Three Cases of Recalcitrant Pediatric Tinea Capitis Successfully Treated with Griseofulvin

Tinea capitis (TC) is a superficial fungal infection of the hair and scalp caused by dermatophytes. Microsporum canis is the most prevalent causative pathogen in some European and Asian countries, including Korea, whereas Trichophyton tonsurans remains the main causative species in the United States, Canada, and Central America1, 2. TC typically presents as single or multiple localized alopecic patches with scales or black dots, predominantly in prepubertal children1, 2.

Systemic antifungal agents are the mainstay treatments for TC, and topical antifungal agents are used only as adjunctive treatments because they do not penetrate the hair follicles3, 4. Common oral antifungal agents for TC include griseofulvin, terbinafine, itraconazole, and fluconazole. The therapeutic responses to these antifungal drugs may vary depending on the causative species, and treatment failure can occur for several reasons, including poor compliance, suboptimal drug absorption, relative insensitivity of the organism, and drug resistance3. Although dermatophytosis resistant to treatment have been increasingly encountered, recalcitrant TC cases have rarely been reported5, 6. Herein, we report three pediatric cases of TC caused by M. canis, which showed unsatisfactory clinical and mycological response to oral terbinafine or itraconazole and responded well to oral griseofulvin.

The study was approved by the Institutional Review Board of Jeonbuk National University (IRB No. 2021-11-055). We received the consent form about publishing all photographic materials from patient’s parents.

Case 1

A 4-year-old healthy boy presented with a 3-month history of a pruritic bald patch on his vertex and occipital scalp. He had no history of contact with animals and had no other notable family or medical history. Before presentation, he had already taken oral terbinafine (250 mg/day) for 8 weeks. Physical examination revealed erythematous, yellow scales and crusted plaques and pustules, highly suggestive of kerion celsi (Fig. 1A). Potassium hydroxide (KOH) examination revealed numerous hyphae and spores engulfing the hair shaft. On the fungal culture, deep yellow and orange pigments on the reverse of the colony were observed, identified as M. canis through polymerase chain reaction (PCR). Routine laboratory findings were normal.

Fig. 1
Clinical course of case 1. At the first visit, which occurred after 8 weeks of oral terbinafine treatment (A), an inflammatory bald patch with a boggy plaque showing pustules and thick crusts was observed on the vertex and occipital scalp. After 4 weeks (B) and 6 weeks (C) of treatment with oral itraconazole, modest clinical improvement was seen with remaining inflammatory erythema and pustules. After 6 weeks (D) and 10 weeks (E) of treatment with oral griseofulvin, the skin lesion showed further improvement with hair regrowth. After 14 weeks of griseofulvin treatment (F), the skin lesion showed complete resolution.

• Click for larger image
• Download as PowerPoint slide

At the initial visit, the treatment regimen was changed to a 4-week course of oral itraconazole (95 mg/day) with ciclopirox shampoo and topical flutrimazole. However, it resulted in modest clinical improvement. Although the yellowish crusts disappeared, the erythematous bald patches with numerous follicular pustules persisted without mycological cure (Fig. 1B). Despite an additional 2-week course of itraconazole, the skin lesions remained largely unchanged with positive KOH findings (Fig. 1C). Therefore, we switched oral itraconazole to griseofulvin (250 mg/day), which produced a rapid clinical response within 2 weeks and significant clinical improvement with hair regrowth at 6 weeks (Fig. 1D). After 10 weeks of griseofulvin treatment, the skin lesions had almost disappeared and remarkable hair regrowth was observed (Fig. 1E). During 6 months of follow-up after oral griseofulvin administration, clinical improvement and mycological cure were achieved without any relevant adverse effects (Fig. 1F).

Case 2

A 3-year-old healthy girl presented with a 2-month history of pruritic scaly bald patches on her vertex and parietal scalp. She had no history of contact with animals. Her family and medical histories were unremarkable. Her previous treatment included 3 weeks of oral terbinafine (62.5 mg/day). Physical examination revealed well-circumscribed hairless patches with severe scales and yellowish discharge (Fig. 2A). The scalp hairs and skin scales were positive for hyphae on KOH examination. M. canis was identified on fungal culture and confirmed by PCR. Routine laboratory findings were normal.

Fig. 2
Clinical course of case 2. At the first examination (A), a localized bald patch completely covered by severe scales was observed despite 3 weeks of treatment with oral terbinafine. After a total of 7 weeks of terbinafine treatment (B), slight clinical improvement was observed. After 6 weeks of itraconazole administration (C), only the scales markedly disappeared, but the inflammatory erythematous bald patch with numerous broken hairs remained. After 4 weeks (D) and 12 weeks (E) of oral griseofulvin treatment, apparent clinical improvement with hair regrowth was observed. After 6 months from the first visit (F), the skin lesion showed complete resolution with remarkable hair regrowth.

• Click for larger image
• Download as PowerPoint slide

She was prescribed an additional 4 weeks of oral terbinafine (62.5 mg/day) with ciclopirox olamine shampoo and topical isoconazole. However, the 7-week course of oral terbinafine provided slight clinical improvement. Although overlying scales were reduced, erythematous crusted patches with severe itching persisted on the scalp (Fig. 2B). Moreover, the hair shafts remained positive on KOH examination. The oral antifungal treatment regimen was changed to itraconazole (60 mg/day), which also resulted in an unsatisfactory clinical response with positive KOH findings. Despite the 6-week course of itraconazole, an erythematous bald patch with numerous broken hairs persisted on the scalp (Fig. 2C). After switching to 4 weeks of oral griseofulvin (125 mg/day), the scalp lesion rapidly improved with hair regrowth (Fig. 2D). On completion of 3 months of griseofulvin, significant clinical improvement and mycological cure were achieved (Fig. 2E). During 6 months of follow-up after oral griseofulvin administration, the alopecic lesion completely resolved without recurrence (Fig. 2F).

The optimal treatment regimen for TC is primarily determined by the causative species, patient characteristics (age and health status), and drug availability3. Appropriate oral treatment based on local epidemiology and the suspected culprit organism should be initiated while awaiting mycological confirmation. Among oral antifungal agents, griseofulvin and terbinafine as first-line treatments and itraconazole as a second-line treatment are used for pediatric TC3. Meta-analysis results suggest that terbinafine is more efficacious against Trichophyton species than griseofulvin, which is more effective against Microsporum species7, 8. However, some oral antifungal agents for TC are not licensed for use or unavailable in certain countries. For instance, in South Korea, terbinafine and griseofulvin are the only antifungal drugs approved for TC treatment in children, with griseofulvin having limited availability. Conversely, azoles (itraconazole and fluconazole) are not licensed for use in children with TC because of safety concerns, including heart failure, and are administered only for off-label use when the expected treatment benefits exceed the known risks. Exceptions may include serious M. canis infections that are unresponsive to terbinafine and when griseofulvin is not available9.

All three children with TC in this case report were initially treated with oral terbinafine in private clinics before the identification of the causative species. Unfortunately, none of them achieved clinical and mycological cure in a prolonged (7~8 weeks) course of oral terbinafine over the standard regimen. Two patients showed poor clinical improvements without mycological cure after the change to 6-week oral itraconazole. Eventually, the recalcitrant cases were successfully treated with oral griseofulvin.

Dermatophytosis resistant to antifungal agents is increasingly emerging as a public health threat in certain endemic areas10, 11. Treatment failure of dermatophytosis is generally defined as lack of clinical and mycological cure to the standard antifungal regimen and may occur for several reasons, as previously mentioned3, 12. All present patients received the standard recommended dose and duration of terbinafine and itraconazole, and an additional 2 to 4 weeks of the same regimen did not result in clinical or mycological cure; thus, drug resistance may be considered to be the main cause of treatment failure, although in vitro susceptibility testing was not performed.

Recalcitrant cases of TC caused by M. canis with terbinafine or itraconazole have rarely been reported6. Failure of treatment with terbinafine or itraconazole may be due to the higher minimum inhibitory concentration of terbinafine (and to some extent itraconazole) than the maximum concentration reported in hair12. Moreover, terbinafine may not reach sufficient concentrations in the hair shafts of children to exhibit fungicidal activity against Microsporum infection because it is not excreted in sweat or sebum in prepubertal children13.

Since the 1950s, griseofulvin has been the drug of choice for pediatric TC, with long-term safety profiles, good patient tolerance, and few known drug interactions. Although newer antifungal drugs have shorter treatment periods than griseofulvin, potentially leading to higher compliance, evidence clearly suggests that griseofulvin is considerably more effective than terbinafine and is not inferior to itraconazole or fluconazole in treating Microsporum TC8. Although griseofulvin remains a licensed drug for pediatric TC treatment in South Korea, it is not directly available through the medical health system. It could be obtained for limited use from overseas manufacturers through the Korea Orphan and Essential Drug Center (https://www.kodc.or.kr/home/main.do), a process that takes at least 4 weeks and causes delay in treatment. Our cases might have been treated effectively with higher doses and longer courses of terbinafine or itraconazole; however, early administration with griseofulvin as the initial treatment would have led to faster complete cure.

We encountered rare cases of recalcitrant M. canis TC in children successfully treated with oral griseofulvin. Although griseofulvin is not licensed for use or not available in many countries, it is one of the most effective agents against Microsporum species and remains the first-line treatment for pediatric TC based on dermatology textbooks and reliable treatment guidelines2, 3, 4.