Onychomycosis: a review Gupta, A.K.; Stec, N.; Summerbell, R.C. ...
Journal of the European Academy of Dermatology and Venereology,
September 2020, 2020-Sep, 2020-09-00, Volume:
34, Issue:
9
Journal Article
Peer reviewed
Onychomycosis is a fungal infection of the nail, causing discoloration and thickening of the affected nail plate, and is the most common nail infection worldwide. Onychomycosis was initially thought ...to be predominantly caused by dermatophytes; however, new research has revealed that mixed infections and those caused by non‐dermatophyte moulds (NDMs) are more prevalent than previously thought, especially in warmer climates. Microscopy and fungal culture are the gold standard techniques for onychomycosis diagnosis, but high false‐negative rates have pushed for more accurate methods, such as histology and PCR. As NDMs are skin and laboratory contaminants, their presence as an infectious agent requires multiple confirmations and repeated sampling. There are several treatment options available, including oral antifungals, topicals and devices. Oral antifungals have higher cure rates and shorter treatment periods than topical treatments, but have adverse side effects such as hepatotoxicity and drug interactions. Terbinafine, itraconazole and fluconazole are most commonly used, with new oral antifungals such as fosravuconazole being evaluated. Topical treatments, such as efinaconazole, tavaborole, ciclopirox and amorolfine have less serious side effects, but also have generally lower cure rates and much longer treatment regimens. New topical formulations are being investigated as faster‐acting alternatives to the currently available topical treatments. Devices such as lasers have shown promise in improving the cosmetic appearance of the nail, but due to a high variation of study methods and definitions of cure, their effectiveness for onychomycosis has yet to be sufficiently proven. Recurrence rates for onychomycosis are high; once infected, patients should seek medical treatment as soon as possible and sanitize their shoes and socks. Prophylactic application of topicals and avoiding walking barefoot in public places may help prevent recurrence.
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The occurrence of hypersensitivity reactions including rare but life‐threatening Stevens–Johnson syndrome (SJS) and drug‐induced hypersensitivity syndrome (HSS) limits the use of the anticonvulsant ...carbamazepine (CBZ). Human leukocyte antigen‐B (HLA)‐B*15:02 and HLA‐A*31:01 have been identified as predictive genetic markers for CBZ hypersensitivity in Asian and European patients. To replicate these genetic associations in pediatric patients from North America with a diverse ethnic background, we investigated HLA‐A*31:01 and HLA‐B*15:02 in 42 children with CBZ hypersensitivity and 91 CBZ‐tolerant children from across Canada. HLA‐A*31:01 was significantly associated with CBZ‐HSS (odds ratio (OR): 26.4, P = 0.0025) and maculopapular exanthema (MPE) (OR: 8.6, P = 0.0037) but not with CBZ‐SJS. Conversely, HLA‐B*15:02 was associated with CBZ‐SJS (OR: 38.6, P = 0.002) but not HSS or MPE. This study is the first to demonstrate the association of HLA‐A*31:01 with CBZ hypersensitivity in children, providing important replication of this association and highlighting the importance of HLA‐A*31:01 as a predictive biomarker across various ancestries.
Clinical Pharmacology & Therapeutics (2013); 94 1, 142–149. doi:10.1038/clpt.2013.55
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Advances in genetic research and molecular biology techniques have made it possible to begin to characterize the underlying genetic factors that predispose patients to serious forms of drug‐induced ...skin injury (DISI). To facilitate research in this area, we have set out standardized phenotypic definitions for (i) Stevens‐Johnson syndrome/toxic epidermal necrolysis (SJS/TEN), (ii) acute generalized exanthematous pustulosis (AGEP), and (iii) hypersensitivity syndrome (HSS; also known as drug reaction with eosinophilia and systemic symptoms (DRESS) and drug‐induced hypersensitivity syndrome (DIHS)). A DISI Expert Working Group comprising participants with varied expertise reviewed and debated current terminology and diagnostic criteria for DISI and agreed on the minimum phenotypic criteria for selected forms of DISI (SJS/TEN, AGEP, and HSS). In addition, an algorithm has been developed to aid appropriate clinical categorization of patients with DISI. These standardized criteria will be important in facilitating adequate and accurate patient recruitment in order to advance research in pharmacogenomic, immunological, mechanistic, and epidemiological studies.
Clinical Pharmacology & Therapeutics (2011) 89 6, 896–901. doi:10.1038/clpt.2011.79
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Linked Article: Murrell et al. Br J Dermatol 2021; 185:745–755.
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5.
Lymphomatoid papulosis: an update and review Martinez‐Cabriales, S.A.; Walsh, S.; Sade, S. ...
Journal of the European Academy of Dermatology and Venereology,
January 2020, 2020-Jan, 2020-01-00, 20200101, Volume:
34, Issue:
1
Journal Article
Peer reviewed
Lymphomatoid papulosis (LyP) is a benign chronic often relapsing skin condition that belongs to the CD30‐positive cutaneous lymphoproliferative disorders. LyP typically presents as crops of lesions ...with a tendency to self‐resolve, and morphology can range from solitary to agminated or diffuse papules and plaques to nodules or tumours. The clinical–histological spectrum can range from borderline cases to overlap with primary cutaneous anaplastic cell lymphoma (pcALCL). Histology and immunophenotype commonly show overlap with other CD30‐positive disorders and sometimes may be identical to pcALCL, making its diagnosis more difficult. Patients with LyP have an increased risk of developing a second neoplasm such as mycosis fungoides, pcALCL and/or Hodgkin lymphoma. Clinical correlation allows its proper classification and diagnosis, which is fundamental for treatment and prognosis. This review focuses on the clinical appearance, histopathological features, diagnosis, differential diagnosis and management of LyP.
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Summary
Background
Rituximab is a promising therapy in pemphigus. However, there is no consensus on optimum dose.
Objectives
To compare the efficacy, in terms of clinical and immunological outcomes ...in patients with pemphigus, of a high (2 × 1000 mg) vs. a low dose (2 × 500 mg) of rituximab.
Methods
This was a randomized, observer‐blinded trial wherein 22 patients with pemphigus were randomized into two treatment groups. Patients received either two doses (day 0 and day 15) of 1000 mg rituximab or 500 mg rituximab, and were followed up for 48 weeks. Clinical activity was assessed by a blinded investigator. Indices of enzyme‐linked immunosorbent assays (ELISAs) for desmoglein (Dsg)1 and Dsg3, and CD19 cell count were examined at regular intervals.
Results
There was no statistically significant difference in early and late clinical end points, and total cumulative dose of corticosteroids between the two groups. At week 40, the fall in Ikeda severity score was significantly more in the 2 × 1000 mg group than in 2 × 500 mg group (P = 0·049). Patients in the 2 × 500 mg group received a significantly higher cumulative dose of azathioprine (P = 0·018). The ELISA indices of Dsg1 and Dsg3 showed a statistically significant decline in the 2 × 1000 mg group only. B cell repopulation occurred earlier in the 2 × 500 mg group by 8 weeks.
Conclusions
A few clinical and immunological study parameters have suggested improved outcomes in patients receiving high‐dose (2 × 1000 mg) rituximab.
What's already known about this topic?
There is no agreement on the optimum dose of rituximab to be used in treating patients with pemphigus.
A single study has reported low‐dose rituximab (2 × 500 mg) to be effective in patients with pemphigus.
What does this study add?
A few clinical (relapse rate, adjuvant requirement) and immunological (fall in desmoglein indices, CD19 cell repopulation) outcomes suggest improved outcomes in patients with pemphigus receiving 2 × 1000 mg rituximab compared with a dose of 2 × 500 mg.
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Androgenetic alopecia, or male/female pattern baldness, is the most common type of progressive hair loss disorder. The aim of this study was to review recent advances in non‐surgical treatments for ...androgenetic alopecia and identify the most effective treatments. A network meta‐analysis (NMA) was conducted of the available literature of the six most common non‐surgical treatment options for treating androgenetic alopecia in both men and women; dutasteride 0.5 mg, finasteride 1 mg, low‐level laser therapy (LLLT), minoxidil 2%, minoxidil 5% and platelet‐rich plasma (PRP). Seventy‐eight studies met the inclusion criteria, and 22 studies had the data necessary for a network meta‐analysis. Relative effects show LLLT as the superior treatment. Relative effects show PRP, finasteride 1 mg (male), finasteride 1 mg (female), minoxidil 5%, minoxidil 2% and dutasteride (male) are approximately equivalent in mean change hair count following treatment. Minoxidil 5% and minoxidil 2% reported the most drug‐related adverse events (n = 45 and n = 23, respectively). The quality of evidence of minoxidil 2% vs. minoxidil 5% was high; minoxidil 5% vs. placebo was moderate; dutasteride (male) vs. placebo, finasteride (female) vs. placebo, minoxidil 2% vs. placebo and minoxidil 5% vs. LLLT was low; and finasteride (male) vs. placebo, LLLT vs. sham, PRP vs. placebo and finasteride vs. minoxidil 2% was very low. Results of this NMA indicate the emergence of novel, non‐hormonal therapies as effective treatments for hair loss; however, the quality of evidence is generally low. High‐quality randomized controlled trials and head‐to‐head trials are required to support these findings and aid in the development of more standardized protocols, particularly for PRP. Regardless, this analysis may aid physicians in clinical decision‐making and highlight the variety of non‐surgical hair restoration options for patients.
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Tinea capitis in children: a systematic review of management Gupta, A.K.; Mays, R.R.; Versteeg, S.G. ...
Journal of the European Academy of Dermatology and Venereology,
December 2018, 2018-Dec, 2018-12-00, 20181201, Volume:
32, Issue:
12
Journal Article
Peer reviewed
Open access
Background
Tinea capitis is the most common cutaneous fungal infection in children.
Objectives
This review aims to evaluate the differences that exist between medications for the treatment of tinea ...capitis, to determine whether there are any significant adverse effects associated and to define the usefulness of sample collection methods.
Methods
We conducted a systematic literature search of available papers using the databases PubMed, OVID, Cochrane Libraries and ClinicalTrials.gov. Twenty‐one RCTs and 17 CTs were found.
Results
Among the different antifungal therapies (oral and combination thereof), continuous itraconazole and terbinafine had the highest mycological cure rates (79% and 81%, respectively), griseofulvin and terbinafine had the highest clinical cure rates (46% and 58%, respectively) and griseofulvin and terbinafine had the highest complete cure rate (72% and 92%, respectively). Griseofulvin more effectively treated Microsporum infections; terbinafine and itraconazole more effectively cured Trichophyton infections. Only 1.0% of children had to discontinue medication based on adverse events. T. tonsurans was the most common organism found in North America, and hairbrush collection method is the most efficient method of sample collection. Additionally, using a hairbrush, toothbrush or cotton swab to identify the infecting organism(s) is the least invasive and most efficient method of tinea capitis sample collection in children.
Conclusions
Current dosing regimens of reported drugs are effective and safe for use in tinea capitis in children.
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Summary
Background Drug‐induced hypersensitivity syndrome (DIHS) is an adverse reaction with clinical signs of fever, rash and internal organ involvement. In the vast majority of patients in Japan, ...the causative drugs for DIHS are limited to the following eight: carbamazepine, phenytoin, phenobarbital, zonisamide, mexiletine, dapsone, salazosulfapyridine and allopurinol. The association of human herpesvirus (HHV)‐6 reactivation with DIHS has been reported by various groups.
Objectives To confirm the relationship between the flaring and severity of DIHS and HHV‐6 reactivation.
Methods We evaluated 100 patients with drug rash and systemic symptom(s) caused by the drugs associated with DIHS. HHV‐6 reactivation was examined by serological antibody assay and quantitative real‐time polymerase chain reaction assay of serial serum samples.
Results Anti‐HHV‐6 IgG titres increased in 62 of 100 patients, 14–28 days after the onset of symptoms. These patients suffered from severe organ involvement and a prolonged course compared with 38 patients showing no reactivation of HHV‐6. Significant amounts of HHV‐6 DNA were detected in serum samples from 18 of the 62 patients. Flaring of symptoms such as fever and hepatitis was closely related to HHV‐6 reactivation in these 18 patients. It should be emphasized that all five patients with fatal outcome and 10 patients with renal failure were in the HHV‐6 reactivation group.
Conclusions A combination of immunological reaction to a drug and HHV‐6 reactivation results in the severe course of DIHS. The demonstration of HHV‐6 reactivation is a useful marker of diagnosis as well as prognosis in DIHS.
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Summary
Background
Onychomycosis is a fungal infection of the nail caused by dermatophytes, yeasts and nondermatophyte moulds that accounts for approximately 50% of all nail‐related disease.
...Objectives
This study aims to assess the effectiveness and safety of monotherapy and combination treatments for toenail onychomycosis using a network meta‐analysis (NMA).
Methods
Quality of evidence was assessed using Cochrane‐compliant rules and the Grading of Recommendations, Assessment, Development and Evaluations (GRADE) approach. Efficacy and safety outcomes were compared using a random‐effects NMA to estimate pooled odds ratios (ORs) of direct and indirect comparisons among oral and topical treatments (PROSPERO 2015: CRD42018086912). There were not enough eligible combination and device‐based therapy trials to include in the NMA.
Results
Of 77 randomized controlled trials, 26 were included in the ORs (8136 patients). There were no significant inconsistencies between the direct and indirect evidence. Relative effects show that the odds of mycological cure with continuous terbinafine 250 mg or continuous itraconazole 200 mg are significantly greater than topical treatments. Fluconazole, pulse regimens of terbinafine and itraconazole, and topical treatments did not differ significantly in the odds of achieving mycological cure. The ORs of adverse events occurring with oral or topical treatments were not significantly different from each other. For mycological cure, evidence was of moderate or high quality while evidence ranged from very low to high quality for adverse events.
Conclusions
Our review suggests that oral and topical treatments for toenail onychomycosis are safe and effective in producing mycological cure.
What's already known about this topic?
Topical treatments traditionally have lower success rates than oral treatments.
Oral treatments have the advantage of shorter treatment durations, but also present challenges in cases of drug–drug interactions or immunosuppression.
A network meta‐analysis (NMA) gathers data from indirect evidence to gain confidence about all treatment comparisons and allows for estimation of comparative effects that have not been investigated in head‐to‐head randomized clinical trials (RCTs).
What does this study add?
This NMA of efficacy and safety includes all RCTs of oral, topical, combination and device‐based treatments for toenail onychomycosis, adhering to the Preferred Reporting Items for Systematic Reviews and Meta‐Analyses (PRISMA) statement for NMA.
The odds of achieving mycological cure with continuous terbinafine 250 mg or continuous itraconazole 200 mg were significantly greater than topical treatments.
Fluconazole, pulse regimens of terbinafine and itraconazole, and topical treatments did not differ significantly in the odds of achieving mycological cure.
Linked Comment: Morris‐Jones. Br J Dermatol 2020; 182:263.
Plain language summary available online
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