Atypical cases of Dowling-Degos disease.

Dowling-Degos disease (DDD) is a rare autosomal dominant condition characterized by multiple, small, round pigmented macules usually arranged in reticular pattern, chiefly distributed in axillae and groins. Here we are reporting three atypical cases of DDD in a family. They had hypopigmented macules with typical features of DDD indicating generalized DDD. Histopathology confirmed the diagnosis. We present these three cases to stress the existence of generalized DDD phenotype in the Indian population.

INTRODUCTION

Dowling–Degos disease (DDD) is a rare autosomal dominant condition characterized by multiple, small, round pigmented macules usually arranged in reticular pattern. It has its onset in adulthood. The lesions are chiefly distributed in axillae and groins, but other areas may be involved, including the intergluteal and inframammary folds, neck, scalp, trunk, and arms. Other features include scattered comedo-like lesions and pitted acneiform scars near the angles of the mouth. The histology is diagnostic.[1]

Dyschromatosis universalis hereditaria (DUH) is an autosomal dominant condition characterized by hyperpigmented macules admixed with hypopigmented lesions involving the trunk, extremities, and the face. It has its onset in early childhood.[2]

Herein we report three cases of DDD in a family with features overlapping with DUH.

CASE REPORT

A 65-year-old male (index case) presented with lesions over his face, trunk, and axillae since the age of 25 years. The lesions initially appeared over the face and later progressed to involve the axillae and trunk. There was no history of consanguinity. He was accompanied by his two sons, 40 years (Case 2) and 28 years (Case 3) of age, who had similar lesions since 23 years of age. He also gave history of similar lesions in his maternal aunt. On examination, all the three cases had reticulate hyperpigmented macules over the neck, both axillae [Figure 1] and flexural aspect of both forearms. Mottled hypopigmented macules were seen over the chest and abdomen [Figure 2]. Perioral and perinasal pitted scars were seen [Figure 3]. Multiple pitted scars and open comedones with few cysts were present over the back [Figure 4], chest and abdomen.

Figure 1

Hyperpigmented macules over the axilla in case 1

Figure 2

Hypopigmented macules over the chest and abdomen in case 1

Figure 3

Pitted scars over the perinasal and perioral area in case 1

Figure 4

Comedones over the back in case 1

A skin biopsy performed from the index case showed elongated branched pigmented rete ridges [Figure 5]. Broad and narrow keratin-filled craters were seen. Deep dermis showed cysts containing keratin flakes lined by thin epithelium. A diagnosis of DDD was arrived at based on the clinical and histopathologic findings, the atypical feature in these three cases being the presence of hypopigmented macules over the chest and abdomen.

Figure 5

Histopathologic examination of the skin biopsy performed from the index case showing elongated branched pigmented rete ridges. (H and E, ×10)

DISCUSSION

DDD is characterized by a triad of reticular pigmentation in the flexures, comedo-like lesions and pitted acneiform scars. The histology is diagnostic, with a distinct form of acanthosis, characterized by an irregular elongation of thin branching rete ridges, with concentration of melanin at the tips (“antler like appearance”). Follicular infundibulum may be involved and in some cases there is follicular plugging.[12] In the present study, all three cases had typical triad and histopathologic features.

The association of DDD with reticulate acropigmentation of Kitamura (RAPK) has been earlier described in the literature.[3456] Vasudevan et al. reported a patient having overlapping features of DDD, RAPK, and reticulate acropigmentation of Dohi (RAPD). There patient had acral pigmentation and palmar pits resembling RAPK with flexural involvement resembling DDD. In addition, he had hypopigmented macules resembling RAPD. They proposed that all these entities may be a part of the single pigmentary disorder.[3] In the present study, all three cases had all features of DDD. Absence of palmar pits and acral pigmentation excluded coexistence of RAPK; however, the presence of hypopigmented macules admixed with hyperpigmented macules on the trunk suggested the coexistence of DUH.

DDD with DUH-like pigmentation has been earlier described in a family.[7] Wu et al.[8] described a family with autosomal dominant inheritance of a skin disorder with clinical features of both DDD and DUH and they coined the term generalized DDD. They believed that number of previously reported cases of DDD-RAPK syndrome or DDD-DUH overlap may be the cases of generalized DDD. They divided different disorders with overlapping clinical or histopathologic features into two major groups.[8]

The first is DDD. Most patients in this group have the characteristic histologic findings of epidermal atropy, elongated rete ridges, horn cyst formation, and hyperpigmented tips. The distribution may be reticulate in flexural areas (classic DDD) or generalized with hypopigmented papules (generalized DDD). Histopathology of hypopigmented area shows elongation of rete ridges, basal hypopigmentation with pigment in the tip of rete ridges. Patients may or may not have atrophic brown macules on the back of hands and feet, palmar pits, and broken epidermal ridges, the entity known as RAPK.[8]

The second major group is dyschromatosis, including DUH and DSH. Clinically, both have hyperpigmented and hypopigmented lesions; and histopathology of hyperpigmented lesions shows basal hyperpigmentation and pigment incontinence, whereas hypopigmented lesions’ shows basal hypopigmentation. Although DUH and DSH have similar histopathologic features, they differ from DDD group.[8] In the present study, cases 1, 2, and 3 had lesions similar to the case described by Wu et al.[8]

Galli Galli disease (GGD) is the name given to a rare form of acantholytic DDD. Verma et al.[9] described a case of GGD in an Indian family where 25 persons had DDD and they have been able to document a heterozygous nonsense mutation c.C10T in exon 1 of the KRT5 gene in four members of the family. All the cases described by them showed a mottled pigmentation comprising hypo- and hyperpigmented asymptomatic macules similar to our case. They pointed out that the hypopigmented lesions in the DDD spectrum has been underreported in India.[9] A similar mutation has been described in Chinese family with DDD with hypopigmented macules adjacent to the classic lesions showing histologic features of DDD.[10]

We present these three cases for their rarity.

Declaration of patient consent

The authors certify that they have obtained all appropriate patient consent forms. In the form the patient(s) has/have given his/her/their consent for his/her/their images and other clinical information to be reported in the journal. The patients understand that their names and initials will not be published and due efforts will be made to conceal their identity, but anonymity cannot be guaranteed.

Financial support and sponsorship

Nil.

Conflicts of interest

There are no conflicts of interest.