Connective tissue diseases

Autoimmune diseases

Systemic lupus erythematosus A multisystem disease Incurable, but treatable Common in post-pubertal young females Remitting-relapsing course Pathogenesis- Small genetic predisposition- F/H +ve in 10% Environmental triggers- UV light, EBV infection, HRT Drugs- procainamide, hydralazine, quinidine, phenytoin Increased apoptosis with deficient phagocytic activity,

exposes nuclear fragments as potential autoAg

Symptoms & signs Fever, malaise, arthralgia/arthritis, myalgia Skin- malar rash, alopecia, oral ulcers Blood- anemia/pancytopenia, APLS Heart- pericarditis, endocarditis-MV/TV,

accelerated atherosclerosis Lung- pleuritis ± effusion, pneumonitis, ILD Kidney- hematuria, proteinuria, ARI/CRI Neuropsychiatric- cognitive dysfunction,

seizures, psychosis, headache

Diagnosis Multiple clinical symptoms/signs + anti-nuclear Ab- sensitive

specially anti-Smith & anti-dsDNA- specific ± SS-A/B- confer risk of cardiac conduction

block in neonates ± APL Ab- risk of thrombosis/pregnancy loss Anti-histone Ab +ve in drug-induced lupus Low complement levels CBC, RFT, urinanalysis Kidney biopsy- for lupus nephritis

Treatment To prevent relapse

& reduce their severity/duration Avoid sunlight exposure Mild disease- NSAIDs, hydroxychloroquine Severe disease- Steroids Immunosuppressants- cyclophosphamide, methotrexate,

azathioprine, mycophenolate mofetil Kidney transplantation- ~30% recurrence

Scleroderma Skin fibrosis, with Raynaud’s phenomenon,

nail-fold capillary changes-dilation/dropout & ANA +ve Limited- anti-centromere +ve or

Systemic- anti-Scl 70 +ve Other organs affected- Heart- hypertension, arrythmia Lung- pulmonary HT, interstitial fibrosis Kidney- malignant HT GIT- dysphagia, GERD, impaired intestinal motility Rx- symptomatic Raynaud’s- calcium channel blockers Skin fibrosis- penicillamine, PUVA, cyclosporin Immunosuppressants- Mtx, azathioprine, mycophenolate, cyclophosphamide Malignant HT- ACEI Px- bad with systemic disease & older age

Sjogren syndrome Sicca- dry- syndrome Autoimmune damage to exocrine glands, producing

saliva & tears Hallmark dry mouth & dry eyes Other- nephritis, neuritis, vasculitis ANA- SSB/La ± SSA/Ro or RF +ve Schirmer test- quantifies tear production DDx- RT, GVHD, lymphoma, sarcoidosis Rx- supportive Complication- NHL, in ~5%

Polymyositis More in females Muscle inflammation, B/L symmetrical,

causing tenderness & weakness, predominantly in proximal muscles

Dysphagia or ILD may be present Dx- Clinical Raised CPK EMG or muscle biopsy Anti-Jo Ab- +ve in >65% Rx- steroids ± immunosuppressants & physiotherapy

Sharp syndrome Mixed connective tissue disease An overlap syndrome, combining features of

SLE, RA, SS, scleroderma & polymyositis Commonly causes- Joint pain & swelling Raynaud phenomenon Sclerodactyly Dry mouth/eyes, etc. Dx- clinical ± anti U1-RNP Ab

Sharp syndrome Mixed connective tissue disease An overlap syndrome, combining features of

SLE, RA, SS, scleroderma & polymyositis Commonly causes- Joint pain & swelling Raynaud phenomenon Sclerodactyly Dry mouth/eyes, etc. Dx- clinical ± anti U1-RNP Ab