Onychomycosis: Diagnosis and definition of cure Scher, Richard K., MD, FACP; Tavakkol, Amir, PhD, Dip Bact; Sigurgeirsson, Bárdur, MD, PhD ...
Journal of the American Academy of Dermatology,
06/2007, Letnik:
56, Številka:
6
Journal Article
Recenzirano
Until now, there has been no agreement on criteria defining resolution of onychomycosis. Most published reports use clinical and mycological cure, which comprises a completely normal-appearing nail ...plate, and negative nail culture and microscopy results, as the end point for defining success of therapeutic intervention. Reported here is the definition of onychomycosis, which delineates both primary and secondary criteria for diagnosis of onychomycosis and identifies clinical and laboratory parameters to define a resolved fungal nail infection. Onychomycosis cure is defined by the absence of clinical signs or the presence of negative nail culture and/or microscopy results with one or more of the following minor clinical signs: (1) minimal distal subungual hyperkeratosis; and (2) nail-plate thickening. Clinical signs indicative of persistent onychomycosis at the end of the observation period include (1) white/yellow or orange/brown streaks or patches in or beneath the nail plate; and (2) lateral onycholysis with subungual debris. Although nail appearance will usually continue to improve after cessation of therapy, the nails may have a persistent abnormal appearance even in cases where treatment has been effective.
Summary
Patient adherence is a key consideration in the choice of a topical regimen for the treatment of onychomycosis. The objective of this study was to investigate patient‐reported outcomes ...(treatment utilisation, adherence and satisfaction) in onychomycosis treated with once‐weekly amorolfine 5% nail lacquer versus once‐daily ciclopirox 8% nail lacquer (Study A) or once‐daily urea 40% ointment/bifonazole 1% cream combination regimen (Study B). Study A: Subjects received amorolfine and ciclopirox on opposite feet for 12 weeks. Study B: Subjects received amorolfine and urea/bifonazole on opposite feet for 6‐7 weeks. Assessments included subject adherence as per label, treatment preference and questionnaire. Study A: More subjects adhered to amorolfine (85%) than to ciclopirox (60%) (P = .025). Overall, subjects were satisfied (95% vs 100%, respectively) and the treatments were balanced in terms of preference (50% vs 45%) at week 12. Study B: More subjects adhered to amorolfine dosage (81.8%) than to the dosage of the urea/bifonazole combination regimen (59.1%) (P = .096). At the end of study, 85.7% of subjects preferred amorolfine versus 14.3% for urea/bifonazole. Fewer subjects experienced local side effects with amorolfine (4.5%) compared to urea (27.3%) and bifonazole (15%). Amorolfine 5% nail lacquer offers a simple and convenient treatment option, which may result in improved patient adherence and consequently lead to improved efficacy and patient satisfaction.
Background Onychomycosis is effectively treated with terbinafine and itraconazole. However, frequent repeated dosing is required, and hepatic and cardiac adverse events may occur. Objectives Evaluate ...efficacy and safety of albaconazole, a novel triazole, for once-weekly treatment of distal subungual onychomycosis of the great toenail. Methods This double-blind, phase II study randomized 584 patients to receive albaconazole 100 to 400 mg or placebo weekly for 24 or 36 weeks. Effective treatment was measured as mycologic cure and clear or almost clear nail at week 52. Results All treatment groups achieved greater effective treatment rates (21%-54%) compared to placebo (1%; P < .001 for all groups) at week 52. Effective treatment was attained at week 24 in ≥5% of patients in most groups. Most adverse events were mild or moderate, and treatment-related adverse events were all ≤3%. No treatment-related hepatic or cardiac serious adverse events were observed. Limitations The follow-up period was likely too short to detect maximal efficacy; cure rates were increasing at study end. The efficacy and tolerability of albaconazole were not compared with other available treatments, and the global change in target toenail scale was subjective. Conclusions Albaconazole was well tolerated at all doses and resulted in high cure rates for onychomycosis.
Atopic dermatitis (AD) primarily affects infants and young children. Although topical corticosteroids (TCSs) are often prescribed, noncorticosteroid treatments are needed because compliance with TCSs ...is poor due to concerns about their side effects. In this longest and largest intervention study ever conducted in infants with mild-to-moderate AD, pimecrolimus 1% cream (PIM) was compared with TCSs.
A total of 2418 infants were enrolled in this 5-year open-label study. Infants were randomized to PIM (n = 1205; with short-term TCSs for disease flares) or TCSs (n = 1213). The primary objective was to compare safety; the secondary objective was to document PIM's long-term efficacy. Treatment success was defined as an Investigator's Global Assessment score of 0 (clear) or 1 (almost clear).
Both PIM and TCSs had a rapid onset of action with >50% of patients achieving treatment success by week 3. After 5 years, >85% and 95% of patients in each group achieved overall and facial treatment success, respectively. The PIM group required substantially fewer steroid days than the TCS group (7 vs 178). The profile and frequency of adverse events was similar in the 2 groups; in both groups, there was no evidence for impairment of humoral or cellular immunity.
Long-term management of mild-to-moderate AD in infants with PIM or TCSs was safe without any effect on the immune system. PIM was steroid-sparing. The data suggest PIM had similar efficacy to TCS and support the use of PIM as a first-line treatment of mild-to-moderate AD in infants and children.
Autoimmune thyroid disease is the most common autoimmune disease and is highly heritable
. Here, by using a genome-wide association study of 30,234 cases and 725,172 controls from Iceland and the UK ...Biobank, we find 99 sequence variants at 93 loci, of which 84 variants are previously unreported
. A low-frequency (1.36%) intronic variant in FLT3 (rs76428106-C) has the largest effect on risk of autoimmune thyroid disease (odds ratio (OR) = 1.46, P = 2.37 × 10
). rs76428106-C is also associated with systemic lupus erythematosus (OR = 1.90, P = 6.46 × 10
), rheumatoid factor and/or anti-CCP-positive rheumatoid arthritis (OR = 1.41, P = 4.31 × 10
) and coeliac disease (OR = 1.62, P = 1.20 × 10
). FLT3 encodes fms-related tyrosine kinase 3, a receptor that regulates haematopoietic progenitor and dendritic cells. RNA sequencing revealed that rs76428106-C generates a cryptic splice site, which introduces a stop codon in 30% of transcripts that are predicted to encode a truncated protein, which lacks its tyrosine kinase domains. Each copy of rs76428106-C doubles the plasma levels of the FTL3 ligand. Activating somatic mutations in FLT3 are associated with acute myeloid leukaemia
with a poor prognosis and rs76428106-C also predisposes individuals to acute myeloid leukaemia (OR = 1.90, P = 5.40 × 10
). Thus, a predicted loss-of-function germline mutation in FLT3 causes a reduction in full-length FLT3, with a compensatory increase in the levels of its ligand and an increased disease risk, similar to that of a gain-of-function mutation.
Effects of susceptibility variants may depend on from which parent they are inherited. Although many associations between sequence variants and human traits have been discovered through genome-wide ...associations, the impact of parental origin has largely been ignored. Here we show that for 38,167 Icelanders genotyped using single nucleotide polymorphism (SNP) chips, the parental origin of most alleles can be determined. For this we used a combination of genealogy and long-range phasing. We then focused on SNPs that associate with diseases and are within 500 kilobases of known imprinted genes. Seven independent SNP associations were examined. Five-one with breast cancer, one with basal-cell carcinoma and three with type 2 diabetes-have parental-origin-specific associations. These variants are located in two genomic regions, 11p15 and 7q32, each harbouring a cluster of imprinted genes. Furthermore, we observed a novel association between the SNP rs2334499 at 11p15 and type 2 diabetes. Here the allele that confers risk when paternally inherited is protective when maternally transmitted. We identified a differentially methylated CTCF-binding site at 11p15 and demonstrated correlation of rs2334499 with decreased methylation of that site.
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