Systemic lupus erythematosus

Systemic lupus erythematosus: butterfly rash, discoid type

SLE is the most common multisystem connective tissue disease SLE is the most common multisystem connective tissue disease. It is characterized by a wide variety of clinical features and a diverse spectrum of autoantibody production. The prevalence varies according to geographical and racial background, from 30/100 000 in Caucasians to 200/100 000 in Afro-Caribbeans.

Aetiology and pathogenesis wide spectrum of autoantibody production results from polyclonal B- and T-cell activation. Many autoantigens in SLE are components of the intracellular and intranuclear machinery. In normal health these antigens are 'hidden' from the immune system and do not provoke an immune response

Etiological Factors & Pathogenesis 1- Genetic factors : Family studies : - High risk in siblings of SLE patients - Up to 50% concordance in monozygotic twins . - Healthy family members of SLE are more likely to have SLE type autoantibodies ( e.g. ANA ) . Positive association of SLE with certain HLA-DR & DQ genes ( including HLA-DR2 & DR3 ) . .

2-Environmental factors environmental factors that associate with flares of lupus-such as sunlight and artificial ultraviolet (UV) light, pregnancy and infection-increase oxidative stress and subsequent apoptosis

Clinical features Arthralgia or arthritis in combination with Raynaud's phenomenon is the most common presentation. It is important to elicit a history of Raynaud's since it is very uncommon for this to associate with other arthropathies such as RA. Raynaud's phenomenon in a teenage girl, with no other associated symptoms and especially if there is a family history, is likely to be idiopathic 'primary' Raynaud's

A variety of joint problems may occur, including migratory arthralgia with mild morning stiffness, tenosynovitis and small joint synovitis that may mimic RA. In contrast to RA, joint deformities are rare. Deformities that do occur result from tendon inflammation and damage rather than from bone erosion ('Jaccoud's arthropathy'

Mucocutaneous features The classic butterfly facial rash (20-30% of patients) is raised and painful or pruritic and occurs in a photosensitive distribution that spares the nasolabial folds. Subacute cutaneous lupus erythematosus (SCLE) rashes are migratory, non-scarring and either papulosquamous (psoriaform) or annular. Discoid lupus lesions are characterised by hyperkeratosis and follicular plugging and may cause scarring alopecia if present on the scalp.

Renal features Renal involvement is one of the main determinants of prognosis, and regular monitoring of urinalysis and blood pressure is essential. The typical renal lesion is a proliferative glomerulonephritis, characterised by heavy haematuria, proteinuria and casts on urine microscopy

Cardiopulmonary features The most common manifestation is chest pain from pleurisy or pericarditis. Myocarditis and sterile Libman-Sacks endocarditis may also occur,. SLE patients with antiphospholipid antibodies are at increased risk of venous thromboembolism, which should always be considered in the presence of chest pain or dyspnoea. Alveolitis and lung fibrosis occur, particularly in overlap connective tissue diseases

Central nervous system features Fatigue, headache, poor concentration and other non-specific features similar to fibromyalgia are common accompaniments of SLE and often occur in the absence of active disease. Specific features of cerebral lupus include visual hallucinations, chorea (also associated with antiphospholipid antibody syndrome), organic psychosis, transverse myelitis and lymphocytic meningitis.

Haematological features Antibody-mediated destruction of peripheral blood cells may cause neutropenia, lymphopenia, thrombocytopenia or haemolytic anaemia. The degree of leucopenia, most commonly lymphopenia, is often a good guide to disease activity. Although the ESR is usually elevated, CRP is often normal unless there is serositis or infection.

Other manifestations Fever, weight loss and mild lymphadenopathy commonly accompany active disease. Gastrointestinal involvement is rare and other causes of abdominal pain should always be considered, e.g. appendicitis, perforation secondary to drugs, or infection

Systemic lupus erythematosus: photosensitivity, face and neck

Systemic lupus erythematosus: alopecia, scalp

Systemic lupus erythematosus: bullous lesions, palate

Subacute cutaneous lupus erythematosus Left, Papulosquamous lesions are characterized by erythematous scaling papules and plaques that resemble psoriasis. The distribution in light-exposed areas suggests photosensitivity. Right, The annular polycyclic lesions have an erythematous, slightly scaling border with central clearing.

Systemic lupus erythematosis: vasculitis, hands

Vasculitis: fingers

Systemic lupus erythematosus: cytoid bodies

Systemic lupus erythematosus: retinal occlusive disease

Diagnosis Investigations : the aims * To confirm or exclude the disease . * To decide the extent of organ involvement . * To follow progression or regression of disease . * Treatment related investigations .

Diagnosis Commonly needed Investigations * Organs evaluations : CBC , Renal functions with urine analysis , Liver functions , ECG …etc . * Autoantibodies : next slide . * S. complement : oftenly reduced in active nephritis . * Partial thromboplastine time & prothrombine time . * Inflammatory markers : very high levels suggests infection .

Diagnosis Some autoantibodies in SLE * ANA : positive in >95% . Poor specificity . * ds DNA antibody : positive in 30 – 50 % . High titer in SLE is specific . Oftenly correlates with activity . * Anti- Sm antibody : positive in 25% . High specificity . * Anti- Ro antibody in 25% , may be positive in ANA -ve cases & in neonatal lupus . * Antiphospholipid antibodies .

Management Medication * Topical agents : - Sun protection factor (25 – 50) with sun avoidance . - Topical steroids . * NSAID : limitations in renal & GIT problems . * Chloroquine : for skin & joint lesions & ? Others . * Aspirin : ( low dose) for thrombotic vascular disorders & fetal losses . * Heparin / Warfarin .

Management Medication * Corticosteroids : - Pulse therapy . Acute or life-threatening disease (i.e. renal, cerebral) requires high-dose corticosteroids (e.g. oral prednisolone 40-60 mg daily or i.v. methylprednisolone 500 mg-1 g) in combination with pulse i.v. (10 mg/kg IV), coupled with cyclophosphamide (15 mg/kg IV), repeated at 2–3-weekly - Oral therapy . Dose according to condition . * Immunosupressive / cytotoxic therapy : - Cyclophosphamide . - Azathioprine . - Mycophenolate mofetil . - MTX , ciclosprine A … * Osteoporosis prevention & hypertension treatment .

Prognosis * With effective therapy the 5 years survival exceeds 90% & 10 years survival exceeds 70% . * Delayed treatment of nephritis is associated with high mortality . * Lupus nephritis occurs in 10% of transplanted kidneys in SLE cases .

Drugs Induced Lupus * Blamed drugs include beta-blockers , angiotensine converting enzyme inhibitors , INH , minocycline , TNF blockers , sulfasalazine …etc . * ANA usually positive . * Renal , CNS involvements & dsDNA antibody are all rare . * Usually resolve within weeks after stopping the drug .