Ichthyosis Bullosa of Siemens: A Rare Sporadic Case with Genetic Confirmation

Dear Editor, Ichthyosis Bullosa of Siemens (IBS) is a rare autosomal dominant disorder first described by Hermann Siemens in 1937, caused by mutations in KRT2, encoding keratin 2e.[1] This leads to the defective keratinization, resulting in superficial blistering, flexural hyperkeratosis, and a characteristic skin peeling phenomenon known as Mauserung. Unlike bullous congenital ichthyosiform erythroderma (BCIE), IBS lacks erythroderma and has milder hyperkeratosis,[2] often leading to misdiagnosis. We present a genetically confirmed sporadic case of IBS, highlighting its diagnostic challenges and therapeutic considerations. A 12-year-old female, born to non-consanguineous parents, presented with progressive hyperkeratotic plaques over the limbs and generalized xerosis as shown in Figure 1a-c. Recurrent blistering since infancy was reported, resolving with hyperpigmentation but without scarring. The blistering episodes diminished with age, while hyperkeratosis progressively worsened. There was no family history of similar conditions, and IgE levels were normal.Figure 1: (a-c) symmetrical dirty grey hyperkeratosis in extremities where it demonstrates typical rippled pattern over knees. (d) Mauserung phenomenon-circumscribed area of focal peeling of skin over bilateralClinical examination revealed well-demarcated hyperkeratotic plaques localized to flexural sites, particularly in the popliteal fossae, with a striking Mauserung phenomenon as shown in Figure 1d. Notably, the face, palms, soles, and mucosa were spared, distinguishing it from other keratinization disorders. Histopathology of a hyperkeratotic lesion demonstrated basket-weave hyperkeratosis and acanthosis as shown in Figure 2b, while biopsy from the Mauserung site revealed intracorneal blistering with hyperkeratosis as shown in Figure 2a.Figure 2: (a) Histopathological findings from area exhibiting mauserung phenomenon shows Intracorneal blistering with hyperkeratosis (H and E, x100). (b) Histopathological findings from hyperkeratotic area shows basket weave hyperkeratosis and acanthosis (H and E, x400)Genetic analysis confirmed a pathogenic missense mutation in KRT2 (NM_000423.3:c.557A>G) as shown in Supplementary File 1, reinforcing the diagnosis.Supplementary File 1: Genetic analysis-missense mutation in KRT2 (NM_000423.3:c.557A>G)IBS remains an underrecognized entity due to its clinical overlap with BCIE. However, the absence of erythroderma, flexural localization of hyperkeratosis, and the presence of Mauserung serve as key distinguishing features. While IBS is typically inherited in an autosomal dominant manner, sporadic mutations, as seen in this case, have been documented.[3,4] Genetic confirmation is crucial in differentiating IBS from other blistering disorders, eliminating diagnostic ambiguity, and guiding targeted management. The patient was started on emollients containing 10% urea and 15% glycolic acid for symptomatic relief. Given the progressive hyperkeratosis, oral isotretinoin (0.5 mg/kg/day) was initiated, with close monitoring for long-term tolerability. Parental counselling was provided regarding the genetic implications and the chronic nature of the disease. The patient remains under follow-up with ongoing clinical improvement. This case reinforces the diagnostic value of genetic analysis in rare keratinization disorders, ensuring precision in classification and management. In contrast to previous reports, where IBS was diagnosed clinically, our case is substantiated by definitive genetic proof, strengthening its reliability. Early diagnosis and appropriate therapeutic intervention can significantly improve the quality of life in paediatric patients with IBS, preventing unnecessary treatments and misclassification with other blistering dermatoses. Consent statement Informed consent was obtained from the patient’s parents for publication. Financial support and sponsorship Nil. Conflicts of interest There are no conflicts of interest.