Prevalence of onychomycosis in patients with diabetes mellitus: A cross-sectional study from a tertiary care hospital in North India.

Background Though diabetes mellitus (DM) is a well-recognised risk factor for onychomycosis (OM), the epidemiology of OM in diabetic patients remains largely unexplored, especially from the Indian subcontinent. Aims and objectives To estimate the prevalence of OM in diabetic patients, to identify and analyse risk factors, and correlate the severity of nail changes with glycemic control (HBA1c). Methods This cross-sectional, analytical study involved 300 diabetic patients. Patients with the clinical diagnosis of OM, supplanted by at least two of the four tests (KOH, culture, onychoscopy and nail histopathology) were considered cases of OM. Demographic and haematological profile was analysed using chi-square test/ Fischer's exact test. Logistic regression was applied to assess the independent risk factors. Results The prevalence of OM in DM patients was 34% (102/300) and significant risk factors included; age >60 years, male gender, closed shoes, disease duration >5 years, high BMI (>25) and lack of awareness about nail changes. Distal and lateral subungual OM (78%) was the commonest presentation followed by proximal subungual OM, superficial OM and total dystrophic OM. Correlation between HbA1c and the number of nails involved was found to be significant. Limitation As cases were recruited from a hospital setting, there could be chances of Berksonian bias. Conclusion The prevalence of OM in diabetic patients is high and the severity of nail changes correlates with HbA1C levels. It is important to diagnose OM early in order to treat and prevent complications.

Fractional CO2 laser with topical 1% terbinafine cream versus oral itraconazole in the management of onychomycosis: A randomized controlled trial.

Background Onychomycosis accounts for 20-40% of all nail disorders. It is difficult to cure with resistance to anti-fungal drugs, their side effects and drug interactions limiting treatment options. Itraconazole is a widely accepted oral medication used for onychomycosis while fractional CO2 laser along with a topical anti-fungal has shown promising results for nail plate clearance in onychomycosis. Aim To compare the efficacy of fractional CO2 laser with 1% terbinafine cream versus itraconazole in the management of onychomycosis. Methods A prospective, randomised, single-centre, two-arm, parallel-group interventional study was conducted at Command Hospital Air Force, Bangalore. Onychomycosis cases confirmed by KOH mount/culture-positive were included. Patients were randomly divided into two groups. Group A received 4 sessions of fractional CO2 laser every fourth week with twice-daily application of 1% terbinafine cream; Group B received one-week pulse therapy with capsule itraconazole once every four-week for three pulses. The response was assessed by Onychomycosis Severity Index, a validated onychomycosis assessment scale, at baseline and at six months. Results Group A had 50 patients with a total of 98 nails. Clinical improvement was seen in 83/98 (84.7%) nails. The average reduction in Onychomycosis Severity Index was 8.65 (P < 0.05). Group B had 50 patients with a total of 136 nails. Clinical improvement was seen in 104/136 (76.5%) nails. The average reduction in Onychomycosis Severity Index was 7.37 (P < 0.05). Both groups showed statistically significant improvement measured by 'Reduction in Onychomycosis Severity Index' at six months; however, there was no significant difference between the two arms. Limitations The main limitations of the study are the small sample size and lack of long-term follow-up to assess recurrence of infection. Conclusion Fractional CO2 laser with 1% terbinafine cream is an effective and safe method for inducing nail clearance in onychomycosis and has efficacy similar to itraconazole pulse therapy.

Effectiveness and safety of topical amphotericin B in 30% dimethyl sulfoxide cream versus 30% dimethyl sulfoxide cream for nondermatophyte onychomycosis treatment: A pilot study.

Background Although topical amphotericin B cream is effective for the treatment of nondermatophyte mold onychomycosis in vitro, studies of its effectiveness and safety in vivo are limited. Objectives We studied the effectiveness and safety of topical 0.3% amphotericin B in 30% dimethyl sulfoxide cream (amphotericin B cream) in nondermatophyte mold onychomycosis using the vehicle cream 30% dimethyl sulfoxide cream as control. Methods This randomized controlled study was conducted between January 2019 and November 2020. Patients diagnosed with nondermatophyte mold onychomycosis were randomly divided into two groups of ten patients each: one treated with amphotericin B cream and the other with the vehicle cream. Clinical and mycological cure as well as safety were evaluated. Results Ten patients each treated with amphotericin B cream and the vehicle cream were included in the study, but only nine patients in the vehicle cream group were available for follow up. All the 19 evaluable patients had distal lateral subungual onychomycosis and the great toenails were affected in 18 (94.7%) of these. Mycological cure was achieved in 8 (80%) patients treated with amphotericin B cream and in 4 (44.4%) patients using the control (vehicle) cream. Clinical cure was achieved in 7 (70%) patients treated with amphotericin B cream, but only in 2 (22.2%) patients on the control cream. No adverse events were observed. Limitations The small sample size and the fact that PCR fungal identification that provides accurate identification of fungal species was not performed are limitations of our study. Conclusion Topical amphotericin B cream was both very effective and safe in the treatment nondermatophyte mold onychomycosis. The control (vehicle) cream containing 30% dimethyl sulfoxide also demonstrated some antifungal activity.

Application of Hansen Solubility Parameters to predict drug-nail interactions, which can assist the design of nail medicines.

We hypothesised that Hansen Solubility Parameters (HSPs) can be used to predict drug-nail affinities. Our aims were to: (i) determine the HSPs (δD, δP, δH) of the nail plate, the hoof membrane (a model for the nail plate), and of the drugs terbinafine HCl, amorolfine HCl, ciclopirox olamine and efinaconazole, by measuring their swelling/solubility in organic liquids, (ii) predict nail-drug interactions by comparing drug and nail HSPs, and (iii) evaluate the accuracy of these predictions using literature reports of experimentally-determined affinities of these drugs for keratin, the main constituent of the nail plate and hoof. Many solvents caused no change in the mass of nail plates, a few solvents deswelled the nail, while others swelled the nail to varying extents. Fingernail and toenail HSPs were almost the same, while hoof HSPs were similar, except for a slightly lower δP. High nail-terbinafine HCl, nail-amorolfine HCl and nail-ciclopirox olamine affinities, and low nail-efinaconazole affinities were then predicted, and found to accurately match experimental reports of these drugs' affinities to keratin. We therefore propose that drug and nail Hansen Solubility Parameters may be used to predict drug-nail interactions, and that these results can assist in the design of drugs for the treatment of nail diseases, such as onychomycosis and psoriasis. To our knowledge, this is the first report of the application of HSPs in ungual research.

Comparative efficacy of continuous and pulse dose terbinafine regimes in toenail dermatophytosis: A randomized double-blind trial.

INTRODUCTION: Dermatophytes are the most frequently implicated agents in toenail onychomycosis and oral terbinafine has shown the best cure rates in this condition. The pharmacokinetics of terbinafine favors its efficacy in pulse dosing. OBJECTIVES: To compare the efficacy of terbinafine in continuous and pulse dosing schedules in the treatment of toenail dermatophytosis. METHODS: Seventy-six patients of potassium hydroxide (KOH) and culture positive dermatophyte toenail onychomycosis were randomly allocated to two treatment groups receiving either continuous terbinafine 250 mg daily for 12 weeks or 3 pulses of terbinafine (each of 500 mg daily for a week) repeated every 4 weeks. Patients were followed up at 4, 8 and 12 weeks during treatment and post-treatment at 24 weeks. At each visit, a KOH mount and culture were performed. In each patient, improvement in a target nail was assessed using a clinical score; total scores for all nails and global assessments by physician and patient were also recorded. Mycological, clinical and complete cure rates, clinical effectivity and treatment failure rates were then compared. RESULTS: The declines in target nail and total scores from baseline were significant at each follow-up visit in both the treatment groups. However, the inter-group difference was statistically insignificant. The same was true for global assessment indices, clinical effectivity as well as clinical, mycological, and complete cure rates. LIMITATIONS: The short follow-up in our study may have led to lower cure rates being recorded. CONCLUSION: Terbinafine in pulse dosing is as effective as continuous dosing in the treatment of dermatophyte toenail onychomycosis.

Onychomycosis: Diagnosis and management.

Onychomycosis is a common nail ailment associated with significant physical and psychological morbidity. Increased prevalence in the recent years is attributed to enhanced longevity, comorbid conditions such as diabetes, avid sports participation, and emergence of HIV. Dermatophytes are the most commonly implicated etiologic agents, particularly Trichophyton rubrum and Trichophyton mentagrophytes var. interdigitale, followed by Candida species and non dermatophytic molds (NDMs). Several clinical variants have been recognized. Candida onychomycosis affects fingernails more often and is accompanied by paronychia. NDM molds should be suspected in patients with history of trauma and associated periungual inflammation. Diagnosis is primarily based upon KOH examination, culture and histopathological examinations of nail clippings and nail biopsy. Adequate and appropriate sample collection is vital to pinpoint the exact etiological fungus. Various improvisations have been adopted to improve the fungal isolation. Culture is the gold standard, while histopathology is often performed to diagnose and differentiate onychomycosis from other nail disorders such as psoriasis and lichen planus. Though rarely used, DNA-based methods are effective for identifying mixed infections and quantification of fungal load. Various treatment modalities including topical, systemic and surgical have been used.Topically, drugs (ciclopirox and amorolfine nail lacquers) are delivered through specialized transungual drug delivery systems ensuring high concentration and prolonged contact. Commonly used oral therapeutic agents include terbinafine, fluconazole, and itraconazole. Terbinafine and itraconazole are given as continuous as well as intermittent regimes. Continuous terbinafine appears to be the most effective regime for dermatophyte onychomycosis. Despite good therapeutic response to newer modalities, long-term outcome is unsatisfactory due to therapeutic failure, relapse, and reinfection. To combat the poor response, newer strategies such as combination, sequential, and supplementary therapies have been suggested. In the end, treatment of special populations such as diabetic, elderly, and children is outlined.

Trichophyton rubrum onychomycosis in an 8-week-old infant.

An 8-week-old infant presented with 7 weeks history of nail involvement and discoloration. Lesions started over the middle fingernail of right hand at 1 week of age, spreading over to other nails within 2 weeks. Only two nails of the feet were spared. On KOH examination, fungal hyphae were seen and culture showed growth of Trichophyton rubrum. The purpose is to report the earliest case of onychomycosis having multiple nail involvement of fingers and toes (18 nails).

An open randomized comparative study to test the efficacy and safety of oral terbinafine pulse as a monotherapy and in combination with topical ciclopirox olamine 8% or topical amorolfine hydrochloride 5% in the treatment of onychomycosis.

BACKGROUND: Onychomycosis is a fungal infection of nails caused by dermatophytes, yeasts and molds. AIMS: To study the efficacy and safety of oral terbinafine pulse as a monotherapy and in combination with topical ciclopirox olamine 8% or topical amorolfine hydrochloride 5% in onychomycosis. METHODS: A clinical comparative study was undertaken on 96 Patients of onychomycosis during the period between August 2005 to July 2006. Forty-eight patients were randomly assigned in group A to receive oral terbinafine 250 mg, one tablet twice daily for seven days every month (pulse therapy); 24 patients in group B to receive oral terbinafine pulse therapy plus topical ciclopirox olamine 8% to be applied once daily at night on all affected nails; and 24 patients in group C to receive oral terbinafine pulse therapy plus topical amorolfine hydrochloride 5% to be applied once weekly at night on all the affected nails. The treatment was continued for four months. The patients were evaluated at four weekly intervals till sixteen weeks and then at 24 and 36 weeks. RESULTS: We observed clinical cure in 71.73, 82.60 and 73.91% patients in groups A, B and C, respectively; Mycological cure rates against dematophytes were 88.9, 88.9 and 85.7 in groups A, B and C, respectively. The yeast mycological cure rates were 66.7, 100 and 50 in groups A, B and C, respectively. In the case of nondermatophytes, the overall response was poor: one out of two cases (50%) responded in group A, while one case each in group B and group C did not respond at all. CONCLUSION: Terbinafine pulse therapy is effective and safe alternative in treatment of onychomycosis due to dermatophytes; and combination therapy with topical ciclopirox or amorolfine do not show any significant difference in efficacy in comparison to monotherapy with oral terbinafine.

Characterization of hot-melt extruded drug delivery systems for onychomycosis.

The objectives of this investigation were to study the physico-chemical properties of hot-melt extruded (HME) films for onychomycosis and to determine the stability of the model antifungal drug incorporated within these films. The influence of etching and instrument variables on the bioadhesion of these drug delivery systems for the human nail was also studied. Six 250 g batches (F1-F6) of hydroxypropyl cellulose (HPC) and/or poly(ethylene oxide) films containing ketoconazole (20%) were extruded using a Killion extruder (Model KLB-100). The thermal properties of HME films were investigated using differential scanning calorimetry (DSC). Scanning electron microscopy (SEM) was used to examine the surface morphology of the films and X-ray diffraction (XRD) was used to investigate the crystalline properties of the drugs, physical mixtures as well as the HME films. Stability studies were performed on the films stored at 25 degrees C/60%RH. The bioadhesive properties of these films were investigated on the human nail (ex vivo) using a Texture Analyzer. The nail samples tested were either non-treated (control) or treated with an etching gel. The parameters measured were peak adhesion force (PAF) and area under the curve (AUC). The Hansen solubility parameter was calculated using a combination of Hoy and Hoftyzer/Van Krevelen methods to estimate the likelihood of drug-polymer miscibility. SEM provided direct physical evidence of the physical state of the drug within the films. The theoretical post-extrusion content of ketoconazole remaining in the six film batches ranged from 90.3% (+/-2.2) to 102.4% (+/-9.0) for up to 6 months and from 83.9% (+/-3.6) to 91.6% (+/-3.0) for up to 12 months. Bioadhesion studies of HPC film tested on 'etched' nails recorded significantly higher PAF and AUC than that of the non-treated 'control' nails. Ketoconazole was found to be relatively stable during the extrusion process. Melting points corresponding to the crystalline drugs were not observed in the processed films. The Hansen solubility parameters predicted miscibility between the polymers and the drug. The predictions of the solubility parameters were in agreement with DSC, XRD and SEM results. Bioadhesion measurements of the film on the human nail substrate were generally higher for the etched nails than that of the control nails.

An open randomized comparative study of oral itraconazole pulse and terbinafine pulse in the treatment of onychomycosis.

BACKGROUND: Onychomycosis is a recalcitrant disease of the nails caused by dermatophytes, yeasts, and molds. AIMS: To compare the clinical efficacy of oral itraconazole pulse therapy and oral terbinafine pulse therapy in onychomycosis. METHODS: A randomized single-blind clinical comparative study was undertaken on 120 patients of onychomycosis during the period March 1999-February 2002. Sixty patients were randomly assigned to receive oral itraconazole 100 mg, two capsules twice daily for seven days a month and the other group of sixty patients received oral terbinafine 250 mg, one tablet twice daily for seven days every month. Four such monthly pulses were administered for each drug. The patients were evaluated at 4-weekly intervals till sixteen weeks and then at 24, 36 and 48 weeks. RESULTS: We observed a clinical cure rate of 82% and mycological cure rate of 90% in the group of patients treated with itraconazole while the group with terbinafine showed clinical and mycological cure rates of 79% and 87% respectively. This difference was not statistically significant. CONCLUSIONS: Both oral itraconazole and terbinafine are effective in the treatment of onychomycosis when administered in the pulse dosage form. Terbinafine is more cost effective while itraconazole has a broader spectrum of antimycotic activity.