Pityriasis rubra pilaris, sometimes also referred to as pityriasis rubra, Besnier's or Devergie's disease, is a rare, chronic skin disease of mainly unknown etiology. Small papules and scaly plaques are characteristic for pityriasis rubra pilaris and the disease may progress to erythroderma.
While sporadic PRP is characterized by an acute onset, familial PRP develops gradually. Patients usually note first symptoms on their scalp and in their face. Papules are not present at the very beginning of the disease, but skin irritation, redness and scales may be observed. These symptoms usually spread from the head to thorax, abdomen and limbs. In the course of the disease, scaly plaques of orange-reddish or salmon color form. They are typically delimited by sharp borders. Redness and thickening of palms and soles indicates palmoplantar keratoderma. Hyperkeratotic areas may have an orange hue and tend to fissure, what causes pain in the affected individual. The Elbows, wrists and dorsal surfaces of proximal phalanges often show signs of follicular hyperkeratosis. Due to their overall aspect, these regions of the skin are sometimes compared to a nutmeg grater. Eventually, the whole body may be affected, but the aforementioned sparing islands are also common. Of note, pruritus is not characteristic for PRP but may be observed in the initial stages of the disease.
Eyes, mucous membranes and nails may also be affected by PRP. With regards to the eyes, the lower lid may turn outward and form an ectropion. Excess dryness of the eye and blurred vision have also been related with PRP. Lacy whitish or grayish papules and plaques affecting the buccal mucosa may cause mucous membrane irritation and pain. Also, generalized erythema and possible mucosal erosions may be detected in the oral cavity . Nail color frequently changes towards a yellow-brownish shade. Longitudinal ridges indicate nail formation problems and may be accompanied by subungual hyperkeratosis and thickened nail plates.
As has been mentioned before, five types of PRP are distinguished according to their clinical picture. They present as follows:
The HIV-associated form of PRP is usually characterized by nodulocystic and pustular acneiform lesions.
There are no specific tests for PRP, thus diagnosis is based on the clinical picture and histological results . Laboratory tests may, however, be applied to rule out potential differential diagnoses and to assess the overall condition of the patient in severe cases of PRP.
Skin biopsies should be analyzed for pathological alterations but will not reveal any pathognomonic findings. Similar to what has been said about laboratory tests, histopathological evaluation of tissue samples mainly aims at ruling out other pathologies. In PRP, alternating hyperkeratosis with ortho- and parakeratosis dominate the stratum corneum of the skin. Parakeratotic features may also be detected in the perifollicular region, the hair follicle is usually plugged. Hypergranulosis is often seen. Dermal papillae are abnormally narrow. Perivascular lymphocytic infiltration is limited. In some samples, acantholysis can be detected .
Possibly due to the low prevalence of the disease, no controlled trails have been carried out regarding PRP treatment. Neither the European Medicines Agency nor the US Food and Drug Administration approved any drug for use in PRP. Thus, any given recommendations are based on empirical analyses. Effectivity and safety are unclear.
In order to treat PRP, topical and systemic medication is often combined. While maximal drug concentrations and thus effectivity may be higher if the skin is treated topically, this approach may be neither suitable nor sufficient for patients suffering from generalized PRP. It is, however, highly recommended for those with circumscribed and mild PRP. In this context, corticosteroids, keratolytics, calcipotriol as well as topical retinoids tretinoin and tazarotene may be utilized .
Systemic retinoids, i.e., synthetic derivatives of retinol, are the medication of choice for treating PRP . If the response to such treatment is not satisfactory, methotrexate may be administered. Methotrexate is also first choice for PRP therapy in patients with contraindications for systemic retinoids . Further therapeutic options may consist in immunomodulatory treatment with of TNF-α inhibitors, azathioprine or cyclosporine.
Some patients may benefit from phototherapy.
Prognosis of familial and sporadic PRP differ widely. While the former usually persists for life, that latter may be self-limiting in between a few years. It is not yet known which event triggers the spontaneous cure of PRP.
Also, there are differences regarding adult and juvenile, classical, circumscribed and atypical forms of PRP. Classic adult PRP has the best prognosis and 80% of these cases resolve spontaneously within three years. However, the disease may also persist for much longer periods of time . In some cases, scarring alopecia remains after healing. As for atypical adult PRP, no rapid spontaneous cure should be expected since the disease often persists for decades. Classic juvenile PRP is generally self-limiting and resolves within a year, atypical juvenile PRP does not. Little is known about the long-term prognosis of circumscribed juvenile PRP.
In general, hereditary and acquired PRP have to be distinguished.
With regards to the former, familial PRP is apparently inherited with an autosomal dominant trait, i.e. males and females may carry the affected chromosome with equal likelihood and will develop the disease even in heterozygous state. Recently, the CARD14 gene that encodes for caspase recruitment domain-containing protein 14 has been related with psoriasis and PRP . CARD14 expression differs between distinct epidermal cell populations and is presumably altered in PRP patients. Other mutations may also trigger PRP, but have not yet been identified. A functional relation between CARD14 and possibly other genes and PRP has yet to be established.
The vast majority of PRP cases occurs sporadically and no specific causes can be identified. It is also not known whether sporadic PRP results from the same pathogenetic mechanisms that are triggered in patients suffering from familial PRP.
PRP is considered a rare skin disease but precise data regarding incidence and prevalence cannot be presented. A study conducted in Great Britain revealed that about 1 in 5000 patients looking for dermatological advice present with PRP .
No preferences regarding distinct races have been determined. The male-to-female ration is presumably one to one .
Little is known about PRP pathogenesis. More light may be shed on this topic if an association of familial PRP with specific gene mutations can be confirmed. Then, assessment of gene functions may help to understand which metabolic pathways are interrupted in PRP patients.
It has been speculated that vitamin metabolism is altered in PRP patients, particularly vitamin A metabolism. The fact that systemic retinoids alleviate symptoms associated with PRP may support this hypothesis. However, reliable data is not available and further research is required to confirm this theory.
Another hypothesis is about PRP being associated with an abnormal immune response that may be triggered by certain pathogens. Isolated case reports related PRP with previous streptococcal infections .
There are no specific recommendations to prevent sporadic PRP.
Patients suffering from chronic, familial PRP may benefit from genetic counseling and prenatal diagnosis. Also, affected parents may have genetic tests run on their newborn in order to better assess their risk for developing the disease. Similarly, family members may be tested to determine whether they are carrying the mutated gene.
Pityriasis rubra pilaris (PRP) is a rare, inflammatory dermatosis that may also be referred to as pityriasis rubra, Besnier's disease or Devergie's disease, whereby the latter names have been chosen in honor of two physicians who described this illness in the nineteenth century.
While some cases of PRP result from an unspecified genetic disorder and are thus deemed familial PRP, no direct causes can be detected for the majority of PRP cases. PRP is a papulosquamous, hyperkeratotic disorder and patients typically present follicular papules, scaling plaques and palmoplantar hyperkeratosis. Although these skin alterations may be found all over the body, patients frequently show apparently healthy skin areas which are known as islands of sparing. Transition from PRP to erythroderma is not clearly defined. Of note, the clinical picture presented by PRP patients may vary widely. Therefore, five different types of PRP are distinguished :
Recently, another type of PRP has been described that has been associated to HIV infections .
Because little is known regarding etiology and pathogenesis of the disease, treatment is rather difficult. Different drugs have been used to treat PRP, but due to the low incidence of the disease reliable data is sparse. Most commonly, systemic retinoids as well as the antifolate drug methotrexate are administered. Also, TNF-α inhibitors have been proposed as potential therapeutic options.
Pityriasis rubra pilaris (PRP) is a rare, chronic skin disease.
While a small share of PRP cases results from genetic disorders, no precise cause could be identified for the sporadic form. More than 90% of all PRP cases are sporadic.
The most common symptoms of PRP are follicular papules, scaling orange-reddish plaques and palmoplantar hyperkeratosis, i.e., a thickening of the skin of hands and feet. Often, scalp and face are affected first, but the disease may spread to thorax, abdomen and limbs. Some people present generalized PRP but do show islands of sparing, areas of the skin that remain unaffected.
PRP may also provoke pathological alterations in eyes, mucous membranes and nails. In this context, the lower lid may turn outwards, dry eyes and blurred vision have been described. With regards to mucous membranes, the oral cavity is usually most severely affected. Papules, plaques and mucosal erosions may cause pain. Nails change color and become yellow-brownish. The nail plate thickens but presents longitudinal ridges.
There are different forms of PRP that may affect children, adolescents and adults and that manifest differently.
There are no specific tests for PRP and the physician will base their diagnosis on symptoms observed during clinical examination and on histopathological analysis of tissue samples. In order to do so, skin biopsies have to be obtained.
The histopathological examination of skin biopsies requires a microscope and is necessary to distinguish PRP from other skin diseases, e.g., from psoriasis or pityriasis rosea. Treatment for each of these diseases is different.
Treatment is symptomatic and consists in topical and systemic administration of vitamin A derivatives, methotrexate or immunomodulatory agents. Data regarding the effectivity of these therapeutic options is sparse and while there are certain standard treatments, therapy will need to be adjusted to the response of the individual patient.
Some forms of PRP, among them the most common, classical juvenile and adult forms, tend to resolve spontaneously within a few years.