A KRT6A mutation p.Ile462Asn in a Chinese family with pachyonychia congenita, and identification of maternal mosaicism: a case report

Background Pachyonychia congenita (PC, OMIM #167200, #167210, #615726, #615728, and #615735) is a rare autosomal dominant disorder caused by keratin gene mutations in KRT6A,KRT6B,KRT6C,KRT16 or KRT17. It is characterized with nail dystrophy and palmoplantar keratoderma (PPK). The most prominent manifestation is plantar pain. This is a further unusual case of parental mosaicism in PC. Although very rare, germ cell mosaicism should be considered when providing genetic counselling for unaffected parents of a child with PC. Case presentation We report the case of a 5-year-old boy with thickening nails and oral leukokeratosis at birth. He began to develop palmoplantar keratoderma at 2 years old and his sister has similar clinical manifestation characterized with nail discoloration and thickening. A previously reported heterozygous mutation, p.Ile462Asn, was identified in KRT6A in the proband and his affected sister. SNaPshot sequencing revealed mosaicism at a level of 2.5% and 4.7% in DNA from blood and hair bulbs from the unaffected mother. HiSeq deep sequencing demonstrated low-grade mosaicism in the patient’s younger sister and parents. Conclusion These findings indicate the ability of WES and SNaPshot sequencing to detect low-frequency mosaic mutations. Although very rare, germinal mosaicism should be considered when genetic counseling is given to families with presumed spontaneous cases of PC.

Clinico-etiological Study of Nail Disorders at a Tertiary Care Center in Maharashtra, India

Background: Nail abnormalities comprise a significant proportion of dermatological disorders. Nail is a window that provides vital clues for any underlying, dermatological, and systemic diseases. Any cutaneous assessment is incomplete without examining nails despite which it is a fairly neglected appendage. Objectives: This study was carried out to document the clinical pattern, determine the etiology, and identify risk factors for various nail changes. Methods: This cross-sectional observational study was conducted on 200 consecutive patients presenting with nail changes to the outpatient department of dermatology and venereal diseases of a tertiary care hospital. The patients were enrolled after obtaining informed consent. A case record form was designed for every patient, including demographic data, nail characteristics, associated dermatological and systemic disease, and investigation details. Results: The mean age of the patients was 37.98 ± 16.79 years with a male preponderance. Occupation (housewife and manual laborer) was observed to be a significant risk factor (P < 0.001) for onychomycosis. The chief complaint related to nails was cosmetic in 49.5% of the cases. Etiology-wise nail changes secondary to dermatological diseases (44%) were the most common, followed by infections (36%); however, among dermatological diseases, psoriasis (42.2%) followed by lichen planus (16.6%) predominated. Although nail pitting was noticed in various conditions, there was a significant association between nail pitting and psoriasis (P < 0.001). Onychomycosis showed a significant association (P < 0.001) with nail discoloration and onycholysis. Distal lateral subungual onychomycosis (61.4%) was the most frequently observed pattern; nevertheless, the most common causative agent was dermatophyte Trichophyton rubrum (58.26%). A nail biopsy was performed on 15 cases, with conclusive findings in 12 patients. Conclusions: Nails should be considered an integral part of the complete dermatological evaluation. The meticulous examination of nails facilitates the early diagnosis of hitherto undetected cutaneous/systemic disease. The nail unit deserves greater attention for better understanding and utilization as a diagnostic tool.

More than Nail Deep: The Effect of Efinaconazole 10% Treatment on the Quality of Life in Patients with Onychomycosis: A post hoc Study

<b><i>Introduction:</i></b> Onychomycosis is a common, difficult-to-treat fungal nail infection. Clinical signs include nail discoloration and thickening, which patients often find embarrassing, causing a negative impact on their quality of life (QOL). <b><i>Methods:</i></b> In this post hoc study, we analyze the effect of efinaconazole 10% solution on a patient’s QOL using patient-reported scores from the OnyCOE-t™ questionnaire (appearance, stigma, physical problems, symptom frequency, symptom bothersomeness, treatment satisfaction, and overall problem). Higher scores corresponded to better functioning, thus higher QOL. <b><i>Results:</i></b> Efinaconazole 10% treatment and clinical efficacy were positively correlated with improved QOL in all domains for all groups, except with symptom bothersomeness (how much the onychomycosis symptoms worried or concerned the patient) for female patients &#x3c;40 years. While still showing improvement in most domains during efficacious treatment, female and younger patients reported lower QOL scores than their male and older counterparts, despite having better clinical outcomes at follow-ups. <b><i>Discussion:</i></b> Female and younger patients appear to be more emotionally bothered by their symptoms, regardless of treatment success or improvement of their nail’s appearance, suggesting that onychomycosis is more than nail deep and has a greater psychological effect on these patients. Therefore, younger female patients may require more assurance and mental support.

Prevalence of Occupational Skin Diseases and its Predisposing Factors in Leather Tanning Workers of Southern India

Skin diseases are a major occupational health issue in tannery workers because of work related exposure to various toxic chemicals used in tanning process. In the present study, prevalence of various skin diseases and predisposing factors in tannery workers were investigated.A cross sectional study including 114 tannery workers (male-89; female-25) employed at different tanneries of Southern India was carried out. Face to face interview with pre-designed questionnaire and health examination was conducted. Skin samples obtained from the participants were subjected to microscopic examination and microbial culture for diagnosis of skin diseases. The prevalence of occupational skin disorders were 39% among the study participants. Contact dermatitis (16%), skin infections (16%), eczematous lesions (7%) and nail discoloration (1.75%) wereidentified. Skin infections of fungal origin were identified among 11.4% of subjects. The skin infections of fungi; tenia corporis, tenia cruris, tenia unguium, tenia versicolor, tenia pedis and Pityriosis versicolor were identified. Bacterial skin infections identified were associated with contact dermatitis. Lack of PPE usage was reported among 30% of workers. Hazardous working environment, chemical exposure, humidity and lack of PPEusage were significantly associated with increased skin disease incidence(p<0.05), indicating the major predisposing factorsfor Occupation skin diseases.The findings of the study emphasize that,workers in the pre-tanning section and tanning sections are more vulnerable to occupational skin diseases.Compliance to use of PPEs, engineering controls to reduce exposure, education, frequent health surveillance and early identification & treatment could mitigate the occupational skindiseasesamongtannery workers.

Bluish-gray fingernail discoloration due to the use of nivolumab

Introduction Immune checkpoint inhibitors have improved clinical outcomes in a wide range of cancers. While skin toxicity is not uncommon with immune checkpoint inhibitors, generalized nail discoloration has not been reported with their use in oncology. Case report Herein, we report a unique case of bluish-gray fingernail discoloration due to nivolumab therapy for relapsed melanoma. Management and outcome: This condition reversed completely 10 weeks after nivolumab discontinuation. Naranjo nomogram assessment renders the causality relationship between nivolumab and nail discoloration probable. Discussion To our knowledge, this is the first case report of an unusual bluish-gray nail discoloration due to therapy with nivolumab. The mechanism by which nivolumab causes this side effect remains to be elucidated.