Zohra Zaidi ( Department of Dermatology, Jinnah Postgraduate Medical Centre, Karachi. )
N. Jafri ( Department of Dermatology, Jinnah Postgraduate Medical Centre, Karachi. )
K.Khan ( Department of Dermatology, Jinnah Postgraduate Medical Centre, Karachi. )
P. Hasan ( Department of Dermatology, Jinnah Postgraduate Medical Centre, Karachi. )
N. Kapadia ( Department of Dermatology, Jinnah Postgraduate Medical Centre, Karachi. )
An open label trial of Lamisil (Terbinafine) 500mg daily for 16 weeks was conducted on 20 patients with Onychomycosis due to candida. Of these, 15 patients could complete the trial. Total number of target nails infected was 21. The follow-up period was from 16 to 52 weeks. At 16 weeks, 71% cases showed clinical improvement and 67% had mycological cure, Thirty-three percent had complete cure at 52 weeks. The results show that Terbinafine is effective against candida but requires a longer duration of treatment. The drug was well tolerated (JPMA 46:258, 1996).
Onychomycosis accounts for about 50% of all nail problems1. The most common pathogens are dermatophytes, but yeast and moulds are also responsible. A number of studies have been done on onchomycosis due to dermatophytes. The results of treatment with allyamines and imidazoles are quite promising2. Few studies have been conducted on onychomycosis due to yeast and moulds. In a developing country like Pakistan women do almost all the housework single bandedly and without protection. Mechanical trauma destroys the cuticle and is responsible for invasion of candida into the nail folds, this then leads to onychomycosis2. Nails infections caused by candida are mostly associated with chronic paronychia or chronic mucocutaneous candidiasis. Candida has also been isolated from the nails showing primary distal and lateral onycholysis3. Most cases of onychomycosis due to yeast are caused by candida albicans Candida albicans and candida parapsilosis are not keratolytic, but can affect the nail fold and nail plate as pathogens4.
Moulds responsible for onychomycosis are also not keratolytic. They live on unkeratinised intercellular cement or take, advantage cf partial denaturing of nail keratin by preexisting trauma or nail disease.Unlike dermatophytes, the moulds colonise m the outer layers of the nail, leuconychia tricophyta is the common manifestation of this nail infection4.
Terbinafine has a broad spectrum of activity against dermatophytes, yensts moulds and dimorphic fungi. In vitro activity is strongest against dermatophytes and as per gillosis. It is fungicidal against candida paTapSiiOsiS but fungistatic against candida albicans. C.andida albicans in mycelial form is
inhibited at 0.26 ug/ml which is easily achieved with therapy in the nail as well as in the stratum corneum of skin5. This study reports an open trial of this drug onychomycosis due to candida.
Patients and Methods
Twenty patients above the age of 18 years v examined locally and systemically at first visit and evaluation foronychomycosis due to candida. They had clinical evide of onychomycosis and a positive culture for candida. clinical parameters were paronychia, onycholysis and hyperatosis. They were rated by means of a 4- point scale absent, l=mild, 2=modcrate, 3=severe). They did not have recent oral or topical antifungal therapy. Pregnant lactating women, patients with diseases that impair absorption of the drug from the gastrointestinal tract and those with se systemic disorder were excluded.
All patients were given Terbinafine 500 mg or orally 16 weeks - They were then seen at 4 weeks interval till weeks and at 6 weeks interval till 52 weeks. At each visi local and mycological examination of the target nail (it infected nail) was done. Blood was examined for haematoh and biochemistry at the first visit and then at 16 weeks which the active therapy was stopped. The investigations done w serum creatinine, uric acid, potassium, SGOT, SGPT, Lt Gamma GT, alkaline phosphatase, total bilirubin, cholesterol and triglycerides. Urine was examined for protein glucose. The proportion of the affected nail was graphically recorded. The length of the unaffected nail was measure each clinical examination. If the clinical parameters showed signs of improvement and the length of the unaffected nail increased on each examination; it signified that the drug was effective. Clinical cure was considered when the nails appeared normal. At each mycological examination, the nails were examined for both microscopy and culture. Nail samples were taken with the help of a dental drill. They were treated with 20% KOH, using gentle heat when required. The presence of budding yeast, mycellium of both were noted. Nail material was cultured on Sabouraud’s dextrose agar without chiorhexamide for candida and mycobiotic agar for dermatophytes. Plates were examined after 3-5 days for candida, and 1-2 weeks for dermatophytes. Tubes showing no growth were discarded after 4 weeks of incubation. Candida isolated were identified by the chlanwdospore formation and biochemical reaction. Mycological cure was considered when the nails were negative both on microscopy and culture and complete cure when the nails had both clinical and mycological cure.
Of the 20 patients enrolled in the study, only 15 could complete it as 3 dropped out due to non-compliance and 2 showed a mixed infection at 4 weeks examination.
The Table shows the clinical profile of the patients. The total number of target infected nails was 21. Of these, 12 had paronychia. The clinical and mycological evaluation is shown in Figure 1.
The therapy was stopped at 16 weeks afterwhich3 more nails had rnvcological cure at 22,28 and 40 weeks. The clinical evaluation of the therapy can be seen in Figure 2.
Of the 11 nails with mild improvement, 3 had a complete cure at 22,28 and 40 weeks whereas 8 cases relapsed. Complete cure at 52 weeks was 33%, The drug was well tolerated, only I patient had epigastric pain which did not require withdrawal of therapy.
Twenty-one target nails were examined for onychomycosis due to candida (Finger nails 15. toe nails 6). Candida albicans was the only pathogen in our study. In a previous study, candida albicans was responsible for 97.5% of cases6. Chronic paronvchia is usually confined to finger nails and so is onychornycosis due to candida albicans4. Candida pampsilosis on the other hand is not associated with chronic paronychia. Infection with dermatophytes and moulds are more common in the toe nails4. Chronic paronychia was present in 12 finger nails. The rest of the target nails had mild to moderate onycholysis. None of our patients had any gross systemic abnormality. This shows that candida can infect nails with onycholysis2,4.
Mean age range in our patients was 38 years and mean duration of infection was 62 months. Most of our patients were housewives who could not avoid working with water nor could they afford any proper protection to their nails because of poverty. Perhaps if the treatment was started early and proper protection provided, the results of the treatment could have been better. The right thumb nail was the most common nail affected in our study. The right middle finger has been reported as the most common nail affected in previous studies. Three target nails showed moderate improvement at 16 weeks and complete cure was seen after stopping of therapy during the follow-up period. This shows the residual effect of the drug. Terbinafine is both keratophilic and lipophilic. It therefore,persists in the nail even after withdrawal of therapy7,8. The drug was well tolerated. Only one patient had epigastric pain, which did not require withdrawal of therapy. In most studies the drug has been well tolerated9-11.
Terbinafine was effective against candida albicans. in our study the drug was given for 16 weeks. onychomycosis due to candida, was treated from 28-48 weeks by other workers3,4. The activity of terbinalinc against candida organisms observed in clinical studies is somewhat better than predicted by these in vitro findings. This relatively high level of clinical efficacy is attributable to inhibition by the Terbinafine of pseudohypheal growth of candida which is thought to be associated with pathogenesis. This form of organism is known to be suppressed with a Terbinafine concentration considerably lower than that required for inhibition in the yeast form7.
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