Secukinumab for lamellar ichthyosis in an adolescent: a case report

Introduction

Epidermolytic disorder of desquamation (EDD), formerly lamellar ichthyosis (LI), is a rare hereditary keratinization disorder, most commonly exhibiting autosomal recessive inheritance. The global incidence is estimated to range from 1 in 200,000 to 1 in 300,000 live births (1). Clinically, individuals with EDD exhibit generalized brown lamellar and armor-like scales, accompanied by classic phenotypes including eyelid ectropion, hypohidrosis, palmoplantar keratoderma and scarring alopecia (2). Its typical histopathological features are hyperkeratosis, focal parakeratosis and mild acanthosis. Autosomal recessive congenital ichthyosis (ARCI) encompasses a group of hereditary keratinization disorders with heterogeneous genetic backgrounds, involving mutations in multiple functional genes related to epidermal differentiation and barrier formation. Recent studies have further clarified the genetic basis, clinical spectrum, and diagnostic strategies of inherited ichthyoses (3-5). Transglutaminase 1 (TGM1) gene mutation is the most common genetic cause of EDD, which encodes transglutaminase 1 and plays a key role in epidermal keratinization and cornified envelope formation (6). A severe case of EDD was managed in the department, with a favorable therapeutic response. The case is detailed below. We present this article in accordance with the CARE reporting checklist (available at https://tp.amegroups.com/article/view/10.21037/tp-2026-1-0127/rc).

Case presentation

A 14-year-old female patient presented with generalized pruritic skin changes exhibiting an armor-like lamellar appearance, persisting since birth. In 2017, the individual was admitted to Dalian Dermatosis Hospital, where a diagnosis of ichthyosis was established. Oral administration of acitretin (10 mg twice daily) was initiated; however, treatment was discontinued due to elevated transaminase levels and intolerable xerosis accompanied by pruritus. Subsequent management involved the use of topical agents and unspecified cleansing products. Despite these measures, there was a progressive worsening of cutaneous lesions, with extensive thick scales forming across the entire body in an armor-like distribution, significantly impairing activities of daily living.

In December 2023, the patient was evaluated at the outpatient department of this hospital. No prior medical conditions were documented, and menstrual history was unavailable. The patient was identified as an orphaned and disabled child under centralized institutional care at the Dalian Social Welfare Institute since birth; consequently, family history could not be ascertained.

Physical examination: physical development was within normal limits, with no apparent deformities. The patient measured 157 cm in height and weighed 43 kg. She had moderate cognitive impairment (unable to perform simple logical reasoning or numerical calculation) and severe communication difficulties: only monosyllabic words could be uttered (expressive language disorder), with limited comprehension of simple daily verbal instructions (mild receptive language disorder); no motor dysfunction was noted. Cognitive and language impairment is not a classic phenotype of EDD. Given the patient’s background as an orphan raised in a welfare institute since birth with unclear early education and care, these manifestations are most likely attributable to the lack of systematic early developmental intervention. No clinical or genetic evidence supports a direct association with her TGM1 gene mutation or EDD as a neurodevelopmental comorbidity. On physical examination in the dermatology department, normal pigmentation and mild keratinization were observed only in limited areas around the eyes and lips. The remaining skin surface was covered with black-brown, warty projections. The affected areas exhibited dryness and were overlaid with thick, armor-like hyperkeratotic scales that were firm and difficult to remove. No erosion, exudation, or eyelid ectropion was found. The fingernails, toenails, and mucous membranes appeared unaffected (Figure 1). On histopathological examination (Figure 2), skin biopsy revealed pronounced lamellar hyperkeratosis with numerous follicular keratotic plugs. The stratum spinosum exhibited thinning, accompanied by mild intercellular edema. Basal cell pigmentation was present, and a mild perivascular lymphocytic infiltrate was identified in the superficial dermis. Genetic testing identified two compound heterozygous pathogenic variants in the TGM1 gene. Both variants were classified as pathogenic according to the ACMG/AMP 2015 guidelines for the interpretation of sequence variants and have been associated with ARCI type 1 [Online Mendelian Inheritance in Man (OMIM): 242300] in previous literature (7,8). Auxiliary examinations showed that results from complete blood count, liver and renal function tests, serum lipid profile, T-SPOT.TB, and lung computed tomography were all within normal limits. Based on the clinical presentation, histopathological findings, and genetic testing, a diagnosis of EDD was established.

Figure 1 Pre-treatment clinical presentation: the entire body surface is covered with black-brown lamellar scales, with a dry and rough texture. This image is published with consent from the patient’s legal guardian.

Figure 2 Histopathological examination of skin lesions from the upper limb (A: H&E ×40; B: H&E ×100; C: H&E ×400): the epidermis appears significantly lamellar and hyperkeratotic, with numerous follicular keratotic plugs. Thinning of the stratum spinosum is observed, accompanied by mild intercellular edema. Basal cell pigmentation is present, along with a mild perivascular lymphocytic infiltrate in the superficial dermis. H&E, hematoxylin and eosin.

Treatment: starting January 22, 2024, subcutaneous secukinumab 150 mg was administered weekly. In addition to secukinumab, the patient received consistent supportive skin care without any other topical medications. Cetaphil Moisturizing Cream was applied to the entire body surface three times daily throughout the entire treatment course. After 8 weeks of treatment (prior to the sixth dose), clinical assessment and photography were performed. Following eight weeks of treatment, retrospective quantitative assessment using the ichthyosis area and severity index (IASI) confirmed a significant clinical response, with substantial reductions noted in both the total IASI score (from 25 to 8), and the individual subscores for erythema and scaling. The Investigator Global Assessment (IGA) also demonstrated a clear improvement in disease severity (9,10). The thick, armor-like scales were markedly attenuated, and the overall skin condition improved significantly; however, mild furfuraceous desquamation and thin grey-brown crusts persisted in localized areas, including the extensor aspects of the extremities and the lumbosacral region (Figure 3). Repeat blood testing demonstrated normal liver and renal function, as well as normal lipid profiles. Thereafter, the frequency of secukinumab administration (150 mg) was reduced to once monthly, and continued follow-up was maintained.

Figure 3 Post-treatment clinical presentation: the previously observed thick, armor-like scales had undergone a marked reduction with nearly complete resolution, and the skin condition showed significant clinical improvement; only minimal furfuraceous desquamation and thin grey-brown scabs were residual in local areas (e.g., the extensor sides of the limbs and the lumbosacral region). This image is published with consent from the patient’s legal guardian.

Ethical considerations

All procedures performed in this study were in accordance with the ethical standards of the institutional and/or national research committee(s) and with the Declaration of Helsinki and its subsequent amendments. Written informed consent was obtained from the patient’s legal guardian for the publication of this case report and accompanying images. A copy of the written consent is available for review by the editorial office of this journal.

Discussion

Based on the medical history, physical findings, auxiliary examinations, and genetic testing, the present patient fulfilled diagnostic criteria for EDD within the ARCI spectrum. Oral acitretin was administered to the patient six years earlier, which is a conventional systemic therapy for keratinization disorders (11,12). However, acitretin has notable adverse effects such as transaminase elevation, hypertriglyceridemia, teratogenicity and aggravated cutaneous pruritus (13), which led to drug discontinuation in this patient due to elevated transaminase levels and intolerable pruritus. As a result, consideration was given to a treatment protocol with a more favorable safety and efficacy profile. Prior studies have demonstrated a strong correlation between erythema and disease severity in individuals with LI and the expression levels of interleukin-17 (IL-17) (14). On this basis, the biologic agent secukinumab was considered. Secukinumab is a recombinant fully human monoclonal immunoglobulin G1 antibody (15).

This biologic selectively binds to the cytokine IL-17, thereby inhibiting the release of pro-inflammatory cytokines and chemokines, as well as preventing their interaction with corresponding receptors. Secukinumab has been widely used in the treatment of moderate to severe plaque psoriasis, psoriatic arthritis, nail psoriasis, moderate to severe palmoplantar pustulosis, generalized pustular psoriasis, erythrodermic psoriasis, active ankylosing spondylitis, and axial spondyloarthritis (16,17). Paller confirmed that the Th17/IL-23 pathway is closely associated with the inflammatory severity of ichthyosis (14), which supports the shared immunological characteristics between ichthyosis and psoriasis. The immune dysregulation-induced epidermal barrier impairment in ichthyosis has a similar pathogenic model to psoriasis, indicating that psoriasis-targeted biologic therapies are potentially applicable to ichthyosis. Targeting the IL-17/IL-23 axis has been proven more effective than TNF-α inhibitors in psoriasis (18-23), providing a theoretical basis for using IL-17 inhibitors in inflammatory EDD.

The underlying rationale for the use of biologic agents in the treatment of ichthyosis is supported by studies conducted by Paller et al. on biologic therapies in this disease group. In one such study published in 2017, the immune profiles of individuals with LI, epidermolytic ichthyosis, congenital reticular ichthyosiform erythroderma, and Netherton syndrome (NS) were assessed and compared with those of healthy controls and individuals with AD and psoriasis (14). Features dominated by IL-17, similar to those observed in psoriasis, were identified across all ichthyosis subtypes. Among these, individuals with NS demonstrated the highest IL-17 expression levels, along with upregulation of the IL-22 pathway. A significant correlation was observed between the IASI-erythema score, IL-17A levels, and transepidermal water loss. Subsequent studies yielded similar findings, with elevated IL-17 levels found in both skin and blood samples (24,25). Luchsinger et al. reported a case series involving four patients with NS who received secukinumab over a treatment duration of 3–12 months, with a reduction in IASI scores from 88% to 55% after 6 months of therapy; it is important to note that in this study, the therapeutic effect of IL-17 inhibitors did not reach a statistically significant difference compared with the placebo group, which may be related to the small sample size of the case series and the significant individual heterogeneity of ichthyosis patients (8). A recent large international multicentric retrospective study by Mazereeuw-Hautier et al. on biologic therapy for congenital ichthyoses enrolled 98 patients with severe hereditary ichthyosis and confirmed that targeted biologic agents targeting the IL-17/IL-23 pathway exhibit significant therapeutic efficacy in ichthyosis patients with obvious inflammatory phenotypes (characterized by erythema, pruritus and inflammatory cell infiltration in pathological examination), with an overall response rate of 46% in inflammatory subtypes; in contrast, the therapeutic response is extremely poor and even completely ineffective in non-inflammatory ichthyosis phenotypes with only simple hyperkeratosis and no obvious inflammatory manifestations, which fully indicates that the presence of inflammatory activation is a key prerequisite for the effective application of IL-17 inhibitors in ichthyosis treatment. The significant therapeutic response of this EDD patient to secukinumab is the result of the combination of multiple factors: first, the patient presented with obvious inflammatory phenotypic characteristics such as generalized pruritus and mild perivascular lymphocytic infiltration in the superficial dermis in histopathological examination, suggesting the potential activation of the Th17/IL-17 inflammatory pathway in the patient, which is the core basis for the targeted efficacy of secukinumab and is consistent with the core conclusion of the above international multicenter study (26); second, the individual genetic heterogeneity of TGM1 gene mutations may lead to different degrees of immune pathway activation in EDD patients, and this patient may have a higher degree of IL-17 pathway activation, making her more sensitive to IL-17 blockade; in addition, the standardized adjuvant skin care and keratolytic treatment throughout the course of treatment effectively repaired the epidermal barrier and reduced local hyperkeratosis, which synergistically enhanced the anti-inflammatory and therapeutic effect of secukinumab.

Secukinumab was ultimately selected for the treatment of this patient. In contrast to conventional systemic therapies, primarily oral tretinoin, which is intended to reduce epidermal thickening and scaling, secukinumab targets erythema and inflammation in ichthyosis (27). This biologic agent represents a targeted therapeutic approach that appears to be both safe and effective in the context of ichthyosis management. A satisfactory clinical response has been observed in this case, and ongoing follow-up are planned.

This study has several limitations. First, as a single case report, the sample size is small, and the long-term efficacy and safety require verification by large‑sample studies. Second, no formal immunological evaluation or inflammatory biomarker analysis was performed to directly confirm IL-17 pathway activation in this patient. Third, the clinical assessment was mainly based on qualitative description and retrospective IASI scoring rather than prospective quantitative evaluation. Further multicenter studies are needed to validate the therapeutic value of secukinumab in hereditary ichthyosis.

Conclusions

This case reports a patient with EDD, or LI, caused by homozygous pathogenic variants of the TGM1 gene, who achieved significant clinical improvement with secukinumab combined with standardized topical skin care. The results suggest that secukinumab targeting the IL-17/IL-23 pathway could be a useful exploratory therapeutic option for EDD (LI) patients with obvious inflammatory phenotypes.

Acknowledgments

We thank the staff for their dedicated work in implementing the study’s intervention and evaluation.

Footnote

Reporting Checklist: The authors have completed the CARE reporting checklist. Available at https://tp.amegroups.com/article/view/10.21037/tp-2026-1-0127/rc

Peer Review File: Available at https://tp.amegroups.com/article/view/10.21037/tp-2026-1-0127/prf

Funding: None.

Conflicts of Interest: Both authors have completed the ICMJE uniform disclosure form (available at https://tp.amegroups.com/article/view/10.21037/tp-2026-1-0127/coif). The authors have no conflicts of interest to declare.

Ethical Statement: The authors are accountable for all aspects of the work in ensuring that questions related to the accuracy or integrity of any part of the work are appropriately investigated and resolved. All procedures performed in this study were in accordance with the ethical standards of the institutional and/or national research committee(s) and with the Declaration of Helsinki and its subsequent amendments. Written informed consent was obtained from the patient’s legal guardian for the publication of this case report and accompanying images. A copy of the written consent is available for review by the editorial office of this journal.

Open Access Statement: This is an Open Access article distributed in accordance with the Creative Commons Attribution-NonCommercial-NoDerivs 4.0 International License (CC BY-NC-ND 4.0), which permits the non-commercial replication and distribution of the article with the strict proviso that no changes or edits are made and the original work is properly cited (including links to both the formal publication through the relevant DOI and the license). See: https://creativecommons.org/licenses/by-nc-nd/4.0/.

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