The florist has sporotrichosis, which is treated with itraconazole; azole antifungal drugs function by inhibiting ergosterol synthesis.
Itraconazole is an antifungal that functions by inhibiting the formation of ergosterol, found in the fungal cell membrane, through blocking fungal CYP450 3A. Specifically, itraconazole inhibits 14-alpha-demethylase, a fungal P450 enzyme that converts lanosterol to ergosterol. Itraconazole also inhibits the human CYP450 system, which can cause drug-drug interactions and affect physiologic processes that rely on the CYP system such as testosterone synthesis. This inhibition of testosterone synthesis can lead to gynecomastia and decreased libido. NOTE: Itraconazole requires an acidic gastric environment for absorption, so concomitant use of acid suppression medications will impair absorption of itraconazole.
Tobin and Jih review sporotrichoid lymphocutaneous infections, which are mainly caused by S. schenckii, N. braziliensis, M. marinum, or L. braziliensis. Infection typically begins at the site of inoculation and spreads in an ascending manner along the lymphatic tract. Treatment typically consists of itraconazole for two to three months.
Como and Dismukes review oral azoles. Azoles function by inhibiting the conversion of lanosterol to ergosterol. The reduction in supply of ergosterol alters the fluidity of the fungal cell membrane, leading to increased permeability and decreased cell growth and replication. Other functions of azoles include inhibition of cellular respiration, interaction with cellular phospholipids, and inhibition of yeast transformation to the mycelial form.
Illustration A demonstrates ascending lymphangitis due to S. schenckii.
These medications do not have gynecomastia as a side effect as experienced by this patient.
Answer 2: Amphotericin binds to ergosterol, forming destructive pores in the cell membrane. Adverse side effects include renal toxicity, hypotension, and arrhythmias.
Answer 3: Terbinafine inhibits squalene epoxidase. Adverse side effects include GI upset, rash, headache, and possible hepatoxicity.
Answer 4: Caspofungin inhibits formation of beta glucan. Adverse effects include flushing, GI upset, headache, fever, and rash.
Answer 5: Griseofulvin disrupts microtubule function thus preventing mitosis. Adverse side effects include a disulfiram-like reaction with ethanol, mental confusion, and headaches.
Tobin EH, Jih WW. Sporotrichoid lymphocutaneous infections: etiology, diagnosis and therapy. Am Fam Physician. 2001 Jan 15;63(2):326-32.
PMID:11201697 (Link to Abstract)
omo JA, Dismukes WE. Oral azole drugs as systemic antifungal therapy. N Engl J Med. 1994 Jan 27;330(4):263-72. Review.
PMID:8272088 (Link to Abstract)