Systemic lupus erythematosus

Systemic lupus erythematosus

1. A non-organ-specific autoimmune disease in which autoantibodies are produced against a variety of autoantigens (eg ANA ). Immunopathology results in polyclonal B -cell secretion of pathogenic autoantibodies causing formation of immune complexes depositing in sites such as the kidneys

2. Epidemiology

   • F:M : 9:1. Prevalence: ~0.2%. Common in: Pregnancy; African-Americans; Asians— and if HLA B 8 , DR 2 or DR 3 +ve. ~10% of relatives of SLE patients are affected. It is a remitting and relapsing illness, with peak age at diagnosis being 30– 40yrs

3. Symptoms & Signs

   • Splenomegaly, lymphadenopathy, alopecia, recurrent abortion, retinal exudates, fibrosing alveolitis, myalgia, anorexia, myositis, migraine

4. Investigations

   • Raised ESR (think of SLE whenever someone has a multisystem disorder and ESR ^ but CRP «). Immunogenetics >95% are ANA +ve. High titer of antibodies directed against double-stranded DNA is nearly exclusive to SLE . Its absence does not exclude it. 11% have false +ve syphilis serology from IgG anticardiolipin antibodies. Antibodies to Ro ( SS - A ), La ( SS - B ), and U 1 ribonuclear protein help define overlap syndromes (eg with Sjögren’s)
   • Monitoring activity
     • 3 best tests: (1) ESR (2) Complement: C 3 |, C 4 |; C 3 d^ (denotes degradation products of C 3 , hence it moves in the opposite way) (3) Double-stranded (antiDS ) DNA antibody titers. Others: Urinalysis, electrolytes, FBC

5. Drug induced lupus

   • This can be caused by isoniazid, hydralazine (in slow acetylators), procainamide, chlorpromazine, minocycline, TNF inhibitors. Lung and skin signs prevail over renal and CNS signs. It remits if the drug is stopped. Sulfonamides and birth control pills may exacerbate idiopathic SLE

6. Antiphospholipid syndrome

   • Either primary or secondary to SLE (20-30%)
   • Antiphospholipid antibodies, anticardiolipin antibody & lupus anticoagulants are present
   • Features of CLOT: Coagulation defect, Livedo reticularis, Obstetric recurrent miscarriage, Thrombocytopenia (low platelets). Prothrombotic tendency,
   • Treatment: Low dose aspirin or warfarin if recurrent thromboses

7. Treatment

   • Refer to a rheumatologist. NSAID s . Sun-block creams. Hydroxychloroquine if joint or skin symptoms are uncontrolled by NSAID s. SE : Irreversible retinopathy— annual ophthalmic referral is recommended. High-dose prednisone is kept for severe episodes, may be combined with other immunosuppressive agents (eg cyclophosphamide), or ‘steroid-sparing agents’, eg azathioprine, methotrexate, or mycophenolate. Low-dose steroids may be of value in chronic disease. Cyclophosphamide is indicated for some nephritides. Azathioprine can be a ‘steroid-sparer’ SE : Lymphoma. Renal transplantation may be needed; nephritis recurs in ~50%, on biopsy, but is a rare cause of graft failure.

8. Revised criteria for diagnosing SLE

   • If 4 out of the 11 are present serially or simultaneously
     • 1. Malar rash (butterfly rash): Fixed erythema, flat or raised, over the malar eminences, tending to spare the nasolabial folds
       • 2. Discoid rash: Erythematous raised patches with adherent keratotic scaling and follicular plugging ± atrophic scarring. Think of it as a 3-stage rash affecting ears, cheeks, scalp, forehead, and chest: Erythema ¬ pigmented hyperkeratotic edematous papules ¬ atrophic depressed lesions
         • 3. Photosensitivity on exposed skin representing unusual reaction to light
           • 4. Oral ulcers: Oral or nasopharyngeal ulceration
             • 5. Arthritis: Non-erosive arthritis involving 2 or more peripheral joints, characterized by tenderness, swelling, or effusion. Joint involvement is seen in 90% of patients. Deforming arthropathy may occur due to capsular laxity (Jaccoud’s arthropathy). Aseptic bone necrosis also occurs
               • 6. Serositis: (a) Pleuritis (b) Pericarditis.
                 • 7. Renal disorders: (a) Persistent proteinuria >0.5g/d (or >3+ on dipstix) OR (b) Cellular casts— may be red cell, granular, or mixed
                   • 8. CNS disorders: (a) Seizures, in the absence of causative drugs or known metabolic imbalance, eg uremia, ketoacidosis, OR (b) Psychosis in the absence of causative drugs/metabolic derangements, as above
                     • 9. Hematological disorders: (a) Hemolytic anemia with reticulocytosis OR (b) Leukopenia, ie WBC <4Þ´10 9 / L on ³2 occasions OR (c) Lymphopenia, ie <1.500Þ´10 9 / L on ³2 occasions OR (d) Thrombocytopenia, ie platelets <100Þ´10 9 / L in the absence of a drug effect
                       • 10. Immunological disorders: (a) AntiDNA antibody to native DNA in abnormal titer OR (b) Anti-Sm antibody to Sm nuclear antigen OR (c) Antiphospholipid antibody +ve based on: (1) an abnormal serum level of IgG or IgM anticardiolipin antibodies, (2) positive result for lupus anticoagulant using a standard method, or (3) false positive serological test for syphilis +ve for >6 months and confirmed by Treponema pallidum immobilization or fluorescent treponemal antibody absorption tests
                         • 11. Antinuclear antibody: Positive in 95%