Updates on Pityriasis Rubra Pilaris: A Scoping Review.

Pityriasis rubra pilaris (PRP) is a rare, inflammatory papulosquamous skin disease with unknown exact etiology. Historically, PRP has been challenging to diagnose, especially during the acute phase, and to treat, due to its unclear pathogenesis. To better inform clinical practice, a literature review was conducted employing a broad search strategy to capture PRP-related published studies between January 1, 2012 to October 31, 2022. Two hundred twenty-one studies were identified, which were categorized into 9 themes: (1) potential causes and triggering factors, (2) comorbidities, (3) diagnostic difficulties, (4) genetics, (5) clinical manifestations and laboratory values, (6) treatment, (7) treatment-related adverse events, (8) quality of life, and (9) other. COVID-19 infection, COVID-19 vaccination, and malignancy were the most commonly reported potential triggering factors. Misdiagnosis is very common during the early acute stages. Pathogenesis and genetic studies have further implicated caspase recruitment domain family member 14 (CARD14) mutations in the development of familial PRP (Type V) and have underlined the overlap between psoriasis and PRP. To date, there are currently no specific and validated scoring systems or tools to assess the severity of PRP. While large, randomized trials are still lacking, biologic agents remain the most effective therapy.

Biologics for inherited disorders of keratinisation: A systematic review.

BACKGROUND/OBJECTIVES: Recent literature highlights the potential of biologics in the management of inherited disorders of keratinisation. In this study, we conducted a systematic review of existing literature on treatment outcomes of inherited keratinisation disorders treated with biologics. METHODS: Eligible records were retrieved through searches of the electronic databases MEDLINE, Embase, PubMed and Scopus. Databases were searched from inception to July 2023 for eligible records. A snowballing method was employed to search the references of the retrieved records for the identification of potentially relevant articles. RESULTS: One hundred and four eligible studies consisting of a total of 166 patients with an inherited disorder of keratinisation were included. Patients had a median age of 19 years (range: 0.5 to 70 years). The most common disorders were Netherton syndrome (n = 63; 38%), autosomal recessive congenital ichthyoses (n = 27; 16%), CARD14-associated papulosquamous eruptions (n = 17; 10%) and familial pityriasis rubra pilaris (PRP) (n = 15; 9%).Of the 207 times biologics were employed, the three most frequently employed biologics were secukinumab (n = 47; 23%), dupilumab (n = 44; 21%) and ustekinumab (n = 37; 18%). Complete remission was observed in 10 (5%) instances, partial remission in 129 (62%), no or limited response to biologic therapy in 68 (32%) cases, and results are still pending in one case. A total of 33 adverse events were reported. CONCLUSIONS: Whilst biologics may be considered in cases of inherited keratinisation disorders recalcitrant to standard therapy, definitive conclusions are prohibited by the low-level of evidence and substantial heterogeneity in methodology across the included studies. Establishment of consensus definitions, and randomised clinical trials may help ascertain the efficacy and safety of biologic therapy in this context and establish the best agent and dosing protocol for each disorder.

A child with CARD14-associated papulosquamous eruption (CAPE) successfully treated with ustekinumab.

CARD14-associated papulosquamous eruption (CAPE) is a rare inflammatory skin eruption that can have features of psoriasis, pityriasis rubra pilaris, and erythroderma. This skin condition is known for its resistance to topical or conventional systemic therapies. Successful treatment of CAPE with anti-IL-12/IL-23 and IL-17 inhibitors has been reported. We present a case of a 2-year-old girl with CAPE who was successfully treated with ustekinumab.

Pityriasis Rubra Pilaris After Moderna COVID-19 Vaccination: A Case Report and Literature Review.

ABSTRACT: To date, over 60% of the world's population has received at least 1 dose of coronavirus disease 2019 (COVID-19) vaccination, with over 12 billion doses administered globally. Commonly reported adverse effects of COVID-19 vaccination include fever, headache, myalgia, and injection site reactions. The spectrum of documented cutaneous reactions after COVID-19 vaccination is broad; however, pityriasis rubra pilaris (PRP) or PRP-like eruption secondary to COVID-19 vaccine is exceedingly rare, with only 17 cases previously reported to date in the English literature. In this article, we describe an additional case of COVID-19 vaccination-associated PRP in a 50-year-old woman with a history of metastatic breast carcinoma, who developed a widespread cutaneous eruption characteristic of PRP, including palmoplantar keratoderma, 10 days after her third dose of Moderna COVID-19 vaccine. Punch biopsy specimen showed epidermal hyperplasia with overlying hyperkeratosis, alternating orthokeratosis and parakeratosis and focal follicular plugging, supporting the diagnosis of PRP. The patient improved within weeks of initiating oral acitretin and topical steroids, with resolution achieved after 3 months of continued therapy. To the best of our knowledge, this is the third reported case of Moderna COVID-19 vaccination-associated PRP and collectively the 18 th after the administration of all COVID-19 vaccines currently available, including Pfizer-BioNTech, and AstraZeneca.

Treatment Options for Juvenile Pityriasis Rubra Pilaris.

Pityriasis rubra pilaris represents a group of familial and acquired disorders of cornification that affect both adult and pediatric patients. Treatment options are difficult to assess through clinical trials, given the rarity of the disorder and its tendency for spontaneous remission. Case reports and case series are therefore the primary means of assessment. Because of the heterogeneity of the disease, there is no universal approach to treatment, and multiple agents may need to be trialed to achieve disease control. At present, topicals are used for most pediatric patients, though monotherapy with topicals is only effective for less severe disease. Despite concerns over their side-effect profiles, oral retinoids are generally accepted as a first-line systemic therapy. However, interleukin-17 inhibitors and ustekinumab, an interleukin-12 and interleukin-23 inhibitor, may soon become first-line systemic treatment as well, given their efficacy and relative safety in trials thus far. Ustekinumab, in particular, is emerging as a first-line agent for patients with pityriasis rubra pilaris with CARD14 gene variations. When these therapies fail, second-line and adjunctive therapies to consider include tumor necrosis factor-alpha inhibitors, methotrexate, and phototherapy. However, further investigation is necessary to assess the safety and efficacy of many of these agents in juvenile pityriasis rubra pilaris.

Ponatinib-Associated Cutaneous Eruptions-A Case Series and Review of Clinicopathologic Findings.

ABSTRACT: Ponatinib is a third-generation tyrosine kinase inhibitor used to treat chronic myeloid leukemia and Philadelphia-positive acute lymphoblastic leukemia. Cutaneous toxicities are a commonly reported side effect of ponatinib treatment with "rash" being one of the most common. Specific subtypes are infrequently reported, but include hyperkeratotic, folliculocentric, ichthyosiform, and pityriasis rubra pilaris-like eruptions. Herein, we highlight the clinicopathologic features of 2 cases of ponatinib-induced pityriasis rubra pilaris-like eruptions. We also classify the clinical and histopathologic features of all previously reported ponatinib-associated eruptions in the literature and discuss treatment and potential diagnostic pitfalls.

Off-label uses of ustekinumab.

Ustekinumab (brand name Stelara®) is a human interleukin-12 and -23 antagonist and has been indicated for the treatments of moderate to severe plaque psoriasis, psoriatic arthritis, Crohn's disease and ulcerative colitis. This review aims to synthesize and interpret the literature evaluating the off-label uses of ustekinumab. We performed searches in PubMed and ClinicalTrials.gov for clinical trials, observational studies, case series, and case reports evaluating label uses of ustekinumab. Studies evaluated the efficacy of ustekinumab for the following conditions: other types of psoriasis (expect plaque psoriasis and psoriatic arthritis), pityriasis rubra pilaris, hidradenitis suppurativa, atopic dermatitis, pyoderma gangrenosum, et al. Based on the available literature, ustekinumab appears to be a potential treatment choice for many other diseases. However, more clinical trials data are needed to adequately assess the safety and efficacy of ustekinumab for the treatment of these conditions.

Pityriasis rubra pilaris heralding diagnosis of urothelial carcinoma: a case report.

Pityriasis rubra pilaris is a papulosquamous inflammatory dermatosis that can be associated with HIV, autoimmunity, infections, certain medications, and neoplasms. Paraneoplastic pityriasis rubra pilaris has previously been reported in association with solid organ malignancies and once with leukemia. Herein, we present an elderly man with paraneoplastic pityriasis rubra pilaris, heralding the diagnosis of low-grade papillary urothelial carcinoma. Our patient's pityriasis rubra pilaris resolved after surgical resection of the tumor.

Successful treatment with ustekinumab in CARD14-associated papulosquamous eruption in a Brazilian child.

CARD14-associated papulosquamous eruption (CAPE) was proposed in 2018 to describe the clinical features of psoriasis and pityriasis rubra pilaris with CARD 14 mutations. We report a 5-month-old female infant who developed CAPE-associated erythroderma. Although she did not respond to conventional therapies, she responded well to ustekinumab treatment at the age of 4 years.