A 68 Y/O M with a Hx of recurrent tophaceous gout, currently stable on medication. He was recently diagnosed with coronary artery disease following an NSTEMI and is initiated on low-dose aspirin for 2° prevention. His renal function is normal. He is concerned about how aspirin might affect his gout management. Initiation of low-dose aspirin in this patient is most likely to directly antagonize the therapeutic effect of which of the following medications by interfering with its renal tubular secretion mechanism?

• Allopurinol

• Febuxostat

• Probenecid

• Colchicine

• Prednisone

Answer explanation

Probenecid is a uricosuric agent that works by inhibiting the reabsorption of uric acid in the proximal renal tubules, thereby promoting its excretion. Low-dose aspirin competes for the same organic anion transport (OAT) system in the renal tubules, which antagonizes the uricosuric effect of probenecid, leading to ↑ serum uric acid and potential treatment failure.

A 34 Y/O F, a landscaper, c/o an intensely pruritic, erythematous, vesicular rash on her forearms and hands x3D. She reports working in a wooded area 2 days prior to rash onset. O/E, there are linear streaks of erythematous papules and vesicles on a swollen, red base over the dorsal aspects of both hands and forearms. Some vesicles are weeping clear fluid. Vitals: stable. What is the most appropriate initial management for this patient's condition?

• Oral acyclovir

• High-potency topical corticosteroids

• Intravenous ceftriaxone

• Griseofulvin therapy

• Topical mupirocin ointment

Answer explanation

The patient presents with a classic case of allergic contact dermatitis, most likely from poison ivy (urushiol-induced), a Type IV hypersensitivity reaction. The linear arrangement of vesicular lesions is a hallmark sign. The primary goal of initial management is to control the inflammation and pruritus. High-potency topical corticosteroids (e.g., clobetasol) are the first-line treatment for localized, severe allergic contact dermatitis. They effectively reduce the local inflammatory response and alleviate symptoms.

A 45 Y/O M presents with a 2-week Hx of cough, SOB, and hemoptysis. He also reports recurrent sinusitis. O/E: BP 150/95, HR 105, RR 22, T 38.1°C. Ix: Serum creatinine is 3.2 mg/dL (was 0.9 mg/dL 6 months ago). Urinalysis shows dysmorphic RBCs and red cell casts. A CXR reveals multiple bilateral nodules, some with cavitation. A renal biopsy confirms pauci-immune, focal necrotizing glomerulonephritis. Which of the following serological markers is most specifically associated with this patient's most likely diagnosis?

• Anti-myeloperoxidase (p-ANCA)

• Anti-glomerular basement membrane (Anti-GBM)

• Antinuclear antibody (ANA)

• Anti-proteinase 3 (c-ANCA)

• Anti-double-stranded DNA (Anti-dsDNA)

Answer explanation

This patient presents with a classic triad of upper respiratory tract symptoms (sinusitis), lower respiratory tract disease (nodules, hemoptysis), and rapidly progressive glomerulonephritis (pauci-immune GN), which is highly characteristic of Granulomatosis with Polyangiitis (GPA). The most specific serological marker for GPA is Anti-proteinase 3 (c-ANCA), found in approximately 80-90% of patients with active, systemic disease.

A. Anti-myeloperoxidase (p-ANCA) is incorrect as it is more commonly associated with Microscopic Polyangiitis (MPA) and Eosinophilic Granulomatosis with Polyangiitis (EGPA), which are differentials but less likely given the prominent sinusitis and cavitating nodules.

A 34 Y/O F with a known Hx of SLE (on hydroxychloroquine and low-dose prednisone) presents to the ED with a 24-hour Hx of acute confusion, headache, and a new-onset focal seizure. O/E: T=38.1°C, BP=150/95 mmHg, HR=105/min. She is disoriented to time and place with R-sided hemiparesis (3/5 power). Initial Ix show: ↓C3/C4, ↑anti-dsDNA titers. An urgent MRI brain reveals multiple, bilateral, small ischemic infarcts in different vascular territories. What is the most definitive Ix to establish the diagnosis?

• Lumbar puncture and CSF analysis

• Electroencephalogram (EEG)

• MR angiography of cerebral vessels

• Brain biopsy

• PET scan of the brain

Answer explanation

 Brain biopsy is the gold standard for definitively diagnosing CNS vasculitis. It provides direct histological evidence of vessel wall inflammation, which is crucial as imaging findings can be non-specific and mimicked by other conditions like infection, coagulopathy (e.g., antiphospholipid syndrome), or embolic events.

A 34 Y/O F with a known Dx of SLE presents with a 4-week Hx of progressive muscle weakness. She reports significant difficulty getting up from a chair and combing her hair. She is currently on hydroxychloroquine for cutaneous and joint symptoms. O/E: Vital signs are stable. Proximal muscle power is 3/5 in the upper and lower extremities. Ix: Creatine Kinase (CK) is significantly elevated at 3500 U/L (N: 22-198). Urinalysis is bland. What is the most appropriate initial management for her current condition?

• Increase dose of hydroxychloroquine

• Initiate high-dose oral prednisone

• Start IV immunoglobulin (IVIG)

• Add methotrexate

• Prescribe a course of NSAIDs

Answer explanation

The patient is experiencing an acute SLE flare manifesting as myositis (inflammatory muscle disease), confirmed by the clinical finding of proximal weakness and a markedly elevated CK. The first-line and most appropriate initial treatment for a moderate-to-severe SLE flare with organ involvement (like myositis) is systemic corticosteroids (e.g., prednisone 1 mg/kg/day) to rapidly control inflammation.

A 34 Y/O M presents with a 3-month Hx of pruritic, erythematous plaques with a silvery scale on his extensor elbows, lower back, and in the R) axilla. Total body surface area (BSA) affected is ~10%. O/E, well-demarcated plaques are noted. Linear plaques are seen along a recent scratch mark on his forearm (Koebner phenomenon). The clinical Dx is plaque psoriasis, but the patient requests a confirmatory test. A skin biopsy is performed. Which of the following histopathological findings is most specific for psoriasis?

• Spongiosis and eosinophilic infiltrate

• Acantholysis with intraepidermal bullae

• Liquefactive degeneration of the basal layer

• Munro's microabscesses

• Hypergranulosis with wedge-shaped acanthosis

Answer explanation

 Munro's microabscesses are collections of neutrophils in the stratum corneum. This finding, along with parakeratosis (retention of nuclei in the stratum corneum) and acanthosis (epidermal hyperplasia), is a classic and highly specific histopathological hallmark of psoriasis vulgaris.

An 8 Y/O F is brought to the clinic c/o severe pain in her R knee that started yesterday. Today, the R knee feels better, but she now has significant pain and swelling in her L ankle. Hx reveals a sore throat approx. 3 weeks ago, which resolved without Rx. O/E, T=38.4°C, HR=110 bpm, BP=100/65 mmHg. Her L ankle is erythematous, warm, and tender. Her R knee shows minimal tenderness. Cardiac auscultation reveals a new holosystolic murmur at the apex radiating to the axilla. ECG shows a prolonged PR interval. Which of the following investigations is most crucial to support the suspected diagnosis?

• Antinuclear antibody (ANA)

• Blood culture

• Anti-streptolysin O (ASO) titer

• Synovial fluid analysis

• Serum uric acid

Answer explanation

The scenerio strongly suggests Acute Rheumatic Fever (ARF) based on the modified Jones criteria: migratory polyarthritis (major), carditis (new murmur, major), fever (minor), and prolonged PR interval (minor), following a recent sore throat. An elevated ASO titer provides crucial evidence of a preceding Group A Streptococcus (GAS) infection, which is a cornerstone for diagnosing ARF.

A 35 Y/O M from a TB-endemic region presents with a 4-month Hx of progressively worsening R knee pain and swelling. The onset was insidious with no Hx of trauma. He reports occasional night sweats but no cough. O/E: BP 120/80, HR 88, T 37.5°C. There is a moderate effusion in the R knee with diffuse tenderness and restricted ROM. The joint is not erythematous or markedly warm. Ix: WBC 9.5x10⁹/L, ESR 60 mm/hr. X-ray of the knee reveals periarticular demineralization and subtle marginal bone erosions. What is the most likely Dx?

• Pyogenic septic arthritis

• Gouty arthritis

• Tuberculous arthritis

• Rheumatoid arthritis

• Osteoarthritis

Answer explanation

The vignette describes a classic presentation of TB arthritis: a chronic, progressive, and insidious monoarthritis (4-month Hx). The patient's origin from an endemic region, presence of constitutional symptoms (night sweats), and elevated ESR are highly suggestive. The physical finding of a "cold" abscess (effusion without significant warmth or erythema) and X-ray findings of periarticular demineralization (osteoporosis) and erosions are characteristic.

A 10 Y/O F is brought to the clinic c/o progressive muscle weakness over 3 months, making it difficult to climb stairs & comb her hair. Hx reveals a purplish rash over her eyelids & red, scaly papules on her knuckles. O/E: Symmetrical proximal muscle weakness (4/5 power). Violaceous discoloration of the eyelids (heliotrope rash) & erythematous papules over the metacarpophalangeal joints (Gottron's papules) are noted. Ix: ↑ CK, ↑ aldolase, & positive anti-Jo-1 antibodies. An X-ray of the thighs reveals subcutaneous sheet-like calcifications. What is the most likely diagnosis?

• Systemic Lupus Erythematosus (SLE)

• Scleroderma

• Dermatomyositis

• Polymyositis

• Juvenile Idiopathic Arthritis (JIA)

Answer explanation

The combination of progressive proximal muscle weakness, pathognomonic skin findings (heliotrope rash and Gottron's papules), elevated muscle enzymes (CK, aldolase), and the presence of dystrophic calcification (calcinosis cutis) is classic for Dermatomyositis, particularly the juvenile form.

A 25 Y/O F presents to the ED with a 1-week Hx of persistent headaches and recent personality changes, including irritability and confusion. Her partner notes she took aspirin for her headache last week with no relief. O/E, she is afebrile with normal vital signs. There is a prominent erythematous, macular rash over her cheeks and the bridge of her nose. Neurological examination is significant for mild cognitive slowing but no focal deficits.

• Reye's Syndrome

• Drug-induced Lupus

• Systemic Lupus Erythematosus (SLE)

• Viral Meningoencephalitis

• Primary CNS Vasculitis

Answer explanation

The patient is a young female presenting with a classic triad for SLE: constitutional/neurological symptoms (headache, personality changes), cutaneous findings (malar "butterfly" rash), and systemic inflammation.[1][2][3] Neuropsychiatric symptoms are a known and serious manifestation of SLE (NPSLE), often related to CNS vasculitis.[4][5] This diagnosis unifies all the clinical findings.