Painful, Pruritic Exacerbated by Heat and Sweating

Collin M. Blattner, BS,* Dustin V. Wilkes, DO,** Dongkun Chang, MD***

*Medical Student, 4th year, Des Moines University, Des Moines, IA **Attending Dermatologist, Department of , JPS Health Network, Fort Worth, TX ***Attending Pathologist, Department of Pathology, JPS Health Network, Fort Worth, TX

Abstract Bullous congenital ichthyosiform erythroderma is a rare that affects 1 in 200,000 people. Management for adults entails symptomatic relief, but infants may require intensive care if substantial blistering is present. We present a case of bullous congenital ichthyosiform erythroderma in a 48-year-old male and provide a discussion about the disease and treatment options.

Introduction and soles with fissures and cracks (Figure 1). There were also few coarse, irregularly shaped, Bullous congenital ichthyosiform erythroderma Brown, cardboard-like scale with desquamation on keratohyalin granules and intracytoplasmic (BCIE) is a rare genodermatosis that was the neck, back, abdomen, and extremities was also , along with involvement of the formerly known as epidermolytic present. The lesions extended to the volar aspect of entire suprabasal layer. This was consistent with (EHK) or epidermolytic (EI). About the wrists, the dorsa of the feet, and the Achilles the diagnosis of BCIE. 50% of cases arise from spontaneous , tendon. Dark-brown hyperkeratosis with mild but autosomal-dominant (AD) and rare scaling, arrayed in a linear fashion, was present in his autosomal-recessive forms also exist.1-3 BCIE axillae, antecubital fossa (Figure 2), and popliteal clinically manifests with erythema, blistering, and erythroderma in infancy, but the severity of disease may decrease over time.1

Case Report A 48-year-old African American male presented for evaluation of blisters and scaling over the entirety of his body since birth. The blisters were painful, pruritic, and made worse by heat and sweating. He had previously used Eucerin lotion without relief. The patient had an otherwise Fig 3. Orthokeratotic hyperkeratosis, unremarkable 12-point review of symptoms , church-spire-like except for mild joint pain, 15 pack-year smoking , and marked vacuolar changes history, and moderate alcohol intake. in the keratinocytes of the upper spinous and granular layers (H&E, 40x) Dermatological examination revealed marked hyperkeratosis, thickened palms with palmoplantar , hyperlinear creases, Discussion BCIE is a rare AD genodermatosis that was first described by Brocq in 1902.4 It is caused by in 1 and keratin 10 that impair formation in the suprabasal keratinocytes, although a case with a novel mutation in the 1A helix initiation motif Fig 2. Antecubital fossa with dark-brown 4 hyperkeratosis and scaling of keratin 1 has been reported. Confirmation of disease can be established by mutation-specific testing for keratin defects using buccal swabs fossa. The hair, teeth, nails, mucosa, and other body or blood.5 Cost constraints prohibited genetic surfaces were spared. The patient’s mother, maternal testing and genetic counseling for our patient, aunt, and two cousins had a similar condition but these services should be offered to affected with pronounced scaling. individuals and families. Patients should also included BCIE, epidermolysis bullosa, lamellar be made aware of the possibility of passing the ichthyosis, X-linked ichthyosis, staphylococcal chromosomal defect on to their children. scalded skin syndrome, Stevens-Johnson syndrome, Clinically, BCIE presents in neonates with and toxic epidermal necrolysis. erythema, widespread superficial blistering, and Two 4mm punch biopsies were taken from erythroderma. If the blisters rupture, they may representative lesions on the abdomen and leave raw, denuded areas that can cause secondary left knee. Histopathological findings revealed , sepsis, dehydration, electrolyte orthokeratotic hyperkeratosis, hypergranulosis, imbalances, and hypothermia. In light of these church-spire-like papillomatosis, and marked concerns, affected newborns should be handled Fig 1. Thickened palm with palmoplantar vacuolar changes in the keratinocytes of the gently and transferred to the intensive care unit keratoderma and hyperlinear creases upper spinous and granular layers (Figure 3). (ICU) immediately after birth. Although a

BLATTNER, WILKES, CHANG Page 19 delicate scale may be present following delivery, Review. hyperkeratosis is seldom noticeable until the References 1. Frost P, Van Scott EJ. Ichthyosiform 13. Li H, Törmä H. Retinoids reduce formation of third month of life. Clinical data from 28 dermatoses. Classification based on anatomic and keratin aggregates in heat-stressed immortalized patients with BCIE in Japan found that 96.4% biometric observations. Arch Dermatol. 1966 keratinocytes from an epidermolytic ichthyosis had rash, 67.9% had erythroderma, and 75% of Aug;94(2):113-26. patient with a KRT10 mutation. Acta Derm patients younger than 20 years had generalized Venereol. 2013 Jan;93(1):44-9. blistering.6 As a person ages, the symptoms 2. Terheyden P, Grimberg G, Hausser I, Rose may wane or even disappear, but the classically C, Korge BP, Krieg T, Arin MJ. Recessive 14. Brecher AR, Orlow SJ. Oral retinoid described “corrugated cardboard” scale persists.6 epidermolytic hyperkeratosis caused by a therapy for dermatologic conditions in children Proliferation of scale allows for the overgrowth previously unreported termination codon and adolescents. J Am Acad Dermatol. 2003 of bacteria, particularly Staphylococcus aureus, that mutation in the keratin 10 gene. J Invest Aug;49(2):171-82; quiz 183-6. Review. 6 Dermatol. 2009 Nov;129(11):2721-3. causes malodor. 15. Ruiz-Maldonado R, Tamayo L. Retinoids in In 1994, DiGiovanna and Bale separated the 3. Tsubota A, Akiyama M, Kanitakis J, Sakai K, disorders of keratinization: their use in children. various clinical presentations of BCIE into two Nomura T, Claudy A, Shimizu H. Mild recessive Dermatologica. 1987;175 Suppl 1:125-32. bullous congenital ichthyosiform erythroderma primary types based on the presence or absence 16. Kragballe K, Steijlen PM, Ibsen HH, van de 5 due to a previously unidentified homozygous of palm and sole hyperkeratosis. The two Kerkhof PC, Esmann J, Sorensen LH, Axelsen keratin 10 nonsense mutation. J Invest Dermatol. primary types were further subdivided into three MB. Efficacy, tolerability, and safety of calcipotriol 2008 Jul;128(7):1648-52. subtypes each that described the various clinical ointment in disorders of keratinization. Results of presentations. Some subtypes have generalized 4. Uezato H, Yamamoto Y, Kuwae C, Nonaka 5 a randomized, double-blind, vehicle-controlled, involvement; others are more localized. EHK K, Oshiro M, Kariya K, Nonaka S. A case of right/left comparative study. Arch Dermatol. is still being used as a synonym for BCIE even bullous congenital ichthyosiform erythroderma 1995 May;131(5):556-60. though multiple unusual subtypes of BCIE (BCIE) caused by a mutation in the 1A helix 7-11 17. Kwak J, Maverakis E. Epidermolytic (annular, linear, cyclic) have been described. initiation motif of keratin 1. J Dermatol. 2005 hyperkeratosis. Dermatol Online J. 2006 Sep The histopathological hallmark of BCIE is Oct;32(10):801-8. “epidermolytic hyperkeratosis” (EHK) despite 8;12(5):6. 5. DiGiovanna JJ, Bale SJ. Clinical heterogeneity the identical finding being present in several 18. Achar A, Naskar B, Laha R, Ray S. in epidermolytic hyperkeratosis. Arch Dermatol. conditions including acanthoma, epidermoid cyst, Epidcermolytic hyperkeratosis: a case report. J 1994 Aug;130(8):1026-35. infundibular cyst, epidermal , hidradenoma, Indian Med Assoc. 2009 Mar;107(3):171-2. nevus comedonicus, seborrheic keratosis, actinic 6. Kurosawa M, Takagi A, Tamakoshi A, 19. Rothnagel JA, Lin MT, Longley MA, Holder keratosis, leukoplakia, basal cell carcinoma, Kawamura T, Inaba Y, Yokoyama K, Kitajima Y, 12 RA, Hazen PG, Levy ML, Roop DR. Prenatal squamous cell carcinoma, and melanoma. Aoyama Y, Iwatsuki K, Ikeda S. Epidemiology diagnosis for keratin mutations to exclude and clinical characteristics of bullous congenital Although no cure exists for BCIE, oral retinoids transmission of epidermolytic hyperkeratosis. ichthyosiform erythroderma (keratinolytic such as isotretinoin, acitretin, and etretinate are Prenat Diagn. 1998 Aug;18(8):826-30. the mainstay of therapy.13 Studies of etretinate ichthyosis) in Japan: results from a nationwide for children with BCIE demonstrated a good survey. J Am Acad Dermatol. 2013 Feb;68(2):278- safety profile and remission rates of 70% to 83. Correspondence: Dustin V. Wilkes, DO; 80%.14 Dosing is started at 1 mg/kg/d to 2 mg/ 7. Lacz NL, Schwartz RA, Kihiczak G. [email protected] kg/d, and once remission is achieved, the dose Epidermolytic hyperkeratosis: a keratin 1 or 10 can be adjusted to the minimal amount necessary mutational event. Int J Dermatol. 2005;44(1):1-6. to keep the skin free of lesions.14 Children who 8. Sheth N, Greenblatt D, McGrath JA. New underwent treatment with oral retinoids had KRT10 gene mutation underlying the annular improved quality of life and enhanced social and variant of bullous congenital ichthyosiform psychological development, and a subset showed erythroderma with clinical worsening during improved physical growth.15 Adjunctive therapies pregnancy. Br J Dermatol. 2007;157:602–4. that provide symptomatic relief include high-dose beta-carotene, topical retinoids, 10% glycerin, 9. Kocaturk E, Zemheri E, Kavala M, Aktas lactic acid, alpha-hydroxy acid, calcipotriol, S, Sarigul S, Sudogan S. Two cases of linear antibacterial soap, and urea.16-18 Proper use of epidermolytic hyperkeratosis: therapeutic emollients and other barrier ointments that challenge with acitretin. Eur J Dermatol. retain moisture are recommended. 2010;20(3):404-5. is a promising new treatment option that is being 10. Chassaing N, Kanitakis J, Sportich S, Cordier- studied at the University of Colorado. Researchers Alex MP, Titeux M, Calvas P, Claudy A, Berbis hope to generate induced pluripotent stem cells P, Hovnanian A. Generalized epidermolytic that allow for genetic correction of the defect in hyperkeratosis in two unrelated children from keratin 1 or keratin 10. parents with localized linear form, and prenatal diagnosis. J Invest Dermatol. 2006;126(12):2715- Conclusion 7. In conclusion, accurate diagnosis of BCIE is 11. Sybert VP, Francis JS, Corden LD, Smith LT, important so that genetic counseling and prenatal 19 Weaver M, Stephens K, McLean WH. Cyclic diagnosis may be offered to affected families. Ichthyosis with Epidermolytic Hyperkeratosis: Management includes oral retinoids for children A Phenotype Conferred by Mutations in the and symptomatic care with proper use of 2B Domain of Keratin K1. Am J Hum Genet. emollients and mild antibacterial cleansers for 1999;64:732–8. adults.14 Infants should be treated in the ICU to prevent secondary infections, sepsis, dehydration, 12. Kumar P, Kumar R, Mandal RK, Hassan S. electrolyte imbalances, or death.14 Systematized linear epidermolytic hyperkeratosis. Dermatol Online J. 2014 Jan15;20(1):21248.

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