Treatment of Lamellar Ichthyosis in a 10-Year-Old Child With Secukinumab

We report a case of a 10-year-old male patient who was born with severe large scaling and erythema, exhibiting a collodion baby presentation, while otherwise being in good general condition. A TGM1 (transglutaminase type 1) heterozygous mutation (c.788G>A and c.1559A>G) was identified. During the medical examination, no signs of erythroderma were noticeable, whereas the presence of large, brownish scales and palmoplantar keratoderma clinically supported the diagnosis of lamellar ichthyosis (LI). Despite the absence of an evident inflammatory component, the patient reported severe itching.

Figure 1 illustrates the congenital phenotype at birth and the clinical presentation at the baseline medical examination.

Ichthyoses are a clinically heterogeneous group of rare genetic skin diseases characterised by an alteration of keratinisation. This condition can manifest in several forms, ranging from dry and scaly skin to thicker plaques and scales [1].

The patient had previously been treated with various topical agents, including emollients with urea and/or salicylic acid, as well as systemic acitretin. These failed to adequately manage symptoms, as well as leading to abdominal pain as a side effect. The initial Children's Dermatology Life Quality Index (CDLQI) score was 20, the Numerical Rating Scale (NRS) of pruritus was 8 and NRS of pain was 6, indicating a significant impact on the patient's quality of life.

Recent studies have highlighted an increase in Th1, Th2 and Th17 cytokines in patients with certain genodermatoses [2]. Specifically, elevated expression of Th17-related cytokines has been observed in the keratinocytes and fibroblasts of patients with ichthyosis vulgaris and Netherton syndrome, supporting their pathogenetic role in pruritus [3].

Given the poor response to conventional therapies and considering the new scientific discoveries on the pathology of this disease [2], treatment with secukinumab was initiated. The dosing regimen followed the protocol for psoriasis: an initial subcutaneous dose of 75 mg at weeks 0, 1, 2, 3 and 4, followed by monthly maintenance dosing.

The CDLQI improved from 20 to 8 (a 60% reduction) after 3 months, maintaining this improvement for 12 months. NRS of itching reduced from 8 to 4 (a 50% reduction) within 3 months and NRS of pain decreased from 6 to 2 (a 66.7% reduction). However, despite the improvement of symptoms, scaling remained unchanged (Figure 1).

During the treatment, the patient experienced an otitis media that resolved in 10 days with antibiotic therapy and without sequelae.

De Greef [4], recently published a case of lamellar ichthyosis treated with acitretin and tralokinumab in a man in his 30s, while Taoming et al. reported a pilot study on combination therapy with secukinumab and dupilumab in Netherton syndrome [5]. These findings suggest a potential role for other biologic drugs, such as anti-IL-13 and anti-IL-4 biologics, in managing the symptoms of this pathology.

Our results support the use of secukinumab for treating the severe form of ichthyosis as a result of its efficacy and safety, which are consistent with reported data in the literature, improving both subjective symptoms and quality of life indicators.

In our patient, while the inflammatory component was not causative, it appeared to significantly contribute to the severe pruritus reported. Notably, despite the absence of a visible erythematous component, the observed improvement suggests the involvement of a subclinical immunological mechanism underlying the pruritus. Furthermore, this case highlights that clinicians prescribing secukinumab monotherapy for lamellar ichthyosis should anticipate improvements in subjective symptoms, such as pruritus and quality of life, rather than visible skin features of the disease.

All patients in this manuscript have given written informed consent for participation in the study and the use of their de-identified, anonymized, aggregated data and their case details (including photographs) for publication.

Francesca Caroppo has been a consultant for Leo Pharma, Sanofi Genzyme, AbbVie, Hollister and Amgen. Anna Belloni Fortina has been a consultant for Almirall, Amgen, Sanofi Genzyme, Pfizer, AbbVie, Leo Pharma, Unifarco, Novartis and Eli Lilly. Roberto Mazzetto, Elisa Milan and Fortunato Cassalia have no conflicts of interest.