Scholarly article on topic 'Annular epidermolytic ichthyosis: A rare phenotypic variant of bullous congenital ichthyosiform erythroderma'

Annular epidermolytic ichthyosis: A rare phenotypic variant of bullous congenital ichthyosiform erythroderma Academic research paper on "Clinical medicine"

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Indian J Dermatol Venereol Leprol
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Academic research paper on topic "Annular epidermolytic ichthyosis: A rare phenotypic variant of bullous congenital ichthyosiform erythroderma"

recurrent nonsense mutation c. 2806C>T, leading to p.R936X in exon 20 of CYLD gene. This study expands the clinical heterogeneity of multiple familial trichoepitheliomas due to the same mutation (c. 2806C>T) in CYLD and contributes to enrichment of the database of the CYLD mutations underlying multiple familial trichoepitheliomas in the Chinese population. In the light of previous studies, our findings also suggest that though the mutation c. 2806C>T in CYLD mainly leads to a "benign' phenotype such as multiple familial trichoepithelioma Brooke-Spiegler syndrome, but may also result in a malignant phenotype.

Qi-Guo Zhang, Yan-Hua Liang

Department of Dermatology, Nanfang Hospital, Southern Medical University, Guangzhou, Guangdong 510515, China

Address for correspondence: Prof. Yan-Hua Liang, Department of Dermatology, Nanfang Hospital, Southern Medical University, Guangzhou, Guangdong 510515, China.



1. Liang YH, Gao M, Sun LD, Liu LJ, Cui Y, Yang S, et al. Two novel CYLD gene mutations in Chinese families with trichoepithelioma and a literature review of 16 families with trichoepithelioma reported in China. Br J Dermatol 2005;153:1213-5.

2. Zhang XJ, Liang YH, He PP, Yang S, Wang HY, Chen JJ, et al. Identification of the cylindromatosis tumor-suppressor gene responsible for multiple familial trichoepithelioma. J Invest Dermatol 2004;122:658-64.

3. Bowen S, Gill M, Lee DA, Fisher G, Geronemus RG, Vazquez ME, et al. Mutations in the CYLD gene in Brooke-Spiegler syndrome, familial cylindromatosis, and multiple familial trichoepithelioma: Lack of genotype-phenotype correlation. J Invest Dermatol 2005;124:919-20.

4. Young AL, Kellermayer R, Szigeti R, Teszas A, Azmi S, Celebi JT. CYLD mutations underlie Brooke-Spiegler, familial cylindromatosis, and multiple familial trichoepithelioma syndromes. Clin Genet 2006;70:246-9.

5. Kazakov DV, Zelger B, Rutten A, Vazmitel M, Spagnolo DV, Kacerovska D, et al. Morphologic diversity of malignant neoplasms arising in preexisting spiradenoma, cylindroma, and spiradenocylindroma based on the study of 24 cases, sporadic or occurring in the setting of Brooke-Spiegler syndrome. Am J Surg Pathol 2009;33:705-19.

Annular epidermolytic ichthyosis: A rare phenotypic variant of bullous congenital ichthyosiform erythroderma

Bullous congenital ichthyosiform erythroderma of Brocq is a rare mechanobullous eruption first described by Brocq in 1902. This autosomal dominant disorder is characterized by blistering and erythroderma in early life with many similarities to epidermolysis bullosa simplex. However, these patients subsequently develop ichthyosis and hyperkeratosis. Epidermolytic hyperkeratosis is the hallmark feature on light and electron microscopy. Annular epidermolytic ichthyosis is a distinct phenotypic variant of bullous congenital ichthyosiform erythroderma characterized by intermittent development of polycyclic, erythematous, scaly plaques on the trunk and proximal extremities.111 Histological features are similar to those of classical epidermolytic hyperkeratosis, and keratin K10 or K1 mutations, similar to those of bullous congenital ichthyosiform erythroderma, have been identified in annular epidermolytic ichthyosis.12-41

A 26-year-old female, born of a non-consanguineous marriage, presented to the dermatology outpatient of Vardhaman Mahavir Medical College and Safdarjung Hospital, New Delhi, India, with a history of generalized recurrentblistering since birth. She had begun to develop hyperkeratotic plaques all over the body since early infancy and by 8 years of age, the lesions had cleared from most areas and had localized to the flexures (neck, cubital fossae, elbows, and wrist) [Figure 1a]. For the past 3 years, she was also developing recurrent episodes of erythematous annular plaques with scaling over the trunk, thighs, and inframammary areas. These lesions increased in size over a period of 8-10 days and later developed peripheral desquamation giving them an annular appearance [Figure 2a and b]. She had given birth to a boy with erythroderma with subsequent development of rippled hyperkeratosis of the flexures [Figure 3a and b]. There was no history of neonatal blistering in the child. Examination of the child revealed polycyclic, psoriasiform, scaly plaques on the trunk and extremities. Clinically, the hair, teeth, and nails were normal. With the provisional differential

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diagnoses of bullous congenital ichthyosiform erythroderma (BCIE) occurring alone, in combination with erythrokeratoderma, or in combination with with psoriasis, a skin biopsy was taken from the annular plaque and a hyperkeratotic lesion that represented the two main clinical aspects of the disease. Light microscopy of the specimens revealed hyperkeratosis, acanthosis, and degeneration of granular layer with dispersion of keratohyalin granules. Vacuolar changes were evident in the keratinocytes of the stratum spinosum [Figure 4]. These findings were consistent with the diagnosis of epidermolytic hyperkeratosis. A complete blood count, liver and kidney function tests, and serum electrolytes were normal. Skin scrapings from the scaly plaques were negative for fungi.

She was initially started on emollients and ciclosporin 3.5 mg/kg body weight because of the presumptive differential diagnosis of psoriasis for the annular plaques. Retinoids were not considered at this point because she was breastfeeding. The erythematous,

Figure 1: (a) Annular psoriasiform plaques over the trunk and extremities and ribbed hyperkeratosis over the flexures. (b) Considerable improvement after treatment with acitretin

Figure 3: (a) Diffuse erythema and creamy white scaling in the child. (b) Peeling of the skin over the soles in the child

annular plaques improved moderately after 6 weeks of treatment. The plaques remained stable for 1 month after which she had a flare of the annular plaques. She was then started on acitretin 0.5 mg/kg/day after detailed counselling regarding contraception. Four weeks later, all the annular plaques disappeared and there was a remarkable improvement in the flexural as well as the annular plaques [Figure 1b]. No recurrence was noted after 2 months. We plan to re-institute acitretin in the event of a relapse. The child was treated with emollients in view of the milder phenotype and the potential side effect profile of acitretin.

The distinct phenotype seen in our patient has only been described in eight families thus far in the literature and we were unable to find any previous cases reported from India [Table 1]. It was first reported in a young female by Sahn et al. in 1992 who also coined the term annular epidermolytic ichthyosis.111 She had bullous and ichthyosiform skin lesions since the age of 8 months. Later, she developed numerous annular and polycyclic, erythematous, hyperkeratotic plaques on the trunk and extremities, which were pruritic, enlarged slowly, and then resolved. Histopathology of the annular plaques revealed

Figure 2: (a) Erythematous polycyclic plaques over the trunk with exfoliation starting from the center. (b) Exfoliation extending toward the periphery giving an annular appearance

Figure 4: Hyperkeratosis, epidermal acanthosis with granular layer degeneration and vacoular alteration in keratinocytes (H and E, x400)

Table 1: Summary of previously reported cases of annular epidermolytic ichthyosis


Case number


Age at presentation and clinical features

Additional features

Mutation analysis

et al., 1992

et al., 1997

1 30/F 27 years of age

Trunk and extremities: Annular and polycyclic, erythematous, hyperkeratotic plaques Itchy, migratory, self-resolving 2 (father) 33/M 31 years of age

Trunk and proximal extremities Numerous migrating, annular, polycyclic erythematous plaques with scaling borders, along with very superficial erosions within these plaques 3 (daughter of 2) 2 months/F 2 months of age

Around the groin and inner side of legs Some coin-sized sharply demarcated erosions

et al., 1998

Sybert et al., 1999

7 (aunt of case 6)

Michael 8, 9, 10, 11

et al., 1999 (members of one family)

Yoneda K et al., 1999

Naik et al.,

12, 13 (mother and son)

3/M 18/M NA/F

48/F 18/M

Bullous and ichthyosiform lesions since 8 months of age Bullous lesions stopped at puberty

Ichthyosiform lesions persisted Bullous and ichthyosiform lesions since birth Bullous lesions stopped at 16 years of age

Generalised bullous lesions and moderate erythema since birth

Trunk and proximal extremities Intermittent episodes of erythematous, scaly, annular, and serpiginous plaques

3 years of age for case 5 and 6 Data for case 7 not available Episodic flares of annular, polycyclic erythematous plaques with scaling

Flares last weeks to months Trunk: Non-migratory psoriasiform erythematous plaques

Intermittent episodes Trunk and proximal extremities: Numerous migrating, annular, and polycyclic erythematous hyperkeratotic plaques by

4 years of age 1 year of age

Trunk and extremities: Episodic, slowly migratory red patches with scaling

Ridged keratotic plaques in the flexures

No blistering at any point of time

Erythema and superficial erosions at birth, which improved during the first few months of life

Palmoplantar hyperkeratosis

Transient blistering at birth Palmoplantar keratoderma

Extensive blistering at birth

Thickened, dirty brown, corrugated plaques over the knees, elbows, and ankles Palmoplantar keratoderma

Not available

Novel dinucleotide mutation (CG to CA) within 2B segment of keratin 10 in the case and his daughter

Novel mutation within the 2B segment of K10, codon 446

Both families revealed heterozygous mutations in K1 codon 479

Heterozygous mutations in the 2B segment of K1 gene

Mutation in K10 gene (1A rod domain)

Not done

M: Male, F: Female, CG: Cytosine guanine, CA: Cytosine adenine

epidermolytic hyperkeratosis. Our case also had a similar presentation. Subsequently, Joh et al. reported a similar condition in a family with two generations being affected. Histological examination showed typical features of epidermolytic hyperkeratosis and molecular analysis revealed a novel dinucleotide mutation within the 2B segment of the keratin 10 gene that was passed on to offspring.[2] Similar cases were reported by Suga et al. in 1998[3] and Sybert et al. in 1999.[4] Molecular analysis of these families revealed mutations in keratin 10 and keratin 1 genes, respectively. Naik reported episodic flares of polycyclic psoriasiform patches in a young woman with a life-long history of palmoplantar keratoderma with histological features of epidermolytic hyperkeratosis.[5]

The molecular mechanisms underlying this particular phenotype of epidermolytic ichthyosis caused by mutations in K1 and K10 are unclear. We were not able to perform the mutation analysis in our patient because the facility was not available in our setting.

Aditi Jha, Jitender Taneja, V. Ramesh,

Avninder Singh1

Department of Dermatology and STD, VM Medical College and Safdarjung Hospital, 1Pathology, Indian Council of Medical Research,

Safdarjung Hospital, New Delhi, India

Address for correspondence: Dr. V. Ramesh, Department of Dermatology and STD, 5th Floor, OPD block, VM Medical College and Safdarjung Hospital, New Delhi - 110 029, India.



1. Sahn EE, Weimer CE Jr, Garen PD. Annular epidermolytic ichthyosis: A unique phenotype. J Am Acad Dermatol 1992;27:348-55.

2. Joh GY, Traupe H, Metze D, Nashan D, Huber M, Hohl D, et al. A novel dinucleotide mutation in keratin 10 in the annular epidermolytic ichthyosis variant of bullous congenital ichthyosis erythroderma. J Invest Dermatol 1997;108:357-61.

3. Suga Y, Duncan KO, Heald PW, Roop DR. A novel helix termination mutation in keratin 10 in annular epidermolytic ichthyosis, a variant of bullous congenital ichthyosiform erythroderma. J Invest Dermatol 1998;111:1220-3.

4. Sybert VP, Francis JS, Corden LD, Smith LT, Weaver M, Stephens K, et al. Cyclic ichthyosis with epidermolytic hyperkeratosis: A phenotype conferred by mutations in the 2B domain of keratin k1. Am J Hum Genet 1999;64:732-8.

5. Naik NS. Annular epidermolytic ichthyosis. Dermatol Online J 2003;9:4.

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Precocious puberty in a 3-year-old child with systematized verrucous epidermal nevus

Widespread epidermal nevi may be associated with extracutaneous findings.111 We herein describe the association of precocious puberty with systematized verrucous epidermal nevus in a child.

A 3-year-old boy presented with hyperpigmented velvety skin lesions over the face, trunk and extremities since the age of 3 months. He was born after a prolonged and difficult delivery assisted by an untrained birth attendant. The child was diagnosed with cerebral palsy. At the age of 3 months, he had an episode of generalized tonic clonic seizures, which was successfully treated with sodium valproate. The child also had motor and speech developmental delay.

On examination, he was irritable. The child's head circumference and weight were at the 50th percentile for his age. His height was appropriate for the age of 3 years and 8 months. Cutaneous examination revealed multiple hyperpigmented velvety and slightly elevated plaques in a blaschkoid distribution over the left side of the forehead, cheeks, neck and trunk. The left upper limb and lower limb were also involved. There was a sharp midline demarcation, with slight extension onto the right side [Figure 1]. He had a large penis and testicles with thick terminal hair in the pubic region [Figure 2]. Central nervous system examination revealed increased tone and exaggerated deep tendon reflexes in both upper and lower limbs, with normal muscle power. Contractures were present at the knee and ankle joints due to spasticity. No abnormality was detected on ocular examination. His IQ assessment showed an IQ of 50, suggestive of mild mental retardation.

Skeletal survey was suggestive of advanced bone age (5-6 years). Magnetic resonance imaging of the brain revealed periventricular leukomalacia (ischemic brain injury). Ultrasound of abdomen was

Figure 1: Multiple hyperpigmented velvety plaques in a blaschkoid distribution over (a) face, (b) right side of trunk, (c) neck and left side of trunk, (d) forearm and hand

Figure 2: Large sized testes and penis with presence of thick terminal hair in the pubic region

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