Dowling-Degos Disease - A Novel Presentation of An Uncommon Disease

Abstract

Dowling-Degos Disease is a rare, pigmentary disorder with variable presentations. The most common among them are hyperpigmented macules and reticulate pigmentary anomaly of flexures. Many other phenotypic variations of Dowling-Degos disease have been reported in literature. We present here a case of Dowling-Degos disease with comedo-like lesions and pits without typical flexural hyperpigmented macules.

Introduction

Reticulate pigmentary disorders are a heterogeneous group comprising of several inherited conditions that are characterized by reticulate hyperpigmentation and several other cutaneous and extracutaneous associations.[1] Dowling-Degos disease is a rare condition inherited as autosomal dominant trait characterized by numerous, asymptomatic, symmetrical, progressive, small, round, pigmented macules over axillae, groin, face, neck, arms and trunk, scattered comedo-like lesions (dark-dot follicles) and pitted acneiform scars.[2] Histopathology is diagnostic. The purpose of this case report is to describe a case with only comedo-like lesions without the typical flexural hyperpigmentation in the background of a positive family history.

Case Report

A 19-year-old female presented with multiple hyperpigmented pits over face, trunk, and groin for last 5 years. The lesions were gradually progressive in nature and asymptomatic. There was history of acne in past which had healed with hyperpigmentation. There was a family history of similar pitted-lesions in three other family members namely her father (aged 55 years), her paternal aunt (aged 45 years) and her paternal aunt's son (aged 25 years) [Figure 1]. Dermatological examination revealed multiple comedo-like lesions about 1–3 mm in size and few papules over face, back, buttocks, and trunk [Figure 2a-c]. Post-acne hyperpigmentation was present over the back [Figure 2c]. Palms and soles were spared. Examination of mucosa, hair and nails was normal. However, systemic examination was within normal limits. Based on the above clinical findings, following differential diagnoses of Familial Dyskeratotic Comedones, Comedonal Darrier's Disease, and Acne Conglobata were considered. A skin biopsy taken from the comedo-like lesions revealed focal slender outgrowths of rete ridges with hyperpigmentation in basal layer showing accentuation in tip of rete ridges along with few attempted horn cysts pointing towards the diagnosis of Dowling-Degos disease [Figure 3a and b]. Examination of the affected family members showed multiple comedo-like lesions (similar to the index case) on a background of reticulate hyperpigmentation (typical of Dowling-Degos disease) over flexures [Figure 4a and b]. However, genetic study for mutation analysis of keratin 5 gene could not be done due to resource and economic constraints. Based on above clinical and histopathological findings, a diagnosis of Dowling-Degos disease was made. The patient was prescribed topical tretinoin (0.05%) cream without much improvement. Subsequently after oral isotretinoin (30 mg) intake for 6 weeks, the patient reported some improvement.

Figure 1.

Pedigree chart of the family showing autosomal dominant inheritance

Figure 2.

(a and b) Multiple comedo-like lesions with few papules over face. (Index case). (c) Multiple comedo-like lesions with few papules over upper back with post acne-hyperpigmentation. (Index case)

Figure 3.

(a) Skin biopsy from the comedo-like lesions showing focal slender outgrowths of rete ridges with hyperpigmentation in basal layer. (H and E, 10×) low power magnification). (b) Basal layer hyperpigmentation showing accentuation in tip of rete ridges along with attempted horn cysts. (H and E, 40×) high power magnification)

Figure 4.

(a and b) Multiple comedo-like lesions with typical reticulate hyperpigmentation over face and axilla. (Father of index case)

Discussion

Dowling-Degos disease is a reticulate pigmentary disorder described by Dowling and Freudenthal with autosomal dominant mode of inheritance but may occur sporadically. Dowling Degos disease has very characteristic clinical and histopathological features. The most common being hyperpigmented macules in a reticulate pattern in the flexures. Associated features include comedo-like papules, perioral pitted scars, epidermoid/trichilemmal cysts,[3] chloracne-like manifestations,[4] generalized variant,[5] association with hidradenitis suppurativa,[6] Galli Galli disease,[7] and overlap with reticulate acropigmentation of Kitamura [RAPK].[8] The diagnosis is quite evident when classical features of the disease are present. However, it may present with significant diagnostic dilemma when classical features are lacking as was seen in our index case. The diagnosis was established after review of histopathological findings and significant positive clinical findings among family members of the index case.

Khandpur et al.[9] presented two cases of Dowling-Degos disease from two families with multiple comedo-like lesions with pitted scars, but unlike our case they had punctate hyperpigmented macules. The histopathology of their case 2 showed normal non-follicular epidermis.

The closest differentials to above described clinical findings include Familial Dyskeratotic Comedones, Comedonal Darrier's disease and acne conglobata. Familial Dyskeratotic Comedones is a rare autosomal dominant condition clinically characterized by numerous, discrete, disseminated, hyperkeratotic papules and comedones involving trunk and distal extremities sparing head and neck.[10] The histopathological evaluation shows crater-like invaginations filled with keratinous material with evidence of dyskeratosis.[10] This diagnosis was excluded in our case as the patient had predominant head and neck involvement without dyskeratosis. Another rare entity which is characterized by similar clinical findings of multiple comedone-like lesions over face, scalp, and upper trunk is Comedonal Darrier's Disease. In addition, it has typical features of Darrier's disease like nail changes and palmar pits with typical histopathological features of corps ronds and grains restricted to follicles.[11] The above described disease was excluded based on the histopathological findings of our case. Acne conglobata, a rare and severe form of acne is characterized by multiple and extensive inflammatory nodules and abscesses and sinus tracts.[12] Multiple polymorphous, grouped comedones are typical. Our case lacked such an extensive and virulent presentation.

Atleast 3 genes have been shown to be associated with Dowling-Degos disease. Flexural Dowling-Degos disease was initially found to be caused by loss of mutations affecting the KRT 5 gene region encoding the initial part of keratin 5.[13] Galli-Galli disease which features acantholysis in histology in addition to clinical and histopathological signs of classical Dowling Degos disease, was also shown to result from mutation in KRT 5.[13] More recently, generalized Dowling-Degos disease was found to be associated with mutation in POFUT1, which encodes protein O-fucosyltransferase and POGLUT1 which encodes for protein O-glucosyltransferase; knock - down of POFUT1 was shown to reduce expression of KRT 5 in keratinocytes.[13]

The clinical features and histopathological changes were memorably described by Wilson-Jones and Grice as “demonstrating dusky dappled disfigurements and dark dot depressions and disclosing digitate down growths delving dermally”.[14] Histopathology of Dowling-Degos disease is diagnostic with a distinctive acanthosis, characterized by downward elongations of thin rete ridges with reticulated or fenestrated patterns with a concentration of melanin at tips and occasional follicular plugging and horn cysts[14,15] which were consistent with our histopathological findings. Kim et al.[3] have published 6 cases of Dowling-Degos disease with histopathological findings consistent with our case and their single patient also showed horn cysts as in our case.

Though there is no definitive cure for Dowling-Degos disease, many different treatment options have been tried in recent years without convincing therapeutic benefits which include depigmenting agents such as hydroquinone, as well as systemic and topical retinoids. Various lasers especially Erbium YAG and fractional Erbium YAG have been beneficial in treating Dowling-Degos disease.[16,17]

Conclusion

Our case exemplifies how in rare circumstances Dowling-Degos disease can present with only comedo-like lesions sine its classical features. Hence clinicians must be aware of such atypical manifestations of such disease for its appropriate diagnosis and management.

Declaration of patient consent

The authors certify that they have obtained all appropriate patient consent forms. In the form the patients have given their consent for 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.