Connective tissue diseases — comprehensive

◆SLE (systemic lupus erythematosus)

• •Young women, especially Black/Hispanic/Asian
• •Classic features: malar rash sparing nasolabial folds, oral ulcers, photosensitivity, serositis, arthritis, nephritis
• •ANA highly sensitive (98%); anti-dsDNA + anti-Smith are specific; low complement (C3/C4) during flares
• •Antiphospholipid syndrome (lupus anticoagulant, anti-β2-GP1) → thromboses, miscarriage
• •Lupus nephritis: classes I–VI; class III/IV (proliferative) need biopsy + immunosuppression
• •Treatment: hydroxychloroquine ALWAYS; steroids for flares; MMF/cyclophosphamide for severe nephritis

◆Sjögren syndrome

• •Dry eyes (keratoconjunctivitis sicca) + dry mouth (xerostomia) + parotid enlargement
• •Anti-Ro (SSA) and anti-La (SSB) antibodies
• •Schirmer test + lip biopsy (focal lymphocytic infiltrate) confirm
• •Associations: RA, SLE, primary biliary cholangitis
• •↑ risk of B-cell lymphoma (MALT in salivary glands)
• •Treatment: artificial tears, pilocarpine for xerostomia, hydroxychloroquine for arthralgias

◆Systemic sclerosis (scleroderma)

• •Diffuse: rapid skin thickening (trunk + proximal extremities), interstitial lung disease (ILD), renal crisis — anti-Scl-70 (topoisomerase I)
• •Limited (CREST): Calcinosis, Raynaud, Esophageal dysmotility, Sclerodactyly, Telangiectasias — anti-centromere antibody
• •Pulmonary hypertension is the leading cause of death in CREST
• •ILD is the leading cause of death in diffuse scleroderma
• •Scleroderma renal crisis: severe HTN + AKI → ACE-INHIBITORS first-line (one of the few times ACE-I is used in scleroderma)
• •No disease-modifying therapy; symptom-targeted: PPIs for GERD, CCBs for Raynaud, sildenafil/bosentan for PAH

◆Polymyositis & dermatomyositis

• •Symmetric proximal weakness over weeks-months; difficulty climbing stairs, brushing hair
• •Dermatomyositis adds: heliotrope rash (eyelids), Gottron papules (MCPs), shawl sign, mechanic hands
• •CK markedly elevated; anti-Jo-1 (antisynthetase syndrome with ILD), anti-Mi-2 (DM with classic skin), anti-SRP (severe necrotizing)
• •Strong association with malignancy in DM > PM — screen at diagnosis
• •Treatment: high-dose steroids + MTX or azathioprine; IVIG for severe; rituximab refractory

◆Polymyalgia rheumatica & fibromyalgia

• •PMR: age >50, bilateral proximal stiffness >30 min, ↑ ESR (often >50), NORMAL CK; rapid response to low-dose prednisone
• •PMR coexists with GCA in 40–50% — always screen for headache/jaw claudication/visual
• •Fibromyalgia: widespread pain >3 months, multiple tender points, NORMAL labs, sleep disturbance, fatigue
• •Fibro management: aerobic exercise, CBT, amitriptyline, duloxetine, pregabalin — NOT opioids, NOT steroids

Autoantibody quick reference