systemic lupus erythromatosus

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