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RHEUMATOLOGY Symptoms Deep aching, cramping pain in thigh pr calf,

Shanida L. Camomot, MD, FPPS, FPRA usually in the vening or during the night;
never present in the morning bilateral;
BENIGN HYPERMOBILITY JOINT SYNDROME (BHJS) responds to massage and analgesia
Signs Physical examination results are normal
- Children with musculoskeletal pain associated with generalized Investigations Laboratory and hagiographical studies are
hypermobility of the joints (or “double-jointedness”) without any normal
associated congenital syndrome or abnormality of connective
tissue - May be precipitated by exercise
- Affects children 3 to 10 years old - Usually relived by massage
- Girls are hypermobile about twice as often as boys are - Occurs evenings or night time lasting minutes to hours and often
- Ballet dancers and musicians interrupting sleep but disappearing by morning
- The cause of pain in hypermobile children with no evidence of - Frequency of attacks varies often following a day of high physical
structural joint damage is not clear activity
- Hypermobility is frequently associated with intermittent pains - Never associated with fever, weight loss, night sweats, easy
following physical activities bruising, or a limp
- Temporomandibular joint dysfunction may be a consequence of - Have completely normal patterns of activity and normal physical
hypermobility examinations during and after the episode
- Mild joint effusions may be observed - Laboratory studies and radiography are normal
- There does not appear to be a greater prevalence of joint - Etiology and pathophysiology of the pain is unknown
dislocation but more frequent ankle sprains have been reported - Theories:
➢ Lower pain threshold
Criteria for Hypermobility ➢ Overuse
➢ Decreased bone strength
➢ Biomechanical abnormalities
➢ Maternal anxiety

Management
- Education of the child and family about the benign nature of the
problem
- Gentle massage with or without analgesics
- For frequent attacks, administration of an evening dose of either
acetaminophen or an NSAID may be preventive

Management
- Reassurance is the initial treatment of hypermobility
- Supportive footwear, taping or bracing of troublesome joints, use
of orthotics and post activity or evening dose of acetaminophen
or a non steroidal anti inflammatory drug (NSAID) may benefit
- More severely affected children may be helped by formal physical
therapy that focuses on reestablishment of normal muscle power
and overall reconditioning
- Although hypermobility may enable a child to be a good gymnast
or ballet dancer, injuries may be more frequent
- Children who “crack their knuckles” are frequently hypermobile

Growing Pains
- A misnomer
- The pain does not coincide with the peak growth of the child
- Benign Nocturnal Pains of Childhood
- Affects 10% to 20% of children
- Most likely to occur in preschool- to school-aged children
- Non-articular
- Affects both lower extremities and is often located deep in the
thigh, shin, and calf or behind the knee
- Children who have unusual symptoms or abnormal findings on
examination (tenderness, local swelling, or erythema) should not
be diagnosed with this condition

Growing Pains (benign nocturnal pains of childhood)

Age at onset 4-12 years old
Sex ratio Probably equal, slightly more girls in some
series

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Diagnostic Tests
- there is no specific screening tests for rheumatic disease
- appropriate testing and work up is directed by the differential
diagnosis

Essential laboratory test for rheumatic disease are:

• CBC
- increased white blood cell count is compatible with malignancy,
infection, systemic, JIA and vasculitis
- Leukopenia can be due to post infectious especially viral SLE or
malignancy
- Lymphopenia is more specific for SLE than is leukopenia
- Platelets are acute phase reactants and are therefore elevated in
inflammation exceptions in: bone marrow-occupying malignancy
exceptions or neuroblastoma, SLE, early Kawasaki disease
- Anemia is nonspecific and maybe due to chronic illness. SLE has
hemolytic type of anemia
• Inflammatory markers
- ESR (erythrocyte sedimentation rate) and CRP ( C reactive
protein)
-
Are more useful in rheumatic disease for following response
to treatment than as diagnostic tests
• Muscle Enzyme markers
- AST (Aspartate aminotransferase)
- ALT (alanine amnotranspeferase)
- Creatinine phopshokinase (CPK)
- Aldolase
- LDH (lactate dehydrogenase)

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Radiologic Investigation of Rheumatic Disease - Can help differentiate osseous cause of joint Ain from other
• Radiography causes, including synovial, neuromuscular or periarticular soft
- Remains the initial and most commonly used means to evaluate tissue disorders
joint abnormalities - Used to assess whether an osseous lesion is solitary or multifocal
- Radiographic features of joint disease and can reveal increase activity across the joint in arthritis or
➢ Osteopenia infection used also to diagnose bone cancers and assess bone
➢ densitometry
Joint effusions
➢ Joint space narrowing with local or diffuse cartilage thinning RHEUMATIC DISEASES OF CHILDHOOD
➢ Bone erosions, subchondral cysts, and bone resorptions
➢ Changes in size of ossification centres MODELS FOR MEDICAL PROBLEM SOLVING
➢ - Algorithmic
Subchondral sclerosis and osteophyte formation
- Hypotheticodeductive
➢ Periosteal new bone formation - Exhaustive
➢ malalignment, subluxation, dislocation - Pattern Recognition
➢ Joint anklylosis
➢ EVALUATION OF SUSPECTED RHEUMATIC DISEASE
Joint disorganisation and destruction - Rheumatic diseases – are a constellation of signs or symptoms,
➢ Soft tissue swelling, atrophy and calcification results of physical examination, autoimmune markers/serologic
➢
Spinal manifestations tests, tissue pathology and imaging
• Sonography - Recognition of clinical patterns remains essential for diagnosis
- because there is no single diagnostic test
Ideal for assessing the pediatric musculoskeletal system, largely
- Evolution of symptoms overtime
because of its ability to visualize intraarticular structures such as
- The primary mimics of rheumatic diseases are infection,
cartilage and thickened synovium without the need fo radiation
malignancy, metabolic, orthopedic and chronic pain conditions
- Very sensitive in detecting joint effusion, particularly in the hip - Exclusion of possible mimicking disorders is essential before
and shoulder where pain film are insensitive initiation of treatment for a presumptive diagnosis, especially
- Can also be used to guide joint aspiration or injection tendons corticosteroids
and ligaments ca be assessed with higher frequency transducers
- SYMPTOMS SUGGESTIVE OF RHEUMATIC DISEASE
Vascular anatomy can be assess by combining sonography with - Arthralgia
doppler effects (synovial hyperemia leads to increased Doppler ➢ Are common in childhood
signal) ➢ Frequent reason for referral to pediatric rheumatologists
-Used to to assess for other periarticular soft tissue abnormalities ➢ Joint pains without physical findings for arthritis
including popliteal cysts or other soft tissue masses ➢ Look and ask for associated signs and symptoms
• Computed tomography scanner (CT scan) - Fatigue
- Generate detailed high resolution images of bone and can be ➢ A nonspecific symptom
used to evaluate the joint space and detect adjacent bone ➢ A common presenting complaint in juvenile dermatomyositis
abnormalities including tarsal coalitions, bone erosion, (JDM)
subchondral cysts or primary osseous lesions such as osteoid ➢ It is also commonly present in SLE, vasculitis, and the
osteoma chronic childhood arthritides
- Myalgia – muscle pain
- Faster and sedation is generally not required for all except for
younger patients
- intravenous contrast may be required for soft tissue assessment
• Magnetic Resonance Imaging (MRI)
- Provides exquisite multiplanar images with superb tissue contrast
- Can define vascular anatomy, often without need for intravenous
contrast
- High cost, limited availability ad the frequent need for sedation
have limited its more widespread used
- The best modality to examine all joint components (except
cortical bone ) including bone marrow, hyaline and fibrocartilage,
ligaments, menisci, synovium and joint capsule, joint fluid and - Many rheumatic diseases have multi-system effects
the ossified cartilaginous skeleton. - Complete physical examination is mandated in any child whom a
- Can be used to demonstrate muscle pathology, typically rheumatic disease is suspected
demonstrating nonuniform, increase signal intensity on T2
weighted images and normal signal on T1-weighted images and
useful in selection of muscle biopsy site
• Arthrography
- Diagnostic study of the joint structures within the body by
injection of x-ray contrast dye
- Intraarticular contrast injection maybe combined with CT or with
MRI to better delineate joint detail including the evaluation of the
intraarticular loose bodies or labral tears within shoulder or hip
joint
• Bone Scintigraphy (bone scan )
- Nuclear scanning test to find certain abnormalities in bone

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“Shawl Sign” (Juvenile Dermatomyositis)

Gottron papules (Juvenile Dermatomyositis)

VASCULITIDES IN CHILDHOOD

VASCULITIS – inflammation of the blood vessel

VASCULOPATHY – broader term; abnormality of blood vessel
(inflammatory, degenerative or result intimal proliferation)

- the onset of some vasculitides (e.g, HSP, KD) is usually abrupt

- Diagnostic characteristics of the disease become apparent in
a few days to a week
- In many of the vasculitides, presentation is more indolent, and
various signs and symptoms developing over weeks to months
are characteristics
- The diagnosis is often difficult and delayed, and it requires a
high index of suspicion and a thorough investigation
- Definitive diagnosis frequently requires a biopsy of one or
more sites, magnetic resonance angiography or arteriography

Epidemiology
- the incidence and prevalence of vasculitis in children are
unknown
- the most common vasculitides are HSP and KD
- There are striking geographic differences in relative disease
frequency IMMUNOGLOBULIN A VASCULITIS (HENOCH SCHONLEIN
- KD and Takayasu arteritis are most prevalent in Japan PURPURA)
- KD and HSP are the most common disorders in north America
and Europe - is the most common vasculitis of childhood
- Characterized by leukocytoclastic vasculitis and
immunoglobulin (Ig) A deposition in the small vessels in the
skin, joints, gastrointestinal tract and kidney

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• Renal manifestations
Epidemiology - occur in up to 50% of children
- incidence of IgAV is estimated at 14-20/100,000 children per - Manifests as hematuria, proteinuria, hypertension, frank
year nephritis, nephrotic syndrome, and acute or chronic renal
- Affects males more than females, with a 1.2-1.8:1 male: failure
female ratio - Progression to end-stage renal disease is uncommon in
- 90% of IgAV cases occur in children, usually between the children (1-2%)
ages of 3 and 10 yr • Neurologic manifestations
- Many cases of IgAV follow a documented upper respiratory - due to hypertension or central nervous system (CNS)
infection vasculitis
- Include intracerebral hemorrhage, seizures, headaches, and
Pathology behavior changes
- skin biopsies demonstrate vasculitis of the dermal capillaries
and postcapillary venules Diagnosis
- Renal histopathology typically shows endocapillary - diagnosis is clinical
proliferative glomerulonephritis, ranging from a focal - At least 25% of cases, the rash appears after other
segmental process to extensive cresenteric involvement manifestations, making early diagnosis challenging
- Immunofluorescence identifies IgA deposition in walls of small
vessels accompanied to a lesser extent by deposition of C3, Laboratory findings
fibrin and IgM - no lab findings is diagnostic
- the exact pathogenesis remains unknown - Non specific findings include leukocytosis, thrombocytosis,
- An infectious trigger is suspected mild anemia, and elevations of erythrocyte sedimentation rate
- The common finding of deposition of IgA, specifically IgA1, (ESR) and C-reactive protein (CRP)
suggest that it is a disease mediated by IgA and IgA immune - Occult blood is frequently found
complexes - Autoantibody testing is not useful diagnostically
- Occasionally cluster in families, suggesting a genetic - Serum IgA values are often elevated but are not routinely
component measured
- HLA-B34 and HLA-DRB1 01 alleles have been linked to HSP - Ultrasound is often used in gastrointestinal complaints to look
nephritis for bowel wall edema or the rare occurrence of an associated
intussusception
Clinical manifestations - Biopsies of skin and kidney can provide important diagnostic
• RASH information, particularly in atypical or severe cases
- hallmark of IgAV is its rash: palpable purpura starting as pink
macules or wheals and developing into petechiae, raised Treatment
purpura, or larger ecchymoses - Supportive
- Bullae and ulcerations sometimes develop - Adequate hydration, nutrition, analgesia and control of
- Skin lesions are usually symmetric and occur in gravity- hypertension
dependent areas (lower extremities) or on pressure points - Steroids are most often used to treat significant
(buttocks) gastrointestinal involvement or other life-threatening
- Skin lesions often evolve in groups, typically lasting 3-10 days, manifestation
and may recur up to 4 mo after initial presentation - Empiric use of prednisone (1mg/kg/day for 1 to 2 wk, followed
by taper) reduces abdominal and joint pain but does not alter
overall prognosis nor prevent renal disease
- Intravenous immune globulin and plasma exchange are
sometimes used in the setting of severe disease
- Other medications: Azathioprine, Cyclophosphamide, and
mycophenolate.
- End-stage renal disease develops in up to 8% of children with
IgAV nephritis

Complications
- Serious gastrointestinal involvement such as intestinal
perforation imparts significant morbidity and mortality
- Renal disease is the major long-term complication
- Renal disease can develop up to 6 months after diagnosis but
rarely does so if the initial urinalyses findings are normal
- Recommended that children undergo serial monitoring of
- Subcutaneous edema localized to the dorsa of hands and feet,
blood pressure and urinalyses for 6 months after diagnosis,
periorbital area, lips, scrotum, or scalp is also common
especially those who presented with hypertension or urinary
abnormalities
• Musculoskeletal involvement
- includes arthritis and arthralgias
Prognosis
- Occur in up to 75% of children
- Overall, the prognosis for childhood is excellent
- Arthritis tends to be self-limited and oligoarticular
- Most children experience an acute, self-limited course
- Predilection for the lower extremities
- 30% of children experience one or more recurrences, typically
- Does not lead to deformities
within 4-6 months of diagnosis
- Arthritis usually resolves within 2 wk but can recur
- Each relapse, symptoms are usually milder than at
• Gastrointestinal in manifestations
presentation
- occur in up to 80% of children include abdominal pain,
- Chronic renal disease develops in 1-2%
vomiting, diarrhea, paralytic ileus, melena, intussusception
and mesenteric ischemia or perforation
- Endoscopic evaluation is usually not needed but may identify
purpura of the intestinal tract
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ANCA ASSOCIATED VASCULITIS (AAVS) myalgias, and arthralgias

- ANCA-associated vasculitides are characterized by small - In WG:
vessel involvement ➢ upper airway involvement (sinusitis, nasal
- Associated with circulating antineutrophil cytoplasmic ulceration, epistaxis, otitis media, and hearing
antibodies (ANCA) loss)
- Pauci-immune complex deposition in affected tissues ➢ lower respiratory tract (cough, wheezing, dyspnea,
- ANCA-associated vasculitis is categorized into three distinct and hemoptysis
forms: ➢ pulmonary hemorrhage
A. Wegener granulomatosis (WG) - Compared with WG in adults, childhood WG is more frequently
B. Microscopic polyangitis (MPA) complicated by subglottic stenosis
C. Churg-Strauss syndrome (CSS) - Inflammation-induced damage to the nasal cartilage can
produce saddle nose deformity in WG
Epidemiology - Perineural vasculitis or direct compression on nerves by
• WG granulomatous lesions can cause cranial and peripheral
- Necrotizing granulomatous small vessel vasculitis that occurs neuropathies
at all ages - Hematuria, proteinuria, and hypertension
- Targets the respiratory tract and the kidneys - Cutaneous lesions include palpable purpura and ulcers
- mean age at diagnosis of 14 yr - Frequencies of organ system involvement throughout the
- female predominance of 3-4:1 disease course in WG are: respiratory tract 84%, kidneys
• MPA 88%, joints 44%, eyes 60%, skin 48%, sinuses 56%, and
- a small vessel necrotizing vasculitis with clinical features nervous system 12%
similar to those of WG - Clinical presentation of MPA closely resembles that if WG,
• CSS although sinus disease is less common
- a small vessel necrotizing granulomatous vasculitis associated - Like WG, CSS frequently causes inflammation of the upper
with a history of refractory asthma and peripheral eosinophilia amd lower respiratory tract, but cartilage destruction is rare
- Unlike in WG, renal involvement in CSS is uncommon, and
Pathology CSS tends to involve nerves, gastrointestinal tract,
- Necrotizing vasculitis is the cardinal histologic feature in EG pericardium, and skin
and MPA
- Kidney biopsies typically demonstrate crescentic Diagnosis
glomerulonephritis with little or no immune complex - WG should be considered in children who have recalcitrant
deposition (“pauci-immune”), in contrast to biopsies from sinusitis, pulmonary infiltrates and evidence of nephritis
patients with SLE - Chest CT may show nodules, ground-glass opacities,
- Granulomatous inflammation is common in WH and CSS, but mediastinal lymphadenopathy, and cavitary lesions
typically not present in MPA - Diagnosis is confirmed by the presence of anti-proteinases 3
- Biopsies showing perivascular eosinophilic infiltrates (anti-PR3)-specific ANCAs (PR3-ANCAs) snd the finding of
distinguish CSS syndrome from both MPA and WG necrotizing granulomatous vasculitis on pulmonary, sinus, or
renal biopsy
Differential Diagnostic Features of Small Vessel Vasculitis - ANCA test result is positive in approximately 90% of children
with WG, and the presence of anti-PR3 increases the
specificity of the test
- In MPA, ANCAs are also frequently present but have reactivity
to myeloperoxidase (MPO-ANCAs)
- MPA can be distinguished from polyarteritis nodosa, (PAN) by
the presence of ANCAs and the tendency for small vessel
involvement
- ANCA test result is positive in approximately 70% of the cases
of CSS, and MPO-ANCAs are more common than PR3-ANCAs
- The presence of chronic asthma and peripheral eosinophilia
suggests the diagnosis of CSS

Laboratory Findings
- Elevated ESR and CRP values, leukocytosis, and
thrombocytosis
- Anemia may be due to chronic inflammation or pulmonary
hemorrhage
- ANCA antibodies show two distinct immunofluorescence
patterns: peri nuclear (p-ANCAs) and cytoplasmic (c-ANCAs)
- WG is strongly associated with c-ANCAs/anti-PR3 antibodies
- Etiology of ANCA-associated vasculitis remains unknown
- Neutrophils and monocytes are activated by ANCAs, Treatment
specifically by the ANCA-associated antigens proteinase-3 - Initial therapy usually consists of corticosteroids (2 mg/kg/day
(PR3) and MPO releasing pro inflammatory cytokines (TNFa oral of 30 mg/kg/day for 1-3 days given intravenously) in
and IL8) conjunction with daily oral cyclophosphamide (2 mg/kg/day)
- Why the respiratory tract and kidneys are preferential targets - Transitioned to a less toxic medication (usually methotrexate
in WG and MPA is unknown or azathioprine) within 3 to 6 months once remission is
- Infectious agents and genetic factors have been implicated in achieved
disease susceptibility Complications
- Upper respiratory tract lesions can invade the orbit and
Clinical Manifestations threaten the optic nerve
- Early disease course is characterized by nonspecific - Lesions in the ear can cause permanent hearing loss
constitutional symptoms including fever, malaise, weight loss, - Pulmonary hemorrhage and upper airway obstruction due to

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subglottic stenosis - Usually indistinguishable from canker sores and appear on the
- Chronic lung disease secondary to granulomatous lips, tongue, palate and elsewhere in the GI tract
inflammation, cavitary lesions, and scarring can predispose to
infectious complications • Anterior uveitis
- Chronic glomerulonephritis may progress to end-stage renal - Has significant morbidity
disease
- Seen in 30-60% of pediatric patients
- Main symptoms: blurred vision, redness, periorbital or global
Prognosis
- Accompanied by disease relapse in approximately 75% of pain and photophobia
patients - Complications include blindness (unusual with treatment),
- Mortality has been reduced with the introduction of glaucoma and cataracts
cyclophosphamide and other immunosuppressive agents
- Children with ANCA-associated vasculitis have fewer • Skin lesions
treatment-associated morbidities and malignancies than - Range from erythema nodosum, papulopustular acneiform
adults. lesions, folliculitis, purpura and ulcers
- Pathergy is also a skin feature that is pustular reaction
BECHET DISEASE AND SJOGREN SYNDROME occurring 24-48hr after a sterile needle puncture or saline
injection (it is not pathognomic of BD)
BECHET DISEASE (BD)
- is classified as a primary variable vessel vasculitis, • Vasculitis
emphasizing the involvement of any size and type (arterial, - Involves both arterial or venous thrombosis and aneurysm
venous) of vessel formation or occlusions or stenosis in arteries of any size
- recognized as an autoinflammatory disease - In children, deep venous thrombosis of the lower limbs is the
- originally described with recurrent oral ulcerations, uveitis and most frequent vasculitic feature
skin abnormalities - Pulmonary aneurysms are the most severe feature if pediatric
BD and associated with the highest mortality
Epidemiology - Coronary artery aneurysm may confuse BD with Kawasaki
- Has a prevalence of 5-7 per 100,000, which makes it more disease
frequent than any other vasculitides such as granulomatosis
polyangiitis (Wegener disease) • Central Nervous System
- Prevalence in children is probably not more than 10% of the - Manifestations in children: meningoencephalitis (headache,
adult counterparts in eastern Mediterranean countries meningismus, cerebrospinal fluid pleocytosis),
- Boys and girls are equally affected encephalomyelitis, pseudotumor cerebri, dural sinus
- Family history of BD is present in approximately 20% of the thrombosis and organic psychiatric disorder (psychosis,
cases depression, dementia)
- Onset in children is 8-12 yr of age - Dural sinus thrombosis is the most common CNS
- Newborns of affected mothers have demonstrated symptoms manifestation in children
of BD
• Gastrointestinal involvement
Etiology & Pathogenesis - Manifests with abdominal pain, diarrhea and intestinal
- Polygenic autoinflammatory disorder ulcerations, most often in the ileocecal region
- Genetic contribution to BD is evident - Gastrointestinal BD may be difficult to distinguish from
- Well known association with HLA-B5101 inflammatory bowel disease
- Autoinflammatory nature of the disease is suggested by the
episodic nature of the disease, absence of identifiable Diagnosis
autoantibodies and the co-association with MEFV - International study group criteria are most widely used
(Mediterranean fever) gene - Require the presence if oral ulcers (at least 3 times per year)
- An infectious agent may be responsible for inducing the along with 2 other major features, including genital ulcers, a
aberrant innate immune system attacks in the genetically positive pathergy test, uveitis and characteristic skin lesions
predisposed host - incomplete or partial Bechet disease-if only 1 of the criteria is
- Infectious agents have been implicated: streptococci, herpes present along with oral ulcerations
simplex virus type 1 and parvovirus B19 - There are no specific laboratory tests
- Acute-phase reactants are often mildly elevated
Clinical Manifestations and Diagnosis - The diagnosis relies on the constellation of symptoms and
- Course of BD is characterized by exacerbations and remissions excluding other causes.
- Mean age of the first symptom is between 8 and 12 yr of age
- The most frequent initial symptom is a painful oral ulcer

• Other Ulcers and Genital Ulcers

- Oral ulcers are often recurrent, may be single or multiple,
range from 2-10mm and may be in any location in the oral
cavity
- Often very painful
- Last 3-10 days and heal without scarring
- Genital ulcers heal with scars and noted in 60% of the patients
after puberty (labia, scrotum, penis, anal area)

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Etiology and Pathogenesis

- Etiology of Sjorgen Syndrome is complex
- Genetically predispositioned and possibly an infectious trigger
- Lymphocytes and plasma cells infiltrate salivary glands,
forming distinct periductal and periacinar foci that becomes
confluent ad may replace epithelial structure

Clinical Manifestations
- Although diagnostic criteria in children has been proposed,
they have not been validated
- Recurrent parotid gland enlargement and parotitis are the
most common manifestations in children (>70%)
- Sicca syndrome (dry mouth, painful mucosa, sensitivity to
spicy foods, halitosis, widespread dental caries) predominate
in adults
- Subjective symptoms of xerostomia complaints are relatively
rare in juvenile cases, perhaps indicating that Sjorgen
Syndrome is a slowly progressive disease
- Increased dental caries
- Decreased sense of smell, hoarseness, chronic otitis media,
leukocytoclastic vasculitis (purpura), diffuse interstitial
lymphocytosis, renal tubular acidosis, arthritis and arthralgia,
cytopenias, optic neuritis, transverse myelitis,
meningoencephalitis
- Serologic markers (antinuclear antibodies, and antibodies to
Ro (SSA) and SSB (La) and articular manifestations are
significantly more frequent in adults
Treatment and Prognosis
Diagnosis
- Azathioprine is highly recommended to treat inflammatory eye
- Clinical presentation of recurrent parotitis and/or recurrent
disease
parotid gland swelling in a child or adolescent is characteristic
- For oral and genital ulcers, topical treatment is recommended
and should raise the suspicion for this disorder
(sucralfate, steroids)
- Diagnosis is based on clinical features supported by biopsy of
- Colchicine is recommended for erythema nodosum or arthritis
salivary or parotid glands demonstrating foci of lymphocytic
in males and females and for genital ulcer in females
infiltration
- In patients without major organ involvement, colchicine
- Schimer Test detects abnormal tear production (<5 mm of
significantly improves oral and genital ulcers, skin features,
wetting of filter paper strip in 5 minutes)
and disease activity.
- Rose-Bengal Staining detects damaged ocular epithelial
- Mortality in children with BD is low except for the pulmonary
conjunctival and corneal cells
aneurysms.
- Young age at onset and male gender are both indicators of a
prolonged disease course.
- The young children who presents with only recurrent oral
mucocutaneous lesions may develop genital ulcerations and
gastrointestinal tract diseases during adolescence.

SJORGEN SYNDROME
- Chronic, inflammatory, autoimmune disease characterized by
progressive lymphocytic and plasma cell infiltration of the
exocrine glands, especially salivary and lacrimal, with
potential for systemic manifestations
- Manifestations: classic symptoms of dry eyes
(keratoconjunctivitis sicca) and dry mouth (xerostomia)

Epidemiology
- Typically manifests at 35-45 years of age
- 90% of cases among women
- Underrecognized in children as symptoms often start in
childhood
- Mean age at diagnosis in children is 9-10 years, 75% are girls
- Can occur as an isolated disorder, referred to as primary
Sjorgen syndrome (sicca complex)
- Occur as secondary Sjorgen syndrome in association with
other rheumatic disorders such as SLE, scleroderma, or mixed
connective tissue disease, and usually precedes the
associated wautoimmune diseases by years

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Differential Diagnosis - Hallmark of SLE is the generation of autoantibodies

- Juvenile recurrent parotitis – characterized by intermittent directed against self-antigens, particularly nucleic acids
unilateral parotid swelling typically lasting only a few days - Individuals with SLE may have markedly increased levels of
- Frequently associated with fever and may undergo remission apoptosis or significantly impaired ability to clear cell debris
with puberty →
- Male predominance - Prolonged exposure to nucleic antigens in the bloodstream
- Seen in younger children (3-6 years of age) and opportunity for their recognition by immune cells, leading
- Absence of focal lymphocytic infiltrates on biopsy to production of autoantibodies by B cells
- Other differential diagnoses: eating disorders, infectious - Individuals with SLE frequently demonstrate abnormal
parotitis (mumps, streptococcal and staphylococcal infections,
cytokine levels (interferon)
Epstein-Barr virus, cytomegalovirus, HIV, parainfluenza,
- Both B and T cells demonstrate functional impairments in
influenza enterovirus) and local trauma to the buccal mucosa
SLE
- B-cell populations have impaired tolerance and increased
Treatment
autoreactivity, enhancing B cells’ ability to produce
- Symptomatic treatment
- Use of artificial tears autoantibodies following exposure to self-antigen
- Massage of the parotids - Increased number of memory T cells and decreased
- Oral lozenges, and fluids to limit the damaging effects of the number and function of T-regulatory cells → display
decreased secretions autoreactivity → resistant to attrition by normal apoptosis
- Corticosteroids, nonsteroidal anti-inflammatory drugs, and pathways
hydroxychloroquine are among the more commonly used
agents for treatment

Complications and Prognosis

- Symptoms of Sjorgen Syndrome develop and progress slowly
- Diminished salivary flow typically remains constant for years
- Increased risk for mucosa associated lymphoid tissue
lymphoma because monoclonal B-lymphocytic foci within
salivary glands or from parenchymal internal organs

SYSTEMIC LUPUS ERYTHEMATOSUS

- SLE is a systemic autoimmune disease

- Characterized by the presence of autoantibodies
- Mean age at pSLE diagnosis is approxiamately 12 to 13 yrs
- Female predominance
- True incidence and prevalence of pSLE is difficult to estimate
Clinical Manifestations
because there have been very few studies focusing on the
pediatric population
- Time to diagnosis of SLE from onset of symptoms is variable
and can range from 1 month to 5 years (median 4 to 8
months)
- 30 years ago the reported survival of pSLE patients at 5 years
was 82.6% and at 10 years 76.1%
- Recent pSLE studies have shown 5-year survival rates of
>95% and 10-year survival rates reported to be as high as
86%
- Should be considered as a potential diagnosis in patient who
presents with multiorgan system disease
- ANA (antinuclear antibodies) are present in >90% of patients
Etiology
- Pathogenesis of SLE remains unknown
- Genetic predisposition to SLE is suggested
- Association with specific genetic abnormalities, including
congenital deficiencies of C1q, C2, and C4 and because of the
finding that individuals with SLE frequently have a family
history of SLE or other autoimmune disease
- Hormonal factors – strong association on women of
reproductive age (estrogen exposure promotes B-cell
autoreactivity)
- Environmental exposures may trigger (infection, drugs)

Pathogenesis

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- Any organ system can be involved in SLE

- Most common presenting complaints of children with SLE
include fever, fatigue, hematologic abnormalities, arthralgia,
and arthritis
- Often characterized by periods of flare and disease quiescence
or may follow a more smoldering disease course
- A disease that evolves over time in each affected individual,
and new manifestations may arise even many years after
diagnosis.

JACCOUD ARTHRITIS
- Deforming arthritis associated with ligament and tendon laxity
is rarely seen in pSLE

RHUPUS
- Destructive arthritis associated with a positive rheumatoid
factor (rare in children)
- More commonly seen is the development of pSLE in patients
with longstanding definite polyarticular or systemic JIA.

Diagnosis

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Rules of 4 remain but new principle: Laboratory Findings:

- There must be at least ONE clinical and ONE immunologic - A positive ANA test result is 95-99% of individuals with SLE
AND (high sensitivity but poor specificity)
- If there is lupus nephritis by biopsy in the setting of ANA or - Up to 20% of healthy individuals have a positive ANA
anti-dsDNA, no further criteria is required - ANA titer are not reflective of disease activity
- ACR Sn 83%; Sp 96% - Antibodies to double-stranded DNA are more specific for SLE,
- SLICC 97%; Sn Sp 84% and in some individuals, anti-dsDNA levels correlate with
- P value 0.005 disease activity, particularly nephritis
- Anti-Sm activity though specific for SLE does not correlate
LUPUS NEPHRITIS with activity
- Significant cause of morbidity and mortality in children - CH50, C3 and C4 are typically decreased inactive disease
- Incidence of nephritis is higher in children - ESR is elevated but CRP does not correlate well with the
- Most common patterns in pSLE: activity for an elevated CRP may reflect infection than disease
1. Proliferative (Class III and IV); activity
2. Mesangial (Class II); and
3. Membranous (Class V) Autoantibodies commonly associated with SLE
- Pathogenesis: immune complex deposition
- Clinical forms:
1. Isolated hematuria
2. Acute nephritic syndrome
3. Nephrotic syndrome
4. Gross hematuria
5. CKD

Management of pSLE
• General:
➢ Counseling, education, team approach
➢ Adequate rest, appropriate nutrition
➢ Vitamin D supplementation and adequate Ca intake
➢ Use of sunscreen
➢ Immunizations
➢ Prompt management of infection
• Indication of NSAID use
➢ Mild constitutional symptoms
➢ Musculoskeletal signs and symptoms
➢ Mild pleuritic and pericarditis
• Indication for Hydroxychloroquine use
➢ Mild systemic disease
➢ Cutaneous disease
➢ Alopecia
➢ Arthritis

Indication and Use of Glucocorticoids

• General systemic disease, cutaneous disease, serositis or
musculoskeletal disease.
➢ Oral Prednison 0.25-0.75 mg/kg/day as single dose

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➢ For serositis: 0.5-1.0 mg/kg/day (maximum of - The vast majority of neonatal lupus cases are associated with
60mg/day) and BID dosing maybe required maternal anti-Ro (also known as SSA) and anti-La antibodies
• Major organ involvement (Renal Class III or IV or NP (also known as SSB)
involvement) - Other autoantibodies include anti-ribonucleoprotein (anti-
➢ Oral Prednisone RNP) are also reported to cause neonatal lupus
➢ Initial 6 weeks: 2 mg/[Link] (maximum of 60-80 - Despite the clear association with maternal autoantibodies,
mg/day) divided TID for 4 weeks then OD their presence alone is not sufficient to cause disease, as <3%
➢ Subsequent 3 months: taper by 10 mg monthly of offspring born to mothers with anti-Ro and anti-La
➢ When dosage reaches 30 mg/day: taper 5 mg q 4- antibodies experience congenital heart block
8 depending on response (flares frequently occur - Noncardiac manifestations are usually reversible
between 20-25 mg/day) - Congenital heart block is permanent
➢ When dosage reaches 20mg/day: slow taper to 2.5 - The rash typically appears within the first 6 wk of life after
mg q6-8 weeks depending on response (flares exposure to ultraviolet light and lasts 3-4 months however, it
frequently occur between 10-15 mg/day) can be presented at birth
➢ When dosage reaches 10-15 mg/day consider - Conduction system abnormalities can be detected in utero
alternate prednisone and when reach 15 mg beginning at 16 week of gestational age
alternate day then slow taper to 2.5-5.0 mg/day
alternate q 3-6 months Clinical Manifestations
➢ May use intravenous pulse methylprednisolone (10- - Cutaneous
30 mg/kg/day; maximum 1 g/day) - Characteristic annular or macular rash typically
affecting the face (especially the periorbital area),
DRUG INDUCED LUPUS trunk, and scalp
- Presence of SLE manifestations triggered by exposure to - Initially reported that there was a female
certain medications predominance in infants with C-NLE
- In individuals prone to SLE, these agents may act as a trigger - Female-to-male ratio of 2:1 to 3:1
for true SLE - The reason for the reported increased incidence in
- In others, these agents provoke a reversible lupus-like females may be related to the fact that estrogens
syndrome enhance surface expression of Ro and La proteins
- Affects males and females equally on keratinocyte cells
- Circulating antihistone antibodies are often present in drug- - Photosensitive
induced SLE - Cytopenias
- Antihistone antibodies are also detected in up to 20% of - Hepatitis
individuals with SLE - Congenital heart block (most feared complication)
- Individuals with drug-induced lupus are less likely to - Conduction system abnormalities:
demonstrate antibodies to double-stranded DNA, ➢ Prolongation PR interval
hypocomplentemia, and significant renal or neurologic ➢ Complete heart block → progressive
disease cardiomyopathy
- In contrast to SLE, manifestations of drug-induced lupus CARDIAC NEONATAL LUPUS
resolve after withdrawal of the offending medication - Most important clinical manifestation
- Signs and symptoms will resolve within 6 months - CHB is seen in 1/14,000 live births in which at least 90% of
the cases of CHB are the result of transplacental passage of
maternal autoantibodies
- In vitro studies suggest that during cardiac development, Ro
and La antigens may be exposed on the surface of cardiac
cells in the proximity of the atrioventricular node, thus making
these antigens accessible to maternal autoantibodies
- Binding incites a local immune response, resulting in fibrosis
within the conduction system
- In the skin, exposure to ultraviolet light results in cell damage
and the exposure of Ro and La antigens, inducing a similar
local inflammatory response that produce the characteristic
NEONATAL LUPUS rash.
- An entity distinct from SLE
- One of the few rheumatic disorders manifesting in the Diagnosis
neonate - Maternal autoantibodies gain access to the fetus via the
- A disease of the developing fetus and neonate characterized placenta at 16th week of gestation
by the present of maternal auto antibodies - All pregnant women with anti Ro and anti La antibody with a
- Referred to as a passively acquired autoimmunity history of offspring with neonatal lupus or congenital heart
block are monitored with regular fetal ECG from 16th week
Etiology and Pathogenesis until delivery
- Neonatal lupus results from the passive transfer of maternal - If fetal bradycardia is found, screening for maternal anti Ro
immunoglobulin (Ig) G autoantibodies to the fetus and anti La is warranted

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- Congenital heart block is irreversible because the AV node

maybe replaced by extensive fibrosis
- Cases of advanced second- or third-degree AV block may be
associated with hydrops fetalis and a high morbidity and
mortality rate
- Neonatal lupus is not characterized by immune dysregulation,
although infants with neonatal lupus are at risk for
autoimmune disease.
- A mother with history of a born child with congenital heart
block has a 15% risk of recurrence with future pregnancies

Treatment
- Cardiac pacing
➢ Has excellent prognosis
➢ If not corrected, children are at risk for exercise
intolerance, arrhythmias and death
- Fluorinated steroid (betamethasone and dexamethasone) are
used because they cross the placenta unmetabolized
- Prednisone and prednisolone are inactive by placental 11-β-
hydroxysteroid dehydrogenase
- IVIG-limited studies
- Usual approach to management of C-NLE is reassurance
offered to the parents and continued observation of the child,
because the natural history of the skin lesions is spontaneous
resolution without scarring.

Course and Prognosis

- Skin, liver and hematological complications generally resolved
with minimal sequelae, whereas CHB is permanent
- Initially reported that children with NLE might be at a high risk
for developing SLE in later life

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