RARE DISEASE
Ichthyosis
Ichthyosis
Ichthyosis
Drug discovery
1
drug
With orphan designation
Overview
Ichthyosis encompasses genetic and acquired disorders of keratinization characterized by dry, thickened, scaling skin due to impaired barrier function and abnormal desquamation. While most forms are inherited (e.g., ichthyosis vulgaris, X-linked, lamellar), acquired cases may arise from systemic diseases or medications. Symptoms range from mild xerosis to life-threatening erythroderma, often with complications like infections, ectropion, and heat intolerance. Management focuses on symptomatic relief through emollients, keratolytics, and retinoids, with emerging therapies targeting underlying genetic mechanisms [1][8][12].
Burden
Categories: rare skin diseases
Research Papers
858 drug discovery papers about Ichthyosis, with 6 first-in-class and 6 next-in-class emerging drug candidates forecasted to outperform the average preclinical success rate. Recent publications:
858 drug discovery papers about Ichthyosis, with 6 first-in-class and 6 next-in-class emerging drug candidates forecasted to outperform the average preclinical success rate. Recent publications:
2026-08-01 | Ichthyosis prematurity syndrome mimicking hyper‐ IgE syndrome due to a novel SLC27A4 variant
For transparency, the peer review documents associated with this article are available at https://doi.org/10.1111/pai.70459. The data that support the findings of this study are available on request from the corresponding author. The data are not publicly available due to privacy or ethical restrictions.
2026-07-28 | Dupilumab Provides Meaningful Clinical Responses in Harlequin Ichthyosis (ABCA12-nEDD): A Report of Two Cases.
Harlequin ichthyosis (HI) is a rare epidermal differentiation disorder characterized by thick hyperkeratotic plates, fissuring, and high neonatal morbidity. Long-term management remains challenging. We report two children with genetically confirmed HI who demonstrated meaningful improvement in pruritus, erythema, scaling, and overall well-being following dupilumab therapy, suggesting a potential role for IL-4/IL-13 blockade as an adjunct or alternative treatment in HI.
2026-07-15 | Physiological and Behavioural Characterisation of a Novel Steroid Sulfatase-Deficient Mouse.
Steroid sulfatase (STS) cleaves sulphate groups from steroid hormones. In humans, STS deficiency is associated with X-linked ichthyosis, an increased predisposition to neurodevelopmental and mood conditions (including Attention Deficit Hyperactivity Disorder, autism, depression and anxiety), and cardiac arrhythmia risk. Until recently, no single-gene 'knockout' mammalian model existed; previous work in such a model is limited to skin phenotypes. We generated a novel C57BL/6J mouse model with a deletion in exon 2 of Sts. We examined gene expression and enzyme activity in liver and brain samples of homozygous mice, and assessed the breeding performance and health of male and female deletion-carriers. Subsequently, we compared performance across a range of behavioural paradigms in wildtype and homozygous male and female mice: elevated plus maze, open field, rotarod, spontaneous alternation, and acoustic startle/prepulse inhibition. We also investigated serum steroid hormone levels by liquid chromatography-mass spectrometry and measured heart weights and two morphological indices (bodyweight/tibia length) post mortem. Homozygous mice almost completely lacked STS expression/activity. Genetically-altered mice exhibited grossly-normal breeding performance, health, and endocrinology. Homozygous mice were more active and had higher normalised heart weights than wildtype mice. We also found significant genotype × sex interactions on bodyweight and on two behavioural measures (potentially reflecting lower anxiety in homozygous males and heightened anxiety in homozygous females). The 'Sts-deletion' mouse represents an experimentally-tractable model in which to identify and characterise phenotypes associated with STS deficiency. The mechanistic basis of the associations described here requires further investigation, and whether these translate to humans remains to be tested.
2026-07-06 | The role of dupilumab in skin microbiome shifts in the Netherton genodermatosis: a case report and review of literature.
Skin dysbiosis plays a crucial role in inflammatory skin diseases, particularly in genodermatoses such as Netherton syndrome (NS). This case report aimed to investigate changes in the skin microbiome of a patient with Netherton syndrome before and during dupilumab therapy, with the goal of expanding the limited evidence currently available on this topic. We report the case of a 35-year-old woman diagnosed with NS at birth, who, prior to dupilumab therapy, presented with atopic dermatitis (AD), ichthyosis linearis circumflexa, and severe pruritus. Dupilumab therapy was initiated, and skin swabs were collected from lesional sites at three different time points: at baseline, after 1 month, and after 1 year of continuous dupilumab therapy. At baseline, a microbiome analysis revealed low microbial diversity with a predominance of Pantoea and Pseudomonas species. After 1 year, a significant increase in microbial diversity, with a predominance of Staphylococcus species and an increase in Malassezia species, was observed. Clinically, the patient experienced remission in parallel with these microbiome shifts. Post-treatment, the skin microbiome showed increased microbial diversity and re-establishment of beneficial commensals, more closely resembling healthy skin. The findings of this case report underscore the role of dupilumab in restoring a healthy skin microbiome along with symptomatological and clinical improvement in the genodermatosis Netherton syndrome.
2026-07-03 | Two clinical observations of keratitis-ichthyosis-deafness syndrome (KID syndrome)
Keratitis-ichthyosis-deafness (KID) syndrome is a rare genetic disorder characterized by erythrokeratoderma, vascular keratitis and sensorineural hearing loss. The disease develops as a result of a mutation in the GJB2 gene encoding the connexin 26 protein, which is expressed in the epidermis and is involved in the formation of gap junctions between epithelial cells that carry out transport of ions and small molecules. Changes in the skin are usually noticed from birth, they may manifest as erythrokeratoderma, psoriasis-like lesions, hyperkeratosis foci, palmoplantar keratoderma. Alopecia totalis progresses with age. Congenital bilateral prelingual sensorineural hearing loss is diagnosed in 90% of patients, and neovascular keratitis — in 95%. Half of the patients experience persistent skin infection, and the development of benign and malignant tricholemmal tumors as well as squamous cell carcinoma is possible. In recent years, a search for drugs capable of restoring the patency of gap junction channels, which significantly improves the skin condition in research animals, has been performed. Effective therapeutic agents will be discovered in the future. Currently, patients are primarily treated symptomatically. We present a case report of two patients suffering from KID syndrome. In both cases, the disease began from birth and was manifested by ichthyosiform erythroderma, palmoplantar keratoderma, alopecia totalis, onychodystrophy, sensorineural deafness, chronic keratitis and photophobia. Despite the full set of diagnostic symptoms, the first patient was diagnosed with KID syndrome at the age of 29, and the second patient — at the age of 10. In the second case, genetic analysis confirmed the GJB2 gene mutation (p.Asp50Asn). The course of the disease was accompanied by a persistent bacterial infection, manifesting as the formation of abscesses, predominantly in the head area, and cracks on the skin of the extremities. An improvement in the skin condition was observed in presence of symptomatic therapy with antibacterial agents, emollients and retinoids.
2026-08-01 | Ichthyosis prematurity syndrome mimicking hyper‐ IgE syndrome due to a novel SLC27A4 variant
For transparency, the peer review documents associated with this article are available at https://doi.org/10.1111/pai.70459. The data that support the findings of this study are available on request from the corresponding author. The data are not publicly available due to privacy or ethical restrictions.
2026-07-28 | Dupilumab Provides Meaningful Clinical Responses in Harlequin Ichthyosis (ABCA12-nEDD): A Report of Two Cases.
Harlequin ichthyosis (HI) is a rare epidermal differentiation disorder characterized by thick hyperkeratotic plates, fissuring, and high neonatal morbidity. Long-term management remains challenging. We report two children with genetically confirmed HI who demonstrated meaningful improvement in pruritus, erythema, scaling, and overall well-being following dupilumab therapy, suggesting a potential role for IL-4/IL-13 blockade as an adjunct or alternative treatment in HI.
2026-07-15 | Physiological and Behavioural Characterisation of a Novel Steroid Sulfatase-Deficient Mouse.
Steroid sulfatase (STS) cleaves sulphate groups from steroid hormones. In humans, STS deficiency is associated with X-linked ichthyosis, an increased predisposition to neurodevelopmental and mood conditions (including Attention Deficit Hyperactivity Disorder, autism, depression and anxiety), and cardiac arrhythmia risk. Until recently, no single-gene 'knockout' mammalian model existed; previous work in such a model is limited to skin phenotypes. We generated a novel C57BL/6J mouse model with a deletion in exon 2 of Sts. We examined gene expression and enzyme activity in liver and brain samples of homozygous mice, and assessed the breeding performance and health of male and female deletion-carriers. Subsequently, we compared performance across a range of behavioural paradigms in wildtype and homozygous male and female mice: elevated plus maze, open field, rotarod, spontaneous alternation, and acoustic startle/prepulse inhibition. We also investigated serum steroid hormone levels by liquid chromatography-mass spectrometry and measured heart weights and two morphological indices (bodyweight/tibia length) post mortem. Homozygous mice almost completely lacked STS expression/activity. Genetically-altered mice exhibited grossly-normal breeding performance, health, and endocrinology. Homozygous mice were more active and had higher normalised heart weights than wildtype mice. We also found significant genotype × sex interactions on bodyweight and on two behavioural measures (potentially reflecting lower anxiety in homozygous males and heightened anxiety in homozygous females). The 'Sts-deletion' mouse represents an experimentally-tractable model in which to identify and characterise phenotypes associated with STS deficiency. The mechanistic basis of the associations described here requires further investigation, and whether these translate to humans remains to be tested.
2026-07-06 | The role of dupilumab in skin microbiome shifts in the Netherton genodermatosis: a case report and review of literature.
Skin dysbiosis plays a crucial role in inflammatory skin diseases, particularly in genodermatoses such as Netherton syndrome (NS). This case report aimed to investigate changes in the skin microbiome of a patient with Netherton syndrome before and during dupilumab therapy, with the goal of expanding the limited evidence currently available on this topic. We report the case of a 35-year-old woman diagnosed with NS at birth, who, prior to dupilumab therapy, presented with atopic dermatitis (AD), ichthyosis linearis circumflexa, and severe pruritus. Dupilumab therapy was initiated, and skin swabs were collected from lesional sites at three different time points: at baseline, after 1 month, and after 1 year of continuous dupilumab therapy. At baseline, a microbiome analysis revealed low microbial diversity with a predominance of Pantoea and Pseudomonas species. After 1 year, a significant increase in microbial diversity, with a predominance of Staphylococcus species and an increase in Malassezia species, was observed. Clinically, the patient experienced remission in parallel with these microbiome shifts. Post-treatment, the skin microbiome showed increased microbial diversity and re-establishment of beneficial commensals, more closely resembling healthy skin. The findings of this case report underscore the role of dupilumab in restoring a healthy skin microbiome along with symptomatological and clinical improvement in the genodermatosis Netherton syndrome.
2026-07-03 | Two clinical observations of keratitis-ichthyosis-deafness syndrome (KID syndrome)
Keratitis-ichthyosis-deafness (KID) syndrome is a rare genetic disorder characterized by erythrokeratoderma, vascular keratitis and sensorineural hearing loss. The disease develops as a result of a mutation in the GJB2 gene encoding the connexin 26 protein, which is expressed in the epidermis and is involved in the formation of gap junctions between epithelial cells that carry out transport of ions and small molecules. Changes in the skin are usually noticed from birth, they may manifest as erythrokeratoderma, psoriasis-like lesions, hyperkeratosis foci, palmoplantar keratoderma. Alopecia totalis progresses with age. Congenital bilateral prelingual sensorineural hearing loss is diagnosed in 90% of patients, and neovascular keratitis — in 95%. Half of the patients experience persistent skin infection, and the development of benign and malignant tricholemmal tumors as well as squamous cell carcinoma is possible. In recent years, a search for drugs capable of restoring the patency of gap junction channels, which significantly improves the skin condition in research animals, has been performed. Effective therapeutic agents will be discovered in the future. Currently, patients are primarily treated symptomatically. We present a case report of two patients suffering from KID syndrome. In both cases, the disease began from birth and was manifested by ichthyosiform erythroderma, palmoplantar keratoderma, alopecia totalis, onychodystrophy, sensorineural deafness, chronic keratitis and photophobia. Despite the full set of diagnostic symptoms, the first patient was diagnosed with KID syndrome at the age of 29, and the second patient — at the age of 10. In the second case, genetic analysis confirmed the GJB2 gene mutation (p.Asp50Asn). The course of the disease was accompanied by a persistent bacterial infection, manifesting as the formation of abscesses, predominantly in the head area, and cracks on the skin of the extremities. An improvement in the skin condition was observed in presence of symptomatic therapy with antibacterial agents, emollients and retinoids.
Access all drug discovery papers and probability of success in trials forecasts:
Access all drug discovery papers and probability of success in trials forecasts:
Drug Discovery Landscape
1 orphan drug designation for Ichthyosis.
1 orphan drug designation for Ichthyosis.
Drug | Therapy type | Regulator | Orphan designation | Approval | Sponsor |
|---|---|---|---|---|---|
urea | small molecules | FDA | 2011-11-07 | — | Orenova Group, LLC |
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