Rheumatology

Question 1

What is the most common extraglandular manifestation of Sjogren Syndrome?

Answer 1

Fatigue and arthralgia: Non-erosive, migratory polyarthralgia resembling rheumatoid arthritis.= jaccoud

Question 2

What are the dermatologic manifestations of extraglandular Sjogren Syndrome?

Answer 2

1. Cutaneous vasculitis:
   • Palpable purpura (cryoglobulinemia-related).
   • Urticarial vasculitis.
2. Annular erythema: Common in Asian patients.
3. Dry skin (xeroderma).

Question 3

What pulmonary complications are seen in Sjogren Syndrome?

Answer 3

1. Interstitial Lung Disease (ILD):
   • Lymphocytic interstitial pneumonia (LIP).= most characteristic
   • Non-specific interstitial pneumonia (NSIP).= most common
2. Airway diseases:
   • Bronchiectasis.
   • Tracheobronchial dryness.
3. Obstructive disease: Small airway disease with airflow limitation.

Question 4

What are the renal manifestations of Sjogren Syndrome?

Answer 4

1. Tubulointerstitial nephritis: Most common.
2. Renal tubular acidosis (RTA): Often type 1 (distal), leading to hypokalemia.
3. Glomerulonephritis: Rare, associated with cryoglobulinemia.
4. Reduced ability to concentrate urine (nephrogenic diabetes insipidus-like syndrome).

Question 5

What are the hematologic complications of Sjogren Syndrome?

Answer 5

1. Non-Hodgkin lymphoma (NHL):
   • Most commonly MALT lymphoma.
   • Risk factors: Persistent parotid swelling, cryoglobulinemia, low C4.
2. Anemia of chronic disease.
3. Leukopenia and thrombocytopenia: Autoimmune-mediated.

Question 6

How does Sjogren Syndrome affect the nervous system?

Answer 6

1. Peripheral neuropathy:
   • Sensory, motor, or sensorimotor neuropathy.
   • Small fiber neuropathy (burning pain).
2. Cranial neuropathy: Trigeminal nerve most commonly affected.
3. CNS involvement:
   • Rare but includes multiple sclerosis-like syndromes or transverse myelitis.

Question 7

What are the cardiovascular manifestations of extraglandular Sjogren Syndrome?

Answer 7

1. Raynaud phenomenon: Reversible vasospasm of extremities.
2. Vasculitis: Cutaneous or systemic small vessel vasculitis.
3. Increased risk of atherosclerosis.

Question 8

What are the gastrointestinal manifestations of Sjogren Syndrome?

Answer 8

1. Dysphagia: Due to esophageal dysmotility or dryness.
2. Autoimmune hepatitis: Overlap with primary biliary cholangitis.
3. Pancreatitis: Rare, immune-mediated.

Question 9

How does Sjogren Syndrome affect the musculoskeletal system?

Answer 9

1. Arthritis:
   • Non-erosive, polyarthritis (resembling RA but seronegative).
   • May involve large or small joints.
2. Myositis: Rare inflammatory muscle disease.

Question 10

What laboratory markers are associated with extraglandular involvement in Sjogren Syndrome?

Answer 10

Cryoglobulins: Associated with vasculitis and lymphoma risk.
• Hypocomplementemia: Low C3/C4 suggests systemic vasculitis or cryoglobulinemia.
• Increased ESR and polyclonal hypergammaglobulinemia.

Question 11

What are the risk factors for lymphoma in Sjogren Syndrome?

Answer 11

• Persistent parotid swelling.
• Low C4 complement levels.
• Presence of cryoglobulins.
• High focus score on salivary gland biopsy.
• Persistent systemic symptoms (e.g., vasculitis).

Question 12

What are the histological findings in Sjogren Syndrome?

Answer 12

• Focal lymphocytic infiltration in exocrine glands (predominantly CD4+ T cells and plasma cells).
• Destruction of glandular architecture.
• Increased risk of progression to MALT lymphoma.

Question 13

What is the management of Sjogren Syndrome (EULAR 2020 Recommendations)?

Answer 13

• General measures:
• Artificial tears, saliva substitutes.
• Avoidance of drying agents (e.g., antihistamines).
• Medications:
1. Pilocarpine or Cevimeline: Improves glandular secretion.
2. Hydroxychloroquine: For arthralgia and systemic symptoms.
3. Glucocorticoids and DMARDs: For severe systemic involvement (e.g., vasculitis, nephritis).
4. Biologics:
• Rituximab for refractory systemic disease or lymphoma.

Question 14

How is glandular dysfunction evaluated?

Answer 14

1. Schirmer’s test: Measures tear production (<5 mm in 5 min is positive).
2. Ocular surface staining: Detects corneal damage (fluorescein dye or lissamine green).
3. Unstimulated salivary flow rate: <0.1 mL/min is diagnostic.
4. Salivary gland biopsy: Gold standard, shows focal lymphocytic sialadenitis.

Question 15

What are the key serological findings in Sjogren Syndrome?

Answer 15

• Anti-SSA (Ro): Highly sensitive (seen in 70–90%).
• Anti-SSB (La): More specific.
Fine speckled pattern : antiRO/LA
• Rheumatoid factor (RF): Positive in 70% of cases.
• ANA: Positive in ~80%.
• Hypergammaglobulinemia (polyclonal).

Question 16

What are the diagnostic criteria for Sjogren Syndrome (ACR/EULAR 2016)?

Answer 16

Total Score ≥4 indicates Sjogren Syndrome:
1. Anti-SSA/Ro antibodies (3 points).
2. Labial salivary gland biopsy with focal lymphocytic sialadenitis (3 points).
3. Ocular staining score ≥5 or van Bijsterveld score ≥4 (1 point).
4. Schirmer’s test ≤5 mm/5 min (1 point).
5. Unstimulated whole salivary flow ≤0.1 mL/min (1 point).

Question 17

What are the two classifications of Sjogren Syndrome?

Answer 17

1. Primary Sjogren Syndrome (pSS): Occurs as an isolated disease.
   
   2. Secondary Sjogren Syndrome: Associated with other autoimmune diseases such as RA, SLE, or systemic sclerosis.

Question 18

What are the main exclusion criteria for Sjogren Syndrome diagnosis?

Answer 18

1. Other systemic autoimmune diseases:
   • Active hepatitis C virus infection.
   • Active HIV infection.
   • Active sarcoidosis.
2. IgG4-related disease: Mimics Sjogren with glandular swelling and systemic involvement
3. Prior head and neck radiation therapy.
4. Current use of anticholinergic drugs: Causes sicca-like symptoms.
5. Graft-versus-host disease (GVHD).
6. Recent lymphoma diagnosis.
7. Amyloidosis: May present with sicca syndrome.

Question 19

Genetics of Sjogren?

Answer 19

HLA DR3
IL 18+ macrophages
T1 cells

Question 20

What are the histopathological hallmarks of IgG4-RD?

Answer 20

1. Dense lymphoplasmacytic infiltrate.
   
   2. Storiform fibrosis.
   3. Obliterative phlebitis.
   4. Increased IgG4+ plasma cells (>10 per HPF, IgG4+/IgG+ ratio >40%).

Question 21

Which organs are commonly affected by IgG4-RD?

Answer 21

• Pancreas (autoimmune pancreatitis type 1).
• Salivary glands (e.g., Mikulicz disease).
• Lacrimal glands.
• Bile ducts (sclerosing cholangitis).
• Retroperitoneum (fibrosis).
• Kidneys (tubulointerstitial nephritis).
• Aorta (IgG4-related aortitis).

Question 22

What are the first-line treatments for IgG4-RD?

Answer 22

1. Glucocorticoids (e.g., prednisone 30–40 mg/day, tapered over 6 months).
   
   2. Rituximab for refractory cases or steroid sparing.

Question 23

What scoring system is used to evaluate IgG4-RD?

Answer 23

The IgG4-RD Responder Index (IgG4-RD RI) to assess disease activity and response to treatment.

Question 24

What is the role of IgG4 levels in diagnosis?

Answer 24

Elevated IgG4 levels support the diagnosis but are not definitive, as they can be normal in some cases or elevated in other conditions.

Question 25

What genetic factors are associated with IgG4-RD?

Answer 25

• HLA-DRB1 and HLA-DQB1 alleles

Question 26

How does IgG4-RD differ from Sjögren’s syndrome?

Answer 26

• IgG4-RD causes painless swelling of salivary/lacrimal glands and storiform fibrosis.
• Sjögren’s syndrome typically presents with sicca symptoms and lymphocytic infiltration without storiform fibrosis

Question 27

What are the pancreatic manifestations of IgG4-RD?

Answer 27

• Autoimmune pancreatitis type 1 (AIP type 1):
• Painless obstructive jaundice.
• Abdominal discomfort or mild pain.
• Diffuse pancreatic enlargement (“sausage-shaped pancreas”).

Question 28

What are the clinical features of IgG4-related salivary and lacrimal gland disease?

Answer 28

• Painless, bilateral swelling of salivary glands (submandibular or parotid).
• Mikulicz disease: Enlargement of both salivary and lacrimal glands.
• Xerostomia (dry mouth) or xerophthalmia (dry eyes) may be present but are less prominent than in Sjögren’s syndrome.

Question 29

What are the biliary and hepatic manifestations of IgG4-RD?

Answer 29

• IgG4-related sclerosing cholangitis (IgG4-SC):
• Jaundice due to bile duct strictures.
• May mimic primary sclerosing cholangitis or cholangiocarcinoma.
• Liver involvement: Elevated liver enzymes or hepatomegaly.

Question 30

What are the renal manifestations of IgG4-RD?

Answer 30

• IgG4-related tubulointerstitial nephritis (TIN):
• Renal mass or reduced kidney function.
• Proteinuria or hematuria in some cases.
• Hypocomplementemia (low complement levels)

Question 31

What are the retroperitoneal and vascular manifestations of IgG4-RD?

Answer 31

• Retroperitoneal fibrosis:
• Flank pain or abdominal discomfort.
• Ureteral obstruction leading to hydronephrosis.
• IgG4-related aortitis/periaortitis:
• Aneurysms or stenosis.
• Abdominal or back pain.

Question 32

What are the pulmonary manifestations of IgG4-RD?

Answer 32

• Pulmonary infiltrates or nodules.
• Pleural thickening or effusions.
• Mimics interstitial lung disease or malignancy.

Question 33

How does IgG4-RD present in the lymph nodes?

Answer 33

• Painless, generalized lymphadenopathy.
• Can be mistaken for lymphoma.

Question 34

What are the orbital manifestations of IgG4-RD?

Answer 34

• Orbital pseudotumor: Proptosis, diplopia, or visual disturbance.
• Involvement of lacrimal glands, orbital muscles, or orbital fat.

Question 35

What are common ENT manifestations of IgG4-RD?

Answer 35

• Sinusitis or nasal obstruction.
• Swelling of the pharyngeal or laryngeal tissues.

Question 36

What are the cardiac manifestations of IgG4-RD?

Answer 36

• IgG4-related pericarditis or myocarditis.
• Coronary arteritis, leading to ischemia

Question 37

What are the spinal or neurological manifestations of IgG4-RD?

Answer 37

• Hypertrophic pachymeningitis: Headache, cranial neuropathies.
• Peripheral nerve involvement: Pain or paresthesia.

Question 38

What symptoms are atypical or against the diagnosis of IgG4-related disease (IgG4-RD)?

Answer 38

1. Severe Sicca Symptoms
2. B Symptoms
3. Rapidly Progressive Organ Damage
4. Painful Gland Swelling
5. Neutrophils involvement
6. Granuloma

Question 39

What does the cytoplasmic ANA pattern suggest?

Answer 39

autoimmune liver diseases, especially in primary biliary cholangitis (PBC).
• It can also be seen in autoimmune hepatitis and myositis.

Question 40

What does the rim or peripheral ANA pattern indicate?

Answer 40

• The rim (peripheral) pattern is characterized by staining at the periphery of the nucleus.
• This pattern is typically associated with anti-dsDNA antibodies, which are highly specific for SLE, especially when there is renal involvement.
• It is also seen in some cases of drug-induced lupus, but less commonly.

Question 41

What does the centromere ANA pattern indicate?

Answer 41

• The centromere pattern is characterized by discrete staining of the centromeres during cell division.
• This pattern is strongly associated with limited cutaneous systemic sclerosis (scleroderma).
• It is seen in patients with CREST syndrome (Calcinosis, Raynaud’s phenomenon, Esophageal dysmotility, Sclerodactyly, Telangiectasia).
• It is also seen in a few cases of primary biliary cirrhosis (PBC).

Question 42

What does the nucleolar ANA pattern indicate?

Answer 42

• The nucleolar pattern is characterized by staining in the nucleolus of the cell nucleus.
• It is most commonly seen in systemic sclerosis (scleroderma), particularly in patients with limited cutaneous systemic sclerosis.
• It is less commonly seen in SLE but may occur in some cases.
• May also be present in polymyositis/dermatomyositis.

Question 43

What does the homogeneous ANA pattern indicate?

Answer 43

• The homogeneous pattern is characterized by uniform staining of the nucleus.
• It is typically associated with anti-dsDNA antibodies and is most commonly seen in Systemic Lupus Erythematosus (SLE).
• Also seen in drug-induced lupus, but it is more commonly associated with active lupus nephritis.

Question 44

What are the initial investigations to diagnose SLE?

Answer 44

1. Antinuclear Antibodies (ANA): Positive in >95% of SLE patients, but not specific.
   
   2. Anti-dsDNA antibodies: Highly specific for renal involvement and disease activity.
   3. Anti-Smith antibodies: Specific for SLE, but not always present.
   4. Complement levels: Decreased C3 and C4 levels indicate active disease.
   5. Urinalysis: Check for proteinuria and hematuria (indicative of lupus nephritis).
   6. Complete blood count (CBC): Anemia, leukopenia, thrombocytopenia are common.
   7. Serum creatinine: To assess renal function.
   8. Lupus anticoagulant, anticardiolipin, and anti-β2-glycoprotein antibodies for antiphospholipid syndrome.

Question 45

How is the diagnosis of SLE confirmed clinically according to the 2019 ACR/EULAR classification criteria?

Answer 45

The diagnosis of SLE is supported by fulfilling 4 of the 11 criteria (with at least one being clinical and one immunologic):
1. Malar rash or discoid rash (clinical).
2. Photosensitivity (clinical).
3. Oral or nasopharyngeal ulcers (clinical).
4. Arthritis (clinical) – non-erosive.
5. Serositis (clinical) – pleuritis, pericarditis.
6. Renal – proteinuria >0.5 g/day or cellular casts (clinical).
7. Neurologic – seizures, psychosis (clinical).
8. Hematologic – hemolytic anemia, leukopenia, thrombocytopenia (clinical).
9. Immunologic:
• Antinuclear antibodies (ANA) (immunologic).
• Anti-dsDNA, anti-Smith, low complement (C3, C4).
• Antiphospholipid antibodies.

Question 46

What is the role of immunofluorescence in Lupus Nephritis diagnosis?

Answer 46

• Immunofluorescence shows granular deposits of IgG, IgA, IgM, C3, and C1q along the glomerular basement membrane, mesangium, and endothelium.
• The pattern is indicative of immune complex deposition, which is characteristic of lupus nephritis.

Question 47

What are the histological features of Lupus Nephritis in kidney biopsies?

Answer 47

• Class I (Minimal mesangial): Mild mesangial hypercellularity with normal glomeruli.
• Class II (Mesangial proliferative): Mesangial cell proliferation and matrix expansion, with normal glomeruli.
• Class III (Focal proliferative): Segmental glomerular inflammation with necrosis and crescent formation in some glomeruli.
• Class IV (Diffuse proliferative): Global glomerular proliferation, with necrosis, crescents, and fibrinoid deposits in affected glomeruli.
• Class V (Membranous): Thickened glomerular basement membranes with subepithelial immune complex deposits.
• Class VI (Advanced sclerosing): Global glomerular sclerosis, leading to end-stage kidney disease.

Question 48

What is the management strategy for SLE in pregnancy?

Answer 48

• Pre-conception counseling:
• Ensure disease control for at least 6 months before pregnancy.
• Avoid teratogenic drugs (e.g., mycophenolate mofetil, cyclophosphamide).
• Monitoring:
• Close monitoring of lupus activity during pregnancy, especially renal function, blood pressure, and fetal well-being.
• Treatment options:
• Hydroxychloroquine, low-dose corticosteroids, and low-dose aspirin to prevent preeclampsia and fetal complications.

Question 49

What is the role of hydroxychloroquine in the management of SLE?

Answer 49

• Hydroxychloroquine is a cornerstone therapy for SLE.
• Mechanism: It inhibits autoimmune activity, reduces flares, and improves survival.
• Indications:
• First-line for cutaneous and musculoskeletal symptoms.
• Prevents flaring, reduces disease activity, and can reduce vascular complications.
• Side effects: Retinal toxicity (regular eye exams are needed).

Question 50

What are the first-line medications for treating moderate to severe SLE?

Answer 50

• Corticosteroids:
• Prednisone is commonly used for its anti-inflammatory and immunosuppressive effects.
• Tapered gradually once disease control is achieved.
• High-dose therapy may be used in acute flares.
• Immunosuppressive drugs:
• Mycophenolate mofetil or azathioprine for organ-threatening manifestations, particularly lupus nephritis.
• Cyclophosphamide may be used in severe cases (e.g., lupus nephritis, CNS involvement).

Question 51

What is the role of biologics in the treatment of SLE?

Answer 51

• Belimumab:
• A monoclonal antibody that inhibits B-lymphocyte stimulator (BLyS), reducing B cell activation and autoantibody production.
• Approved for patients with active SLE who are not responding to conventional therapy.
• Rituximab:
• A B cell depleting therapy, used in refractory SLE and in cases of severe lupus nephritis.

Question 52

How is lupus nephritis managed?

Answer 52

• Induction therapy:
• Cyclophosphamide or mycophenolate mofetil (preferred in many cases) for severe lupus nephritis (Class III/IV).
• High-dose corticosteroids to control inflammation.
• Maintenance therapy:
• Mycophenolate mofetil or azathioprine to prevent relapse.
• Hydroxychloroquine can be used for its renal-protective effects.
• Renal replacement therapy: In cases of end-stage renal disease, dialysis or renal transplantation may be required.

Question 53

Which drugs have a higher risk of causing Drug-Induced Lupus (DILE)?

Answer 53

• Procainamide and hydralazine: Particularly associated with high risk due to dose and duration of therapy.
• Isoniazid and minocycline: Known to cause lupus-like symptoms more commonly.
• Methyldopa: Known to cause lupus-like syndromes in pregnant women.

Question 54

What are the laboratory findings in Drug-Induced Lupus (DILE)?

Answer 54

• Antinuclear antibodies (ANA): Often positive, particularly anti-histone antibodies.
• Anti-dsDNA: Typically negative in DILE (distinguishing it from classic SLE).
• Complement levels: Normal, unlike in SLE where complement levels may be low.
• Urinalysis: Generally normal, as renal involvement is rare in DILE.

Question 55

What is the pathogenesis of Systemic Lupus Erythematosus (SLE)?

Answer 55

• Autoimmunity: Loss of immune tolerance, leading to the production of autoantibodies against self-antigens, including nuclear antigens (e.g., DNA, histones).
• Genetic Factors: Associations with HLA-DR2 and HLA-DR3.
• Environmental Triggers: UV radiation, infections (e.g., Epstein-Barr virus), medications, and hormonal factors (e.g., estrogen).
• Immune Complex Formation: Autoantibodies form immune complexes that deposit in tissues, leading to inflammation and damage.

Question 56

What laboratory findings are characteristic of SLE?

Answer 56

1. Positive ANA (antinuclear antibody): Highly sensitive but not specific.
   
   2. Anti-dsDNA: Specific to SLE, often associated with lupus nephritis.
   3. Anti-Smith (anti-Sm): Specific for SLE but less common than anti-dsDNA.
   4. Low complement levels: C3 and C4 levels are low due to immune complex formation.
   5. Antiphospholipid antibodies: Associated with thromboembolic events and recurrent pregnancy loss.
   6. Urinalysis: Proteinuria, hematuria, and cast formation suggest lupus nephritis.

Question 57

What is discoid lupus erythematosus (DLE)?

Answer 57

• Description: Chronic form of cutaneous lupus with raised, scaly, erythematous plaques that often heal with scarring and hypo/hyperpigmentation.
• Location: Typically affects sun-exposed areas like the face, scalp, ears, and neck.
• Significance: Can progress to systemic lupus (SLE) but can also occur as a skin-limited disease

Question 58

What is subacute cutaneous lupus erythematosus (SCLE)?

Answer 58

• Description: Characterized by scaly, annular or polycyclic erythematous plaques, often with minimal scarring.
• Location: Upper body (shoulders, upper arms, chest), sun-exposed areas.
• Association: Commonly associated with anti-Ro/SSA antibodies.
• Clinical Relevance: More often seen in SLE but may also occur in isolated SCLE

Question 59

What are the common renal manifestations in SLE?

Answer 59

Lupus nephritis: A hallmark complication of SLE, characterized by immune complex deposition in the glomeruli.

Question 60

What are the cardiovascular manifestations in SLE?

Answer 60

• Pericarditis: Inflammation of the pericardium, causing chest pain, friction rub, and ECG changes.
• Libman-Sacks endocarditis: Non-bacterial thrombotic endocarditis with vegetations on valve leaflets.
• Atherosclerosis: Increased risk of premature coronary artery disease and thrombosis due to persistent inflammation and antiphospholipid syndrome.
• Myocarditis: Rare, but can cause heart failure or arrhythmias.

Question 61

How does SLE affect the lungs?

Answer 61

• Pleuritis: Chest pain and pleuritic breathing pain due to inflammation of the pleura.
• Pleural effusion: Often bilateral and may be associated with exudates in the pleural fluid.
• Interstitial lung disease (ILD): Progressive dyspnea and restrictive lung patterns in chronic SLE.
• Pulmonary hypertension: Can occur in advanced disease, leading to right heart failure.

Question 62

What are the neurological manifestations of SLE?

Answer 62

• Cognitive dysfunction (lupus fog): Difficulty concentrating, memory problems, and cognitive impairment.
• Seizures: Often due to lupus cerebritis or antiphospholipid syndrome.
• Psychosis: Hallucinations, paranoia, or delusions due to central nervous system (CNS) lupus.
• Headaches: Common, often with a migraine-like pattern.
• Stroke: Increased risk of ischemic stroke due to antiphospholipid antibodies and thrombosis.

Question 63

What is the gastrointestinal (GI) involvement in SLE?

Answer 63

• Lupus mesenteric vasculitis: Rare but can cause abdominal pain, nausea, and vomiting due to blood flow issues to the intestines.
• Hepatitis: Mild liver dysfunction or autoimmune hepatitis can occur, but is less common.
• Peritonitis: Rare but can occur as part of the generalized inflammatory process.

Question 64

What are the hematologic manifestations of SLE?

Answer 64

• Anemia: Often due to hemolysis (autoimmune hemolytic anemia) or chronic disease.
• Leukopenia: Reduced white blood cell count, especially lymphopenia.
• Thrombocytopenia: Decreased platelet count, which may predispose to bleeding.
• Positive Coombs test: Indicating autoimmune hemolytic anemia.
• Antiphospholipid syndrome: Increased risk of thrombosis and recurrent pregnancy loss

Question 65

What are the musculoskeletal manifestations of SLE?

Answer 65

• Non-erosive arthritis: Affects small joints (hands, wrists, knees), causing pain and swelling but no joint damage.
• Osteonecrosis: Increased risk, particularly in the femoral head.
• Myositis: Muscle inflammation, sometimes with elevated muscle enzymes (CK)

Question 66

What is Antiphospholipid Antibody Syndrome (APS)?

Answer 66

• Thrombosis (venous and arterial)
• Pregnancy-related complications (miscarriage, preeclampsia, premature birth)
• Thrombocytopenia

Question 67

What are the diagnostic criteria for APS?

Answer 67

• Clinical Criteria:
• One or more episodes of venous or arterial thrombosis.
• Pregnancy morbidity: One or more unexplained deaths of a normal fetus (≥10 weeks) or premature births (<34 weeks) due to preeclampsia or placental insufficiency.
• Laboratory Criteria:
1. Lupus anticoagulant (LA)
2. Anticardiolipin antibodies (aCL) (IgG/IgM)
3. Anti-β2-glycoprotein I antibodies (anti-β2GPI)
• Diagnosis: Requires one clinical and one laboratory criterion, confirmed at least 12 weeks apart.

Question 68

What is the pathophysiology of APS?

Answer 68

• Immune Mechanism: aPLs bind to β2-glycoprotein I, which in turn binds to phospholipids on endothelial cells, platelets, and trophoblasts.
• Endothelial Activation: Activation of endothelial cells causes inflammation, prothrombotic state, and impaired fibrinolysis.
• Platelet Activation: aPLs promote platelet aggregation and microthrombosis, leading to vascular occlusion.
• Complement Activation: aPLs form immune complexes that activate the complement system, exacerbating inflammation and clotting.

Question 69

How is APS managed in pregnancy?

Answer 69

• Anticoagulation:
• LMWH (enoxaparin) is preferred over warfarin during pregnancy due to safety concerns.
• Low-dose aspirin (81 mg) is used for prophylaxis.
• Monitoring:
• Regular ultrasounds to assess fetal development and placental function.
• Monitoring for preeclampsia and thrombosis.

Question 70

What is the management of APS?

Answer 70

• Anticoagulation:
• Warfarin (INR goal 2.0–3.0) for secondary prevention of thrombosis.
• Low-molecular-weight heparin (LMWH) or unfractionated heparin for acute thrombosis or during pregnancy.
• Aspirin: Low-dose aspirin (81 mg daily) for prophylaxis, especially in primary APS or pregnancy-associated APS.
• Pregnancy:
• Low-dose aspirin and LMWH are the mainstay.
• Close monitoring of fetal growth and placental function is necessary.
• For severe cases or refractory APS: Rituximab and other immunosuppressive agents may be considered.

Question 71

What are the key organ manifestations of Antiphospholipid Syndrome (APS)?

Answer 71

• Neurological: Stroke, TIA, seizures, cognitive dysfunction, headaches (migraine).
• Renal: Chronic kidney disease (CKD), hypertension due to renal thrombosis.
• Cardiovascular: Myocardial infarction (MI), Libman-Sacks endocarditis, pulmonary hypertension.
• Skin: Livedo reticularis, skin ulcers, alopecia.
• Gastrointestinal: Mesenteric ischemia, pancreatitis.
• Hematological: Thrombocytopenia, anemia, coagulation abnormalities (lupus anticoagulant).
• Ophthalmologic: Retinal artery/vein occlusion, visual disturbances.
• Obstetric: Recurrent pregnancy loss, preeclampsia, IUGR, stillbirth.
• Pulmonary: Pulmonary embolism (PE), pulmonary hypertension.
• Endocrine: Thyroid dysfunction (Hashimoto’s, Graves’ disease).

Question 72

What gastrointestinal manifestations are seen in systemic sclerosis?

Answer 72

• Esophageal dysmotility: Leading to dysphagia and gastroesophageal reflux disease (GERD) due to smooth muscle atrophy.
• Gastric antral vascular ectasia (GAVE): “Watermelon stomach”, characterized by chronic bleeding and iron deficiency anemia.
• Small bowel involvement: Malabsorption, bloating, and diarrhea due to motility dysfunction.
• Colonic involvement: Constipation and pseudoblockage due to colonic hypomotility

Question 73

What are the skin manifestations in systemic sclerosis?

Answer 73

• Raynaud’s phenomenon: Early sign, causing color changes in fingers in response to cold/stress.
• Sclerodactyly: Thickening and tightness of the skin on fingers, leading to claw-like deformities.
• Telangiectasias: Dilated blood vessels on the skin, commonly on face, hands, and mucous membranes.
• Digital ulcers: Painful, non-healing ulcers on fingers or toes.
• Calcinosis: Calcium deposits under the skin (more common in limited form).

Question 74

What are the pulmonary complications in systemic sclerosis?

Answer 74

• Interstitial lung disease (ILD): Leading cause of morbidity and mortality in diffuse scleroderma, presenting with dyspnea and dry cough.
• Pulmonary hypertension (PH): Seen primarily in limited cutaneous scleroderma, leading to right heart failure.
• Pulmonary fibrosis: Common in both subtypes but more severe in dcSSc.

Question 75

What are the cardiac manifestations of systemic sclerosis?

Answer 75

• Conduction abnormalities: Sinus node dysfunction, AV block, and arrhythmias due to fibrosis of the conduction system.
• Myocardial fibrosis: Can lead to diastolic dysfunction and heart failure.
• Pulmonary hypertension: Contributes to right heart failure.

Question 76

What renal complications are associated with systemic sclerosis?

Answer 76

• Scleroderma renal crisis (SRC): A life-threatening condition characterized by acute-onset hypertension, renal failure, and microangiopathic hemolytic anemia.
• Pathogenesis: Intimal hyperplasia and vascular occlusion of renal arteries.
• Treatment: ACE inhibitors are used to manage blood pressure and prevent kidney damage.

Question 77

What are the key autoantibodies seen in systemic sclerosis?

Answer 77

• Anti-Scl-70 (anti-topoisomerase I): Associated with diffuse cutaneous scleroderma and lung involvement.
• Anti-centromere antibodies: Typically seen in limited cutaneous scleroderma and pulmonary hypertension.
• Anti-RNA polymerase III: Associated with a higher risk of renal crisis.
• Anti-fibrillarin: Seen in overlap syndromes with features of systemic lupus erythematosus or polymyositis.

Question 78

What are the treatment options for systemic sclerosis?

Answer 78

• Immunosuppressive therapy:
• Methotrexate or mycophenolate mofetil for cutaneous fibrosis and pulmonary fibrosis.
• Cyclophosphamide for lung disease and severe manifestations.
• Pulmonary hypertension: Treated with bosentan, sildenafil, and prostacyclin analogs.
• ACE inhibitors: For managing scleroderma renal crisis and hypertension.
• PPI therapy: To control GERD and esophageal dysmotility.
• Vasodilators: Calcium channel blockers or nitroglycerin for Raynaud’s phenomenon

Question 79

What is CREST syndrome, and how is it related to systemic sclerosis?

Answer 79

CREST syndrome is a subtype of limited cutaneous systemic sclerosis (lcSSc) characterized by:
1. Calcinosis: Calcium deposits in skin and soft tissues.
2. Raynaud’s phenomenon: Episodic vasospasm in fingers/toes triggered by cold or stress.
3. Esophageal dysmotility: Dysphagia and GERD due to esophageal smooth muscle dysfunction.
4. Sclerodactyly: Thickening and tightening of the skin on fingers, leading to deformities.
5. Telangiectasias: Dilated capillaries on skin, often on face, hands, or mucosa.

Question 80

Key Features of CREST syndrome?

Answer 80

• Associated with anti-centromere antibodies.
• Higher risk of pulmonary arterial hypertension (PAH).

Question 81

What is Very Early Systemic Sclerosis (VEScS)?

Answer 81

VEScS is the earliest detectable stage of systemic sclerosis (SSc)
1. Raynaud’s Phenomenon: Often the first clinical manifestation.
2. Autoantibodies: Presence of anti-nuclear antibodies (ANA), anti-Scl-70, or anti-centromere antibodies.
3. Nailfold Capillaroscopy Abnormalities:
• Enlarged capillaries.
• Dropout areas.
• Microhemorrhages.
4. Early Organ Involvement:
• Mild esophageal dysmotility.
• Initial signs of interstitial lung disease (ILD) or pulmonary hypertension (PH) on screening tests.
5. Skin Involvement: Minimal or absent skin thickening in this stage.

Question 82

What are the key etiological factors in systemic sclerosis?

Answer 82

1. Genetic Factors:
   • HLA Associations: HLA-DRB1, HLA-DQB1.
   • Polymorphisms in genes related to immune regulation (e.g., STAT4, IRF5) and fibrosis (e.g., TGF-β pathway).
   • Familial clustering in some cases.
2. Environmental Triggers:
   • Silica exposure: Seen in miners and construction workers.
   • Solvents and chemicals: Trichloroethylene, vinyl chloride, and benzene.
   • Drugs: Bleomycin, penicillamine, and cocaine (rare causes).
3. Autoimmune Dysregulation:
   • Loss of immune tolerance leads to autoreactive T-cells and B-cells.
   • Production of autoantibodies (e.g., anti-Scl-70, anti-centromere).
4. Vascular Injury:
   • Endothelial cell dysfunction triggers vasculopathy and microvascular changes.
5. Fibrotic Pathway Activation:
   • Overactivation of TGF-β (transforming growth factor-beta), leading to excessive collagen deposition and fibrosis.

Question 83

What are the clinical stages of Raynaud Phenomenon?

Answer 83

Tri-phasic Color Changes:
1. White (Pallor): Due to vasospasm and ischemia.
2. Blue (Cyanosis): Deoxygenation of blood in stagnant capillaries.
3. Red (Rubor): Reactive hyperemia after reperfusion.

Question 84

What are the key investigations for Raynaud Phenomenon?

Answer 84

1. Nailfold Capillaroscopy:
   • Normal in primary Raynaud’s.
   • Abnormal capillary loops in secondary Raynaud’s.
   
   2. Autoantibody Testing:
      • Anti-centromere (associated with systemic sclerosis).
      • Anti-Scl-70, ANA for systemic involvement.
   3. Doppler Ultrasound or Angiography: For severe cases with digital ischemia.

Question 85

How is scleroderma (systemic sclerosis) classified?

Answer 85

1. Systemic Sclerosis (SSc)• a. Limited Cutaneous Systemic Sclerosis (lcSSc):
   • Skin involvement: Confined to face, neck, and distal extremities (below elbows/knees).
   • Associated features:
   • CREST syndrome (Calcinosis, Raynaud’s, Esophageal dysmotility, Sclerodactyly, Telangiectasia).
   • Anti-centromere antibodies.
   • Higher risk of pulmonary arterial hypertension (PAH).
   • Gradual progression.
   • b. Diffuse Cutaneous Systemic Sclerosis (dcSSc):
   • Skin involvement: Involves trunk, proximal limbs, and distal areas.
   • Associated features:
   • Early and significant organ involvement (lungs, kidneys, heart).
   • Higher risk of scleroderma renal crisis.
   • Associated with anti-Scl-70 (anti-topoisomerase I) antibodies.
   • Rapid progression.
2. Localized Scleroderma• Skin involvement only, without systemic organ involvement.
   • Subtypes:
   • Morphea: Localized patches of thickened skin.
   • Linear Scleroderma: Affects one side of the body, often in children.
   • En Coup de Sabre: Linear scleroderma affecting the forehead and scalp.
3. Overlap Syndromes• Features of systemic sclerosis with other autoimmune diseases (e.g., SLE, polymyositis).

Question 86

What are the characteristic autoantibodies associated with diffuse and limited systemic sclerosis?

Answer 86

• Diffuse SSc: Anti-Scl-70 (anti-topoisomerase I) antibodies.
• Limited SSc: Anti-centromere antibodies.