Classic Pityriasis Rubra Pilaris Research Articles

Severe and Prolonged Liver Damage in Pityriasis Rubra Pilaris Treated with acitretin: a Case Report

Acitretin is a systemic retinoid that is used in dermatology for treatment of various inflammatory and especially hyperkeratotic diseases. Elevation of liver enzymes may occur occasionally but normally resolves spontaneously, at the latest after termination of acitretin. However, it can very rarely develop into a life-threatening adverse event including drug-induced liver injury (DILI). A 45-year-old man with classical pityriasis rubra pilaris, a frequently severe, inflammatory skin disease, was started on acitretin. After a seemingly harmless elevation of transaminases, a few weeks after initiation of acitretin, the patient experienced a dramatic course of liver injury with hepatic jaundice though acitretin was stopped immediately. Eventually, laboratory values recovered upon high-dose oral prednisolone therapy. Prescribing physicians should keep in mind that acitretin might induce severe liver injury. Even after termination of acitretin laboratory values should be monitored for a while in order to recognize symptomless but harmful drug-induced liver injury in time.

Classic Juvenile Pityriasis Rubra Pilaris Treated with Oral Alitretinoin

Dear Editor: Pityriasis rubra pilaris (PRP) is a papulosquamous disorder of unknown etiology. Although treatment of PRP is challenging, oral retinoids, including acitretin and isotretinoin, are used as first-line treatment. Recently, alitretinoin, a novel panagonist retinoid, has been reported to be effective for PRP. Here, we described a case of refractory PRP that showed remarkable response to alitretinoin. A 37-year-old man, presenting with relapsing skin lesions over the whole body since 1 year of age, had been diagnosed with and treated for PRP since he was 10 years old. He had a familial PRP history on his mother's side. Physical examination at the first visit revealed erythematous pruritic scaly papuloplaques on the trunk and lower extremities, which was not distinctive due to previous treatments in other hospitals (Fig. 1A, B). Palmoplantar keratoderma was mildly observed. Neither follicular hyperkeratosis nor generalized erythroderma with island of normal skin was seen. The skin biopsy from the left thigh revealed regular acanthosis with broad rete ridge, parakeratosis, and perivascular lymphocytic infiltration with occasional eosinophils (Fig. 1C). There was no confluent hypergranulosis or alternating orthokeratosis and parakeratosis. Classic juvenile PRP was diagnosed. Several treatment options were administered for 1 year in our hospital, which included neotigasone 20~30 mg for 13 months, narrow-band ultraviolet-B phototherapy for 6 months, methotrexate 12.5 mg per week for 1 month, prednisolone 0.5~5 mg for 12 months, and superpotent topical steroid for 6 months. However, none of these treatments led to stable remission. Therefore, oral alitretinoin (30 mg daily) was initiated and continued for 5 months, combined with superpotent topical steroid. The skin lesions and pruritus significantly disappeared in 4 weeks and were not aggravated for 5 months (Fig. 2). Also, there were no side effects except mild dryness. Laboratory test did not show any abnormalities including serum cholesterol. The patient stated that alitretinoin was most effective and tolerable compared with other therapies. Therefore, we decided to continue the same dosage of alitretinoin as far as it was well-tolerated. Fig. 1 Clinical findings of pityriasis rubra pilaris presented at the first visit to our hospital. Multiple erythematous scaly papuloplaques on (A) the trunk and (B) the lower extremities. (C) Histopathologic findings revealed regular acanthosis with broad rete ... Fig. 2 No skin lesion was seen on the (A) trunk and (B) lower extremities after the 5 months course of oral alitretinoin. PRP can be clinically divided into 6 subtypes1. It comprises an adult-onset (classic or atypical adult type), juvenile-onset (classic, circumscribed or atypical juvenile type) and human immunodeficiency virus-associated form. Classic juvenile PRP begins in the first 2 years after birth, showing similar features of classic adult type. Systemic retinoids such as acitretin and isotretinoin have antiproliferative, immuno-modulatory, and anti-inflammatory effects that are mediated by intranuclear retinoid acid receptors (RARs). However, alitretinoin (9-cis-retinoic acid) uniquely binds not only to RARs, but also to retinoid X receptors with high affinity. Owing to this dual interaction, alitretinoin may be more effective than conventional retinoids2. Moreover, alitretinoin inhibits production of nitric oxide and proinflammatory cytokines such as tumor necrosis factor-α, interleukin-1β and interleukin-12p403. In addition, alitretinoin results in fewer mucocutaneous side effects than other retinoids2. To our knowledge, only few cases of adult-onset PRP treated with alitretinoin have been reported2,3,4,5. This is the first case of refractory classical juvenile PRP that responded well to alitretinoin. In conclusion, alitretinoin could be a promising alternative for treating refractory classic juvenile PRP.

The Incidence of Acantholysis in Pityriasis Rubra Pilaris-Histopathological Study Using Multiple-Step Sections and Clinicopathologic Correlations.

The classical histopathological findings in the epidermis of pityriasis rubra pilaris (PRP) do not include acantholysis; however, acantholysis was described in several case reports and a few series of PRP with variable frequencies. We sought to establish the incidence of acantholysis in biopsies from consecutively referred PRP cases using multiple-step sections and clinicopathologic correlations. Twenty-three biopsies from 12 consecutively referred patients with classical (type 1) PRP were studied histopathologically. Each specimen was completely step sectioned. The clinical files of the patients were also reviewed. Small foci of acantholysis were observed in some of the step sections of 5 of 23 (22%) biopsies obtained from 4 patients. Three biopsies showed suprabasal acantholysis, 1 of which also demonstrated mild dyskeratosis and 2 showed midepidermal acantholytic foci as well. The remaining 2 biopsies demonstrated midepidermal and subcorneal acantholysis, respectively. Small erosions were described in the physical examination of 2 of the 4 (50%) patients with acantholysis and in 1 of the 8 (12.5%) patients without acantholysis. The number of cases. Small foci of acantholysis may be found in the minority of PRP biopsies, and it may be related to small erosions clinically in some patients.

Adult onset pityriasis rubra pilaris

Pityriasis rubra pilaris (PRP) has always been an intriguing topic ever since its inception. It is a group of chronic disorders characterized by reddish orange plaques with pityriasiform scaling showing follicular keratoses, palmoplantar keratoderma, and sometimes, erythroderma. It occurs all over the world but with racial variations. Its incidence might vary and the age at onset, behavior, clinical appearance, and prognosis are considered to be very important for its classification. It may manifest either as Type I classical adult onset PRP, Type II atypical adult (onset) PRP, or Type VI PRP (HIV-associated PRP pityriasis rubra pilaris) in contrast to classical juvenile (Type III) and circumscribed juvenile (Type IV) encountered among children. Its diagnosis is largely clinical with microscopic pathology being a useful supplement, but it continues to be a therapeutic dilemma. We review the epidemiology of adult onset PRP here and take stock of the prevalent treatment options.

Juvenile onset classical pityriasis rubra pilaris: every patient may not require systemic therapy.

Juvenile onset classical Pityriasis Rubra Pilaris (PRP), although rare, is the most common presentation of PRP in children. It has good prognosis and resolution over a few months. Use of potentially hazardous systemic drugs in a disease, that is likely to resolve spontaneously, needs to be assessed carefully. We report a 09 years old boy suffering from this rare disorder, whose disease is well under control with emollients and a combination of diluted topical steroids and keratolytics, for over 06 months.

Enhanced Expression of p53 Protein in Pityriasis Rubra Pilaris

p53 is a phosphoprotein, known since 1992 as a “guardian” of the genome (1, 2). A mutation in the p53 gene coding this protein, which activation protects the organism from tumourigenesis, has been found in more than half of all human tumour types (3). DNA damaging agents induce p53 protein activity, which leads to cell cycle arrest in the G1 or G2 phase and, in the case of ineffective DNA repair, apoptosis is initiated (4). p53 immunoreactivity has also been found in non-tumourigenic inflammatory skin diseases, e.g. psoriasis, chronic dermatitis, lupus erythematosus and lichen planus (5), often with contro-versial results. p53 is also detectable in normal skin, using various methods of antigen retrievals, especially after ultraviolet (UV) exposure, but at very low levels (6).Pityriasis rubra pilaris (PRP) is a rare hyperkeratotic, papulo-squamous skin disorder with unknown aetio-logy. Although the first case was described in 1828, until now the pathogenesis of this rare disorder is still a matter for debate. A few possible mechanisms are considered: abnormal vitamin A metabolism in the skin, association with internal malignancies, immune system dysregulation (PRP often appears simultaneously with autoimmune diseases) and associations with infections, particularly human immunodeficiency virus. Hereditary forms of PRP are very rare (7, 8). Experimental stu-dies showed that epidermal cells in PRP lesions have increased labelling index compared with normal skin keratinocytes, similarly to findings in psoriatic skin (9, 10). PRP presents with some histological features simi-lar to psoriasis, especially hyperkeratosis, parakeratosis and acanthosis (7, 8, 11), which could result from cell cycle disturbances in the keratinocytes.The present study was undertaken to evaluate ex-pression of p53 protein in the lesional skin of patients with type I classic PRP (confirmed by histological examination).PATIENTS AND METHODS

Pityriasis Rubra Pilaris and Cyclosporine

Pityriasis rubra pilaris (PRP) has been classified into five subtypes by Griffiths. 1 Type I, classic adult PRP , is the most common subtype, representing over 50% of cases. Systemic retinoids (etretinate and isotretinoin) and antimetabolites (methotrexate and azathioprine) are effective treatments of PRP. 2 The use of cyclosporine for treatment of PRP was first discussed in 1989. 3 We present a case of successful treatment of adult-onset PRP with lose-dose cyclosporine. Complete clearance of PRP was achieved with no recurrence for over 2 years. Report of a Case. A 60-year-old white woman was evaluated by her primary dermatologist for a 1-month history of a pruritic facial rash. A preliminary diagnosis of facial dermatitis led to treatment with oral prednisone (80 mg/ d). However, the facial rash worsened, and the palms soon appeared yellowish and thickened. Within 2 months of onset, a widespread eruption of pruritic erythematous plaques appeared over much