Pityriasis Rubra Pilaris: An Updated Review of Clinical Presentation, Etiopathogenesis, and Treatment Options.

Pityriasis rubra pilaris (PRP) is a rare papulosquamous reaction pattern with a significant impact on quality of life. Type I PRP is the most common PRP variant, presenting as erythematous papules emerging in a follicular distribution and later coalescing into plaques with characteristic islands of sparing; histologically, an alternating pattern of orthokeratosis and parakeratosis is considered the hallmark of PRP (checkerboard hyperkeratosis). Other PRP variants (types II-V) differ in their age of onset and clinical presentation. Type VI PRP is a rare PRP subtype associated with human immunodeficiency virus infection and is occasionally associated with diseases of the follicular occlusion tetrad. Caspase recruitment domain family, member 14 (CARD14)-associated papulosquamous eruption and facial discoid dermatitis are newly described disease states that have an important clinical overlap with PRP, creating shared conundrums with respect to diagnosis and treatment. The etiology inciting PRP often remains uncertain; PRP has been suggested to be associated with infection, malignancy, or drug/vaccine administration in some cases, although these are based on case reports and causality has not been established. Type V PRP is often due to inborn CARD14 mutations. Furthermore, recent literature has identified interleukin-23/T-helper-17 cell axis dysregulation to be a major mediator of PRP pathogenesis, paving the way for mechanism-directed therapy. At present, high-dose isotretinoin, ixekizumab, and secukinumab are systemic agents supported by single-arm prospective studies; numerous other agents have also been trialed for PRP, with variable success rates. Here, we discuss updates on clinical manifestations, present new insights into etiopathogenesis, and offer a survey of recently described therapeutic options.

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 treatment options: A retrospective case series from a tertiary hospital.

Pityriasis rubra pilaris (PRP) is a group of uncommon chronic inflammatory skin conditions with unclear pathophysiology and etiology. To date there is limited published literature and no clinical guidelines for the management of PRP. Infliximab, alone or in combination, is the most widely published successful treatment for adults and etanercept for pediatric populations. We present a case series of patients diagnosed with PRP. Retrospective data were collected from a tertiary Australian dermatology department between January 2010 and December 2019 on patients with PRP. Electronic medical records and pathology database were searched. A total of 13 patients were included. Twelve of the 13 patients used topical agents and three patients attempted narrow-band ultraviolet B phototherapy. All patients received acitretin as first line systemic agent with the dose varying from 10 to 50 mg daily. Six patients treated with acitretin reported adverse events, requiring dose reduction or cessation. Of the nine patients who did not receive a biologic agent, complete clearance of PRP was achieved in five cases. At least one biologic agent was used in four cases with two experiencing a marked improvement. Overall, complete clearance was achieved in six patients. PRP continues to be a challenge to treat with many treatment options used with variable efficacy.

Pitiriasis rubra pilaris tratada con lámpara excímero / Pityriasis rubra pilaris treated with excimer lamp

Resumen La pitiriasis rubra pilaris, es una dermatosis inflamatoria papuloescamosa e hiperqueratósica de origen desconocido y de progresión crónica, la cual puede evolucionar incluso a eritrodermia. El presente caso trata de un paciente de 27 años portador del virus de inmunodeficiencia humana, diagnosticado con pitiriasis rubra pilaris tipo IV, inicialmente tratado con corticosteroide tópico y fototerapia, por cuatro meses. Sin embargo, presentó reactivación de las lesiones, por lo que se recurrió a la aplicación de lámpara excímero, utilizada en otras patologías dermatológicas, mas no de uso habitual en la pitiriasis rubra pilaris.

Abstract Pityriasis Rubra Pilaris is an inflammatory papulosquamous and hyperkeratic dermatosis of unknown cause and chronic progression which can envolve even into erythroderma. This case deals with a 27-year old male patient carrier of VIH who was diagnosed with PRP type IV. Initially, it was treated with topical corticosteroid and phototherapy for four months. However, it showed reactivation of the injuries; therefore, excimer lamp was employed, which is used in other dermatologic pathologies but it is not a regular treatment for PRP type IV.

Erythrodermic pityriasis rubra pilaris treatment: Two case reports and literature review.

Pityriasis rubra pilaris (PRP) is a rare inflammatory dermatosis characterized by hyperkeratotic follicular papules and erythematous-desquamative plaques that tend to progressively evolve into erythroderma. Treatment is challenging given that international guidelines are not available and large-scale trials do not exist. Traditionally, many topical and systemic drugs had been used as consolidated agents; recently, biologicals are gaining increasing importance, promisingly dominating the therapeutic scenario ahead. Herein, we present a case series showing the "past" and the "future" therapeutic approaches to erythrodermic PRP, one case treated with acitretin and nb-UVB phototherapy combination, while the other with ustekinumab, performing also a throughout literature review.

Treatment of pityriasis rubra pilaris type I: a systematic review.

Pityriasis rubra pilaris (PRP) is an uncommon papulosquamous inflammatory disease of the skin, which may progress to erythroderma. The diagnosis is based on both clinical and histopathological findings. There are numerous treatment options in the literature, but often reported as unsuccessful. To summarize the therapy of type I PRP in a systematic manner. We performed a systematic search following the PRISMA Guidelines based on PubMed, Web of Science, and Medline databases using the term 'pityriasis rubra pilaris treatment' (in German and English) on human subjects, published between 1997 and 2017, documenting therapy for PRP type I. A total of 449 records were identified; 148 full-text articles were assessed for eligibility and 105 articles were included in the qualitative synthesis. We identified mainly individual case reports, a few retrospective studies, and small case series. No randomized controlled trials were found. Treatment options included topical and systemic agents, and physical modalities. Based on our review, we suggest a continuous topical treatment and, when appropriate, in combination with phototherapy. As first-line therapy, we recommend a retinoid, and as second-line, a combination of retinoid and methotrexate (considering the patient's condition and side effects), azathioprine, or cyclosporine A. Biologicals can be used as third-line therapy. In case of treatment failure, biologicals can be combined with a retinoid, methotrexate, or cyclosporine A. Randomized controlled clinical trials are needed in order to provide an evidence-based high-quality standardized treatment for patients with PRP type I.

Case of pityriasis rubra pilaris progressed to generalized erythroderma following blockade of interleukin-17A, but improved after blockade of interleukin-12/23 p40.

We report herein a case of a 72-year-old man with pityriasis rubra pilaris (PRP) that was refractory to conventional therapies. His skin lesions progressed to generalized erythroderma despite anti-interleukin (IL)-17A antibody therapy. Topical corticosteroids, emollients, systemic retinoid, methotrexate, cyclosporin and phototherapy yielded no therapeutic response. However, blockade of IL-12/23 p40 dramatically improved his cutaneous lesions. Complete remission was achieved 4 weeks after the first injection of ustekinumab and maintained for more than 48 weeks. Our data indicate that IL-12 was associated with the onset of PRP in this patient, rather than IL-23. IL-12 is critical for the differentiation of T-helper (Th)1 cells. Thus, the Th1 pathway may be associated with the onset of PRP.

Systemic therapies of pityriasis rubra pilaris: a systematic review.

Pityriasis rubra pilaris (PRP) is a rare papulosquamous disorder. Treatment is challenging; the armamentarium consists of topical corticosteroids, phototherapy, classic systemic treatments such as retinoids or immunosuppressive drugs, and most recently biologicals. However, the relative effectiveness of therapies is unclear. Our objective was to review the published literature on systemic treatment of PRP. A systematic review was conducted on PubMed and the Cochrane Library up to 5 September 2017. Studies evaluating any systemic treatments of PRP (except for historical treatments) were included. Overall, 182 studies met the predefined inclusion criteria, and reported on 475 patients and 652 courses of treatment. 42.0 % (225/514) of all patients treated with retinoids achieved an excellent response (isotretinoin: 61.1 % [102/167], etretinate: 47 % [54/115], and acitretin: 24.7 % [43/174]) compared to an excellent response rate of 33.1 % (53/160) with methotrexate. Therapy with biologicals was successful in 51.0 % of patients (71/133) (ustekinumab: 62.5 % [10/16], infliximab: 57.1 % [28/49], etanercept: 53.3 % [16/30], and adalimumab: 46.4 % [13/28]). This review balances effectiveness, side effects, experience, and drug costs in order to suggest a treatment regimen starting with isotretinoin as first-line, methotrexate as second-line and biologicals as third-line treatment for this difficult-to-treat dermatosis.

[Pityriasis rubra pilaris]. / Pityriasis rubra pilaire.

Pityriasis rubra pilaris is a rare heterogeneous dermatosis associating three clinical signs to different degrees: follicular corneal papules, reddish-orange palmoplantar keratoderma and erythematosquamous lesions that may in some cases be very extensive, interspersed with patches of healthy skin. The aetiology is unclear, and in most cases, the trigger factors consist of trauma or infection, probably in subjects with an existing predisposition. In other cases, the condition is associated with immunological disorders or, in familial cases, genetic keratinisation abnormalities similar to ichthyosis. Given the widely varying signs, several classifications have been proposed, based on clinical criteria and outcomes. The outcome varies in accordance with the clinical forms involved. Therapeutic approaches are poorly qualified and there have been no clinical trials due to the rarity of the disease. However, the best results appear to have been obtained using oral retinoids, with second-line therapy comprising methotrexate and cyclosporine. The landscape of therapeutic strategy seems to be changing with the advent of new anti-tumour necrosis factor and anti-interleukin-12/23 antibodies.

A Review on Pityriasis Rubra Pilaris.

Pityriasis rubra pilaris (PRP) is an idiopathic, papulosquamous inflammatory dermatosis. It is characterized by hyperkeratotic follicular papules coalescing into orange-red scaly plaques, islands of sparing, and palmoplantar keratoderma. PRP can be subdivided into six clinical subtypes according to Griffiths' classification, based on age of onset, disease extent, prognosis, and other associated features. The sixth subtype of PRP occurs in individuals affected by HIV infection, and retroviral screening in all de novo cases of PRP is advised. Other reported associations include various infections, autoimmunity, drugs, and malignancies, although the true significance of these is still unclear. The genetic basis for familial cases, most commonly categorized under the fifth subtype, has been mapped to gain of function mutations in the caspase recruitment domain family, member 14 (CARD14) gene. Treatment of PRP remains a challenge to this day due to a paucity of high-quality evidence. Therapeutic regimens have been guided mostly by case reports and case series, with the mainstay of treatment being oral retinoids. Recently, biologics have emerged as a promising treatment for PRP. We present a review of the clinicopathologic features, pathogenesis, associated disorders, and treatment of PRP, with an emphasis and critical appraisal of the existing literature on the latter.

Beneficial effect of ustekinumab in familial pityriasis rubra pilaris with a new missense mutation in CARD14.

Pityriasis rubra pilaris (PRP) represents a group of rare chronic inflammatory skin disorders in which around one in 20 affected individuals show autosomal dominant inheritance. In such cases there may be gain-of-function mutations in CARD14, encoding caspase recruitment domain-containing protein 14 (CARD14), which activates the noncanonical nuclear factor (NF)-κB pathway, thereby promoting cutaneous inflammation. Here we report a mother and son with PRP due to a new missense mutation in CARD14 and describe the beneficial clinical effects of ustekinumab, a monoclonal antibody against interleukins 12 and 23, in both patients. A 49-year-old woman and her 20-year-old son had lifelong, generalized, patchy erythematous scale with a few islands of sparing, as well as minor nail ridging and mild palmoplantar keratoderma, features consistent with generalized PRP. Topical steroids, phototherapy and oral retinoids proved ineffective. Following informed consent, Sanger sequencing of CARD14 in both individuals revealed a new heterozygous single-nucleotide transversion in exon 4, c.356T>G, resulting in the missense mutation p.Met119Arg. Ustekinumab, at a dose of 45 mg every 12 weeks, brought about a significant physical and emotional improvement in both the mother and son within a few days of the initial dose, which was sustained on maintenance dosing. This report highlights the therapeutic potential of biologics that downregulate NF-κB signalling in familial PRP with mutations in CARD14.

[Pityriasis rubra pilaris]. / Pityriasis rubra pilaire: une dermatose mal connue.

Pityriasis rubra pilaris is a rare heterogeneous disorder characterized by follicular keratosis, perifollicular erythema and palmoplantar hyperkeratosis. The aetiology is still unknown. In the majority of cases some triggering factors are found such as trauma or bacterial infection, possibly on a predisposed condition. In other cases, some immunological disorders are associated, and in familial cases a genetic disorder of keratinization has been suggested. The evolution is variable according to the clinical type. The treatment is not well defined, and there is a lack of clinical trials. The best results however are obtained with oral retinoids, methotrexate or ciclosporine as alternative therapy. New TNF inhibitors and anti-IL-12/23 showed a good result and could be have interest in the future.

Ustekinumab. Otros usos. Otras formas de psoriasis. Otras patologías cutáneas / Ustekinumab. Other uses. Other forms of psoriasis. Other skin conditions

Ustekinumab es un anticuerpo monoclonal humano anti interleucina 12 y 23. En los ensayos clínicos pivotales quedó probada su eficacia y seguridad a nivel de la psoriasis en placas moderada-severa. Asimismo, cabe destacar que en dichos ensayos se utilizó también el índice de severidad de psoriasis ungueal para evaluar su efectividad en la psoriasis ungueal. Los pacientes tratados en el ensayo PHOENIX 1 (n=545) mostraron que las lesiones ungueales mejoraron de forma progresiva hasta la semana 52, si bien en la semana 12, después de dos dosis de ustekinumab, la mediana de la mejoría de las puntuaciones NASPI respecto al valor basal fue del 25%, llegando al 50% en la semana 24. Por otro lado, desde su reciente incorporación, ustekinumab también se ha empleado en otras formas de psoriasis (pustulosa, palmo-plantar, eritrodérmica) y también en otras enfermedades (pitiriasis rubra pilaris, hidradenitis supurativa y dermatitis atópica) (AU)

Ustekinumab is a human monoclonal antibody directed against IL-12 and IL-23. Pivotal clinical trials have proven its efficacy and safety in the treatment of moderate to severe plaque psoriasis. The same trials have also evaluated the efficacy of this drug in nail psoriasis using the Nail Psoriasis Severity Index (NAPSI). Patients treated in the PHOENIX 1 trial (n=545) showed progressive improvement in NAPSI scores up to week 52. At week 12, after 2 doses of ustekinumab, the median improvement from baseline was 25% and at week 24, it was 50%. Since its recent approval for the treatment of moderate to severe plaque psoriasis, ustekinumab has been used to treat other forms of psoriasis (pustular, palmoplantar, and erythrodermic psoriasis) and other diseases (pityriasis rubra pilaris, hidradenitis suppurativa, and atopic dermatitis) (AU)

Pityriasis Rubra Pilaris Treated with Infliximab / 대한피부과학회지

Pityriasis rubra pilaris (PRP) is a chronic papulosquamous disorder of unknown etiology, which may pose therapeutic challenges. There is currently no universally effective treatment for PRP, and some cases are resistant to multiple topical and systemic therapies. Systemic retinoids, methotrexate, several immunosuppressive agents and phototherapy have all been used with varying degrees of success. Recently, a few reports have appeared in the literature, concerning the use of biologics in combination therapies and/or in refractory PRP cases. We report a case of PRP similar to type II with juvenile onset, which was recalcitrant to traditional topical and systemic therapy. He was successfully treated with anti-TNF-alpha monoclonal antibody, infliximab. The patient showed resolution with minimal disease activity, and was maintained on acitretin and emollients. The response to infliximab in our patient and in the previously reported cases confirms a role of anti-TNF-alpha therapy as an effective option in the treatment of PRP.

Pityriasis rubra pilaris: a review of diagnosis and treatment.

Pityriasis rubra pilaris (PRP) is a rare inflammatory dermatosis of unknown etiology, and finding a successful therapy can be challenging. PRP occurs equally in men and women. In some patients, associated autoimmune diseases, infections, or malignancies are possible trigger factors. PRP shows a bimodal age distribution, peaking in the first as well as in the fifth to sixth decade. Its classification into five subgroups is based on age at onset, clinical course, morphologic features, and prognosis. More than 50% of patients are best classified as type I with adult-onset PRP. This form is also characterized by high spontaneous remission rates (80%) within 1-3 years. Clinically, the classical adult (type I) and classical juvenile (type III) forms appear to be the same except for the patient's age. Recently, the designation of a new category of PRP (type VI) has been proposed that is characterized by the presence of HIV infection with different clinical features and a poorer prognosis. Typical morphologic features of PRP are erythematosquamous salmon-colored plaques with well demarcated islands of unaffected skin. Often, keratoderma of the palms and soles is present. In patients with extensive disease, ectropion is a dreaded complication. Histology shows hyperkeratosis, alternating orthokeratosis and parakeratosis in a checkerboard pattern, and focal acantholytic dyskeratosis. Descriptions and therapeutic experiences are mainly based on case reports. Mostly, systemic retinoids, methotrexate, and other immunosuppressive agents as well as UV light therapy are applied, with varying response rates. In recent years, treatment with so-called 'biologics' is becoming more and more popular for treating recalcitrant PRP. We present a review of the clinical features, histopathologic findings, classification, differential diagnoses, and treatment of PRP.

Pityriasis rubra pilaris sensitive to narrow band-ultraviolet B light therapy.

Pityriasis rubra pilaris (PRP) is a rare skin condition which typically presents in adults as red-orange plaques with islands of sparing, perifollicular keratotic papules, waxy palmoplantar keratoderma, and erythema with fine, diffuse scale. Currently, there are no well-established treatment guidelines for this condition. This is party due to a lack of universally effective treatments for PRP, with some cases being resistant to multiple topical and systemic therapies. Systemic retinoids have been used with some success. Several phototherapy regimens have lead to variable results. The authors present a case of PRP, unresponsive to 6 month treatment of isotretinoin, that was subsequently treated with narrow-band ultraviolet B (NB-UVB) light therapy with complete resolution after four months of light treatment. The observed clinical benefit may encourage future phototesting and consideration of NB-UVB light therapy in recalcitrant PRP cases.

Acute juvenile pityriasis rubra pilaris: a case report after mononucleosis infection.

A 24-year-old male boy presented dermatosis which first appeared acutely after an infection at age 17. Clinical and histopathologic examinations were consistent with a diagnosis of juvenile pityriasis rubra pilaris type III. Treatment with UVB narrow-band led to complete resolution of the dermatitis within 1 year. Pityriasis rubra pilaris is a papulosquamous disorder of unknown etiology, which can be treated with retinoids, methotrexate, cyclosporine, and narrow-band phototherapy.

Infliximab monotherapy as first-line treatment for adult-onset pityriasis rubra pilaris: case report and review of the literature on biologic therapy.

Pityriasis rubra pilaris (PRP) is a rare, chronic papulosquamous disorder of unknown etiology that often progresses to disabling palmoplantar keratoderma and erythroderma. There is currently no universally effective treatment for PRP, and some cases are resistant to multiple topical and systemic therapies. Systemic retinoids, methotrexate, several immunosuppressive agents, fumaric acid esters, stanozolol, and phototherapy have all been used with varying degrees of success. Recently, a few reports have appeared in the literature concerning the use of biologics in combination therapies and/or in refractory PRP cases. We report a case of type I adult-onset PRP successfully treated with infliximab monotherapy as initial systemic therapy, and provide a comprehensive literature review on biologic therapy for PRP. The complete and persistent response to infliximab in our patient and in the previously reported cases confirms a role for anti-tumor necrosis factor-alfa therapy as an effective option in the treatment of PRP. Further studies are warranted to evaluate possible differences in efficacy among the different biologics.

Exacerbation of pityriasis rubra pilaris under efalizumab therapy.

A 60-year-old woman, diagnosed as having psoriasis vulgaris in 2004 and unresponsive to standard therapies, received weekly subcutaneous injections with efalizumab. Within 9 weeks of treatment a massive aggravation of skin lesions occurred with widespread orange-tinged erythroderma, islands of normal skin on the back and the inner side of the forearms and palmoplantar hyperkeratosis. A biopsy confirmed the clinical diagnosis of pityriasis rubra pilaris. After discontinuation of efalizumab and treatment with oral corticosteroids, acitretin (30 mg/day) and PUVA therapy, the skin lesions continuously improved. Efalizumab, a fully humanized monoclonal antibody against CD11a, inhibits various T cell processes important in the pathogenesis of psoriasis. Efalizumab has been approved for the treatment of moderate to severe psoriasis, but there are no reports in the literature on the use of efalizumab for pityriasis rubra pilaris.

Clinical improvement of pityriasis rubra pilaris with efalizumab in a pediatric patient.

Pityriasis rubra pilaris has no single effective therapy and there are some cases resistant to multiple treatments. Psoriasis has clinical and therapeutic response overlaps with pityriasis rubra pilaris and there are several therapies common to both, such as retinoids, methotrexate, cyclosporine A, phototherapy, and most recently infliximab. We report a case of a 10-year-old boy with pityriasis rubra pilaris unresponsive to topical corticosteroids, salicylic acid, pimecrolimus, calcitriol, calcipotriol, ultraviolet B targeted phototherapy, isotretinoin, systemic PUVA, acitretin, and etanercept. He was treated with efalizumab 1 mg/kg weekly and a successful outcome was obtained with a 50% improvement after the first dose. The patient remains in remission after 9 months of treatment.