Phase 3 efficacy and safety of abrocitinib in adults with moderate-to-severe atopic dermatitis after switching from dupilumab (JADE EXTEND).

BACKGROUND: Abrocitinib efficacy by prior dupilumab response status in patients with moderate-to-severe atopic dermatitis has not previously been assessed in phase 3 studies. OBJECTIVE: Examine efficacy and safety of abrocitinib among patients who received prior dupilumab. METHODS: Patients with moderate-to-severe atopic dermatitis received abrocitinib 200 mg or 100 mg once daily in JADE EXTEND (phase 3 extension) after dupilumab in double-blind, placebo-controlled phase 3 JADE COMPARE. RESULTS: Among prior dupilumab responders, ≥75% improvement in Eczema Area and Severity Index was achieved in 93.5% and 90.2% of patients who received 12 weeks of abrocitinib 200 mg and 100 mg, respectively; ≥4-point improvement in Peak Pruritus Numerical Rating Scale was achieved in 89.7% and 81.6%, respectively. Among prior dupilumab nonresponders, ≥75% improvement in Eczema Area and Severity Index was achieved with abrocitinib 200 mg and 100 mg in 80.0% and 67.7% and ≥4-point improvement in Peak Pruritus Numerical Rating Scale in 77.3% and 37.8%, respectively. Most common adverse events among abrocitinib-treated patients were nasopharyngitis, nausea, acne, and headache. Conjunctivitis occurred less frequently with abrocitinib in comparison to prior dupilumab. LIMITATIONS: Short-term, 12-week analysis; no placebo arm. CONCLUSION: Efficacy and safety profile of abrocitinib in JADE EXTEND supports the role of abrocitinib as a treatment for patients with moderate-to-severe atopic dermatitis, regardless of prior dupilumab response status.

Wound healing protects against chemotherapy-induced alopecia in young rats via up-regulating interleukin-1ß-mediated signaling.

Wound healing is a complex process regulated by various cell types and a plethora of mediators. While interactions between wounded skin and the hair follicles (HFs) could induce HF neogenesis or promote wound healing, it remains unknown whether the wound healing-associated signaling milieu can be manipulated to protect against alopecia, such as chemotherapy-induced alopecia (CIA). Utilizing a well-established neonatal rat model of CIA, we show here that skin wounding protects from alopecia caused by several clinically relevant chemotherapeutic regimens, and that protection is dependent on the time of wounding and hair cycle stage. Gene expression profiling unveiled a significant increase in interleukin-1 beta (IL-1ß) mediated signaling by skin wounding. Subsequently, we showed that IL-1ß is sufficient and indispensable for mediating the CIA-protective effect. Administration of IL-1ß alone to unwounded rats exhibited local CIA protection while IL-1ß neutralization abrogated CIA protection by wounding. Mechanistically, IL-1ß retarded postnatal HF morphogenesis, making HFs at the wound sites or IL-1ß treated areas damage-resistant while the rats developed total alopecia elsewhere. We conclude that wound healing switches the cutaneous cytokine milieu to an IL-1ß-dominated state thus retarding HF growth progression and rendering the HFs resistant to chemotherapy agents. In the future, manipulation of HF progression through interfering with the IL-1ß signaling milieu may provide therapeutic benefits to a variety of conditions, from prevention of CIA to inhibition of hair growth and treatment of hirsutism.

Epithelialization in Wound Healing: A Comprehensive Review.

Significance: Keratinocytes, a major cellular component of the epidermis, are responsible for restoring the epidermis after injury through a process termed epithelialization. This review will focus on the pivotal role of keratinocytes in epithelialization, including cellular processes and mechanisms of their regulation during re-epithelialization, and their cross talk with other cell types participating in wound healing. Recent Advances: Discoveries in epidermal stem cells, keratinocyte immune function, and the role of the epidermis as an independent neuroendocrine organ will be reviewed. Novel mechanisms of gene expression regulation important for re-epithelialization, including microRNAs and histone modifications, will also be discussed. Critical Issues: Epithelialization is an essential component of wound healing used as a defining parameter of a successful wound closure. A wound cannot be considered healed in the absence of re-epithelialization. The epithelialization process is impaired in all types of chronic wounds. Future Directions: A comprehensive understanding of the epithelialization process will ultimately lead to the development of novel therapeutic approaches to promote wound closure.

A systematic approach to Afro-textured hair disorders: dermatoscopy and when to biopsy.

Trichoscopy facilitates the diagnosis of various hair and scalp disorders and is often useful in predicting the disease course. However, to date, few studies describe the dermoscopic findings unique to Afro-textured hair. This article reviews what is currently known regarding trichoscopy and discusses its usefulness in this population.

Acne in patients with skin of color: practical management.

Acne vulgaris is a prevalent and non-discriminatory condition affecting individuals of all races and ethnicities. As people with skin of color make up a rapidly expanding segment of the US population, dermatologic care must evolve accordingly to address their distinct concerns. Patients with skin of color with acne can be particularly challenging, given their potential for cosmetically disturbing complications, including post-inflammatory hyperpigmentation and keloid development. A variety of treatments have been shown to be effective in preventing or treating these complications. Topical retinoids are considered first-line therapy for acne in patients of color; topical alternatives include azelaic acid, dapsone, and antimicrobials. Hydroquinone may be used in combating post-inflammatory hyperpigmentation, specifically. For more severe acne, oral agents, including oral antibiotics or isotretinoin, may be used. Most recently, various lasers and phototherapies have been suggested for their safety and efficacy in patients with skin of color with acne. Ultimately, recognizing the clinical and histologic differences, as well as the variations in treatment regimens for darker skin types will allow for better care and patient satisfaction.

The importance of wound biopsy in the accurate diagnosis of acral malignant melanoma presenting as a foot ulcer.

Neoplastic changes arising at the sites of chronic, nonhealing wounds are not uncommon; however, they often go undiagnosed. We report a case of rapidly progressing plantar melanoma presenting as a chronic, nonhealing ulcer. A 46-year-old patient presented at a specialized Wound Healing Center with an enlarging painful ulcer on the right heel of 3 months duration. The wound was biopsied and specimens were sent for examination at the Wound Pathology service at the Department of Dermatology and Cutaneous Surgery, University of Miami. Histology demonstrated features consistent with acral malignant melanoma. Immunohistochemistry using melanocytic markers MART-1, S-100, HMB-45 revealed positive staining indicating the presence of malignant cells, and D2-40 staining showed lymphatic invasion of the tumor in the wound biopsy specimen. The case presented here underscores the importance of wound biopsying in the diagnosis of malignancies associated with nonhealing wounds.

Persistent adeno-associated virus 2 and parvovirus B19 sequences in post-mortem human cerebellum.

We previously reported in a large cohort (N = 104) of post-mortem tissues the detection of both the non-pathogenic adeno-associated virus (AAV2) in approximately 13% and the pathogenic human parvovirus B19 (B19) in approximately 42% of human brains, particularly the dorsolateral prefrontal cortex. Multiple animal parvoviruses target the developing cerebellum (CBLM) resulting in hypoplasia and ataxia, but very little is known about the human parvoviruses and their ability to infect or cause disease in the CBLM. We have now confirmed in the above cohort the presence of AAV2 and B19 sequences in the CBLM. Our results show that approximately 27% and approximately 70% of human CBLM are positive by nested polymerase chain reaction for AAV2 and B19 sequences, respectively. We also document in a second cohort (N = 10) the presence of AAV2 (50%) and B19 (100%) sequences in the CBLM and correlate our results for B19 with studies from matched sera. Eighty percent (80%) of this cohort was positive for anti-B19 IgG, while none were IgM+, suggesting that most individuals had been previously infected with B19 but none acutely. To our knowledge, this study is the first to demonstrate that both AAV2 and B19 sequences are present at relatively high frequencies in the CBLM and are likely due to persistent rather than acute infection. Further studies will lead to insights into AAV2- and/or B19-CBLM interactions including mechanisms of infection, persistence, and possibly neuropathology, including cerebellar hypoplasia and ataxia.