Download systemic connective tissue diseases

SYSTEMIC CONNECTIVE TISSUE
DISEASES
DR CB NEL
INTRODUCTION
• Multiple body systems involved
• Wide spectrum of clinical manifestations
• Aetiology is multifactorial
SYSTEMIC LUPUS ERYTHEMATOSUS
SLE
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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
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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
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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
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Pleurisy
Pleural effusion
Interstitial lung disease
Lung fibrosis
Pericarditis
Myocarditis
Libman-Sacks endocarditis (non-infective vegetations)
LIBMAN-SACKS ENDOCARDITIS
CLINICAL FEATURES
• Nervous system
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Headaches
dysfunction
Visual hallucinations
Chorea
Psychosis
Seizures
Aseptic meningitis
Neuropathies
Transvers myelitis
CLINICAL FEATURES
• Secondary Antiphospholipid syndrome
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Recurrent arterial and venous thromboses
Recurrent fetal losses
Thrombocytopenia
Antiphospholipid antibodies (lupus anticoagulant, β2 glycoprotein 1,
anticadiolipin)
– Life-long warfarin therapy required
• Non-specific
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Lymphadenopathy
Fever
Weight loss
Fatigue
SPECIAL INVESTIGATION
• FBC
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Haemolytic anaemia (Coombs positive)
Thrombocytopenia
Lymphopenia
Neutropenia
• Kidney function
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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
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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)
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Calcinosis
Raynaud’s
Oesophageal dysfunction
Sclerodactyly
Telangiectasia
• Aetiology of systemic sclerosis is unknown
CLINICAL FEATURES
• Cutaneous
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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
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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)
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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)
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Can be precipitated by corticosteroids
Malignant hypertension
Renal failure
Death
Treatment with ACE-inhibitors
INVESTIGATIONS
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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
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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
POLYMYOSITIS
AND
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
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Corticosteroids
Alcohol
Statins
Fibrates
• Infections
– HIV
– Cytomegalovirus
– schistosomiasis
CAUSES OF PROXIMAL MUSCLE WEAKNESS
• Metabolic
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Vit D deficiency
Hypocalcaemia
Hypokalaemia
Uraemia
Hepatic failure
• Rheumatological
– RA
– SLE
– Scleroderma
CLINICAL FEATURES
• Polymyositis
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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
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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
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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?