ABD - American Board of Dermatology Dermatologic Pharmacology Questions and Answers 1 — Questions and Answers
Question 1: A 58-year-old male with extensive plaque psoriasis is being managed with weekly low-dose methotrexate. To mitigate the risk of hepatotoxicity, which of the following is the most crucial long-term monitoring strategy according to consensus guidelines?
- Annual liver biopsy regardless of other findings
- Monthly assessment of serum aminotransferases and periodic procollagen III aminopeptide (PІІІNP) levels (Correct answer)
- Bi-annual abdominal ultrasound to assess for hepatic steatosis
- Weekly complete blood count with differential
Correct answer: Monthly assessment of serum aminotransferases and periodic procollagen III aminopeptide (PІІІNP) levels
Consensus guidelines for monitoring methotrexate-induced hepatotoxicity in psoriasis focus on regular laboratory surveillance. This includes frequent monitoring of liver transaminases (e.g., ALT) and, in many guidelines, periodic assessment of PIIINP, a marker of fibrogenesis. Liver biopsy is reserved for patients with persistently elevated liver enzymes or PIIINP levels, or those with multiple risk factors for liver disease. Abdominal ultrasound is not a primary screening tool for fibrosis. While a weekly CBC is essential for monitoring for myelosuppression, it does not assess for hepatotoxicity.
Question 2: A 45-year-old patient with onychomycosis is prescribed a course of oral itraconazole. The patient also takes atorvastatin for hyperlipidemia. This drug combination significantly increases the risk for which of the following adverse events?
- Serotonin syndrome
- QT prolongation and Torsades de Pointes
- Rhabdomyolysis (Correct answer)
- Aplastic anemia
Correct answer: Rhabdomyolysis
Itraconazole is a potent inhibitor of the cytochrome P450 3A4 (CYP3A4) enzyme system. Atorvastatin, lovastatin, and simvastatin are metabolized by CYP3A4. Co-administration of itraconazole leads to significantly elevated plasma concentrations of the statin, which dramatically increases the risk of myopathy and rhabdomyolysis. The other options are not characteristic interactions for this specific drug pair.
Question 3: A 66-year-old male with dermatitis herpetiformis is started on dapsone. Before initiating therapy, which laboratory test is mandatory to prevent a severe, dose-related adverse reaction?
- HLA-B*57:01 allele testing
- Thiopurine methyltransferase (TPMT) activity
- Serum creatinine and BUN
- Glucose-6-phosphate dehydrogenase (G6PD) level (Correct answer)
Correct answer: Glucose-6-phosphate dehydrogenase (G6PD) level
Dapsone can induce oxidative stress on red blood cells, leading to hemolysis. Patients with a G6PD deficiency have a reduced ability to protect their red blood cells from this oxidative damage, placing them at high risk for severe, dose-dependent hemolytic anemia upon starting dapsone. Therefore, screening for G6PD deficiency is required before initiating therapy.
Question 4: Tazarotene is a third-generation topical retinoid used for acne and psoriasis. Its therapeutic effect is primarily mediated through selective binding to which of the following receptors?
- Retinoid X receptors (RXR-α and RXR-γ)
- Retinoic acid receptors (RAR-β and RAR-γ) (Correct answer)
- Peroxisome proliferator-activated receptor gamma (PPAR-γ)
- Vitamin D receptor (VDR)
Correct answer: Retinoic acid receptors (RAR-β and RAR-γ)
Tazarotene is a prodrug that is converted to its active form, tazarotenic acid. Tazarotenic acid exerts its effects by selectively binding to retinoic acid receptors (RARs), with a particular affinity for RAR-β and RAR-γ. It has little to no affinity for retinoid X receptors (RXRs). This receptor selectivity is thought to contribute to its specific clinical effects and side-effect profile.
Question 5: A dermatologist prescribes topical 5-fluorouracil (5-FU) cream for a patient with multiple actinic keratoses on the face. What is the primary mechanism of action of this agent?
- It acts as a Toll-like receptor 7 (TLR7) agonist, inducing a local immune response.
- It inhibits dihydrofolate reductase, blocking the synthesis of purines.
- It functions as a pyrimidine analog that inhibits thymidylate synthase, disrupting DNA synthesis. (Correct answer)
- It binds to tubulin, preventing microtubule formation and arresting cells in metaphase.
Correct answer: It functions as a pyrimidine analog that inhibits thymidylate synthase, disrupting DNA synthesis.
5-fluorouracil is a pyrimidine analog that, once converted to its active metabolite fluorodeoxyuridine monophosphate (FdUMP), forms a stable complex with the enzyme thymidylate synthase. This action blocks the synthesis of thymidine, a necessary component of DNA, leading to cell death in rapidly proliferating cells such as those in actinic keratoses.
Question 6: The FDA has issued a boxed warning for topical calcineurin inhibitors, such as tacrolimus and pimecrolimus. What is the primary concern cited in this warning?
- A high risk of systemic absorption leading to acute renal failure.
- The potential for severe cutaneous atrophy and striae formation with long-term use.
- A theoretical risk of malignancy, including skin cancer and lymphoma, although a causal link has not been established. (Correct answer)
- The development of tachyphylaxis, rendering the medication ineffective after several months of use.
Correct answer: A theoretical risk of malignancy, including skin cancer and lymphoma, although a causal link has not been established.
The boxed warning for topical calcineurin inhibitors (TCIs) states that although a causal relationship has not been definitively established, rare cases of malignancy (e.g., skin cancer and lymphoma) have been reported in patients treated with TCIs. This warning was based largely on data from systemic use in transplant patients and animal studies, and its application to topical use remains controversial.
ABD - American Board of Dermatology Dermatologic Pharmacology Questions and Answers 1
A 58-year-old male with extensive plaque psoriasis is being managed with weekly low-dose methotrexate.
To mitigate the risk of hepatotoxicity, which of the following is the most crucial long-term monitoring strategy according to consensus guidelines?