A 62-year-old male presented for consultation with a chief complaint of an “itchy red rash.” The eruption had begun on the head and upper trunk and spread down his trunk and extremities. He later developed “skin thickening” on his hands and feet and was unable to work. The patient had been previously treated with phototherapy and became worse after several sessions.Pityriasis rubra pilaris (PRP), a rare papulosquamous disease, was unknowingly discovered by Tarral in 1828 and subsequently was not recognized as this disease entity until Devergie described it in 1856. The term pityriasis rubra pilaris was later coined by Besnier in 1889.1,2
What’s Your Diagnosis?
Diagnosis: Pityriasis Rubra Pilaris
This inflammatory, hyperproliferative disease has a bimodal age distribution, with peaks occurring in childhood (0 to 20 years) and adulthood (40 to 60 years). Occurring equally in men and women, PRP shows a predilection for males, with childhood onset.3 The frequency of disease ranges from 1/5,000 to 1/50,000, depending on the population.1,3 Although PRP is commonly acquired, a familial form has been reported.
Clinically, PRP is characterized by follicular hyperkeratosis with central plugging, palmoplantar keratoderma and scaly erythematous patches that progress to generalized erythroderma. Classically, patients present with a single erythematous patch. As these patches enlarge, hyperkeratotic follicular papules begin to appear on the dorsal aspect of the trunk and upper and lower extremities and eventually coalesce with an erythematous perifollicular halo.2,4 The disease eventually progresses to a generalized eruption with characteristic “skip spots” or “islets of sparing” of unaffected skin scattered throughout the body. Also notable are increased scales on the palms, soles and scalp. The erythema is distinctive in that it appears yellowish and proceeds in a cephalic to caudal direction. Lesions usually begin on the upper half of the body in adults; children, on the contrary, present with manifestations on the lower half of the body.1,4 Commonly, nails can become discolored and demonstrate thickening of the nail plate, subungual hyperkeratosis and splinter hemorrhages.6 With extensive disease, ectropion may be observed.1 Classically, mucosal membranes are rarely affected, and hair and teeth are usually not involved.2,7 Itching and burning have been described in less than 20% of patients.8
Griffiths Classification Scheme
Griffiths developed a classification scheme that depicted PRP as five types based on clinical onset, presentation and prognosis.9
Type I, accounting for more than 50% of cases, is classic adult-type PRP, occurring commonly in the fifth to sixth decade. This disease type has the best prognosis, with 80% of patients in remission within 3 years.
Type II, atypical adult onset, differs from type I, because of its longer duration and morphological features. This disease, which can persist for more than 20 years, is distinguished by its ichthyosiform scale on the lower extremities and decreased scalp hair.
Type III, classical juvenile PRP, occurs in the first 2 years of life. Similar to type I in presentation, this disease usually resolves in less than 3 years.
Type IV, the most common juvenile form, is associated with prepubertal children and is characterized by circumscribed areas of follicular hyperkeratosis and erythema on the knees and elbows.
Type V is a chronic atypical juvenile PRP that appears in the first few years of life. Patients commonly have follicular hyperkeratosis and erythema. This type is distinctive in that most cases of familial PRP belong to this group.2,9
Other classification schemes have been proposed, including those developed by Gelmitti et al, Piamphongsant and Akaraphant, and Miralles et al.10,11,12
The disease is generally diagnosed clinically. A biopsy for histological confirmation can be performed. Due to common clinical and histopathological features, PRP is easily confused with psoriasis. The differential diagnosis may also include seborrheic dermatitis, phrynoderma, lichen planopilaris, T-cell lymphoma, atypical keratosis pilaris, follicular eczema, erythrokeratodermas, and subacute cutaneous lupus erythematous.1,2,3
It has been found that PRP is associated with immunodeficient states, particularly HIV and those with impaired immunity.12 Medical conditions including hypothyroidism, myasthenia gravis, celiac sprue, and diabetes mellitus type I have been observed with this papulosquamous disease.1,2 Juvenile types of PRP demonstrate increased incidence in children with T-cell impairment, hypogammaglobulinemia and decreased IgA.2
Although the etiology of PRP is unknown, multiple hypotheses have been proposed. Hyperproliferation and inflammation are basic components. Numerous reports have discussed the relationship between vitamin A metabolism and PRP. Evidence of decreased levels of vitamin A in these patients has been controversial.1,3 Although Finzi et al suggested retinol-binding protein, a carrier protein of vitamin A, may play a role,13 there has been no clear evidence that demonstrates this carrier is a direct cause of PRP.2 The clinical improvement with the administration of retinoids further implicates vitamin A as an etiologic factor;14 however, recent literature suggests that the success of these agents may be due to non-keratinizing actions.1,15 PRP also may have an autoimmune component due to its increased incidence in patients with autoimmune diseases including hypothyroidism, celiac sprue, and myasthenia gravis.1
An association between PRP and HIV as well as other immunologic abnormalities may provide further support for an altered immune component.1 In children, it has been reported that PRP may follow infection and trauma.3 Genetics may also play a role since familial PRP shows both autosomal dominant and recessive inheritance with variable expressivity and reduced penetrance.1,16 This familial type may be related to activation of keratin proteins; specifically, keratins 6, 16, and 17 have been discussed in the literature.16 Malignancy has also been theorized to be involved in the pathogenesis of the disease.1
Common features of PRP microscopically include psoriasiform hyperplasia, alternating orthokeratosis and parakeratosis in vertical and horizontal directions, hypergranulosis, thick suprapapillary plates, broad rete ridges, sparse superficial perivascular lymphocytic infiltration and narrow dermal papillae.17 (See Figures 1 and 2.) For diagnostic reasons, it can be more helpful to obtain a biopsy of a follicular papule that is likely to show follicular hyperkeratosis and plugging of the follicular infundibulum. Also characteristic of PRP is hypertrophy of the erector pili.2 Distinctive features of the disease are acantholysis and focal acantholytic dyskeratosis, which aid in distinguishing PRP from psoriasis.17 In general, biopsies are used for confirmation, not to replace clinical diagnosis.
Due to the rarity of PRP and lack of numerous controlled studies, patients are frequently treated on a case-by-case basis, often relying on recommendations provided by case reports. Additionally, efficacy of treatment may be dependent on the type of PRP and underlying diseases.2 Therefore, treatment of PRP remains challenging. However, the overlapping nature of psoriasis and PRP provides therapeutic options that may be common to both diseases.
The most widely used therapies include retinoids and methotrexate.18 Retinoids are used as first-line therapy, particularly in type I, adult-onset PRP. Although their exact mechanism of action in PRP is unclear, isoretinoin, etretinate, and acitretin involve stabilization of kertinization and can provide marked improvement in a majority of patients.15 Administration of oral vitamin A, commonly used in the past, has been reported to show minimal clinical improvement and its use has been replaced by treatment with retinoids.18 Methotrexate is another effective treatment option. It can be used for severe or refractory cases, alone or in combination with retinoids.14,19
Immunosuppressant drugs such as cyclosporine and azathioprine have shown variable results and may be only effective in a small population of patients, such as those with type V, atypical juvenile PRP.1,2,18 Biologic agents are beginning to become prominent alternatives in those patients who are recalcitrant to traditional therapies. Given the similarity between psoriasis and PRP, infliximab and other anti-TNF antibodies, as well as T-cell modulators such as efalizumab, have also shown favorable outcomes in patients with PRP.20 Phototherapy has also been utilized in the treatment of PRP; however, reports reveal that it is ineffective and may even exacerbate symptoms.14,15,21
Juvenile types, particularly type III, may be conservatively managed due to their favorable prognosis. Children may be treated with a short course of oral retinoids, if they present with severe disease.3 Additionally, symptomatic relief may be provided by topical emollients, keratolytics, and corticosteroids and used as adjuvants to the therapies mentioned above.1