S50 Letters
J AM ACAD DERMATOL AUGUST 2008
Congenital Darier disease To the Editor: Darier disease (DD), or keratosis follicularis, an autosomal dominant genodermatosis, is characterized by multiple pruritic, hyperkeratotic papules and plaques primarily in seborrheic areas of the head, neck, and trunk, and may be accompanied by palmar pitting, nail dystrophy, and oral lesions.1 The diagnosis of DD is based on positive family history, diagnostic histopathologic, features and the presence of mutations in the ATP2A2/SERCA gene.2 The onset of this chronic disease typically ranges from 6 to 20 years of age, with a peak incidence between the ages of 11 and 15 years.3 In this report, we describe an unusual congenital presentation of DD in a 10-month-old girl. A developmentally normal 10-month-old girl with no siblings was seen for a 2.2-cm 3 0.6-cm pinkishred, poorly defined, slightly raised thin rough plaque on the medial surface of the right buttock. Lateral to the plaque was a 1-cm 3 1-cm poorly defined pink macule (Fig 1). While the more medial of the lesions had been present since birth, the second appeared at 5 months of age. The lesions did not urticate (negative Darier’s sign), and no other lesions were noted. Based on the clinical history of turning ‘‘beet red,’’ the initial differential diagnoses included resolving infantile hemangioma, inflammatory linear verrucous epidermal nevus, and mastocytoma. A biopsy of the congenital lesion was performed. Microscopic examination revealed confluent acantholytic dyskeratosis and keratinocytes containing clumped keratohyalin granules in an eosinophilic cytoplasm (‘‘corps ronds’’) and small, seed-shaped cells with pyknotic elongate nuclei (‘‘corps grains’’; Fig 2). Further questioning revealed a significant positive family history for DD (Fig 3). Given this, a diagnosis of DD was favored. Reports of congenital acantholytic dyskeratosis, although rare, do exist.4,5 Huh et al4 report a newborn male presenting with brown verrucous papules on the trunk and limbs in a Blaschkoid distribution with no other abnormalities, a negative family history, and no detectable SERCA mutations in either uninvolved or involved skin.4 Follow-up at 1 year showed more raised and pruritic lesions which were unresponsive to topical treatment with vitamin D3. Bergua et al5 report a newborn girl presenting with an erosive plaque on the thigh and crusty papules in the groin and neck, no other abnormalities, and a negative family history (the family declined testing for SERCA gene mutations).5 Six months later, a follow-up physical examination revealed stable lesions in the groin and neck with spontaneous clearing of the thigh
Fig 1. Thin, rough plaque and poorly defined macule on the buttocks.
Fig 2. Histopathologic features of confluent acantholytic dyskeratosis with corps ronds and corps grains. (Hematoxylineeosin stain; original magnification: 320.)
plaque. Authors of both cases were loath to assign a definitive diagnosis of DD in the absence of a positive family history or SERCA mutation and preferred to label their patients with a diagnosis of ‘‘acantholytic dyskeratotic epidermal nevus’’ and ‘‘congenital acantholytic dyskeratotic dermatosis,’’ respectively. In summary, this case is notable for the site of involvement, unusual clinical appearance, and congenital onset. Burge and Wilkinson3 have indicated that the cut-off point for DD is at the level of the sacrum and that it is ‘‘unusual for [the] buttocks to be affected.’’3 The genetics of DD indicate the existence of two mosaic forms, types 1 and 2, both clinically distinguished by manifestations of the cutaneous traits.6 Given that the severity of the disease in both types is a reflection of the heterozygosity for the underlying postzygotic mutation, it is anticipated that our patient will develop more typical features of DD with time.
Letters S51
J AM ACAD DERMATOL VOLUME 59, NUMBER 2
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editors. Fitzpatrick’s color atlas and synopsis of clinical dermatology. New York: McGraw-Hill; 2005. pp. 88-9. Burge S, Wilkinson J. DariereWhite disease: a review of the clinical features in 163 patients. J Am Acad Dermatol 1992;27:40-50. Huh W, Fujiwara K, Takahashi H, Kanitakis J. Congenital acantholytic dyskeratotic epidermal naevus following Blaschko’s lines versus segmental Darier’s disease. Eur J Dermatol 2007;17:130-2. Bergua P, Puig L, Fernandez-Figueras MT, Baselga E, Alomar A. Congenital acantholytic dyskeratotic dermatosis: localized Darier disease or disseminated benign papular acantholytic dermatosis? Pediatr Dermatol 2003;20:262-5. Happle R. A rule concerning the segmental manifestation of autosomal dominant skin disorders. Arch Dermatol 1997; 133:1505-9. doi:10.1016/j.jaad.2008.02.015
Bilateral nevus of Ito and nevus spilus in the same patient
Fig 3. Patient’s pedigree for Darier disease with age and location of onset (when known). Note the clearly autosomal dominant nature in the Darier disease pedigree.
Grace Fong,a Laura Capaldi, MD,b Susan M. Sweeney, MD,c Karen Wiss, MD,c and Meera Mahalingam, MD, FRCPathd Medical student,a Division of Dermatology,b and Departments of Medicine and Pediatrics,c University of Massachusetts Medical School, Worcester, Massachusetts; Dermatopathology Section,d Department of Dermatology, Boston University School of Medicine, Boston, Massachusetts Funding sources: None. Conflicts of interest: None declared. Correspondence to: Meera Mahalingam, MD, Department of Dermatology, Boston University School of Medicine, J-609 Albany St., Boston, MA 02118 E-mail:
[email protected] REFERENCES 1. Cambiaghi S, Brusasco A, Grimalt R, Caputo R. Acantholytic dyskeratotic epidermal nevus as a mosaic form of Darier’s disease. J Am Acad Dermatol 1995;32:284-6. 2. Wolff K, Johnson RA, Suurmond D. Miscellaneous epidermal disorders: Darier’s disease. In: Wolff K, Johnson RA, Suurmond D,
To the Editor: A 57-year-old Caucasian woman presented with a bilateral pigmented, gray-blue patch on her back. The hyperpigmentation appeared during puberty and was always asymptomatic. Physical examination revealed macular gray-blue hyperpigmentation on the right and left side of the back extending to the supraclavicular area and proximal upper aspect of arms clinically characteristic of nevus of Ito (Fig 1). The patient also had a congenital patch of hyperpigmentation containing darkly pigmented macules on the left lumbar area, consistent with a nevus spilus. Histologic examination from the bilateral grayblue patch on her back showed normal epidermis and a few spindle-shaped melanocytes containing melanin, which were sparsely scattered between the collagen bundles in the mid dermis, whose axis were parallel to the skin surface (Fig 2). Fontana-Masson silver stain revealed abundant brown pigment within the cytoplasm of the spindle cells, which also showed immunoreactivity for S-100 protein, Melan-A, and HMB-45. Histopathologic examination from a cafe´ au laitecolored background pigmentation of the lumbar area containing darkly pigmented macules showed increased pigmentation in the basal layer of the epidermis, lentiginous epidermal hyperplasia, and an increased number of single melanocytes along the dermoepidermal junction. The final diagnosis was a bilateral nevus of Ito and a nevus spilus. The patient is being followed up annually without any evidence of systemic involvement. Nevus of Ito, nevus of Ota, and Mongolian spot are 3 variants of dermal melanocytoses and each of them can be distinguished by their clinical manifestations.1 In general they are rare in Caucasians.
