Case report
Dyschromatosis universalis hereditaria: a case report Shiva Kumar, MD, Okade Rajendra, MD, and Harish Prasad, MD
Department Of Dermatology, Venereology and Leprosy, Sri Devaraj Urs Medical College, Kolar, Karnataka, India Correspondence Shiva Kumar, MD Department of Dermatology Venereology and Leprosy Sri Devaraj Urs Medical College No. 66, 11th cross Indiranagar 1st stage Bangalore 560038 India E-mail: [email protected] Conflicts of interest: None.
342
A 25-year-old man, born of non-consanguineous parents, presented with asymptomatic pigmented macules, which started at 12 years of age, over the trunk and progressively involving the whole body, palms, soles, and oral cavity. In due course, hypopigmented macules appeared within the hyperpigmented skin, nails became dystrophic, skin markings over hypopigmented macules decreased, and dermatoglyphics over tips of all fingers disappeared. He also had hyperhidrosis and increased lacrimation. There was no history of any preceding dermatoses, drug intake, systemic illness, or exposure to chemicals. Developmental milestones were normal, and family history was unremarkable. Cutaneous examination revealed symmetrically distributed reticulated, hyper- and hypopigmented macules over the whole body, sparing the face (Fig. 1). Hypopigmented macules showed minimal atrophy with absence of skin markings. There was no erythema or telangiectasia. Palms and soles showed hyperpigmentation interspersed with depigmented macules (Fig. 2). All the fingertips and hypopigmented macules showed absence of dermatoglyphics (Fig. 3). Nails were dystrophic with a few showing pterygium formation. Buccal mucosa, palatal mucosa, and tongue showed leukokeratosis (Fig. 4). Hair was normal over the scalp with canities over the beard area. Teeth and other mucosa were normal. Other systems were normal clinically. International Journal of Dermatology 2014, 46, 342–345
Histopathology of the skin showed varying degrees of basal layer pigmentation and pigmentary incontinence. Histopathology from oral mucosa showed focal dyskeratotic changes. Routine hemogram, biochemistry tests,
Figure 1 Generalized, reticulated, hyper- and hypopigmented macules over body ª 2013 The International Society of Dermatology
Kumar et al.
Dyschromatosis universalis hereditaria
Case report
serum electrolytes, liver function tests, renal function tests, and urine and stool examination were all within normal limits. Ultrasonogram of the abdomen was normal. Discussion
Figure 2 Hyper- and hypopigmented macules over the sole with loss of dermatoglyphics over hypopigmented macules
Figure 3 Total loss of dermatoglyphics over fingertips
Figure 4 Oral leukokeratosis involving hard palate and
tongue ª 2013 The International Society of Dermatology
Reticulate pigmentary dermatoses consist of a heterogeneous group of rare disorders characterized by hyperpigmented macules coalescing in a reticular pattern, interspersed with hypopigmented macules.1 The differential diagnoses of generalized reticulate pigmentary dermatoses are dyschromatosis universalis hereditaria (DUH), dyskeratosis congenita, dermatopathia pigmentosa reticularis, and Naegeli–Franceschetti–Jadassohn syndrome (Table 1) 1. Dyschromatosis universalis hereditaria, first described in 1929 by Toyamo,2 is a rare, clinically heterogeneous genodermatosis characterized by hyper- and hypopigmented macules forming a reticulate pattern.1 The exact pathogenesis of DUH is unknown. A variable autosomal inheritance has been described, and a few sporadic cases have also been reported.3,4 The age of onset of lesions is usually in the first few months of life; however, sporadic cases can manifest at a later date as described in our case. DUH may be associated with abnormalities of hair, teeth, nails, and various other systems,3,5 high tone deafness,6 small stature,6 and ocular albinism.7 The essential features of dyskeratosis congenita are atrophy, telangiectasia, and pigmentation of skin (poikiloderma), nail dystrophy, and oral leukoplakia.8 Bone marrow failure and malignancy9 develop in the second and third decades. Our case had no poikiloderma, bone marrow involvement, or signs of malignancy. Dermatopathia pigmentosa reticularis features a clinical triad of reticulate hyperpigmentation, non-scarring alopecia, and onychodystrophy.8 Other associations include adermatoglyphia,10 hypohidrosis11 or hyperhidrosis,10 palmoplantar hyperkeratosis, and non-scarring blisters on the dorsum of the hands and feet.11 Our case had no alopecia, palmoplantar hyperkeratosis, or blistering and had absence of dermatoglyphics only over fingertips. Naegeli–Franceschetti–Jadassohn syndrome is a form of ectodermal dysplasia affecting sweat glands, nails, teeth, and skin, characterized by complete absence of dermatoglyphics, reticulate hyperpigmentation that disappears with age,12 palmoplantar keratoderma, decreased sweating, enamel defects, dental anomalies, skin blistering, and nail dystrophy.13 Our case had progressive hypo- and hyperpigmentation, partial loss of dermatoglyphics, hyperhidrosis, and no keratoderma or dental enamel anomalies. Cutaneous dyschromias with overlapping of various clinical features make diverse differential diagnoses (Table 1). Our case showed features typical of DUH International Journal of Dermatology 2014, 46, 342–345
343
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Case report
Dyschromatosis universalis hereditaria
Kumar et al.
Table 1 Showing comparison of clinical features of all reticulated pigmentary disorders and our case Clinical features
DUH
DKC
DPR
NFJS
Our case
Pigmentation
Reticulated, welldemarcated and irregular brown macules admixed with various sized hypopigmented macules1
Reticulate pigmentation with atrophy and telangiectasia8 (poikiloderma)
Reticulate pigmentation8
Brown reticulate pigmentation, which decreases after puberty12
Generalized reticulate hypo- and hyperpigmentation
Hair
Abnormalities reported3,5
Normal
Non-scarring alopecia8
Alopecia reported12
Normal
Nails
Nail dystrophy3,5
Nail dystrophy with failure of the nails to form a nail plate8
Nail dystrophy8
Nail dystrophy Brittle fingernails, Nail dystrophy12
Dental anomalies
Enamel defects3,5
Normal
Normal
Enamel defects12
Normal
Oral mucosa
Pigmentation of oral mucosa and tongue13
Leukokeratosis of the oral mucosa8
Normal
Normal
Leukokeratosis involving tongue, buccal mucosa, hard and soft palate
Palms and soles
Pigmentation reported
Normal
Pigmentation
Palmoplantar keratoderma, punctate keratosis
Hypo- and hyperpigmentation
Dermatoglyphics
Normal
Normal
Adermatoglyphia10
Complete absence12
Absent over fingertips and over hypopigmented areas
Sweating
Normal
Normal
Hypo- or hyperhidrosis
Decreased sweating12
Hyperhidrosis
Other associations
High tone deafness,
Skin blistering, growth retardation12
None
Bone marrow failure,
Small stature,6ocular albinism7
Malignancy9
Non-scarring blisters Over dorsa of hand and feet11, pigmentation of optic fundus
DKC, dyskeratosis congenita; DPR, dermatopathia pigmentosa reticularis; DUH, dyschromatosis universalis heriditaria; NFJS, Naegeli–Franceschetti–Jadassohn syndrome.
associated with oral leukokeratosis, involvement of palms and soles, absence of dermatoglyphics over fingertips, and hypopigmented macules, hyperhidrosis, and onychodystrophy encompassing features of all other reticulate pigmentary dermatoses. Despite its rarity, DUH assumes significance as several rare associations are reported.14 Our patient interestingly had oral leukokeratosis and absence of dermatoglyphics over fingertips, not reported to date with classical dyschromia of DUH. References 1 Griffiths WAD. Reticulate pigmentary disorders – a review. Clin Exp Dermatol 1984; 9: 439–450.
International Journal of Dermatology 2014, 46, 342–345
2 Toyama J. Dyschromatosis symmetrica hereditaria. Jap J Dermatol 1929; 29: 95–96. 3 Hawsawi KA, Aboud KA, Ramesh V, Aboud DA. Dyschromatosis universalis hereditaria: report of a case and review of the literature. Pediatr Dermatol 2002; 19: 523–526. 4 Gharpuray MB, Tolat SN, Patwardhan SP. Dyschromatosis: its occurrence in two Indian families with unusual feature. Int J Dermatol 1994; 33: 391–392. 5 Sethuraman G, Thappa DM, Vijaikumar M, et al. Dyschromatosis universalis hereditaria: a unique disorder. Pediatr Dermatol 2000; 17: 70–72. 6 Rycroft RJG, Calnan CD, Wells RS. Universal dyschromatosis, small stature and high tone deafness. Clin Exp Dermatol 1977; 2: 45–48.
ª 2013 The International Society of Dermatology
Kumar et al.
7 Schnur RE, Heymann WR. Reticulate hyperpigmentation. Semin Cutan Med Surg 1997; 16: 72–80. 8 Heimer WL, Brauner G, James WD. Dermatopathia pigmentosa reticularis: a report of a family demonstrating autosomal dominant inheritance. J Am Acad Dermatol 1992; 26: 298–301. 9 Baykal C, Kavak A, Gülcan P, Buyukbabani N. Dyskeratosis congenita associated with three malignancies. J Eur Acad Dermatol Venereol 2003; 17: 216–218. 10 Maso MJ, Schwartz RA, Lambert WC. Dermatopathia pigmentosa reticularis. Arch Dermatol 1990; 126: 935–939. 11 Gahlen W. Dermatopathia pigmentosa reticularis hypohidrotica et atrophica. Dermatol Wochenschr 1964; 150: 193–198.
ª 2013 The International Society of Dermatology
Dyschromatosis universalis hereditaria
Case report
12 Sparrow GP, Sammam PD, Wells RS. Hyperpigmentation and hypohidrosis (the Naegeli-Francescetti-Jadassohn syndrome): report of a family and review of literature. Clin Exp Dermatol 1976; 1: 127–140. 13 Lugassy J, Itin P, Ishida-Yamamoto A, et al. NaegeliFranceschetti-Jadassohn syndrome and dermatopathia pigmentosa reticularis: two allelic ectodermal dysplasias caused by dominant mutations in KRT14. Am J Hum Genet 2006; 79: 724–730. 14 Binitha MP, Thomas D, Asha LK. Tuberous sclerosis complex associated with dyschromatosis universalis hereditaria. Indian J Dermatol Venereol Leprol 2006; 72: 300–302.
International Journal of Dermatology 2014, 46, 342–345
345
Dyschromatosis universalis hereditaria: a case report Shiva Kumar, MD, Okade Rajendra, MD, and Harish Prasad, MD
Department Of Dermatology, Venereology and Leprosy, Sri Devaraj Urs Medical College, Kolar, Karnataka, India Correspondence Shiva Kumar, MD Department of Dermatology Venereology and Leprosy Sri Devaraj Urs Medical College No. 66, 11th cross Indiranagar 1st stage Bangalore 560038 India E-mail: [email protected] Conflicts of interest: None.
342
A 25-year-old man, born of non-consanguineous parents, presented with asymptomatic pigmented macules, which started at 12 years of age, over the trunk and progressively involving the whole body, palms, soles, and oral cavity. In due course, hypopigmented macules appeared within the hyperpigmented skin, nails became dystrophic, skin markings over hypopigmented macules decreased, and dermatoglyphics over tips of all fingers disappeared. He also had hyperhidrosis and increased lacrimation. There was no history of any preceding dermatoses, drug intake, systemic illness, or exposure to chemicals. Developmental milestones were normal, and family history was unremarkable. Cutaneous examination revealed symmetrically distributed reticulated, hyper- and hypopigmented macules over the whole body, sparing the face (Fig. 1). Hypopigmented macules showed minimal atrophy with absence of skin markings. There was no erythema or telangiectasia. Palms and soles showed hyperpigmentation interspersed with depigmented macules (Fig. 2). All the fingertips and hypopigmented macules showed absence of dermatoglyphics (Fig. 3). Nails were dystrophic with a few showing pterygium formation. Buccal mucosa, palatal mucosa, and tongue showed leukokeratosis (Fig. 4). Hair was normal over the scalp with canities over the beard area. Teeth and other mucosa were normal. Other systems were normal clinically. International Journal of Dermatology 2014, 46, 342–345
Histopathology of the skin showed varying degrees of basal layer pigmentation and pigmentary incontinence. Histopathology from oral mucosa showed focal dyskeratotic changes. Routine hemogram, biochemistry tests,
Figure 1 Generalized, reticulated, hyper- and hypopigmented macules over body ª 2013 The International Society of Dermatology
Kumar et al.
Dyschromatosis universalis hereditaria
Case report
serum electrolytes, liver function tests, renal function tests, and urine and stool examination were all within normal limits. Ultrasonogram of the abdomen was normal. Discussion
Figure 2 Hyper- and hypopigmented macules over the sole with loss of dermatoglyphics over hypopigmented macules
Figure 3 Total loss of dermatoglyphics over fingertips
Figure 4 Oral leukokeratosis involving hard palate and
tongue ª 2013 The International Society of Dermatology
Reticulate pigmentary dermatoses consist of a heterogeneous group of rare disorders characterized by hyperpigmented macules coalescing in a reticular pattern, interspersed with hypopigmented macules.1 The differential diagnoses of generalized reticulate pigmentary dermatoses are dyschromatosis universalis hereditaria (DUH), dyskeratosis congenita, dermatopathia pigmentosa reticularis, and Naegeli–Franceschetti–Jadassohn syndrome (Table 1) 1. Dyschromatosis universalis hereditaria, first described in 1929 by Toyamo,2 is a rare, clinically heterogeneous genodermatosis characterized by hyper- and hypopigmented macules forming a reticulate pattern.1 The exact pathogenesis of DUH is unknown. A variable autosomal inheritance has been described, and a few sporadic cases have also been reported.3,4 The age of onset of lesions is usually in the first few months of life; however, sporadic cases can manifest at a later date as described in our case. DUH may be associated with abnormalities of hair, teeth, nails, and various other systems,3,5 high tone deafness,6 small stature,6 and ocular albinism.7 The essential features of dyskeratosis congenita are atrophy, telangiectasia, and pigmentation of skin (poikiloderma), nail dystrophy, and oral leukoplakia.8 Bone marrow failure and malignancy9 develop in the second and third decades. Our case had no poikiloderma, bone marrow involvement, or signs of malignancy. Dermatopathia pigmentosa reticularis features a clinical triad of reticulate hyperpigmentation, non-scarring alopecia, and onychodystrophy.8 Other associations include adermatoglyphia,10 hypohidrosis11 or hyperhidrosis,10 palmoplantar hyperkeratosis, and non-scarring blisters on the dorsum of the hands and feet.11 Our case had no alopecia, palmoplantar hyperkeratosis, or blistering and had absence of dermatoglyphics only over fingertips. Naegeli–Franceschetti–Jadassohn syndrome is a form of ectodermal dysplasia affecting sweat glands, nails, teeth, and skin, characterized by complete absence of dermatoglyphics, reticulate hyperpigmentation that disappears with age,12 palmoplantar keratoderma, decreased sweating, enamel defects, dental anomalies, skin blistering, and nail dystrophy.13 Our case had progressive hypo- and hyperpigmentation, partial loss of dermatoglyphics, hyperhidrosis, and no keratoderma or dental enamel anomalies. Cutaneous dyschromias with overlapping of various clinical features make diverse differential diagnoses (Table 1). Our case showed features typical of DUH International Journal of Dermatology 2014, 46, 342–345
343
344
Case report
Dyschromatosis universalis hereditaria
Kumar et al.
Table 1 Showing comparison of clinical features of all reticulated pigmentary disorders and our case Clinical features
DUH
DKC
DPR
NFJS
Our case
Pigmentation
Reticulated, welldemarcated and irregular brown macules admixed with various sized hypopigmented macules1
Reticulate pigmentation with atrophy and telangiectasia8 (poikiloderma)
Reticulate pigmentation8
Brown reticulate pigmentation, which decreases after puberty12
Generalized reticulate hypo- and hyperpigmentation
Hair
Abnormalities reported3,5
Normal
Non-scarring alopecia8
Alopecia reported12
Normal
Nails
Nail dystrophy3,5
Nail dystrophy with failure of the nails to form a nail plate8
Nail dystrophy8
Nail dystrophy Brittle fingernails, Nail dystrophy12
Dental anomalies
Enamel defects3,5
Normal
Normal
Enamel defects12
Normal
Oral mucosa
Pigmentation of oral mucosa and tongue13
Leukokeratosis of the oral mucosa8
Normal
Normal
Leukokeratosis involving tongue, buccal mucosa, hard and soft palate
Palms and soles
Pigmentation reported
Normal
Pigmentation
Palmoplantar keratoderma, punctate keratosis
Hypo- and hyperpigmentation
Dermatoglyphics
Normal
Normal
Adermatoglyphia10
Complete absence12
Absent over fingertips and over hypopigmented areas
Sweating
Normal
Normal
Hypo- or hyperhidrosis
Decreased sweating12
Hyperhidrosis
Other associations
High tone deafness,
Skin blistering, growth retardation12
None
Bone marrow failure,
Small stature,6ocular albinism7
Malignancy9
Non-scarring blisters Over dorsa of hand and feet11, pigmentation of optic fundus
DKC, dyskeratosis congenita; DPR, dermatopathia pigmentosa reticularis; DUH, dyschromatosis universalis heriditaria; NFJS, Naegeli–Franceschetti–Jadassohn syndrome.
associated with oral leukokeratosis, involvement of palms and soles, absence of dermatoglyphics over fingertips, and hypopigmented macules, hyperhidrosis, and onychodystrophy encompassing features of all other reticulate pigmentary dermatoses. Despite its rarity, DUH assumes significance as several rare associations are reported.14 Our patient interestingly had oral leukokeratosis and absence of dermatoglyphics over fingertips, not reported to date with classical dyschromia of DUH. References 1 Griffiths WAD. Reticulate pigmentary disorders – a review. Clin Exp Dermatol 1984; 9: 439–450.
International Journal of Dermatology 2014, 46, 342–345
2 Toyama J. Dyschromatosis symmetrica hereditaria. Jap J Dermatol 1929; 29: 95–96. 3 Hawsawi KA, Aboud KA, Ramesh V, Aboud DA. Dyschromatosis universalis hereditaria: report of a case and review of the literature. Pediatr Dermatol 2002; 19: 523–526. 4 Gharpuray MB, Tolat SN, Patwardhan SP. Dyschromatosis: its occurrence in two Indian families with unusual feature. Int J Dermatol 1994; 33: 391–392. 5 Sethuraman G, Thappa DM, Vijaikumar M, et al. Dyschromatosis universalis hereditaria: a unique disorder. Pediatr Dermatol 2000; 17: 70–72. 6 Rycroft RJG, Calnan CD, Wells RS. Universal dyschromatosis, small stature and high tone deafness. Clin Exp Dermatol 1977; 2: 45–48.
ª 2013 The International Society of Dermatology
Kumar et al.
7 Schnur RE, Heymann WR. Reticulate hyperpigmentation. Semin Cutan Med Surg 1997; 16: 72–80. 8 Heimer WL, Brauner G, James WD. Dermatopathia pigmentosa reticularis: a report of a family demonstrating autosomal dominant inheritance. J Am Acad Dermatol 1992; 26: 298–301. 9 Baykal C, Kavak A, Gülcan P, Buyukbabani N. Dyskeratosis congenita associated with three malignancies. J Eur Acad Dermatol Venereol 2003; 17: 216–218. 10 Maso MJ, Schwartz RA, Lambert WC. Dermatopathia pigmentosa reticularis. Arch Dermatol 1990; 126: 935–939. 11 Gahlen W. Dermatopathia pigmentosa reticularis hypohidrotica et atrophica. Dermatol Wochenschr 1964; 150: 193–198.
ª 2013 The International Society of Dermatology
Dyschromatosis universalis hereditaria
Case report
12 Sparrow GP, Sammam PD, Wells RS. Hyperpigmentation and hypohidrosis (the Naegeli-Francescetti-Jadassohn syndrome): report of a family and review of literature. Clin Exp Dermatol 1976; 1: 127–140. 13 Lugassy J, Itin P, Ishida-Yamamoto A, et al. NaegeliFranceschetti-Jadassohn syndrome and dermatopathia pigmentosa reticularis: two allelic ectodermal dysplasias caused by dominant mutations in KRT14. Am J Hum Genet 2006; 79: 724–730. 14 Binitha MP, Thomas D, Asha LK. Tuberous sclerosis complex associated with dyschromatosis universalis hereditaria. Indian J Dermatol Venereol Leprol 2006; 72: 300–302.
International Journal of Dermatology 2014, 46, 342–345
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