Two sisters with familial dyskeratotic comedones

ARTICLE

Auteur(s) : Christian HALLERMANN^1,2, Hans Peter BERTSCH¹

¹ Department of Dermatology, University Hospital Goettingen, Germany
² Department of Dermatology and Allergology, Hannover Medical University, Ricklinger Straße 5, D-30449 Hannover, Germany

Article accepted on 04/05/2004

Familial dyskeratotic comedones (FDC) is a genodermatosis with autosomal dominant inheritance. Since its first introduction in 1972 by Carneiro, 5 additional publications presented further affected families [1-6]. The disease is characterized by the familial occurrence of hyperkeratosis papules, resembling open comedones or cutaneous horns. The skin lesions are usually located on the extremities, trunk and face. We report on a further affected family with typical clinical and histological findings.

Case presentation

A 28 year old woman presented with asymptomatic comedo-like lesions on the face, neck, chest and the extensor sites of the upper arms (Fig. 1). The lesions first appeared in early childhood and increased until now. There were no significant changes during puberty. There was no history of severe acne vulgaris. The patient is otherwise healthy.
There were identical findings in 2 punch biopsies from different sites (Fig. 2). Within both specimens, there were crateriform invaginations of the epidermis, filled with abundant parakeratotic keratin. The invaginated epithelium demonstrated focal acantholysis and marked dyskeratoses. Single dyskeratotic cells are reminiscent of corps ronds in Darier’s disease.
Treatment with topical retinoids showed a slight improvement after 8 weeks but without satisfying results. Oral treatment with isotretinoin showed no effect. Small areas were treated successfully with the use of CO₂ laser. Because of the disseminated distribution of the lesions this kind of treatment was only applied focally.
The patient’s sister presented with similar lesions on the extensor sites of the arms. A third sister is not affected. Neither affected sister has children. Unfortunately there is no further family history available regarding their parents’ involvement.

Discussion

FDC is a rare genodermatosis with inheritance of autosomal dominant characteristics. It is listed in OMIM, a database for genodermatoses [7]. To our knowledge, until now 13 patients from 6 families, including our patients, have been described [1-5]. Van Geel presented a table with a detailed review of the existing case reports in 1999 [4]. FDC are characterized by keratotic papules and comedo-like lesions. They are usually asymptomatic but may cause pruritus. They usually appear in childhood and may affect both sexes equally. Until now the scalp, palms and soles were spared in all except one case [1]. There are no associated symptoms of hair, nail anomalies or involvement of the oral cavity. The lesions are usually generalized showing a predilection of the upper arms, the trunk and the face.
So far the nature of the disease is not clear. Ständer et al. described an irregular distribution of keratohyalin granules detected by immunohistological staining for the filaggrin antigene. They describe a regular distribution of different keratin types in the lesions. They mention diminished desmosomes detected on electron-microscopy and concluded from their analyses a lack of cell differentiation in keratinocytes [5]. In our opinion the histology shares many features with other dyskeratotic acantholytic diseases like Hailey-Hailey disease or Darier’s disease. For that reason it seems to be of special interest to investigate mutations of calcium canal encoding genes in further cases [8, 9].
In our case therapy with topical or systemic retinoids was not sufficient. This is in line with the observations made by Hall et al. and Van Geel et al. The results of CO₂ laser ablation was effective but the therapy is not applicable for generalized lesions. Satisfying results with Co₂ laser therapy were also seen by Ständer et al.
The diagnosis of FDC can be established by its typical clinical presentation, which easily distinguishes FDC from Darier disease or warty dyskeratoma, which may come with a similar histology. Because of the widespread distribution of the lesions FDC differs from nevus comedonicus, which also presents with comedones. Acne vulgaris is usually more inflammatory and the histology is different. Keratosis pilaris and Kyrle Disease has to be distinguished by histology. n

References

1. Carneiro SJ, Dickson JE, Knox JM. Familial dyskeratotic comedones. Arch Derm 1972; 105: 249-51.

2. Hall JR, Holder W, Knox JM, Knox JM, Verani R. Familial dyskeratotic comedones: a report of three cases and review of the literature. J Am Acad Derm 1987; 17: 808-14.

3. Leppard BJ. Familial dyskeratotic comedones. Clin Exp Derm 1982; 7: 329-32.

4. Van Geel NAC, Kockaert M, Neumann HAM. Familial dyskeratotic comedones. Brit J Derm 1999; 140: 956-9.

5. Stander S, Rutten A, Metze D. Familial dyskeratotic comedones. A rare entity Hautarzt 2001; 52: 533-6.

6. Price M, Russel Jones R. Familial dyskeratotic comedones. Clin Exp Dermatol 1985; 10: 147-53.

7. Online Mendelian Inheritance in Man, OMIM (TM). Johns Hopkins University, Baltimore, MD. MIM Number: 120450, 12/17/1999. World Wide Web URL: http://www.ncbi.nlm.nih.gov/omim/

8. Hu Z, Bonifas JM, Beech J, Bench G, Shigihara T, Ogawa H, Ikeda S, Mauro T, Epstein EH Jr. Mutations in ATP2C1, encoding a calcium pump, cause Hailey-Hailey disease. Nat Genet 2000; 24: 61-5.

9. Ruiz-Perez VL, Carter SA, Healy E, Todd C, Rees JL, Steijlen PM, Carmichael AJ, Lewis HM, Hohl D, Itin P, Vahlquist A, Gobello T, Mazzanti C, Reggazini R, Nagy G, Munro CS, Strachan T ATP2A2 mutations in Darier’s disease: variant cutaneous phenotypes are associated with missense mutations, but neuropsychiatric features are independent of mutation class. Hum Mol Genet 1999; 8: 1621-30.