Autoimmune-Mediated Diseases

Question 1

Systemic Lupus Erythmatosus (SLE)

Answer 1

Classic Systemic autoimmune disease and is of unknown cause.

Question 2

Etiology of Systemic Lupus Erythmatosus (SLE)

Answer 2

Predominantly affects women of childbearing age.

Question 3

Pathogenesis of Systemic Lupus Erythmatosus (SLE)

Answer 3

Immune complexes (e.g. DNA-anti-DNA) are inadequately cleared. Immune complexes become trapped in the kidney glomeruli. Binding to Fc receptors on phagocytes causes kidney inflammation. Disease fluctuates with periods of flares and clinical quiescence. Long term leads to internal organ damage from inflammation and medication use.

Question 4

Clinical Features of Systemic Lupus Erythmatosus (SLE)

Answer 4

Can affect any and all organs. Clinical syndrome: Skin rashes, Arthritis, Pleuropericarditis, Glomerulonephritis, Nervous system, Hemolytic anemia.

Question 5

Labs/Tests of Systemic Lupus Erythmatosus (SLE)

Answer 5

Immunological disorder: Antinuclear antibodies, Anti-dsDNA antibodies, Anti-Sm antibodies, Anti-phospholipid antibodies, Increased IgG and IgM levels, Low C3 and C4 levels.

Question 6

Management of Systemic Lupus Erythmatosus (SLE)

Answer 6

Skin- Hydroxychloroquine
Pleuritis/pericarditis- NSAIDs, corticosteroids
Nephritis- Cyclophosphamide, mofetil mycophenolate
Arthritis- NSAIDs, methotrexate
Cerebritis- Pulse corticosteroids
APL Syndrome- Anticoagulation (warfarin, heparin)
AIHA- Corticosteroids, IVIG, splenectomy

Question 7

Anti-Phospholipid Antibody Syndrome

Answer 7

Recurrent vascular thrombosis and/or recurrent pregnancy loss in the presence of positive athiphospholipid (aPL) antibodies

Question 8

Etiology of Anti-Phospholipid Antibody Syndrome

Answer 8

Recognize plasma proteins that bind to anionic phospholipids such as cardiolipin (not to the phospholipids themselves)
Most common targets: β2 glycoprotein 1 and prothrombin
Lupus anticoagulants: a subset of aPL (often reactive with β2GP1) that interfere with in vitro phospholipid-dependent tests of coagulation (PT, aPTT, kaolin clotting time, dRVVT)
20-40% of SLE patients are aPL positive
Less than half of these patients have venous/arterial thrombosis or miscarriages (= anti-phospholipid syndrome, APS)
~25% of women with recurrent pregnancy loss have APS

Question 9

Epidemiology of Anti-Phospholipid Antibody Syndrome

Answer 9

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Question 10

Clinical Features of Anti-Phospholipid Antibody Syndrome

Answer 10

1. Vascular thrombosis (arterial, venous, or small vessel thrombosis confirmed by Doppler or histopathology).
2. Pregnancy morbidity- Unexplained fetal loss at or beyond 10th week of gestation. Premature births at or before 34th week of gestation because of severe preeclampsia, eclampsia, or placental insufficiency or
   Three or more unexplained consecutive spontaneous abortions before the 10th week of gestation

Question 11

Labs/Tests of Anti-Phospholipid Antibody Syndrome

Answer 11

Presence of Vascular Thrombosis, Pregnancy morbidity,

Laboratory criteria:

1. Lupus anticoagulant: LAC present,
2. Anticardiolipin antibody: aCL of IgG/IgM present,
3. Anti-B2-glcoprotein I antibody of IgG/IgM present via ELISA.

Question 12

Management of Anti-Phospholipid Antibody Syndrome

Answer 12

Warfarin is the drug of choice long term.

Question 13

Sjogren’s Syndrome

Answer 13

Chronic immune mediated inflammatory disorder of exocrine gland dysfunction. (infiltration of mononuclear cells leads to glandular destruction)

Question 14

Etiology of Sjogren’s Syndrome

Answer 14

More common in women

Question 15

Poor Prognostic of Sjogren’s Syndrome

Answer 15

Can lead to lymphoma (B-cell); usually indolent, give Rituximab

Question 16

Clinical Features of Sjogren’s Syndrome

Answer 16

Clinical syndrome: Dry mouth (xerostomia) & Dry eyes.
Increased incidence of B cell lymphoma, Extraglandular involvement. Can also include systemic features: fatigue, fever, weight loss and lymphadenopathy. Can have neurologic involvement (PNS).

Question 17

Labs/Tests of Sjogren’s Syndrome

Answer 17

1. Subjective and objective evidence of dry eyes and dry mouth. 2. Presence of 1 of 4 Anti-bodies (ANA, RF, Anti-Ro, Anti-La) *** [Anti-La and Anti-Ro are aka SS-B and SS-A respectively]. 3. Exclusion of underlying disease. …….. SCHIRMER TEST- tear production, ROSE BENGAL TEST - look for red spots on the eye (keratoconjunctivitis sicca); LIP BIOPSY Glands are preserved (early), Glands destroyed late in disease, Foci (> 50 lymphocytes/plasma cells), Focus score > 1 per 4 mm2. (look for unstimulated salivary flow)

Also a/w Hypergammaglobulinemia and Lymphoplasmacytic infiltrates in salivary glands

Question 18

Management of Sjogren’s Syndrome

Answer 18

Artificial tears and saliva. Salivary stimulators/Fluoride. Tx of Systemic Manifestations with NSAIDS and Anti-malarial agents. Pilocarpine for systemic tx of exocrine dysfunction.

Question 19

Main exocrine gland affected by Sjogens’s

Answer 19

Lacrimal and Salivary

Question 20

Most common extraglandular feature is (articular/extraarticular) and the presence of ____________.

Answer 20

articular; Raynaud phenomenon

Question 21

Cutaneous lupus

Answer 21

A. Acute cutaneous lupus: Photosensitive and associated with systemic lupus. Usually with active disease (Usually lasts weeks-months).

B. Chronic cutaneous lupus (discoid lupus): Atrophy, scarring and hair loss. Hyper/hypopigmentation. Low risk of SLE.

Question 22

Patient with SLE:

Answer 22

Initial complaints were muscle pain, painful swollen joints, skin rash, and low grade fever. Antinuclear antibody test (ANA) positive. Anti-double stranded DNA antibodies present. Treated with hydroxychloroquine, azathioprine, and prednisone: improved.

Patient moved, lost health insurance, and stopped treatment. Developed new rash and abnormal kidney function (increased creatinine, hematuria, proteinuria). Anti-double stranded DNA antibodies increased. Low C3 and C4. Kidney biopsy was performed.

Treated with high dose IV methylprednisolone followed by prednisone. Long-term immunosuppression with mofetil mycophenolate (MMF). After 4 months, anti-DNA and complement levels returned to normal. Protein and blood in the urine disappeared. Kidney function returned to almost normal.

Question 23

Dx of SLE

Answer 23

Coombs positive autoimmune hemolytic anemia (AIHA) in lupus. Caused by “warm” autoantibodies. Usually recognize Rh antigens. Detected by direct Coombs test
Antibodies may be present without AIHA. Mediated directly by autoantibodies against RBCs (not by immune complexes).

Question 24

Polymyositis and Dermatomyositis

Answer 24

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Question 25

Anti-synthetase autoantibody syndrome

Answer 25

Polymyositis with autoantibodies against a tRNA synthetase [Histidyl tRNA synthetase (Jo-1), alanyl, glycyl, isoleucyl, etc.]. High frequency of interstitial lung disease, Raynaud’s phenomenon: inflammatory arthritis, and “mechanic’s hands”

Question 26

Scleroderma

Answer 26

Clinical syndrome: Proximal scleroderma, Sclerodactyly, Digital ulcers/scars, Pulmonary fibrosis, Raynaud’s phenomenon. Immunological disorder: Antinuclear antibodies, Anti-Scl70 antibodies, Anti-RNA polymerase I/III, Anti-fibrillarin, Anti-centromere (CREST).

Question 27

Limited forms of scleroderma

Answer 27

1. CREST syndrome (calcinosis, Raynaud’s, esophageal dysmotility, sclerodactyly, telangiectasias); 2. Morphea; 3. Linear scleroderma.

Question 28

Classification of scleroderma

Answer 28

1. Systemic sclerosis | 2. Localized scleroderma

Question 29

Systemic sclerosis

Answer 29

Diffuse cutaneous scleroderma (distal and proximal extremity and truncal skin thickening); Limited cutaneous scleroderma (e.g. CREST syndrome): (skin thickening restricted to the fingers, hands, and face).

Question 30

Localized scleroderma

Answer 30

Morphea and Linear scleroderma

Question 31

Skin changes in Scleroderma

Answer 31

Sclerodactyly- Flexion contractures and acroosteolysis

Question 32

Currently the most common cause of death in scleroderma

Answer 32

Interstitial lung disease

Question 33

Interstitial Lung Diseases:

Answer 33

Ground glass infiltrates and fibrosis, primarily at the lung bases on MRI. Patients should be screened with PFTs (abnormal DLCO and TLC). Confirmation with high resolution CT scan of the chest. Therapy: cyclophosphamide (mofetil mycophenolate also may be effective).

Question 34

Scleroderma: Pulmonary hypertension

Answer 34

Definition: Mean PA pressure > 25 mm Hg at rest or 30 mm Hg during exercise. Most common in patients with longstanding (10-30 years) limited cutaneous scleroderma (e.g. CREST). Rapidly progressive: normal exercise tolerance -> oxygen dependence over 6-12 months. Low DLCO with normal lung volumes is suspicious. Mean survival ~ 2 years. Treatment: endothelin inhibitors, e.g. bosentan (Tracleer), sildenafil (Revatio), and IV prostaglandins

Question 35

Scleroderma renal crisis: now treatable or preventable with ACE inhibitors

Answer 35

Most patients should be treated with an ACE inhibitor | Target blood pressure: 100-110 systolic

Question 36

Peripheral vascular manifestations of scleroderma: Raynaud’s phenomenon

Answer 36

Three phases: Vasoconstriction (white pallor) Cyanosis (blue) Vasodilation and reactive hyperemia (red)

Question 37

Peripheral vascular manifestations:

Answer 37

Digital ulcers and acrogangrene

Question 38

Limited scleroderma

Answer 38

Better Prognosis of Limited Scleroderma. Clinical manifestations (vs. diffuse scleroderma): Relatively more common: Telangiectasias, Pulmonary HTN, Anti-centromere antibodies. Relatively less common: Renal crisis, Skeletal myopathy, Cardiomyopathy, Joint contractures

Question 39

CREST syndrome: clinical manifestations

Answer 39

Calcinosis, Raynaud’s, Esophageal dysmotility, Sclerodactyly, Telangiectasias

Question 40

Prognosis: Survival in scleroderma varies by __________.

Answer 40

Serological group. Centromere has longest survival then topoisomerase.

Question 41

Tx for Scleroderma

Answer 41

Scleroderma kidney- ACE inhibitor Skin changes- Nothing is effective Interstitial Lung Disease- Cyclophosphamide, MMP Pulmonary HTN- Endothelin inhibitors, prostacyclin Raynauds- Calcium channel blocker, (bosentan) Acrogangrene- Same as Raynaud’s plus prostacyclin

Question 42

Dx of SLE

Answer 42

H & P; with laboratory testing. NO CURE Kidney biopsy helps determine therapy for lupus nephritis. Focal proliferative(Class III) & Diffuse proliferative(Class IV):Proteinuria (often > 0.5 grams per 24 hours), blood in the urine. Diffuse form progresses rapidly. Membranous(Class V): Proteinuria (often > 4 grams per 24 hours without much blood); slowly progressive.