Dr HabeebResident
Medicine Unit-1BMCH
Introduction
Systemic Lupus erythromatosus is a rare, autoimmune based chronic inflammatory disease of un-known aetiology.
Maybe confined to the skin or may involve multiple organs system.
Some 90% of affected patients are female.
Peak age at onset is 20 to 30 years.
Lupus is associated with morbidity and a five-fold increase in mortality mainly because of an increased risk of premature cardiovascular disease.
Most common cause of death are infections and Renal Failure.
Pathophysiology
SLE is characterized by hyper-reactivity of B lymphocytes, hypergammaglobulinaemia, multiple autoantibodies, circulating immune complexes, and complement activation (low C3 , C4).
Autoantibodies to self antigens, increased apoptosis and impaired clearance of apoptotic bodies play an important role. Tissue damage is the result of immune complex deposition as well as direct cellular injury.
History and Examination…..
1. Constitutional SymptomsPatient may present with symptoms such as Fever, Weight loss , fatigue and malaise
History and Examination…..
1. Constitutional Symptoms2. Arthritis
Arthralgia is a common symptom, occurring in 90% ofpatients, and is often associated with early morning stiffness, joint deformity may occur but erosion does not.
History and Examination…..
1. Constitutional Symptoms2. Arthritis3. Raynaud’s Phenomenon
Raynaud’s associated with SLE needs to be differentiated from primary Raynaud’s, which is common in healthy young women.
History and Examination…..
1. Constitutional Symptoms2. Arthritis3. Raynaud’s Phenomenon4. Skin involvement
3 types of skin lesions:Malar Rash classically butterfly rash, Discoid Rash which is scaring and may cause Alopecia if on scalp & subacute cutaneous lupus erythromatosus rash which is migratory and non-scaring
History and Examination…..
1. Constitutional Symptoms2. Arthritis3. Raynaud’s Phenomenon4. Skin involvement5. Kidney
Typical renal lesion is a proliferative glomerulonephiritis , characterized by haematuria, proteinuria and casts on urine microscopy.
History and Examination…..
1. Constitutional Symptoms2. Arthritis3. Raynaud’s Phenomenon4. Skin involvement5. Kidney6. Cardiovascular
Pericarditis, Myocarditis & less commonly Libman–Sacks endocarditis can occur. Increased risk of stroke & MI due to increased atherosclerosis.
History and Examination…..
1. Constitutional Symptoms2. Arthritis3. Raynaud’s Phenomenon4. Skin involvement5. Kidney6. Cardiovascular7. Lungs
Lung involvement manifests as pleurisy or pleural effusion. Other features include pneumonitis, atelectasis, reduced lung volume and pulmonary fibrosis.
History and Examination…..
1. Constitutional Symptoms2. Arthritis3. Raynaud’s Phenomenon4. Skin involvement5. Kidney6. Cardiovascular7. Lungs8. Neurological
Fatigue, headache and poor concentration are common. More specific features of cerebral lupus include visual hallucinations, chorea, organic psychosis, transverse myelitis and lymphocytic meningitis.
History and Examination…..
1. Constitutional Symptoms2. Arthritis3. Raynaud’s Phenomenon4. Skin involvement5. Kidney6. Cardiovascular7. Lungs8. Neurological9. Hematological
Neutropenia, lymphopenia, thrombocytopenia orhaemolytic anaemia may occur, due to antibody mediated destruction of peripheral blood cells.
History and Examination…..
1. Constitutional Symptoms2. Arthritis3. Raynaud’s Phenomenon4. Skin involvement5. Kidney6. Cardiovascular7. Lungs8. Neurological9. Hematological10.Gastrointestinal
Mouth ulcers may occur and may or may not be painful.Mesenteric vasculitis is a serious complication, which can present with abdominal pain, bowel infarction or perforation.
Diagnostic Criteria
Diagnostic Criteria
1. Malar Rash2. Oral Ulcers3. Discoid Rash4. E “Hematological”5. Renal Involvement6. Neurological 7. Photosensitivity8. Arthritis9. Immunological10.Serositis11.ANA
Mnemonic “Modern Paisa” to memorize the criteria
Fixed erythema, flat or raised over the malar eminences, sparing the nasolabial folds
Diagnostic Criteria
1. Malar Rash2. Oral Ulcers3. Discoid Rash4. E “Hematological”5. Renal Involvement6. Neurological 7. Photosensitivity8. Arthritis9. Immunological10.Serositis11.ANA
Mnemonic “Modern Paisa” to memorize the criteria
Oral or nasopharyngeal ulceration, usuallypainless
Diagnostic Criteria
1. Malar Rash2. Oral Ulcers3. Discoid Rash4. E “Hematological”5. Renal Involvement6. Neurological 7. Photosensitivity8. Arthritis9. Immunological10.Serositis11.ANA
Mnemonic “Modern Paisa” to memorize the criteria
Erythematous raised patches with adherent keratotic scaling and follicular plugging; atrophic scarring may occur in the older lesions
Diagnostic Criteria
1. Malar Rash2. Oral Ulcers3. Discoid Rash4. E “Hematological”5. Renal Involvement6. Neurological 7. Photosensitivity8. Arthritis9. Immunological10.Serositis11.ANA
Mnemonic “Modern Paisa” to memorize the criteria
Haemolytic anaemia, leucopaenia (<4000 mm),lymphopaenia (<1500/mm), thrombocytopaenia(<100,000/mm
Diagnostic Criteria
1. Malar Rash2. Oral Ulcers3. Discoid Rash4. E “Hematological”5. Renal Involvement6. Neurological 7. Photosensitivity8. Arthritis9. Immunological10.Serositis11.ANA
Mnemonic “Modern Paisa” to memorize the criteria
Persistent proteinuria greater than 0.5 gm/dayor greater than 3+ on dipstick or Cellular casts
Diagnostic Criteria
1. Malar Rash2. Oral Ulcers3. Discoid Rash4. E “Hematological”5. Renal Involvement6. Neurological 7. Photosensitivity8. Arthritis9. Immunological10.Serositis11.ANA
Mnemonic “Modern Paisa” to memorize the criteria
Seizures or psychosis, other causes ruled out
Diagnostic Criteria
1. Malar Rash2. Oral Ulcers3. Discoid Rash4. E “Hematological”5. Renal Involvement6. Neurological 7. Photosensitivity8. Arthritis9. Immunological10.Serositis11.ANA
Mnemonic “Modern Paisa” to memorize the criteria
Skin rash on exposed areas as a result of unusual reaction to sunlight
Diagnostic Criteria
1. Malar Rash2. Oral Ulcers3. Discoid Rash4. E “Hematological”5. Renal Involvement6. Neurological 7. Photosensitivity8. Arthritis9. Immunological10.Serositis11.ANA
Mnemonic “Modern Paisa” to memorize the criteria
Non-erosive arthritis involving two or moreperipheral joints, characterised by tenderness,swelling or effusion
Diagnostic Criteria
1. Malar Rash2. Oral Ulcers3. Discoid Rash4. E “Hematological”5. Renal Involvement6. Neurological 7. Photosensitivity8. Arthritis9. Immunological10.Serositis11.ANA
Mnemonic “Modern Paisa” to memorize the criteria
Anti-DNA antibodies in abnormal titre or presence of antibody to Sm antigen or positive antiphospholipid antibodies
Diagnostic Criteria
1. Malar Rash2. Oral Ulcers3. Discoid Rash4. E “Hematological”5. Renal Involvement6. Neurological 7. Photosensitivity8. Arthritis9. Immunological10.Serositis11.ANA
Mnemonic “Modern Paisa” to memorize the criteria
Pleuritis, by history of pleuritic pain or rub heard by a physician or evidence of pleural effusion on CXR or CT or Pericarditis by ECG or evidence of pericardial effusion
Diagnostic Criteria
1. Malar Rash2. Oral Ulcers3. Discoid Rash4. E “Hematological”5. Renal Involvement6. Neurological 7. Photosensitivity8. Arthritis9. Immunological10.Serositis11.ANA
Mnemonic “Modern Paisa” to memorize the criteria
A significant titre by ImmunoFlurescent method in the absence of the other causes of positive ANA
Diagnostic Criteria
1. Malar Rash2. Oral Ulcers3. Discoid Rash4. E “Hematological”5. Renal Involvement6. Neurological 7. Photosensitivity8. Arthritis9. Immunological10.Serositis11.ANA
Mnemonic “Modern Paisa” to memorize the criteria
A significant titre by ImmunoFlurescent method in the absence of the other causes of positive ANA
Workup…
Workup…
Blood CP Anemia,Leukopenia & Thrombocytopenia which characterize active Lupus
Following biochemical investigations are routinely carried out:
Workup…
Blood CP
Urine AnalysisHematuria, Proteinuria, Casts
Following biochemical investigations are routinely carried out:
Workup…
Blood CP
Urine Analysis
Creatinine
Routinely done to assess Kidney function
Following biochemical investigations are routinely carried out:
Workup…
Blood CP
Urine Analysis
Creatinine
ESR
Routinely done to assess Kidney function
Following biochemical investigations are routinely carried out:
Workup…
These are repeated periodically (monthly or at longer intervals).Immunology investigations
• ANA (not required to be repeated)• Anti-dsDNA• ENAs (Antibodies to extractable nuclear an(SSA), La (SSB), Smith etc.• C3, C4• Antiphospholipid antibodies
Others:X-ray chest
Investigations Depending on Systemic Involvement
Workup…
Disease Activity Assessment
Disease Activity Assessment
Periodic CBC and urine analysis are mandatory. Active lupus is characterised by anaemia, leucopaenia,
lymphopaenia, and thrombocytopaenia Proteinuria and active urinary sediment point to active
glomerulonephritis. Rising anti-dsDNA titres and falling C3 C4 levels.
Treatment
Prevention
All patients with lupus erythematosus should be counseled on photoprotection, including protecting skin from sunlight and avoiding sun exposure during peak hours (i.e., between 10 AM and 2 PM).
Broad-spectrum sunscreen that contains titanium, zinc, Mexoryl (L’Oreal), or Helioplex(Neutrogena) should be used whenever patients are outdoors.
Photoprotective clothing, available from multiple vendors, is useful for limiting sun exposure.
Medium-potency topical corticosteroidsUse of triamcinolone 0.1% cream (Flutex) for lesions on the head and neck up to 2 weeks
Foam or liquid- or lotion based corticosteroids for the scalp lesions.Intralesional corticosteroids may cause mild discomfort, atrophy of the skin or subcutis, or stretch marks. Topical calcineurin inhibitors such as pimecrolimus (Elidel) or tacrolimus (Protopic) may be used for maintenance treatment Recurrent or refractory lesions require systemic treatment.
Treatment of Cutaneous Lupus Erythematosus
Antimalarials hydroxychloroquine (HCQ) are disease-modifying agents that limit the progression of lupus.
Hydroxychloroquine at 200 mg daily for 2 weeks and then increased to 400 mg daily.
Hydroxychloroquine exerts its effects within 2 to 3 months of beginning treatment.
Treatment of Systemic Lupus Erythematosus
• Depending on end-organ involvement in SLE, immunosuppression with systemic corticosteroids such as prednisone at doses of 1 mg/kg/day is appropriate.
• Steroid-sparing drugs such as methotrexate , acitretin or mycophenolate mofetil are added.
Treatment of Systemic Lupus Erythematosus cont……
Arthralgia can usually be managed with acetaminophen or nonsteroidal antiinflammatory drugs (NSAIDs). Hydroxychloroquine 200 mg twice daily can be added. Methotrexate 7.5 to 25 mg PO once weekly with folic acid 1mg daily .Azathioprine (Imuran) 0.5 to 2 mg/kg with monitoring of CBC & LFTs. Low-dose glucocorticoids (prednisone 5–10 mg/day) may be used as a bridge to steroid-sparing therapy and to treat intermittent flares.
Treatment of Musculoskeletal Manifestations
Lupus Nephritis is one of the severe manifestation of renal disease and Treatment should be coordinated with a rheumatologist or nephrologist.
Class I disease no therapy.
Class II can be treated with prednisone (20 mg/day for 6 weeks to 3 months)Class III and IV disease treated with prednisone(1 mg/kg/day) for 6 weeks ,maintenance of 10 to 15 mg/day. In addition cytotoxic therapy with Cyclophosphamide 0.5 to 1 g/m BSA monthly for 6 months and tapered to every 3 monthsClass V disease can be treated with prednisone alone, similar to class II disease
Treatment of Renal Manifestations
Neuropsychiatric Symptoms can range from mild to severe headache, aseptic meningitis, neuropathy, myelopathy, cognitive dysfunction, seizures, cerebritis, and stroke.
For seizures, antiepileptic therapy is used.
Lupus cerebritis and transverse myelitis are two of the more serious manifestations that need to be treated emergently with aggressive immunosuppression.
Treatment includes high-dose corticosteroids and cyclophosphamide, similar to treatment for lupus nephritis.
Treatment of Nervous System Manifestations
SPECIAL PROBLEMS
Fertility, Pregnancy, Contraception
Infections
SLE in Elderly
• Steroids, hydroxychloroquine, and azathioprine can be continued during pregnancy.
• Cyclophosphamide, methotrexate, and mycophenolate should be discontinued 3 to 6 months before conception.
• Cyclophosphamide therapy carries the risk of age dependent ovarian failure.
• Intrauterine contraceptive devices should be avoided.• Oestrogen-containing contraceptives should be avoided with
APS
Fertility, Pregnancy, Contraception
• Patients with SLE are particularly susceptible to infections • Candida, Herpes, Salmonella & Mycobacteria and capsulated
organisms (Pneumococcus, Meningococcus and H. influenzae).
• Increased susceptibility is due to low complement levels, prednisolone (>20 mg/d), immunosuppressives, splenic hypofunction.
• Prevention of infection with chemoprophylaxis and vaccination is advised.
Infections
• SLE in the elderly is a milder disease.• Characterized by insidious onset, longer duration of disease• Lower incidence of renal, musculoskeletal, skin and
neurological manifestations.
SLE in Elderly
Drug-Induced SLE
• ANA, anti-histone antibodies, and LE cells are characteristic features of drug induced SLE.
• Clinical features are mild; renal and neurological involvement
is rare.
• Symptoms resolve on withdrawal of the offending drug
• Antibody titres may continue to remain elevated for a long time.
Drug-Induced SLE
Drug-Induced SLE
o Procainamideo Quinidine
o Hydralazineo Methyldopao Chlorpromazineo Isoniazid
More commonly
Less common