Dyschromias: A Series of Five Interesting Cases from India.

Dyschromatosis is a pigmentary genodermatosis which presents with hyper and hypopigmented skin lesions giving a mottled appearance. It is a rare entity in India reported mainly in the East Asian population. Classically, two forms have been described; dyschromatosis universalis hereditaria (DUH) and dyschromatosis symmetrica hereditaria. Here we report four cases of DUH and one case of dyschromatosis symmetrica hereditaria from India.

What was known?

Dyschromatosis universalis hereditaria (DUH) and dyschromatosis symmetrica hereditaria (DSH) are reticulate pigmentary dermatoses which mainly have an autosomal dominant inheritance.

Epilepsy, short stature, deafness, Dowling-Degos disease, albinism, tuberous sclerosis, ocular abnormalities, photosensitivity, learning difficulties, mental retardation, insulin-dependent diabetes mellitus, and erythrocyte, platelet, and tryptophan metabolism abnormalities are the rarely reported associations of DUH.

Introduction

Dyschromatosis is a rare genodermatosis which is characterized by hyper and hypo pigmented macules of variable shape and size.[1] Both autosomal dominant and autosomal recessive forms have been reported.[2] These disorders are reported mainly from Japan. Only a few cases have been reported from other countries. Hence, we are reporting five cases from India.

Case Report

Case one was a 30-year-old male patient who presented with asymptomatic multiple hypopigmented, and hyperpigmented skin lesions all over the body [Figure 1a and b] since the age of 10 years. The initial lesions started in the chest and then spread to the entire body in 2 years. There was no history of photosensitivity or handling of any chemical or any history of drug intake. None of the family members was affected. The skin did not reveal atrophy or telangiectasia. His palms, soles, and mucous membranes were within normal limits. Hair and nails were normal. Systemic examination was normal. Skin biopsy from the hyperpigmented macules showed the increased melanin pigmentation [Figure 2a], and the hypopigmented macules showed a marked decrease in the epidermal basal melanin [Figure 2b]. Based on these findings, a diagnosis of dyschromatosis universalis hereditaria (DUH) was made.

Figure 1

(a and b) Case one with multiple hypopigmented and hyperpigmented macules all over the body

Figure 2

Photomicrograph depicting marked increase in the epidermal basal melanin from the hyperpigmented macules (a) and decrease in the epidermal basal melanin from the hypopigmented macules (b) of all the five cases (H and E, ×400)

Case two was a 22-year-old male presenting to our outpatient department with asymptomatic multiple hypo and hyperpigmented macules all over the body [Figure 3] since 12 years. There was no other significant positive clinical findings.

Figure 3

Case two with multiple hypopigmented and hyperpigmented macules all over the body

Case three was a 14-year-old boy who presented with similar lesions all over the body [Figure 4a and b] since the age of 2 years. His palms [Figure 5] and soles also showed similar mottled pigmentation. He was born to parents of second degree consanguinous marriage. He also had multiple verucca vulgaris over the left arm and dorsum of hands [Figure 4c]. He had recurrent upper respiratory tract infections and severe growth retardation and mental retardation. Peripheral blood smear showed a normocytic normochromic blood picture with leucopenia and eosinophilia.

Figure 4

Case three with similar reticulate pigmentation all over the body (a and b); broad nasal bridge, long philtrum (a) with verucca vulgaris on the dorsum of right hand (c)

Figure 5

Depicts case three and case four with palms showing similar mottled pigmentation

Case four was the 9-year-old sibling of the 14-year-old boy who revealed similar lesions all over the body [Figure 6] since 9 months of age. Similar lesions were seen in his palms [Figure 5] and soles also. He had recurrent pyodermas [Figure 6a] since birth. On examination, he had molluscum contagiosum lesions [Figure 6b] on the face. Both the siblings also had a broad nasal bridge, long philtrum, and high arched palate. The possibility of primary immunodeficiency was kept and baseline immunodeficiency workup was done. His serum immunoglobulin assay was normal and human immunodeficiency virus one and two tests (ELISA) were negative. Both the brothers had hypopigmented, and hyper pigmented macules of varying sizes all over the body. Histopathology showed similar features as that of the first case.

Figure 6

Case four with similar reticulate pigmentation all over the body, abscess over the forehead, molluscum contagiosum; broad nasal bridge, long philtrum

Based on these findings, a diagnosis of DUH was made in all the four cases. The other differential diagnosis in all these four cases included xeroderma pigmentosum, dyschromatosis symmetrica hereditaria, dyschromic amyloidosis, and disorders due to chemical exposure such as diphenylcyclopropenone, and monobenzyl ether of hydroquinone. Absence of photosensitivity, atrophy, telangiectasia, eye involvement and benign nature of the condition makes xeroderma pigmentosum unlikely. These lesions were differentiated from DSH in which the lesions occur in a more acral distribution. The disorder was also differentiated from dyschromic amyloidosis by the absence of predominant lesions in the sun exposed areas and absence of amyloid deposits in the papillary dermis.

Case five was a 21-year-old male who presented with asymptomatic multiple hypo and hyperpigmented skin lesions over the extremities [Figure 7] since the age of 1-year. There was no family history of similar lesions. His palms and soles were normal. There was no other significant positive history. Biopsy from the hypopigmented macules showed decreased melanin pigmentation whereas biopsy from the hyperpigmented macules showed increased focal melanin in the basal layer. Based on these clinical features, a diagnosis of dyschromatosis symmetrica hereditaria was made. Other possibilities such as DUH, and reticulate acropigmentation of Kitamura were included in the differentials. DUH was ruled out as it is characterized by more extensive lesions including the non acral/unexposed areas of the body. Further, the disease is differentiated from reticulate acropigmentation of Kitamura by the absence of atrophic macules, palmar pits or breaks in the epidermal ridge pattern.

Figure 7

Case five with similar lesions over the extremities

The features of all these five cases have been summarized in Table 1.

Table 1

Summarizes the clinical features of the five cases of dyschromias

Discussion

Reticulate pigmentary dermatoses (RPD) comprise a rare group of disorders, characterized by hyperpigmented and hypopigmented macules coalescing to form a reticular pattern.[3] RPDs are divided into two broad categories: Acral RPD and generalized RPD. The various acral RPD includes reticulate acropigmentation of Kitamura, acropigmentation of Dohi, acromelanosis heterochromia extremitarium, and dyschromatosis symmetrica hereditaria (DSH). The differential diagnoses of generalized RPD are DUH, dermatopathia pigmentoreticularis, Naegeli-Franceschetti-Jadassohn syndrome, and dyskeratosis congenita (DKC).[4]

Dyschromatosis is a spectrum of disease which includes DUH, dyschromatosis symmetrica hereditaria (DSH) or acropigmentation of Dohi and a segmental form called unilateral dermatomal pigmentary dermatosis.[5] Dyschromatosis symmetrica hereditaria was first described by Toyama in 1929.[6] DUH, a rare autosomal dominant genodermatosis was first described by Ichikawa and Hiraga in 1933.[7] DUH is characterized by the presence of both hyperpigmented and hypopigmented, small, irregular macules distributed symmetrically all over the body.[8] Most cases present early in life.[4] Late onset of the disease has been reported.[9] These cases usually do not progress or worsen as age advances, once well established.[10] The pigmented macules vary in size and depth of color.[10] Theses macules are usually smaller (1–5 mm), but larger macules measuring up to 15 cm have been reported.[9] The trunk and the extremities are commonly involved.[11] The face is generally not involved, and there is sparing of the palms, soles, and mucous membranes.[8]

Various systemic associations including small stature and high-tone deafness,[12] Dowling-Degos disease,[8] X-linked ocular albinism,[8] tuberous sclerosis[8] have been described. Many other associated conditions have been reported, such as ocular abnormalities, photosensitivity, learning difficulties, mental retardation, epilepsy, insulin-dependent diabetes mellitus, and erythrocyte, platelet and tryptophan metabolism abnormalities.[9] DUH is thought to occur secondary to the interference with the neural-melanocytic interaction in early embryonic life in those who are genetically susceptible.[10] The gene responsible for DUH has been mapped to 6q24.2-q25.2 (OMIM 127500). Because the exact biochemical basis of the gene defect is unknown, the diagnosis generally relies on the external phenotype.[8]

Here we report four cases of DUH. Two cases had a family history of similar complaints. One case was associated with mental and growth retardation, recurrent respiratory tract infection, verucca vulgaris; and his younger brother had recurrent pyoderma with molluscum contagiosum. Both the brothers had characteristic facies of high arched palate, broad nasal root, and long philtrum.

We also report one case of dyschromatosis symmetrica hereditaria in a 21-year-old male patient presenting with similar macules over the extremities. Patients with dyschromatosis symmetrica hereditaria (Reticulate acropigmentation of Dohi) present with hyperpigmented and hypopigmented macules on the face and the dorsal aspects of the extremities.[13] It was thought to occur secondary to mutations in RNA specific adenosine deaminase gene.[14] Skin lesions remain localized on extremities in nearly half of the patients and involve face and extremities in the remaining half.[15] Most cases of DSH are inherited as autosomal dominant, although an autosomal recessive variant of DHS has been reported.[16] Later, novel mutations in the ADRA1 were reported in Chinese families confirming that this gene is responsible for DSH in the different ethnic group.[1718] More recently, Suzuki et al. reported 16 novel mutations in the ADRA1 without identifying such mutations in patients with DUH.[19] In a recent ultra-structural skin investigation, Nuber et al. indicated that DUH is a disorder of melanosome synthesis rate or melanocyte activity and not a disorder of melanocyte number.[20]

Conclusion

Dyschromatosis is a benign condition which is usually not associated with systemic involvement which has to be differentiated from conditions like xeroderma pigmentosum, DKC. We report these cases because of their rare occurrence and characteristic facies of high arched palate, broad nasal root, and long philtrum; recurrent respiratory tract infections, verucca vulgaris, molluscum contagiosum, and pyodermas as an association of DUH has not been reported to the best of our knowledge.

Financial support and sponsorship

Nil.

Conflicts of interest

There are no conflicts of interest.

What is new?

DUH and DSH can present without a family history of similar complaints which has been rarely reported

DUH can be associated with characteristic facies of high arched palate, broad nasal root and long philtrum, recurrent respiratory tract infections, verucca vulgaris, molluscum contagiosum, and pyodermas.