Diagnóstico

Avaliação para LES EVALUATION FOR SYSTEMIC LUPUS ERYTHEMATOSUS History Physical examination Specific cutaneous lesions Non-specific cutaneous lesions Lymphadenopathy, arthritis Laboratory tests ANA with profile (dsDNA, Sm) Urinalysis CBC with differential, platelets Chemistries (BUN, creatinine) Erythrocyte sedimentation rate Complement levels (C3, C4)

FAN 1/3 indivíduos aparentemente normais vão ter FAN reator 1:40 – 13% 1:80 – 5% 1 :160 FAN reator NÃO é indicador nem de doença sistêmica nem de Lúpus

THE AMERICAN COLLEGE OF RHEUMATOLOGY 1982 REVISED CRITERIA FOR CLASSIFICATION OF SYSTEMIC LUPUS ERYTHEMATOSUS Criterion Definition 1. Malar rash Fixed erythema, flat or raised, over the malar eminences, tending to spare the nasolabial folds 2. Discoid rash Erythematous raised patches with adherent keratotic scaling and follicular plugging; atrophic scarring may occur in older lesions 3. Photosensitivity Skin rash as a result of unusual reaction to sunlight, by patient history or physician observation 4. Oral ulcers Oral or nasopharyngeal ulceration, usually painless, observed by physician

Eritema Malar

Lesões discóides

Ulcerações orais

Fotossensibilidade

THE AMERICAN COLLEGE OF RHEUMATOLOGY 1982 REVISED CRITERIA FOR CLASSIFICATION OF SYSTEMIC LUPUS ERYTHEMATOSUS 5. Arthritis Non-erosive arthritis involving two or more peripheral joints, characterized by tenderness, swelling or effusion 6. Serositis a) Pleuritis–convincing history of pleuritic pain, rubbing heard by a physician, or evidence of pleural effusion OR b) Pericarditis–documented by ECG, rub or evidence of pericardial effusion 7. Renal disorder a) Persistent proteinuria greater than 0.5 g/day or greater than 3+ if quantitation not performed OR b) Cellular casts–may be red cell, hemoglobin, granular, tubular or mixed

Artrite

Serosite

Alterações renais persistentes

8. Neurologic disorder a) Seizures–in the absence of offending drugs or known metabolic derangements, e.g. uremia, ketoacidosis or electrolyte imbalance OR b) Psychosis–in the absence of offending drugs or known metabolic derangements, e.g. uremia, ketoacidosis or electrolyte imbalance 9. Hematologic disorder a) Hemolytic anemia with reticulocytosis OR b) Leukopenia–less than 4000/mm3 total WBC on two or more occasions OR c) Lymphopenia–less than 1500/mm3 on two or more occasions OR d) Thrombocytopenia–less than /mm3 in the absence of offending drugs

Alterações neurológicas

Alterações hematológicas

10. Immunologic disorder a) Anti-DNA antibody to native DNA in abnormal titer OR b)Anti-Sm: presence of antibody to Sm nuclear antigen OR c) Positive finding of antiphospholipid antibodies based on: (1) an abnormal serum level of IgG or IgM anticardiolipin antibodies; (2) a positive test result for lupus anticoagulant using a standard methods; or (3) a false- positive serologic test for syphilis known to be positive for at least 6 months and confirmed by Treponema pallidum immobilization or fluorescent treponemal antibody absorption test (FTA-ABS) 11. Antinuclear antibody An abnormal titer of antinuclear antibody by immunofluorescence (or an equivalent assay) at any point in time and in the absence of drugs known to be associated with ‘drug-induced lupus’ syndrome

Alterações imunológicas Anti Smith Anti-DNA dupla hélice Anti-fosfolipídeos (1997 ) Anti-cardiolipina (IgG or IgM) VDRL falso positivo (> 6 meses) Anticoagulante lúpico

FAN ou ANA Periférico Nucleolar Difuso Pontilhado

Auto-anticorpos em LES AUTOANTIBODIES ASSOCIATED WITH LUPUS ERYTHEMATOSUS AutoantibodyMedian prevalence [*] Molecular specificityClinical associations High specificity for SLE DsDNA [†] (homogéneo) 60% 75% ADouble-stranded (native) DNA LE nephritis; monitoring activity of SLE Sm (pontilhado grosso) 30% 20% ASplicesome RNP (ribonucleoprotein particles involved in splicing pre-mRNA) − Protecao renal rRNP7%Ribosomal P proteins (proteins involved in ribosome function) Neuropsychiatric LE

Low specificity for SLE ANA (most common IF patterns: homogeneous, peripheral) 99% ssDNA70% 90% ADenatured DNAPossible risk for SLE in DLE patients; also seen in RA, DM/PM, MCTD, SSc, SjS, localized scleroderma C1q60%C1q component of complement Severe SLE, hypocomplementemic urticarial vasculitis syndrome PCNA50%A component of multiprotein complexes involved in cell proliferation − U1RNP50%Splicesome RNPOverlapping features with other CTD; MCTD (100%) Ro (SS-A)50%hYRNP (quality control function for misfolded RNA molecules) SCLE (75–90%), neonatal LE/congenital heart block (99%), SCLE–SjS overlap, SjS

Histones40% 70% AHistonesDrug-induced SLE, RA Cardiolipin50%Cardiolipin, a negatively charged phospholipid Recurrent spontaneous abortions, thrombocytopenia, and hypercoagulable state in SLE (cutaneous manifestations include livedo reticularis, leg ulcers, acral infarction/ulceration, hemorrhagic cutaneous necrosis); clinical associations strongest with IgG class of anticardiolipin b2 glycoprotein I25%An important cofactor for cardiolipin in cardiolipin autoantibody assays Relatively high risk of thrombosis in SLE and primary antiphospholipid antibody syndrome Rheumatoid factor25%Fc portion of IgG La (SS-B)20%hYRNPSCLE (30–40%), SCLE– SjS overlap, primary SjS (20%) Ku10%DNA end-binding repair protein complex Overlap with other CTD such as DM/PM, SSc Alpha-fodrin10%An actin-binding protein found at the periphery of chromaffin cells that may be involved in secretion SjS