What is the recommended treatment for Majocchi’s granuloma and how should therapy be modified in patients with hepatic impairment?

Majocchi's Granuloma: Treatment Recommendations

First-Line Treatment

Oral terbinafine 250 mg once daily is the preferred systemic antifungal for Majocchi's granuloma, continued until complete clinical resolution, typically requiring 4-8 weeks of therapy. 1, 2

• Terbinafine is the most frequently utilized agent in clinical practice, achieving clinical resolution in 96.6% of cases with a median treatment duration of 31.5 days 1
• This agent is preferred due to its superior efficacy, favorable safety profile, and fungicidal activity against dermatophytes, particularly Trichophyton rubrum (the most common causative organism) 2
• Treatment must be continued until lesions are completely resolved—topical agents alone are insufficient due to the deep dermal and follicular location of infection 2

Alternative Systemic Options

Itraconazole pulse therapy (200 mg twice daily for 1 week, repeated after 2-week intervals) represents an effective alternative, with most patients achieving cure after 2-3 pulses. 3

• Seven patients treated with itraconazole pulse therapy achieved clinical and mycological cure: one patient after one pulse, three after two pulses, and three after three pulses 3
• Almost complete cure was observed before the second pulse in patients requiring multiple cycles, with full resolution within 2 weeks of completion 3
• Itraconazole remains detectable in tissue for months after discontinuation, providing sustained antifungal activity 3

For refractory cases failing terbinafine or itraconazole, voriconazole should be considered, particularly when bacterial superinfection is suspected. 4

• One case report demonstrated complete resolution after approximately 4 months of voriconazole treatment in a patient who failed both itraconazole and terbinafine 4
• Consider bacterial culture if lesions show purulent drainage or fail to respond to standard antifungal therapy, as mixed infections with organisms like Klebsiella pneumoniae can occur 4

Modifications for Hepatic Impairment

Terbinafine is contraindicated in patients with active or chronic liver disease (Child-Pugh C) and should be used with extreme caution in mild-to-moderate hepatic impairment (Child-Pugh A/B). 5, 6, 7

Pre-Treatment Requirements in Hepatic Impairment:

• Obtain baseline liver function tests (ALT, AST) and complete blood count before initiating terbinafine 6, 7
• Terbinafine undergoes biliary excretion as the main route of elimination, making hepatic function critical 5
• No dose adjustment is required for Child-Pugh A/B, but vigilant monitoring is mandatory 5

Monitoring During Treatment:

• Repeat liver function tests if the patient develops symptoms suggestive of hepatotoxicity (anorexia, nausea, vomiting, jaundice, dark urine, pale stools) 7
• Monitor for hepatitis prodromal syndrome, which necessitates immediate drug discontinuation 5
• Patients with pre-existing deranged liver function tests require monitoring throughout treatment 7

Alternative Agents for Severe Hepatic Impairment:

• Itraconazole pulse therapy may be preferred in patients with hepatic compromise, as intermittent dosing reduces cumulative drug exposure 3
• Consider fluconazole 450 mg weekly for at least 6 months as a third-line option, though it is less effective than terbinafine or itraconazole 7
• Growth factors (G-CSF, GM-CSF) may be needed if hematologic adverse events occur, particularly in patients with compromised hepatic synthetic function 5

Critical Clinical Pearls

Common pitfall: Misdiagnosis due to prior topical corticosteroid use, which is the most common predisposing factor (55% of cases) and can mask typical dermatophyte features. 2

• Immunosuppressant and topical corticosteroid use are common prior to MG development 1
• Always obtain histopathological confirmation with fungal culture before initiating prolonged systemic therapy 1, 2
• Potassium hydroxide (KOH) examination should be performed before any topical steroid application for erythematous squamous dermatoses 2

The lower extremities are the most common site historically, but facial involvement has predominated in the past 5 years, requiring heightened clinical suspicion in atypical locations. 2

Adjunctive topical antifungals (e.g., luliconazole cream twice daily) can be added to systemic therapy but should never be used as monotherapy. 8