Lecture #128: Rheumatology 2: Systemic Rheumatologic Disease

What is the sequence of autoimmunity pathogenesis?

Genetic susceptibility, breakdown of self tolerance, environmental triggers, tissue damage, activation of self reactive lymphocytes, further tissue damage

What are the key characteristics of autoimmune diseases?

Chronic course, relapses and remissions, progressive nature, systemic involvement, underlying immune response abnormalities, hypersensitivity type II and III reactions

What is the mechanism of hypersensitivity type II reactions?

Antibodies bind to cell surface antigens causing direct cell destruction

What is the mechanism of hypersensitivity type III reactions?

Immune complex deposition of antigen antibody complexes with complement activation leading to tissue damage

What are the epidemiologic demographics of SLE?

Female predominance 9:1, onset typically 20–40 years, more common and severe in African, Hispanic and Asian populations

How is SLE defined?

Autoimmune inflammatory disorder with autoantibodies to nuclear antigens causing multi organ involvement via immune complex deposition

What is the core pathophysiology of SLE?

Type III hypersensitivity with antibody antigen complexes depositing in capillaries leading to organ damage

What factors contribute to SLE pathogenesis?

Genetic predisposition, defective tolerance, defective clearance of apoptotic bodies, environmental triggers such as UV light and certain drugs

Which drugs are associated with SLE?

Hydralazine, procainamide, D penicillamine

What are common clinical presentations of SLE?

Fever, malar rash, discoid rash, pleuritis, pericarditis, cytopenias, non erosive arthritis, seizures, psychosis, renal disease

What is the most common skin manifestation of SLE?

Malar rash, also called butterfly rash, resolves without scarring

What are the characteristics of discoid rash in SLE?

Chronic cutaneous lesions with potential scarring, often localized

How are joints affected in SLE?

Non erosive arthritis, spares DIP joints, no abnormalities on X ray

What are pulmonary manifestations of SLE?

Pleuritis, acute lupus pneumonitis, chronic fibrotic pneumonitis, pulmonary hypertension

What is the cardiac manifestation of SLE?

Libman Sacks endocarditis affecting mitral valve

What are renal findings in SLE?

Proteinuria, red cell casts, immune complex deposition in glomeruli, nephritis

What are neurologic manifestations of SLE?

Central symptoms such as headache, confusion, seizures, peripheral neuropathy, autonomic dysfunction including Raynaud phenomenon

What is the key diagnostic lab test for SLE?

Antinuclear antibody test, highly sensitive but not specific

What additional antibodies help diagnose SLE?

Anti dsDNA, anti Sm, antiphospholipid antibodies, decreased complement levels

What are the characteristics of the ANA test?

Low cost, highly sensitive near 100 percent, variable specificity, improved accuracy with additional antibody testing

What ANA staining pattern is associated with SLE?

Homogeneous staining pattern associated with anti dsDNA antibodies

What is required for SLE diagnosis using ACR EULAR criteria?

Score of 10 or more with at least one clinical criterion required for diagnosis

What are first line medications for mild SLE?

NSAIDs for joint pain, hydroxychloroquine for rash and joint symptoms

What is the role of hydroxychloroquine in SLE?

Reduces rash and joint pain, decreases incidence of severe disease

How are corticosteroids used in SLE?

Topical for skin lesions, oral or IV for severe systemic disease, taper to lowest effective dose

What immunosuppressive drugs are used in SLE?

Cyclophosphamide, mycophenolate mofetil, belimumab, rituximab

What is the non pharmacologic management of SLE?

UV avoidance, exercise, weight control, cardiovascular and renal screening, emotional support, multidisciplinary care

What is the epidemiology of systemic sclerosis?

Female predominance 3:1, onset 25–55 years, peak 50–60, more severe in African American patients

How is systemic sclerosis defined?

Fibrotic disease affecting skin and internal organs with excessive collagen deposition

What is the key pathophysiologic feature of systemic sclerosis?

Excess collagen production leading to fibrosis of skin and organs

What is the classic symptom of systemic sclerosis?

Raynaud phenomenon present in almost all patients

What are the characteristics of Raynaud phenomenon?

Episodic vasoconstriction causing numbness and tingling in fingers and toes, often triggered by cold or stress

What is the difference between Raynaud disease and Raynaud phenomenon?

Raynaud disease is primary and idiopathic, Raynaud phenomenon is secondary to another condition

What are the components of CREST syndrome?

Calcinosis cutis, Raynaud phenomenon, esophageal motility disorder, sclerodactyly, telangiectasia

What is calcinosis cutis?

Calcium deposits in skin and soft tissues

What is sclerodactyly?

Skin thickening and tightening of fingers leading to decreased mobility

What is telangiectasia?

Dilated superficial blood vessels visible on skin

What laboratory findings are seen in systemic sclerosis?

ANA positive, anti SCL 70 antibodies, anti centromere antibodies, anti RNA polymerase III antibodies

What is the significance of anti SCL 70 antibodies?

Associated with both forms of systemic sclerosis

What is the significance of anti centromere antibodies?

Associated with limited form of systemic sclerosis

What is the significance of anti RNA polymerase III antibodies?

Associated with diffuse systemic sclerosis and renal disease

What is the treatment for Raynaud phenomenon in systemic sclerosis?

Calcium channel blockers

How are gastrointestinal symptoms managed in systemic sclerosis?

Proton pump inhibitors, prokinetic agents such as metoclopramide or erythromycin

What immunosuppressive treatments are used in systemic sclerosis?

Methotrexate, cyclophosphamide, IVIG, rituximab, tocilizumab

Why is prednisone avoided in systemic sclerosis?

Increases risk of renal crisis

What is the overall approach to treating systemic sclerosis?

Symptom based, multidisciplinary care, nutritional support, counseling, prognosis discussion

What is the epidemiology of Sjogren syndrome?

Female predominance 16:1, common age 50–60, often associated with other autoimmune diseases

What organs are targeted in Sjogren syndrome?

Exocrine glands including lacrimal and salivary glands, also lungs, thyroid, kidneys, skin, muscle

What are the key symptoms of Sjogren syndrome?

Dry eyes, dry mouth, keratoconjunctivitis sicca, xerostomia

What are the diagnostic criteria for Sjogren syndrome?

Salivary gland biopsy inflammation, anti Ro SSA or anti La SSB antibodies, dry eye or mouth symptoms for at least 3 months

What is the pathogenesis of Sjogren syndrome?

Inflammatory infiltration of glands by T and B cells progressing to dominant B cell clone

What complication is associated with Sjogren syndrome?

Increased risk of lymphoma in about 5 percent of patients

What is the treatment of Sjogren syndrome?

Cyclosporine ocular for dry eyes, pilocarpine for dry mouth, prednisone for severe systemic inflammation, avoidance of atropine like drugs

What diseases are associated with Sjogren syndrome?

Rheumatoid arthritis, Raynaud phenomenon, thyroiditis