● Clinical features

○ Constitutional: → fatigue (most common), fever (low grade), weight loss,

○ Joints (> {{c1::90}}% of cases)
■ Arthritis & arthralgia
■ Distal symmetrical polyarthritis: most commonly affects the joints
of the → fingers, carpal joints, and the knee
● Longdtanding SLE arthritis leads to → Jaccoud’s
arthropathy: deformities due to ligament laxity, but still
non-erosive .
○ Skin ({{c2::85}}% of cases)
■ Malar rash (butterfly rash): flat or raised fixed erythema over
both malar eminences (nasolabial folds tend to be spared)
■ {{c3::Raynaud }} Phenomenon ⇒[Image]
● It’s an exaggerated vasospasm of the small
arteries/arterioles in the fingers (and sometimes toes, nose,
ears).
● Triggered by cold or emotional stress.
● Classic color changes (triphasic response):
○ White (pallor): Blood flow cut off ⇒ ischemia.
○ Blue (cyanosis): Deoxygenated blood pools.
○ Red (hyperemia): Rebound dilation when blood flow
returns ⇒ throbbing pain, tingling.
● Symptoms:
○ Fingers feel cold, numb, or painful.
○ After warming, they may tingle or burn.
■ Photosensitivity → maculopapular rash
■ Discoid rash ← [Image]
● causes scarring alopecia
■ {{c4::Nonscarring }}alopecia (except with discoid rashes)
■ {{c5::Ora/Nasal }}ulcers (usually painless)
■ {{c6::Periungual telangiectasia}} : dilated capillaries
“telangiectasia” at the skin folds around the fingernails“ungual”,
appearing as small red dots. [Image]
○
○ Less common
■ Hematological
● Cytopenias: Leukopenia, lymphopenia, autoimmune
hemolytic anemia, thrombocytopenia
● petechiae due to cytopenias
■ MSK: {{c7::myalgia/myositis}}
■ Serositis: {{c8::pleuritis}} and {{c8::pericarditis}} ⇒
effusions
■ Kidneys: {{c9::nephritis}} with proteinuria (affects 50% of the
patients)
■ Heart
● Pericarditis, myocarditis, endocarditis ({{c10::Libman-
Sacks}} endocarditis)
○ SLE causes LSE : form of noninfectious endocarditis
seen in systemic lupus erythematosus.
● {{c11::Aortic valve}} lesions
● Coronary artery disease
■ Lungs
● Pneumonitis
● Interstitial lung disease
● Pulmonary hypertension
■ Vascular
● Vasculitis
● Thromboembolism (APS)
■ Neurological
 ● Seizures
● Psychosis
● Personality changes
● Lupus cerebritis
○ entral nervous system involvement in systemic lupus
erythematosus that is characterized by brain
dysfunction due to inflammation, thrombosis, or
autoantibody-mediated injury.
■ GI
● Nausea, vomiting, abdominal pain
● Vasculitis, pancreatitis, hepatitis
■ Optha
● Diagnosis
○ Clinically diagnosed
■ {{c12::The 2019 EULAR/ACR classification criteria for SLE}} may
be considered to further support the diagnosis, but do not need
to be fulfilled to establish a diagnosis of SLE. take the highest
point
● Always take the highest single item in each domain.
● Add across domains⇒ if ≥10 points, classify as SLE.
● Requirements
○ Positive antinuclear antibody (ANA) titer ≥ 1:80 on
HEp-2 cells or equivalent positive test as an
obligatory entry criterion
○ Additive weighted criteria grouped into 7 clinical and
3 immunological domains
○ Total score ≥ 10 points (with at least one clinical
criterion) to classify as SLE
○ The clinical domains and their weights include:
■ Constitutional: Fever (2 points)
■ Hematologic: Leukopenia (3),
thrombocytopenia (4), autoimmune hemolysis
(4)
■ Neuropsychiatric: Delirium (2), psychosis (3),
seizure (5)
■ Mucocutaneous: Non-scarring alopecia (2),
oral ulcers (2), subacute cutaneous or discoid
lupus (4), acute cutaneous lupus (6)
■ Serosal: Pleural or pericardial effusion (5),
acute pericarditis (6)
■ Musculoskeletal: Joint involvement (6)
■ Renal: Proteinuria >0.5g/24h (4), renal biopsy
class II or V lupus nephritis (8), renal biopsy
class Ill or IV lupus nephritis (10)
○ The immunological domains and their weights include
■ Antiphospholipid antibodies: Anti-cardiolipin or
anti-ß2GP1 antibodies or lupus anticoagulant
(2)
■ Complement proteins: Low C3 or low C4 (3),
low C3 AND low C4 (4)
■ SLE-specific antibodies: Anti-dsDNA antibody
or anti-Smith antibody (6)
○ Lab tests
■ Antinuclear antibodies (ANAs) if + request → Anti-dsDNA
antibodies & Anti-Sm antibodies
■ Anti-dsDNA antibodies
● Autoantibodies against {{c13::double-stranded DNA}}
● Highly specific for SLE
■ Anti-Sm antibodies
 ● Autoantibodies against {{c14::Smith antigens}} (nonhistone
nuclear proteins)
● Highly specific for SLE
■ Antiphospholipid antibodies
○ [Image]
○ Levels correlate with disease activity (especially lupus nephritis activity).?
→ anti dsDNA
○ Sicca syndrome, neonatal lupus → anti-ro/SSA , anti-la/SSB
○ Other lab abnormalities
■ CBC: cytopenias
■ Elevated ESR, CRP
■ RFT: proteinuria, high creatinine..
○ Histopathology
■ Skin biopsy
● Consider in patients with atypical dermatologic presentation
or no response to initial therapy.
● {{c15::Lupus band test (LBT)}}: a direct
immunofluorescence staining technique used to detect
immunoglobulin and complement component deposits along
the dermoepidermal junction in affected and unaffected skin
in patients with SLE
■ {{c16::Kidney biopsy}}: in case of suspected lupus nephritis
● Lupus Nephritis
○ Pathological classes and presentations of Lupus nephritis
■ Lupus nephritis (LN) is a serious manifestation of SLE, occurring in
approximately {{c17::50}}% of patients, typically within
{{c17::the first 3-5 years of disease.}}
● Renal biopsy is essential for classification, prognosis, and
treatment guidance.
● The International Society of Nephrology/ Renal Pathology
Society (ISN/RPS) classification system divides LN into six
classes
○ Class I: Minimal mesangial lupus nephritis
○ Class II: Mesangial proliferative lupus nephritis
○ Class III: Focal lupus nephritis
○ Class IV: Diffuse lupus nephritis
○ Class V: Membranous lupus nephritis
○ Class VI: Advanced sclerosing lupus nephritis
○ Class I: Minimal mesangial LN
■ Normal light microscopy, immune deposits in
mesangium on immunofluorescence/ electron
microscopy
■ Typically mild urinary abnormalities, excellent
prognosis
○ Class II: Mesangial proliferative LN
■ Mesangial hypercellularity and matrix
expansion with mesangial immune deposits
■ Presents with mild proteinuria and/or
hematuria, good prognosis
○ Class III: Focal LN (<50% of glomeruli)
■ Segmental or global endocapillary and/or
extracapillary glomerulonephritis
■ Subclassified as active (A), chronic (C), or
mixed (A/C) lesions
■ Presents with proteinuria, hematuria,
hypertension, moderate renal impairment
■ Higher risk of progression without treatment
○ Class IV: Diffuse LN (≥50% of glomeruli)
 ■ Similar histology to Class Ill but more
extensive involvement
■ Divided into segmental (IV-S) or global (IV-G)
and active/chronic lesions
■ Presents with nephrotic syndrome,
hypertension, renal impairment
■ High risk of progression to end-stage renal
disease without aggressive treatment
○ Class V: Membranous LN
■ Global or segmental subepithelial immune
deposits with glomerular basement membrane
thickening
■ Often presents with nephrotic syndrome, may
have associated hypertension
■ May occur in combination with Class Ill or IV
(Class V+III or V+IV) 3
○ Class VI: Advanced sclerosing LN
■ >90% glomerulosclerosis without residual
activity
■ Represents chronic, irreversible damage with
poor prognosis
● Treatment
○ Lifestyle modifications → smoking cassation & sun protection, healthy
lifestyle, vaccination
○ Pharmacological
■ Antimalarials
● Hydroxychloroquine ← cornerstone of SLE therapy (All pts) .
Improves survival, reduces flares, protects organs.
■ Corticosteroids ← For moderate–severe disease or acute flares.
● Use the {{c18::lowest dose for the shortest time}}
(because of side effects like osteoporosis, infection, CVD
risk).
■ Life-long {{c19::immunosuppressants}}
● Immunosuppressive agents (to reduce steroid need and
control {{c20::organ }}involvement):
○ Methotrexate ← musculoskeletal, cutaneous disease.
■ SE
● Hepatotoxicity (fibrosis, cirrhosis with
long-term use)
● Bone marrow suppression
● Pulmonary fibrosis
● Teratogenic
● GI upset, stomatitis
● Requires folic acid supplementation
○ Azathioprine ← maintenance, steroid-sparing.
■ SE
● Bone marrow suppression (esp. with
TPMT deficiency)
● GI upset
● Hepatotoxicity
■ Increased infection risk
○ Mycophenolate mofetil (MMF) ← first-line for lupus
nephritis (induction + maintenance).
■ SE
● GI upset (nausea, diarrhea, abdominal
pain)
● Bone marrow suppression (leukopenia,
anemia, thrombocytopenia)
● Infection risk (opportunistic)
 ● Teratogenic
○ Cyclophosphamide ← severe organ-threatening
disease (e.g., Class IV LN, neuropsychiatric SLE).
■ SE
● {{c21::Hemorrhagic cystitis}} (due to
acrolein metabolite ⇒ prevent with
{{c22::mesna + hydration}})
● Bone marrow suppression
● Infertility/ovarian failure
● Secondary malignancies (esp. bladder
cancer, hematologic cancers)
● Infection risk
○ Calcineurin inhibitors (tacrolimus, cyclosporine) ←
membranous LN, or steroid-sparing.
■ SE
● Nephrotoxicity
● Hypertension
● Neurotoxicity (tremor, headache,
seizures)
● Gingival hyperplasia (esp.
cyclosporine)
● Hirsutism (cyclosporine)
■ Biologics
● Belimumab ⇒anti-BLyS, for active autoantibody-positive SLE
despite standard therapy.
● Rituximab ⇒ anti-CD20, for refractory SLE (off-label).
● Anifrolumab ⇒ anti-type I interferon receptor, for moderate–
severe SLE.
■ {{c23::NSAIDs}} for symptomatic relief / mild musculoskeletal pain
and serositis
○ Pharmacotherapy
■ Severe or organ-threatening disease
● Induction therapy
○ High-dose IV glucocorticoids + other
immunosuppressive agents
○ Used until symptom remission or low disease activity
is achieved
● Maintenance of remission
○ Hydroxychloroquine with or without lower dose
glucocorticoids
○ AND/OR immunosuppressants or biological agents
■ imp Hydroxychloroquine side effect → : request ophthalmologic
screening at baseline, after 5 years, and yearly thereafter. (Long
term use ⇒ retinal toxicity)
■ [Image]
● Prognosis
○ 5-year survival: >90%, but mortality 2–3× higher than general population.
○ Early death: disease activity, infections
○ Late death: CVD, malignancy
○ Worse prognosis: male, young onset, non-Caucasian, low SES, severe
renal/CNS/pulmonary disease, APS, anemia, hypocomplementemia, anti-
dsDNA, persistent proteinuria, early organ damage
○ SDI: tracks irreversible organ damage, predicts long-term mortality
○ Redness In Cheeks” (malar rash): {{c24::Renal}} disease,
{{c24::Infections}}, and {{c24::Cardiovascular}} complications are the
three most common causes of death in SLE.
● Secondary APS
○ APS = autoimmune thrombosis +/or {{c25::pregnancy complications}} +
{{c25::persistent antiphospholipid antibodies}}
 ■ Lupus anticoagulant (LA)
■ Anticardiolipin antibodies (aCL)
■ Anti-β2 glycoprotein I antibodies (anti-β2GPI)
○ Secondary APS: occurs in SLE patients
○ Manifestations: DVT, PE, stroke, MI, recurrent miscarriage, preeclampsia,
thrombocytopenia, livedo reticularis, heart valve lesions
○ Diagnosis: → ≥1 clinical (thrombosis/ obstetrics)+ ≥1 lab criterion
(antibodies on ≥2 occasions ≥12 weeks apart)
○ Treatment:
■ Acute thrombosis
● Heparin +warfarin (INR 2–3 venous, 2.5–3.5 arterial)
■ Recurrent thrombosis:
● Higher intensity, LMWH, hydroxychloroquine/statins
■ Obstetric APS: Low-dose aspirin + heparin throughout pregnancy
● Drug Induced Lupus (DIL)
○ DIL = drug-triggered, lupus-like syndrome, milder than idiopathic SLE
■ Symptoms: Fever, arthralgia, myalgia, serositis; {{c26::rare}}
renal/CNS involvement
○ Lab clues: → ANA+, antihistone Ab+, anti-dsDNA/anti-Smith usually
negative
○ Common drugs → : Hydralazine, procainamide, isoniazid, quinidine,
minocycline, TNF-α inhibitors
○ Treatment: Stop drug; {{c27::corticosteroids}} if severe