Lupus By: Brittni McClellan

Lupus - description Description: Genetics: Whites: HLA-DR2 and DR3 Autoimmune disease characterized by production of antibodies to various components of cell nucleus Variety of clinical manifestations (Multisystem) 20% Begins in Childhood, F:M = 3-5:1 Genetics: Whites: HLA-DR2 and DR3 Blacks: DR2 and DR7

Lupus – H&P Patient History: Photosensitivity/Malar Rash Systemic Complaints: Fevers, Fatigue, and Malaise Raynaud’s Phenomenon Joint Pain Alopecia Chest Pain: Pericarditis/Pleural Effusions

Lupus – H&P Serositis: Neurologic: Constitutional Symptoms: Renal: Signs and Symptoms: Immune Complex– Mediated Vasculitis Leukopenia Renal Failure – Serositis: Usually seen as pericarditis or pleuritis, Lymphopenia Cutaneous lesions: Thrombocytopenia Serositis: Neurologic: Erythematous Malar or “Butterfly” Rash Pericarditis Depression Pleuritis Maculopapular Rashes Seizures Peritonitis Periungual Erythema Organic Brain Syndromes Constitutional Symptoms: Mucosal Membrane Vasculitis Peripheral Neuropathies Arthritis: Renal: Fatigue Symmetric and Non-Erosive Mesangial Changes Weight Loss Hematologic: Glomerulonephritis Fever Hemolytic Anemia Hypertension Anemia of Chronic Disease Nephrotic Syndrome

Lupus – signs and symptoms

Lupus - Diagnosis Immunoserology: Diagnosis: Diagnostic Criteria: 4/11 Malar (Butterfly) Rash Discoid Rash Photosensitivity Oral/Nasal Ulcers Arthritis Cytopenia: Anemia Leukopenia Lymphopenia Thrombocytopenia Neurologic Disease: Seizures or Psychosis Nephritis: >0.5 g/d Proteinuria or Cellular Casts Serositis: Pleuritis or Pericarditis Positive Immunoserology: Antibodies to double-stranded DNA or Smith nuclear antigen, false-positive serologic test for syphilis, lupus r anticoagulant, or Immunoserology: Antinuclear Antibody (ANA): Best Initial Test High Sensitivity, Low Specificity Anti-Double Stranded DNA (dsDNA): Rises During Flares Low Sensitivity, High Specificity Indicates Renal Disease Anti-Smith: Antibody to snRNPs Highest Specificity Anti-Ro/Anti-La: Seen in Sjogren Syndrome Higher Risk of Neonatal Lupus in Pregnant Women Anti-Histone Antibody: Drug-Induced Lupus

Lupus - Diagnosis Diagnosis: CBC: Pancytopenia Anemia Leukopenia Lymphopenia Thrombocytopenia Other laboratory abnormalities: Decreased Complement Levels (C3/C4/CH50) Increased ESR Increased PTT: Lupus Anticoagulant increases the risk for thrombi and miscarriages  Associated with Antiphospholipid Syndrome Urinalysis: >0.5 g/d Proteinuria Cellular Casts

Lupus – treatment Medication NSAIDS: Musculoskeletal/Mild Systemic Complaints Can Exacerbate Renal Disease Ibuprofen: Causes Aseptic Meningitis in Some Patients Hydroxychloroquine: Controls Cutaneous Manifestations Minimizes Lupus Flares Steroids: Systemic and Renal Manifestations Immunosuppressants: Examples: Cyclophosphamide, Mycophenolate Mofetil Renal Manifestations Methotrexate: Arthritic Symptoms Daily Baby Aspirin Antiphospholipid Syndrome ACE-Is: Prevent Renal Damage and Proteinuria

Question 1 A 29-year-old woman with a 3-year history of systemic lupus erythematosus (SLE) presents to her rheumatologist for routine follow up. Her course has been complicated by lupus nephritis (baseline creatinine 1.1 mg/dL) and she has been on stable doses of methotrexate and hydroxychloroquine for the last 2 months following a flare. Which of the following lab values can be used to best monitor this patient's disease? Anti-nuclear antibody Anti-dsDNA antibody Anti-Smith antibody Anti-RNP antibody CH50 level Antinuclear Antibody (ANA): Best Initial Test High Sensitivity, Low Specificity Anti-Double Stranded DNA (dsDNA): Rises During Flares Low Sensitivity, High Specificity Indicates Renal Disease Anti-Smith: Antibody to snRNPs Highest Specificity Anti-Ro/Anti-La: Seen in Sjogren Syndrome Higher Risk of Neonatal Lupus in Pregnant Women Anti-Histone Antibody: Drug-Induced Lupus b) Anti-dsDNA antibody

Question 2 A 27-year-old woman presents to her primary care physician for evaluation of malaise, joint pains, and rash. Over the last 1-2 months, she has felt generally unwell with fatigue and low-grade fever. More recently, she has started to experience joint pains in her hands and noticed a rash over her face after sun exposure. She is otherwise healthy and takes no medications. Examination reveals an erythematous rash with a small amount of underlying edema (Figure A). Which of the following is the most common cardiac manifestation of this patient's underlying condition? Pericarditis Myocarditis Conduction arrhythmias Valvular disease Coronary artery disease This patient presents with a clinical history consistent with systemic lupus erythematosus (SLE). The most common cardiac manifestation of SLE is pericarditis.  SLE can affect the heart in numerous ways. Most commonly it causes pericarditis, with a pericardial effusion present in as many as half of patients. Patients are not typically symptomatic from pericarditis, but suggestive history includes substernal, pleuritic chest pain with an audible rub on examination. SLE can also cause valvular disease, most often mitral regurgitation. Large verrucous vegetations (typically mitral, aortic, or tricuspid) in the context of SLE is referred to as Libman-Sacks endocarditis.  Snyder et al. discuss the diagnosis and management of acute pericarditis. ECG findings in acute pericarditis include widespread concave ST-segment elevations and depression of the PR-segment. They highlight predictors of severe illness, including high fever, evidence of tamponade or a large effusion, or subacute onset; these factors warrant strong consideration of inpatient admission rather than outpatient treatment.  Farzaneh-Far et al. present a series of 200 patients with SLE who underwent extensive cardiac evaluation. They sought to assess the relationship between the presence of antiphospholipid antibodies (APL) and cardiac disease. They found a strong correlation between the presence of high levels of APL and mitral valve disease, including nodules and valvular regurgitation. APL levels did not correlate with altered LV size or function.  Figure A shows a typical "butterfly" (or malar) rash in a patient with SLE. This rash is photosensitive, spares the nasolabial folds, and occurs in up to half of patients with SLE.  Incorrect Answers:  Answer 2: Myocarditis can occur with SLE, and similarly is often asymptomatic, but is less common than pericarditis.  Answer 3: Conduction abnormalities typically represent scarring damage from prior myocarditis in SLE. When present, it is often a transient first-degree AV block.  Answer 4: Mitral valve disease (especially with resultant regurgitation) is a common cardiac manifestation of SLE, but pericarditis is more common. Mitral valve disease is especially associated with Libman-Sacks endocarditis.  Answer 5: Patients with SLE are at markedly increased risk for coronary artery disease, but it is still less common than pericarditis as a cardiac manifestation of SLE. a) Pericarditis