Onychomycosis in children: a survey of 46 cases

Transcription

1 Original article Onychomycosis in children: a survey of 46 cases C. Romano, 1 M. Papini, 2 A. Ghilardi 1 and C. Gianni 3 1 Department of Dermatology, University of Siena, Siena, 2 Medical and Surgery Department, Dermatology Unit of Terni, University of Perugia, Perugia and 3 Department of Dermatology, San Paolo Hospital, University of Milan, Milan, Italy Summary This is a retrospective study of the agents, clinical aspects, sources of infection and therapy of onychomycosis in children. In the period , we observed 46 consecutive children, until 16 years of age with onychomycosis (29 boys, 17 girls, mean age 10.8 years). Dermatophytes were isolated in 30 cases (Trichophyton rubrum in 22 cases, Trichophyton mentagrophytes in five, Epidermophyton floccosum in two and Trichophyton violaceum in one) and Candida spp. in 16, associated with Trichophyton rubrum in two. Moulds were isolated in three children (Fusarium oxysporum in one, Scopulariopsis brevicaulis in another and Aspergillus fumigatus associated with Trichophyton rubrum in a third). The commonest features were distal and distolateral subungual hyperkeratosis in dermatophyte infections (93%) and onychodystrophy and paronychia in Candida infections (56% and 50% respectively). Forty patients achieved clinical and mycological recovery. It is appropriate to suspect onychomycosis in children, perform microbiological diagnosis and undertake early treatment. An approach of this kind may help to prevent nail dystrophy and the spread of infection. Key words: onychomycosis, dermatophytes, Candida, moulds, children. Introduction In paediatric patients, nail alterations may be an expression of onychomycosis or may accompany skin diseases, such as psoriasis, eczema, lichen planus, ichthyosis and Darier s disease or they may be related to perionyx or (for example, of bacterial origin) or trauma. Diagnosis of nail alterations may be exclusively clinical paronychia if the morphological changes are characteristic and associated with evident skin disease. However, often the skin disease has minor clinical expression and the nail alterations may be ambiguous; in such cases clinical diagnosis may not be sufficient. Similarly, onychomycosis cannot always be diagnosed with certainty from clinical manifestations, and if suspected, mycological examination should be carried out. Although onychomycosis is a very common superficial fungal disease, it is considered rare in children. Correspondence: Clara Romano, Department of Dermatology, University of Siena, Via Monte Santo, 3, Siena, Italy. Tel.: Fax: mondelli@unisi.it Accepted for publication 19 July 2005 Patients and methods This is a retrospective study based on the information obtained from the medical records of three Italian mycology units of dermatology departments in Siena, Terni and Milan, in the period from May 1989 to May All centres used the same form (see below), which was sent to the data centre in Siena for processing. The three centres used the same standardised methods to identify mycetes: (a) direct microscope examination of pathological material (soaked in 30% KOH) and (b) culture on Sabouraud glucose agar with chloramphenicol (CAF) or CAF and cycloheximide. Plates were incubated at 27 C and checked periodically for 45 days. Identification of Candida was based on the classical microbiological criteria. Identification of dermatophytes and moulds in culture was based on macroand microscopic characters of the colonies that grew, according to the criteria of Rebell and Taplin [1] for dermatophytes and De Hoog and Guarro [2] for moulds. The pathogenetic significance of nondermatophytic agents was confirmed by repeating culture twice whenever the first culture produced mould. This procedure excluded cases of contamination. 430 Ó 2005 Blackwell Publishing Ltd Mycoses, 48,

2 Onychomycosis in children Case inclusion criteria were: age up to 16 years and positive direct microscope mycological examination and culture. The form was designed to obtain information on age, sex, clinical aspect, mycete isolated, past or present mycotic infections (of nails or other parts of the body), source of infection (human, animal or tellurian), risk factors (type of shoes usually worn, lifestyle and sporting activity), concomitant skin or systemic diseases and therapies undertaken (type of drug, route of administration, duration of therapy and side effects). When systemic therapy was prescribed, it was preceded and followed by routine haematology and blood chemistry evaluations. For lesions refractory to treatment, humoral and cell-mediated immune status was investigated to rule out immunodeficiency. Follow-up was at least a year in all the cases and included microbiological confirmation of recovery. Each centre communicated the total number of children suffering from nail alterations of nonmycotic origin (microbiologically excluded) observed in the study period. Differences between groups with Candida and dermatophytes were evaluated by Student s t-test for unpaired data in relation to age and by chi-squared test in relation to sex and site of lesion. 12 ± 3.8 years (range 3 16). The mycosis affected the feet in 27 cases, hands in two and both hands and feet in one. The most frequent clinical manifestation was distal and distolateral subungual hyperkeratosis (93%) (Figs 1 and 2). The source of infection was human. Family members were identified in six cases. Family members had tinea pedis in four cases, tinea cruris in one case and onychomycosis in another case. Nine children practised sport (swimming or soccer) and habitually wore sporting shoes made of synthetic materials. Fourteen patients also had tinea pedis. Other skin diseases were present in four cases: congenital ichthyosis in one case and atopic dermatitis in three cases. The mycotic manifestations of these four children had been attributed to eczema or ichthyosis and treated with cortisone creams, delaying correct diagnosis. Fourteen patients were treated with systemic and topical therapy, 11 with systemic alone and five with topical drugs only. Twenty-five patients achieved clinical and mycological recovery, two improved but did not recover completely, two were lost to follow-up after an initial improvement and one (case no. 22, with mixed infection) did not respond to therapy. Side effects were not observed in any case. Results In the study period, a total of 289 cases of nail alterations were observed: 46 were onychomycoses and the others (243) were nonmycotic onychodystrophies. Direct microscope examination was positive in all 46 cases, revealing typical structures of the fungi subsequently isolated in culture. There were 29 boys and 17 girls, mean age 10.8 years. Twenty-five cases were in the year age group and the other 21 were under 10 years. A single mycete was isolated in 43 cases, with mixed infection in the other three. The patients were divided into three groups according to the causal agent isolated. Dermatophyte group The dermatophytes isolated were Trichophyton rubrum (22 cases), Trichophyton mentagrophytes (five cases), Epidermophyton floccosum (two cases) and Trichophyton violaceum (one case). Clinical, mycological and therapeutic details are reported in Table 1. Mixed infection was found in three of 22 cases of infection caused by Trichophyton rubrum, the other agents being Candida albicans (case no. 20), Candida parapsilosis (case no. 21) and Aspergillus fumigatus (case no. 22) respectively. The patients were 21 boys and nine girls with a mean age of Candida group In the Candida group, C. albicans was isolated in 13 cases, C. parapsilosis in two and Candida krusei in one. The patients were eight boys and eight girls with a mean age of 9.1 ± 5.2 years (range 13 months 16 years). Clinical, mycological and therapeutic details are reported in Table 2. Two cases had mixed infection with T. rubrum (cases 20 and 21, Table 1). The prevalent clinical manifestations were onychodystrophy in nine (Fig. 3) and perionyxis in eight. The mycosis affected the hands in 12 cases and the feet in four. No risk factors were identified. Six patients were treated with topical therapy alone, four with topical and systemic therapy, four with topical therapy and removal of the affected nail lamina and two with systemic therapy alone. All patients recovered after therapy. The mean age of children with onychomycosis caused by dermatophytes was significantly greater than the age of those with Candida (P ¼ 0.031). Of the body parts the hands were most frequently affected by mycosis caused by Candida and the feet were most often affected by dermatophytosis (chi-squared with Yates correction 19.14, P < 0.001). No difference was found in the distribution of causal agents between boys and girls (chi-squared 1.79, P ¼ 0.18). Ó 2005 Blackwell Publishing Ltd Mycoses, 48,

3 C. Romano et al. Table 1 Demographic, mycological, clinical and therapeutic details in children with dermatophyte infections. No. Age Sex Fungi isolated Clinical manifestations Therapy 1 Follow-up 1 8 F Trichophyton rubrum Distal subungual hyperkeratosis first of big toenails and then other nails. Down syndrome. Terbinafine 125 mg day )1 for 2 months 2 13 F T. rubrum Distolateral hyperkeratosis of right big toenail Urea 40% ointment and topical imidazole twice a day for 6 months 3 13 F T. rubrum Distolateral subungual hyperkeratosis of big toenails 4 14 F T. rubrum Distal subungual hyperkeratosis of big toe nails and 2nd right toenail 5 15 F T. rubrum Distal subungual hyperkeratosis and leuco nychia of right big toenail Terbinafine 250 mg day )1 for 2 months Terbinafine 250 mg day )1 for 2 months Terbinafine 250 mg day )1 for 2 months and topical imidazole twice a day for 3 months 6 3 M T. rubrum Distal hyperkeratosis of 4 5th left toenails Terbinafine 62.5 mg day )1 for 2 months 7 8 M T. rubrum Hyperkeratosis and distolateral onycholysis of Griseofulvin 500 mg day )1 12 weeks and left big toenail cyclopyroxolamine lotion 8 8 M T. rubrum Distal hyperkeratosis of 2nd right toenail Topical imidazole twice a day for a month 9 8 M T. rubrum Distal hyperkeratosis of right big toenail Terbinafine 250 mg day )1 for 2 months 10 8 M T. rubrum Distal subungual hyperkeratosis of left big Terbinafine 125 mg day )1 for 2 months toenail 11 9 M T. rubrum Distolateral subungual hyperkeratosis of right big toenail M T. rubrum Hyperkeratosis and distal onycholysis of left big toenail Terbinafine 250 mg day )1 and topical imi dazole for 2 months Terbinafine 250 mg day )1 for 2 months and topical imidazole twice a day for 2 months M T. rubrum Distolateral hyperkeratosis of left big toenail Terbinafine 250 mg day )1 8 weeks and amorolfin lacquer M T. rubrum Distal subungual hyperkeratosis of big toe nails and 2nd left toenail M T. rubrum Distal subungual hyperkeratosis of big and 2nd toenails M T. rubrum Lateral subungual hyperkeratosis of right big toenail Terbinafine 250 mg day )1 for 2 months and topical imidazole for 2 months Griseofulvin 500 mg day )1 and topical imi dazole for 3 months M T. rubrum Lateral leuconychia of right big toenail Itraconazole 200 mg twice a day for 1 week month )1 for 3 months M T. rubrum Distal subungual hyperkeratosis of 2nd left fingernail M T. rubrum Lateral subungual hyperkeratosis of left big toenail F T. rubrum + Candida albicans Distal subungual hyperkeratosis of big toe nails M T. rubrum + Candida parapsilosis Onychodystrophy and onycholysis of left thumb Topical imidazole for 4 months Clinical improvement without myco logical recovery Terbinafine 250 mg day )1 for 1 month and topical imidazole for 2 months Clinical improvement without myco logical recovery after 3 months, lost to follow-up after 1 year Terbinafine 250 mg day )1 for 3 months Fluconazole 100 mg day )1 for 30 days, 50 mg for 15 days and topical clotrimazole for 6 months Fluconazole 100 mg day )1 for 40 days and topical clotrimazole for 2 months 432 Ó 2005 Blackwell Publishing Ltd Mycoses, 48,

4 Onychomycosis in children No improvement Urea 40% and topical imidazole for 5 months Distal subungual hyperkeratosis of all toenails. Siali dosis 22 7 F T. rubrum + Aspergillus fumigatus Terbinafine 125 mg day )1 for 2 months Distolateral subungual hyperkeratosis of right big toenail 23 9 F Trichophyton mentagrophytes 24 5 M T. mentagrophytes Distal subungual hyperkeratosis of right big toenail Topical imidazole twice a day for 3 months M T. mentagrophytes Hyperkeratosis and onycholysis of right big toenail Terbinafine 250 mg day )1 for 1 month and topical imidazole twice a day for 3 months M T. mentagrophytes Distal subungual hyperkeratosis of big toenails and Griseofulvin 500 mg day )1 and topical imi Improvement without micological 2nd left toenail dazole for 3 months recovery M T. mentagrophytes Leuconychia of 3 4th right toenails Terbinafine 250 mg day )1 8 weeks and cyclopyroxolamine lotion Clinical improvement without mycologi cal recovery, lost to follow-up at 1 year Griseofulvin 500 mg day )1 6 weeks and cyclopyroxolamine lotion Distal subungual hyperkeratosis of finger and toe nails F Epidermophyton floccosum Itraconazole 200 mg twice a day for 1 week month )1 for 3 months Terbinafine 250 mg day )1 for 2 months M E. floccosum Distal subungual hyperkeratosis of big toenails and 2nd and 3rd left toenails M Trichophyton violaceum Distal subungual hyperkeratosis and onycholysis of right big toenail 1 Oral administration unless otherwise specified. Figure 1 Onychomycosis caused by Trichophyton rubrum: two small whitish cuneiform patches, originating from lateral folds of left big toe and extending towards the centre of the nail, in a 16-year-old boy (case no. 19). Figure 2 Onychomycosis caused by Trichophyton rubrum: opaque yellowish fourth and fifth nails of left foot in a 3-year-old boy (case no.6). Mould group The moulds isolated were Fusarium oxysporum in one case, Scopulariopsis brevicaulis in another, and Aspergillus fumigatus associated with Trichophyton rubrum in a third. Onychomycosis caused by F. oxysporum was diagnosed in a 15-year-old girl. It manifested as a yellowishwhite patch, which grew rapidly in size, on the lateral part of the nail of the right index finger. When examined 3 weeks later, the nail was yellowish laterally and proximally, with initial signs of onycholysis and slight perionyxis. The girl was fond of gardening and had frequent contact with soil. She was successfully treated with terbinafine 250 mg day )1 for 2 months and with topical imidazole. Ó 2005 Blackwell Publishing Ltd Mycoses, 48,

5 C. Romano et al. Table 2 Demographic, mycological, clinical, and therapeutic details in children with Candida infection. No. Age Sex Fungi isolated Clinical manifestations Therapy 1 Follow-up 1 1 F Candida albicans Onychodystrophy of left thumbnail Topical clotrimazole for 2 months 2 2 F Candida albicans Onychodystrophy of second left fingernail Topical clotrimazole for 2 months 3 6 F Candida albicans Onychodystrophy and perionyx of first and second right fingernails 4 9 F Candida albicans Onychodystrophy, onycholysis and perionyx of third left fingernail 5 12 F Candida albicans Perionyx and destruction of lamina of second right fingernail 6 2 M Candida albicans Onycholysis and perionyx of second right fingernail Removal of infected nail and topical clotri mazole for 3 months Topical imidazole twice a day for 2 months Lost to follow-up Fluconazole 100 mg day )1 for 20 days, then 50 mg day )1 for 20 days and topical clo trimazole Removal of infected nail and topical clotri mazole twice a day for 3 months 7 6 M Candida albicans Onychodystrophy of right big toenail Removal of infected nail and topical clotri mazole twice a day for 4 months 8 9 M Candida albicans Onychodystrophy and onycholysis of fourth left fingernail 9 9 M Candida albicans Distolateral onycholysis and perionyx of fourth left fingernail M Candida albicans Distal subungual hyperkeratosis and perionyx of second, third and fourth right fingernails M Candida albicans Onychodystrophy and perionyx of second left fingernail M Candida albicans Distal subungual hyperkeratosis of big toe nails Removal of infected nail and topical clotri mazole twice a day for 2 months Topical clotrimazole twice a day for 2 months Fluconazole 100 mg for 20 days then 50 mg for another 20 days Fluconazole 50 mg day )1 for 8 weeks Fluconazole 100 mg day )1 for 30 days, top ical clotrimazole twice a day for 4 months 13 8 F Candida parapsilosis Onychodystrophy of third right toenail Topical clotrimazole for 3 months 14 5 F Candida krusei Perionyx of second and third right fingernails Topical clotrimazole twice a day for 3 months Two other cases with Candida had also Trichophyton rubrum infection (case nos 20 and 21 of Table 1). 1 Oral administration unless otherwise specified. 434 Ó 2005 Blackwell Publishing Ltd Mycoses, 48,

6 Onychomycosis in children performed in all patients and humoral and cell-mediated immunity in forms resistant to treatment were in the normal range. Discussion Figure 3 Onychomycosis caused by Candida: thick dystrophic right thumb nail in a 6-year-old girl. Figure 4 Onychomycosis caused by Scopulariopsis brevicaulis: distal subungual hyperkeratosis and onycholysis of the right thumb in a 7-year-old boy. Onychomycosis caused by S. brevicaulis was diagnosed in a 7-year-old boy with Rett syndrome. The mycosis developed after repeated trauma to the right thumb, manifesting with distal subungual hyperkeratosis and onycholysis (Fig. 4). The boy achieved recovery after topical therapy with cyclopyroxolamine for 4 months. The case with A. fumigatus and T. rubrum was a 7-year-old girl who suffered from bone marrow deficit because of sialidosis (case no. 22, Table 1). The mycosis manifested with distal subungual hyperkeratosis of all toenails, which were ochre yellow in colour. The patient also had tinea pedis. Although the girl was treated with 40% urea and bifonazole lotion twice a day for 5 months, the clinical manifestations remained practically unchanged. Duration of nail infection varied from a few months to 5 years in the three groups. Routine blood chemistry Onychomycoses are frequent in elderly persons and their prevalence increases with ageing of the population. 3, 4 They more commonly affect toenails than fingernails and are rare in children. The rarity of onychomycosis in subjects under the age of 16 years has been attributed to many factors. These include differences in nail plate structure, less exposure to trauma with respect to adults and faster linear nail growth than in adults (which means faster elimination of the fungus). 5 Apart from isolated reports 6, 7 there have been very few reviews and these reveal only slight differences in the percentage of nail infections in children in the various geographical areas. These differences may partly depend on different recruitment criteria and the different age ranges considered. 5, 8 In Europe, only 0.6% of children under 18 years of age seem to be affected, against 10 20% of adults and 15 80% of elderly people. 3 In South Africa, a prevalence of 0.2% was reported in the 1970s 9 which matches the prevalence found in a prospective survey of school children carried out in Europe (UK) in In the 1990s, a North- American multicentre survey reported a prevalence of 0.44%. 10 A significant number of reports also came from central America: in Mexico, 34 cases were found in children under 15 years of age 11 and in Guatemala, 26 cases were diagnosed in the age range 2 12 years. Only six of them had been referred with suspected onychomycosis; in the others it was diagnosed during the course of dermatological examination. 8 This suggests that like tinea pedis, onychomycosis may be misrecognised in children. 12, 13 It is difficult to determine whether there has been a real increase in the incidence of onychomycoses in children in recent years, or whether they were underrecognised in the past or both. 14 Of the five known clinical types of onychomycosis (distal and lateral subungual, proximal subungual, white superficial, endonyx and total dystrophic), the most frequent in children is distal and lateral subungual. Dermatophytes are the most common cause of these infections and the most frequently reported organism is T. rubrum. Other agents include T. mentagrophytes, Microsporum canis, Trichophyton tonsurans 11, 15 and rarer dermatophytes, such as Trichophyton equinum. 16 The source of infection by dermatophytes is often a family member. There is Ó 2005 Blackwell Publishing Ltd Mycoses, 48,

7 C. Romano et al. often a family medical history of dermatophytosis and the same causal agent is isolated in other family members. 5, 8 Predisposing factors include contact with animals, swimming, sporting activity, trauma and immunosuppression (because of drugs or HIV). 17 Reports of onychomycosis caused by Candida spp. in children are even less than those caused by dermatophytes. Sometimes there are cases of mixed infection, in which it is not unusual to isolate T. rubrum. InCandida spp. infections, onychodystrophy may be associated with perionyxis. Two frequently isolated species are 18, 19 C. albicans and C. parapsilosis. Nondermatophytic moulds have been reported as agents of onychomycoses in adults (for example Scopulariopsis, Aspergillus, Alternaria, Acremonium, Fusarium and Scytalidium). Their frequency has increased in recent years at different latitudes as well as in Europe, especially Italy Scopulariopsis brevicaulis is the mould most frequently isolated in Italy. Infection manifests as distal subungual onychomycosis. The second most frequently isolated mould is F. oxysporum which generally produces white superficial onychomycosis with perionyx. The third is Aspergillus spp. Contact with soil is a common source of infection. Onychomycosis is not easy to treat in adults. In children it may be difficult to decide whether or not an oral antifungal agent is indicated for onychomycoses caused by dermatophytes and Candida. According to Gupta [24], topical antifungal agents may be sufficient for mild cases, whereas oral therapy is required when the onychomycosis is moderate to severe, with nail matrix involvement. As in adults, the most widely used topical treatments include imidazoles, 8% cyclopyroxolamine and 5% amorolfin. 17 Tolnaphthate solution has been used after curetting superficial debris 6 and various combinations, such as bifonazole and urea, 25 have also been described. Certain oral drugs used only to treat adults earlier, usually for long periods, as in cases of onychomycosis, have recently become available for the therapy of mycoses in children. The new oral antifungal agents itraconazole, 26, 27 terbinafine 28 and fluconazole 29 are effective and safe in children, if used at appropriate doses for sufficient periods. As a general rule, older children can undertake the same therapy as adults, whereas the dose should be adjusted according to the body weight and age for younger children. In line with other studies we found a predominance of childhood cases of onychomycoses caused by dermatophytes, with T. rubrum the most frequent, and Candida in second place. As recently reported in France, 30 we found that onychomycoses are not rare under 17 years of age. In patients with onychomycosis caused by dermatophytes, predisposing factors were sports shoes, repeated trauma during soccer and soaking of the skin because of frequent bathing. Our patients often had one or more predisposing factors, including a family history of tinea and swimming or soccer. Tinea pedis was often associated with the nail infection. Involvement of all 10 toenails was found in a girl with Down syndrome, a disease in which a higher prevalence of onychomycoses has been reported. 31 Half the patients had a history of infection exceeding 1 year and four cases were also affected by other skin diseases which delayed correct diagnosis. Therapy was topical alone in 15 cases affected by dermatophyte and Candida infections and topical combined with systemic in the others. The systemic antimycotics used at doses recommended in the literature 10 were griseofulvin, terbinafine, fluconazole and itraconazole, with satisfactory results in most cases. An interesting observation emerging from our study was the excellent tolerance of all systemic therapies used, even when prolonged for 8 weeks. In no case were there side effects necessitating suspension of therapy. Alternatives to griseofulvin, which concentrate and remain active in the nail for long periods, were well tolerated in our study, enabling complete recovery and briefer periods of therapy. With regard to moulds, in the F. oxysporum case, the response to terbinafine and topical imidazole was good and led to clinical and mycological recovery from an infection which is often refractory to antimycotics. 32 was also achieved in the case with S. brevicaulis (treated with topical cyclopyroxolamine), whereas in the mixed infection with T. rubrum and A. fumigatus (treated with 40% urea and bifonazole lotion), the clinical manifestations remained practically unchanged in time, presumably because of the poor general condition of the child, affected by sialidosis, a severe hereditary neurological storage disease. We have observed more children with onychomycosis in the last 3 years than ever in the past. This may be largely because of greater attention of paediatricians towards the problem of onychomycosis, with more referrals to mycology units. It is to be hoped that children with dermatitis of the feet be sent more systematically to dermatology departments so that childhood onychomycoses can be diagnosed earlier. Early diagnosis prevents nail dystrophy, enables early therapy and avoids spread of infection. Onychomycosis caused by certain moulds needs to be diagnosed early because it is potentially life-threatening in immunodeficient patients Ó 2005 Blackwell Publishing Ltd Mycoses, 48,

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