1. SYSTEMIC CONNECTIVE TISSUE DISEASES DR CB NEL

2. INTRODUCTION Multiple body systems involved Wide spectrum of clinical manifestations Aetiology is multifactorial

3. SYSTEMIC LUPUS ERYTHEMATOSUS

4. SLE Predominantly females, 9:1 ratio Peak onset second and third decades More common in persons of Afro-Caribbean origin Several autoantibodies associated with SLE

5. CLINICAL FEATURES Raynaud’s phenomenon – Colour changes of mainly the digits provoked by cold or emotion White (vasoconstriction) Blue (cyanosis) Red (reactive hyperemia) – Secondary if associated SLE – Broad spectrum of causes (Talley and O’Connor) Musculosketal – Mild morning stiffness – Migratory arthralgia – Small joint synovitis – Joint deformities are rare – Non-erosive x-ray changes

6. RAYNAUD’S PHENOMENON

7. CLINICAL FEATUES Cutaneous lesions Lupus specific – Acute Malar ”butterfly” rash Generalized erythema – Subacute Annular Papulosquamous (psoriasiform) – Chronic Discoid Lupus profundus Non-lupus specific – Vasculitis – Livedo reticularis – Non-scarring alopecia – Panniculitis

8. MALAR RASH

9. SUBACUTE CUTANEOUS LUPUS

10. DISCOID LUPUS

11. CLINICAL FEATUES Renal – Proteinuria, haematuria, casts on urine microscopy – Proliferative glomerulonephritis – Six classes of nephritis according to histology Cardiopulmonary – Pleurisy – Pleural effusion – Interstitial lung disease – Lung fibrosis – Pericarditis – Myocarditis – Libman-Sacks endocarditis (non-infective vegetations)

12. LIBMAN-SACKS ENDOCARDITIS

13. CLINICAL FEATURES Nervous system – Headaches – dysfunction – Visual hallucinations – Chorea – Psychosis – Seizures – Aseptic meningitis – Neuropathies – Transvers myelitis

14. CLINICAL FEATURES Secondary Antiphospholipid syndrome – Recurrent arterial and venous thromboses – Recurrent fetal losses – Thrombocytopenia – Antiphospholipid antibodies (lupus anticoagulant, β2 glycoprotein 1, anticadiolipin) – Life-long warfarin therapy required Non-specific – Lymphadenopathy – Fever – Weight loss – Fatigue

15. SPECIAL INVESTIGATION FBC – Haemolytic anaemia (Coombs positive) – Thrombocytopenia – Lymphopenia – Neutropenia Kidney function – dipstix (proteinuria, haematuria) – Microscopy for active sediment (red cell, white cell and hyaline casts) – U&E can still be normal in advanced disease – Urine protein/Creatinine ratio – 24hrs urine protein

16. SPECIAL INVESTIGATION ESR and CPR – ESR elevated in active disease – CRP often normal in active disease Autoantibodies – ANA (high sensitivity, low specificity) – Anti-double-stranded DNA (ds-DNA) specific for SLE – Anti-Smith (anti-Sm) specific for SLE – Antiphospholipid antibodies

17. LUPUS CLASSIFICATION CRITERIA Need four of the eleven criteria for diagnosis

19. MANAGEMENT NO curative treatment available Treat symptoms Treat complications/Life threatening disease aggressively with immunosuppressants

20. SYSTEMIC SCLEROSIS

21. Peak onset fourth and fifth decade 4:1 female predominance Divided into – Diffuse cutaneous systemic sclerosis (DCSS) – Limited cutaneous systemic sclerosis (LCSS) “CREST” syndrome (many patients with LCSS) – Calcinosis – Raynaud’s – Oesophageal dysfunction – Sclerodactyly – Telangiectasia Aetiology of systemic sclerosis is unknown

23. CLINICAL FEATURES Cutaneous – Raynaud’s early in disease – Sclerodactyly (skin tight, shiny, and thickened) – Calcinosis (subcutaneous calcium deposits) – Thinning and radial furrowing of the lips – Telangiectasia – In LCSS skin involvement distal to knees and elbows and include the face – In DCSS skin involve proximal to knees and elbows and include the trunk

24. FACE IN DIFFUSE SCLEROMERMA

25. HANDS IN SCLERODERMA

26. CLINICAL FEATURES Musculoskeletal – Arthralgia, – Morning stiffness – Flexor tenosinivits – Decreased hand movement due to skin rather the joints

27. CLINICAL FEATURES Gastro-intestinal features – Lower oesophagus (smooth muscle atrophy, fibrosis) Acid reflux Dysphagia Barrett’s esophagitis Carcinoma – Stomach Early satiety Outlet obstruction

28. CLINICAL FEATURES Gastro-intestinal features – Small intestine Malabsorption due to bacterial overgrowth Bloating and pain – Large bowl Dilatation with pseudo-obstruction Rectal incontinence

29. CLINICAL FEATURES Cardiorespiratory features – Pulmonary involvement major cause of mortality – Pulmonary fibrosis mainly in diffuse disease – Pulmonary hypertension mainly in limited systemic sclerosis

30. CLINICAL FEATURES Renal features – Hypertensive renal crisis (diffuse disease) Can be precipitated by corticosteroids Malignant hypertension Renal failure Death Treatment with ACE-inhibitors

31. INVESTIGATIONS ANA positive Anti-topoisomerase I antibodies in diffuse disease Anti-centromere antibodies in limited disease Antibodies not in all patient Still mainly a clinical diagnosis

32. MANAGEMENT Raynaud’s – Avoid cold, smoking, vasoconstrictors e.g.. B-blockers – Keep the whole body warm – Vasodilators e.g.. Ca-channel blockers (nifedipine), Angiotensin II receptor antagonists (losartan) PPI in oesophageal involvement Pulmonary hypertension – Vasodilators – Prostaglandin analogues – 5-phosphodiesterase inhibitors e.g.. Viagra – Heart-lung transplants

33. MANAGEMENT Interstitial lung disease – High doses corticosteroids – Immunosuppressants e.g.. Cyclophosphamide Skin – Moisturizing creams, emulsifying ointments – Aggressive treatment of ulcers Treat the cause Prevent secondary infections

34. POLYMYOSITIS AND DERMATOMYOSITIS

35. Rare 40-60yrs of age at onset Possible paraneoplastic manifestation dermatomyositis > polymyositis

36. CAUSES OF PROXIMAL MUSCLE WEAKNESS Inflammatory – Polymyositis – Dermatomyositis Endocrine – Hypo/hyperthyroidism – Cushing’s syndrome – Addison’s disease Genetic – Muscular dystrophies Drugs/toxins – Corticosteroids – Alcohol – Statins – Fibrates Infections – HIV – Cytomegalovirus – schistosomiasis

37. CAUSES OF PROXIMAL MUSCLE WEAKNESS Metabolic – Vit D deficiency – Hypocalcaemia – Hypokalaemia – Uraemia – Hepatic failure Rheumatological – RA – SLE – Scleroderma

38. CLINICAL FEATURES Polymyositis – Symmetrical proximal weakness – Lower limbs mostly first – Difficulty in raising from a chair – Difficulty in climbing stairs – Insidious onset over weeks – Systemic features (fever, fatigue, weight loss) common – Respiratory muscle involvement is life-threatening

39. CLINICAL FEATURES Dermatomyositis – Proximal muscle weakness + typical skin manifestations – Skin manifestations: Gottron’s nodules and plaques Heliotrope rash (over eye lids) Peri-orbital oedema V-sign (erythematous rash, anterior neck and thorax) Shawl-sign (erythematous rash, shoulders0

40. GOTTRON’S

41. HELIOTROPE RASH AND PERI-ORBITAL OEDEMA

42. SHAWL SIGN

43. V-SIGN

44. INVESTIGATIONS Raised Total-CK EMG – confirm myositis and exclude neuropathy Muscle biopsy – identify type of myositis MRI- identify areas of abnormal muscle

45. MANAGEMENT Initially high doses of corticosteroids (1mg/kg/day) Taper according to response Sometimes more potent immunosuppressant needed e.g.. Azathioprine, methotrexate

46. MIXED CONNECTIVE TISSUE DISEASE A SPECIFIC ENTITY Features of – RA – SLE – Scleroderma – Polymyositis Serology: positive anti-RNP (other serology negative)

47. SJӦGREN’S SYNDROME Lymphocytic infiltration of salivary and lachrymal glands Glandular fibrosis and exocrine failure Primary or secondary Dry eyes, dry mouth, vaginal dryness, dry cough, dry skin Fatigue, non-erosive arthritis, Raynaud,s 40-Time increase risk for lymphoma Anti-Ro(SS-A) and anti-LA(SS-B) anti-bodies Symptomatic treatment

48. DRY MOUTH IN pSS

49. BILAT PAROTID GLAND ENLARGEMENT IN pSS

50. QUESTIONS?