Systemic Lupus Erythematosus SLE The term lupus, which is Latin for wolf, was developed in the 13th Century and is commonly used for the disease technically known as systemic lupus erythematosus or SLE for short. Lupus got its name because it was thought to look like the lesions found on patient’s faces, which resembled a wolf’s bite. Dr. M Jokar

Definition Lupus: wolf Chronic Unknown etiology Connectie tissue dis. Autoimmune Multisystem

Lupus Types SLE DLE(Discoid lupus erythematosus) Drug induced lupus Neonatal lupus

Epidemiology Prevalence 40-150 in 100000 Urban area > rural areas

Epidemiology Race The prevalence of SLE is higher among Asians, Afro-Americans, Afro-Caribbeans, and Hispanic American

Epidemiology Sex: 95% in women Children 3:1 In adults 7-15:1 Older individuals 8:1

Epidemiology Age: all ages but more common in child- bearing ages 20% <16 years 65% 16-55 years 15% >55 years

Pathogenesis Abnormal immune response B and T cell hyperactivity Genetic background + Environmental factors Abnormal immune response B and T cell hyperactivity Autoantibodies Immue complexes Tissue damage

Genetic background Evidence for genetic predisposition: concordance in monozygotic 24-58% first degree relatives 5-12% genes: C4AQO HlA-DR2 HLA-DR3

Environmental factors UV-B(sometimes UV-A) Chemicals: hydrazines-hair dye? Viruses Drugs Sex hormones Stress Foods

Autoantibodies ANA Anti-DNA Anti-Sm Anti-RNP ,Anti-Ro=SS-A , Anti-La=SS-B Anti-Histone , Antiphospholipid , Antiplatelet Antierythrocyte , Antilymphocyte Antineuronal

Clinical manifestations Most patients experience exacerbations interspersed with periods of relative quiescence. True remissions with no symptoms and requiring no therapy occur in up to 20% but are usually not permanent. Systemic symptoms are usually prominent and include fatigue, malaise, fever, anorexia, and weight loss.

Clinical manifestations Can affect any organ in the body including the joints, skin, lungs, heart, blood, kidney, or nervous system. Can range from mild to life threatening. No two people will have identical symptoms. Systemic lupus erythematosus (SLE) can affect any system or organ in the body including the joints, skin, lungs, heart, blood, kidney, or nervous system. Symptoms of SLE can range from being minor to very serious or life threatening. A person may experience very little to no pain or they may experience extreme pain, especially in the joints. There may be no skin involvement or rashes that are disfiguring. They may have no organ involvement or extreme organ damage. Generally, no two people with systemic lupus will have identical symptoms. Most often when people mention "lupus," they are referring to the systemic form of the disease.

Musculoskeletal Almost all patients experience arthralgias and myalgias most develop intermittent arthritis Joint deformities are unusual Erosions are rare Myopathy and myositis Osteoporosis and AVN

Cutaneous Manifestations Malar ("butterfly") rash

Cutaneous Manifestations Discoid lupus erythematosus (DLE)

DISCOID LUPUS Affects the skin, hair or mucous membranes. Identified by a rash or lesions. Negative or low titer ANA. Diagnosed by biopsy of rash. 10% will evolve into SLE. Discoid or Cutaneous lupus (skin) lupus (DLE): affects primarily the skin, but may also involve the hair and mucous membranes. There is more than one type of cutaneous lupus, which can cause different looking rashes and symptoms. These include: Acute cutaneous lupus erythematosus (ACLE) Subacute cutaneous lupus erythematosus (SCLE) Chronic cutaneous lupus erythematosus (CCLE) or Discoid lupus erythematosus (DLE) Cutaneous lupus is usually identified by a rash or lesions that appear on the face, neck, and/or scalp (or other sun exposed areas). The lesions can appear patchy, crusty and cause scarring. Cutaneous lupus does not generally involve the body's internal organs. Therefore, the ANA test, which is a blood test used to help diagnose systemic lupus, may be negative in these patients. However, in some patients with discoid lupus, the ANA test is positive, but at a low level or "titer." Cutaneous lupus is diagnosed by examining a biopsy of the skin rash. In approximately 10 percent of patients, cutaneous lupus will evolve into the systemic form of the disease. This cannot be predicted or prevented. Treatment of cutaneous lupus will not prevent its progression to the systemic form, and individuals who progress to the systemic form probably had systemic lupus with the rash as their initial symptom. Topical and interlesional corticosteroids are usually effective for localized lesions, antimalarials or thalidomide may be needed for more generalized lesions.

Cutaneous Manifestations Maculopapular rash Subacute cutaneous lupus erythematosus (SCLE) Alopecia Photosensitivity Other rashes:maculopapular,urticaria, bullae, erythema multiforme

Alpecia

Renal Manifestations One-half have clinical nephritis Most have immunoglobulins deposited in glomeruli Early in the disease most are asymptomatic Urinalysis shows hematuria, cylindruria, and proteinuria

WHO classification of lupus nephritis Class I: normal Class II: mesangial lupus nephritis Class III:focal proliferative nephritis CLASS IV:diffuse proliferative nephritis Class V : membranous lupus nephritis Class VI: ESRD

Nervous System CNS PNS

CNS Any region of the brain can be involved in SLE Mild cognitive dysfunction is the most Seizures ,Headaches, demyelinating disorders, cerebrovascular disease, movement disorders, aseptic meningitis, myelopathy, subarachnoid hemorrhage Psychosis,mood disorders, depression and anxiety

PNS Mononeuropathy Polyneuropathy Mononeuritis multiplex Acute demyelinating polyneuropathy (Guillain-Barre)

Vascular System Thrombosis, emboli vasculitis Atherosclerosis Raynauds phenomenon

Hematologic Manifestation Anemia: Anemia of chronic disease,hemolytic anemia Leukopenia (usually lymphopenia) Thrombocytopenia Antiphospholipid antibodies and lupus anticoagulant Bleeding syndromes Splenomegaly,lymphadenopathy

Heart Pericarditis Myocarditis Valvular insufficiency (usually aortic or mitral) Libman-Sacks endocarditis Myocardial infarcts

Respiratory tract Pleurisy and pleural effusions pneumonitis Interstitial pneumonitis leading to fibrosis Pulmonary hypertension Respiratory distress syndrome Intraalveolar hemorrhage Infections

Gastrointestinal System Nausea, diarrhea, and vague discomfort Peritonitis Vasculitis of the intestine Acute pancreatitis Hepatitis Hepatomegaly

Ocular Manifestation Retinal vasculitis conjunctivitis episcleritis optic neuritis sicca syndrome

LABORATORY MANIFESTATIONS CBC:anemia, leukopenia, lymphopenia, and thrombocytopenia ESR,CRP Urinalysis :proteinuria, hematuria, and cellular or granular casts

LABORATORY MANIFESTATIONS Immunologic tests: ANA AntiDNA AntiSm Anticardiolipin C3,C4,CH50

PREGNANCY Fertility rates are normal Spontaneous abortion and stillbirths are frequent (10 to 30%), especially in women with LA and/or aCL Disease flares in a small proportion, especially during the 6 weeks postpartum

Neonatal lupus Caused by transmission of maternal anti-Ro across the placenta Transient skin rash Permanent heart block Transient thrombocytopenia

Renal and CNS involvement are rare DRUG-INDUCED LUPUS Drugs:procainamide, hydralazine, isoniazid, chlorpromazine, D-penicillamine, methyldopa, quinidine, interferon a, and possibly hydantoin, ethosuximide, and oral contraceptives Clinical manifestations: systemic complaints arthralgias; polyarthritis and pleuropericarditis Renal and CNS involvement are rare Lab:All patients have ANA and most have antibodies to histones,

DRUG-INDUCED LUPUS Anti dsDNA and hypocomplementemia are rare Anemia, leukopenia, LA, aCL, thrombocytopenia,,, false-positive VDRL, and positive direct Coombs' tests can occur Symptoms rarely persist more than 6 months; ANA may persist for years

PROGNOSIS Survival : 90 to 95% at 2 years 82 to 90% at 5 years Poor prognosis factors: high serum creatinine,Black Race ,hypertension,nephrotic syndrome thrombocytopenia, serious CNS involvement antibodies to phospholipids

Causes Of Death Cardiac involvement Pulmonary involvement CNS involvement Renal involement Infections

DIAGNOSIS Medical history (including family history) Complete physical examination Laboratory tests Skin or kidney biopsy

ACR DIAGNOSTIC CRITERIA Skin criteria 1. Butterfly rash 2. Discoid rash 3. Photosensitivity 4. Oral ulcers Systemic criteria 5. Arthritis 6. Serositis 7. Kidney disorder 8. Neurologic disorder To assist the physician in the diagnosis of lupus, the American College of Rheumatology (ACR) has developed a set of classification criteria used to help distinguish lupus from other diseases. A person should have four or more of these symptoms to suspect lupus. It is important to remember that the symptoms do not have to occur at the same time, and the criteria do not include all possible symptoms of lupus like fever, fatigue, hair loss, or Raynaud's phenomenon. The criteria are meant only to help with diagnosis. Butterfly or Malar Rash Rash over the cheeks and/or nose. Discoid Rash Red raised patches anywhere on the skin, but usually in the sun exposed areas of the face, arms, neck, hands. Photosensitivity Reaction to sunlight, resulting in the development or increase in skin rash or general feeling of illness. Oral Ulcers Ulcers in the nose or mouth, usually painless. Arthritis Non-erosive arthritis involving two or more peripheral joints (arthritis in which the bones around the joints do not become destroyed). Serositis Pleuritis or pericarditis – pain in the chest with deep breathing. Renal Disorder Excessive protein and/or cellular casts (abnormal elements the urine, derived from red and/or white cells and/or kidney tubule cells) in the urine. Neurologic Disorder Seizures (convulsions) and/or psychosis. Hematologic Disorder Hemolytic anemia (low red blood cell count), leukopenia (low white blood cell count) or thrombocytopenia (low platelet count). Immunologic Disorder Positive LE prep test, positive anti-DNA test, positive anti-Sm test or false positive syphilis test (VDRL). Antinuclear Antibody Positive test for antinuclear antibodies. Laboratory criteria 9. Hematologic abnormalities 10. Immunologic disorder 11. Antinuclear antibody

COMMON LUPUS MEDICATIONS NSAIDs Antimalarials Corticosteroids Immunosuppressants Investigational (research) Medications play an important role in the care of people with SLE. For most people with lupus, effective treatment can minimize symptoms, reduce inflammation, and maintain normal body functions. Treatment approaches are based on the specific needs and symptoms of each person. The medication prescribed usually depends on which organ(s) are involved and the severity of the involvement. The choice of drugs is highly individualized and typically changes often during the course of the disease. The medications used in the management of lupus include: ·        NSAIDs ·        Antimalarials ·        Corticosteroids ·        Immunosuppressants ·        Investigational (research)