Rheumatology and Immunology Practice Questions

Q: A 45-year-old male presented with severe pain in the knee and shoulder joints. A diagnosis of rheumatoid arthritis was made, and the patient was started on methotrexate 15mg weekly. However, after 6 months of methotrexate therapy, recurrent episodes of arthritis continued. The physician wants to add another DMARD that inhibits pyrimidine synthesis by inhibiting the dihydroorotate dehydrogenase enzyme. Which of the following drugs is the physician considering?

Leflunomide. ### Explanation **Correct Answer: C. Leflunomide** **Mechanism of Action:** Leflunomide is a prodrug that is converted into its active metabolite, **A77 1726**. This metabolite acts by inhibiting the mitochondrial enzyme **dihydroorotate dehydrogenase (DHODH)**. This enzyme is critical for the **de novo synthesis of pyrimidines** (specifically UMP). Since activated T-lymphocytes depend on de novo synthesis for proliferation (rather than the salvage pathway), leflunomide effectively arrests the cell cycle in the G1 phase, reducing the inflammatory response in Rheumatoid Arthritis (RA). **Analysis of Incorrect Options:** * **A. Sulfasalazine:** Its exact mechanism in RA is not fully understood but is thought to involve inhibition of NF-ΙB and prostaglandin synthesis [2]. It does not inhibit pyrimidine synthesis. * **B. Infliximab:** This is a chimeric monoclonal antibody that acts as a **TNF-α inhibitor** [3]. It does not interfere with metabolic enzymes. * **C. Abatacept:** This is a fusion protein that acts as a **T-cell costimulation modulator** by binding to CD80/86 on antigen-presenting cells, preventing it from interacting with CD28 on T-cells. **High-Yield Clinical Pearls for NEET-PG:** * **Loading Dose:** Leflunomide has a very long half-life (approx. 2 weeks); hence, a loading dose was traditionally used, though often skipped now to reduce GI side effects. * **Teratogenicity:** It is highly teratogenic (Category X). If a patient wishes to become pregnant, a **Cholestyramine washout** procedure is required to accelerate drug elimination. * **Side Effects:** Hepatotoxicity (monitor LFTs) and alopecia are common [2]. * **Triple Therapy:** In RA, "Triple Therapy" usually refers to the combination of Methotrexate + Sulfasalazine + Hydroxychloroquine. Leflunomide is often used as an alternative to Methotrexate [1] or in combination with it in refractory cases [2].

Q: A 62-year-old male presented to the outpatient department with joint pain. The image shows findings from synovial fluid analysis. Which of the following drugs is used for the permanent treatment of this condition?

Febuxostat. ***Febuxostat*** - **Febuxostat** is a **xanthine oxidase inhibitor** used for **permanent urate-lowering therapy** in gout, particularly when **allopurinol is contraindicated** or not tolerated. - It effectively reduces **serum uric acid levels** below target (<6 mg/dL) for long-term prevention of **recurrent gout attacks** and **tophi formation**. *Colchicine* - **Colchicine** is used only for **acute gout attack management** and **prophylaxis during initiation** of urate-lowering therapy, not for permanent treatment. - It works by **inhibiting neutrophil migration** and **reducing inflammation** but does not lower **serum uric acid levels**. *Allopurinol* - **Allopurinol** is the **first-line urate-lowering therapy** for gout, also a **xanthine oxidase inhibitor** like febuxostat. - While effective for permanent treatment, **febuxostat is preferred** when allopurinol causes **hypersensitivity reactions** or is **contraindicated in renal impairment**. *Dexamethasone* - **Dexamethasone** is a **corticosteroid** used only for **acute gout flare management**, particularly when **NSAIDs or colchicine are contraindicated**. - It provides **anti-inflammatory effects** during acute attacks but has **no role in permanent uric acid control** or gout prevention.

Q: Which of the following is strongly associated with spondyloarthropathies?

HLAB27. **Explanation:** The **Spondyloarthropathies (SpA)** are a group of multisystem inflammatory disorders that share common clinical features and a strong genetic association with **HLA-B27** [1]. **Why HLA-B27 is correct:** HLA-B27 is a Class I Major Histocompatibility Complex (MHC) molecule. It is the strongest known genetic risk factor for the entire SpA group, which includes Ankylosing Spondylitis (AS), Psoriatic Arthritis, Reactive Arthritis, and Enteropathic Arthritis [1]. The association is strongest in **Ankylosing Spondylitis**, where >90% of white patients are HLA-B27 positive [1]. The molecule is thought to contribute to disease pathogenesis through "misfolding" or by presenting "arthritogenic peptides" to T-cells, triggering an autoimmune response. **Analysis of Incorrect Options:** * **HLA-DR3:** Strongly associated with **Systemic Lupus Erythematosus (SLE)**, Sjögren’s syndrome, and Type 1 Diabetes Mellitus [3]. * **HLA-DR4:** Classically associated with **Rheumatoid Arthritis (RA)** and Pemphigus Vulgaris. (Note: HLA-DRB1 alleles are the "shared epitope" in RA). * **HLA-B8:** Associated with Myasthenia Gravis, Graves' disease, and Celiac disease. **High-Yield Clinical Pearls for NEET-PG:** * **Mnemonic for SpA (PEAR):** **P**soriatic arthritis, **E**nteropathic arthritis, **A**nkylosing spondylitis, **R**eactive arthritis [3]. * **Key Features:** Seronegativity (RF negative), Sacroiliitis, Enthesitis (inflammation where tendons/ligaments insert into bone), and Uveitis [1]. * **Bamboo Spine:** A classic radiological finding in advanced Ankylosing Spondylitis due to syndesmophyte formation [2]. * **Schober’s Test:** Used to assess restricted lumbar motion in AS.

Q: All of the following statements about Antiphospholipid Antibody Syndrome (APLS) are true, EXCEPT:

A single titre of anticardiolipin is diagnostic.. **Explanation:** Antiphospholipid Antibody Syndrome (APLS) is a systemic autoimmune disorder characterized by venous or arterial thrombosis and/or pregnancy complications in the presence of persistent antiphospholipid antibodies. **Why Option A is the correct answer (The Exception):** A single positive titer of anticardiolipin (aCL) is **not diagnostic**. According to the Revised Sapporo Criteria, laboratory diagnosis requires the presence of antibodies (aCL, Anti-̢2 glycoprotein I, or Lupus Anticoagulant) on **two or more occasions, at least 12 weeks apart**. This is to ensure the antibodies are persistent and not transiently elevated due to infections or medications. **Analysis of other options:** * **Option B:** Recurrent fetal loss (especially after 10 weeks of gestation) is a hallmark clinical criterion for APLS due to placental infarction and thrombosis. * **Option C:** APLS can cause pulmonary hypertension, most commonly via **Chronic Thromboembolic Pulmonary Hypertension (CTEPH)** resulting from recurrent pulmonary emboli. * **Option D:** Long-term anticoagulation with **Warfarin** (Vitamin K Antagonist) is the standard of care for secondary prevention of thrombotic events in APLS. (Note: DOACs are generally avoided in "triple-positive" APLS patients). **High-Yield Clinical Pearls for NEET-PG:** * **The "APLS Paradox":** It causes a **prolonged aPTT** *in vitro* (due to interference with phospholipids in the assay), but causes **thrombosis** *in vivo*. * **False Positive VDRL:** Patients often show a false-positive syphilis test because the VDRL reagent contains cardiolipin. * **Catastrophic APLS (Asherson’s Syndrome):** A rare, life-threatening form involving multiorgan failure due to small vessel occlusion. * **Treatment in Pregnancy:** Warfarin is teratogenic; therefore, pregnant women are treated with **Low Molecular Weight Heparin (LMWH) and Low-dose Aspirin**.

Q: Shrinking lung/kidney is seen in which of the following conditions?

SLE. **Explanation:** **1. Why SLE is the correct answer:** **Shrinking Lung Syndrome (SLS)** is a rare but characteristic complication of **Systemic Lupus Erythematosus (SLE)**. It is characterized by progressive dyspnea, reduced lung volumes (restrictive pattern on PFTs), and an elevated diaphragm on chest X-ray, notably *without* significant interstitial fibrosis or pleural disease [1]. The underlying pathophysiology is attributed to **diaphragmatic dysfunction** or weakness, likely due to a chronic phrenic neuropathy or primary myopathy [1]. Regarding the **"Shrinking Kidney,"** chronic lupus nephritis leads to progressive scarring and atrophy, resulting in small, echogenic kidneys on ultrasound—a hallmark of end-stage renal disease (ESRD) in SLE patients. **2. Why other options are incorrect:** * **Scleroderma (Systemic Sclerosis):** Typically causes **Interstitial Lung Disease (ILD)** and pulmonary hypertension. While it causes renal crisis, it does not classically present with the "shrinking lung" clinical triad [1]. * **Rheumatoid Arthritis:** Primarily associated with ILD (UIP pattern), pleural effusions, and Caplan syndrome, rather than diaphragmatic dysfunction. * **Dermatomyositis:** Frequently associated with rapidly progressive ILD (especially with anti-MDA5 antibodies) and respiratory muscle weakness, but "Shrinking Lung Syndrome" is a term specifically reserved for SLE in medical literature. **3. High-Yield Clinical Pearls for NEET-PG:** * **SLS Triad:** Dyspnea + Reduced lung volumes + Elevated hemidiaphragms [1]. * **PFT in SLS:** Shows a **Restrictive pattern** (decreased FVC and TLC) but a **normal DLCO** (when adjusted for lung volume), which helps differentiate it from ILD. * **Libman-Sacks Endocarditis:** Another high-yield SLE-specific finding (sterile vegetations on both sides of valves). * **Most common lung finding in SLE:** Pleurisy/Pleural effusion (not SLS) [1].

Q: A young female presents with diminished pulses in the upper limb and hypertension. What is the most likely diagnosis?

Takayasu Arteritis. ### Explanation **Correct Answer: A. Takayasu Arteritis** [1] **Why it is correct:** Takayasu Arteritis (TA) is a chronic, large-vessel vasculitis that primarily affects the **aorta and its main branches**. It is most common in **young females** (usually <40 years). The inflammation leads to arterial stenosis, which results in the classic clinical triad: 1. **Diminished or absent pulses** (hence the name "Pulseless Disease"). 2. **Blood pressure discrepancy** between the arms. 3. **Hypertension**, which is typically **renovascular** in origin due to narrowing of the renal arteries. **Why the other options are incorrect:** * **B. Coarctation of Aorta:** While it causes hypertension and pulse disparity, it typically presents with diminished pulses in the **lower limbs** (radio-femoral delay) rather than the upper limbs. * **C. Giant Cell Arteritis (GCA):** Although also a large-vessel vasculitis, GCA almost exclusively affects patients **older than 50**. It typically involves the temporal artery, presenting with headaches and jaw claudication. * **D. Polyarteritis Nodosa (PAN):** This is a **medium-vessel** vasculitis. While it causes hypertension (renal artery involvement), it does not typically cause the loss of peripheral pulses in the upper limbs and is associated with Hepatitis B. **High-Yield Clinical Pearls for NEET-PG:** * **Gold Standard Investigation:** Digital Subtraction Angiography (shows "string of pearls" or tapered narrowing). * **Classification Criteria:** Age 10 mmHg difference in systolic BP between arms, and bruits over the aorta/subclavian arteries. * **Most common involved artery:** Subclavian artery. * **Treatment:** Glucocorticoids are the first-line therapy.

Q: All of the following are true regarding Anti-phospholipid Syndrome EXCEPT:

It is associated with recurrent placental hemorrhage.. **Explanation:** Antiphospholipid Syndrome (APS) is an autoimmune prothrombotic state characterized by the presence of antiphospholipid antibodies (aPL). **Why Option C is the correct answer (The Exception):** APS is fundamentally a **prothrombotic** condition, not a hemorrhagic one. The pathophysiology involves the activation of coagulation cascades and inhibition of fibrinolysis, leading to **thrombosis** of the uteroplacental vessels. This causes placental infarction, fetal growth restriction, and fetal loss. It is **not** associated with recurrent placental hemorrhage; rather, it causes "white infarcts" due to ischemia. **Analysis of other options:** * **Option A:** APS can be primary or secondary. Secondary APS is most commonly associated with **Systemic Lupus Erythematosus (SLE)**. Approximately 30-40% of SLE patients test positive for aPL. * **Option B:** The hallmark of obstetric APS is **thrombosis of the spiral arteries** and uteroplacental vessels, leading to placental insufficiency. * **Option C:** Anti-cardiolipin antibodies can cross-react with the cardiolipin antigen used in the **VDRL/RPR tests**, leading to a **Biological False Positive (BFP)** result for syphilis. **NEET-PG High-Yield Pearls:** * **Sapporo Criteria:** Diagnosis requires 1 Clinical (Vascular thrombosis or Pregnancy morbidity) + 1 Laboratory criterion (Lupus anticoagulant, Anti-cardiolipin IgG/IgM, or Anti-β2-glycoprotein I). * **Pregnancy Morbidity:** Defined as ≥3 unexplained abortions ( 10 weeks), or ≥1 preterm birth (<34 weeks) due to eclampsia/placental insufficiency. * **Management:** Low-dose Aspirin (LDA) + Low Molecular Weight Heparin (LMWH) is the gold standard during pregnancy. Warfarin is contraindicated (teratogenic).

Q: Which of the following HLA antigens is associated with Sjögren's syndrome?

Sjögren's syndrome. The association between Human Leukocyte Antigens (HLA) and autoimmune diseases is a high-yield topic for NEET-PG. **Sjögren’s syndrome** is strongly associated with **HLA-DR3** and **HLA-B8**. In primary Sjögren’s syndrome, these genetic markers are linked to the production of specific autoantibodies, namely **Anti-Ro (SS-A)** and **Anti-La (SS-B)** [1]. **Analysis of Options:** * **Sjögren’s Syndrome (Correct):** The primary HLA associations are **HLA-DR3** and **HLA-DQ2**. These alleles are often part of a conserved haplotype (A1-B8-DR3) seen in several autoimmune conditions. * **Systemic Lupus Erythematosus (SLE):** While SLE also shares an association with **HLA-DR2** and **HLA-DR3**, the question specifically targets the classic association for Sjögren's in this context [1]. * **Scleroderma (Systemic Sclerosis):** This is more commonly associated with **HLA-DR1, DR5, and DQB1**, though the associations are weaker than in other rheumatological conditions. * **Ankylosing Spondylitis:** This is the classic "textbook" association with **HLA-B27** (seen in >90% of patients). It belongs to the Seronegative Spondyloarthropathies group. **NEET-PG Clinical Pearls:** * **Schirmer’s Test:** Used to quantify tear production (Positive if <5 mm in 5 mins). * **Extraglandular Manifestation:** The most serious complication of Sjögren’s is a 40-fold increased risk of **B-cell MALT Lymphoma**. * **Diagnostic Marker:** Anti-Ro/SS-A is the most specific initial antibody; however, a **minor salivary gland biopsy** (showing lymphocytic focus score ≥1) remains the gold standard [1].

Question 1

A 45-year-old male presented with severe pain in the knee and shoulder joints. A diagnosis of rheumatoid arthritis was made, and the patient was started on methotrexate 15mg weekly. However, after 6 months of methotrexate therapy, recurrent episodes of arthritis continued. The physician wants to add another DMARD that inhibits pyrimidine synthesis by inhibiting the dihydroorotate dehydrogenase enzyme. Which of the following drugs is the physician considering?

Accepted Answer

Leflunomide

Answer

Sulfasalazine

Answer

Infliximab

Answer

Abatacept

Question 2

A 62-year-old male presented to the outpatient department with joint pain. The image shows findings from synovial fluid analysis. Which of the following drugs is used for the permanent treatment of this condition?

Accepted Answer

Febuxostat

Answer

Colchicine

Answer

Allopurinol

Answer

Dexamethasone

Question 3

Which of the following is strongly associated with spondyloarthropathies?

Accepted Answer

HLAB27

Answer

HLADR3

Answer

HLADR4W

Answer

HLAB8

Question 4

All of the following statements about Antiphospholipid Antibody Syndrome (APLS) are true, EXCEPT:

Accepted Answer

A single titre of anticardiolipin is diagnostic.

Answer

It commonly presents with recurrent fetal loss.

Answer

It may cause pulmonary hypertension.

Answer

Warfarin is given as treatment.

Question 5

All of the following are included in the Sydney revision of the Sapporo criteria for Antiphospholipid antibody syndrome EXCEPT:

Accepted Answer

Livedo reticularis

Answer

Vascular thrombosis

Answer

3 or more unexplained spontaneous abortions

Answer

Lupus anticoagulant in plasma

Question 6

Shrinking lung/kidney is seen in which of the following conditions?

Accepted Answer

SLE

Answer

Scleroderma

Answer

Rheumatoid arthritis

Answer

Dermatomyositis

Question 7

A young female presents with diminished pulses in the upper limb and hypertension. What is the most likely diagnosis?

Accepted Answer

Takayasu Arteritis

Answer

Coarctation of Aorta

Answer

Giant Cell Arteritis

Answer

Polyarteritis Nodosa

Question 8

All of the following are true regarding Anti-phospholipid Syndrome EXCEPT:

Accepted Answer

It is associated with recurrent placental hemorrhage.

Answer

It is associated with SLE.

Answer

It is associated with thrombosis of uteroplacental vessels.

Answer

It can give false positive results in syphilis.

Question 9

Which of the following HLA antigens is associated with Sjögren's syndrome?

Accepted Answer

Sjögren's syndrome

Answer

Systemic lupus erythematosus

Answer

Scleroderma

Answer

Ankylosing spondylosis

Question 10

A 30-year-old woman with Sjogren syndrome presents with a 24-hour history of a purpuric skin rash. Which of the following is the most likely diagnosis?

Accepted Answer

Hypersensitivity vasculitis

Answer

Buerger disease

Answer

Giant cell granulomatous arteritis

Answer

Wegener granulomatosis

Rheumatology and Immunology — MCQs

Rheumatology and Immunology — MCQs

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