This document discusses several connective tissue diseases including systemic lupus erythematosus, scleroderma, Sjogren syndrome, polymyositis, and Sharp syndrome. Systemic lupus erythematosus is a multisystem autoimmune disease most common in young females, with symptoms involving multiple organ systems. Scleroderma involves skin fibrosis and internal organ involvement. Sjogren syndrome causes dryness from immune damage to exocrine glands. Polymyositis features muscle inflammation. Sharp syndrome is an overlap syndrome combining features of systemic lupus erythematosus, rheumatoid arthritis, Sjogren syndrome, scleroderma, and polymyositis.

1. Connective tissue diseases
Autoimmune diseases

2. 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

3. 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

4. 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

5. 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

6. 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

7. 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%

8. 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

9. 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

10. 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