Onychomycosis in childhood: a current perspective with emphasis on the review of treatment

Abstracts

A prevalência da onicomicose na infância, principalmente quando provocada por dermatófitos e Candida sp, tem aumentado. Tais infecções em crianças parecem infreqüentes em países desenvolvidos, mas não são excepcionais na América Latina. O objetivo principal deste trabalho foi analisar a literatura médica atual. Foi observada a onicomicose por dermatófitos em crianças com idade a partir de dois anos. A faixa entre 12-16 anos é a mais afetada (66,4%), provavelmente devido aos fatores de risco aumentado, como a prática de esportes e os hormônios da puberdade. Os pais foram a fonte de infecção em 46,2% dos casos, e 65% dos parentes de pacientes apresentavam onicomicose ou tinea pedis. As unhas dos dedos dos pés são afetadas por dermatófitos, sendo mais freqüente a onicomicose distal subungueal (88,5%); contudo, também se observam as formas superficial branca e branca subungueal proximal. A suspeita de diagnóstico é obtida com o exame clínico, mas a confirmação micológica é necessária. Os principais agentes dermatófitos são: T. rubrum (69%-92,7%), T. tonsurans (8,8%), T. mentagrophytes var interdigitale (5,4%) e M. canis (2,9%). A griseofulvina constitui o tratamento de primeira linha, mas itraconazol, fluconazol e terbinafina também são recomendados para o tratamento sistêmico. O tratamento tópico com ciclopirox a 8%, amorolfina a 5% e uréia a 40% associada a bifonazol a 1% pode ser considerado alternativa terapêutica. Dada a escassez de relatos de onicomicose em crianças, não foi possível uma conclusão sobre a melhor abordagem terapêutica. Mais dados clínicos são necessários para estabelecer o perfil de segurança dos novos agentes antimicóticos a fim de determinar a conduta ideal na onicomicose infantil.

criança; onicomicose

REVIEW ARTICLE

Onychomycosis in childhood: a current perspective with emphasis on the review of treatment^*

Roberto Arenas^I; Julieta Ruiz-Esmenjaud^II

^IM.D., Chief of the Mycology Section

^IIM.D., Visiting Dermatologist. Department of Dermatology

^{Correspondence}

SUMMARY

The prevalence of onychomycosis in childhood has been increasing, mainly caused by dermatophytes and also by Candida sp. These infections in children seem to be infrequent in the developed countries, while in Latin American they are not exceptional. Our main objective was to analyze the current medical literature. We have found dermatophyte onychomycosis in children as young as 2 years. The 12-16-year-old age group is reported as the most affected (66.4%), probably related to increased risk factors, such as sports and puberty/hormones. The source of infection was the parents in 46.2%, and 65% of relatives had onychomycosis or tinea pedis.

Toenails are affected in dermatophyte infections and the most frequent variety is distal subungual onychomycosis (88.5%), but we also observed the white superficial form and the proximal white subungual form.

Diagnosis is suspected on clinical examination, but mycological confirmation is necessary. The main dermatophyte agents are: T. rubrum (69%-92.7%), T. tonsurans (8.8%), T. mentagrophytes var interdigitale (5.4%) and M. canis (2.9%).

Griseofulvin is the first line treatment, but itraconazole, fluconazole and terbinafine are also recommended for systemic treatment. Topical treatment with 8% cyclopirox, 5% amorolfine and 40% urea plus 1% bifonazole may be a therapeutic alternative.

Since few reports are available regarding onychomycosis in children, we were not able to conclude which is the best therapeutic approach. More clinical data are needed to establish the safety profile of the new antimycotic drugs to determine the optimal management of onychomycosis in childhood.

Key-words: child; onychomycosis.

INTRODUCTION

In a relatively recent review of nail diseases in children, only five lines were written about onychomycosis. This review demonstrates the paucity of data on this subject in the literature.¹

Onychomycosis is the most common nail disease in adults. In various studies the prevalence ranged from 2.7% to 13%. Recently the prevalence of onychomycosis in North America has been estimated to be from 6.8% to 13.4%.² Onychomycosis in children used to be more frequent in the fingernails and usually caused by Candida sp as a secondary pathogen. However, during the last twenty years its frequency in children has been increasing, and nowadays dermatophyte infections are more prevalent in this pediatric group. These infections in children seem to be infrequent in developed countries, whereas in Latin America they are not uncommon.³ The percentage of dermatophyte onychomycosis found in children is 0.2% to 0.44% in North America,⁴ but the prevalence of onychomycosis in children from surveys conducted in different parts of the world may range from 0.1% to 2.6% (mean 0.3%), if it is in fact present (Table I).^5-12

The low frequency of onychomycosis in children can be attributed to: faster nail growth, smaller surface area for invasion, reduced likelihood of trauma, lower incidence of tinea pedis and less contact with infective spores.

Patients with Down's syndrome may have a higher prevalence of onychomycosis.^13,14 In a descriptive, open and transversal assay on 217 patients with Down's syndrome in Mexico, the authors have found 55 (25.3%) patients with onychomycosis, but only in patients older than 7 years of age.¹⁵

In the Nineteenth Century onychomycosis was more common in children with tinea capitis, possibly due to the transmission of the fungal infection from the scalp to the fingernails. The changes in epidemiology and the high cure rates of tinea capitis have probably contributed to the decreased prevalence of fingernail onychomycosis.¹⁶ Nevertheless, we must also examine for concomitant tinea capitis and tinea pedis.

Nowadays onychomycosis more commonly involves toenails than fingernails, except in Candida infection. Toenails are affected in dermatophyte infections in children in 81.8% to 96.2% and can begin at the age of 2; but the 12-16 year-old age group is reported as the most affected (66.4%), probably related to increased risk factors, such as sports and puberty/hormones.¹⁷ The first step for developing onychomycosis is the presence of tinea pedis, which has been found in 14% of the feet of Mexican children with a positive KOH.¹⁸ The source of infection was the parents in 46.2%, and in 65% a relative had onychomycosis or tinea pedis.^4,19 Familial infection seems to be the leading risk factor for the development of onychomycosis in prepubertal children. When a child has onychomycosis or tinea pedis, every effort should be made to look for a similar infection in family members. This is especially true since genetic and environmental factors may play a role in its pathogenesis.^19,20

The clinical presentation and the etiological agent do not differ from those in adults.

The most frequent variety is distal subungual onychomycosis (88.5%), but the white superficial form and the proximal white subungual form have also been observed.

The most common dermatophytes involved are: T. rubrum, 69% and 82.4 in two Mexican papers and 92.7% in a French communication,^3,10,17 T. tonsurans (8.8%), T. mentagrophytes var interdigitale (5.4%) and M. canis (2.9%).^3,10,17

Analysis of nail samples is particularly valuable for onycholysis which may be a sign of onychomycosis as well as psoriasis, or congenital onychodystrophy. Diagnosis is suspected on clinical examination, but mycological confirmation is needed.

DISCUSSION

The current treatment of onychomycosis is with topical or systemic antimycotic drugs. Griseofulvin probably remains the best choice for dermatophytosis because of its good tolerance in children, however it is not easily available in some countries, but easily available in the United States of America. The strategy for the management of dermatomycoses in children has generally been to avoid oral antifungal agents, whenever possible, and to evaluate carefully the risk/benefit ratio of the selected treatment. Griseofulvin, ketoconazole, itraconazole, fluconazole and terbinafine are recommended for systemic treatment and these drugs appear to be well tolerated. Gupta et al, (Canada) treated 17 pediatric cases with itraconazole, fluconazole and terbinafine and found a good response to all three treatments.⁴

A range of fluconazole doses, from 3 to 6 mg/kg daily, has been used in pediatric patients. These treatments have been beneficial in the treatment of fungal episodes including fungemia in pediatric infections.^21,22 Also this treatment schedule has been tried on a weekly basis, in single doses for 12-16 weeks for fingernails and 18-26 weeks for the toenails; however this drug is not FDA approved for nails in the U.S.A.

Jones reported that terbinafine was effective in nine (82%) of 11 patients.^23,24 Terbinafine can be used as in adults and it requires 6 weeks of continuous therapy for fingernails and 3 months for toenails. The suggested dose is 250 mg/day when a patient's weight exceeds 40 kg, 125 mg/day for a weight of 20 to 40 kg, and 62.5 mg/day for children weighing less than 20 kg.

The suggested optimum dosage of itraconazole for the treatment of dermatomycoses has been 5 mg/kg daily or 1 week pulse.²⁵ Continuous dosing with itraconazole 5 to 7 mg/kg daily produced clinical and mycological clearing in all seven children with onychomycosis, two of whom had Candida albicans infection. Gupta et al,⁴ were the first to publish the treatment of onychomycosis with itraconazole pulse-therapy in children.

A brief report in the Japanese literature discussed the treatment of 6 children, 4 with fluconazole and 2 with itraconazole. Cure was achieved in 4, and one failure in each group (26). A total of 17 patients from 3 to 14 years old (8 females, 9 males, with a mean age of 8.5 years) were treated for toenail (83%) and fingernail onychomycosis (2%). The history of disease ranged from 2 months to 5 years (10.8 months). Itraconazole pulse-therapy has also been used in 7 pediatric patients. The authors used the following dosage (5 mg/kg): 10-15 kg weight (100 mg every other day); 6-20 kg weight (100 mg daily); 21-40 kg weight (100 mg twice daily); more than 40 kg (200 mg twice daily). The duration of treatment ranged from 3 to 5 months. Follow up was done at month 6 in 15 of 17 patients. Cure was observed in 16 and no relapse was observed in 2 to 5 years. Both continuous and itraconazole pulse-therapy have been found to be safe and well tolerated in children.²⁷ Baran recommend pulsed-therapy every 2 weeks for 2 months in fingernails and every 3 weeks for three months in toenails. The suggested dose is 200 mg/twice a day when the weight exceeds 50 kg, 200 mg/day for a weight of 40 to 50 kg, 100 mg/day for a weight of 20 to 40 kg and 5 mg/kg daily for children weighing less than 20 kg. An oral solution is available at 3 mg/kg/day.²⁸ Gupta has suggested a dosage regimen for systemic antimycotic drugs when they must be used in the treatment of onychomycosis in children (Table 2).

Topical therapies have generally been ineffective in onychomycosis, particularly when there is significant nail plate disease or nail matrix involvement. In children the nail plate is thinner than in adults, with a structure that may facilitate penetration of drug. Topical formulations with 8% cyclopirox, 5% amorolfine and 40% urea plus 1% bifonazole may be a therapeutic alternative. The safety and efficacy of a two-phase topical treatment with bifonazole-urea ointment was tested in twenty five children (all <16 years old) with onychomycosis. In the first phase, the ointment was administered under occlusion until the nail was removed non-traumatically. The observed cure rate was 65% of cases.²⁹

None of the systemic antifungal drugs have been approved for use in dermatophyte onychomycosis in children (FDA), but they are used in outpatient clinics as a routine treatment in many undeveloped countries. This emphasizes the need for clinical judgement to assess the potential benefits and risks to the patient.

Some advise carrying out blood tests every 8 weeks including: electrolyte levels (itraconazole, fluconazole), liver function tests, and complete blood count with a differential.³⁰ In exceptional cases of children treated with Itraconazole, a reversible and slightly elevated alkaline phosphatase and SGOT test have been observed.²⁵ There is also an additional concern with terbinafine, because 35% of the drug is metabolized by cytochrome P-450 (isoenzyme CYP2D6).³¹

The availability of a liquid formulation may increase compliance in children. In some countries griseofulvin oral suspension is still available. Fluconazole powder can be reconstituted to yield a suspension. The current itraconazole liquid formulation is not recommended for children since the concentration of the cyclodextrin vehicle may be associated with side effects such as diarrhea.³² For children who are unable to swallow pills of itraconazole, capsules can be broken and the powder can be mixed with food such as jelly or bread.⁴ In Mexico some dermatologists count the number of itraconazole pellets (730 to 800 for itraconazole), depending upon body weight.³³

As few reports are available about onychomycosis in children, we were not able to conclude which one is the best therapeutic approach. More clinical data are needed to establish the safety profile of the new antimycotic drugs to determine the best management of onychomycosis in children. These drugs should be carefully evaluated in a larger cohort of children with onychomycosis. q

REFERENCES

Received in June, 20^th of 2002

Approved by the Consultive Council and accepted for publication in September, 05^th of 2003

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*

Work done at Department of Dermatology "Dr. Manuel Gea Gonzalez" General Hospital, Mexico City and presented in the World Congress of Pediatric Dermatology, CanCun, Mexico, 20-24 October, 2001.

Publication Dates

• Publication in this collection
  09 June 2004
• Date of issue
  Apr 2004

History

• Received
  20 June 2002
• Accepted
  05 Sept 2003