Indian Journal of Dermatology
: 2021  |  Volume : 66  |  Issue : 2  |  Page : 224-

A case of annular epidermolytic ichthyosis resulting from a de novo mutation, p.I479T, in Keratin 1 Gene

Lihong Chen, Cheng Quan, Jie Zheng, Meng Pan, Xiaoqing Zhao 
 Department of Dermatology, Rui Jin Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai, China

Correspondence Address:
Xiaoqing Zhao
Department of Dermatology, Ruijin Hospital, No. 197, Rui Jin Er Road, Huangpu District, 200025, Shanghai


We report a case of annular epidermolytic ichthyosis (AEI) resulting from de novo keratin 1 gene mutation. AEI is a rare autosomal dominantly inherited cornification disorder and is a distinct phenotypic variant of bullous congenital ichthyosiform erythroderma. Blisters and erosions in AEI are widespread; hence, initially, it is sometimes mistaken with epidermolysis bullosa, acrodermatitis enteropathica, and staphylococcal scalded skin syndrome. Genetic tests including next-generation sequencing and Sanger sequencing are essential for AEI diagnosis. AEI is treated symptomatically by wound dressing, prevention of infection, and the use of emollients, humectants, and keratolytic products; topical or systemic retinoids may also prove helpful.

How to cite this article:
Chen L, Quan C, Zheng J, Pan M, Zhao X. A case of annular epidermolytic ichthyosis resulting from a de novo mutation, p.I479T, in Keratin 1 Gene.Indian J Dermatol 2021;66:224-224

How to cite this URL:
Chen L, Quan C, Zheng J, Pan M, Zhao X. A case of annular epidermolytic ichthyosis resulting from a de novo mutation, p.I479T, in Keratin 1 Gene. Indian J Dermatol [serial online] 2021 [cited 2021 Dec 8 ];66:224-224
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Annular epidermolytic ichthyosis (AEI) is a rare autosomal dominant cornification disease that results from keratin 1 or keratin 10 gene mutations.[1] It is a distinct phenotypic variant of bullous congenital ichthyosiform erythroderma and is characterized by intermittent episodes of polycyclic, erythematous, scaly plaques on the trunk and proximal extremities.[1] Here, we report a case of AEI that resulted from a de novo keratin 1 gene (KRT 1) mutation.

 Case History

A 4-month-old girl was referred to the outpatient clinic due to intermittent episodes of erythema, blistering, and scaling [Figure 1]a and [Figure 1]b since 2 days old, with each episode lasting for 2–4 weeks. The patient was initially diagnosed with staphylococcal scalded skin syndrome (SSSS), but no improvement was observed after systemic antibiotic therapy. Her blisters presented with positive Nikolsky's sign and have improved spontaneously for several months. However, polycyclic erythema and scaling developed on her trunk and extremities. During the interim periods, the lesions partially remitted. From 8 months old, she had palmoplantar hyperkeratosis and annular hyperkeratotic plaques on her trunk. None of her family members reported similar symptoms.{Figure 1}

A skin biopsy of a bullous lesion from the left thigh was done, and hematoxylin–eosin staining revealed an intraepidermal vesicle in the upper epidermis, intracellular vacuolation and irregular eosinophilic granules in the superficial layers of the epidermis [Figure 1]c and [Figure 1]d. Direct immunofluorescence and indirect immunofluorescence staining for IgA, IgG, IgM, and C3 were negative. In addition, next-generation sequencing was performed and revealed a heterozygous transition mutation, 1436T→C, in the KRT 1, which was confirmed by Sanger sequencing [Figure 1]e, indicating an isoleucine-to-threonine amino acid change in codon 479 (Ile479Thr). No mutation was detected in brother [Figure 1]e and her parents [Supplementary Figure 1]. Based on the clinical and genetic profile, the patient was diagnosed with AEI. Our patient was then given an emollient and diluted bleach baths with minimal improvement.[INLINE:1]


AEI or cyclic ichthyosis with epidermolytic hyperkeratosis (CI-EH) was first reported by Sahn et al. in 1992[1] in eight families and two sporadic patients [Table 1]. AEI was characterized by blistering and scaling at birth and in the perinatal period, developing later in life into annular or polycyclic hyperkeratotic lesions. It was described as a relatively mild epidermolytic hyperkeratosis, and due to the widespread blisters and erosions, epidermolytic ichthyosis patients might be misdiagnosed with SSSS or epidermolysis bullosa simplex. Its typical histological features are vacuolar degeneration and coarse keratohyalin granules in the granular layer.{Table 1}

Specific KRT 1 and KRT 10 mutations have been identified to cause AEI.[2],[3],[4] Keratin 1 (K1) is a member of the keratin family, and compared to keratin 10 (K10), K1 is specifically expressed in the spinous and granular layers of the epidermis. Keratins share a basic structural organization, with four helical or coiled-coil segments.[5] In our case, the mutation resides in the C-terminal aspect of helix 2B of K1, a highly conserved portion.[5] Ile479Thr eliminates stabilizing hydrophobic interactions from the isoleucine and adds hydrogen bonding from the threonine side chain.[5] Moreover, palmoplantar keratinocytes express K1 but not K10; hence, the palmoplantar hyperkeratosis that developed later in our case was consistent with KRT 1 mutation rather than KRT 10. Although skin manifestation and mutation were not observed in her parents and elder brother [Figure 1e and Supplementary Figure 1], we believe that our patient had a de novo mutation of KRT 1.

AEI treatment is symptomatic. When blistering is prominent, treatment is focused on wound dressing and infection prevention. Emollients, humectants, and keratolytic products are usually recommended as maintenance treatment, and topical or systemic retinoids may also be helpful.

In conclusion, we report a de novo heterozygous transition mutation of the KRT 1 gene in an infant, presenting a mild form of epidermolytic hyperkeratosis, which needs to be differentiated from other bullous diseases.

Patient's consent

The patient's consent to use photographs that may reveal the identity of the patient is enclosed.

Declaration of patient consent

The authors certify that they have obtained all appropriate patient consent forms. In the form the patient(s) has/have given his/her/their consent for his/her/their images and other clinical information to be reported in the journal. The patients understand that their names and initials will not be published and due efforts will be made to conceal their identity, but anonymity cannot be guaranteed.

Financial support and sponsorship

This work was supported by grants from the National Natural Science Foundation of China (81803134).

Conflicts of interest

There are no conflicts of interest.


1Sahn EE, Weimer CE Jr, Garen PD. Annular epidermolytic ichthyosis: A unique phenotype. J Am Acad Dermatol 1992;27:348-55.
2Sybert 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;6:732-8.
3Joh 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 ichthyosiform erythroderma. J Invest Dermatol 1997;108:357-61.
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5Bunick CG, Milstone LM. The X-ray crystal structure of the keratin 1-keratin 10 helix 2B heterodimer reveals molecular surface properties and biochemical insights into human skin disease. J Invest Dermatol 2017;137:142-50.