CPSP style questions on the topic SLE, Sjoren syndrome, scleroderma and mixed connective tissue disease. Explanation and key at the end

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CPSP-Style MCQs: SLE, Sjögren Syndrome, Scleroderma & MCTD

SECTION A — SYSTEMIC LUPUS ERYTHEMATOSUS (SLE)

Q1. A 26-year-old woman presents with a facial rash, joint pain, and fatigue. She is found to have proteinuria of 0.8 g/day, lymphopenia (1200/mm³), and a positive ANA. Which antibody, if positive, would be MOST specific for SLE?

A. Anti-Ro (SS-A)
B. Anti-dsDNA
C. Anti-histone
D. Rheumatoid factor
E. Anti-La (SS-B)

Q2. A 30-year-old woman with known SLE presents with new-onset seizures. Her serum shows low C3, low C4, high anti-dsDNA, and urinalysis shows red cell casts. How many ACR classification criteria for SLE does she currently meet (based on the information given)?

A. 3
B. 4
C. 5
D. 6
E. 7

Q3. The malar butterfly rash of SLE characteristically:

A. Involves the nasolabial folds
B. Causes scarring and atrophy
C. Spares the nasolabial folds
D. Occurs in more than 80% of SLE patients
E. Is always present at diagnosis

Q4. A 28-year-old woman with SLE has a positive VDRL but negative FTA-ABS. She has no history of syphilis. This finding is best explained by:

A. Recent syphilitic infection
B. False-positive VDRL due to antiphospholipid antibodies
C. HIV co-infection
D. Drug-induced lupus
E. Cross-reaction with anti-Ro antibodies

Q5. Which of the following drugs is MOST commonly implicated in drug-induced lupus?

A. Hydralazine
B. Rifampicin
C. Hydroxychloroquine
D. Cyclophosphamide
E. Methotrexate

Q6. A 25-year-old woman with SLE has had multiple second-trimester pregnancy losses, deep vein thrombosis, and a positive lupus anticoagulant. What is the MOST likely associated syndrome?

A. Neonatal lupus
B. Antiphospholipid antibody syndrome
C. Drug-induced lupus
D. Mixed connective tissue disease
E. Libman-Sacks endocarditis

Q7. Regarding renal involvement in SLE, which of the following is CORRECT?

A. Persistent proteinuria >0.5 g/day fulfills a diagnostic criterion
B. Membranous nephropathy (Class V) is the most common pattern
C. Renal involvement occurs in less than 20% of patients
D. Hematuria alone is sufficient to diagnose lupus nephritis
E. Complement levels are typically elevated during active nephritis

Q8. A 24-year-old woman with SLE is started on hydroxychloroquine. What is the MOST important long-term side effect to monitor?

A. Hepatotoxicity
B. Retinal toxicity
C. Pulmonary fibrosis
D. Nephrotoxicity
E. Bone marrow suppression

Q9. Which of the following is the MOST common hematologic finding in SLE?

A. Thrombocytopenia
B. Hemolytic anemia with positive Coombs test
C. Leukopenia/lymphopenia
D. Neutrophilia
E. Polycythemia

Q10. The 5-year survival rate after diagnosis of SLE is approximately:

A. 60%
B. 70%
C. 80%
D. 90%
E. 95%

SECTION B — SJÖGREN SYNDROME

Q11. A 45-year-old woman presents with dry eyes and dry mouth for 2 years. Schirmer test shows <8 mm wetting in 5 minutes. Minor salivary gland biopsy shows focal lymphocytic infiltrate with a focus score ≥1. Anti-Ro and anti-La antibodies are positive. What is the MOST likely diagnosis?

A. Sarcoidosis
B. Secondary Sjögren syndrome
C. Primary Sjögren syndrome
D. HIV-associated salivary gland disease
E. IgG4-related disease

Q12. The Schirmer II test for Sjögren syndrome involves:

A. Instilling fluorescein into the conjunctival sac
B. Measuring salivary flow after candy stimulation
C. Stimulating the nasolacrimal reflex via a nasal swab to measure tear flow
D. Biopsy of the parotid gland
E. Measuring serum amylase

Q13. In Sjögren syndrome, the MOST serious long-term complication that necessitates regular surveillance is:

A. Secondary RA
B. Lymphoma (non-Hodgkin type)
C. Pulmonary fibrosis
D. Renal tubular acidosis
E. Primary biliary cirrhosis

Q14. A patient with known rheumatoid arthritis develops dry eyes and dry mouth. Serologic tests show elevated RF (>1:320) and positive anti-SS-A. Minor salivary gland biopsy is positive. This presentation is BEST classified as:

A. Primary Sjögren syndrome
B. Sicca syndrome
C. Secondary Sjögren syndrome
D. Undifferentiated connective tissue disease
E. Mixed connective tissue disease

Q15. Rose bengal staining in Sjögren syndrome is used to demonstrate:

A. Salivary gland infiltration
B. Corneal or conjunctival epithelial damage (keratoconjunctivitis sicca)
C. Anti-Ro antibody presence
D. Parotid duct obstruction
E. Lymphocytic sialadenitis

Q16. Which of the following autoantibodies is MOST strongly associated with neonatal lupus in offspring of Sjögren syndrome patients?

A. Anti-La (SS-B)
B. Anti-Ro (SS-A)
C. Anti-dsDNA
D. Anti-Sm
E. Anti-U1RNP

Q17. A patient with primary Sjögren syndrome develops recurrent parotid gland enlargement and B-symptoms (fever, weight loss, night sweats). The NEXT most appropriate investigation is:

A. Repeat minor salivary gland biopsy
B. Serum complement levels
C. CT scan of the neck and chest + LDH
D. Anti-dsDNA levels
E. Anti-centromere antibody

SECTION C — SYSTEMIC SCLEROSIS (SCLERODERMA)

Q18. A 40-year-old woman presents with skin tightening of the fingers and face, Raynaud phenomenon, esophageal dysmotility, and telangiectasias. Which antibody is MOST likely to be positive?

A. Anti-Scl-70 (anti-topoisomerase I)
B. Anti-centromere antibody
C. Anti-dsDNA
D. Anti-U1RNP
E. Anti-Jo-1

Q19. CREST syndrome is a variant of which condition?

A. Diffuse systemic sclerosis
B. Mixed connective tissue disease
C. Limited systemic sclerosis
D. Primary Sjögren syndrome
E. Polymyositis

Q20. Anti-Scl-70 (anti-topoisomerase I) antibody in systemic sclerosis is MOST associated with:

A. Limited skin disease and good prognosis
B. Diffuse skin involvement, pulmonary fibrosis, and peripheral vascular disease
C. CREST syndrome and late visceral involvement
D. Pulmonary hypertension without fibrosis
E. Renal crisis prevention

Q21. Which of the following is the MOST common visceral complication causing morbidity and mortality in systemic sclerosis?

A. Esophageal dysmotility
B. Scleroderma renal crisis
C. Pulmonary hypertension and interstitial lung disease
D. Cardiac fibrosis
E. Hepatic fibrosis

Q22. A 50-year-old woman with diffuse systemic sclerosis presents with severe hypertension (BP 190/110), elevated creatinine, and microangiopathic hemolytic anemia. This presentation is MOST consistent with:

A. Lupus nephritis
B. TTP/HUS
C. Scleroderma renal crisis
D. Malignant hypertension from essential hypertension
E. Anti-GBM disease

Q23. The PRIMARY mechanism of organ damage in systemic sclerosis involves:

A. Immune complex deposition
B. CD8+ T cell-mediated cytotoxicity
C. Vascular injury, autoimmunity, and fibroblast activation leading to collagen deposition
D. Type IV hypersensitivity
E. Complement-mediated lysis

Q24. Raynaud phenomenon in systemic sclerosis differs from primary Raynaud disease in that:

A. It is more common in young women
B. It is provoked by cold exposure
C. It is associated with digital ulcers, gangrene, and systemic features
D. It resolves spontaneously
E. It does not require treatment

SECTION D — MIXED CONNECTIVE TISSUE DISEASE (MCTD)

Q25. A 32-year-old woman presents with Raynaud phenomenon, swollen fingers, myositis, and arthritis. ANA shows a very high titre with a speckled pattern. Which antibody is MOST diagnostic of MCTD?

A. Anti-dsDNA
B. Anti-Sm
C. Anti-U1RNP
D. Anti-Ro (SS-A)
E. Anti-centromere

Q26. MCTD is defined by overlapping features of which three conditions?

A. SLE, RA, and dermatomyositis
B. SLE, scleroderma, and polymyositis
C. Sjögren, scleroderma, and RA
D. SLE, Sjögren, and polymyositis
E. RA, polymyositis, and vasculitis

Q27. Which of the following features is characteristically ABSENT or rare in MCTD compared to SLE?

A. Arthritis
B. Malar rash
C. Major CNS disease and severe proliferative glomerulonephritis
D. Pulmonary hypertension
E. Esophageal dysmotility

Q28. The HLA genotypes linked to MCTD are:

A. HLA-B27 and HLA-B51
B. HLA-DR4 and HLA-DR2
C. HLA-DR3 and HLA-B8
D. HLA-A2 and HLA-DR7
E. HLA-Cw6 and HLA-DR1

Q29. A 38-year-old woman with MCTD develops nephrotic-range proteinuria and severe hypertension. The serologic finding MOST likely to correlate with this renal involvement is:

A. High anti-U1RNP titres
B. Positive anti-Sm and high anti-dsDNA antibodies
C. Elevated anti-centromere antibodies
D. High RF titres
E. Positive anti-Ro antibodies

Q30. What percentage of patients with MCTD eventually develop features that reclassify them under a specific connective tissue disease after long-term follow-up?

A. 10%
B. 25%
C. 40%
D. 60%
E. 80%

ANSWER KEY WITH EXPLANATIONS

Q1 — B. Anti-dsDNA Anti-dsDNA and anti-Sm are found almost exclusively in SLE, making them the most specific antibodies. Anti-dsDNA also correlates with disease activity, especially lupus nephritis. Anti-Ro (SS-A) is seen in Sjögren syndrome, neonatal lupus, and ANA-negative SLE. Anti-histone is associated with drug-induced lupus. RF is non-specific. (Textbook of Family Medicine 9e; Harrison's Principles 22E)

Q2 — D. 6 She meets: (1) neurologic disorder (seizures), (2) renal disorder (proteinuria + red cell casts), (3) immunologic (high anti-dsDNA implied by question context / low complement), (4) ANA positive. The question also states lymphopenia and joint pain — adding hematologic and arthritis criteria. Count: seizures + renal casts + proteinuria (these count as ONE renal criterion) + lymphopenia + ANA + anti-dsDNA = 6 criteria. A minimum of 4 out of 11 ACR criteria are required for diagnosis. (Textbook of Family Medicine 9e)

Q3 — C. Spares the nasolabial folds The malar butterfly rash is fixed erythema over the malar eminences that characteristically SPARES the nasolabial folds. It occurs in only about one-third of SLE patients (not 80%+), does not scar (unlike discoid lesions), and is often triggered by sun exposure. (Textbook of Family Medicine 9e; ACR Criteria Table)

Q4 — B. False-positive VDRL due to antiphospholipid antibodies SLE is associated with antiphospholipid antibodies (lupus anticoagulant, anticardiolipin), which cause a biologically false-positive VDRL/RPR test. The FTA-ABS (specific treponemal test) is negative, confirming no true syphilis infection. This is one of the immunologic ACR criteria for SLE. (Textbook of Family Medicine 9e, ACR criterion 10d)

Q5 — A. Hydralazine Classic drugs causing drug-induced lupus include hydralazine, procainamide, isoniazid, minocycline, and methyldopa. Anti-histone antibodies are characteristic. Drug-induced lupus typically spares the kidneys and CNS. Hydroxychloroquine is actually used to TREAT SLE. (Standard pharmacology; Harrison's 22E)

Q6 — B. Antiphospholipid antibody syndrome Recurrent pregnancy losses (especially second-trimester), DVT, and positive lupus anticoagulant are the hallmarks of antiphospholipid antibody syndrome (APS), which is closely associated with SLE. Libman-Sacks endocarditis is a cardiac manifestation of APS/SLE but does not explain the full clinical picture here. (Textbook of Family Medicine 9e; Standard rheumatology)

Q7 — A. Persistent proteinuria >0.5 g/day fulfills a diagnostic criterion ACR criterion #7 for SLE includes persistent proteinuria >0.5 g/day OR >3+ on dipstick, OR cellular casts. Renal involvement (lupus nephritis) actually occurs in up to 50% of patients. During active nephritis, complement levels (C3, C4) are typically LOW (consumed), not elevated. WHO/ISN Class III (focal) and Class IV (diffuse) proliferative are the most common and most severe patterns. (Textbook of Family Medicine 9e, ACR criteria)

Q8 — B. Retinal toxicity Hydroxychloroquine can cause irreversible retinopathy (bull's-eye maculopathy) with long-term use, especially at doses >5 mg/kg/day. Annual ophthalmologic screening is recommended. It is not hepatotoxic, nephrotoxic, or a cause of pulmonary fibrosis. (Goldman-Cecil Medicine; Standard pharmacology)

Q9 — C. Leukopenia/lymphopenia Leukopenia (<4000/mm³) or lymphopenia (<1500/mm³) is the MOST common hematologic abnormality in SLE, though hemolytic anemia with positive Coombs test is the most specific. Thrombocytopenia also occurs but is less frequent than lymphopenia. Neutrophilia is not a feature. (Textbook of Family Medicine 9e)

Q10 — D. 90% The 5-year survival rate following SLE diagnosis is approximately 90%. Survival has dramatically improved with better immunosuppressive therapy, early diagnosis, and management of renal and cardiovascular complications. (Textbook of Family Medicine 9e)

Q11 — C. Primary Sjögren syndrome The patient has objective evidence of dry eyes (Schirmer test <8 mm/5 min), dry mouth (positive biopsy, focus score ≥1), and serologic autoimmunity (anti-Ro, anti-La). There is no associated connective tissue disease mentioned, making this PRIMARY Sjögren syndrome. Sarcoidosis, HIV, and hepatitis are exclusion criteria. (Textbook of Family Medicine 9e, San Diego Criteria)

Q12 — C. Stimulating the nasolacrimal reflex via a nasal swab to measure tear flow The Schirmer II test stimulates the nasolacrimal reflex by inserting a cotton swab into the nostril, then measures the increase in tear flow for both eyes over 5 minutes. A result of <8 mm wetting is abnormal. This differs from Schirmer I (baseline tearing without stimulation). (Textbook of Family Medicine 9e)

Q13 — B. Lymphoma (non-Hodgkin type) Sjögren syndrome carries a significantly elevated risk of developing non-Hodgkin lymphoma (especially MALT lymphoma of the parotid). This is the most serious long-term complication and requires surveillance. Risk factors include persistent parotid enlargement, splenomegaly, lymphadenopathy, cryoglobulinemia, and low C4. (Standard rheumatology/oncology; Brenner and Rector's Kidney)

Q14 — C. Secondary Sjögren syndrome Secondary Sjögren syndrome is diagnosed when the classic sicca features (dry eyes and dry mouth with objective confirmation) occur in association with another autoimmune disease, such as RA, SLE, polymyositis, or scleroderma. San Diego Criteria define this as Category II. (Textbook of Family Medicine 9e, San Diego Criteria)

Q15 — B. Corneal or conjunctival epithelial damage (keratoconjunctivitis sicca) Rose bengal staining highlights devitalized or damaged corneal and conjunctival epithelial cells, providing objective evidence of keratoconjunctivitis sicca. It is a key diagnostic test in the evaluation of Sjögren syndrome-related ocular dryness. (Textbook of Family Medicine 9e)

Q16 — B. Anti-Ro (SS-A) Anti-Ro (SS-A) antibodies cross the placenta and are strongly associated with neonatal lupus, particularly neonatal complete heart block (congenital heart block). Hydroxychloroquine during pregnancy in mothers with previous affected infants may reduce recurrence risk. Anti-La (SS-B) is also associated but less strongly than anti-Ro. (Comprehensive Clinical Nephrology 7e)

Q17 — C. CT scan of the neck and chest + LDH B-symptoms (fever, weight loss, night sweats) with recurrent parotid enlargement in a Sjögren patient should raise strong suspicion for lymphoma transformation. The next step is staging CT of neck/chest/abdomen and LDH measurement. If suspicious, tissue biopsy (PET-guided) follows. (Standard rheumatology/oncology)

Q18 — B. Anti-centromere antibody The clinical picture describes CREST syndrome (Calcinosis, Raynaud, Esophageal dysmotility, Sclerodactyly, Telangiectasia) - the limited form of systemic sclerosis. Anti-centromere antibody is strongly associated with limited systemic sclerosis/CREST. Anti-Scl-70 (topoisomerase I) is associated with diffuse systemic sclerosis with pulmonary fibrosis. (Robbins & Kumar Basic Pathology; Robbins, Cotran & Kumar Pathologic Basis of Disease)

Q19 — C. Limited systemic sclerosis CREST syndrome is a presentation of LIMITED systemic sclerosis. It features relatively mild, distally confined skin involvement (fingers and face), late visceral involvement, and is associated with anti-centromere antibody. Diffuse systemic sclerosis has widespread skin involvement and early visceral disease. (Robbins & Kumar Basic Pathology)

Q20 — B. Diffuse skin involvement, pulmonary fibrosis, and peripheral vascular disease Anti-Scl-70 (anti-DNA topoisomerase I) is highly specific for systemic sclerosis and is associated with diffuse cutaneous involvement, higher risk of interstitial pulmonary fibrosis, and peripheral vascular disease. Anti-centromere is associated with limited disease and better prognosis. (Robbins & Kumar Basic Pathology; Robbins, Cotran & Kumar Pathologic Basis of Disease)

Q21 — C. Pulmonary hypertension and interstitial lung disease While esophageal dysmotility is the MOST common visceral manifestation overall, the major causes of morbidity and MORTALITY are pulmonary hypertension (especially in limited SSc/CREST) and interstitial lung disease/pulmonary fibrosis (especially in diffuse SSc with anti-Scl-70). Renal crisis is now less fatal since ACE inhibitor introduction. (Robbins & Kumar Basic Pathology)

Q22 — C. Scleroderma renal crisis Scleroderma renal crisis presents with abrupt-onset severe hypertension, oliguric acute kidney injury, and microangiopathic hemolytic anemia (MAHA) in patients with diffuse systemic sclerosis. It is a medical emergency. ACE inhibitors (captopril) are the treatment of choice. This differs from TTP/HUS by the clinical context and absence of neurologic findings. (Comprehensive Clinical Nephrology 7e; Robbins & Kumar)

Q23 — C. Vascular injury, autoimmunity, and fibroblast activation leading to collagen deposition Systemic sclerosis pathogenesis involves three interrelated processes: (1) autoimmunity with CD4+ T cell activation and cytokine release (IL-13, TGF-β), (2) vascular microvascular injury with endothelial damage and platelet aggregation, and (3) progressive fibrosis from fibroblast activation and excessive collagen deposition. There is no significant role for immune complex deposition (as in SLE) or complement-mediated lysis. (Robbins & Kumar Basic Pathology)

Q24 — C. It is associated with digital ulcers, gangrene, and systemic features Secondary Raynaud phenomenon in systemic sclerosis is more severe than primary Raynaud disease. It may cause digital ulcers, tissue infarction, and gangrene, and is associated with abnormal nailfold capillaroscopy and systemic autoimmune disease. Primary Raynaud is benign, affects young women, and rarely causes tissue damage. (Standard rheumatology)

Q25 — C. Anti-U1RNP The hallmark antibody of MCTD is anti-U1RNP (against the ribonuclease-sensitive extractable nuclear antigen U1RNP), present at very high titres with a speckled ANA pattern. Anti-dsDNA and anti-Sm are found in SLE; anti-centromere in limited scleroderma; anti-Jo-1 in polymyositis/dermatomyositis. (Brenner and Rector's Kidney)

Q26 — B. SLE, scleroderma, and polymyositis MCTD (Sharp syndrome) is defined by overlapping features of SLE, scleroderma (systemic sclerosis), and polymyositis. The classic triad includes Raynaud phenomenon, swollen hands/fingers, and myositis with high-titre anti-U1RNP. (Brenner and Rector's Kidney)

Q27 — C. Major CNS disease and severe proliferative glomerulonephritis Despite many overlapping features with SLE, patients with MCTD (especially those with documented anti-U1RNP antibodies) characteristically have a LOW frequency of major CNS disease and severe proliferative glomerulonephritis. This is a distinguishing feature from SLE. Pulmonary hypertension and esophageal dysmotility are common in MCTD. (Brenner and Rector's Kidney)

Q28 — B. HLA-DR4 and HLA-DR2 MCTD has genetic linkage to HLA-DR4 and HLA-DR2 genotypes, similar to some other autoimmune conditions. HLA-B27 is associated with spondyloarthropathies; HLA-DR3/B8 with primary Sjögren and SLE; HLA-Cw6 with psoriasis. (Brenner and Rector's Kidney)

Q29 — B. Positive anti-Sm and high anti-dsDNA antibodies In MCTD, renal disease is more common when there is evidence of "SLE-like" serology - particularly high anti-dsDNA and anti-Sm antibody positivity. The anti-U1RNP titre itself does NOT correlate with renal involvement. Low complement is also more closely linked to SLE-pattern nephritis within MCTD. (Brenner and Rector's Kidney)

Q30 — C. 40% A longitudinal study of 161 MCTD patients followed for 8 years found that 60% remained as unclassified MCTD, while approximately 40% evolved into a defined CTD: 17% systemic sclerosis, 9% SLE, 2.5% RA, and 11.5% undifferentiated CTD. Anti-dsDNA predicted evolution toward SLE; hypomotility of the esophagus or sclerodactyly predicted evolution toward systemic sclerosis. (Brenner and Rector's Kidney)

QUICK REFERENCE: KEY ANTIBODIES

Antibody	Disease Association
Anti-dsDNA	SLE (specific; tracks disease activity)
Anti-Sm	SLE (highly specific)
Anti-histone	Drug-induced lupus
Anti-Ro (SS-A)	Sjögren, neonatal lupus, ANA-negative SLE
Anti-La (SS-B)	Sjögren syndrome
Anti-U1RNP	MCTD (hallmark)
Anti-Scl-70 (anti-topo I)	Diffuse systemic sclerosis (pulmonary fibrosis)
Anti-centromere	Limited systemic sclerosis / CREST
Anti-Jo-1	Polymyositis / dermatomyositis
Antiphospholipid	APS (thrombosis, pregnancy loss in SLE)

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