The Role of Antihistamines and Dupilumab in the Management of Alopecia Areata: A Systematic Review.

BACKGROUND: Approximately 30% to 40% of alopecia areata (AA) patients have atopic dermatitis. Studies suggest that antihistamines and dupilumab may be effective treatments; however, the potential benefit of these therapies as either adjunct or monotherapy has yet to be elucidated. OBJECTIVE: To evaluate the use of antihistamines and dupilumab in the treatment of AA. METHODS: A literature search was conducted in August 2021 according to PRISMA guidelines. Inclusion criteria were articles describing the use of antihistamines or dupilumab for AA or those discussing AA development as an adverse event of these therapies. RESULTS: Forty-two articles with 395 patients describe the use of antihistamines or dupilumab in AA. The most common antihistamine regimens were oxatomide 30 mg twice a day, fexofenadine 60 or 120 mg/day, and ebastine 10 mg/day; and the majority of cases reported significant hair regrowth, decreased pruritus, and erythema. Studies on the use of dupilumab for AA demonstrated remarkable hair growth in some patients (n=23), no change in others (n=3), and no new hair loss in a patient with resolved alopecia universalis (AU) (n=1). In contrast, dupilumab therapy for AD has been implicated as a cause of AA (n=21), drug-induced alopecia (n=2), and AA-like psoriasis (n=1). CONCLUSION: Current literature is promising for the use of antihistamines as adjunct treatments for AA, while monotherapy needs to be further explored. The role of dupilumab in AA treatment and/or development also requires further research.J Drugs Dermatol. 2022;21(10):1070-1083. doi:10.36849/JDD.6553.

Utility of Naltrexone Treatment for Chronic Inflammatory Dermatologic Conditions: A Systematic Review.

Importance: Dermatology is encountering increasing rates of autoimmune disease manifesting in primary skin conditions that are difficult to treat without a risk of immunosuppression. Naltrexone is an orally active opioid antagonist that influences a variety of systemic pathways, including the immune system, in low doses of 1.5 to 4.0 mg/d. This phenomenon has piqued the interest of researchers and practitioners in regard to low-dose naltrexone's potential in the treatment of several autoimmune conditions. Objective: To review the existing literature on naltrexone treatment for dermatologic conditions. Evidence Review: A primary literature search was conducted using PubMed in April 2018 for all articles published from 1971 to April 2018. Search terms consisted of naltrexone or low dose naltrexone or low-dose naltrexone and dermatology or skin or hair or nails. Reviews, animal studies, and nondermatologic and pharmacologic studies were excluded. Findings: From 1037 articles, 22 were deemed to be appropriate for inclusion in this review for a qualitative synthesis. The 22 articles included randomized clinical trials, case reports, and series. There were 7 articles on low-dose naltexone, 1 on topical naltrexone, and 14 on high-dose naltrexone use in dermatology. In high, low, and topical doses, naltrexone was effective in treating pruritus attributable to atopic dermatitis, prurigo nodularis, cholestatsis, burn injury, systemic sclerosis, Hailey-Hailey disease, and lichen planopilaris. High-dose naltrexone was ineffective in treating flushing and uremic pruritus most likely because of the lack of opioid involvement in the pathophysiologic mechanisms of these conditions. Conclusions and Relevance: The findings suggest that low-dose naltrexone is safe and effective in the treatment of Hailey-Hailey disease and lichen planopilaris and both low- and high-dose naltrexone successfully treat pruritus attributable to various pathologic conditions; however, more adverse effects occurred in those taking high doses. Low-dose naltrexone has the potential for the treatment of chronic inflammatory skin conditions; however, additional evidence is needed for dosing and long-term treatment guidelines.

Cutaneous anaplastic large-cell lymphoma should be evaluated for systemic involvement regardless of ALK-1 status: case reports and review of literature.

Anaplastic large-cell lymphoma (ALCL) is a lymphoma that expresses CD30. Cutaneous ALCL presents either as primary cutaneous disease or as secondary skin involvement due to the systemic disease. Herein, we describe two patients who presented to dermatology for evaluation of skin lesions diagnosed by non-dermatologists as a cutaneous abscess and lupus erythematosus, respectively. Upon investigation by a team of medical dermatologists and dermatopathologists, systemic ALCL with secondary skin involvement was discovered in both patients. The majority of cases of systemic ALCL with cutaneous involvement express anaplastic lymphoma kinase-1 (ALK-1), and are associated with a more favorable prognosis than ALK-1-negative cases. However, cutaneous ALCL regardless of ALK-1 status may be secondary to systemic lymphoma. This article stresses the importance of dermatologists being aware of the diagnosis of systemic lymphoma based on cutaneous findings, and being aggressive in initiating appropriate diagnostic testing. Primary cutaneous ALCL and systemic ALCL are reviewed.

Atypical presentations of herpesvirus infections in patients with chronic lymphocytic leukemia.

The characteristic presentation of herpesvirus infections is a vesicular rash. The initial lesions appear as erythematous papules that turn into grouped vesicles and pustules eventuating into crusts. In most cases, the features are so characteristic that a diagnosis can be made by history and physical examination without further diagnostic testing. However, patients who are immunosuppressed (including those with hematologic malignancies) often have atypical presentations of herpesvirus infections. These cases require a high index of suspicion and appropriate diagnostic testing for proper management. In this report, we describe two patients with chronic lymphocytic leukemia who developed atypical presentations of herpes zoster and herpes simplex infections. Herpetic infections should always be in the differential diagnosis of cutaneous ulcerations with necrosis in patients who are immunocompromised. Because of the atypical appearance of the lesions, the diagnosis may be confused or mistaken for several other conditions.

Physiologic anemic macules.

Anemic-appearing macules of the extremities that fluctuate with temperature and position have been referred to as Bier spots. After review of the literature and innumerable clinical presentations, we propose that the best description and better nomenclature is physiologic anemic macules. We present the case of a 27-year-old woman with physiologic anemic macules and review the history of this condition.

Concurrent punctate keratosis of the palmar creases and focal acral hyperkeratosis.

We report a patient with punctate keratosis of the palmar creases appearing concurrently with focal acral hyperkeratosis. This presentation is a unique coexistence of 2 simple and punctate hereditary palmoplantar keratodermas.

Eyebrow loss: clinical review.

Loss of eyebrow hair may come to the attention of the dermatologist as a presenting complaint or as an unexpected finding on routine physical examination. Because eyebrows serve important cosmetic and social roles, their loss can be quite distressing to patients. While eyebrow loss may be an isolated finding of no medical consequence, it may also be an initial manifestation of a systemic condition. Loss of eyebrows has numerous causes including primary dermatoses, endocrinopathies, autoimmune conditions, infections, neoplasms, trauma, exogenous agents, and genetic diseases. We present a systemic review of eyebrow loss, including an algorithm that can be used to direct the work-up of patients presenting with this condition.

A review of the chemopreventive and chemotherapeutic effects of topical and oral retinoids for both cutaneous and internal neoplasms.

Retinoids, a group of compounds encompassing Vitamin A and its analogs, have been shown to inhibit tumor growth in laboratory studies. Based on these findings, a number of clinical trials have been conducted to investigate the chemoprotective and chemotherapeutic effects of retinoids. This paper reviews the current database regarding the use of oral and topical retinoids in the prevention and treatment of cutaneous and internal malignancies. Clinical studies have shown that retinoids have beneficial effects in the prevention and treatment of certain neoplasms. In view of the heightened concern of malignancy associated with the use of biologic agents in the treatment of psoriasis, retinoids may be an attractive option for combination therapy with the biologic agents. Future clinical investigations are needed to precisely define how this combination will fit into the treatment algorithm for moderate-to-severe psoriasis.

Update on the mechanisms and efficacy of biological therapies for psoriasis.

Biologically based agents (biologics) are novel therapeutic options in the treatment of moderate-to-severe psoriasis. Unlike traditional systemic anti-psoriatic drugs, which are chemically synthesized, these agents are unique in that they are derived from living organisms and hence called "biologics." In addition, they are the first group of "custom-designed" molecules that precisely target steps in the pathogenesis of psoriasis. The specificity of these biologics can theoretically avoid the side effects of the prebiologically developed systemic agents including the effects of hepatotoxicity, nephrotoxicity, and bone marrow suppression. However, there is also a tendency for a more precisely targeted agent to have a less overall efficacy. Due to the varying efficacies and high costs of the new biologic agents that are currently approved for psoriasis in the United States, the precise way they fit into the range of treatments for moderate-to-severe psoriasis should be defined pending future clinical experiences.

Diffuse gingival enlargement.

Diffuse gingival enlargement is defined as an excessive growth of periodontal tissue. It can be considered a relatively common finding, as thousands of patients have been described in the literature. Patients may seek medical attention because of pain, tenderness, interference with speech and/or mastication, halitosis, or unsightly appearance, or gingival enlargement may be an unexpected finding on routine physical examination. Diffuse gingival enlargement has numerous causes, including poor dental hygiene, medications, serious systemic illnesses, genetic conditions, other specific physiologic states, or it may be idiopathic. Given the large number of possible underlying conditions, the work-up of a patient presenting with diffuse gingival enlargement may seem daunting. We present a systemic review of diffuse gingival enlargement, including an algorithm that can be used to direct the work-up of patients presenting with this condition.