SYSTEMIC CONNECTIVE TISSUE DISEASES

DR CB NEL

INTRODUCTION

• Multiple body systems involved

• Wide spectrum of clinical manifestations

• Aetiology is multifactorial

SYSTEMIC LUPUS ERYTHEMATOSUS

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

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

RAYNAUD’S PHENOMENON

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

MALAR RASH

SUBACUTE CUTANEOUS LUPUS

DISCOID LUPUS

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)

LIBMAN-SACKS ENDOCARDITIS

CLINICAL FEATURES

• Nervous system– Headaches– dysfunction– Visual hallucinations– Chorea– Psychosis– Seizures– Aseptic meningitis– Neuropathies – Transvers myelitis

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

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

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

LUPUS CLASSIFICATION CRITERIA

Need four of the eleven criteria for diagnosis

MANAGEMENT

• NO curative treatment available

• Treat symptoms

• Treat complications/Life threatening disease aggressively with immunosuppressants

SYSTEMIC SCLEROSIS

• 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

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

FACE IN DIFFUSE SCLEROMERMA

HANDS IN SCLERODERMA

CLINICAL FEATURES

• Musculoskeletal – Arthralgia,– Morning stiffness – Flexor tenosinivits – Decreased hand movement due to skin rather the joints

CLINICAL FEATURES

• Gastro-intestinal features– Lower oesophagus (smooth muscle atrophy, fibrosis)

• Acid reflux• Dysphagia• Barrett’s esophagitis• Carcinoma

– Stomach• Early satiety• Outlet obstruction

CLINICAL FEATURES

• Gastro-intestinal features– Small intestine

• Malabsorption due to bacterial overgrowth• Bloating and pain

– Large bowl• Dilatation with pseudo-obstruction• Rectal incontinence

CLINICAL FEATURES

• Cardiorespiratory features– Pulmonary involvement major cause of mortality– Pulmonary fibrosis mainly in diffuse disease– Pulmonary hypertension mainly in limited systemic

sclerosis

CLINICAL FEATURES

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

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

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

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

POLYMYOSITISAND

DERMATOMYOSITIS

POLYMYOSITIS AND DERMATOMYOSITIS

• Rare• 40-60yrs of age at onset• Possible paraneoplastic manifestation

dermatomyositis > polymyositis

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

CAUSES OF PROXIMAL MUSCLE WEAKNESS

• Metabolic– Vit D deficiency– Hypocalcaemia– Hypokalaemia– Uraemia– Hepatic failure

• Rheumatological– RA – SLE– Scleroderma

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

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

GOTTRON’S

HELIOTROPE RASH AND PERI-ORBITAL OEDEMA

SHAWL SIGN

V-SIGN

INVESTIGATIONS

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

MANAGEMENT

• Initially high doses of corticosteroids (1mg/kg/day)• Taper according to response• Sometimes more potent immunosuppressant needed

e.g.. Azathioprine, methotrexate

MIXED CONNECTIVE TISSUE DISEASE

• A SPECIFIC ENTITY• Features of– RA– SLE– Scleroderma– Polymyositis

• Serology: positive anti-RNP (other serology negative)

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

DRY MOUTH IN pSS

BILAT PAROTID GLAND ENLARGEMENT IN pSS

QUESTIONS?