Biologics for Treatment of Pityriasis Rubra Pilaris: A Literature Review.

OBJECTIVE: To describe the published efficacy and adverse event rates associated with existing biologics for the treatment of pityriasis rubra pilaris (PRP). DATA SOURCES: A literature review using the PubMed database (January 1990-July 2023) was conducted. Multiple search combinations were conducted using "pityriasis rubra pilaris" and various biologics as keywords to identify relevant articles. STUDY SELECTION AND DATA EXTRACTION: Inclusion criteria included all study types that were published within the past 30 years in English and mentioned at least one biologic and PRP. A preliminary search yielded a total of 499 results. After screening using inclusion and exclusion criteria, 77 relevant articles (69 case reports, 5 case series, 2 clinical trials, and 1 retrospective analysis) were analyzed. DATA SYNTHESIS: TNF-α inhibitors have been evaluated and are effective in treating PRP. However, recent treatment with anti-interleukin (IL)-17 and anti-IL-23 therapies such as ustekinumab, secukinumab, and ixekizumab are emerging as new treatment options with a mean improvement in PRP Area and Severity Index scores, change in severity of erythema, scaling, and thickness of PRP lesions. From initial clinical trials, secukinumab and ixekizumab are promising treatment options for achieving remission. RELEVANCE TO PATIENT CARE AND CLINICAL PRACTICE: This review compares the efficacy for numerous biologics and a discussion to guide clinicians on benefits and risks in choosing a biologic for PRP patients. CONCLUSIONS: Biologics may be a favourable treatment option leading to greater patient adherence due to reduced dosing frequencies, improvement in quality of life, and reduction in frequency and severity of flares.

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.

Pityriasis rubra pilaris with erythema gyratum repens-like eruption and resolution with ustekinumab.

Erythema gyratum repens (EGR) is a rare paraneoplastic disorder often preceding the diagnosis of underlying malignancy by 9 months on average, while pityriasis rubra pilaris (PRP) is an uncommon papulosquamous inflammatory disease. We present the case of a 58-year-old woman with an EGR-like eruption transforming from resolving PRP, without associated malignancy. Her rash dramatically resolved within a month of ustekinumab initiation, which supports this presentation as a unique entity.

Early Presentation of Pityriasis Rubra Pilaris Mimicking Tinea Corporis: Diagnostic Challenges of a Rare Skin Condition.

BACKGROUND Pityriasis rubra pilaris (PRP) is a rare chronic inflammatory skin condition characterized by follicular, papulosquamous, reddish-orange scaling, palmoplantar keratoderma, and erythema with islands of sparing. Its heterogeneous clinical presentation makes the diagnosis of PRP quite challenging, especially at the initial presentation, as it can mimic common skin conditions. CASE REPORT We present a case with an early presentation of PRP in a 61-year-old Malay woman with underlying uncontrolled diabetes, and discuss evolving clinical course of her disease. She presented to a primary care clinic with a 3-week history of itchy, ring-like skin lesions that started on her neck and chest but subsequently spread widely on her chest, back, and upper extremities. She was first treated as having extensive tinea corporis but responded poorly to multiple courses of antifungal treatment. An initial skin biopsy that was taken at the dermatology clinic revealed features suggestive of erythema annulare centrifugum. However, despite topical steroid treatment, her skin condition evolved further and she developed generalized erythroderma along with follicular hyperkeratosis and palmoplantar keratoderma. A repeat biopsy finally confirmed the diagnosis of PRP. CONCLUSIONS Making the diagnosis of PRP is challenging for clinicians. However, clinicians should approach any common skin problem that does not respond to treatment appropriately, with consideration of other uncommon skin disorders. A repeat skin biopsy may be considered if there are any doubts about the diagnosis. A clinical and histopathological correlation is important to aid in the diagnosis of PRP.

Beyond plaque psoriasis - pathogenesis and treatment of other psoriasis phenotypes.

PURPOSE OF REVIEW: Psoriasis vulgaris is the commonest presentation of psoriatic disease, but morphologic variants such as pustular psoriasis (PP) and a closely related disease, pityriasis rubra pilaris (PRP), have been known for a long time, have been associated with rheumatologic manifestations indistinguishable from psoriatic arthritis (PsA) that may go unrecognized, and often represent a therapeutic conundrum. There is recent evidence that underlying genetic and pathogenetic differences may provide the basis for newer therapeutic approaches. RECENT FINDINGS: This narrative review highlights the clinical, genetic and pathogenetic characteristics of PP and PRP, their association with PsA and recent developments in their treatment, especially with biologic agents targeting IL-36 and other cytokines of pathogenic relevance. SUMMARY: The clinical manifestations of PP and PRP are less well known to rheumatologists than those of psoriasis, and recent advances in our insight on their pathogenesis may eventually overcome the therapeutic difficulties faced by dermatologists and rheumatologists in the management of these diseases and their rheumatologic manifestations.

Paraneoplastic Pityriasis Rubra Pilaris Preceding Leukemia.

ABSTRACT: Pityriasis rubra pilaris (PRP) is a rare, chronic papulosquamous disorder that presents with scaling plaques, palmoplantar keratoderma, and keratotic follicular papules. Typically, there are distinctive unaffected areas referred to as "islands of sparing." Pityriasis rubra pilaris has been associated with various immunodeficient states and malignancies.The authors conducted a literature review using MEDLINE, PubMed, and Google Scholar, documenting all known cases of PRP associated with malignancy; 15 cases were found in the literature. They also present the case of a 49-year-old White man who, prior to referral to dermatology, was seen in urgent care for widespread pruritic rash. Physical examination in the dermatology clinic revealed confluent, scaly erythematous papules coalescing into plaques with island of sparing involving the trunk and upper and lower extremities. Bilateral palms and soles showed hyperkeratosis with fissuring. He was diagnosed with PRP after punch biopsy and began a new course of topical corticosteroid therapy. Hematology was consulted because of abnormal complete blood count results, and he was subsequently diagnosed with chronic lymphoid leukemia.Treatment of PRP is largely based on clinical experience and may involve corticosteroids, immunomodulators, or biologic therapy. The relationship between PRP and malignancy is unknown. Current theories postulate it may be driven by tumor production of functional peptides or antigen cross-reactivity between cancer cells and the skin. This is the second reported case of PRP as a manifestation of leukemia, and the first of chronic lymphoid leukemia. Although not yet understood, the documented relationship between PRP and malignancy prompts screening for cancer in all patients with new-onset PRP.

Acantholytic pityriasis rubra pilaris associated with topical use of imiquimod 5%: case report and literature review

Abstract Topical use of immune response modifiers, such as imiquimod, has increased in dermatology. Although its topical use is well tolerated, it may be associated with exacerbations of generalized cutaneous inflammatory diseases, possibly through the systemic circulation of pro-inflammatory cytokines. This report describes a case of development of pityriasis rubra pilaris, a rare erythematous-papulosquamous dermatosis, in a woman aged 60 years during treatment with imiquimod 5% cream for actinic keratosis. It evolved with erythrodermic conditions and palmoplantar keratoderma, presenting progressive clinical resolution after the introduction of methotrexate. The authors emphasize the importance of recognizing possible systemic reactions associated with the topical use of imiquimod.

Histopathologic findings characteristic of CARD14-associated papulosquamous eruption.

BACKGROUND: Pathogenic mutations in caspase recruitment domain-containing protein 14 (CARD14) lead to CARD14-associated papulosquamous eruption, which shares clinicopathologic findings with psoriasis and pityriasis rubra pilaris. We aimed to describe distinguishing histopathologic features of CARD14-associated papulosquamous eruption. METHODS: This retrospective study examined the histopathologic features of specimens from patients with confirmed CARD14-associated papulosquamous eruption and adult patients with plaque psoriasis and pityriasis rubra pilaris. RESULTS: Lesional skin biopsies from patients with CARD14-associated papulosquamous eruption consistently showed alternating checkerboard parakeratosis and orthokeratosis, acanthosis without acantholysis, and dilated vessels in the dermal papillae, with some cases also showing follicular plugging. CONCLUSION: CARD14-associated papulosquamous eruption has a range of findings, with a predominance of features typically associated with pityriasis rubra pilaris.

Acantholytic pityriasis rubra pilaris associated with topical use of imiquimod 5%: case report and literature review.

Topical use of immune response modifiers, such as imiquimod, has increased in dermatology. Although its topical use is well tolerated, it may be associated with exacerbations of generalized cutaneous inflammatory diseases, possibly through the systemic circulation of pro-inflammatory cytokines. This report describes a case of development of pityriasis rubra pilaris, a rare erythematous-papulosquamous dermatosis, in a woman aged 60 years during treatment with imiquimod 5% cream for actinic keratosis. It evolved with erythrodermic conditions and palmoplantar keratoderma, presenting progressive clinical resolution after the introduction of methotrexate. The authors emphasize the importance of recognizing possible systemic reactions associated with the topical use of imiquimod.

Pityriasis rubra pilaris as a systemic disease.

Pityriasis rubra pilaris (PRP) is a rare inflammatory skin disorder of unknown etiology, initially described in 1835. It is characterized by keratotic follicular papules, well-demarcated salmon-colored erythematous scaly plaques interspersed with distinct islands of uninvolved skin, and palmoplantar keratoderma. Is PRP a systemic disease? Skin is mainly affected in PRP. Despite its clinical heterogeneity, PRP could be associated with a variety of rheumatologic, infectious, neoplastic, and other extracutaneous manifestations. We accept the hypothesis of not only an association but also a causative relation between skin and systemic manifestations with possible common underlying pathomechanisms such as systemic immunologic processes and superantigen mimicry.

Circumscribed Juvenile Pityriasis Rubra Pilaris (Type 4) Koebnerising after a Hot Water Burn: Mild Disease with Maximum Koebner Response.

Dear Editor, Pityriasis rubra pilaris (PRP) is a chronic, inflammatory, papulosquamous skin disorder that is characterized by follicular hyperkeratosis and reddish-orange, scaling dermatitis with islands of normal skin (1,2). PRP is classified into 5 groups based on clinical features. Type 4 PRP is characterized by well-demarcated, hyperkeratotic erythematous plaques localized on the elbows and knees with palmoplantar keratoderma (1,2). An 8-year-old girl presented to our clinic with erythematous plaques on both elbows, the legs, and the knees. Plantar keratoderma was noticed on clinical examination. The lesions had started on the elbows and knees about a year ago. The lesions on the leg were surrounded by an irregular, hyperpigmented border. On close inspection, the plaques were formed by follicular papules and mild desquamation was noticed. Upon questioning, it was learned that the lesions on the leg with hyperpigmented borders had emerged after a hot water burn three months ago and that they were localized exactly on the burned areas of the skin (Figure 1). A biopsy was performed on the new lesions, and histopathological evaluation revealed parakeratosis with alternating orthokeratosis, irregular hyperkeratosis, keratotic plugs, and a mild perivascular lymphocytic infiltration around the blood vessels (Figure 2). A diagnosis of PRP was established. The Koebner phenomenon (KP) is described as the development of lesions in previously normal skin after exposure to internal or external trauma such as surgical incisions, burns, friction, insect bites, and allergic and irritant reactions (3). The pathogenesis of KP is not fully understood, but epidermal cell injury and dermal inflammation have been proposed as having a role in the pathophysiology (4). Experimental studies on the mechanism of KP have been performed mostly on patients with psoriasis (3). Disease severity, early age of disease onset, and multiple previous therapies have been found to be associated with KP (5,6). KP has previously been reported after injury with the sharp end of a stick in type 3 PRP, a generalized PRP form (7). However, our patient was diagnosed with type 4 PRP, which is a localized form of the disorder. Griffiths reported type 4 PRP does not evolve to generalized forms (8). In this respect, our case was interesting as maximum Koebner response was observed despite the mild PRP. We therefore believe that disease severity is not a determining factor in KP and that the severity of skin damage plays a crucial role. We also think that changes in the cytokine milieu in the burn area may be responsible for KP, as levels of IL-17 and IL-22, which have been shown to be upregulated in burns, also play a role in PRP pathogenesis (9,10). The disease onset at an early age might have also had a contributing role in the Koebner response in this patient. The hyperpigmented borders of the Koebnerized plaques were also notable as they were spared from KP. Some spared areas were also seen within the Koebnerized plaques themselves. A threshold level of trauma is thought to be necessary for inducing KP (3). The clinical picture of our patient may indicate that the skin damage was much less severe in some areas of the burn, especially in the periphery, and that KP was therefore not observed in these areas. Our case clearly demonstrates that the Koebner response is not related to disease severity. We believe that the type of trauma is an important factor in determining the severity of skin damage and the changes in the cytokine milieu in the involved skin. Early disease onset also seems to contribute to the development of KP. Further studies investigating the mechanism of KP in various skin disorders are necessary. As far as we are aware, this is the first case reporting Koebnerization in the circumscribed juvenile form of PRP.

Pityriasis Rubra Pilaris With Extensive Follicular Acantholysis Resembling Pemphigus Vulgaris: A Case Report.

Pityriasis rubra pilaris (PRP) is a rare, chronic, heterogeneous, papulosquamous inflammatory dermatosis of unknown etiology. Although erythematous scaly patches characterize the classic presentation of PRP, a broad range of clinical presentations has been reported. Histologically, PRP is characterized by psoriasiform acanthosis with alternating orthokeratosis and parakeratosis and rarely small acantholytic foci. In this article, we report a patient who presented with diffuse erythroderma and extensive acantholysis mimicking pemphigus vulgaris histologically.

Secukinumab emerges as a rapidly effective therapy for pityriasis rubra pilaris.

Refractory pityriasis rubra pilaris (PRP) often is treated off-label with the same biologic therapies that are approved for the treatment of psoriasis, most commonly tumor necrosis factor (TNF) α antagonists and ustekinumab; however, the IL-17A antagonist secukinumab also has shown efficacy in the treatment of PRP. We report 2 new cases of severe refractory PRP that responded rapidly to treatment with secukinumab.

Pityriasis rubra pilaris-like erythroderma secondary to phosphoinositide 3-kinase inhibition.

BACKGROUND: Phosphoinositide 3-kinase (PI3K) inhibitors are a class of small-molecule inhibitors approved for the treatment of certain leukaemias and lymphomas. Their dermatological adverse event profile is poorly described. AIM: To characterize a rare cutaneous adverse event from PI3K inhibitors in order to help dermatologists and oncologists identify and effectively manage such eruptions. METHODS: This was a retrospective analysis of patients receiving PI3K inhibitors referred to the Skin Toxicities Program in The Center for Cutaneous Oncology. RESULTS: Three patients on PI3K inhibitors for treatment of malignancy developed diffuse erythroderma and keratoderma. Clinical and histopathological findings were consistent with pityriasis rubra pilaris (PRP)-like reactions. All patients improved with topical and oral corticosteroids, oral acitretin, and drug discontinuation. CONCLUSIONS: PRP-like cutaneous eruptions may develop secondary to PI3K inhibition. Early dermatological evaluation of cutaneous toxicities to PI3K inhibitors as well as rapid initiation of disease-specific treatments may help keep patients on life-prolonging anti-cancer therapies.

Recalcitrant psoriasiform dermatosis of the face: Is it related to pityriasis rubra pilaris?

BACKGROUND: There are patients with recalcitrant psoriasiform plaques that do not fit into conventional categories of facial dermatoses. Our study aims to describe the clinicopathological characteristics of several patients with a unique presentation of persistent psoriasiform facial rashes. METHODS: This retrospective cross-sectional study analyzed clinical and histological data of known cases of recalcitrant psoriasiform dermatosis of the face diagnosed at National Skin Centre, Singapore, over 10 years. RESULTS: There were 8 Chinese patients with mean age at onset of 29 years. Majority had pink to pink-orange well-defined plaques with dry scale (n = 6, 75%), distributed mostly on the cheeks (100%) and chin (n = 7, 88%). Hyperkeratosis, parakeratosis, preserved granular layer and psoriasiform hyperplasia were showed in all biopsies. Other common findings included subtle subcorneal acantholysis, "checkerboard" alternating ortho-/parakeratosis, vacuolated keratinocytes and follicular plugging. All patients showed little treatment response. One patient eventually developed features of type II pityriasis rubra pilaris (PRP). Our study was limited by its small sample size and lack of a pre-existing diagnostic code. CONCLUSIONS: This recalcitrant psoriasiform facial dermatosis seems to be a distinct entity, with consistent and reproducible clinical features and a PRP-like histology, bearing some resemblance to the recently described condition-facial discoid dermatosis.