Review of Ruxolitinib for Treatment of Non-Segmental Vitiligo.

OBJECTIVE: To review the pharmacokinetics, efficacy, and safety of topical ruxolitinib for treatment of nonsegmental vitiligo. DATA SOURCES: Literature published between January 1983 and October 2022 was reviewed from MEDLINE and ClinicalTrials.gov. STUDY SELECTION AND DATA EXTRACTION: Relevant articles in English and data from clinical trials were included. DATA SYNTHESIS: In 2 phase II trials, treatment with ruxolitinib cream showed significant improvements in Vitiligo Area Scoring Index (VASI) scores compared with controls. The 1.5% concentration applied twice daily showed the best results after 52 weeks, with 50% VASI improvement in 58% of patients, 75% VASI improvement in 52% of patients, and 90% VASI improvement in 33% of patients. In 2 phase III trials, more patients achieved at least 75% improvement in facial VASI at 24 weeks (primary endpoint; trial 1: 29.9%, trial 2: 29.9%) than controls (trial 1: 7.5% [P < 0.0001], trial 2: 12.9% [P < 0.01]). Common adverse effects were erythema, pruritus, and acne; all events were mild. RELEVANCE TO PATIENT CARE AND CLINICAL PRACTICE IN COMPARISON TO EXISTING DRUGS: This review summarizes the pharmacokinetics, efficacy, and safety data regarding topical ruxolitinib for vitiligo. Ruxolitinib is associated with significant clinical improvements with low bioavailability and minimal adverse effects compared with conventional topical steroids, calcineurin inhibitors, phototherapy, and depigmentation agents. CONCLUSIONS: Ruxolitinib cream is the first therapy approved by the Food and Drug Administration for repigmentation of nonsegmental vitiligo. Clinicians should consider these benefits when recommending treatment as conventional therapies may be time-intensive and carry greater risks of adverse effects.

Review of Baricitinib in the Treatment of Alopecia Areata.

BACKGROUND: Alopecia areata (AA) is a debilitating autoimmune disease that results in non-scarring hair loss. Baricitinib is the Food and Drug Administration (FDA) approved treatment for AA.  Objective: Review the mechanism of action, pharmacokinetics, pharmacodynamics, efficacy, and safety of baricitinib in the treatment of AA.  Methods: A literature review was conducted using the MEDLINE (PubMed) and EMBASE databases for articles published between January 2010 to November 2022. Articles in English discussing baricitinib's efficacy and safety in AA, pharmacodynamic, and pharmacokinetic profiles were included. RESULTS: Two identical phase III trials (BRAVE-AA1 and BRAVE-AA2) were evaluated. A greater percentage of subjects receiving baricitinib 4 mg or 2 mg dose achieved a Severity of Alopecia Tool score equal to or less than 20 vs placebo. In BRAVE-AA1, for 4 mg, 2 mg, and placebo, respectively, these values were 38.8%, 22.8%, and 6.2%; in BRAVE-AA2, these values were 35.9%, 19.4%, and 3.3% (P<0.001). DISCUSSION: Baricitinib is the first FDA-approved treatment for AA. Other treatments for AA are used off-label with variable efficacy. Baricitinib is associated with black-box warnings due to adverse effects (AEs) associated with other Janus Kinase (JAK) inhibitors or use in other diseases. In the two large AA trials, AEs were considered mild or moderate; those reported more often with baricitinib than placebo included acne, elevations of low- and high-density lipoprotein cholesterol, and elevation of creatinine kinase. Baricitinib is a relatively tolerable and safe therapeutic alternative for severe AA, although additional study is needed to assess its long-term efficacy and safety.  Citation: Singh R, Driscoll MS. Review of baricitinib in the treatment of alopecia areata. J Drugs Dermatol. 2023;22(9):935-939. doi:10.36849/JDD.7357.

Melanoma risk after in vitro fertilization: A review of the literature.

BACKGROUND: The role of female sex hormones in the pathogenesis of malignant melanoma (MM) remains controversial. Although melanocytes appear to be hormonally responsive, the effect of estrogen on MM cells is less clear. Available clinical data does not consistently demonstrate that increased endogenous hormones from pregnancy or increased exogenous hormones from oral contraceptive pills and hormone replacement affect MM prevalence and outcome. OBJECTIVE: We sought to examine potential associations between in vitro fertilization (IVF) and melanoma. METHODS: A literature review was conducted. Primary outcomes were reported as associations between IVF and melanoma risk compared with the general population. Secondary outcomes included associations stratified by type of IVF regimen and subgroup, such as parous versus nulliparous patients. RESULTS: Eleven studies met our inclusion criteria. Five studies found no increased risk for MM among IVF users compared with the general population. Two studies found an increase in MM in clomiphene users, and 4 studies found an increase in MM among patients who were gravid or parous either before or after IVF. CONCLUSION: The reviewed studies do not reveal consistent patterns of association between IVF and MM among all infertile women. However, the data indicates a potential increased risk for MM in ever-parous patients treated with IVF. High-quality studies including a large number of MM cases that control for well-established MM risk factors are needed to adequately assess the relationship between IVF and MM, particularly among ever-parous women.

Pregnancy and melanoma.

Malignant melanoma is the most common malignancy during pregnancy, and is diagnosed during childbearing age in approximately one-third of women diagnosed with melanoma. The impact of hormonal changes during pregnancy and from iatrogenic hormones on melanoma is controversial. Women undergo immunologic changes during pregnancy that may decrease tumor surveillance. In addition, hormone receptors are found on some melanomas. In spite of these observations, the preponderance of evidence does not support a poorer prognosis for pregnancy-associated melanomas. There is also a lack of evidence that oral contraceptives or hormone replacement therapy worsens melanoma prognosis.

Nevi and pregnancy.

Changes in the moles of pregnant women are frequently attributed to pregnancy, but recent studies suggest that pregnancy does not induce significant physiologic changes in nevi. It is common for nevi on the breasts and abdomen to grow with normal skin expansion, but studies that have examined melanocytic nevi on the backs or lower extremities have found no significant changes in size during pregnancy. Several studies have also investigated the belief that moles darken during pregnancy and have found insufficient evidence to support this idea. Dermoscopically, transient changes have been identified, but none are suggestive of melanoma. Results vary in terms of histologic changes seen in samples taken from pregnant women, but all authors agree that any histopathologic features consistent with melanoma should be viewed as melanoma and not attributed to pregnancy. Biopsy specimens should be obtained promptly from any changing mole that would raise concern for malignancy in a nonpregnant patient. Such procedures can be performed safely during pregnancy.

Discoid lupus erythematosus of the palms: A case report.

Discoid lupus erythematosus is an autoimmune connective-tissue disease that represents a subset of conditions on the cutaneous lupus spectrum. The lesions are characterized by disk-shaped plaques on photo-exposed skin with inflammatory hyperpigmentation and adherent scale. Here, we present a patient with a rare manifestation of discoid lesions on the palms.

A Histologic Timeline of a Delayed Hypersensitivity Reaction after the COVID-19 Pfizer Booster.

A 54-year-old man presented with worsening bilateral rashes on legs and arms 7 days after receiving his BNT162b2 mRNA COVID-19 (Pfizer) vaccine booster. He developed burning on his palms about 5 days after receiving the booster. On day 6, he observed significant edema on his fingers and palms in addition to thin erythematous papules on his forearms. On day 7, he developed edema on his bilateral dorsal feet, and thin erythematous plaques on his shins. He stated that the rashes were pruritic. He had no rashes following the first two doses of the Pfizer vaccine. He denied having any history of skin disease, autoimmune disease, or allergies. Physical examination revealed multiple thin erythematous papules coalescing into thin plaques on his flexor forearms, and thin erythematous plaques on his dorsal feet (Figure 1). Three 4-mm punch biopsies were performed on his left flexor forearm. The biopsies were carried out at papules present for different lengths of time. Papules at biopsy sites "A," "B," and "C" were present for approximately 24-36 hours, 12-18 hours, and 3-6 hours, respectively (Figure 1).

A United States expert consensus to standardise definitions, follow-up, and treatment targets for extra-intestinal manifestations in inflammatory bowel disease.

BACKGROUND AND AIMS: Extra-intestinal manifestations (EIMs) are a common complication of inflammatory bowel diseases (IBD), affecting up to half of the patients. Despite their high prevalence, information on standardised definitions, diagnostic strategies, and treatment targets is limited. METHODS: As a starting point for a national EIM study network, an interdisciplinary expert panel of 12 gastroenterologists, 4 rheumatologists, 3 ophthalmologists, 6 dermatologists, and 4 patient representatives was assembled. Modified Delphi consensus methodology was used. Fifty-four candidate items were derived from the literature review and expert opinion focusing on five major EIMs (erythema nodosum, pyoderma gangrenosum, uveitis, peripheral arthritis, and axial arthritis) were rated in three voting rounds. RESULTS: For use in a clinical practice setting and as part of the creation of a prospective registry of patients with EIMs, the panel developed definitions for erythema nodosum, pyoderma gangrenosum, uveitis, peripheral arthritis, and axial arthritis; identified the appropriate and optimal subspecialists to diagnose and manage each; provided methods to monitor disease course; offered guidance regarding monitoring intervals; and defined resolution and recurrence. CONCLUSIONS: Consensus criteria for appropriate and optimal means of diagnosing and monitoring five EIMs have been developed as a starting point to inform clinical practice and future trial design. Key findings include straightforward diagnostic criteria, guidance regarding who can appropriately and optimally diagnose each, and monitoring options that include patient and physician-reported outcomes. These findings will be used in a national multicenter study network to optimise the management of EIMs.

Melanoma in pregnancy.

Since the early 1950s clinicians have been concerned about the impact of pregnancy on malignant melanoma (MM). Case reports and case series described a grave prognosis for women diagnosed with MM during pregnancy. Today MM in pregnancy takes on enhanced significance as more women delay childbearing into their 30s and 40s, and the incidence of MM during pregnancy may be expected to increase. In addition, relative immunosuppression during pregnancy theoretically may favor the potential for MMs to behave more aggressively. This article compiles the most recent clinical, epidemiologic, and laboratory studies to guide clinicians in addressing the issue of melanoma in pregnancy. Herein we address the prognosis, characteristics, evaluation, treatment, and how to counsel women diagnosed with MM during pregnancy, including the potential consequences for the fetus. Overall, our analysis reveals that there is no effect on survival in women diagnosed with localized MM during pregnancy; likewise, pregnancies prior or subsequent to a diagnosis of MM do not impact prognosis. Strong epidemiologic evidence shows no enhanced risk of developing MM associated with oral contraceptive pill use. Although a smaller number of studies have addressed hormonal replacement therapy and risk of MM, these studies do not suggest a higher risk of MM. As for the fetus, risk of metastasis to the placenta and/or fetus is extremely low, and seems to occur exclusively in women with widely metastatic MM.

Deleterious side effects of nutritional supplements.

Vitamin and mineral supplement consumption is widespread. They are taken for a variety of conditions, including dermatologic disorders. Although consumers often assume these supplements are safe, excessive consumption of supplements may have deleterious effects. Such vitamin supplements include vitamin A, niacin, biotin, vitamin D, and vitamin E, and specific mineral supplements include zinc, copper, and iron. These supplements may have a number of potential adverse effects.

Hormone therapy and melanoma in women.

Although primary cutaneous melanoma accounts for approximately 3% of all malignant skin tumors, it has the greatest contribution to skin cancer-related death. Sex-specific differences in melanoma tumor behavior have been described, and melanoma pathogenesis may be hormonally mediated. This review aims to summarize the literature to date regarding the effects of hormone therapy on melanoma in women. Women's exogenous hormone use has changed dramatically over the past few decades. Thus, we focus on studies investigating the associations between oral contraception, fertility treatments, menopausal hormone therapy (MHT), and melanoma. Across hormone therapy types, there does not appear to be a well-established association between exogenous female hormones and melanoma incidence. However, MHT practices and formulations vary significantly across countries. Although MHT does not appear to increase melanoma risk in studies from the United States, conflicting results have been observed in Europe. Unopposed estrogen MHT formulations require further investigation to determine a clear pattern between hormone use and the development of melanoma.

Pediatric sweet syndrome.

Pediatric Sweet syndrome is a rare dermatosis often triggered by a prodromal illness or infection and characterized histologically by a dense neutrophilic infiltrate. We report a 2-year-old girl with a classic presentation of Sweet syndrome following an acute thumb paronychia, who had a negative history of malignancy or immunodeficiency.

Comorbidities of hidradenitis suppurativa: A review of the literature.

BACKGROUND: Hidradenitis suppurativa (HS) is a chronic inflammatory skin condition that affects the follicular portion of folliculopilosebaceous units. It causes painful nodules, abscesses, and draining sinus tracts throughout multiple regions of the body. HS primarily affects women; the overall HS prevalence in women is three times that in men. Although cutaneous disease itself causes substantial morbidity, recent evidence has shown that HS is a systemic inflammatory disease with multiple associated comorbidities. OBJECTIVE: A review of the literature was conducted to elucidate existing information on this topic to assist in clinical decision-making for dermatologists. METHODS: A review of the literature using the PubMed database was conducted with the search term "hidradenitis suppurativa comorbidities". The search was conducted from March 3, 2019 to March 20, 2019, and yielded 55 articles, case reports, and reviews. RESULTS: Metabolic and cardiovascular comorbidities were the most commonly associated with HS. HS has a significant comorbidity burden beyond the skin, including metabolic, cardiovascular, endocrine, gastrointestinal, rheumatologic, and psychiatric disorders, which collectively decrease the quality of life of patients. CONCLUSIONS: Dermatologists should be aware of these associations to encourage appropriate screening and referral for management of these disorders.

Is substance use disorder more prevalent in patients with hidradenitis suppurativa?

Hidradenitis suppurativa (HS) is a chronic inflammatory skin condition that disproportionately affects women and is associated with significant physical and psychosocial impact. Recent studies have reported an increased prevalence of substance abuse among patients with HS, including increased alcohol, opioid, and cannabis use. Whether substance use disorder is more prevalent among patients with HS is controversial because these data come from small studies and a major confounder is that patients with HS are often prescribed opioids for HS-associated pain. This review summarizes the current literature on substance use in HS to investigate whether substance use disorder is more likely in this patient population. We also highlight possible cofounders and areas of unmet need in HS that are potential causes of abuse, such as adequate pain control and impaired quality of life, and suggest opportunities for provider intervention. Evidence suggests that there is an increased prevalence of substance use disorder in patients with HS, but the full extent is still difficult to determine. However, with early screening and appropriate referrals to specialists, dermatologic providers may properly intervene and prevent substance use disorder in patients with HS.

Report of a case: primary mucinous carcinoma of the skin.

Primary mucinous carcinoma of the skin is an extremely rare adnexal tumor that is thought to originate from eccrine sweat glands. The neoplasm usually arises on the head and neck, with the most commonly involved area being the periorbital region. The tumor is typically a solitary, asymptomatic nodule, cyst, or ulcer that is slow growing with low metastatic potential. However, post-excisional local recurrence is common, affecting up to 36 percent of patients. Since primary mucinous carcinoma of the skin is such a rare neoplasm (fewer than 130 cases have been reported to date), a complete workup should be conducted to rule out other internal malignancies that may metastasize to the skin. We report a case of primary mucinous carcinoma of the skin, and discuss the clinical presentation, histology, treatment, course, and prognosis.

Hormones, nevi, and melanoma: an approach to the patient.

For many years, clinicians have been concerned about a potential adverse effect of pregnancy-associated hormones and exogenous hormones on melanocytic nevi and malignant melanoma. Today, these issues are more significant as women have delayed childbearing into their 30's and 40's, and the likelihood of diagnosis with melanoma during pregnancy is enhanced. More recent clinical, epidemiologic, and laboratory studies have shed some light on the relationship among hormones, nevi, and melanoma in pregnancy.

Prognosis for women diagnosed with melanoma during, before, or after pregnancy: Weighing the evidence.

Approximately one third of women who are diagnosed with malignant melanoma are of childbearing age. Therefore, it is not surprising that some studies have found malignant melanoma to be one of the most common malignancies diagnosed in pregnant women. The impact of pregnancy-related hormonal changes on melanoma development and progression remains controversial. Women undergo immunologic changes during pregnancy that may decrease tumor surveillance. Additionally, hormone receptors are found on some melanomas. Unfortunately, many of the past and even recent studies that have been published and are reviewed herein did not uniformly use appropriate control groups, account for confounding covariates, or employ appropriate statistical analysis, which makes it difficult to rely on the conclusions they reach. However, a review of the better controlled and preponderant studies demonstrates that pregnancy-associated melanomas are not associated with a poorer prognosis.