Pityriasis Rubra Pilaris

Article Author:
Falon Brown
Article Editor:
Talel Badri
Updated:
2/22/2019 6:45:14 PM
PubMed Link:
Pityriasis Rubra Pilaris

Introduction

Pityriasis rubra pilaris (PRP) is a rare inflammatory papulosquamous disorder of unknown etiology. There are 6 distinct subtypes which occur in both children and adult which occur striking variation. Fundamental elements noted across all subtypes include distinct, well-demarcated plaques of various sizes with characteristic reddish-orange hue, may have varying degrees of the scale. More generalized subtypes often demonstrate intervening areas of unaffected skin, known as "islands of sparing," which is a signature characteristic of PRP. There is a broad spectrum of presentations from mild disease isolated to extremities to severe disease at times evolving into diffuse erythroderma.[1][2][3][4][5]

Etiology

The exact etiology of PRP remains elusive. Some cases of PRP-like eruptions have been related to medication intake or vaccination.

Epidemiology

PRP occurs worldwide with no predilection for gender or ethnicity. There is a lack of information in the literature regarding the true incidence or prevalence of PRP. One British study, estimated an incidence of 1 in 5000 new patient visits to a dermatologist in the outpatient setting, while another Indian study suggests 1 in 50,000 visits. Dr. Andrew Griffith, in an address to members of the British Association of dermatology in 2003, suggested a prevalence of 2.5 million cases in all totaling on average 1 case per 400,000 of the population.

There appears to be a bimodal age distribution with peaks during the first to second and fifth to sixth decades of life. Most cases appear to be sporadic, though familial cases have been reported in up to 6.5% of cases. Familial inheritance pattern appears to be autosomal dominant with variable penetrance in most cases. However, autosomal recessive patterns have also been demonstrated.

Pathophysiology

Pathogenesis of PRP remains unclear though several prominent hypotheses exist including dysfunction in keratinization or vitamin A metabolism, autoimmune mechanism, abnormal immunologic triggers, such as infection or ultraviolet (UV) exposure given evidence of does photo triggered and/or photoactivated cases or trauma.

Genetics seem to play a role in the development of at least some cases of PRP, most prominently noted in the type-V PRP variant. A clear association with a gain-of-function mutation in the CARD14, also known as the psoriasis susceptibility (PSOR2), a gene that encodes for the member 14 protein which is an activator of NF-kappa beta. Incidentally, similar mutations have been noted in patients with sporadic PRP.  Further research is needed.

Human immunodeficiency virus (HIV) has been associated with the development of type-VI PRP.

Histopathology

Histologically PRP presents with irregular, psoriasiform acanthosis of the epidermis along with a very characteristic overlying "checkerboard" pattern of parakeratosis (alternating vertical and horizontal ortho-and parakeratosis). Often predominant follicular plugging with shoulder parakeratosis is noted. Thick, rather than thin, suprapapillary plates and lack of neutrophils in the stratum corneum may help distinguish PRP from psoriasis. Variable mild superficial perivascular lymphohistiocytic infiltrate, occasional epidermal spongiosis and focal acantholytic dyskeratosis have been reported but are not consistently found.

History and Physical

The spectrum of PRP has been divided 5 distinct subtypes using a widely accepted classification scheme initially proposed by Griffiths in 1980 publication. The original 5 subtypes were based upon the age of onset, lesion distribution, and prognosis. Subsequently, a sixth subtype was added due to a recent association with HIV which presents as a distinct entity.[6][7][8][9]

  • Type I: classical adult onset
  • Type II: atypical adult onset
  • Type III: classical juvenile onset
  • Type IV: circumscribed juvenile onset
  • Type V: atypical juvenile onset
  • Type VI: HIV-associated

The cardinal features that appear across subtypes in variable degrees include red-orange papules and plaques, hyperkeratotic follicular papules, and palmoplantar hyperkeratosis. Lesions are generally asymptomatic though a small portion of patients endorses mild pruritus. 

Type I PRP is the classic adult variant which affects 55% of patients and is the most common in adults. The most distinguishing features are classic red-orange papules and plaques with islands of sparing, perifollicular keratotic papules, and waxy palmoplantar keratoderma. This variant is typically self-limited. Prognosis is good since eighty percent of these patients resolve within 3 years.

  • The classic sequence of signs in type I PRP begins with a diffuse fine scale seen on the scalp, which may be mistaken for seborrheic dermatitis. Scalp findings might initially be mild, however, often rapidly progresses to diffuse scaly erythema of the scalp. Similarly, patients may provide a history of solitary red-orange to salmon color macule, or small group of follicular papules noted on either dorsal fingers or head and neck. Within weeks to months, more macules and papules erupt and often coalescing into patches and plaques that progress in a cephalocaudal manner appear. Characteristic hyperkeratotic follicular papules are prominent both within the patches of erythema and within adjoining areas of uninvolved skin. Various terms including “nutmeg grater” or “exaggerated gooseflesh” have been used to describe these follicular-based papules. Involved skin is often sharply demarcated from adjacent uninvolved skin producing a very characteristic phenomenon coined “islands of sparing” or “skip areas.” At times, the disease may even evolve in to diffuse erythroderma. Complications of erythroderma including subsequent ectropion have been reported.
  • Another characteristic finding, also notable in children, is a unique red-orange waxy palmoplantar keratoderma (PPK) so-called “sandal-like” PPK which may coincide with, prior to, or after the development of other clinical findings. Nail involvement varies hyperkeratotic nail plate with a yellow-brown discoloration and subungual debris most classically noted. Mucosal involvement is quite rare when present typically presents as white papules or plaques on buccal mucosa similar to lichen planus.

Type II PRP is the atypical adult variant which affects 5% of patients, typically middle-aged adults. Clinical findings of type II vary from the typical in that these patients present with eczematous changes of the skin, ichthyosiform scale on lower extremities, coarse laminated palmoplantar keratoderma, and alopecia is common. It is also atypical in that it follows a much more chronic course in 80% of cases.

Type III, classic juvenile PRP, typically occurs within the first 2 years of life or in adolescence. Only 10% of cases fall into this category. It mirrors the sequence and findings found in type-I PRP. Prior data noted that most patients clear within three years. More recent studies have challenged this notion citing more protracted course similar to type IV.  

Type-IV PRP, known as circumscribed juvenile PRP, is the only focal variant. Typically occurs in pre-pubertal children. Affecting 25% of involved of total cases this variant is the most common form found in children. Clinically they present with sharply demarcated grouped follicular papules on an erythematous based are noted on the elbows, knees and over bony prominences. These patients seem to have variable course given discrepancies in literature, which may be related to spontaneous remissions and exacerbations.

Type-V PRP is an atypical generalized juvenile variant which affects 5% of patients. It is a non-remitting hereditary condition with classic characteristics similar to type III with additional scleroderma-like changes involving the palms and soles.

Lastly, type-VI PRP occurs in patients with HIV-infection. Similar to type I PRP, these patients present with generalized PRP, frequently complicated by erythroderma. Papules of type VI are more conspicuous with a combination of inflammatory papules and prominent keratotic spicules. Similar follicular occlusion occurs in other disease processes that have been noted to occur concurrently with this version of the disease, including hidradenitis suppurativa and acne conglobata. This subtype appears to have a poor prognosis and often recalcitrant to therapy.

Evaluation

PRP is diagnosed based on classic clinical and histopathological features. Studies have not identified serologic or immunohistochemical markers to assist in the diagnosis.

Treatment / Management

In many cases, PRP is self-limited and asymptomatic therefore does not necessarily require treatment.

The treatment of PRP can be challenging, and no universal approach exists. There are no treatments approved by the US Food and Drug Administration. Most practitioners recommend combination therapy with topical for symptomatic management and systemic therapy aimed at reducing inflammation. Topical agents which have shown promise especially in mild disease include emollients, keratolytic agents, such as urea, salicylic acid, or alpha-hydroxy acid containing preparations, topical corticosteroids, tazarotene, and topical calcineurin inhibitors. Generally accepted first-line systemic agent for both adults and children is oral retinoids. Oral isotretinoin, 1 to 1.5 mg/kg per day, has been shown to induce clearance in as little as 3 to 6 months. Methotrexate alone or in combination with oral retinoids has also been used frequently. However, combination therapy increased the risk for systemic toxicity. Recently, some case reports and small case series have shown a possible role for biologic immunosuppressive agents typically used in the treatment of psoriases such as TNF-alpha inhibitors and secukinumab and ustekinumab. Although the risk of photo-triggered and/or photoactivated disease UV-light therapy has been implemented in certain cases, including narrowband UVB, UVA1, or PUVA in combination with an oral retinoid with some success. 

Differential Diagnosis

The differential diagnosis for PRP varies greatly depending on the subtype. In general, all must be distinguished from other papulosquamous diseases, especially psoriasis.

As there are various combinations of specific signs and symptoms that occur in PRP each must be considered and differentiated. Common findings listed below along with pertinent differentials:

  • Scalp: Early scalp disease of PRP can be quite variable from fine to large scale typically on an erythematous base the hallmark is the rapid progression and severity of the disease. Should be distinguished from the waxy scale seborrheic dermatitis and well demarcated, hyperkeratotic, silvery scale of psoriasis.
  • Palmoplantar keratoderma: The characteristic red-orange color and variable associated edema helps to distinguish keratoderma of PRP from psoriasis, ichthyosis, hereditary palmoplantar keratoderma, and erythrokeratodermia.
  • Nail changes: Yellow–brown hyperkeratotic nails with variable subungual debris in combination with skin finding often may be mistaken for with psoriasis. It is important to note that no changes involving proximal nail matrix or nail bed, such as nail pits or oil spots, occur in PRP which in many cases can assist in distinguishing one from another.
  • Erythroderma: History alone may assist in distinguishing PRP from other major causes of generalized erythroderma however biopsy is often necessary. Some of the most well-documented causes of erythroderma include psoriasis, atopic dermatitis, drug reactions, cutaneous T-cell lymphoma, congenital ichthyosis, paraneoplastic and graft versus host disease.
  • Atypical PRP, including type II and V, both present with ichthyosiform changes and should be distinguished from other forms of acquired and congenital ichthyoses.
  • Spiny follicular papules of type-IV PRP in isolation may be mistaken for lichen spinulosus and keratosis pilaris. Eventually, the clinical course should distinguish these entities.

Enhancing Healthcare Team Outcomes

PRP is a very rare skin disorder that may be encountered by the primary care provider and nurse practitioner. Because there is no laboratory test to make a diagnosis, the patient should be referred to the dermatologist for further workup. Once diagnosed, the treatment can be challenging. In many cases, PRP is self-limited and asymptomatic therefore does not necessarily require treatment. There are no treatments approved by the US Food and Drug Administration. Most practitioners recommend combination therapy with topical for symptomatic management and systemic therapy aimed at reducing inflammation. Topical agents which have shown promise especially in mild disease include emollients, keratolytic agents, such as urea, salicylic acid, or alpha-hydroxy acid containing preparations, topical corticosteroids, tazarotene, and topical calcineurin inhibitors. Generally accepted first-line systemic agent for both adults and children is oral retinoids. Recently, some case reports and small case series have shown a possible role for biologic immunosuppressive agents typically used in the treatment of psoriases such as TNF-alpha inhibitors and secukinumab and ustekinumab. The prognosis for this skin disorder remains unknown because the disorder is so rare, there has not been adequate long term follow up.[10] (Level V)



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