Paraneoplastic pityriasis rubra pilaris: case report and literature review

Pityriasis rubra pilaris (PRP; MIM 173200) is an uncommon papulosquamous inflammatory dermatosis. Only a few cases of PRP associated with an underlying malignancy have been documented. We investigated a 59‐year‐old patient presenting with a fulminant form of PRP recalcitrant to systemic retinoid therapy, in whom the skin disease heralded a diagnosis of cholangiocarcinoma. We searched the MEDLINE database to find articles reporting on similar associations of PRP with malignancies. We identified 10 studies linking PRP and malignancies, but an association between PRP and cholangiocarcinoma has not yet been reported.     

Pityriasis rubra pilaris: algorithms for diagnosis and treatment

Pityriasis rubra pilaris (PRP) is a rare inflammatory skin disease that affects men and women of all ages and also children. The clinical appearance of PRP is highly variable, as is the individual prognosis. Therefore, stratifying PRP into six disease subtypes represents a first step to personalized medicine for this rare inflammatory skin disease. The next step should be to associate specific therapeutic strategies with these subtypes of PRP. However, no randomized, controlled trials on the treatment of PRP have been performed. Consequently, the actual treatment algorithm for PRP will be based on clinical experience, small case series and case reports. The majority of published evidence is on type I PRP, whereas the treatment experience for other clinical types of PRP is still sparse and has to be gained. Nevertheless, it is now time to start developing valid algorithms as a basis for the diagnosis and treatment of PRP based on the data available. This review makes use of algorithms developed in psoriasis and atopic eczema and puts together recent insights into the pathogenesis, diagnosis and treatment experience of PRP. The innovative intention of this appraisal is to develop a structured algorithm for PRP treatment that should be further developed going forward.     

Pityriasis rubra pilaris: the clinical context of acantholysis and other histologic features

Background Acantholysis has been described in biopsies of pityriasis rubra pilaris (PRP), but this has not been emphasized in the dermatology literature. It is helpful for dermatologists to associate acantholysis with PRP in the correct clinical setting. Objective This study aims to further elucidate the clinical context and associated histologic features of acantholysis in PRP. Methods Eight cases of PRP with acantholysis, 16 other cases of PRP, 26 cases of psoriasis, and 17 cases of erythroderma of different causes were studied in an academic setting. Results The presence of acantholysis initially confounded the diagnosis in two cases of PRP. Acantholysis was focal or extensive and resembled Darier’s disease, Hailey–Hailey disease, or pemphigus vulgaris. Acantholysis was seen in biopsies from early, isolated papulosquamous lesions from the trunk as well as from erythroderma. By comparison, 26 cases of psoriasis and 17 cases of erythroderma showed only focal acantholysis in two cases of erythroderma. Conclusions Acantholysis is a histologic feature of PRP and can serve as a histologic clue to the diagnosis of PRP before the onset of erythroderma. Eosinophils and/or a lichenoid infiltrate may also be evident.     

Refractory pityriasis rubra pilaris treated with etanercept,adalimumab, or ustekinumab: A retrospective investigation

Pityriasis rubra pilaris (PRP) is a rare, difficult to treat papulosquamous disorder that responds variably to retinoids and immunosuppression. Successful use of biologics for treating PRP has been described in the literature by case reports and a limited number of case series. To provide additional data, we retrospectively analyzed cases of PRP treated with biologics at our institution. We identified seven patients with a clear diagnosis of PRP treated with adalimumab, etanercept, and/or ustekinumab at our institution from January 1, 2014 to April 1, 2017. Six of seven patients had type I, adult acquired PRP, and one had type V atypical juvenile PRP. In response to tumor necrosis factor (TNF)‐α inhibition, two patients had marked responses (>75% improvement in involved body surface area), while three patients failed to show any improvement on a TNF‐α inhibitor. In two cases of PRP refractory to TNF‐α inhibition, ustekinumab resulted in a partial response (<75% improvement) in one patient and no response in the other. Compared to other published data, our cohort was substantially more resistant to treatment with biologics, a finding which may provide valuable perspective for dermatologists managing refractory PRP in the future.     

Pityriasis rubra pilaris in association with laryngeal carcinoma

Pityriasis rubra pilaris (PRP) is a rare group of hyperkeratotic, papulosquamous diseases that can be acquired or inherited. Cases of PRP associated with malignancy have been rarely reported. We report a case of 46‐year‐old man who presented with rapidly progressing PRP as a possible initial cutaneous symptom of a previously undiagnosed laryngeal carcinoma. Microlaryngoscopy was performed because of the patient’s hoarseness, and this revealed leucoplakia on the left vocal cord. Histopathological examination led to the diagnosis of squamous cell carcinoma in situ. After surgical treatment, the clinical signs of PRP began to resolve, and the patient was free of skin lesions at follow‐up. This case represents a rare coexistence of PRP with malignancy, and indicates that PRP can occur as paraneoplastic dermatosis associated with laryngeal cancer.     

The clinical and histomorphological features of pityriasis rubra pilaris

Pityriasis rubra pilaris (PRP) is an idiopathic erythematous scaling eruption which can be difficult to distinguish from psoriasis. We explored the clinical features, including background medical illnesses and potential triggers in patients with PRP, and also its histomorphologic spectrum. Patients with PRP were selected by natural language search of dermatopathology databases containing 250 000 cases accessioned over a 3-year period. A detailed medical history was obtained on each patient via office chart review and patient interviews. We compared the histologic findings in skin biopsies from patients with PRP to those of biopsies matched for site and age from control patients with psoriasis. Certain aspects of the clinical presentations encountered in the study group patients have not been previously emphasized, including eruptions compatible with a vesiculobullous disorder in 4 patients. Several patients had evidence of underlying iatrogenic or systemic immune dysregulatory states and certain triggers could be isolated such as emotional stress and prior exposure to microbial pathogens. Histomorphologic features predictive of PRP included follicular plugging, an increased granular cell layer, and acantholysis. While seen in a minority of biopsies of PRP, morphologic discriminators supportive of a diagnosis of psoriasis included neutrophils in the parakeratotic scale crust, and dermal papillae capillary ectasia with vessels lying in direct apposition to the epidermis. Other morphologic features were encountered in biopsies of PRP which have received little emphasis in the dermatopathology literature, including epithelial atrophy, significant dermal inflammation, the presence of eosinophils and plasma cells within the inflammatory infiltrates, an abnormal granular cell layer, and epidermolytic hyperkeratosis, albeit none were statistically signficant predictors of PRP over psoriasis. Nevertheless, their identification emphasizes the varied histologic spectrum of PRP. The almost ubiquitous finding of acantholysis and the presence of an abnormal granular cell layer in many biopsies of PRP suggests that abnormal keratins or defects in the retinol signalling pathway may be of pathogenetic importance.     

Platelet-rich plasma improves the therapeutic efficacy of mesenchymal stem cells by enhancing their secretion of angiogenic factors in a combined radiation and wound injury model

Delayed wound healing after radiation exposure can cause serious cutaneous damage, and its treatment is a major clinical challenge. Although mesenchymal stem cells (MSCs) have emerged as a promising therapeutic agent in regenerative medicine, they alone do not produce satisfactory effects in a combined radiation and wound injury (CRWI) model. Here, we investigated the therapeutic effect of combined umbilical cord blood-derived (UCB)-MSCs and platelet-rich plasma (PRP) treatment on wound healing in a CRWI mouse model. First, we assessed the release of cytokines from UCB-MSCs cultured with PRP and observed changes in the expression of angiogenic factors. The angiogenic paracrine factors from UCB-MSCs cultured with PRP were assessed in human umbilical vein endothelial cells (HUVECs). To assess therapeutic efficacy, UCB-MSCs and PRP were topically implanted into a CRWT mouse model. Vascular endothelial growth factor (VEGF), a pro-angiogenic growth factor, urokinase-type plasminogen activator and contributor to VEGF-induced signalling were more highly expressed in conditioned media of UCB-MSCs cultured with PRP than in that of UCB-MSCs alone. Furthermore, conditioned media of UCB-MSCs cultured with PRP increased the formation of tube-like structures in HUVECs. Co-treatment of UCB-MSCs and PRP in a CRWI mouse model increased the wound closure rate and angiogenesis compared with an untreated irradiated group. Moreover, increased expression of VEGF and CD31 were observed in the wound tissue of co-treated mice compared with untreated irradiated mice. PRP stimulates the release of angiogenic factors from UCB-MSCs, and combined therapy of UCB-MSCs and PRP improves regeneration efficacy by enhancing angiogenesis in a CRWI model.     

Pityriasis rubra pilaris in the setting of HIV infection: clinical behaviour and association with explosive cystic acne

The development of pityriasis rubra pilaris (PRP) in three patients with human immunodeficiency virus (HIV) infection is described. Two of the patients had onset of severe generalized cystic acne concomitant with their development of PRP. PRP and acne conglobata should be added to the group of cutaneous disorders that can present in a more virulent manner in the setting of HIV infection. The association of cystic acne with PRP and their response to treatment are discussed.     

Changing forms of juvenile pityriasis rubra pilaris—a case report

Pityriasis rubra pilaris (PRP) is a rare disease affecting both males and females. The aetiology is unknown, but it has an ill-defined relationship with psoriasis. Within the spectrum of PRP certain disease patterns are recognized, and regarded by many as helpful prognostic indicators. Griffiths has suggested a clinically based classification based on a series of 98 patients seen at St John's Hospital, London between 1950 and 1972 (Table 1). Classical type 1 PRP is an erythematous squamous disorder typically showing follicular hyperkeratosis, perifollicular erythema and sharply demarcated islands of unaffected skin. The palms and soles become hyperkeratotic and often exhibit a characteristic orange hue. Type III PRP is the juvenile counterpart of classical type I PRP. The following case report describes a patient who presented with type III PRP but later went on to develop the type IV or circumscribed, juvenile onset PRP.     

Penicillin and vitamin A as possible therapeutic agents in pityriasis rubra pilaris

Pityriasis rubra pilaris (PRP) is a rare skin disorder with versatile clinical presentations. A 62‐year‐old Caucasian woman with progressive erythroderma and classic adult (type I) PRP is presented. Treatment with systemic steroids and methotrexate produced no improvement. Clinical remission was achieved after systemic therapy with penicillin (both intravenous and intramuscular) and vitamin A. The therapy of PRP is reviewed, focusing on a possible infectious genesis of PRP as well as the role of antibiotics in its management.     

HIV-associated pityriasis rubra pilaris responsive to triple antiretroviral therapy

HIV-associated pityriasis rubra pilaris (PRP) or PRP type VI designates a new distinctive entity reported in HIV patients. It is characterized by cutaneous lesions of PRP and variable association with lesions of acne conglobata, hidradenitis suppurativa and lichen spinulosus. We report a patient with HIV-associated PRP which was treated by triple antiretroviral therapy (zidovudine, lamivudin and saquinavir) with complete response. The patient has remained free from symptoms for 20 months of follow-up. We review the clinical features, pathology, evolution, treatment and possible aetiology of this recently described entity.     

Pityriasis rubra pilaris type 1 spontaneously resolving after 20 years

Pityriasis rubra pilaris (PRP) is an uncommon, idiopathic, papulosquamous eruption. We report a longitudinal study of a patient with PRP type 1 who was treated with retinoid therapy for 9 years and whose symptoms resolved spontaneously after 20 years. There are no data in the literature on the disease course of PRP type 1 persisting beyond the usual 3 years. This case highlights both the extreme chronicity of PRP and the possibility of remission after many years of active disease.     

Platelet-rich plasma with keratinocytes and fibroblasts enhance healing of full-thickness wounds

Advances in tissue engineering led to the development of various tissue-engineered skin substitutes (TESS) for the treatment of skin injuries. The majority of the autologous TESS required lengthy and costly cell expansion process to fabricate. In this study, we determine the possibility of using a low density of human skin cells suspended in platelet-rich plasma (PRP)-enriched medium to promote the healing of full-thickness skin wounds. To achieve this, full-thickness wounds of size 1.767 cm² were created at the dorsum part of nude mice and treated with keratinocytes (2 × 10⁴ cells/cm²) and fibroblasts (3 × 10⁴ cells/cm²) suspended in 10% PRP-enriched medium. Wound examination was conducted weekly and the animals were euthanized after 2 weeks. Gross examination showed that re-epithelialization was fastest in the PRP+cells group at both day 7 and 14, followed by the PRP group and NT group receiving no treatment. Only the PRP+cells group achieved complete wound closure by 2 weeks. Epidermal layer was presence in the central region of the wound of the PRP+cells and PRP groups but absence in the NT group. Comparison between the PRP+cells and PRP groups showed that the PRP+cells-treated wound was more mature as indicated by the presence of thinner epidermis with single cell layer thick basal keratinocytes and less cellular dermis. In summary, the combination of low cell density and diluted PRP creates a synergistic effect which expedites the healing of full-thickness wounds. This combination has the potential to be developed as a rapid wound therapy via the direct application of freshly harvested skin cells in diluted PRP.     

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.     

PRP with subcorneal acantholysis: case report and review

Although the clinical findings of pityriasis rubra pilaris (PRP) are striking, the microscopic diagnosis can be difficult because changes can be subtle and can overlap with other skin diseases. Suprabasal acantholysis can be seen in PRP, mimicking pemphigus vulgaris. We report a patient with PRP whose initial biopsies demonstrated subcorneal acantholysis mimicking pemiphigus foliaceus.     

Effectiveness of platelet‐rich plasma in healing necrobiosis lipoidica diabeticorum ulcers

Necrobiosis lipoidica diabeticorum (NLD) is a chronic condition, which is characterized by single or multiple lesions on the legs, and occurs in 0.3% of patients with diabetes. Recently, platelet‐rich plasma (PRP) has been used in several clinical settings to promote sustained healing and better outcome. We propose the use of PRP for the treatment of NLD‐associated recalcitrant wounds. In this study, 15 patients were treated with homologous PRP; all showed marked enhancement in wound healing without any adverse effects. After PRP application, advanced dressings were used until closure of the lesion was obtained, which was complete for all our patients. We therefore propose the use of PRP for recalcitrant wounds in patients with NLD.     

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.     

Photosensitive pityriasis rubra pilaris

Exacerbation of pityriasis rubra pilaris (PRP) with ultraviolet exposure is well recognized. However, the initial presentation of PRP in a photoexposed distribution is infrequently reported, and only rarely confirmed with phototesting. We describe such a case of photosensitive PRP. Phototesting revealed exquisite ultraviolet (UV) sensitivity, which was particularly marked to UVB, a feature shared with previously reported cases.     

Synergistic effect of platelet-rich plasma injections and scalp lifting in androgenetic alopecia

Androgenetic alopecia (AGA) is a common hair loss disorder, especially in men and the elderly. In this study, we analyzed the therapeutic effects of platelet-rich plasma (PRP) injections and embedded sutures in patients with AGA. In each participant, we administered different treatments in one area of hair loss that was divided into four sections. Each section received one of the following treatments: No treatment, PRP injection, suture embedding, and combined PRP injection/suture-embedded areas. The thickness of the scalp, and scalp perfusion were measured using an ultrasound imaging system and Moor FLPI full-field laser perfusion imaging system, respectively. The diameters of the hair were measured using optical microscopy. Our results show that PRP injection treatments increased the diameter of the hair (P = 0.034), and the combined PRP injection/suture-embedded treatments had a significant effect on the thickness of the scalp (P = 0.002), the blood flow (P = 0.014) through the scalp, and the diameter of the hair (P = 0.013). This study has demonstrated that there is a synergistic effect between PRP injections and suture embedding for increasing the thickness and blood flow of the scalp, and diameter of the hair. Combined PRP injection/suture-embedded PRP injections might have therapeutic benefit for patients with AGA.