinine Activation of neutrophils
or 44.2 µmol/L increased to 2.77 mg/dL by endotoxins and other
from 0.96mg/dL peptides leading to
injury

● Risk Factors for pseudomembranous colitis (PMC)

○ Most often associated with severe ​Clostridium difficile​ infection (CDI)

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 ○
CDI - Acquired in association with antimicrobial use → disruption of normal colonic
microbiota
○ Risk of acquisition of CDI increases in proportion to length of hospital stay
○ Other identified risks:
■ Older age
■ Greater severity of underlying illness
■ GI surgery
■ Enteral tube feeding
■ Antacid treatment
● Management and Prevention
○ Discontinuation of ongoing antibiotic if possible
○ Oral vancomycin, fidaxomicin, or metronidazole
○ Preventing transmission of C. ​difficile
■ Gloving of personnel, elimination of used contaminated electronic thermometers
■ Use of hypochlorite for environmental decontamination
■ Hand washing recommended during outbreaks
○ Reducing the risk of infection if the organism is transmitted
■ Restricting use of specific antibiotics
■ Use of monoclonal antibodies, vaccines and biotherapeutics containing live
organisms

● Prolonged fever, polyarthritis, and ulcerating skin lesions (MANTILLA, MACARUBBO, MENDOZA
WILLIAM)
Case: 41/F, prolonged fever, ARTHRITIS, ulcerating skin lesions (bx:scrofuloderma), ANA 1:160
● Fever of Unknown Origin
○ illness of >3 weeks’ duration with fever of ≥38.3°C (101°F) on two occasions and an
uncertain diagnosis despite 1 week of inpatient evaluation
○ Currently: In-hospital evaluation requirement has been eliminated from the definition AND
immunocompromised patients have been excluded
○ New definition:
■ Fever >38.3°C (101°F) on at least two occasions
■ Illness duration of ≥3 weeks
■ No known immunocompromised state
■ Diagnosis that remains uncertain after a thorough history-taking, physical
examination, and obligatory investigations

MAJOR ETIOLOGIC CATEGORIES OF FUO

Infections Bacterial, viral, fungal, parasitic

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 *If px is presenting with unexplained symp.
Localized to CNS, GIT, or joints =>DO PCR
TESTING FOR T. WHIPPLEI

*Up to 50% of cases outside Western

nations are due to
tuberculosis

Systemic rheumatic and autoimmune

diseases, vasculitis, granulomatous
Non-infectious inflammatory disease diseases,
autoinflammatory
syndromes

Neoplasms Hematologic, solid and benign tumors

Thermoregulatory disorders Central or peripheral

Miscellaneous

● Treatment:
○ Empirical therapeutic trails with antibiotics, glucocorticoids, or anti-TB agents should be
avoided in FUO except when a px.’s condition is slowly deteriorating.
○ ANTIBIOTICS AND ANTI-TB THERAPY
■ Hemodynamic instability or neutropenia = good indication for antibiotic tx.
■ If fever doesn’t respond after 6 weeks of empirical anti-Tb tx, consider another
disease.
○ COLCHICINE, NSAIDs, GLUCOCORTICOIDS
■ NSAIDs and glucocorticoids can mask fever while permitting the spread of
infection or lymphoma => therefore, these should be avoided unless infectious
disease and malignant lymphoma have been largely ruled out and inflammatory
dse. Is probable.
○ ANAKINRA
■ A naturally occuring IL-1 receptor antagonist that blocks both IL-1a and IL-1B
● Poncet’s Disease
○ reactive symmetric form of polyarthritis that affects persons with visceral to disseminated
TB
○ rare, aseptic complication of active TB or the administration of BCG
○ Progressive monoarticular swelling and pain develop over months and years; systemic sx.
Seen only in half cases (eg. insidious fever and weakness)
○ Mostly in young adults suffering from extrapulmonary TB (also in those who have HIV or
immunocompromised)
○ Oligoarthritis or polyarthritis of large or small joints, or both (book: primarily involves the
large weight-bearing joints [hips, knees, and ankles)]
○ Diagnosis: No mycobacteria found in joints. Joint fluid yields ave. 20,000/uL with~50%
neutrophils. (+) acid fast in less than ⅓ of case, (+) culture in 80% cases, showing
granulomatous inflammation
○ Radiograph: peripheral erosions at points of synovial attachment, periarticular osteopenia,
and joint-space narrowing.
○ Mgt: Same as pulmo TB (2HRZE + 4HR) for 6-9 mos
● Differential Dx
○ SLE
○ Infectious/TB Arthritis
○ Reactive Arthritis/Poncet’s

Similarities of SLE and Mycobacterial Infection

Clinical Manifestations

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 fever, weight loss, anorexia, general
Constitutional signs and symptoms
malaise, weakness, lymphadenopathy

persistent fever, arthralgia, arthritis,

pleural and pericardial effusion,
Extrapulmonary TB and SLE neurologic
manifestations

Laboratories, Ancillaries

anemia of chronic disease

elevated acute phase reactants
pleural and pericardial effusion on chest X-rays

Differences in SLE vs Mycobacterial Infection

Clinical Manifestations

Cutaneous manifestations (e.g. malar rash, oral

SLE
ulcers, alopecia)

PTB: with/without cough

Mycobacterial infection (TB)
EPTB: ?

Laboratory Parameters

Leukopenia, lymphopenia, thrombocytopenia,

SLE autoimmune hemolytic anemia, (+)serology (ANA,
anti-dsDNA, anti-Sm)

Mycobacterial infection esp TB (+) sputum AFB, (+) TST/IGRA

Prophylaxis and Treatment of Nontuberculous mycobacteria (NTM) Disease

● nodular/bronchiectatic disease:​ 3X weekly

clarithromycin​(1,000mg) or azithromycin
(500 mg), rifampin(600 mg), and
ethambuto​l(25 mg/kg)

MAC Pulmonary ● fibrocavitary MAC lung disease or severe

Disease nodular/ bronchiectatic disease:​ daily
clarithromycin(500–1,000mg) or
azithromycin(250 mg), rifampin(600 mg) or
rifabutin(150–300 mg),and ethambutol(15
mg/kg) with consideration of 3X weekly
amikacin or streptomycin

● Clarithromycin(1,000mg/d) or
Disseminated MAC azithromycin (250 mg/d) and
Disease ethambutol(15 mg/kg/d) with or without
rifabutin(150–350 mg/d)

● AIDS patients with CD4 T-lymphocyte

Prophylaxis of counts less than 50 cells/l
Disseminated ● Azithromycin 1,200 mg/week or
MAC Disease clarithromycin 1,000 mg/day, alternative
Rifabutin 300 mg/day

Treatment of ● surgical excision, >90% cure rate

NTM Cervical ● macrolide-based regimen should be

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 Lymphadenitis considered for patients with extensive
MAC lymphadenitis or poor response to
surgical therapy

3. Fever, dysuria, and oligoarthritis (MONDELO, MARAMBA, PAMATIAN)

Case: 62/M, left hip pain, [alcoholic, with renal failure, increased creatinine]
● Key Points for Discussion:
○ Disseminated Gonococcal Infection
○ Infectious Arthritis
● Info about the case:
○ Sexual history = important!
○ Ask about hx of stone passage (urolithiasis)
○ First aid for acute gouty attack: cold compress
○ If patient is already taking allopurinol, he/she must continue
○ NSAIDs + Allopurinol -- not for Acute gout - anything that will alter uric acid levels in the
blood will exacerbate the symptoms
○ NSAIDs + colchicine = Acute Gouty Arthritis (traditional = no adjustment)
○ NSAIDs contraindication: kidney problem - always consider Renal function
○ Short-acting / Intra-articular Steroids -- if there is really a need for an anti-inflammatory
and patient cannot take NSAIDs due to kidney problems
● Principles of Management of Septic Arthritis:
○ DRAINAGE
○ ANTIBIOTIC
● Gonococcal arthritis ​(more common than true gonococcal septic arthritis)
○ Consequence of bacteremia arising from gonococcal infection or more frequently, from
asymptomatic gonococcal mucosa colonization of the urethra, cervix or pharynx
○ Greatest risk: during menses and pregnancy
○ Strains that are most likely to cause DGI:
■ Those which produce transparent colonies in culture
■ Type IA outer membrane protein
■ AUH-auxotroph type
○ Joint involvement: asymmetric UE > LE; knees, elbow, ankle, wrist
○ Triad of DGI:
■ Tenosynovitis
■ Migratory polyarthritis
■ Dermatitis
○ Bacterial dissemination:
■ Menstruation
■ IUD
■ Complement deficiencies (complements involved in the assembly of MAC
[C5-C9])
○ Risk factors:
■ Urban; IV drug use
■ Female > Male - because of Opa protein which helps for penetration
■ Low socioeconomic status
■ Previous history of gonococcal infection
■ Low education
■ Pregnancy
■ Pelvic operations
■ Patient: (+) prostitution (+) previous gonococcal infection
○ Clinical manifestations:
■ Bacteremic (less commonly seen nowadays)
● higher temperature; chills more frequently accompany their fever
● painful joints; often occur together with tenosynovitis and skin lesions
● polyarthralgias (knees, elbows, and more distal to joints axial skeleton is
generally spared)

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 ● skin lesions such as papules and pustules, often with hemorrhagic
component (usually on extremities)
● DDx: RA
■ Joint-localized stage with suppurative arthritis
● involves 1 or 2 joints - most often the knees, wrist, ankle, elbows in
decreasing order of frequency)
● most patients who develop gonococcal septic arthritis do so without prior
polyarthralgias or skin lesions
○ In the absence of symptomatic genital infection, it cannot be
distinguished from septic arthritis caused by other pathogens
○ rarely, osteomyelitis complicates septic arthritis involving small
joints of hand
● DGI triad (dermatitis, tenosynovitis and asymmetric arthritis) can be seen
here
■ Arthritis symptoms similar to those seen in DGI occur in meningococcemia. A
dermatitis-arthritis syndrome, purulent monoarthritis and reactive polyarthritis have
been described and all respond to IV penicillin.
■ Complications (rare): Gonococcal endocarditis and meningitis
○ Diagnosis:
■ Imaging
● Ultrasound: Useful for determining inflammation and fluid accumulation
(fluid = black)
● > 6.5 - 7.5 mL = fluid in periosteal neck
● Compare with the unaffected side: (+) if >2 mm difference
● (+) halo sign = flexor tendonitis with surrounding fluid collection (not
arthritis)
■ it is difficult to isolate gonococci from synovial fluid and blood, specimens for
culture should be obtained from potentially infected mucosal sites
● Modified Thayer-Martin agar
○ Always request if with ​clinical suspicion
○ What if agar is not available?
■ Hx & PE + Gram stain of penile discharge
■ Therapeutic trial
○ Treatment:
■ In treating patients with gonococcal infection, ALWAYS treat his COUSINS
(Package deal)​: ​Chlamydia trachomatis and ​Mycoplasma urealyticum with
Azithromycin
■ IV Ceftriaxone 1 g q 24h + single dose of Azithromycin 1 g
■ 4 - 6 weeks (complicated)
■ 250 mg IM Ceftriaxone + Azithromycin / Doxycycline (uncomplicated)
■ INITIAL THERAPY:
● Patients tolerant of beta-lactam drugs - ​Ceftriaxone (1g IM or IV q24h -
recommended) or Cefotaxime or Ceftizoxime (both 1g IV q8h) +
Doxycycline 100mg bid for 7 days
● Once local and systemic signs are clearly resolving, 7-day course of
therapy can be completed with an oral ​fluoroquinolone (ciprofloxacin
500mg bid) if the organism is known to be susceptible. If
penicillin-susceptible organisms are isolated, ​amoxicillin (500mg tid) ​may
be used.
● Patients allergic to beta-lactam drugs ​- Spectinomycin​ (​ 2g IM q12h)
■ CONTINUATION THERAPY:​ Cefixime (400 mg PO bid) for 2 more weeks
● This is the ​Step-down treatment ​after ​48 hours
● Rationale: Cefixime is an ​oral​ gonococcal-effective antibiotic.
■ Hospitalization is indicated if:
● Diagnosis is uncertain
● Patient has localized joint disease that requires aspiration
● Patient cannot be relied on to comply with treatment

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 ● *OPEN DRAINAGE - necessary only occasionally (for management of hip
infections that may be difficult to drain percutaneously
■ NSAIDs - alleviate pain and hasten clinical improvement of affected joints
■ Suppurative arthritis ​- usually responds to needle aspiration of involved joints and
7-14 days of antibiotic treatment
○ Prevention:
■ Patient’s last sexual encounter >60 days before onset of symptoms or diagnosis =
most recent sexual partner should be treated
■ Abstain from sexual intercourse until therapy is completed and until they and their
sex partners no longer have symptoms
● Infectious Arthritis/Septic Arthritis
○ Most common Cause:
■ Staphylococcus aureus
■ Neisseria gonorrhoeae​ - Sexually active
○ Remember: ​ All inflamed joints are in need of rapid evaluation
○ If the joint is red, swollen and tender: Infectious arthritis unless proven otherwise
○ Destroys articular cartilage rapidly
○ Acute presentation: Think Bacterial etiology
○ Subacute or Chronic: Mycobacterial or Fungal etiology
○ Most common route: Hematogenous
○ Polymicrobial infections: Consider in ​Trauma​ or ​DM patients
○ Clinical Manifestation: monoarthritis (Most common: KNEE)
○ Differential Diagnosis: Cellulitis, Bursitis and Acute Osteomyelitis
○ Remember: ​Decreased range of motion with Septic Arthritis
○ Radiographic:
■ Ultrasound; Plain radiograph and CT or MRI - Shows signs of inflammation
(effusion, narrowing; poor prognosis)
○ Laboratory Findings:
■ Do Arthrocentesis
■ Request: Microbiology, Cell count (Bacterial: 25,000-250,000/cumm; >90% PMN)
■ Definitive Diagnosis: ID of pathogen through culture from synovial fluid or
blood
● Or via Nucleic Acid Amplification Test and Immunologic techniques
● Bottomline: You must identify the pathogen
○ Treatment for Nongonococcal Bacterial Arthritis
■ Principle: 1. Drainage and 2. Systemic Antibiotic (Always Bactericidal - do
not give static)
■ Empiric Therapy based on the Smear
● IV 3rd gen cephalosporin (cefotaxime: 1g q8h) or (ceftriaxone: 1-2 g q
24h)
○ Adequate for most community acquired infections in adults when
no organisms on smears)
● IV vancomycin (2g q 4h)
○ Gram-positive cocci
● In the Philippines, more common is MSSA so use oxacillin or nafcillin (2g
q 4h) for 4 weeks
● Aminoglycosides with 3rd gen or an Antipseudomonal antibiotics
○ For IV drug users and suspected with P. aeruginosa
● 2nd or 3rd gen Fluoroquinolones (Levofloxacin) for 3-4 weeks
○ For enteric gram negative
● Penicillin G (2 MU IV q4h) for 2 weeks
○ Pneumococcal and Streptococcal
● Cefotaxime or Ceftriaxone for 2 weeks
○ For Penicillin resistant ​Streptococcus pneumoniae and
Haemophilus influenzae
■ Drainage
● Needle aspirations - For readily accessible joints (knee)
● Arthrotomy

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 ○ Best management for hip infection which threatens the viability of
the femoral head
○ Remove loculation and debride infected synovium, cartilage or
bone
■ Other management:
● Timely drainage
● Immobilization is for pain control only and avoid weight bearing until
inflammation subsides
● Frequent Passive motion of the joint
● Maintain full mobility of the joint

4. Prolonged fever and cervical lymphadenopathy (JOSE, MAÑEGO, LAPITAN)

Case: 27/M, prolonged fever (6 weeks duration)
● Monospot test performed to R/O infectious mononucleosis
● Anemia in a male patient: ​red flag
○ Get retic count and compute for PRI
○ RBC destruction / production failure / blood loss
● DDx:
○ Pulmonary tuberculosis
○ Chronic viral infection (EBV/CMV/HIV)
○ Malignancy (lymphoma)
● RPI > 2
○ Blood loss
○ Hemolysis/RBC destruction
○ Decreased production
● Initial diagnosis: Community-acquired Pneumonia with Oral thrush
● 4 types of fever:
○ Classic
○ Nosocomial
○ Neutropenic
○ FUO with HIV infection
● Fever of unknown origin (FUO)
○ >4 weeks of outpatient or >3 days of hospital admission
○ Think of: infection / malignancy / rheumatic autoimmune disease
● Clues for PCP: ssx with elevated LDH, bilateral hilar infiltrates, rhonchi
● Definitive diagnosis: Methenamine silver staining
● Steroids
○ Principle: given to reduce overwhelming inflammation
○ Indication:
■ Severe PCP
■ TB meningitis
■ TB pericarditis
■ Adrenal insufficiency secondary to sepsis
● Course of HIV Infection

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 ○ Eclipse Phase
■ 0-10 days
■ Virus cannot be detected in the plasma
○ Acute HIV infection (Primary Infection)
■ Acute Retroviral Syndrome
● Disseminated infection
● Seeding of lymphoid organs
■ Mononucleosis-like symptoms appear 3-6 weeks after initial HIV exposure
■ Duration of symptoms: 10-28 days
■ Low CD4, High viremia
○ Clinical Latency
■ virus is replicating (may last for 10 years)
■ CD4 is consumed
■ HIV-infected cells at LN and lymphoid organs
○ Elevated HIV Expression
○ Clinical Disease
■ Advanced HIV/ AIDS
● CD4 count < 200/uL
● increased susceptibility to opportunistic infections
● progressive depletion of CD4 count
○ Death
● Staging

Laboratory Axis Clinical Axis

Total Lymphocyte CD4 Count** Stage 1 Stage 2 Stage 3 Stage 4

Count*

A > 2000 > 500 1A 1B 3A 4A

B 1000-2000 200-500 1B 2B 3B 4B

C < 1000 < 200 1C 2C 3C 4C

*RR TLC: 1500-4000/ mm3, ** RR CD4: 450-1400/mm3, STAGES IN RED ARE DEFINED ​AIDS

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● Work up for HIV
○ Serologic Determination of ANTIGEN
■ RT PCR amplifies HIV RNA (viral load)
● Marker of disease progression
● Monitor response to HAART
■ P24 antigen capture
● Low levels may be detected by EIA soon after infection
● But undetectable once complexed with p24 antibodies
● NAT: combines P24 antigen with antibody testing (4th generation)
○ Serologic Determination of ANTIBODIES
■ Screening: ELISA
● Detects IgG & IgM
● (-) result does not rule out HIV in a susceptible host, may be false (+) due
to cross-reaction
■ Confirmatory: Western blot assay
● Viral core protein- p24
● Envelope glycoproteins- gp41, gp120, gp160
○ Window period:
■ 3rd gen Antibody: 22 days
■ Standard Antigen: 16 days
■ Nucleic acid: minus 4-6 days
● Other Work up
○ Tuberculosis
■ TB culture: also for other Mycobacteria spp, may show resistance to other drugs
■ Gene xpert: PCR + rifampin resistance; rapid (<24h)
○ STI - syphilis, Hepatitis B, Hepatitis C
■ High risk for co-infection in an immunocompromised host
○ Since CD4 <50
■ Mycobacterium avium intracellulare
■ Toxoplasma gondii infection - neurologic exam
■ Cytomegalovirus infection - ophthalmologic exam (blurring of vision)
● Treatment
○ Goals
■ Control HIV infection (LOW HIV RNA viral load - <50 copies/ mL)
■ Restore immune status (HIGH CD4 T cell count- > 500 cells/uL)
○ HAART (Highly Active Antiretroviral Therapy)
■ Initiate to ALL HIV-infected patients regardless of CD4 count
■ Combination therapy
● disrupt multiple viral processes (sites) to suppress replication
● Avoid development of drug resistance

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 ● Preferred regimen: 2 NRTI + NNRTI/Protease inhibitor/Integrase strand
transfer inhibitor
● Example: Tenofovir + Lamivudine + Efavirenz or Lopinavir/ritonavir or
Dolutegravir
■ Limitation
● NOT curative due to infected cells in latency areas (ex. brain, lymph
nodes, bone marrow)
● HIV drug resistance and intraclass cross-resistance
● Short- and long-term toxicities
○ HIV with Hep B
■ Do not give antibiotics for HIV only
■ Drugs:
● Tenofovir + Lamivudine
● Tenofovir + Emtricitabine
○ HIV & MTB
○ Start ART and HRZE simultaneously, except if the infection is in the CNS
○ Treatment of HIV and non-HIV patients with tuberculosis is the same

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ALGORITHMS AND TABLES FROM READING ASSIGNMENTS (MABANTA, PLES)

ID ALGORITHMS AND TABLES

TETANUS

RABIES

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LEPTOSPIROSIS

CHOLERA

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MALARIA

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SCHISTOSOMIASIS

MENINGITIS

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PSEUDOMONAS

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SYPHILIS

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URETHRITIS

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RHEUMA
DIAGNOSIS OF MSK COMPLAINTS

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GLOSSARY OF MSK TERMS

SYNOVIAL FLUID ANALYSIS & INTERPRETATION

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DIAGNOSTIC IMAGING FOR MSK DISORDERS

CRITERIA FOR DIAGNOSIS OF INFLAMMATORY MYOPATHIES

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COMMON CONDITIONS IN THE DIFFERENTIAL DIAGNOSIS OF FIBROMYALGIA

CLINICAL FEATURES OF ANTIPHOSPHOLIPID SYNDROME

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LIMITED VS DIFFUSE CUTANEOUS SYSTEMIC SCLEROSIS

PATHOGENESIS OF SYSTEMIC SCLEROSIS

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CLINICAL ORGAN DEVELOPMENT OF SYSTEMIC SCLEROSIS

SJOGREN’S SYNDROME

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