My Clinical Notes

 

SLE

 

• Has an episodic course with relapses and remissions
• More common in African American women
• Onset between age 20-40

 

Aetiology

• Family historyMHC association, HLA-DR3 and HLA-B8 in Caucasians and HLA-DR2 in Japanese
• Inherited deficiency in complement C2 and C4 in some patients
• Sex hormone status

 

Immunological factors

• B cell activation and production of autoantibodies
• Immune complex formation
• Impaired T cell regulation
• Increased inflammatory cytokines

 

Environmental triggers

• SLE not associated with anti-dsDNA can be triggered by;
  • Hydralazine
  • Methydopa
  • Isoniazid
  • D-penicillamine
• Flare ups can be induced by;
  • OCP and HRT
  • Ultraviolet light can also trigger

 

Pathogenesis

• Failure to clear apoptotic material effectively
• Nuclear constituents e.g. DNA and histones are released and inefficient removal may lead to them being presented in excess or abnormally
• Antibodies are produced against nuclear antigens – Ro and La

 

Pathology

• Characterised by widespread vasculitis affecting capillaries, arteriole and venules
• Fibrinoid is an amorphous eosinophilic material and is found along blood vessels and tissue fibres
• Synovium of joint can contain immune complexes

 

Clinical features

• General features;
  • Fever
  • Malaise
• Musculoskeletal
  • Symmetrical small joint arthralgia
  • Rarely tendon contracture and bony erosions
  • Rarely aseptic necrosis
  • Myalgia and rarely myositis
• Skin
  • Butterfly erythema
  • Vasculitis of finger tips, nail folds, purpura and urticaria
  • Photosensitivity
  • Raynaud’s phenomenon
• Lungs
  • Bilateral recurrent pleurisy and pleural effusions
  • Pneumonitis and atelectasis may develop leading to a restrictive lung pattern
• Heart/Cardiovascular system
  • Pericarditis and pericardial effusions
  • Myocarditis leading to arrhythmias
  • Non-infective endocarditis affecting the mitral valve – Libman-Sacks syndrome
  • Increased artherosclerotic disease
• Kidneys
  • Glomerulonephritis
• Nervous system
  • Depression
  • Epilepsy
  • Migraine
  • Cerebellar ataxia
  • Aseptic meningitis
  • CN lesions
• Eyes
  • Retinal vasculitis
  • Episcleritis
  • Conjunctivis
  • Optic neuritis
  • Secondary Sjogren’s syndrome
• GI tract
  • Mouth ulcers
  • Inflammatory lesions of the small bowel caused by mesenteric vasculitis

 

Investigations

• Bloods – raised ESR, leucocytopenia, thrombocytopenia
• Serum antinuclear antibodies – anti-dsDNA, anti-RNA (Ro, LA)
• Rheumatoid factors
• Complement levels – reduced during active disease
• Anti-phospholipids antibodies;
  • Anti-cardiolipin
  • Anti-b2 glycoprotein 1
  • Lupus anticoagulant
• Raised immunoglobulins
• Histology

 

Management

• Drug therapy should be used for active disease
• NSAIDs
• Antimalarial drugs (chloroquine) to control skin rashes
• Corticosteroids orally or I.V
• Immunosuppressive drugs e.g. Azothioprin, cyclophosphamide, Mycophenolate for severe disease
• Anti-CD20 monoclonal

 

Pregnancy

• Fertility normal
• Increased miscarriages may be due to anti-phospholid antibodies
• Remission or exacerbation may occur
• Fetal mortality is high with renal involvement and anti-phospholipid antibodies

 

 

Antiphospholipid Syndrome

 

• Associated with autoantibodies which are specific for negatively charged phospholipids
• Small proportion of patients have SLE
• Associated with recurrent arterial and venous thrombosis and recurrent miscarriages
• Other features;
  • Thrombocytopenia
  • Chorea, migraine, epilepsy
  • Valvular heart disease
  • Cutaneous manifestations e.g. livedo reticularis
  • Positive Coomb’s test

 

Systemic (Scleroderma)

 

• Highest mortality of autoimmune rheumatic disease
• More common in women
• Age of onset 30-50

 

Pathology/pathogenesis

• Vascular lesions;
  • Involves arteries, arterioles and capillaries
  • Endothelial cells damage leads to release of endothelin-1 which causes vasoconstriction
  • Increased vascular permeability
  • Adhesion molecule upregulation
  • CD4 T cell infiltration
  • Damage to small blood vessels leads to obliterative arterial lesions and ischaemia
  • Increased fibrosis in skin and internal organs
• Antinuclear antibodies are produced

 

Clinical features

• Raynaud’s phenomenon
• Limited cutaneous scleroderma
  • Fixed flexion deformity of fingers
  • Beaked nose
  • Microstomia
  • Associated with CREST syndrome – calcinosis, Raynaud’s oesophageal involvement, sclerodactyly and telangiectasia
• Diffuse cutaneous scleroderma
  • Diffuse swelling and stiffness of fingers is usually followed by extensive sclerosis which can involve most of the body. May result in;
    • Oesophageal involvement
    • Anal incontinence
    • Pseudo-obstruction
• Renal involvement – acute or chronic
• Lung disease –fibrosis and pulmonary hypertension
• Myocardial fibrosis leading to arrhythmias and conduction defects

 

Investigations

• FBC – normocytic normochromic anaemia
• U&E’s
• Autoantibodies;
• Anti-nucleolar
• Anti-RNA Pol
• Rheumatoid factor
• ANA
• Urine – microscopy, proteinuria
• Imaging;
  • CXR
  • Hands
  • Barium swallow
  • CT

 

Management

• Treatment should be organ based
• Regular exercise and skin lubrication
• Raynaud’s may be improved by hand warmers, vasodilators
• Oesophageal symptoms – PPI
• Renal involvement – ACEi
• I.V prostacyclin may help digital ischaemia
• Pulmonary hypertension – oral vasodilators, oxygen and warfarin
• Pulmonary fibrosis – immunosuppression

 

• Pulmonary involvement accounts for 50% of scleroderma related deaths

 

Polymyositis and Dermatomyositis

 

Polymyositis

• Inflammation of striated muscle leading to proximal muscle weakness
• When skin is involved it is call dermatomyositis
• Rare – occurring in all ages and races
• Genetic predisposition related to HLA-B8/DR3

 

Clinical subsets are;

• Adult polymyositis
• Adult dermatomyositis
• Adult polymyositis, dermatomyositis with malignancies
• PM/DM in association with other CT diseases
• Childhood DM

 

Adult Polymyositis

• Women more commonly affected than men
• Onset can be acute or insidious
• Progressive proximal muscle weakness
• Wasting of shoulder and pelvic girdle
• Pain and tenderness are uncommon
• Involvement of pharyngeal, laryngeal and respiratory muscles leads to dysphagia, dysphonia and respiratory failure
• Raynaud’s phenomenon can be seen in some patients
• Hardening and fissuring of the skin over the pulp of the fingers (mechanics hands) is common

 

Adult Dermatomyositis

• Also more common in women
• Heliotrope (purple) discolouration of the eyelids and periorbital oedema
• Scaly-purple-raised patches occur over the extensor surfaces of joints and tendons
• Ulcerative vasculitis and calcinosis of the subcutaneous tissue
• Muscle weakness
• Myalgia
• Polyarthritis
• Raynaud’s phenomenon
• Long term muscle fibrosis and contractures of joints occurs

 

Associated with CT diseases

• Association with SLE, RA and systemic scleroderma
• Associated with deforming arthritis, malar rash, skin sclerosis

 

Association with malignancies

• Associated with a wide variety of cancers
• Associated cancer may not become apparent for years, refractory dermatomyositis should prompt a search for occult malignancy
• Some malignancy can predate the dermatomyositis particularly in males. These include cancers of;
  • Lung
  • Ovary
  • Breast
  • Stomach

 

Childhood dermatomyositis

• Commonly affects children between 4 and 10
• Rash of dermatomyositis accompanied by muscle weakness
• Ulcerative skin vasculitis is common
• Recurrent abdo pain can occur because of vasculitis
• Muscle atrophy, subcutaneous calcification and contractures may occur

 

Investigations

• Serum creatine kinase can be raised
• ESR
• Serum autoantibodies – ANA, rheumatoid factor
• EMG shows triad of features;
• Spontaneous fibrillation potentials at rest
• Short duration potentials on voluntary contractions
• Discharge of repetitive potentials on mechanical stimulation
• MRI to detect abnormal muscle
• Needle muscle biopsy – fibre necrosis and inflammatory infiltrate
• Malignancy screening

 

Treatment

• Prednisolone
• Steroid sparing agents - Methotrexate, Azothioprine, Ciclosporin, Cyclophosphamide, Mycophenolate
• Intravenous immunoglobulin

This entry was posted on Tuesday, November 6th, 2007 at 6:34 pm and is filed under Rheumatology. You can follow any responses to this entry through the RSS 2.0 feed. You can leave a response, or trackback from your own site.