SNOMEDCT: 3755001; ICD10CM: L44.0; ICD9CM: 696.4; ORPHA: 2897; DO: 9212;
| Location | Phenotype |
Phenotype MIM number |
Inheritance |
Phenotype mapping key |
Gene/Locus |
Gene/Locus MIM number |
|---|---|---|---|---|---|---|
| 17q25.3 | Pityriasis rubra pilaris | 173200 | Autosomal dominant | 3 | CARD14 | 607211 |
A number sign (#) is used with this entry because of evidence that pityriasis rubra pilaris (PRP) is caused by heterozygous mutation in the CARD14 gene (607211) on chromosome 17q25.
Pityriasis rubra pilaris is an uncommon skin disorder characterized by the appearance of keratotic follicular papules, well-demarcated salmon-colored erythematous plaques covered with fine powdery scales interspersed with distinct islands of uninvolved skin, and palmoplantar keratoderma. Most cases are sporadic, although up to 6.5% of PRP-affected individuals report a positive family history. The rare familial cases show autosomal dominant inheritance with incomplete penetrance and variable expression: the disorder is usually present at birth or appears during the first years of life and is characterized by prominent follicular hyperkeratosis, diffuse palmoplantar keratoderma, and erythema, with only a modest response to treatment (summary by Fuchs-Telem et al., 2012).
Pityriasis rubra pilaris is 'characterized by scaly and horny productions situated chiefly in the sebaceous follicles and by a more or less generalized hyperemia' to use the words of DeVergie who first described it (Zeisler, 1923) in a man and his son and 2 daughters. The lesions consist 'of acuminate follicular plugging about the dorsal aspects of the hands and feet, and large plaquelike, scaling psoriasiform lesions of the extensor surfaces of the arms, legs and thighs as well as the neck and calves.'
Weiner and Levin (1943) reported a mother and 4 of her children with PRP. The mother and her affected father, brother, and sister had previously been reported by Zeisler (1923). The patients studied by Weiner and Levin (1943) all had onset of skin lesions between the first and second year of life, and the disorder became more intense with age. Characteristically the lesions were less intense during warm weather, particularly in childhood, but never resolved completely. All of the affected individuals were otherwise healthy. The mother and her 15-year-old son had acuminate follicular plugging on the dorsa of the hands and feet, with plaque-like, scaling psoriasiform lesions of the extensor surfaces of the arms, legs, and thighs as well as the neck and calves. There was some involvement of the face in both, and the mother had the characteristic waxy yellow appearance of her palms and soles. Her 3 daughters, aged 13, 12, and 8 years, had lesions of less severity in direct proportion to their ages, and no psoriasiform plaques were present. Weiner and Levin (1943) followed the patients for 2 years and observed that treatment with vitamin A and carotene resulted in improvement of lesions beyond that occurring seasonally, but the lesions never completely cleared, and the lesions always recurred when treatment was stopped.
Beamer et al. (1972) contrasted the acquired and hereditary forms of pityriasis rubra pilaris, stating that the hereditary form tends to be less severe and more limited in extent.
Kint et al. (1972) described 6 affected individuals over 3 generations of a family with PRP. Onset of disease was between 4 months and 10 years of age, and there was variable expressivity and incomplete penetrance. A biopsy of affected skin from the proband, a 5-year-old girl, revealed hyperkeratosis with focal parakeratosis, follicular plugging, and moderate acanthosis. A perivascular infiltrate in the upper dermis consisted primarily of lymphocytes and histiocytes.
In 4 individuals from 3 generations of a family of Ukrainian ancestry, Vanderhooft et al. (1995) described the clinical features of pityriasis rubra pilaris. There was one instance of male-to-male transmission. All affected individuals demonstrated erythematous scaly skin with follicular prominence and islands of sparing. Immunocytochemistry and immunoblot analysis suggested abnormality of keratins.
Sehgal et al. (2000) described a 55-year-old mother and 33-year-old son with PRP, as well as 2 sporadic patients. The mother and son both had onset of PRP in childhood, with lesions beginning on the head. They reported seasonal exacerbations and relative remissions. Examination revealed erythematous and scaly follicular papules, some of which coalesced to form plaques. The lesions were innumerable and occupied the skin of the neck, chest, upper extremities, abdomen, thighs, legs, and dorsa of the feet. Dorsa of the fingers, palms, and soles showed conspicuous 'islets of sparing.' The nails were brittle, discolored, and had subungual hyperkeratotic pitting and transverse ridging. Histopathology showed mild to moderate hyperkeratosis with focal parakeratosis and hypergranulosis. There was associated mild acanthosis apparent in the form of broad and blunted rete ridges, and focal keratotic plugging was a regular feature. Focal collections of mononuclear cells were seen in the dermis, and acute inflammatory changes were striking, with mild spongiosis in elongated rete ridges. Sehgal et al. (2000) noted that the clinical features and microscopic findings in sporadic and familial PRP are similar.
Sehgal et al. (2002) examined a 45-year-old man with a 2-year history of PRP, as well as his affected 42-year-old sister and 38-year-old brother. All 3 had erythematous and scaly papules conforming to a follicular and/or extra-follicular pattern, coalescing in places to form plaques. The majority of the lesions were covered with grayish-white scales. The lesions were located on the neck, chest, upper extremities. abdomen, thighs, legs, and dorsae of the hands and feet. There was conspicuous presence of apparently normal skin in 'islets of sparing.' Nails, palms, and soles were also spared. Histologic sections of lesion biopsies showed changes typical of PRP and were identical in all 3 patients.
Thomson and Moss (2007) reported a mother and 2 daughters with PRP. The 33-year-old mother developed PRP at age 12 years; there was no prior family history of PRP, psoriasis (see 177900), or atopy (see 147050). She presented with a cephalocaudal eruption of follicular hyperkeratotic papules progressing to generalized erythroderma with islands of sparing. She also had a scaly scalp, yellow thickening of the palms and soles, and subungual hyperkeratosis. The clinical diagnosis of PRP was supported by histologic findings of hyperkeratosis, patchy parakeratosis varying in both horizontal and vertical planes, and follicular plugging. Her first daughter was born with thick scales on the scalp and areas of superficial peeling on the face, palms, soles, and genital region. Within weeks she developed follicular erythematous papules on the face, trunk, and limbs, which enlarged into pink plaques with a scaly edge. There was no palmoplantar thickening. A skin biopsy was consistent with PRP, showing orthokeratosis and parakeratosis alternating in both the vertical and horizontal directions, lipping of the follicular ostia, and associated follicular plugging. The second daughter was born with similar clinical findings to those of her sister, although she was less severely affected. At the ages of 9 months and 3 years, respectively, the girls' skin disease was well-controlled on emollients and intermittent use of mild topical steroids, and the older daughter's skin was mostly clear.
Fuchs-Telem et al. (2012) studied 4 families segregating autosomal dominant PRP. Age of onset ranged from 4 to 36 months of age. All affected individuals showed well-demarcated erythematous plaques coalescing into large areas interspersed with islands of normal skin, follicular papules or accentuation, palmoplantar keratoderma, and a lack of psoriasis-associated nail changes. Histopathology of skin lesions showed alternating orthokeratosis and parakeratosis, acanthosis with broadening of the rete ridges, follicular plugging, lymphocytic infiltrate in the dermis, and a lack of neutrophils in the epidermis.
Sehgal and Srivastava (2006) noted that Western blot analysis of involved skin in PRP has shown expression of keratin 17, 16, and 6, indicating keratinocyte activation.
Classification
Griffiths (1984, 1992) devised a classification of both sporadic and familial cases of PRP based on age of onset, clinical features, and prognosis, along with a relative frequency of each type: type I, or classic adult PRP, present in 55% of cases; type II, or atypical adult PRP, present in 5%; type III, or classic juvenile PRP, present in 10%; type IV, or circumscribed juvenile PRP, present in 25%; and type V, or atypical juvenile PRP, present in 5%. Fuchs-Telem et al. (2012) stated that familial PRP belongs to the type V group. It is usually present at birth or appears during the first years of life and runs a chronic course. It is characterized by prominent follicular hyperkeratosis, diffuse palmoplantar keratoderma, and erythema. Response to treatment is disappointing.
Sehgal and Srivastava (2006) stated that the pattern of inheritance of PRP is largely autosomal dominant with variable expressivity but noted that autosomal recessive inheritance had also been reported.
Fuchs-Telem et al. (2012) genotyped members of a family segregating autosomal dominant pityriasis rubra pilaris and identified 2 regions of interest. Fine mapping using microsatellite markers in this family and 2 additional families with PRP revealed linkage in all 3 families to chromosome 17q25.3, with a combined lod score of 3.73. Critical recombination events set the 5-Mb disease interval between markers D17S722 and D17S668.
After next-generation sequencing failed to identify the proximal cause of autosomal dominant pityriasis rubra pilaris mapping to chromosome 17q25 in 3 families, Fuchs-Telem et al. (2012) sequenced functionally relevant candidate exons within the critical interval and identified heterozygosity for a missense mutation and a nonsense mutation in the CARD14 gene (607211.0006 and 607211.0007, respectively) that segregated with disease in each family. In 2 patients from a fourth family with PRP, they identified a heterozygous splice site mutation (607211.0008). Fuchs-Telem et al. (2012) noted that penetrance was incomplete in some of the families, suggesting a possible role for additional modifying traits, epigenetic factors, or environmental elements in determining the phenotypic expression of the causative mutations.
Beamer, J. E., Newman, S. B., Reed, W. B., Cram, D. Pityriasis rubra pilaris. Cutis 10: 419-421, 1972.
Fuchs-Telem, D., Sarig, O., van Steensel, M. A. M., Isakov, O., Israeli, S., Nousbeck, J., Richard, K., Winnepenninckx, V., Vernooij, M., Shomron, N., Uitto, J., Fleckman, P., Richard, G., Sprecher, E. Familial pityriasis rubra pilaris is caused by mutations in CARD14. Am. J. Hum. Genet. 91: 163-170, 2012. [PubMed: 22703878] [Full Text: https://doi.org/10.1016/j.ajhg.2012.05.010]
Griffiths, A. Pityriasis rubra pilaris: etiologic considerations. (Commentary) J. Am. Acad. Derm. 10: 1086-1088, 1984. [PubMed: 6736336] [Full Text: https://doi.org/10.1016/s0190-9622(84)80365-5]
Griffiths, W. A. D. Pityriasis rubra pilaris: the problem of its classification. (Letter) J. Am. Acad. Derm. 26: 140-141, 1992. [PubMed: 1732330] [Full Text: https://doi.org/10.1016/s0190-9622(08)80543-9]
Kint, A., De Bie, S., Geerts, M.-L., T'Kint, R. Pityriasis rubra pilaris, a familial condition. Arch. Belg. Derm. Syph. 28: 371-376, 1972. [PubMed: 4670284]
Parish, L. C., Woo, T. H. Pityriasis rubra pilaris in Korea. Treatment with methotrexate. Dermatologica 139: 399-403, 1969. [PubMed: 5371703] [Full Text: https://doi.org/10.1159/000253946]
Sehgal, V. N., Bajaj, P., Jain, S. Pityriasis rubra pilaris (PRP): report of four cases. J. Derm. 27: 174-177, 2000. [PubMed: 10774144] [Full Text: https://doi.org/10.1111/j.1346-8138.2000.tb02146.x]
Sehgal, V. N., Jain, S., Kumar, S., Bhattacharya, S. N., Sardana, K., Bajaj, P. Familial pityriasis rubra pilaris (adult classic-I): a report of three cases in a single family. Skinmed. 1: 161-164, 2002. [PubMed: 14673347] [Full Text: https://doi.org/10.1111/j.1540-9740.2002.01663.x]
Sehgal, V. N., Srivastava, G. (Juvenile) pityriasis rubra pilaris. Int. J. Derm. 45: 438-446, 2006. [PubMed: 16650174] [Full Text: https://doi.org/10.1111/j.1365-4632.2006.02666.x]
Thomson, M. A., Moss, C. Pityriasis rubra pilaris in a mother and two daughters. (Letter) Brit. J. Derm. 157: 183-204, 2007. [PubMed: 17578441] [Full Text: https://doi.org/10.1111/j.1365-2133.2007.07903.x]
Vanderhooft, S. L., Francis, J. S., Holbrook, K. A., Dale, B. A., Fleckman, P. Familial pityriasis rubra pilaris. Arch. Derm. 131: 448-453, 1995. [PubMed: 7726588]
Weiner, A. L., Levin, A. A. Pityriasis rubra pilaris of familial type: experience in the therapy with carotene and vitamin A. Arch. Derm. Syph. 48: 288-296, 1943.
Zeisler, E. P. Pityriasis rubra pilaris--familial type. Arch. Derm. Syph. 7: 195-208, 1923.