Systemic Lupus Erythematosus (SLE) - PDF

Systemic Lupus Erythematosus (SLE) Present by Tihong Shao Department of Rheumatology and Immunology The First Affiliated Hospital of Anhui Medical University What is SLE A chronic autoimmune disease of unknown cause Affect virtually any organ of the body Prominent f...

Systemic Lupus Erythematosus (SLE) Present by Tihong Shao Department of Rheumatology and Immunology The First Affiliated Hospital of Anhui Medical University What is SLE A chronic autoimmune disease of unknown cause Affect virtually any organ of the body Prominent feature of the disease Immunologic abnormalities, especially the production of a number of antinuclear antibodies (ANA) Epidemiology of SLE Key Data Incidence: 1–25/100,000 (North America, South America, Europe, Asia) Prevalence (US): 20–150/100,000 Demographics Sex: Female-to-male ratio: Children: 3:1, Adults: 7–15:1 Age of Onset: 65%: 16–55 years, 20%: 55 years Pathogenesis of SLE Key Factors Immune Abnormalities Autoantibodies: Bind self-antigens, form immune complexes, and cause inflammation Contributing Factors Genetic: No single high-risk gene; susceptibility arises from combined genetic influences. Hormonal: Estradiol, progesterone, and prolactin impact disease expression. Environmental: UV light, infections (e.g., EBV), stress, and smoking. Pathogenesis of SLE  Clinical manifestations Major clinical features and organ involvement Constitutional symptoms Fatigue (80-100%): most common complaint Fever (≥50%): typically reflects active disease Myalgia Weight change: weight loss and weight gain Musculoskeletal Features Arthritis and arthralgias (≥90%): mild arthralgias to more severe arthropathy Nonerosive arthritis migratory, polyarticular, and symmetrical Hand deformity Jaccoud arthropathy, typically easily reducible Tendinopathy (10-44%) epicondylitis, rotator cuff tendinitis, Achilles tendinitis etc. Mucocutaneous involvement Acute cutaneous lupus erythematosus (ACLE) Subacute cutaneous lupus erythematosus (SCLE) Chronic cutaneous lupus erythematosus (CCLE) Major categories of cutaneous LE Acute cutaneous lupus erythematosus (ACLE) Localized ACLE (ie, malar rash, butterfly rash) Generalized ACLE: Involves widespread erythematous lesions across sun- exposed areas Toxic epidermal necrolysis-like ACLE: extensive skin detachment  Acute cutaneous lupus erythematosus An erythematous, edematous eruption is present on Malar erythema and subtle edema are present in the malar area in a patient with SLE. Note the sparing this patient with SLE. of the nasolabial folds. Subacute cutaneous lupus erythematosus (SCLE) Annular SCLE: Characterized by ring-shaped or polycyclic erythematous lesions, often with central clearing. These are commonly found in sun- exposed areas and are highly photosensitive. Papulosquamous SCLE: Resembles psoriasis, presenting as erythematous, scaly plaques, typically on the upper back, chest, and shoulders. Subacute cutaneous lupus erythematosus Multiple erythematous, scaly papules are present on the upper back. Erythematous, annular plaques with scale. Chronic cutaneous lupus erythematosus (CCLE) Discoid lupus erythematosus (DLE): 1.Localized: Lesions above the neck (face, scalp). 2.Generalized: Lesions on the head, neck, and other body parts. 3.Hypertrophic: Rare, thick warty plaques (face, arms, upper torso). Impact: Scarring and pigmentation changes, leading to cosmetic and psychosocial challenges.  Discoid lupus erythematosus Well-defined, erythematous plaques with scale on the A well-defined, erythematous cheek plaque with scale, pigmentary alteration, and scarring  Discoid lupus erythematosus Follicular plugging is evident with discoid Discoid LE affecting the scalp and face. There are lupus erythematosus involving the scalp. discoid plaques over eyebrows, forehead, and scalp, with postinflammatory peripheral hyperpigmentation, central depigmentation, scarring, and alopecia. Cutaneous immunopathology and the lupus band test (a) Light microscopy reveals thickening of the dermal–epidermal junction and inflammatory cells associated with a dermal appendage (hematoxylin and eosin stain). (b) At a higher power, immunofluorescence demonstrates IgM and C3b at the dermal– epidermal junction (bright green horizontal band seen midway through this section). Cardiac involvement and vascular manifestations Cardiac involvement Pericardium: 25% Myocardium: uncommon but may be severe Valves: Verrucous (Libman-Sacks) endocarditis Conduction System: uncommon Coronary Arteries: with an increased risk of accelerated atherosclerosis and coronary artery disease (CAD) Pericarditis in SLE Overview: Prevalence: Affects 25% of SLE patients Clinical Features: Acute Pericarditis: Precordial chest pain, pericardial rub, or asymptomatic. Pericardial Effusions: Usually small; tamponade (incipient/overt) possible.  Radiographic features of Pericardium Plain radiograph: globular enlargement of the Axial CT: Pericardial effusion (simple fluid density), measuring cardiac shadow giving a water bottle configuration up to 21 mm in depth. Myocarditis in SLE Prevalence: Occurs in 8-25% of SLE patients, more common in Black populations. Echocardiographic finding: Global/patchy hypokinesis in 6% of patients. Clinical Manifestations: Symptoms: Tachycardia, unexplained cardiomegaly, heart failure, arrhythmias. Valvular Disease in SLE Key Features: Prevalence: ~10% of SLE patients via echocardiography. Libman-Sacks Endocarditis: Verrucous vegetations found on Aortic valve and Left atrium Associated with anti-phospholipid antibodies  Gross Specimen and pathological section of Verrucous endocarditis Verrucous endocarditis with valvular vegetations Libman-Sacks endocarditis. Two verrucae on the surface (arrows). The vegetations had not been observed by of this valve contain fibrin and necrotic cell debris. echocardiography, although a cardiac murmur had been Inflammatory cells are localized primarily at the heard by auscultation. endocardial surface (hematoxylin and eosin stain).  Conduction Abnormalities in SLE Common Defects: Sinus Tachycardia: 18% prevalence. QT Prolongation: 17% prevalence. Atrial Fibrillation: 9% prevalence. Association with Autoantibodies: Mechanism: Conduction system may be replaced by fibrous tissue, resembling congenital complete heart block seen with anti-Ro antibodies. Clinical Manifestations of CAD in SLE Symptoms: May present with exertional chest pain, angina. Atypical symptoms (dyspnea, diaphoresis) or asymptomatic in some patients. Prevalence: 43% of SLE patients have perfusion abnormalities despite nonspecific complaints (e.g., chest discomfort, dyspnea). Cardiac involvement and vascular manifestations Vascular manifestations Raynaud phenomenon: up to 50% Vasculitis: 11-36% Thromboembolic disease Raynaud Phenomenon in SLE Prevalence: Affects up to 50% of SLE patients. Pathophysiology: Vasospastic process induced by cold. Clinical Features: Intermittent acral pallor, followed by cyanosis and erythroderma.  Raynaud Phenomenon in SLE (Panel A) Sharply demarcated pallor in several fingers resulting from the closure of digital arteries. (Panel B) Digital cyanosis of the fingertips resulting from vasoconstriction in the thermoregulatory vessels in the skin.  Vasculitis in SLE Prevalence: 11% to 36% of SLE patients. Vascular Involvement: Affects all vessel sizes, predominantly small vessels Clinical Manifestations: Small-Vessel Vasculitis: Cutaneous lesions (palpable purpura, petechiae, papulonodular lesions, livedo reticularis, panniculitis, splinter hemorrhages, superficial ulcerations). Medium/Large-Vessel Vasculitis: Less common but can involve peripheral nerves, lungs, pancreas, kidneys. Thromboembolic Disease in SLE Prevalence: common, particularly with antiphospholipid antibodies. Types of Thromboembolic Disease: Arterial Thrombotic Events (ATE) Venous Thrombotic Events (VTE) Lupus Nephritis (LN) in SLE Prevalence: Up to 50% of patients with SLE develop kidney disease during their illness. LN typically occurs early in the disease course. 10% of patients with LN will progress to end-stage kidney disease (ESKD).  Pathogenesis of LN Immune Complex Formation: primarily driven by anti-dsDNA Key Mechanisms: Neutrophil Activation, Complement Activation, Proinflammatory Cytokines Other Mechanisms: Endothelial Damage Autoantibody Production Clinical Features of LN Key Manifestations: Proteinuria (often nephrotic range) and nephrotic syndrome. Kidney abnormalities often emerge within 6-36 months of SLE diagnosis. Elevated creatinine in about 30% of SLE patients. Evaluation and Diagnosis of LN When to Suspect LN: Active urinary sediment: hematuria, cellular casts, proteinuria, elevated serum creatinine, or decreased eGFR. Serological markers: elevated anti-dsDNA and low C3/C4 Routine Monitoring: Testing includes urinalysis, serum creatinine, and anti-dsDNA levels. Establishing the Diagnosis of LN Kidney Biopsy: Gold standard for confirming LN diagnosis. Essential to: Define kidney involvement Exclude other causes of kidney injury Determine histopathologic subtype (activity, chronicity). When to Perform Kidney Biopsy: Clinical/laboratory evidence of kidney involvement: Proteinuria >500 mg/day Active urinary sediment (dysmorphic RBCs, cellular casts) Elevated serum creatinine or decreased GFR. Characteristic Histopathologic Findings in LN "Full House" Immunofluorescence Pattern Glomerular Deposits Tubuloreticular Inclusions Histopathologic Classification of LN 1.Minimal Mesangial LN (Class I) 1. Rare, normal urinalysis, and no kidney function impairment. 2. Mesangial immune deposits (immunofluorescence/electron microscopy). 2.Mesangial Proliferative LN (Class II) 1. Microscopic hematuria/proteinuria, no nephrotic syndrome. 2. Mesangial hypercellularity or matrix expansion, limited subendothelial/subepithelial deposits. 3.Focal LN (Class III) 1. Less than 50% glomeruli involved, segmental glomerulonephritis. 2. Proteinuria, hematuria, and hypertension common. 4.Diffuse LN (Class IV) 1. More than 50% glomeruli affected, endocapillary or extracapillary glomerulonephritis. 2. Nephrotic syndrome, hypocomplementemia, elevated anti-dsDNA. 5.Lupus Membranous Nephropathy (Class V) 1. Nephrotic syndrome, subepithelial deposits. 2. May present with normal complement levels and undetectable anti-dsDNA.  Other Forms of Lupus Kidney Disease Tubulointerstitial Nephritis Vascular Disease Lupus Podocytopathy Collapsing Glomerulosclerosis Drug-Induced Lupus Mesangial Proliferative Glomerulonephritis Light micrograph of a mesangial glomerulonephritis showing segmental areas of increased mesangial matrix and cellularity (arrows).  Proliferative Lupus Nephritis Light micrograph showing areas of cellular proliferation (arrows) and by thickening of the glomerular capillary wall (due to immune deposits) that may be prominent enough to form a "wire loop" (arrowheads). Immunofluorescence microscopy showing massive IgG deposition Kidney biopsy from a patient with diffuse proliferative lupus nephritis showing, on immunofluorescence microscopy, massive, lumpy deposits of IgG. Light micrograph showing lupus membranous nephropathy Diffuse thickening of the glomerular capillary wall being the major abnormality (short arrows). Focal areas of mesangial expansion and hypercellularity (long arrows)  Esophageal Involvement in SLE Common Symptoms: Dysphagia, chest pain, heartburn, regurgitation, odynophagia. Underlying Causes: Esophageal motility disorders (20–70%) Mechanism: Inflammation, ischemia, or vasculitis. Esophageal motility disorders Esophageal Spasm Esophageal Distal Normal esophageal Magnified Image Esophagitis Gastric Involvement in SLE Peptic Ulcer Disease: Symptoms: Epigastric pain/discomfort, early satiety, nausea, or asymptomatic. Risk Factors: NSAIDs, Helicobacter pylori, and NSAID-glucocorticoid interaction. Peptic Ulcer Gastroscopy showed gastric ulcer and bleeding Small Bowel Involvement in SLE Intestinal Pseudo-obstruction Overview: Rare SLE complication, mimics mechanical obstruction without anatomical lesions. Symptoms: Abdominal pain, bloating, distension (acute, recurrent, or chronic). Pathogenesis: Likely immune complex deposition, vasculitis, ischemia, and hypomotility.  Small Bowel Involvement in SLE Protein-losing Enteropathy Overview: Rare, often in young women with severe, multi-organ SLE. Symptoms: Profound edema, hypoalbuminemia (no nephrotic proteinuria). Diarrhea in 50% of cases. Hepatic Involvement in SLE Common Findings: Liver test abnormalities are common Causes: Drug-induced damage, steatosis, viral hepatitis, vascular thrombosis, autoimmune hepatitis, or SLE itself. Hepatic Involvement in SLE Autoimmune Hepatitis Prevalence: Rare in SLE (1.3–4.7%). Characteristics: ANA/ASMA positivity, histological autoimmune features. Lupus Hepatitis Features: Elevated transaminases (mild to severe). Nonspecific symptoms: fatigue, anorexia, jaundice, hepatomegaly. Positive ribosomal P antibody; lymphocytic periportal infiltration.  Pancreatic Involvement in SLE Acute Pancreatitis in SLE Prevalence: Occurs in 2–8% of SLE patients. Clinical Presentation: Severe, persistent epigastric pain radiating to the back. Serum amylase/lipase elevated ≥3 times normal. Elevated amylase can occur without pancreatitis in SLE.  Mesenteric Vasculitis in SLE Overview: Rare, life-threatening complication of SLE. Symptoms: Chronic: Postprandial pain, food aversion, weight loss, nausea, vomiting, diarrhea. Acute: Mesenteric thrombosis/infarction → perforation, peritonitis, acute abdomen. CT findings in lupus mesenteric vasculitis (LMV) a. LMV can develop from the upper to the lower gastrointestinal tract. b. Comb sign: Engorged mesenteric vessels (CT sagittal view). c. A target sign at the level of the duodenum (arrow). d. Target signs (short arrows), comb sign (long arrow), mesenteric fat attenuation, and ascites in the abdominal cavity (asterix). e. Diffuse thickening of the large- intestine bowel wall (arrows). f. rectal involvement in LMV that shows the typical target sign (arrow).  Peritonitis And Ascites in SLE Primary Peritonitis: Rare, develops during lupus flares. Acute: Mimics surgical abdomen but may be masked by immunosuppressives. Chronic: Painless ascites develops gradually. Ascites in SLE: Rare, possible causes include: Direct: Chronic lupus peritonitis. Indirect: Congestive heart failure. Hypoalbuminemia (nephrotic syndrome, protein-losing enteropathy). Pulmonary involvement in SLE Pleural Disease Prevalence: Up to 93% in autopsy series. Manifestations: Pleuritic Chest Pain: With or without effusion; transient rub aids diagnosis. Pleural Effusions: Bilateral (50%), exudative, elevated pleural LDH. Small to large; fluid ranges from serous to bloody. Symptoms: Cough, dyspnea, fever. Fibrothorax: Rare, leads to dyspnea by restricting lung expansion. Chest Imaging of Pleural Effusions CT scan of the chest illustrates bilateral pleural effusions. Acute Lupus Pneumonitis Prevalence: Uncommon, occurring in 1-12% of SLE patients. Clinical Manifestations: Rapid onset: Fever, cough (± hemoptysis), dyspnea. Signs: Tachypnea, tachycardia, hypoxemia, basilar crackles. Often the first manifestation of SLE (~50%). Chest Imaging of Lupus Pneumonitis Axial CT images show bilateral zones of GGO and consolidation with septal and interstitial thickening. (GGO - Ground-glass opacities )  Pulmonary Hemorrhage in SLE Prevalence: Rare complication, occurring in ~0.9% of SLE patients. Clinical Manifestations: Acute onset over ~3 days: Dyspnea, cough, and hemoptysis. Severe cases: Alveolar bleeding → anemia. Chest Imaging of Pulmonary Hemorrhage (A) Chest X-ray where bilateral pulmonary infiltrates were observed. (B) Computed axial tomography (CT) scan where mixed basal pulmonary infiltrates and alveolar collapse were observed.  Interstitial Lung Disease in SLE Prevalence: Reported in 3-9% of SLE patients. Histopathologic Patterns: Nonspecific interstitial pneumonia (NSIP) – Most common pattern. Other Patterns: UIP, OP, LIP Clinical Presentation: Insidious onset of chronic cough, dyspnea, and reduced exercise tolerance. Physical exam: Basilar crackles; some may be asymptomatic. usual interstitial pneumonia (UIP), organizing pneumonia (OP), lymphocytic interstitial pneumonia (LIP)  Chest Imaging of Interstitial Lung Disease NSIP pattern: reticular opacities and irregular linear opacities (minor subpleural reticulation) Thromboembolic Disease in SLE Increased Risk of Venous Thromboembolism (VTE): Hospitalized SLE patients: 1.23-fold higher risk compared to non-autoimmune patients. Key Risk Factors: Membranous nephropathy. Antiphospholipid antibodies. Pulmonary Hypertension in SLE Causes of PH in SLE: Pulmonary arterial hypertension (PAH), including lupus-associated PAH and pulmonary veno-occlusive disease (PVOD). Advanced interstitial lung disease (ILD) with hypoxemia. Thromboembolic disease. Left ventricular dysfunction. Prevalence and Severity: Rare but severe complication. Estimated prevalence of severe PH: ~1% in lupus clinics. Pulmonary Hypertension in SLE Common Symptoms: Dyspnea (abrupt with exertion, associated with oxygen desaturation). Palpitations, fatigue, impaired exercise tolerance. Weakness, syncope, peripheral edema, increased abdominal girth. Associated Factors: Raynaud phenomenon, elevated rheumatoid factor, anti-RNP antibodies, and antiphospholipid antibodies.  Shrinking Lung Syndrome (SLS) Epidemiology Occurs in 1–6% of patients with SLE. Typically manifests ~4 years after SLE diagnosis. Clinical Features Symptoms: Dyspnea, pleuritic chest pain (65%). Neurologic and neuropsychiatric involvement Stroke Seizures Altered Mental Status Cognitive Impairment Inflammatory and Demyelinating Disease Other Neurologic and Psychiatric Symptoms Peripheral nervous system manifestations  Stroke in SLE Epidemiology Stroke in 1-19% of SLE patients. Relative risk: Ischemic stroke; Intracerebral hemorrhage; Subarachnoid hemorrhage. Mechanisms Antiphospholipid antibodies (aPL): Arterial thrombosis, cardiogenic embolism, cerebral venous thrombosis. Cardioembolic causes: Valvular disease, atrial fibrillation (10% of patients). Atherosclerosis: Hypertension and other risk factors. Seizures in SLE Prevalence and Risk Factors Seizures occur in 4–12% of SLE patients over 1–8 years. Clinical Features Most seizures are localization-related (focal): Impaired awareness (complex partial seizures). Secondary generalization to bilateral tonic-clonic seizures.  Altered Mental Status in SLE Clinical Features 1.Acute Confusional State/Delirium: Symptoms: memory deficits, linear thinking impairment, and affective changes. 2.Psychosis: Occurs in 1-2% of SLE patients, usually within 1-3 years of diagnosis.  Cognitive Impairment in SLE Prevalence: Affecting ~38% of patients in a meta-analysis of 2463 individuals. Clinical Features: Symptoms: “Brain fog,” affecting attention, working memory, and processing speed. Glucocorticoids exacerbate verbal memory deficits. Inflammatory and Demyelinating Diseases Optic neuritis Myelitis Aseptic meningitis Chorea Hematologic abnormalities Anemia Leukopenia Thrombocytopenia Pancytopenia Thrombotic and Bleeding Complications Antiphospholipid antibodies and antiphospholipid syndrome Hematologic abnormalities-Anemia Prevalence most common hematologic abnormality, affects more than half of patients Symptoms fatigue, irritability, pallor, dyspnea, tachycardia, and, if severe, hemodynamic compromise. When anemia is related to hemolysis, patients can develop jaundice and/or dark urine Anemia Evaluation Causes associated with active SLE Anemia of chronic disease/anemia of inflammation (ACD/AI) Autoimmune hemolytic anemia (AIHA) Acquired aplastic anemia (autoimmune destruction of hematopoietic cells in the bone marrow) Thrombotic thrombocytopenic purpura (TTP) Catastrophic antiphospholipid syndrome (CAPS) Hematologic abnormalities- Leukopenia Lymphocytopenia Absolute lymphocyte count (ALC)