Differentiating clinical characteristics of perianal inflammatory bowel disease from perianal hidradenitis suppurativa.

BACKGROUND: Perianal draining tunnels in hidradenitis suppurativa (HS) and perianal fistulizing inflammatory bowel disease (IBD) present diagnostic and management dilemmas. METHODS: We conducted a retrospective chart review of patients with perianal disease evaluated at Mayo Clinic from January 1, 1998, through July 31, 2021. Patients' demographic and clinical data were extracted, and 28 clinical features were collected. After experimenting with several machine learning techniques, random forests were used to select the 15 most important clinical features to construct the diagnostic prediction model to distinguish perianal HS from fistulizing perianal IBD. RESULTS: A total of 263 patients were included (98 with HS, 100 with IBD, and 65 with both IBD and HS). Patients with HS had a higher mean body mass index, a higher smoking rate, and more commonly showed cutaneous manifestations of tunnels and comedones, while fistulas, abscesses, induration, anal tags, ulcers, and anal fissures were more common in patients with IBD. In addition to having lesions in the perianal area, patients with IBD often had lesions in the buttocks and perineum, while those with HS had additional lesions in the axillae and groin. Among the statistically significant features, the 15 most important were identified by random forest: fistula, tunnel, digestive symptom, knife-cut ulcer, perineum, body mass index, age, axilla, abscess, tags, smoking, groin, genital cutaneous edema, erythema, and bilateral/unilateral. CONCLUSIONS: The results of this study may help differentiate perianal lesions, especially perineal HS and fistulizing perineal IBD, and provide promise for a better therapeutic outcome.

Dermatologic surgeons' approaches to acral lentiginous melanoma: a survey of the American College of Mohs Surgery.

Acral lentiginous melanoma (ALM) is a subtype of melanoma that primarily affects ethnic minorities and is associated with poor outcomes. Racial inequalities in melanoma survival, particularly between Blacks and Whites, have been well documented in the literature. There are limited data on the role of surgical approach to ALM and its contribution to the existing disparities in ALM survival. Thus, this study aimed to investigate the role of surgical approach to ALM among Mohs surgeons. The survey was distributed to members of the American College of Mohs Surgery (ACMS), with 43 physicians completing the survey. The results showed that there was no consensus among Mohs surgeons regarding the surgical approach for ALM, even for advanced stages. 74% respondents performed complete circumferential peripheral and deep margin assessment (CCPDMA) for ALM, including Mohs micrographic surgery (MMS) or en face staged excision. However, barriers such as limited training, low comfort operating on acral sites, and inadequate access to specialized biopsies were reported. Treatment recommendations varied widely regardless of the ALM stage, with no significant differences based on exposure to ALM during training, practice setting, or percent of skin of color patients served. These findings highlight the lack of guidelines and the need for more data on outcomes to support optimal management of ALM. The study emphasizes the importance of addressing healthcare disparities and improving survival outcomes, particularly for ethnic minorities affected by ALM. Consensus guidelines could help standardize treatment approaches and potentially reduce disparities in ALM management.

Neutrophilic eccrine hidradenitis: a retrospective study.

BACKGROUND: Neutrophilic eccrine hidradenitis (NEH) is a benign neutrophilic dermatosis not well recognized beyond an association with malignancy. Although the disease is commonly reported in adults with malignancy, this association is uncommon in children. The diagnosis of NEH is predominantly based on histologic findings to exclude alternative diagnoses for adults, but biopsy is not usually required for children. METHODS: A retrospective study was performed of adult and pediatric patients diagnosed with NEH at three Mayo Clinic sites from January 1, 1992, to January 1, 2022. The aim of this study was to elucidate risk factors for NEH and its clinical characteristics, treatment options, and natural course. Clinical information and pathologic results were collected from health records. Available pathologic slides were reviewed with a dermatopathologist. RESULTS: Of 47 patients identified, 33 had either histologic or clinical confirmation of the diagnosis; 21 were adults (64%), and 12 were children (36%). Most adults (16/21; 76%) had underlying malignancy and received chemotherapy. Five adults (24%) were classified as having idiopathic NEH, and they were younger and had higher NEH recurrence rates than the other adults. Only one pediatric patient (8%) had underlying malignancy. For 10 children (83%), NEH was preceded by strenuous activity. Initial findings of idiopathic NEH were palmoplantar eruptions for both adult and pediatric patients, whereas malignancy-associated NEH commonly involved the face and axillae. CONCLUSIONS: Among adults, NEH is commonly associated with malignancy and chemotherapy. Among children, idiopathic NEH occurs primarily after overexertion, and malignancy is highly unlikely to be the cause of NEH.

Iatrogenic Demodex folliculitis: A case report.

Demodex folliculorum is a commensal mite that inhabits the orifices of cutaneous pilosebaceous follicles. Overgrowth of these organisms can lead to Demodex folliculitis, which typically presents as papules and pustules predominantly involving the temples, cheeks, and occasionally the chest. We present a 51-year-old woman with iatrogenic Demodex folliculitis secondary to immunosuppressive treatment for an autoimmune connective tissue disease. Histopathological exam of a skin biopsy, which revealed follicular Demodex mites, confirmed the diagnosis. The eruption was treated with oral ivermectin and topical metronidazole gel, and the patient's immunosuppressive regimen was decreased, resulting in marked improvement in the eruption within 6 weeks and no worsening of her underlying autoimmune disorder. This case emphasizes the importance of considering Demodex folliculitis in the differential diagnosis of a new onset rash in the context of immunosuppressive treatment.

Infantile perianal pyramidal protrusion: A retrospective review of 27 patients.

BACKGROUND: Infantile perianal pyramidal protrusion (IPPP) is a rare benign skin condition that is typically seen in infant girls. This condition is often mistaken for other skin lesions such as acrochordons, condyloma acuminatum, and sequelae of sexual abuse. Many clinicians are unfamiliar with IPPP which can lead to aggressive workup and treatment. The purpose of this study was to elucidate demographic data, clinical features, diagnostic workup, and management of IPPP in a large cohort of patients seen at an academic medical center. METHODS: A retrospective review of patients diagnosed with IPPP at Mayo Clinic, Rochester, MN was conducted. Demographic data, examination findings, diagnostic workup, and treatments were noted. RESULTS: Twenty-seven patients with IPPP, 24 of which were girls and 3 were boys from the ages of 1 day to 4 years (mean 10.8 months, median 8.6 months) were identified. Symptoms were reported in 63% (17/27) of patients. Four patients received treatment with topical corticosteroid or local anesthetic. No patient underwent skin biopsy. CONCLUSION: IPPP is commonly observed in healthy prepubertal girls. Constipation is a common symptom. Awareness of this entity may prevent overtreatment and unnecessary evaluation.

Continuous positive airway pressure device-associated nonhealing ulcer on the nasal dorsum: chondrodermatitis nodularis nasi.

With increasing use of positive airway pressure devices for disordered breathing during sleep, appreciation for potential associated side effects is essential. Chondrodermatitis nodularis nasi is a rare variant of chondrodermatitis nodularis chronic helicis that presents as a nonhealing erosion or ulcer on the nose and can occur in association with chronic use of positive airway pressure devices. We present a case of symptomatic chondrodermatitis nodularis nasi associated with continuous positive airway pressure use, fully responsive to treatment, and propose that this condition is highly underrecognized. Dermatology referral can assist in diagnosis, management, and exclusion of cutaneous malignancy. CITATION: Reinhart JP, Isaq NA, Peters MS, Vidal NY. Continuous positive airway pressure device-associated nonhealing ulcer on the nasal dorsum: chondrodermatitis nodularis nasi. J Clin Sleep Med. 2023;19(6):1157-1159.

A Practical Guide to the Diagnosis, Evaluation, and Treatment of Cutaneous T-Cell Lymphoma.

Cutaneous T-cell lymphomas are a clinically and histopathologically heterogenous group of disorders, encountered in dermatologic practice. In this article, we provide a detailed practical guide to the evaluation, diagnosis, and management of common cutaneous T-cell lymphomas. Emphasis is placed on the clinical evaluation including the role of the dermatologist in the accurate assessment of body surface area involvement for disease staging, appropriate biopsy techniques, and key considerations, recent advances in the molecular genetic characteristics of disease, and common treatment approaches.

Phosphorylation of a Conserved Tyrosine in the Papillomavirus E2 Protein Regulates Brd4 Binding and Viral Replication.

The papillomavirus (PV) E2 protein coordinates viral transcription and genome replication. Following a strategy to identify amino acids in E2 that are posttranslationally modified, we reported that tyrosine kinase fibroblast growth factor receptor 3 (FGFR3) complexes with and phosphorylates E2, which inhibits viral DNA replication. Here, we present several lines of evidence indicating that tyrosine (Y) 138 of HPV-31 E2 is a substrate of FGFR3. The active form of FGFR3 bound to and phosphorylated the region of amino acids (aa) 107 to 175 in HPV-31 E2. The E2 phenylalanine (F) mutant Y138F displayed reduced FGFR3-induced phosphotyrosine. A constitutive kinase-active FGFR3 inhibited wild-type (WT) E2-induced E1-dependent DNA replication, while the 138F mutant retained activity. The tyrosine to glutamic acid (E) mutant Y138E, which can mimic phosphotyrosine, failed to induce transient DNA replication, although it maintained the ability to bind and localize the viral DNA helicase E1 to the viral origin. The bromodomain-containing protein 4 (Brd4) binds to E2 and is necessary for initiation of viral DNA synthesis. Interestingly, the Y138E protein coimmunoprecipitated with full-length Brd4 but was defective for association with its C-terminal domain (CTD). These results imply that the activity of the FGFR3 kinase in the infected epithelial cell restricts the HPV replication program through phosphorylation of E2 at Y138, which interferes with E2 binding to the Brd4 CTD, and that this interaction is required for initiation of viral DNA synthesis.IMPORTANCE Human papillomaviruses (HPVs) are highly infectious pathogens that commonly infect the oropharynx and uterine cervix. The idea that posttranslational modifications of viral proteins coordinates viral genome replication is less explored. We recently discovered that fibroblast growth factor receptor 3 (FGFR3) phosphorylates the viral E2 protein. The current study demonstrates that FGFR3 phosphorylates E2 at tyrosine 138, which inhibits association with the C-terminal peptide of Brd4. This study illustrates a novel regulatory mechanism of virus-host interaction and provides insight into the role of Brd4 in viral replication.

Positively Charged Oligo[Poly(Ethylene Glycol) Fumarate] Scaffold Implantation Results in a Permissive Lesion Environment after Spinal Cord Injury in Rat.

Positively charged oligo[poly(ethylene glycol) fumarate] (OPF+) scaffolds loaded with Schwann cells bridge spinal cord injury (SCI) lesions and support axonal regeneration in rat. The regeneration achieved is not sufficient for inducing functional recovery. Attempts to increase regeneration would benefit from understanding the effects of the scaffold and transplanted cells on lesion environment. We conducted morphometric and stereological analysis of lesions in rats implanted with OPF+ scaffolds with or without loaded Schwann cells 1, 2, 3, 4, and 8 weeks after thoracic spinal cord transection. No differences were found in collagen scarring, cyst formation, astrocyte reactivity, myelin debris, or chondroitin sulfate proteoglycan (CSPG) accumulation. However, when scaffold-implanted animals were compared with animals with transection injuries only, these barriers to regeneration were significantly reduced, accompanied by increased activated macrophages/microglia. This distinctive and regeneration permissive tissue reaction to scaffold implantation was independent of Schwann cell transplantation. Although the tissue reaction was beneficial in the short term, we observed a chronic fibrotic host response, resulting in scaffolds surrounded by collagen at 8 weeks. This study demonstrates that an appropriate biomaterial scaffold improves the environment for regeneration. Future targeting of the host fibrotic response may allow increased axonal regeneration and functional recovery.