Chronic inflammatory autoimmune connective tissue disorder with periods of relapse and remission - involves almost every organ system. 90% female. Onset usually 2nd to 4th decades of life. Reported prevalence varies but considered about 1 in 2000 – large geographic and ethnic variations (eg up to 4x more common in blacks and Hispanics in USA than whites).
Many factors implicated – hormonal (high incidence in females of child bearing age), environmental (infection, UV light), genetic (weak positive association with HLA-DR2 and HLA-DR3 and a negative association with HLA-DR4 and HLA-DR5)
A number of drugs have been identified causing a drug induced variant of SLE – most well established are hydralazine, methyldopa, isoniazid, chlorpromazine and possibly dilantin, penicillamine and quinine.
Antinuclear antibodies (present in 90+%) form immune complexes trigger tissue damage. Predominant pathological lesions are fibronoid necrosis in small blood vessels (vasculitis), membranes (eg pleura) and joint capsules. Immune complexes are found deposited in kidneys and blood vessels – occasionally elsewhere.
Clinical findings vary early diagnosis is difficult. Most common presentation is young female with polyarthritis and fatigue. Fatigue of early SLE is similar to a chronic influenza and may lead to initial diagnosis of chronic fatigue syndrome. May begin abruptly with fever (resembles acute infection) – or may develop insidiously over years with episodes of malaise and fever. Most common clinical presentations include fatigue, malaise, fever, weight loss, marked musculoskeletal symptoms.
Manifestations of disease may occur in any organ system:
• Joint symptoms – ranges from intermittent joint pain to acute polyarthritis. Symmetrical. Later joint deformity without erosions (Jaccoud’s arthropathy). Occurs in 90% - may be presenting feature in up to 50%
• Inflammatory myositis diffuse muscular tenderness and atrophy
• Osteonecrosis/avascular necrosis – in up to 14%; commonly the femoral head, carpel bones of wist and head of humerus; increased risk due to use of corticosteroids
• Osteoporosis – in up to 60%; especially lumbar spine – may be effect of corticosteroids
• Cutaneous lesions – facial butterfly erythema occurs in 50% (Discoid lupus erythematosus); firm maculopapular lesions on face and exposed areas of neck, upper chest and elbow; nail changes like onychomycosis; Raynauds phenomenon; photosensitvity (get rash over exposed areas); hypertrophic lesions on palms and soles; alopecia
• Pleurisy, pneumonitis, pulmonary hypertension
• Splenomegaly and liver enlargement
• Eyes - retinopathy
• Cardiovascular (premature/accelerated atherosclerosis, myocarditis, vasculitis, pericarditis, myocardial disease, peripheral vascular disease, pulmonary hypertension)
• Blood – normochromic normocytic anaemia, lymphopenia, neutropenia, thrombocytopenia
• Central nervous system – headaches, aseptic meningitis, personality changes & psychoses, stroke, epilepsy, transverse myelopathy, mononeuritis multiplex
• Psychiatric (organic brain syndrome, psychosis, neurocognitive dysfunction, depression, mood disorder) – in up to 50% (may be higher if minor symptoms included)
• Renal – lupus nephritis (in up to 50%) - common manifestation is proteinuria – due to glomerulonephritis and renal failure; less common in older onset cases
• most common causes of death in those with SLE are infection, renal disease (nephritis), cardiovascular disease and involvement of the CNS.
Nearly all are positive for ANA (detected by indirect immunoflourescence); hypergammaglobulinaemia, R factor, positive Coomb’s test; mild normochromic normocytic anaemia. CRP is generally not elevated in active disease.
Levels of some antibodies parallel disease activity.
Diagnosis – based on organ involvement and demonstration of immunologic abnormalities; there is no pathognomonic marker
American Collage of Rheumatology Criteria for classification of SLE – at least four of following 11 criteria: malar rash, discoid rash, photosensitvity, oral ulcers, arthritis, seroisitis, renal disorder, neurologic disorder, haematologic disorder, immunologic disorder, antinuclear antibodies. This criteria is for classification and not necessarily diagnosis, as they may not be sensitive enough in early or mild cases.
Discoid Lupus Erythematosus:
Confined to the skin. Raynauds and chilblains/erythema pernio are common.
Skin lesions are well-demarcated indurated round/oval lesions with scaling and keratotic plugs – most commonly on head and neck. Usually exacerbated by sunlight.
5% develop SLE
Treatment – topical corticosteroids; sunscreens; avoidance of sunlight
Involvement of foot:
• Similar pattern of symmetric polyarthritis as rheumatoid arthritis – but not severe enough to cause erosions (Jaccoud’s arthropathy) – the deformities are passively correctable .
• Feet are often ‘tender’ with HAV and flat feet.
• Sensory (sometimes motor) peripheral neuropathy is infrequent, but can occur early.
• Purpura may occur in feet as result of cutaneous vasculitis.
• Hypertrophic lesions can occur on plantar surface of feet.
• Higher risk of stress fractures (due to osteoporosis). Other bone lesions in feet include small well defined radiolucent areas subchondrally surrounded by normal or sclerotic bone in small joints of hands and feet – ‘periarticular cystic lesions’ . Avascular necrosis of talus and Friebergs infarction of metatarsals can also occur
• Also get nail dystrophies (in up to 25%), osteonecrosis, nailfold capillary abnormalities, chilblains, Raynauds phenomena, vasculitis and peripheral vascular disease gangrene.
• Chilblain lupus erythematosus (Hutchinson’s) is a more chronic form with chilblains on digits, calves and heels – chilblains often persistent and a high number of this type go on to full SLE – treatment of the chilblains associated with the LE are difficult.
• Peripheral neuropathy occurs in 5-27% - mostly a progressive sensorimotor axonopathy of the longer nerves. Nerve conduction velocities fluctuate over time .
• Case has been reported of a sudden onset of drop foot and hyperesthesia in lower extremity (similar to Guillain-Barre syndrome) as presenting feature of SLE .
• Another case has been reported of initial presenting feature being painful plantar lesions.
• Two cases of ulcerating plantar keratoderma’s and fissures that were resistant to treatment
Clinical diversity makes it difficult to manage.
Support and counselling – patient support groups are helpful
For skin lesions – sun screens; protective clothing; topical agents (corticosteroids, calcipotriene, retinoids).
Acute active stages - corticosteroids
Long term - 1) NSAID’s (first line drug, especially for initial minor manifestations)
2) Antimalarials (especially hydroxychloroquine for in those with skin and joint involvement; also shown to be effective in acute attacks)
3) Corticosteroids (cornerstone of management, but increasing concern at long term use due to musculoskeletal damage and increased risk for cardiovascular disease)
4) Thalidomide is used in treatment resistant cutaneous forms (improvement in >80%, but risk of foetal abnormalities and neuropathy)
5) Immunosuppressive drugs (eg methotrexate, cyclosporine, mycophenolate mofetil, intravenous immunoglobulin)
6) Biological interventions and manipulations (eg plasmaphoresis, immunoadsorption, anti-CD40L)
Monitoring for development of complications – especially renal disease.
Ethnicity, socioeconomic status, education achievement and psychosocial factors influence outcomes of treatment .