Alternative titles; symbols
SNOMEDCT: 403810008; ORPHA: 89843;
| Location | Phenotype |
Phenotype MIM number |
Inheritance |
Phenotype mapping key |
Gene/Locus |
Gene/Locus MIM number |
|---|---|---|---|---|---|---|
| 3p21.31 | Epidermolysis bullosa pruriginosa | 604129 | Autosomal dominant; Autosomal recessive | 3 | COL7A1 | 120120 |
A number sign (#) is used with this entry because of evidence that dystrophic epidermolysis bullosa (DEB) pruriginosa is caused by heterozygous or compound heterozygous mutation in the COL7A1 gene (120120).
See also autosomal dominant DEB (131750) and autosomal recessive DEB (226600), allelic disorders with overlapping phenotypes.
Dystrophic epidermolysis bullosa is an inherited skin fragility disorder associated with anchoring fibril abnormalities and sublamina densa blistering.
EB pruriginosa is a rare distinct clinical subtype of dystrophic EB in which skin fragility, blistering, and scar formation are associated with intense pruritus, nodular prurigo-like lichenified lesions, nail dystrophy, and variable presence of albopapuloid lesions (McGrath et al., 1994; Cambiaghi et al., 1997). The onset of these clinical features may be evident in early childhood, but in some cases is delayed until the second or third decade of life. Autosomal dominant, autosomal recessive, and sporadic inheritance patterns have all been described in this disorder.
Drera et al. (2006) reported 7 unrelated Italian patients with EB pruriginosa. Three patients had a family history of the disorder consistent with autosomal dominant inheritance. Six patients reported onset of symptoms at birth or early childhood. Most had relatively mild skin involvement with blistering lesions located primarily at trauma sites. Four patients reported gradual amelioration during childhood or adolescence. Other disease features included nail dystrophy, skin atrophy and milia formation, and a single patient had albopapuloid lesions. All patients reported worsening of the skin phenotype after the onset of itching. Physical exam showed excoriated and lichenified papules, nodules, and plaques associated with scarring on the shins, foot dorsum, elbows, wrists, and back. Pruritus occurred at puberty in 4 patients and in adulthood in 3. Pruritus was severe, generalized, and unresponsive to conventional therapies. Two patients had increased serum IgE. Skin biopsies showed deposition of variable amounts of collagen VII at the dermal-epidermal junction.
Ee et al. (2007) reported a Chinese-Singaporean family with autosomal dominant EB pruriginosa. The proband was a 53-year-old woman with a blistering skin eruption over the back, nape of the neck, both shins, and elbows. She had a history of intermittent blistering since age 25 years. The blisters were provoked by scratching and were pruritic; mucous membranes were not affected. Physical examination showed linear erosions and hypertrophic scars on the affected areas with some milia formation. Skin biopsy showed blister formation below the lamina densa and decreased numbers of anchoring fibrils in nonblistered skin. At least 5 of her sibs were similarly affected.
The transmission pattern of epidermolysis bullosa pruriginosa in patients 1, 4, and 6 reported by Mellerio et al. (1999) was consistent with autosomal dominant inheritance. The transmission pattern in patient 5 of Mellerio et al. (1999) was consistent with autosomal recessive inheritance. The heterozygous mutation in the COL7A1 gene in 1 patient with epidermolysis bullosa pruriginosa reported by Drera et al. (2006) occurred de novo.
The possibility of additional immune-mediated factors in the pathogenesis of this characteristic form of epidermolysis bullosa has been suggested and was supported by the report of Yamasaki et al. (1997) describing clinical improvement with cyclosporin A. In the patients studied by Mellerio et al. (1999), there was no evidence for other causes of itching, such as thyroid dysfunction or low ferritin levels. They pointed out, however, that because the pathophysiology of itch is poorly understood, other potential modifying factors may be elucidated.
In affected members of a Taiwanese pedigree with autosomal dominant EB pruriginosa, Lee et al. (1997) identified a heterozygous mutation in the COL7A1 gene (120120.0017). Mellerio et al. (1999) identified the same mutation in a British family with dominant epidermolysis bullosa pruriginosa.
Mellerio et al. (1999) identified mutations in the COL7A1 gene (see, e.g., 120120.0020) in 5 unrelated patients with EB pruriginosa. One patient was compound heterozygous for 2 mutations (120120.0018; 120120.0019).
Drera et al. (2006) identified 9 mutations in the COL7A1 gene among 7 unrelated Italian patients with EB pruriginosa (see, e.g., 120120.0032; 120120.0033). Six of the mutations had previously been reported in EB patients without pruriginosa (see, e.g., 120120.0009; 120120.0010).
Drera et al. (2006) stated that 16 distinct mutations in the COL7A1 gene had been reported in patients with EB pruriginosa.
Ee et al. (2007) identified a heterozygous mutation in the COL7A1 gene (G2251E; 120120.0014) in affected members of a Chinese-Singaporean family with dominant inheritance of EB pruriginosa.
Cambiaghi, S., Brusasco, A., Restano, L., Cavalli, R., Tadini, G. Epidermolysis bullosa pruriginosa. Dermatology 195: 65-68, 1997. [PubMed: 9267744] [Full Text: https://doi.org/10.1159/000245691]
Drera, B., Castiglia, D., Zoppi, N., Gardella, R., Tadini, G., Floriddia, G., De Luca, N., Pedicelli, C., Barlati, S., Zambruno, G., Colombi, M. Dystrophic epidermolysis bullosa pruriginosa in Italy: clinical and molecular characterization. Clin. Genet. 70: 339-347, 2006. [PubMed: 16965329] [Full Text: https://doi.org/10.1111/j.1399-0004.2006.00679.x]
Ee, H. L., Liu, L., Goh, C. L., McGrath, J. A. Clinical and molecular dilemmas in the diagnosis of familial epidermolysis bullosa pruriginosa. J. Am. Acad. Derm. 56: S77-S81, 2007. [PubMed: 17434045] [Full Text: https://doi.org/10.1016/j.jaad.2006.10.017]
Lee, J. Y., Pulkkinen, L., Liu, H.-S., Chen, Y.-F., Uitto, J. A glycine-to-arginine substitution in the triple-helical domain of type VII collagen in a family with dominant dystrophic epidermolysis bullosa pruriginosa. J. Invest. Derm. 108: 947-949, 1997. [PubMed: 9182828] [Full Text: https://doi.org/10.1111/1523-1747.ep12296242]
McGrath, J. A., Schofield, O. M. V., Eady, R. A. J. Epidermolysis bullosa pruriginosa: dystrophic epidermolysis bullosa with distinctive clinicopathological features. Brit. J. Derm. 130: 617-625, 1994. [PubMed: 8204470] [Full Text: https://doi.org/10.1111/j.1365-2133.1994.tb13109.x]
Mellerio, J. E., Ashton, G. H. S., Mohammedi, R., Lyon, C. C., Kirby, B., Harman, K. E., Salas-Alanis, J. C., Atherton, D. J., Harrison, P. V., Griffiths, W. A. D., Black, M. M., Eady, R. A. J., McGrath, J. A. Allelic heterogeneity of dominant and recessive COL7A1 mutations underlying epidermolysis bullosa pruriginosa. J. Invest. Derm. 112: 984-987, 1999. [PubMed: 10383749] [Full Text: https://doi.org/10.1046/j.1523-1747.1999.00614.x]
Yamasaki, H., Tada, J., Yoshioka, T., Arata, J. Epidermolysis bullosa pruriginosa (McGrath) successfully controlled by oral cyclosporin. (Letter) Brit. J. Derm. 137: 308-310, 1997. [PubMed: 9292092]