Dermatologic Fungal Neglected Tropical Diseases-Part II. Management and Morbidity.

In this part 2 of a 2-part continuing medical education series, the management, outcomes, and morbidities for fungal skin neglected tropical diseases (NTDs), including eumycetoma, chromoblastomycosis, paracoccidioidomycosis, sporotrichosis, emergomycosis, talaromycosis, and lobomycosis are reviewed. While fungal skin NTDs are associated with poverty in resource-limited settings, they are more often associated with immunosuppression and global migration in the United States. These infections have a high morbidity burden, including disfigurement, physical disability, coinfection, malignant transformation, mental health issues, and financial impact. For most fungal skin NTDs, management is difficult and associated with low cure rates. Dermatologists play a central role in initiating appropriate treatment early in disease course in order to improve patient outcomes.

Diagnosis and management of longitudinal erythronychia: A clinical review by an expert panel.

Longitudinal erythronychia (LE) is defined as a longitudinal red band of the nail(s) and is classified as localized (involvement of 1 nail) or polydactylous (involvement of more than 1 nail). The differential diagnosis is distinct for these classifications. The etiologies of localized longitudinal erythronychia are most frequently benign subungual neoplasms and less often malignancies. Polydactylous longitudinal erythronychia is typically secondary to regional or systemic diseases, including lichen planus and Darier disease. LE is a common but underrecognized clinical finding. Increased dermatologist awareness of the clinical characteristics and differential diagnosis for LE is necessary given the possibility for malignancy and associated systemic disease. In this clinical review, the clinical features, differential diagnosis, evaluation, and management of LE are described.

Clinical Course, Antifungal Susceptibility, and Genomic Sequencing of Trichophyton indotineae.

Importance: Trichophyton indotineae is an emerging dermatophyte causing outbreaks of extensive tinea infections often unresponsive to terbinafine. This species has been detected worldwide and in multiple US states, yet detailed US data on infections with T indotineae are sparse and could improve treatment practices and medical understanding of transmission. Objective: To correlate clinical features of T indotineae infections with in vitro antifungal susceptibility testing results, squalene epoxidase gene sequence variations, and isolate relatedness using whole-genome sequencing. Design, Setting, and Participants: This retrospective cohort study of patients with T indotineae infections in New York City spanned May 2022 to May 2023. Patients with confirmed T indotineae infections were recruited from 6 New York City medical centers. Main Outcome and Measure: Improvement or resolution at the last follow-up assessment. Results: Among 11 patients with T indotineae (6 male and 5 female patients; median [range] age, 39 [10-65] years), 2 were pregnant; 1 had lymphoma; and the remainder were immunocompetent. Nine patients reported previous travel to Bangladesh. All had widespread lesions with variable scale and inflammation, topical antifungal monotherapy failure, and diagnostic delays (range, 3-42 months). Terbinafine treatment failed in 7 patients at standard doses (250 mg daily) for prolonged duration; these patients also had isolates with amino acid substitutions at positions 393 (L393S) or 397 (F397L) in squalene epoxidase that correlated with elevated terbinafine minimum inhibitory concentrations of 0.5 µg/mL or higher. Patients who were treated with fluconazole and griseofulvin improved in 2 of 4 and 2 of 5 instances, respectively, without correlation between outcomes and antifungal minimum inhibitory concentrations. Furthermore, 5 of 7 patients treated with itraconazole cleared or had improvement at the last follow-up, and 2 of 7 were lost to follow-up or stopped treatment. Based on whole-genome sequencing analysis, US isolates formed a cluster distinct from Indian isolates. Conclusion and Relevance: The results of this case series suggest that disease severity, diagnostic delays, and lack of response to typically used doses and durations of antifungals for tinea were common in this primarily immunocompetent patient cohort with T indotineae, consistent with published data. Itraconazole was generally effective, and the acquisition of infection was likely in Bangladesh.

Nails in older adults.

As the world's population of adults greater than 60 years old continues to increase, it is important to manage nail disorders that may impact their daily lives. Nail disorders may have significant impact on quality of life due to decreased functionality, extreme pain, or social embarrassment. In this review, we discuss nail disorders affecting older patients, including physiologic, traumatic, drug-induced, infectious, environmental, inflammatory, and neoplastic conditions. Diagnosis of these conditions involves a detailed history, physical examination of all 20 nails, and depending on the condition, a nail clipping or biopsy and/or diagnostic imaging. Nails grow even more slowly in older adults compared to younger individuals, and therefore it is important for accurate diagnosis, and avoidance of inappropriate management and delay of treatment. Increased awareness of nail pathologies may help recognition and management of nail conditions in older adults.

Nail disorders are common amongst older adults and may cause decreased functionality, pain, psychosocial problems and impact quality of life.Many nail conditions, both physiologic or pathologic, may have similar presentation in older adults. Confirmation testing is important to avoid inappropriate or delayed treatment.The increased frequency of comorbidities, drug interactions, polypharmacy, and mental or physical limitations with aging must be considered when managing care of older patients with nail disorders.

Assessing melanoma prognosis: the interplay between patient profiles, survival, and BRAF, NRAS, KIT, and TWT mutations in a retrospective multi-study analysis.

The incidence and prevalence of melanoma are increasing globally, presenting a significant public health concern. The main genetic drivers of melanoma include BRAF, NRAS, KIT and triple wild-type (TWT) mutations. Little is known about the effects of these mutations on outcomes in terms of demographics and patient characteristics. We examined differences in melanoma mortality risk and mutation count across mutation type and patient disease profile. We extrapolated primary melanoma patient data from 14 studies via the cBioportal database. Patients were divided into demographic groups and classified according to BRAF, NRAS, KIT and TWT mutation status. Analyses included two-sample Student t-test and two-way analysis of variance tests analysis with Tukey's post hoc test. Survival outcomes were compared via Kaplan-Meier curve and Cox regression. NRAS-mutated patients exhibited decreased overall survival compared to BRAF-mutated patients. Male patients had higher mutation counts across all gene groups than females, with the fewest TWT mutations in comparison to BRAF, NRAS and KIT mutations. Males also exhibited increased mortality risk for NRAS, KIT and TWT mutations compared to BRAF mutations. An unknown primary melanoma was associated with increased mortality risk across all gene groups. NRAS-mutated acral melanoma patients had an increased mortality risk compared to NRAS-mutated cutaneous melanoma patients. Older patients had a higher mortality risk than younger patients. Patients with heavier versus lower weights had lower mortality risk, which was more pronounced for BRAF-mutated patients. These relationships highlight the importance of demographic and pathologic relationships to aid in risk assessment and personalize treatment plans.

Expanding the Differential Diagnosis of the Painful Nail: A Case of an Onychopapilloma with Neuroma.

Introduction: Onychopapilloma most commonly presents as longitudinal erythronychia, but diagnosis may be challenging in some cases due to varied clinical presentations. Most patients with onychopapillomas do not report associated pain but instead more commonly report functional interference. Case Report: We present a case of a 74-year-old female with a 5-year history of splitting and lifting of the right thumbnail, accompanied by nail sensitivity and intermittent painful throbbing. Clinical examination was significant for a less than 1 mm red line with distal onycholysis. Love's test and a cold test performed with ice pack were negative. X-ray of the right thumb was negative for erosion or exostosis. Nail biopsy was performed, and dermatopathology was consistent with onychopapilloma with a concomitant traumatic neuroma. Conclusion: We report a case of onychopapilloma with a concomitant traumatic neuroma. Subungual neuromas are extremely rare and have not previously been associated with onychopapilloma. Our case supports the expansion of the differential diagnosis for a painful nail and demonstrates the importance of diagnostic confirmation with biopsy and histopathology.

Atypical Presentation of Pemphigus Vulgaris: Nail Involvement in a 20-Year-Old Male.

Pemphigus vulgaris (PV) mainly causes blistering of the skin and mucous membranes, with nail unit involvement being rare. Nail involvement may serve as an indicator of disease severity. We present a case of a 20-year-old male with PV who had both cutaneous and nail findings, with nail changes corresponding with disease severity. The patient with biopsy-confirmed PV, on prednisone and mycophenolate, presented to the emergency department with an acute flare of PV and severe mandibular pain and lymphadenopathy. At follow-up in our outpatient department, the physical examination was significant for onychomadesis and onycholysis of the fingernails. Prednisone and mycophenolate dosages were increased, and rituximab infusions were initiated. Bullae and mucosal lesions resolved on the follow-up, and nail changes improved. This case appends an unusual perspective to the limited literature on PV-associated nail changes, especially in younger patients. It advocates for meticulous history taking and physical examination and supports a correlation between nail symptoms and PV disease severity.