Medicine Exam 5: Rheumatology: Connective Tissue Disorders

Lecture 7

Signs and Symptoms of SLE –Neurologic

Very advanced, not in younger patients - Psychosis - Cognitive impairment - Seizures - Peripheral and cranial neuropathies - Transverse myelitis - Stroke - Depression

Systemic Sclerosis (Scleroderma) – Classification

Two forms: - Limited (80%) – CREST syndrome - Diffuse (20%)

Nail fold infarcts

Small areas of necrosis near nail folds; may indicate vasculitis or systemic disease.

Discoid rash

Round, scaly, erythematous plaques with central clearing and scarring; common in lupus. Present in discoid and systemic lupus

Periungual erythema

Redness around nail folds; suggests inflammation, often in dermatomyositis or lupus.

Fingertip lesions

Painful or ulcerative skin changes at fingertips; often seen in connective tissue disorders.

Polymyositis Diagnostic Findings

Normal Muscle Border of muscle bundle (fascicle) Normal muscle fibers Blood vessel “When normal muscle fibers are viewed under a microscope, they look like puzzle pieces that fit together neatly.” Polymyositis Inflammatory cells Invasion of fibers by inflammatory cells “In polymyositis, inflammatory cells of the immune system invade previously healthy muscle cells, which become rounded and variable in size.”

ANA

Nonspecific to SLE, does indicate autoimmune conditions

Treatment of SLE

Must be individualized to patient presentation

Signs and Symptoms of SLE – Skin

Most Important - Malar rash (“butterfly”) - Discoid rash Other - Panniculitis - Fingertip lesions - Periungual erythema - Nail fold infarcts - Splinter hemorrhages - Alopecia - Raynaud’s phenomenon

Polymyositis & Dermatomyositis Complications

Malignancy: - Ovarian: screen with transvaginal ultrasound, CT scan, CA-125 level - Lung - Pancreatic - Stomach - Colorectal - Non-Hodgkin lymphoma Respiratory muscle weakness: - Hypoxia - CO₂ retention

Autoantibodies SLE

Lupus Specific - Anti-dsDNA - Anti-Smith Other - ANA - Anti-phospholipid antibodies - Anti-histone antibodies

Splinter hemorrhages

Linear reddish-brown streaks under nails; associated with trauma or systemic illness.

Raynaud Treatment

Lifestyle Modification Non/Pharm Options

Sjogren Syndrome – Signs and Symptoms

Keratoconjunctivitis sicca Xerostomia Loss of taste and smell

Panniculitis

Inflammation of subcutaneous fat causing tender nodules; may be associated with autoimmunity.

Alopecia

Hair loss from scalp or body; may be patchy, diffuse, or scarring in autoimmune conditions.

Hydroxychloroquine (Plaquenil)

first line therapy in SLE other organ effects = add on to this treatment

Malar rash (“butterfly”)

Erythematous rash over cheeks and nose, sparing nasolabial folds; seen in lupus.

Raynaud’s phenomenon

Episodic color changes in fingers/toes (white-blue-red) triggered by cold or stress.

Anti-histone antibodies SLE

drug-induced lupus

Other types of Lupus

Discoid Lupus Drug-Induced Lupus Neonatal Lupus

Raynaud Step 3: Rubor

Capillaries are still dilated, but are now carrying oxygenated blood. Relaxation of vasospasm and greatly increased blood flow. Fingers appear red.

Raynaud Step 2: Cyanosis

Capillaries and venules dilate in response to ischemia and are filled with deoxygenated blood. Vasospasm continues, with capillaries and venules filled with deoxygenated blood. Fingers appear blue

The limited symptoms of scleroderma are referred to as CREST Syndrome

C – Calcinosis: Calcium deposits in the skin R – Raynaud’s phenomenon: Spasm of blood vessels in response to cold or stress E – Esophageal dysfunction: Acid reflux and decrease in motility of esophagus S – Sclerodactyly: Thickening and tightening of the skin on the fingers and hands T – Telangiectasias: Dilation of capillaries causing red marks on surface of skin

Raynaud Step 1: Ischemia

Blood flow to capillaries is impeded, resulting in digital ischemia. Vasospasm of the artery results in vascular occlusion, preventing blood flow to capillaries. Fingers appear white.

Connective Tissue

Any type of biologic tissue that supports, binds together, and protects organs: - Fat - Bone - Cartilage

Prevent opportunistic infections

Annual flu shot, pneumonia vaccine q5yrs

Connective Tissue Disorders: Autoimmune

Acquired autoantibody over time - Rheumatoid arthritis - Systemic lupus erythematosus - Scleroderma - Sjogren’s syndrome - Polymyositis & Dermatomyositis - Psoriatic arthritis

Scleroderma- survival

9-year survival rate ~40% - Mortality due to lung disease (MC), heart disease, or renal disease - Better prognosis: no severe organ involvement within 3 years of diagnosis

Anti-phospholipid antibodies SLE

· false-positive RPR · well-known immunologic phenomenon where patients with SLE may test falsely positive for syphilis on the RPR (Rapid Plasma Reagin) test due to the presence of anti-phospholipid antibodies (aPL).

Second-line for SLE resistant to corticosteroids

· Cyclophosphamide · Mycophenolate · Azathioprine · Belimumab = injection, more advanced treatment

Signs and Symptoms of SLE – Constitutional & Musculoskeletal

· Constitutional · Arthralgias · Skin · Ophthalmologic · Pulmonary · Renal · Cardiac · Vascular · Neurologic

Raynaud Initial Phase

• Well demarcated pallor or cyanosis - Initially affects 1–2 fingers, eventually involves palm as well - Typically spares thumbs

Systemic Sclerosis (Scleroderma) – Etiology & Pathophysiology

• Unknown cause – mechanisms include: - Autoimmunity - Endothelial cell damage - Increased production of ECM - Diffuse fibrosis of the skin and internal organs = Increased collagen deposition

Raynaud Phenomenon – Prognosis

• Typically benign - In secondary cases, can be more severe → ulcerations, gangrene

Raynaud Phenomenon – Pharmacologic Treatment

• Treatment of choice = calcium channel blocker - Nifedipine

Prognosis of SLE

• Ten-year survival >85% - Relapsing/remitting course - Bimodal mortality pattern - Higher malignancy risk (lymphoma, lung, and cervical CA) - Kidney disease → dialysis - Avascular necrosis of bone

3. Identify and interpret any diagnostic or therapeutic procedures utilized in the management of the above disorders

• Systemic Lupus Erythematosus (SLE): - Diagnostic: ANA, anti-dsDNA, anti-Smith, antiphospholipid antibodies, anti-histone antibodies (drug-induced), serum complement levels - Therapeutic: hydroxychloroquine, NSAIDs, corticosteroids (for severe disease), cyclophosphamide, mycophenolate, azathioprine, belimumab - Sjogren’s Syndrome: - Diagnostic: CBC, ANA, RF, anti-SSA (Ro), anti-SSB (La), anti-thyroid antibodies, Schirmer’s test, lip biopsy, parotid biopsy - Therapeutic: artificial tears, ocular cyclosporine, hydration, sugar-free gum/candy, pilocarpine, cevimeline, prednisone for systemic features - Raynaud’s Phenomenon: - Diagnostic: autoantibodies, nail fold capillary exam (immersion oil + ophthalmoscope) - Therapeutic: calcium channel blockers (nifedipine), cervical/digital sympathectomy, lifestyle modifications - Dermatomyositis & Polymyositis: - Diagnostic: elevated AST/ALT, CK, aldolase, ANA, anti-Jo-1, anti-Mi-2, anti-SRP, anti-155/140, MRI, muscle biopsy - Therapeutic: corticosteroids, methotrexate, azathioprine, IVIG (dermatomyositis resistant to prednisone), hydroxychloroquine, sun avoidance - Scleroderma: - Diagnostic: CBC, ANA, anti-SCL-70, anti-centromere, anti-RNAP, ESR, urinalysis - Therapeutic: calcium channel blockers, prednisone (caution), ACE-inhibitors, PPI, pro-kinetic agents, antibiotics, tocilizumab, cyclophosphamide, mycophenolate, sildenafil, prostaglandins

4. Given a clinical scenario, appropriately diagnose and recommend treatments and/or managements of the disorders listed in the above objectives

• Systemic Lupus Erythematosus (SLE): - Diagnose using ≥4 of 11 criteria including malar rash, arthritis, renal disease, neurologic symptoms, autoantibodies - Recommend hydroxychloroquine as first-line; corticosteroids for severe disease; immunosuppressants for refractory cases - Sjogren’s Syndrome: - Diagnose with dry eyes/mouth, positive SSA/SSB, Schirmer’s test, lip biopsy - Recommend artificial tears, pilocarpine, hydration, prednisone for systemic features - Raynaud’s Phenomenon: - Diagnose based on episodic pallor/cyanosis/redness, nail fold capillary exam, autoantibodies - Recommend lifestyle modification, calcium channel blockers, sympathectomy if severe - Dermatomyositis: - Diagnose with proximal muscle weakness, heliotrope rash, Gottron papules, elevated CK, muscle biopsy - Recommend corticosteroids, methotrexate, IVIG for refractory cases, hydroxychloroquine for skin - Polymyositis: - Diagnose with progressive proximal muscle weakness, elevated CK, MRI, muscle biopsy - Recommend corticosteroids, methotrexate, azathioprine - Scleroderma: - Diagnose based on skin thickening, Raynaud’s, autoantibodies (SCL-70, centromere, RNAP), organ involvement - Recommend symptomatic management: calcium channel blockers, ACE inhibitors, immunosuppressants for lung disease, PPI for GI symptoms

Autoimmune Disease: Common signs/symptoms

• Synovitis = joint - Pleuritis = pleura - Myocarditis - Endocarditis - Pericarditis - Peritonitis = abdomen - Vasculitis = blood vessels - Myositis = rare autoimmune condition that causes chronic inflammation and progressive weakness in skeletal muscles. - Skin rash - Nephritis = kidneys

Drug-Induced Lupus

• Symptoms similar to SLE but resolve within 6 months of d/c offending med

Signs and Symptoms – Dermatomyositis

• Symptoms of polymyositis plus dermatologic manifestations = Dusky red, malar distribution with surrounding facial erythema - “Shawl sign” - Heliotrope rash - Gottron papules: violaceous lesions over DIP, PIP, MCP joints - Gottron sign: erythema on extensor surfaces of fingers, elbows, and knees

Sjogren Syndrome – Treatment

• Symptomatic treatment: - Artificial tears - Ocular cyclosporine - Hydration - Sugar-free gum or hard candy - Pilocarpine or cevimeline for xerostomia - Avoid atropine, decongestants - Good oral hygiene - Severe systemic features (vasculitis, painful neuropathy): - Prednisone

Treatment – Scleroderma

• Symptomatic and supportive – no therapy alters disease progression - Raynaud’s: calcium channel blocker (nifedipine) - Myositis: prednisone – increased risk of scleroderma renal crisis = Caution - Scleroderma renal crisis/hypertension: ACE-inhibitors - GI manifestations: diet modification, PPI, pro-kinetic agents, antibiotics for malabsorption - Interstitial Lung Disease: tocilizumab, cyclophosphamide, mycophenolate - Pulmonary HTN: sildenafil, prostaglandins

Arthralgia SLE: S/S

• Swan-neck deformity without changes on x-ray

Raynaud Phenomenon – Lifestyle Modification Treatment

• Stay warm!! - Avoid hand injuries = Lotion to dry skin - Avoid smoking - Avoid decongestants, diet pills, amphetamines = Sympathomimetic → vasoconstriction

Signs and Symptoms –Limited Scleroderma

• Skin hardening limited to face and hands - GI Symptoms – constipation/diarrhea, malabsorption, pseudo-obstruction CREST - Calcinosis cutis - Raynaud phenomenon - Esophageal dysmotility - Sclerodactyly - Telangiectasia

Signs and Symptoms – Diffuse Scleroderma

• Skin hardening can involve entire body - Thick, hide-like skin - Loss of skin folds - Tendon friction rubs over forearms and shins = Unique to diffuse scleroderma - GI Symptoms – constipation, diarrhea, malabsorption, pseudo-obstruction - Constitutional – weight loss, malaise, arthralgias

Scleroderma CBC Findings

• Renal Crisis: hemolytic anemia

Diagnosis – Polymyositis

• Progressive muscle weakness, weeks – months - Proximal muscles of upper and lower extremities, and neck = Dysphagia due to difficulty initiating swallowing - Legs before arms - Spares face and eyes

Signs and Symptoms – Polymyositis

• Principal complaint/sign = muscle weakness - Difficulty getting out of a chair or climbing stairs

Signs and Symptoms of SLE – Pulmonary

• Pleurisy - Pleural effusion - Bronchopneumonia - Pneumonitis - Restrictive lung disease - Alveolar hemorrhage

Signs and Symptoms of SLE – Cardiac

• Pericarditis - Libman-Sacks endocarditis = Mitral regurgitation - Heart failure

Primary Raynaud’s phenomenon

• Occurs in 2–6% of adults - Primarily affects young women (15–30 y/o)

Arthralgias Treat SLE

• NSAIDs

Diagnostic Testing Polymyositis & Dermatomyositis– Imaging & Biopsy

• MRI: Detects muscle involvement, Guides biopsy sites - Confirmatory test = muscle biopsy - Both biopsy = lymphoid inflammatory infiltrates - Dermatomyositis biopsy: abnormalities localized to perivascular region

Systemic lupus erythematosus (SLE)

• Most common and most serious - Affects many parts of body (skin, kidneys, heart, lungs, etc)

Signs and Symptoms of SLE –Vascular

• Mesenteric vasculitis

Connective Tissue Disorders: Inherited

• Marfan syndrome - Ehlers-Danlos syndrome - Osteogenesis imperfecta

Serum complement level SLE

• Low during exacerbation, return to normal with remission Nonspecific to lupus, indicates presence of inflammation

Signs and Symptoms – Scleroderma Organ Damage

• Kidneys: - Scleroderma Renal Crisis - Interstitial lung disease - Cardiac: - Pericarditis - Heart block - Myocardial fibrosis - Right heart failure due to pulmonary HTN

Signs and Symptoms of SLE – Renal

• Interstitial nephritis - Glomerulonephritis: · Mesangial · Focal proliferative · Diffuse proliferative · Membranous

Raynaud Recovery phase

• Intense redness - Throbbing pain - Swelling - Paresthesia

Signs and Symptoms – Additional Scleroderma Features

• Initial presentation = Raynaud’s - Non-pitting subcutaneous edema with pruritus - Telangiectasias, pigmentation/depigmentation - Ulceration around fingertips - Dysphagia and GERD

Raynaud Phenomenon – Pathophysiology

• Initial phase: - Excessive vasoconstriction - Recovery phase: - Excessive vasodilation

Raynaud Phenomenon – Signs and Symptoms

• Initial phase and recovery phase - Most commonly affects fingers - Other involved areas: toes, nose, ears - Primary Raynaud’s – symmetric; secondary may be unilateral - Nail fold capillary changes seen in secondary RP associated with scleroderma

Corticosteroids Treat SLE

• Indications: glomerulonephritis (reversible), hemolytic anemia, pericarditis or myocarditis, alveolar hemorrhage, CNS involvement, TTP - Not indicated: minor arthritis, skin rash, leukopenia, AOCD

Sjogren Syndrome – Etiology & Pathophysiology

• HLA-DR3 association - Immune-mediated dysfunction of lacrimal and salivary glands = Lymphocyte and plasma cell infiltration - Can be isolated (“primary”) or associated with RA, SLE, or other autoimmune conditions

Autoimmune Disease: Common lab findings

• Hemolytic anemia = autoimmune - Thrombocytopenia - Leukopenia - Ig deficiency or excess - Positive ANA - Cryoglobulins = abnormal blood proteins that precipitate at cold temperatures and can cause systemic inflammation, especially in blood vessels (vasculitis) - Antiphospholipid antibodies = clotting issues - Elevated CK - Low complement - Test false positive for syphilis (RPR)

Constitutional SLE: S/S

• Fever - Anorexia/weight loss - Malaise

Raynaud Phenomenon – Etiology

• Exaggerated response of digital arterioles to cold or emotional stress - Primary: idiopathic - Secondary: symptom of underlying rheumatic disease = Scleroderma

1f. Scleroderma

• Etiology & Pathophysiology: - Unknown cause - Mechanisms include: autoimmunity, endothelial cell damage, increased production of ECM - Diffuse fibrosis of the skin and internal organs - Increased collagen deposition - Two forms: Limited (80%) – CREST syndrome; Diffuse (20%) - Clinical Presentation – CREST Syndrome (Limited): - Calcinosis cutis - Raynaud phenomenon - Esophageal dysmotility - Sclerodactyly - Telangiectasia - Skin hardening limited to face and hands - GI symptoms: constipation/diarrhea, malabsorption, pseudo-obstruction - Clinical Presentation – Diffuse Scleroderma: - Skin hardening can involve entire body - Thick, hide-like skin - Loss of skin folds - Tendon friction rubs over forearms and shins (unique to diffuse) - GI symptoms: constipation, diarrhea, malabsorption, pseudo-obstruction - Constitutional: weight loss, malaise, arthralgias - Additional Signs and Symptoms: - Initial presentation = Raynaud’s - Non-pitting subcutaneous edema with pruritus - Telangiectasias, pigmentation/depigmentation - Ulceration around fingertips - Dysphagia and GERD - Organ Damage: - Kidneys: scleroderma renal crisis - Cardiac: pericarditis, heart block, myocardial fibrosis, right heart failure due to pulmonary HTN - Interstitial lung disease - Workup: - CBC: mild anemia (chronic disease/inflammation) - Renal crisis: hemolytic anemia - Autoantibodies: ANA, Anti-SCL-70 (diffuse), Anti-centromere (limited), Anti-RNAP (severe disease, increased mortality) - ESR usually normal - Urinalysis: proteinuria if renal involvement - Management: - Symptomatic and supportive – no therapy alters disease progression - Raynaud’s: calcium channel blocker (nifedipine) - Myositis: prednisone (caution – increased risk of renal crisis) - Scleroderma renal crisis/hypertension: ACE-inhibitors - GI: diet modification, PPI, pro-kinetic agents, antibiotics for malabsorption - Interstitial lung disease: tocilizumab, cyclophosphamide, mycophenolate - Pulmonary HTN: sildenafil, prostaglandins - Prognosis: - CREST (limited) has better prognosis than diffuse - Limited disease: life-threatening pulmonary hypertension, finger loss due to digital ischemia - 9-year survival rate ~40% - Mortality due to lung, heart, or renal disease - Better prognosis: no severe organ involvement within 3 years of diagnosis

1b. Sjogren’s Syndrome

• Etiology & Pathophysiology: - HLA-DR3 association - Immune-mediated dysfunction of lacrimal and salivary glands - Lymphocyte and plasma cell infiltration - Can be isolated (“primary”) or associated with RA, SLE, or other autoimmune conditions - Clinical Presentation: - Keratoconjunctivitis sicca: dry eyes, foreign body sensation - Xerostomia: dry mouth, difficulty swallowing food, difficulty speaking, poor dentition, loss of taste and smell - Systemic Findings: - Dysphagia - Small vessel vasculitis - Pleuritis - ILD - Peripheral neuropathy - Pancreatitis - Renal Tubular Acidosis - Chronic interstitial nephritis - Thyroid disease - Significantly increased risk of lymphoma - Workup: - CBC: anemia, leukopenia (mild), eosinophilia - Autoantibodies: ANA, RF, Anti-SSA (Ro), Anti-SSB (La), Anti-thyroid antibodies - Schirmer’s test – quantifies tear production - Lip biopsy – lymphoid foci in salivary glands - Parotid biopsy – useful if diagnosis unclear - Management: - Symptomatic treatment: artificial tears, ocular cyclosporine, hydration, sugar-free gum or hard candy - Pilocarpine or cevimeline for xerostomia - Avoid atropine, decongestants - Good oral hygiene - Severe systemic features (vasculitis, painful neuropathy): prednisone

1c. Raynaud’s Phenomenon

• Etiology & Pathophysiology: - Exaggerated response of digital arterioles to cold or emotional stress - Primary: idiopathic; occurs in 2–6% of adults, primarily affects young women (15–30 y/o) - Secondary: symptom of underlying rheumatic disease (e.g., scleroderma) - Initial phase: excessive vasoconstriction - Recovery phase: excessive vasodilation - Clinical Presentation: - Initial phase: well-demarcated pallor or cyanosis, affects 1–2 fingers, eventually involves palm, spares thumbs - Recovery phase: intense redness, throbbing pain, swelling, paresthesias - Most commonly affects fingers; also toes, nose, ears - Primary Raynaud’s – symmetric; secondary may be unilateral - Nail fold capillary changes seen in secondary RP associated with scleroderma - Workup: - Autoantibodies to rule out secondary cause - Examine nail fold capillary pattern – abnormal in scleroderma - Grade B immersion oil + ophthalmoscope - Management: - Lifestyle: stay warm, avoid hand injuries, use lotion, avoid smoking, avoid decongestants, diet pills, amphetamines (sympathomimetics → vasoconstriction) - Pharmacologic: calcium channel blocker (nifedipine) - Surgical: cervical or digital sympathectomy - Complications & Prognosis: - Typically benign - In secondary cases, can be more severe → ulcerations, gangrene

1d. Dermatomyositis

• Etiology & Pathophysiology: - Autoimmune, inflammatory disease of muscle fibers - Vascular inflammation → indirect myocyte injury - Clinical Presentation: - Symptoms of polymyositis plus dermatologic manifestations - Dusky red, malar distribution with surrounding facial erythema - “Shawl sign” - Heliotrope rash - Gottron papules: violaceous lesions over DIP, PIP, MCP joints - Gottron sign: erythema on extensor surfaces of fingers, elbows, and knees - Workup: - Labs: elevated liver enzymes (AST, ALT), CK, aldolase; ESR/CRP usually normal - Autoantibodies: ANA, Anti-Mi-2 (dermatomyositis), Anti-Jo-1, Anti-SRP, Anti-155/140 (associated with malignancy) - MRI: detects muscle involvement, guides biopsy sites - Muscle biopsy: lymphoid inflammatory infiltrates; abnormalities localized to perivascular region - Management: - Corticosteroids - Methotrexate - Azathioprine - IVIG for dermatomyositis resistant to prednisone - Skin disease: hydroxychloroquine (Plaquenil), limit sun exposure - Complications: - Malignancy: ovarian (screen with transvaginal ultrasound, CT, CA-125), lung, pancreatic, stomach, colorectal, non-Hodgkin lymphoma - Respiratory muscle weakness: hypoxia, CO₂ retention

1e. Polymyositis

• Etiology & Pathophysiology: - Autoimmune, inflammatory disease of muscle fibers - CD8+ mediated, direct myocyte injury - Clinical Presentation: - Principal complaint/sign = muscle weakness - Difficulty getting out of a chair or climbing stairs - Progressive muscle weakness over weeks to months - Proximal muscles of upper and lower extremities, and neck - Dysphagia due to difficulty initiating swallowing - Legs before arms - Spares face and eyes - Workup: - Labs: elevated liver enzymes (AST, ALT), CK, aldolase; ESR/CRP usually normal - Autoantibodies: ANA, Anti-Jo-1 (most common, specific), Anti-SRP (rapidly progressive, severe disease), Anti-155/140 (associated with malignancy) - MRI: detects muscle involvement, guides biopsy sites - Muscle biopsy: lymphoid inflammatory infiltrates - Management: - Corticosteroids - Methotrexate - Azathioprine - Complications: - Malignancy: ovarian, lung, pancreatic, stomach, colorectal, non-Hodgkin lymphoma - Respiratory muscle weakness: hypoxia, CO₂ retention

1a. Systemic Lupus Erythematosus (SLE)

• Etiology & Pathophysiology: - Autoantibodies to nuclear antigens - Hormonal influence - HLA-DR2, HLA-DR3 - Trapping of antigen-antibody complexes in capillaries of organ structures - Antibody-mediated destruction of host cells (platelets) - Clinical Presentation: - Constitutional: fever, anorexia/weight loss, malaise - Arthralgias, Swan-neck deformity without x-ray changes - Skin: malar rash, panniculitis, discoid rash, fingertip lesions, periungual erythema, nail fold infarcts, splinter hemorrhages, alopecia, Raynaud’s phenomenon - Ophthalmologic: conjunctivitis, photophobia, monocular blindness, blurry vision, cotton-wool spots - Pulmonary: pleurisy, pleural effusion, bronchopneumonia, pneumonitis, restrictive lung disease, alveolar hemorrhage - Cardiac: pericarditis, Libman-Sacks endocarditis, mitral regurgitation, heart failure - Vascular: mesenteric vasculitis - Neurologic/Psychiatric: psychosis, cognitive impairment, seizures, neuropathies, transverse myelitis, stroke, depression - Renal: glomerulonephritis (mesangial, focal proliferative, diffuse proliferative, membranous), interstitial nephritis - Workup: - Diagnostic criteria: 4 of 11 including kidney disease, neurologic disease, autoantibodies, discoid rash, arthritis, malar rash, photosensitivity, serositis, oral ulcers, positive ANA - Autoantibodies: ANA, anti-dsDNA, anti-Smith, antiphospholipid antibodies, false-positive RPR, anti-histone antibodies (drug-induced) - Serum complement: low during exacerbation, normal in remission - Management: - Hydroxychloroquine (Plaquenil): first-line - Skin: sun avoidance, topical corticosteroids - Arthralgias: NSAIDs - Corticosteroids for severe manifestations (e.g., glomerulonephritis, CNS involvement) - Second-line: cyclophosphamide, mycophenolate, azathioprine, belimumab - Complications: - Opportunistic infections (early mortality) - Atherosclerosis/chronic inflammation (late mortality) - MI incidence 5x general population - Higher malignancy risk (lymphoma, lung, cervical CA) - Kidney disease → dialysis - Avascular necrosis of bone - Prognosis: - Ten-year survival >85% - Relapsing/remitting course - Bimodal mortality pattern - Better outcomes with early detection and specialist care

Diagnostic Testing Polymyositis & Dermatomyositis – Labs

• Elevated liver enzymes (AST, ALT) - Muscle enzymes: - CK , - Aldolase - Inflammatory markers (ESR, CRP) usually normal

Prognosis SLE: Bimodal mortality pattern

• Early years (0-20) after diagnosis – mortality due to opportunistic infections - Later years after diagnosis – mortality due to atherosclerosis/chronic inflammation = MI incidence 5x > general population

Sjogren Syndrome – Systemic Findings

• Dysphagia - Small vessel vasculitis - Pleuritis - ILD - Peripheral neuropathy - Pancreatitis - Renal Tubular Acidosis - Chronic interstitial nephritis - Thyroid disease - Significantly increased risk of lymphoma

SLE Affects multiple organ systems

• Due to trapping antigen-antibody complexes in capillaries of organ structures - Antibody mediated destruction of host cells (platelets) - side effects present where complexes form

Xerostomia

• Dry mouth - Difficulty swallowing food - Difficulty speaking - Poor dentition

Keratoconjunctivitis sicca

• Dry eyes - Foreign body sensation

Autoimmune Disease: Common treatments

• Disease-modifying anti-rheumatic drugs (DMARDS; synthetic or biologic) Decrease immune system activity to decrease inflammation

Discoid Lupus

• Disease limited to skin Look similar to ringworm

Diagnostic Criteria for SLE

• Diagnosis: 4/11 of the following criteria: Important - Autoantibodies: anti-dsDNA, Anti-smith, APLA - Positive ANA Other - Kidney disease: Proteinuria, Cellular casts - Neurologic disease: Seizures, Psychosis - Discoid rash - Arthritis - Malar rash - Photosensitivity - Serositis - Oral ulcers

Prognosis – Scleroderma

• CREST (limited scleroderma) has better prognosis than diffuse scleroderma - Limited disease: - Life-threatening pulmonary hypertension - Finger loss due to digital ischemia

Polymyositis & Dermatomyositis Treatment Options

• Corticosteroids - Methotrexate - Azathioprine - Dermatomyositis resistant to prednisone = IVIG Skin disease: - Hydroxychloroquine (Plaquenil) - Limit sun exposure

Signs and Symptoms of SLE – Ophthalmologic

• Conjunctivitis - Photophobia - Transient or permanent monocular blindness - Blurry vision - Cotton-wool spots on retina

Connective Tissue: Main components

• Collagen - Elastin

Idiopathic Inflammatory Myopathies

• Chief complaint: muscle weakness - Polymyositis - Dermatomyositis - Inclusion body myositis

Raynaud Phenomenon – Surgical sympathectomy

• Cervical - Digital

Diagnostic Testing – Scleroderma

• CBC: mild anemia (chronic disease/inflammation) - Autoantibodies - Inflammatory markers – ESR usually normal - Urinalysis: Proteinuria if renal involvement

Sjogren Syndrome – Diagnostic Testing

• CBC: anemia, leukopenia (mild), eosinophilia - Autoantibodies: - Schirmer’s test – quantifies tear production - Lip biopsy – lymphoid foci in salivary glands - Parotid biopsy – can be useful if diagnosis unclear

Neonatal Lupus

• Baby born to mom with lupus – symptoms resolve in a few months

Skin Lesions Treat SLE

• Avoid sun exposure - Topical corticosteroid

Prevent atherosclerosis/ chronic inflammation

• Avoid smoking and control modifiable cardiac risk factors

Etiology & Pathophysiology Idiopathic Inflammatory Myopathies

• Autoimmune, inflammatory disease of muscle fibers - Polymyositis: CD8+ mediated, direct myocyte injury - Dermatomyositis: Vascular inflammation → indirect myocyte injury

2b. Differential Diagnosis – Joint Swelling

• Autoimmune connective tissue disorders associated with joint swelling: - SLE: arthritis (included in diagnostic criteria) - Sjogren’s syndrome: systemic inflammation may contribute to joint swelling - Scleroderma: tendon friction rubs, subcutaneous edema - Dermatomyositis and Polymyositis: muscle inflammation may mimic joint swelling - Other autoimmune conditions mentioned: - Rheumatoid arthritis - Psoriatic arthritis