|Year : 2015 | Volume
| Issue : 2 | Page : 99-101
Epidermolytic hyperkeratosis with Vitamin D deficiency rickets in a 5-year-old Indian girl
Amrita Roy1, Debalina Sarkar2, Pranab Kumar Dey3, Sumita Pal4
1 Department of Paediatrics, AMRI Hospitals, Salt Lake, Kolkata, West Bengal, India
2 Department of Paediatrics, Medical College, Calcutta National Medical College, Kolkata, West Bengal, India
3 Department of Paediatrics, Midnapore Medical College, Midnapore, West Bengal, India
4 Department of Paediatrics, Calcutta National Medical College, Kolkata, West Bengal, India
|Date of Web Publication||9-Apr-2015|
I3B, Shyam Square East, Kolkata - 700 003, West Bengal
Source of Support: None, Conflict of Interest: None
We report a 5-year-old child with hyperkeratotic lesions over upper and lower limbs, with bowing of legs and limping. It was proved to be epidermolytic hyperkeratosis (EHK) with nutritional rickets on the basis of clinical, biochemical, radiological and histopathological findings. Although many cases of lamellar ichthyosis and X-linked ichthyosis with rickets have been reported, the association of EHK with rickets is rare (the first such association being reported in 2004). Such association being rare demands careful follow-up for signs and symptoms of rickets so that treatment can be started early.
Keywords: Epidermolytic hyperkeratosis, rickets, Vitamin D deficiency
|How to cite this article:|
Roy A, Sarkar D, Dey PK, Pal S. Epidermolytic hyperkeratosis with Vitamin D deficiency rickets in a 5-year-old Indian girl. Indian J Paediatr Dermatol 2015;16:99-101
|How to cite this URL:|
Roy A, Sarkar D, Dey PK, Pal S. Epidermolytic hyperkeratosis with Vitamin D deficiency rickets in a 5-year-old Indian girl. Indian J Paediatr Dermatol [serial online] 2015 [cited 2020 Feb 18];16:99-101. Available from: http://www.ijpd.in/text.asp?2015/16/2/99/152134
| Introduction|| |
Epidermolytic hyperkeratosis (EHK), also known as bullous congenital icthyosiform erythroderma is an autosomal dominant disease with an estimated prevalence of 1 in 100,000-200,000 people. Association of rickets with EHK is very rare. Only seven reports in literature exist mentioning such association, although the association of rickets with other forms of ichthyosis is common.
| Case report|| |
A 5-year-old girl presented with dark, scaly, warty, hyperkeratotic plaques over both limbs that gradually progressed over 2 years. There was associated bowing of legs and limping gait for the past 1-year. She was born out of consanguineous marriage (first degree relative) as an appropriate for gestational age baby with 47 cm length. According to the mother, the baby was born bright red with few vesico-bullous lesions over the body. These lesions gradually increased over 1-year, being prominent at sites of friction where the skin underwent erosion, peeling and widespread denudation without scarring. Subsequently the bullae and erythroderma subsided but the skin became dry, thick, warty, scaly with recurrent skin infections. There was a history of recurrent episodes of wheeze associated lower respiratory tract infections since 6 months of age, none requiring hospitalization. She has two other elder siblings, but none of her family members have similar issues.
On examination, there was hyperkeratotic, scaly, warty, plaque like lesions over her extremities with relative sparing of the face, neck, palms and soles [Figure 1]. The lesions had nonhystrix brown scales. Mucosae, teeth and hair were normal. Along with this, the child had genu varum, anterior bowing of legs, limping gait and widening of the wrists. Examination of the chest, abdomen and central nervous system did not reveal any abnormality.
Laboratory examination revealed normal complete hemogram, peripheral blood smear examination, renal and liver function tests. Serum calcium was 7.8 mg/dl (normal 9-11 mg/dl), serum phosphorus was 3 mg/dl (normal 3.8-6.5 mg/dl) and serum alkaline phosphatase was 627 u/L (normal 145-200 u/L), serum parathormone was 63 pg/ml (1.0-5.2 pg/ml), 25-hydroxy-Vitamin D level was 4.2 ng/ml (8-38 ng/ml) and urinary calcium excretion was 10 mg/day (25-300 mg/day). Ultrasonography of the abdomen and pelvis did not reveal any abnormality. X-rays of the knee and wrist revealed marked splaying, fraying and cupping of the distal metaphyses and widening of the growth plate [Figure 2]. Hearing and vision assessment revealed no abnormality. Histopathological examination of skin biopsy showed marked acanthosis, hyperkeratosis and vacuolar degeneration of the upper epidermis with perivascular lymphoid infiltrate of dermis.
|Figure 2: X-ray wrist showing splaying, fraying and cupping of the distal metaphyses and widening of the growth plate|
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In view of the above findings, a diagnosis of EHK with nutritional rickets was made and the child was started on parenteral Vitamin D3 (6 lakhs IU, intramuscular) and oral calcium supplementation (500 mg twice daily) for 6 months. Regular sun exposure for at least 20 min/day was advised, and 10% urea in aqueous cream with white paraffin was advised for the skin lesions. Treatment with calcipotriene could not be done due to financial constraints. Follow-up after 3 months revealed marked improvement in the radiological findings, normal serum calcium (10 mg/dl), phosphorus (5 mg/dl), alkaline phosphatase (165 u/L), parathormone (4.2 pg/ml) and 25-hydroxy-Vitamin D3 (27 ng/ml) but minimal change in the skin condition.
| Discussion|| |
Epidermolytic hyperkeratosis is primarily a disorder of keratinization involving keratin 1 and/or 10  and is inherited in an autosomal dominant fashion. Spontaneous mutations are common. Around half of the patients have no family history but have new mutational events.  Estimated prevalence of the disease is around 1 in 100,000-200,000. Sporadic EHK due to postzygotic spontaneous mutation during embryogenesis can present in a mosaic pattern of skin involvement. EHK was first described in 1902 by Brocq to distinguish it from nonblistering congenital ichthyotic erythroderma.  The disease has been linked to gene clusters 12q and 17q.  Areas of hyperkeratosis alternating with normal skin are often distributed in streaks along Blaschko's lines. 
The characteristic histopathology of vacuolar degeneration of epidermis and associated hyperkeratosis are the hallmarks of the disease. The disease usually presents at birth with redness, blistering and peeling, gradually developing over time to evolve into hyperkeratosis with/without erythroderma.
In our patient, absence of palmar/plantar hyperkeratosis, generalized distribution of the lesion, lack of hystrix pattern of scaling and digital contracture along with typical histopathological findings lead us to the diagnosis of EHK [No palm sole involvement - (NPS) without hystrix scales (NPS type 2)].
In children with various forms of ichthyosis, rickets may develop due to defective synthesis of Vitamin D owing to diseased epidermis or loss of calcium through skin, leading to elevated parathormone levels and low Vitamin D3 levels as postulated by Milstone et al.  Although rickets have been described in association with lamellar ichthyosis and X-linked ichthyosis, very few case reports in literature exist correlating rickets with EHK; one such reported by Perosa et al. in 2004  and two such from India too. , In a study of 41 Sudanese children with rickets attributed to Vitamin D deficiency, 3 children were reported to have ichthyosis.  Factors associated may be poor penetration of sunlight owing to keratinocyte proliferation, increased cholesterol catabolism involving Vitamin D receptors, associated Vitamin D dependent rickets or less sun exposure. 
Because of the almost similar clinical features, EHK needs to be distinguished from two other very similar conditions: Ichthyosis bullosa of Siemens and ichthyosis hystrix of Curth and Macklin. In the former, very superficial epidermal fragility is present. In the latter, hyperkeratosis is widespread, patchy, thick, grey-brown, present especially over the extensor surfaces with absence of blistering. 
The importance in identifying this disorder lies in the fact that EHK appears to be extremely refractory to treatment and in the majority of the cases lifelong Vitamin D and calcium supplementation may be necessary. Although the rachitic features improved with supplementation of Vitamin D and calcium, there was no improvement in the skin condition. This finding was similar to that observed by Thacher et al. 
Therefore in severe ichthyosis, evaluation should be done for rickets, especially in developing countries where there is a background of Vitamin D deficiency to detect it at the earliest as such patients often need lifelong supplementation with Vitamin D and calcium.
| Acknowledgment|| |
Department of Pathology and Biochemistry, Medical College and Hospitals, Kolkata.
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[Figure 1], [Figure 2]