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E-IJD-CASE REPORT
Year : 2014  |  Volume : 59  |  Issue : 6  |  Page : 634
A case of lamellar ichthyosis with rickets and carcinoma of the hypopharynx


Department of Dermatology, Sri Ramachandra University, Chennai, Tamil Nadu, India

Date of Web Publication30-Oct-2014

Correspondence Address:
Aditya Kumar Bubna
Department of Dermatology, Sri Ramachandra University, Porur, Chennai - 600 116, Tamil Nadu
India
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Source of Support: None, Conflict of Interest: None


DOI: 10.4103/0019-5154.143585

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   Abstract 

Lamellar ichthyosis (LI) is an autosomal recessive disorder rarely associated with systemic organ involvement and development of carcinoma. Rickets has occasionally been described with LI owing to impaired vitamin D synthesis following altered keratinization. There has also been a high association of cutaneous cancers in patients of LI. We as Dermatologists should therefore be very meticulous while doing a full work up of these patients. We report here a case of LI associated with rickets and carcinoma of the hypopharynx.


Keywords: Lamellar ichthyosis, rickets, carcinoma of hypopharynx


How to cite this article:
Bubna AK, Veeraraghavan M, Anandan S, Rangarajan S. A case of lamellar ichthyosis with rickets and carcinoma of the hypopharynx. Indian J Dermatol 2014;59:634

How to cite this URL:
Bubna AK, Veeraraghavan M, Anandan S, Rangarajan S. A case of lamellar ichthyosis with rickets and carcinoma of the hypopharynx. Indian J Dermatol [serial online] 2014 [cited 2021 Oct 28];59:634. Available from: https://www.e-ijd.org/text.asp?2014/59/6/634/143585

What was known?
LI is an inherited disorder of keratinization associated with rickets and cutaneous cancers. Dysregulated vitamin D metabolism and excessive calcium loss through the skin is associated with rickets and later cancer development.



   Introduction Top


Ichthyosis is a heterogeneous group of skin disorders characterized by generalized scaling. Lamellar ichthyosis (LI) is an autosomal recessive disorder and has been known by several terms including non-bullous congenital icthyosiform erythroderma, non-erythrodermic autosomal recessive LI, ichthyosis congenital and classic LI. [1] LI is known to be associated with rickets owing to the dysregulated vitamin D metabolism in the skin because of the abnormal keratinization, and later development of carcinoma. [2] An association of LI with hypopharngeal carcinoma and rickets together has not been reported until date. Whether there is an association of the same with vitamin D deficiency per se is still uncertain. We hereby present this case report as the first ever reported case of having the three clinical conditions together.


   Case Report Top


A 45 year old man presented to the Department of Dermatology, with the complaints of scaly lesions over the body since birth with dysphagia for the past 1 month [Figure 1]. A history of collodion membrane at birth, which peeled off 40 days after birth was noted, which was followed by scaly lesions over the body with winter exacerbation. There was a history of seizures since birth for which the patient was on phenobarbitone. Recently, watering of eyes and dysphagia for solids observed with no other significant co-morbidities. General examination revealed a poorly nourished individual with bowing of both legs [Figure 2]. Cardiovascular examination showed a pre-systolic murmur in the aortic region, and occasional rhonchi in respiratory examination.
Figure 1: Well-defi ned ichthyotic scales over the face and the trunk with mild ectropion both the eyes

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Figure 2: Both lower limbs showing bowing of the tibia with the characteristic ichthyotic scales over the shins

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Dermatologic examination revealed diffuse thickening of skin with visible ichthyotic scales predominantly over the face, extremities, and lateral aspect of the abdomen. Mild hyperpigmentation of the palms and soles, dystrophic changes in nails, with ectropion of lower eyelids were observed. Radiography of both lower limbs showed the characteristic bowing of both tibia [Figure 3]. Histopathologic examination of the skin showed epidermal hyperkeratosis and mild parakeratosis with extension and blunting of the rete ridges [Figure 4]. Upon suggestions from otorhinolaryngology regarding hoarseness of voice, we conducted a laryngoscopic examination, which showed a proliferative growth involving the right pyriform fossa and extending to the postcricoid region. An endoscopic biopsy from the growth revealed a moderate to well differentiated squamous cell carcinoma [Figure 5].
Figure 3: Radiographic fi ndings showing the characteristic bowing of the tibia

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Figure 4: H and E section of the skin showing compact orthohyperkeratosis, variable mild focal parakeratosis with extension and blunting of the rete ridges in the epidermis. Minimal changes in the dermis

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Figure 5: Squamous cell carcinoma of the hypopharynx showing increased mitotic figures and nuclear atypia

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Hematologic investigations showed reduced serum calcium levels (6.3 mg/dL), reduced vitamin D3 levels (9 ng/mL) and an increased level of alkaline phosphatase (291 International Units [IU]). Bone scan revealed increased tracer uptake in the right femur and the left tibia, otherwise normal. Electrocardiography showed sinus rhythm with premature atrial complexes, aberrant conduction, low voltage QRS complex (Q-wave, R-wave and S-wave), nonspecific T-wave abnormality and prolonged QT interval. Echocardigraphy showed high frequency ectopics, mild mitral and tricuspid regurgitation.

Diagnosis of LI with rickets and carcinoma hypopharynx was made based on the clinical findings, biochemical and histopathology and radiography reports. Patient was started on Cap Acitretin 25 mg once at night, Vitamin D 2000 IU daily as advised by the endocrinologist and white soft paraffin as an emollient prescribed. Patient was referred to the Department of Otorhinolaryngology for the management of the growth in the hypopharynx. Within a month our patient succumbed to the laryngeal malignancy and expired.


   Discussion Top


LI is a congenital autosomal recessive disorder. [3] Infants with LI are often born preterm and maybe encased in a taut membrane that resembles a collodion and hence the term collodion baby. However, the collodion membrane is not specific for LI and can also be seen as a manifestation of congenital ichthyosiform erythroderma. [3]

It is caused by transglutaminase (TGM1) gene mutation that encodes the transglutaminase1 (TGase1) enzyme which is critical for the assembly of the cornified cell envelope in the terminally differentiating keratinocytes. TGase1 is a complex enzyme existing as both cytosolic and membrane bound forms. Moreover TGase1 is proteolytically processed and the major functionally active form consists of three polypeptides forming a 67/33/10 kDa complex. [3],[4],[5],[6],[7],[8] Other genetic defects included higher filaggrin expression in scales.

Clinically patients with LI present as large dark brown firmly adherent scales over the scalp, limbs and abdomen mainly, but may involve other sites also. In severely affected patients, the thick rigid scales are intermittently shed causing deep painful fissures especially around the flexures and on the digits, palms and soles. Other features include limitation of joint movements, flexion contractures, digital sclerodactyly, palmoplantar keratoderma, scarring alopecia and persistent ectropion, congenital hypoplasia of nasal and aural cartilage and impaired sweating. The child has a normal growth and intellect. Severe forms of LI seldom improve with age and psychological problems resulting from cosmetic effects and limited mobility can lead to isolation, depression and poor school performance. [9]

Treatment includes emollients, keratolytics, topical calcipotriol, 10% urea, topical N-acetyl cysteine and topical tazarotene 0.05% gel. In severe cases Acitretin 0.5-0.75 mg/kg/day.

LI is known to be associated rarely with systemic organ involvement. Few case reports with LI associated with either rickets [10],[11] or carcinoma [12],[14] have been observed. This is the first report presenting with both rickets and carcinoma in one patient. Sethuraman et al.,[10] have shown an association of LI with rickets. Similarly Thacher et al.,[11] reported the association of LI with nutritional rickets. Elbaum et al.,[12] reported two cases of LI who later developed squamous cell carcinoma. The development of squamous cell carcinoma has also been reported in a patient of non-bullous congenital ichthyosiform erythroderma by Arita et al.,[13] . Kampp et al.,[14] have reported a case of basal cell carcinoma masquerading as chronic ectropion in a patient of LI. We present our case wherein the patient had rickets as well as cancer of the hypopharynx with LI. Such a case of LI with rickets and carcinoma has not been reported before and we present it to you for its rarity. Cutaneous malignancies have been well associated with LI. A recently published meta-analysis study on serum 25-hydroxyvitamin D in colorectal cancer, revealed intake of vitamin D could minimize the risk of colorectal cancer. [15] Thus an association of mucosal malignancies with decreased levels of vitamin D3 has been seen too. Similar studies have shown deficiency of vitamin D in association with prostate and ovarian cancer risk. [16],[17],[18] However, hypopharyngeal carcinoma in association with LI and rickets is being reported for the first time. Whether there is an underlying gene mutation responsible or due to vitamin D deficiency per se for the underlying malignancy is still uncertain and at present literature too is unavailable for the same. Further molecular studies may help in this particular scenario. We as dermatologists tend to overlook systemic involvement in LI, which must be given due importance.


   Acknowledgment Top


Mr. Himavanth Reddy Kambalachenu, Department of Biomedical Sciences, Sri Ramachandra University, Chennai, India.

 
   References Top

1.Williams ML, Elias PM. Genetically transmitted and generalised disorders of cornification. Dermatol clin 1987;5:155-78.  Back to cited text no. 1
    
2.Traupe H, Kolde G, Happle R. Autosomal Dominant Ichthyosis: A new skin disorder. Clin Genet 1984;26:457-61.  Back to cited text no. 2
    
3.Schachner LA, Hansen RC. Ichthyosis and disorders of cornification. In Paediatric Dermatology. 2 nd ed. New York: Churchill Livingstone; 1996. p. 413-64.  Back to cited text no. 3
    
4.Hazell M, Marks R. Heterogeinity in autosomal recessive ichthyosis: Clinical and biochemical differentiation of lamellar ichthyosis and non-bullous congenital ichthyosiform erythroderma. Arch Dermatol 1985;121:477-88.  Back to cited text no. 4
    
5.Williams ML. Ichthyosis: Mechanisms of disease. Pediatr Dermatol 1992;9:365-8.  Back to cited text no. 5
    
6.Van Hoojdonk CAEM, Steijlen PM, Bergers M, Mier PD, Traupe E, Happle R. Epidermal transglutaminase in ichthyosis. Acta Dermato Venerol 1991;71:173-5.  Back to cited text no. 6
    
7.Hohl D, Huber M, Frenk E. Analysis of the cornified cell envelope in lamellar ichthyosis. Arch Dermatol 1993;129:618-24.  Back to cited text no. 7
    
8.Russell LJ, DioGiovanna JJ, Hashem N, Compton JG, Bale SJ. Linkage of autosomal recessive lamellar ichthyosis to chromosome 14q. Am J Hum Genet 1994;55:1148-52.  Back to cited text no. 8
    
9.Burns T, Breathnach S, Cox N, Griffiths C. Disorders of keratinisation. Rooks Textbook of Dermatology. 7 th ed. Vol. 2. Wiley Blackwell; 2004. p. 34.20-34.23.  Back to cited text no. 9
    
10.Sethuraman G, Khaitan BK, Dash SS, Chandramohan K, Sharma VK, Kabra M, et al. Ichthyosiform erythroderma with rickets: Report of five cases. Br J Dermatol 2008;158:657.  Back to cited text no. 10
    
11.Thacher TD, Fischer PR, Pettifor JM, Darmstadt GL. Nutritional Rickets in Ichthyosis and Response to Calcipotrione. Pediatrics 2004;114:119-23.  Back to cited text no. 11
    
12.Elbaum DJ, Kurz G, MacDuff M. Increased incidence of cutaneous carcinomas in patients with congenital ichthyosis. J Am Acad Dermatol 1995;33:884-6.  Back to cited text no. 12
    
13.Arita K, Akiyama M, Tsuji Y, Iwao F, Kodama K, Shimizu H. Squamous cell carcinoma in a patient with non-bullous congenital ichthyosiform erythroderma. Br J of Dermatol 2003;148:367-369.  Back to cited text no. 13
    
14.Kampp JT, Kouba DJ, Fincher EF, Moy RL. Basal cell carcinoma masquerading as the chronic ectropion of lamellar ichthyosis. Dermatol Surg 2008;34:963-7.  Back to cited text no. 14
    
15.Gorham ED, Garland CF, Garland FC, et al. Optimal vitamin D status for colorectal cancer prevention: A quantitative meta-analysis. Am J Prev Medicine 2007;32:210-6.  Back to cited text no. 15
    
16.Grant WB. Lower vitamin D production from solar ultraviolet B irradiance may explain some differences in cancer survival rates. J Natl Med Assoc 2006;26:2687-99.  Back to cited text no. 16
    
17.Giovannucci E. The epidemiology of vitamin D and cancer incidence and mortality: A review (United States). Cancer Causes Control 2005;16:83-95.  Back to cited text no. 17
    
18.Schwartz GG, Hanchette CL. UV, latitude, and spatial trends in prostate cancer mortality: All sunlight is not the same (United States). Cancer Causes Control 2006;17:1091-1.  Back to cited text no. 18
    

What is new?
Mucosal malignancies like colorectal cancer and prostatic and ovarian cancers have been associated with defi ciency of vitamin D. Hypopharngeal cancer in association with LI and rickets has not been reported so far, however, whether it is a coincidence or a clear cut association, only further studies could help in elucidating this relationship and whether a prophylaxis of vitamin D supplementation could help in slowing the pathogenesis of the malignancy.


    Figures

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



 

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    Abstract
   Introduction
   Case Report
   Discussion
   Acknowledgment
    References
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