Dowling-Degos Disease with Reticulate Acropigmentation of Kitamura: Two Facets of a Single Disease Complex

Sir, Dowling-Degos disease (DDD) is an uncommon, autosomal dominant genodermatosis[1] with no racial or sex predilection usually presenting in late childhood or adolescence. It is characterized by numerous, symmetrical, reticulate hyperpigmented macules generally present over the axilla, groin, neck, face, arms, and trunk along with perioral pitted scars and comedo-like lesions.[2,3] It is caused by the loss of mutations affecting the KRT5 gene, a region encoding the initial part of keratin 5.[4] Reticulate acropigmentation of Kitamura (RAK) is also a reticulate pigmentary disorder characterized by atrophic, hyperpigmented macules presenting on acral skin.[5] Both these disorders are variable phenotypic expressions of a single spectrum of disease. A 33-year-old female presented to our outpatient department with a history of progressive, generalized, nonpruritic, hyperpigmented macules for 3 years [Figures 1 and 2]. The lesions began initially on the face, spreading toward the neck, sun-exposed part of the chest, axillae, both forearms, and dorsa of bilateral hands and feet. Multiple palmar and plantar pits were present with no discontinuity in dermatoglyphics [Figures 3 and 4]. Hair, nails, and buccal, labial, and vulvar mucosae were normal. The patient was born into a nonconsanguineous marriage. On further history, the patient revealed the presence of similar lesions in her mother and her daughter.Figure 1: Hyperpigmented macules seen on the faceFigure 2: Hyperpigmented macules seen on the neck and photo-exposed area of the chestFigure 3: Multiple palmar pits along with hyperpigmented macules on the flexor aspect of both forearmsFigure 4: Multiple plantar pits with normal dermatoglyphicsThe patient's mother was a 60-year-old female with asymptomatic, dark-colored macules since the age of 20 years. These lesions began initially over the arms and slowly progressed to involve the other parts of the body such as face, neck, axilla, and extremities. Few open comedones were observed over the upper back along with multiple perioral pitted scars. Buccal, labial, and vulvar mucosae were normal. The patient's daughter, a 16-year-old female, had also started developing similar small, progressive pigmented macules on her face and neck. Multiple milia were present over her nose and cheeks for 1 year. No significant abnormality was noted in the oral and vulvar mucosae. A detailed family history was obtained from the patient to assemble a pedigree chart that shows the affected individuals in the family across three generations [Figure 5]. It is noteworthy that usually, the clinical features of DDD are present during adolescence or in late childhood, as was the case in the mother and daughter of the primary patient. However, the patient herself has only been presenting with the symptoms since the age of 30 years, which is later than usual.Figure 5: Pedigree chart detailing the affected individuals across three generations in the familySkin biopsy was taken from lesions on the right arm of the 33-year-old female patient, and histopathological examination revealed mild hyperkeratosis, diffuse deposits of melanin in rete ridges, and chronic perivascular infiltrate [Figures 6 and 7].Figure 6: Skin biopsy revealing mild hyperkeratosis, diffuse deposits of melanin in rete ridges, and chronic perivascular infiltrate (H and E stain, ×10)Figure 7: Skin biopsy showing diffuse deposits of melanin in rete ridges (H and E stain, ×40)DDD and RAK are rare disorders which are not associated with the risk of mortality. Multiple therapies from topical hydroquinone to modalities such as laser have been tried, but the low efficacy and adverse effects of treatment sum to social anxiety and discomfort resulting in poor quality of life.[6] DDD and RAK are both uncommon hyperpigmentary genodermatoses which affect flexures and extremities, respectively. Therefore we are documenting these distinctive cases of DDD with overlapping features of RAK in three generations of a family. These three cases are also being presented to stress the existence of DDD phenotype in Indian population. Literature search revealed a few cases presenting with features of both DDD and RAK.[5,7-9] Recent genetic studies done to investigate this overlap revealed that DDD occurred due to a defect in KRT5, POFUT1 and POGLUT1 genes and RAK was due to ADAM10 gene.[10] The polygenic nature of DDD supports the possibility of RAK genes being involved in the same clinical spectrum.[5] This case further connects the hypothesis that overlaps between DDD and RAK might be a single complex disease showing its different facets. 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.