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E–CASE REPORT
Year : 2013  |  Volume : 58  |  Issue : 3  |  Page : 244
Ichthyosis associated with rickets in two Indian children


Department of Dermatology, Seth G.S. Medical College and K.E.M. Hospital, Mumbai, Maharashtra, India

Date of Web Publication20-Apr-2013

Correspondence Address:
Bhavana Doshi
C/O Uday Khopkar, Department of Dermatology, Seth G.S. Medical College and K.E.M. Hospital, Parel, Mumbai, Maharashtra
India
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Source of Support: None, Conflict of Interest: None


DOI: 10.4103/0019-5154.110877

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   Abstract 

We wish to report two cases of rickets due to vitamin D deficiency secondary to underlying ichthyotic skin disorder. The first case is of an 8-year-old male with history of multiple fluid-filled lesions over the body that would rupture to heal with thickening and scaling of skin, suggestive of epidermolytic hyperkeratosis, and the second is of a 14-year-old female with thick, large, quadrilateral scales over the extremities and back clinically consistent with lamellar ichthyosis. Both showed improvement with parenteral vitamin D3 and oral calcium supplements in addition to topical emollients.


Keywords: Epidermolytic hyperkeratosis, lamellar ichthyosis, rickets


How to cite this article:
Kothari D, Doshi B, Garg G, Khopkar US. Ichthyosis associated with rickets in two Indian children. Indian J Dermatol 2013;58:244

How to cite this URL:
Kothari D, Doshi B, Garg G, Khopkar US. Ichthyosis associated with rickets in two Indian children. Indian J Dermatol [serial online] 2013 [cited 2019 Jan 24];58:244. Available from: http://www.e-ijd.org/text.asp?2013/58/3/244/110877

What was known? 1. Rickets is a constitutional disease with vitamin D deficiency being the most common cause of rickets in infancy and dietary calcium deficiency as an important cause of nutritional rickets in young children in India. 2. Defective synthesis of vitamin D in the diseased epidermis and excessive loss of calcium through skin in turn puts the children with ichthyosis at increased risk of rickets



   Introduction Top


Rickets is a vitamin D deficiency disorder caused by failure of the osteoid to calcify in the growing bones of children and adolescents. Type 1 rickets is vitamin D dependent, whereas type 2 rickets is vitamin D non-dependent. Occurrence of rickets in patients of ichthyosis is an uncommon but preventable complication. Dark-skinned children with ichthyosis are prone to develop rickets since poor penetration of sun rays leads to reduced synthesis of vitamin D for the given amount of sun exposure. [1]


   Case Reports Top


Case 1

An 8-year-old boy born of non-consanguineous marriage was brought with thick, dark skin lesions all over the body since 1.5 months of age and inability to walk since the past 5 months. The mother gave history of multiple fluid-filled lesions over the bilateral thighs at birth, which ruptured to heal with thickening and scaling of skin. This process continued to occur all over the body till the age of 7 years. There was history of fracture of the left forearm, followed by that of the right forearm 1 year back, causing deformities of both upper extremities. There was no history of similar complaints in other family members.

Cutaneous examination revealed generalized hyperkeratotic, verrucous and velvety plaques all over the body with predominant involvement of the axillae, wrists, buttocks and popliteal fossae [Figure 1]. There was relative sparing of the face and complete sparing of the palms and soles. Mucosae, hair, teeth and nails were normal. Bony examination revealed mild left-sided scoliosis and deformity of the left hand. There was a bowline deformity of the right forearm and bowing of both the legs.
Figure 1: Generalized hyperkeratotic verrucous plaques predominantly over the bilateral wrist and knee in the first case

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Blood investigations including complete hemogram, renal function tests and liver function tests inclusive of serum proteins were within normal limits. Serum calcium (7.2 mg/dL) and 25-OH vitamin D3 (11.3 ng/mL) levels were low, whereas serum alkaline phosphatase level (1396.80 IU/L) was markedly high. Ultrasonography of the abdomen and pelvis was normal. X-ray of the limbs showed marked cupping and fraying of the distal metaphyses with coarse tubercular pattern and osteopenia. There was bilateral pseudo-fracture of the ulna, radius and tibia along with malunion of the radius, ulna and bowing of tibia [Figure 2]. Skin biopsy showed features of epidermolytic hyperkeratosis [Figure 3].
Figure 2: X-ray of upper limb showed marked cupping and fraying of distal metaphyses and tibia along with malunion of radius and ulna and bowing of tibia

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Figure 3: Skin biopsy from the hyperkeratotic plaque over the arm shows lamellar orthokeratoses and epidermolytic hyperkeratosis on H and E, stain (×20)

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On the basis of clinicopathologic correlation, the diagnosis of epidermolytic hyperkeratosis associated with active nutritional rickets was reached.

Case 2

A 14-year-old girl born of non-consanguineous marriage presented with thick, dark skin lesions since birth and pain in both knee joints since the past 4 years. She also had deformities of both the knees with difficulty in getting up from squatting position since the last 3 years. A history of collodion membrane at birth, followed by its spontaneous shedding a few days later, was elicited. This was followed by appearance of thick large scales all over the body, which was associated with periodic shedding. There was history of similar skin findings in the younger 11-year-old male sibling without any skeletal signs and symptoms. The mother also gave a history of avoidance of going out of the house during daytime due to social embarrassment and heat intolerance.

On cutaneous examination, there was diffuse thickening and hyperpigmentation of the skin with thick, large, quadrilateral scales that were free at the edges and adherent in the center. The lesions were distributed over the extremities and the back [Figure 4]. Hyperkeratosis of palms and soles was seen. Hair, teeth, nails and mucosa were un-involved. Bilateral genu valgum [Figure 4], wrist widening, double malleoli and rachitic rosary were noted.
Figure 4: Thickening and hyperpigmentation of the skin with few quadrilateral scales over the dorsa of the hands and legs with genu valgum in the second case

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Blood investigations including complete hemogram, renal function tests and liver function tests, inclusive of serum proteins, were within normal limits. Serum calcium (7.79 mg/dL) and 25-OH vitamin D3 were low (12.25 ng/mL), whereas serum alkaline phosphatase (3090.00 IU/L) and parathyroid hormone levels (530.0 pg/mL) were significantly raised. X-rays of the limbs showed marked cupping and fraying of distal metaphyses with coarse trabecular pattern, osteopenia, pseudo-fracture of bilateral ulna, radius and tibia along with bowing of both the tibia [Figure 5]. Skin biopsy showed compact ortho-hyperkeratosis with focal parakeratosis, normal granular layer, papillomatosis and mild perivascular lymphocytic infiltrate in papillary dermis [Figure 6].
Figure 5: X-ray of the lower limb showed coarse tubercular pattern, pseudofracture, osteopenia and bowing of tibia

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Figure 6: Skin biopsy from the scaly plaque on the shin shows compact ortho-hyperkeratosis with focal parakeratosis, normal granular layer and mild acanthosis on H and E, stain (×10)

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On the basis of clinical features and investigations, a diagnosis of lamellar ichthyosis with active nutritional rickets was reached in the second case.

Rickets was treated in both these cases with parenteral vitamin D3, 6 lac IU single dose and 1500 mg of oral calcium daily for 1 month, showing gradual clinical improvement like reduction in joint pain and performance of activities of daily living. Serum calcium (8.8 mg/dL) and alkaline phosphatase (564 IU/L) improved over a period of 2 months in the first case, whereas serum calcium (8.43 mg/dL) and alkaline phosphatase (1480 IU/L) improved within 1 month in the second. Both the cases are currently orally taking 400 IU of vitamin D3 along with 500 mg of calcium salt daily.

For the treatment of ichthyosis, the first case was started on capsule isotretinoin 10 mg daily for 6 months, followed by 15 mg daily for 4 months for the underlying skin condition. Topically, 3% salicylic acid, white soft paraffin and liquid paraffin were applied daily.

In view of thin scales, the second patient was treated with only topical application of liquid paraffin and white soft paraffin with evidence of partial improvement in skin condition over the next 2 months.


   Discussion Top


Rickets is a constitutional disease of infancy and childhood, characterized by impairment of general health, arrested growth and abnormalities of the developing bone. While vitamin D deficiency is the most common cause of rickets in infancy, dietary calcium deficiency is an important cause of nutritional rickets in young children in India. [2],[3]

Rickets has been previously reported to occur in association with lamellar ichthyosis, [4] epidermolytic hyperkeratosis, [5] X-linked ichthyosis, [6] ichthyosis vulgaris [6] and non-bullous ichthyosiform erythroderma. [6] In a series of 41 Sudanese children with nutritional rickets, three were found to have ichthyosis. [7]

Epidermis is rich in 7-dehydrocholesterol, which is present in the cell membrane of keratinocytes. On sun exposure, 7-dehydrocholesterol is converted to cholecalciferol (vitamin D3) in keratinocytes. Cholecalciferol undergoes hydroxylation in two steps, first in the liver to produce calcidiol and then in the kidney to produce calcitriol, which is the active product of vitamin D3. This conversion requires 25-hydroxyvitamin D 1α hydroxylase, which is highly regulated by parathyroid hormone. [8] Monocytes and keratinocytes are also capable of converting calcidiol to calcitriol. The keratinocytes are the only cells in the body having the entire pathway of vitamin D synthesis. However, its contribution toward total body calcitriol levels is minimal. Calcitriol increases the concentration of calcium and phosphorus in the extracellular fluid and maintains calcification of bones, primarily at the growing metaphysical end and later throughout all osteoids of the skeleton.

In hypocalcemic stage, serum parathyroid hormone (PTH) secretion increases, which in turn increases the renal phosphorus loss leading to decreased deposition of calcium in the bones. Due to defective synthesis of vitamin D in the diseased epidermis and excessive loss of calcium through skin, stimulation of PTH secretion occurs, which in turn puts the children with ichthyosis at increased risk of rickets. [9]

In a country like ours, where lack of fortification of dairy products and food fats with vitamin D contributes to nutritional vitamin D deficiency, [4] a low calcium and high phytate diet along with reduced vitamin D synthesis in dark-complexioned skin further increases the risk of occurrence of rickets.

The contributing factors proposed for development of rickets in underlying ichthyotic skin disorders are: (i) increased keratinocyte proliferation resulting in poor penetration of sunlight, [10] (ii) defective vitamin D synthesis in the diseased epidermis causing vitamin D-dependent rickets, [11] (iii) excessive loss of calcium through skin shedding, [4] (iv) limited sun exposure [10] due to heat intolerance as well as due to social constraints resulting from cosmetic reasons [7] and (v) use of systemic retinoids, which reduces the calcium absorption from the gut. A table differentiating ichthyosis-associated rickets with nutritional rickets has been given below [Table 1].
Table 1: Differences between ichthyosis-associated rickets and nutritional rickets


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Hence, the occurrence of rickets in our cases can be attributed to both nutritional vitamin D deficiency and the underlying ichthyotic disorders.

Epidermolytic hyperkeratosis and lamellar ichthyosis are life-long conditions and the most refractory forms of ichthyosis. All such patients should be considered for lifelong "rickets prophylaxis" with vitamin D supplements periodically along with counseling, pertaining to adequate exposure to sunlight.

Treatment of skin manifestations of EHK and LI is not usually very satisfactory, and includes keratolytics, antiseptic washes, topical calcipotriol, alfa hydroxy acids and oral retinoids, all of which lead to partial improvement. However, treating the underlying ichthyotic condition is important as it may probably contribute in restoring back the normal vitamin D metabolism.[12]

 
   References Top

1.Norman AW. Sunlight, season, skin pigmentation, vitamin D, and 25-hydroxyvitamin D: Integral components of the vitamin D endocrine system. Am J Clin Nutr 1998;67:1108-10.  Back to cited text no. 1
    
2.Balasubramanian K, Rajeswari J, Gulab, Govil YC, Agarwal AK, Kumar A, et al. Varying role of vitamin D deficiency in the etiology of rickets in young children vs. adolescents in northern India. J Trop Pediatr 2003;49:201-6.  Back to cited text no. 2
    
3.Pettifor JM. Nutritional rickets: Deficiency of vitamin D, calcium, or both? Am J Clin Nutr 2004;80:1725-9.  Back to cited text no. 3
    
4.Sethuraman G, Khaitan B, Dash S, Chandramohan K, Sharma V, Kabra M, et al. Ichthyosiform erythroderma with rickets: Report of five cases. Br J Dermatol 2008;158:603-6.  Back to cited text no. 4
    
5.Nayak S, Behera SK, Acharjya B, Sahu A, Mishra D. Epidermolytic hyperkeratosis with rickets. Indian J Dermatol Venereol Leprol 2006;72:139-42.  Back to cited text no. 5
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6.Milstone LM, Bale SJ, Insogna KL. Secondary hyperparathyroidism in patients with ichthyosis is not caused by vitamin D deficiency or ingestion of retinoids. Arch Dermatol 1993;129:648.  Back to cited text no. 6
    
7.El Hag Al, Karrar ZA. Nutritional vitamin D deficiency rickets in Sudanese children. Ann Trop Pediatr 1995;15:69-76.  Back to cited text no. 7
    
8.Holick MF. Vitamin D Deficiency. N Engl J Med 2007;357:266-81.  Back to cited text no. 8
    
9.Milestone LM, Ellison AF, Insogna KL. Serum parathyroid hormone level is elevated in some patients with disorder of keratinization. Arch Dermatol 1992;128:926-30.  Back to cited text no. 9
    
10.Griffiths WAD, Judge MR, Liegh IM. Disorders of keratinization. In: Champion RH, Burton JL, Burns DA, Breathnach SM, editors. Rook's Textbook of Dermatology. 6 th ed. Oxford: Blackwell Science; 1998. p. 1483-588.  Back to cited text no. 10
    
11.Chouhan K, Sethuraman G, Gupta N, Sharma VK, Kabra M, Khaitan BK, et al. Vitamin D deficiency and rickets in children and adolescents with ichthyosiform erythroderma in type IV and V skin. Br J Dermatol 2012;166:608-15.  Back to cited text no. 11
    
12.Marwaha RK, Tandon N, Reddy D, Reddy HK, Aggarwal R, Singh R, et al. Vitamin D and bone mineral density status of healthy school children in northern India. Am J Clin Nutr 2005;82:477-82.  Back to cited text no. 12
    

What is new? 1. Lack of food fortification with vitamin D, along with reduced vitamin D synthesis in dark.complexioned skin further increases the risk of occurrence of rickets in children with ichthyosiform disorders in our country. 2. Children with ichthyosis may require life.long prophylaxis of calcium and vitamin D


    Figures

  [Figure 1], [Figure 2], [Figure 3], [Figure 4], [Figure 5], [Figure 6]
 
 
    Tables

  [Table 1]



 

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