Pathology · patient case with 3 questions
Joints, immunosuppression and a sore mouth
demo: 58-year-old female
chief: Painful mouth ulcers that appeared over the last three weeks and are interfering with eating.
history: Seropositive rheumatoid arthritis for eleven years, currently in low disease activity. She was also treated for latent tuberculosis before starting her biologic.
meds: Methotrexate 20 mg weekly with folic acid. Adalimumab (Humira) every other week. She completed a nine-month course of isoniazid last year.
findings: Multiple shallow, painful ulcers on the buccal mucosa and lateral tongue with erythematous halos. No vesicles. Mild pallor of the conjunctivae.
Question 1
Which laboratory test is most important to obtain before continuing her care given the methotrexate and adalimumab combination?
Show answer and explanation
Correct answer: B. Serum creatinine with a complete blood count and liver enzymes
- A. Thyroid function is not affected by methotrexate or adalimumab and is not part of routine monitoring for them.
- B. Correct. Methotrexate is cleared renally, so a rising creatinine causes the drug to accumulate and become toxic. Standard monitoring pairs renal function with a complete blood count, because methotrexate suppresses marrow and causes macrocytic anaemia and neutropenia, and with liver enzymes because of hepatotoxicity.
- C. Amylase relates to pancreatic and salivary pathology and has no role in monitoring either of these agents.
- D. A lipid panel is a cardiovascular risk tool, not a safety monitor for these drugs.
Note: The recall keyed this simply as 'creatinine test.' That is defensible because renal clearance governs methotrexate toxicity, but the real-world panel is creatinine plus CBC plus liver enzymes, and for a patient on a TNF inhibitor also a check for reactivated infection.
Question 2
Her oral ulceration is most likely a direct effect of which agent, and by what mechanism?
Show answer and explanation
Correct answer: D. Methotrexate, through folate antagonism impairing epithelial turnover
- A. Folic acid is given precisely to reduce methotrexate mucosal and marrow toxicity. Deficiency, not supplementation, causes ulceration.
- B. Isoniazid can cause a lupus-like syndrome and peripheral neuropathy, but she completed that course a year ago, so it cannot explain ulcers appearing three weeks ago.
- C. TNF inhibitors increase infection risk and can provoke lupus-like and psoriasiform reactions, but they are not a common direct cause of aphthous-like ulceration in the way methotrexate is.
- D. Correct. Methotrexate inhibits dihydrofolate reductase, starving rapidly dividing cells of the thymidine they need. Oral and gastrointestinal mucosa turn over quickly, so stomatitis and ulceration are among the earliest and most common toxicities. Folic acid supplementation reduces but does not eliminate the risk.
Question 3
What is the principal adverse effect that required monitoring during her isoniazid course?
Show answer and explanation
Correct answer: A. Hepatitis
- A. Correct. Isoniazid hepatotoxicity ranges from asymptomatic transaminase elevation to fulminant hepatitis, and the risk rises with age and alcohol use. Liver enzymes are checked at baseline and periodically. Isoniazid also causes peripheral neuropathy by interfering with pyridoxine, which is why vitamin B6 is co-prescribed.
- B. Ototoxicity, both cochlear and vestibular, is again a streptomycin and aminoglycoside effect.
- C. Orange staining of urine, sweat and tears, which permanently discolours soft contact lenses, is the signature of rifampin.
- D. Nephrotoxicity is a feature of aminoglycosides such as streptomycin, not isoniazid.