Darier disease—A review highlighting new insights from the Darier Disease International Task Force

Abstract

Darier disease (DD) is a rare autosomal dominant genodermatosis. This comprehensive review, developed by the Darier Disease International Task Force (DDITF), consolidates current knowledge on the genetic basis, molecular pathophysiology, clinical presentation, diagnosis and management of DD, offering a global perspective that unites shared expertise. The disease arises from pathogenic variants in the ATP2A2 gene, which encodes sarco/endoplasmic reticulum Ca²⁺‐ATPase isoform 2 (SERCA2), leading to disrupted calcium homeostasis and impaired desmosomal integrity. Clinically, DD is classified based on lesion type (classic vs. non‐classic) and is often accompanied by significant extracutaneous manifestations. Management remains challenging and requires a multifaceted approach, including topical therapies, systemic retinoids and lifestyle modifications. Emerging treatments that target the underlying molecular mechanisms offer promise for improved outcomes. This review aims to provide an updated reference and practical guidance for clinicians involved in the care and study of DD.

This review provides a global, clinically focused overview of DD, detailing cutaneous and extracutaneous manifestations, disease classification and severity scoring. It emphasizes early recognition, multidisciplinary management and practical guidance for dermatologists to apply evidence‐based care in diverse skin phototypes.

Why was the study undertaken?

This review was undertaken to address major gaps in clinical knowledge of Darier disease. Many clinicians remain unfamiliar with its full range of cutaneous and extracutaneous manifestations, contributing to delayed diagnosis and suboptimal care. By synthesizing current international evidence and expert consensus from the Darier Disease International Task Force, established in 2025 and comprising 50 specialists from 25 countries, this review provides a comprehensive, up‐to‐date resource to support clinicians and improve patient management.

What does this study add?

This review provides both comprehensive knowledge and clinically‐oriented guidance on Darier disease. It covers genetic and molecular pathophysiology, clinical phenotypes, differential diagnosis (clinical and histological), disease classification, severity scoring, investigations and potential extracutaneous manifestations. Illustrated with clinical photographs, it outlines approaches to patient management and summarizes collective international expertise from the Darier Disease International Task Force, offering an expert‐based practical resource for clinicians to improve diagnosis, treatment and holistic care of patients with this rare genodermatosis.

What are the implications of this study for disease understanding and/or clinical care?

This review aims to improve understanding of Darier disease in its full clinical and multisystem complexity. By highlighting the need for interdisciplinary care, genetic consultation and evidence‐based management, it provides clinicians with practical guidance for diagnosis and treatment. Greater familiarity with cutaneous and extracutaneous manifestations, severity assessment and holistic patient management will facilitate earlier intervention, optimize multidisciplinary care and ultimately improve outcomes for patients worldwide.

INTRODUCTION

Darier disease (DD) (Darier‐White disease) was first described in 1889 by Jean Darier and James Clarke White. ¹ , ² DD, a rare autosomal dominant genodermatosis (OMIM # 124200), results from a mutated ATP2A2, which encodes the sarco‐endoplasmic reticulum calcium‐ATPase 2 (SERCA2) pump ³ and which was discovered by Alain Hovnanian's group in 1999. ⁴ , ⁵ Although most cases are familial, de novo mutations are well documented. The underlying pathophysiology involves disrupted calcium homeostasis, primarily within keratinocytes. ³ The cutaneous and extracutaneous presentations of DD are heterogeneous and vary with age. ⁶ , ⁷ Symptoms include pain, burning, tingling, pruritus and malodour. ⁸ DD has a negative impact on patients' health‐related quality of life (HRQL), which correlates with total body surface area affected and clinical severity. ⁹

The review was developed through a comprehensive literature evaluation, clinical experience from international centres and multiple structured discussions. It summarizes the collective knowledge and extensive clinical experience of the Darier disease International Task Force (DDITF)—an expert group of 50 international dermatologists specializing in DD, established in February 2025. We are honoured to have received the prestigious endorsement of the International League of Dermatological Societies (ILDS) for the DDITF. This review includes members of the European Reference Network (ERN) with whom we are honoured to collaborate on the topic of DD. It is designed not only to provide a comprehensive overview of the disease but, more importantly, to serve as a practical guide for clinicians worldwide who are managing patients with DD.

EPIDEMIOLOGY

The prevalence of DD is estimated between 1 in 30,000 and 1 in 100,000 in European populations, based on studies from Scotland, northern England and Denmark. ¹⁰ , ¹¹ , ¹² The disease typically first manifests between the ages of 6 and 20 years, with no significant sex predilection. Penetrance is generally complete by adulthood, although expressivity is highly variable. While most cases are familial, approximately 14% may arise from de novo mutations. No clear genotype–phenotype correlation has been established, and even within families, the clinical phenotype can vary considerably. ¹⁰ , ¹¹ , ¹² Epidemiological studies from outside Europe further support the global distribution of DD. A study from Singapore reported an incidence of 3.1 per million per decade, with demographic and clinical characteristics similar to those described in Western populations. ¹³ Additional reports from Israel and Tunisia confirm similar patterns in inheritance, age of onset and phenotypic heterogeneity, underscoring the worldwide occurrence of this disorder. ¹⁴ , ¹⁵ However, DD may be underdiagnosed when symptoms are subtle or mild, and in some regions, confirmatory diagnostic testing may not be readily available.

GENETICS

The defective gene in DD was identified by positional cloning on chromosomal region 12q23‐24 in 1993. ⁴ ATP2A2 encodes for sarcoplasmic/endoplasmic reticulum calcium ATPase2 (SERCA2). SERCA2 is a calcium pump transporting Ca²⁺ from the cytosol to the lumen of the endoplasmic reticulum (ER) where it is stored at high concentration. ATP2A2 is transcribed into three different isoforms resulting from alternative splicing. SERCA2a is expressed in the slow‐twitched skeletal muscles and cardiac muscle, whereas SERCA2b is the major isoform in the human epidermis. ¹⁶ , ¹⁷ SERCA2 contains three cytoplasmic domains (the actuator, phosphorylation and ATP‐binding domains) and 11 transmembrane helices where the two Ca²⁺ binding sites are located ¹⁸ (Figure 1).

FIGURE 1.

(a) The SERCA2 transmembrane protein is a calcium pump that transports Ca²⁺ from the cytosol to the endoplasmic reticulum of keratinocytes. Its dysfunction in Darier disease leads to disrupted calcium homeostasis, impaired intercellular adhesion, ER stress, and abnormal keratinocyte differentiation. (b) Schematic domain structure of the SERCA2 protein adapted from Sakuntabhai et al., ⁴ Ringpfeil et al., ¹⁹ and Takeichi et al. ²⁰ with modifications. Courtesy of Professor T. Takeichi.

The Human Gene Mutation Database (HGMD) reports 294 distinct pathogenic variants described in individuals with DD (October 2025). Missense mutations altering the protein function represent the most frequent variants (47%). Other pathogenic variants include small deletions (21%), nonsense variants (8.3%), splicing defects (12.2%), small insertions (8.8%) and gross deletions/insertions/duplications and complex rearrangements (2.7%). ²¹ They are distributed throughout the gene. Several missense and nonsense variants have been shown to impair Ca²⁺ transport, supporting a mechanism of haploinsufficiency. ²² There is no obvious genotype–phenotype correlation, although missense variants were more frequently reported in severe forms. ⁵ , ²³ The clinical variability for the same mutation within or between families suggests that additional genetic, epigenetic and/or environmental factors could play a role in the disease phenotype. Segmental Darier corresponds to Darier mosaicism (type 1) where the disease is limited to Blaschko's lines resulting from pathogenic variants in ATP2A2 restricted to developmental body segments. ²⁴ In rare instances, persistent Darier lesions were associated with the presence of second‐hit somatic variants in the ATP2A2 gene (type 2 mosaicism). ²⁵ Grover disease has been shown to be caused by ‘acquired’ mosaicism for somatic variants of ATP2A2 in the lesional skin. ²⁶

Genetic counselling based on ATP2A2 mutational analysis is crucial for patients and their relatives. While typical clinical morphology and histopathologic features are sufficient to make the diagnosis, identifying pathogenic ATP2A2 variants can confirm the diagnosis in mild, sporadic or ambiguous cases. However, the absence of detectable variants or the presence of variants of uncertain significance does not exclude DD, complicating counselling. Additionally, intra‐ and interfamilial variability for the same variant further challenges genetic counselling.

PATHOGENESIS

SERCA2 plays a key role in Ca²⁺ homeostasis by replenishing the ER Ca²⁺ pool from cytosolic Ca²⁺. ¹⁸ Loss‐of‐function SERCA2 variants result in diminished Ca²⁺ pools in DD keratinocytes which has profound consequences on cell‐to‐cell adhesion, ER stress and epidermal differentiation. ²⁷ , ²⁸ , ²⁹ , ³⁰ Decreased ER Ca²⁺ stores have been shown to impair adherens‐junction and desmosome formation and to induce ER stress. E‐cadherin, desmoglein 3, desmocollin 2/3 and desmoplakin are reduced at the plasma membrane and show partial retention in DD keratinocytes. ³¹ , ³² These abnormalities were reversed in vitro by miglustat treatment, a glucosidase inhibitor and pharmacological chaperone, which could improve the folding of junctional proteins. ³³ UVB‐light and heat may aggravate clinical symptoms during summer, UV‐mediated suppression of ATP2A2 was reported. ³⁴ Abnormal Ca² homeostasis is likely to dysregulate the expression of several genes in the epidermal differentiation complex that are known to play a key role in terminal keratinocyte differentiation. Other studies have implicated decreased intracellular sphingosine‐1 phosphate, abnormal distribution of prurigenic ATP receptors and increased TRPC1 expression. ³⁵ , ³⁶ Loss of SERCA2 has also been shown to impair the membrane translocation of protein kinase C alpha, a known regulator of desmoplakin‐intermediate filament association and desmosome assembly. ³⁷ Recently, downregulation in actin‐regulating genes was reported in DD patients. ³⁸ Increased MAPK signalling and ERK hyperphosphorylation have been reported in SERCA2‐deficient hTERT‐immortalized keratinocytes and organotypic epidermal tissues. ³⁹ Reversion of cell‐to‐cell adhesion defects with MEK inhibitors in vitro suggests this class of drugs as a potential therapeutic option for DD patients, which was substantiated in a recent case report. ⁴⁰ Finally, several recent studies report an increased IL‐17 or IL‐23 cytokine signalling in the lesional skin of patients with DD as well as increased Th17 cells in the circulation and skin of DD patients. ⁴¹ These observations have led to the successful treatment of a few DD patients with secukinumab or guselkumab. ⁴²

CUTANEOUS IMMUNOBIOLOGY

The role of cutaneous immunity in DD remains uncertain though cutaneous microbiome dysbiosis (discussed below) may suggest innate immune system dysregulation. Lesional skin exhibits a CD4⁺ T‐cell–dominated infiltrate with reduced Langerhans and dendritic cells, indicating impaired local surveillance, ⁴³ while transcriptomics show upregulated repair, antimicrobial and inflammatory pathways, potentially driven by dysbiosis. ⁴⁴ , ⁴⁵ The Th17/IL‐23 axis may play an important role, with IL‐17 cytokines and Th17 cells elevated at psoriasis‐like level. ³⁸ , ⁴¹ , ⁴⁶ IL‐23/IL‐17–targeting biologics can improve skin disease and pruritus, though effects vary and may be transient. ⁴¹ , ⁴⁷ , ⁴⁸ Additional reports of benefit with IL‐4/IL‐13 blockade point to type 2 immunity in subsets. ⁴⁹ Whether these inflammatory pathways are a primary driver of DD pathology or a secondary effect from an impaired skin barrier remains uncertain. ⁵⁰ Overall, DD likely results from combined defects in both keratinocyte differentiation and immune regulation, shaped by intrinsic Ca2+ signalling abnormalities, barrier impairment, dysbiosis and Th17/Th2‐mediated inflammation.

SKIN DYSBIOSIS

Recent studies show that the skin microbiome in DD displays distinct dysbiosis, with reduced microbial diversity, loss of commensal organisms and pathogen overgrowth. Lesional skin has significantly lower microbial richness and evenness than non‐lesional or healthy skin. Cutibacterium acnes (formerly P. acnes) and C. acnes subspecies defendens are markedly reduced, even in non‐lesional sites. ⁵¹ Commensals such as Micrococcus luteus and Staphylococcus hominis are also underrepresented. ⁴⁵ Lesional sites are consistently dominated by Staphylococcus spp., particularly S. aureus, ⁴⁵ , ⁵¹ which correlates with disease severity ⁴⁵ , ⁵² and malodour. ⁴⁵ S. aureus was isolated from 68% of lesional and 47% of nasal cultures among 75 patients, with culture‐positive patients exhibiting more extensive and severe disease. ⁵² Overall, Staphylococcus species are strongly associated with DD lesions and dysbiosis. ⁴⁴ , ⁴⁵ , ⁵¹ DD also predisposes patients to cutaneous herpes simplex virus (HSV) superinfection, which can cause acute, sometimes severe, exacerbations of the disease and systemic illness. ⁵³ , ⁵⁴

CLINICAL FEATURES

Skin and nails

Clinical presentation

DD shows marked variability in clinical presentation and severity, both between and within families, ranging from subtle palmar or nail changes to extensive cutaneous involvement. Severe cases are typically associated with earlier disease onset. ⁶ , ⁴² , ⁵⁵

The cutaneous manifestations of DD are the predominant pathology; however, DD also involves important extracutaneous features, reflecting its nature as a multi‐organ disease (Table 1). ⁵⁵ The wide variability of DD lesions underscores the need for a standardized classification system that differentiates between classical and non‐classical forms (Table 2). Classical lesions are common and disease‐defining, including keratotic papules, pits, wart‐like lesions and nail abnormalities. Non‐classical lesions are less common, occurring in a subset of patients, and include acral keratoderma, leukodermic macules, giant comedones, vegetative plaques and acral haemorrhagic blisters. This distinction forms the basis for classifying DD itself as classical (only classical lesions) or non‐classical (at least one non‐classical lesion). Differentiating between transient and persistent lesions is also important for assessing response to treatment, and recent findings link persistent lesions to second‐hit somatic ATP2A2 mutations. ²⁵

TABLE 1.

The NOBEL acronym. A concise clinical framework and communication tool for potential multisystem involvement.

Note: The NOBEL acronym represents neurological, ocular, buccal/parotid, emotional and learning domains. This scoring system allows standardised documentation of systemic involvement, facilitating communication among specialists and emphasizing the potential extracutaneous manifestations of DD. NOBEL score for systemic involvement in DD: 0 = no involvement, 1 = involvement of the specified system: N (0/1), O (0/1), B (0/1), E (0/1), L (0/1). For example, a patient with DD with recurrent parotid gland obstruction, bipolar disorder and dyslexia but no history of neurological or ocular findings will have the following NOBEL score: N₀ O₀ B₁ E₁ L₁. This acronym was developed by the author group and is intended to be used as a practical clinical tool.

Abbreviation: DD, Darier disease; EEG, electroencephalogram.

TABLE 2.

Classification of DD according to the type of lesion.

Abbreviation: DD: Darier disease.

To evaluate skin severity and monitor cutaneous treatment response, we recommend using the Darier Skin Activity Score Investigator Global Assessment (DSAS‐IGA). The DSAS‐IGA assesses keratotic papules only, evaluating their affected body surface area and secondary changes such as oozing and crusting. It was specifically designed to capture changes in the variable lesions, as persistent lesions do not reliably reflect treatment response. Accordingly, the DSAS‐IGA is tailored for classical DD, and a separate assessment system is required for non‐classical DD ⁶ (Table 3).

TABLE 3.

Darier skin activity score investigator global assessment (DSAS‐IGA). ²⁵

Abbreviation: BSA, body surface area.

Classical and non‐classical lesions are summarized here:

1. Classical lesions:

   1. Keratotic papules (Figure 2): The typical lesions are 1–2 mm, thickened and scaly, reddish brown, greasy papules which sometimes become confluent into plaques and which favour seborrhoeic distributions (e.g. scalp, face, neck, upper trunk) but may also affect other locations. ⁶ , ⁵⁵
   2. Wart‐like lesions (Figure 3): 2–5 mm skin‐coloured to brownish flat‐topped, acral lesions usually located on the dorsal aspect of hands and/or feet that become more prominent upon immersing the hands in water, a phenomenon known as the wet hand sign. ⁴² Acrokeratosis verruciformis of Hopf is a clinical term used to describe persistent, flat‐topped, wart‐like papules on the dorsal hands and feet, which are clinically and histologically indistinguishable from lesions of DD. Both are allelic disorders caused by ATP2A2 pathogenic variants, though there remains debate as to whether they represent distinct entities or variable expressions of the same condition. ⁵⁶
   3. Acral pits (Figure 4): small, sharply demarcated, depressed lesions located on acral skin (palms, soles or distal phalanges), often presenting as flat‐based lesions with indentation that may be solitary or multiple and may be surrounded by a raised hyperkeratotic rim.
   4. Nail changes are characteristic and include longitudinal erythronychia and leukonychia (‘candy‐canes appearance’), longitudinal ridging and fissuring, and wedge‐shaped subungual hyperkeratosis. The nails are often brittle and exhibit distal V‐shaped notches. Rarely, complete nail dystrophy may occur (Figure 5). ⁶

2. Non‐classical lesions

1. Vegetative plaques (Figure 6): exophytic, papillomatous or verrucous plaques that develop most commonly in intertriginous areas due to chronic maceration, secondary bacterial or fungal infection and persistent inflammation. These lesions are characterized clinically by thickened, moist, malodorous and sometimes crusted plaques.

2. Keratoderma: punctate or flat‐topped hyperkeratotic papules and plaques affecting the palms and soles.

3. Leukodermic macules (Figure 7): well‐demarcated, hypopigmented, usually guttate lesions that can occur on the trunk, extremities or face.

4. Giant comedones (Figure 8): large, keratin‐filled follicular plugs that usually appear as brown or black papules or plaques, most commonly on the forehead, cheeks and upper trunk.

5. Acral bullous lesions (haemorrhagic and non‐haemorrhagic) (Figure 9): Haemorrhagic blisters are often accompanied by dark red to purpuric macules and papules, typically precipitated by trauma. Non‐haemorrhagic blisters contain clear or serous fluid.

FIGURE 2.

(a–c). Classical lesions: Keratotic papules on the left neck (a), chest (b) and scrotum (c). Courtesy of Professor R. P. Dodiuk‐Gad and Professor L. Gupta.

FIGURE 3.

(a, b). Classical lesions: Wart‐like lesions on the dorsum of the foot (a) and dorsum of the hand (b). Courtesy of Professor R. P. Dodiuk‐Gad and Professor L. Gupta.

FIGURE 4.

Classical lesions: Acral pits. Courtesy of Professor R. P. Dodiuk‐Gad.

FIGURE 5.

(a, b). Classical lesion: Nail changes (a) distal V‐shaped notching; (b) longitudinal fissures and leukonychia. Courtesy of Professor R.P Dodiuk‐Gad and Professor L. Gupta.

FIGURE 6.

(a, b). Non‐classical lesions: Vegetative plaques on the buttocks (a) and left posterior auricular area and neck (b). Courtesy of Professor R. P. Dodiuk‐Gad.

FIGURE 7.

(a, b). Non‐classical lesions. Leukodermic macules on the back (a) and leg (b). Courtesy of Professor R. P. Dodiuk‐Gad and Professor L. Gupta.

FIGURE 8.

Non‐classical lesion. Giant comedones. Courtesy of Professor R. P. Dodiuk‐Gad.

FIGURE 9.

(a–c). Non‐classical lesions. Acral bullous lesions: (a) haemorrhagic, (b) non‐haemorrhagic, (c) Close‐up of panel b. Courtesy of Professor R. P. Dodiuk‐Gad.

Table 4 summarizes the clinical differential diagnoses of DD, organized according to classical and non‐classical lesion types.

TABLE 4.

Clinical differential diagnoses of DD based on classical and non‐classical lesions.

Symptoms

The symptoms of DD commonly include malodour, pruritus and pain. When a secondary infection develops, even if mild, signs and symptoms may intensify, leading to increased erythema, exudation, crusting and tenderness of the affected areas.

Mucous membranes (oral and genital)

While less common than skin lesions, oral (Figure 10) and genital (Figure 11) mucosal involvement represents an important yet often overlooked manifestation of DD. ⁵⁷ , ⁵⁸ , ⁵⁹ , ⁶⁰ , ⁶¹ Table 5 provides a detailed overview of their clinical features and anatomical distribution. ⁵⁵ , ⁵⁷ , ⁶² Additional gastrointestinal involvement has been reported. ⁶³

FIGURE 10.

Oral mucosal lesions. Whitish papules of varying size with a central depression. Courtesy of Professor L. Gupta.

FIGURE 11.

Mucosal involvement of the vulva. Courtesy of Professor R. P. Dodiuk‐Gad.

TABLE 5.

DD mucous membrane involvement (oral and genital).

Extracutaneous features of DD

In addition to its cutaneous manifestations, DD is associated with important extracutaneous features that should be assessed in all patients (Table 1). Some associations are well established, while others require further study.

Neuropsychiatric findings and learning disabilities

Neuropsychiatric disorders are common, occurring in 37–50% of patients with DD. ⁷ , ¹⁴ The spectrum of disorders includes depression, anxiety, schizophrenia, bipolar and personality disorders. ⁶⁴ Compared to population controls, studies have demonstrated an increased relative risk for bipolar disorder, schizophrenia, ⁶⁴ depression and anxiety disorder, ⁶⁵ as well as elevated risks of Parkinson's disease, vascular dementia and epilepsy. ⁶⁶

Suicidal ideation was reported to affect 30% of DD patients. ⁷ , ¹⁴ This risk of suicide is three times higher compared to control populations. ⁶⁷ Epilepsy was reported in 3% of the DD population. ⁷ An increased risk for attention‐deficit hyperactivity disorder (ADHD) is possible, ⁶⁸ though more studies are needed to explore the neuropsychiatric manifestations. Learning disability was reported in up to 41% of DD patients ⁶⁸ and the risk of being diagnosed with intellectual disability was six times higher compared to population controls. ⁶⁹ Additionally, DD is associated with an increased incidence of cognitive impairment ⁷⁰ and substance misuse disorder. ⁷¹ The SERCA2b isoform of SERCA2 is widely expressed throughout the central nervous system and impaired calcium homeostasis in neural tissue is postulated to be responsible for the observed increased risk of neuropsychiatric dysfunction and learning disabilities in DD. ⁷² , ⁷³ The psychosocial burden of dealing with this complex chronic disease with limited treatments creates additional major emotional challenges for patients.

Ocular involvement

Ocular involvement has been reported in patients with DD and includes chronic blepharitis, dry eyes and hyperkeratotic eyelid lesions. Corneal epithelial abnormalities, such as corneal ulceration and infectious keratitis, have also been observed. ⁷⁴ , ⁷⁵ , ⁷⁶ Blackman and colleagues identified corneal changes or keratotic plaques on the eyelids in 16 of 21 patients. ⁷⁷ Eyelid involvement, blepharitis and a short tear film break up time were identified in a large proportion of 36 individuals with DD, leading to dry eyes and eye fatigue in over one‐third. ⁷⁴

Parotid gland

Parotid gland involvement is a less recognized extracutaneous manifestation of DD. ⁵⁸ , ⁵⁹ , ⁶⁰ Intermittent parotid swelling has been reported in up to 30% of patients and is often associated with oral mucosal involvement. Sialographic findings frequently reveal ductal strictures, suggesting an obstructive rather than a primary inflammatory or neoplastic process. ⁵⁷ ATP2A2 variants are proposed to affect calcium homeostasis, not only in keratinocytes but also in ductal epithelial cells of the parotid gland, leading to impaired secretion and ductal obstruction. ⁷⁸ , ⁷⁹

Cardiac disease

The SERCA2a isoform is predominantly expressed in the myocardium ⁸⁰ and dysregulated expression and function of the protein has been associated with heart failure (HF). ⁸¹ , ⁸² However, a relationship between DD and HF has only recently been described. In a Swedish epidemiological study, Bachar‐Wickström et al. identified a risk ratio for HF of 1.59 (CI 1.16–2.19) in individuals with DD in whom this complication tended to occur several years earlier than controls. ⁸³ Further studies are needed to explore cardiac risks in DD.

Diabetes mellitus

ER stress has been associated with pancreatic beta cell dysfunction ⁸⁴ and dysregulation of SERCA pumps has been shown in both type 1 and 2 diabetes mellitus (DM). ⁸⁵ A Swedish population study identified an increased RR in DD of 1.74 for type 1 DM, but not for type 2 DM (0.88). ⁸⁶ Further studies are needed to explore the risk of DM in DD.

Recognition of potential extracutaneous manifestations of DD is crucial for accurate diagnosis, comprehensive management and improved patient outcomes. Traditionally regarded as a purely cutaneous disorder, DD is increasingly recognized as having variable extracutaneous manifestations. To support a systematic patient evaluation, we introduce the NOBEL score—with an acronym representing Neurological, Ocular, Buccal/Parotid, Emotional and Learning domains—summarized in Table 1. The NOBEL acronym is a concise clinical framework and communication tool for multisystem assessment in DD.

If future evidence confirms associations with cardiac involvement, diabetes mellitus or other systemic features in DD, the NOBEL acronym can be expanded accordingly.

CLINICAL ASSESSMENT

A comprehensive clinical assessment of patients with DD should include a thorough medical history and physical examination, considering the multisystemic nature of the disorder and the variability phenotype (cutaneous and extracutaneous). A multidisciplinary approach involving dermatologists, geneticists, psychiatrists, ophthalmologists and other specialists is often necessary for optimal management. To facilitate this process, we have developed a practical, structured guide (Table 6 history taking in DD and Table 7 assessment of patients with suspected or confirmed DD).

TABLE 6.

Key elements of history taking in DD.

TABLE 7.

Laboratory assessment of patients with suspected or confirmed DD.

Abbreviations: HIV, human immunodeficiency virus; HSV, herpes simplex virus; KOH, potassium hydroxide; PCR, polymerase chain reaction.

^a Not essential, only if possible.

Dermoscopy

Dermoscopy can facilitate early diagnosis of DD and is particularly useful for identifying non‐classical or subtle lesions, especially in seborrhoeic areas. As a non‐invasive tool, dermoscopy may also assist in assessing treatment response over time. ⁸⁷ For optimal evaluation, the use of standardized dermoscopic terminology, as recommended by the International Dermoscopy Society guidelines, is suggested. ⁸⁸ , ⁸⁹ , ⁹⁰

The dermoscopic features of DD were first described by Vázquez‐López et al. in 2004, with subsequent studies providing more detailed characterizations of these patterns. ⁸⁷ , ⁹⁰ , ⁹¹ , ⁹² , ⁹³ , ⁹⁴ In recent years, dermoscopy has gained recognition as a valuable, non‐invasive diagnostic aid for DD, enabling differentiation from other papulosquamous, acantholytic or keratotic dermatoses. ⁹⁰ The most consistent dermoscopic findings reflect the disease's core histopathological features: central keratotic structures, such as yellowish‐brown, polygonal, roundish or star‐shaped areas representing hyperkeratosis and dyskeratosis, typically surrounded by a whitish halo that correlates histologically with acanthosis. A pinkish, homogeneous structureless background reflecting dermal inflammation is frequently observed. Additional features may include linear or dotted vessels and whitish scales. In addition to descriptive terminology, metaphoric terms such as ‘cracked riverbed‐like’ or ‘tire‐tread’ like appearance are sometimes used to describe yellowish‐brown areas with surrounding white or yellow scaling, mimicking fissures or cracks, a relatively characteristic feature of DD ⁹⁵ , ⁹⁶ (Figure 12). Nail dermoscopy (onychoscopy) in DD often reveals longitudinal erythronychia terminating in a characteristic V‐shaped notch at the distal edge (Figure 5). ⁸⁹ , ⁹⁶

FIGURE 12.

(a–c) Dermoscopy features of skin lesions in patients with DD. (a) Central polygonal yellowish‐brown areas surrounded by whitish halo and in the background pink structureless areas. (b) Metaphoric terms ‘cracked riverbed‐like’ appearance with pink‐reddish areas along with yellow scales. (c) A combination of polygonal yellowish‐brown areas surrounded by a whitish halo, together with erosions, pink‐reddish structureless areas and white scales. Courtesy of Professor M. Medvecz and Dr. D. Plázár.

There remains a significant unmet need for large, methodologically robust studies on the dermoscopy of DD. To date, most available studies have been limited by small sample sizes. Future research should include larger cohorts with clear differentiation between classical and non‐classical variants. Such studies will be essential to establish consistent dermoscopic criteria and enhance diagnostic precision in DD.

Histopathology

The histopathologic hallmark change in DD is acantholytic dyskeratosis (Figure 13) (Table 8). ⁹⁷ , ⁹⁸ Due to faulty cellular adhesion and severing of desmosomes, acantholysis appears as separation between individual keratinocytes which generally retain their rounded shape. Generally, acantholysis occurs at the suprabasal level, where small clefts may form, though the full thickness of the epidermis may be involved occasionally. ⁹⁹ In addition, acantholysis may extend down hair follicles, ⁹⁸ while eccrine acantholysis is quite rare. Acantholysis is accompanied by dyskeratosis or abnormal cornification of epidermal keratinocytes. Round cells with eosinophilic cytoplasm and hyperchromatic nuclei, with clear halos in the granular layer are referred to as corps ronds, while smaller elongated cells with compressed nuclei in the stratum corneum are termed grains. Hyperkeratosis with or without parakeratosis may be seen, as may hyperkeratotic follicular plugs. ¹⁰⁰ Thicker clinical lesions may be associated with acanthosis or rarely pseudoepitheliomatous change (generally, in the setting of persistent trauma and/or bacterial superinfection). ¹⁰⁰ In a minority of cases, cornoid lamellae‐type changes can be observed. ⁹⁸ A clue to DD compared to some of its microscopic mimics (e.g. warty dyskeratoma) is the multifocality of the acantholytic dyskeratosis. ⁹⁸ Histologic assessment should include evaluation for herpetic superinfection ⁵⁴ characterized by chromatin margination, multinucleated keratinocytes and tissue necrosis. ¹⁰¹ Clinical correlation remains essential for accurate diagnosis.

FIGURE 13.

(a, b) Histopathologic features of Darier disease. (a) Multiple foci of acantholytic dyskeratosis are observed (haematoxylin‐and‐eosin stain, original magnification ×10), with characteristic suprabasilar acantholysis, corps ronds and corps grains (haematoxylin‐and‐eosin stain, original magnification ×20) (b). Courtesy of Professor J. Lehman.

TABLE 8.

Microscopic differential diagnoses of DD.

Disease	Acantholytic dyskeratosis characteristics	Distinguishing features from Darier disease	Reference(s)
Grover disease	Acantholytic dyskeratosis	Presence of eosinophils, lichenoid inflammation, eczematous changes including spongiosis	[19]
Hailey‐Hailey disease	Acantholysis involving entire epidermis	Absence of dyskeratosis favours Hailey‐Hailey	[97]
Warty dyskeratoma	Focal acantholytic dyskeratosis	Solitary lesion; often follicular‐based; lack of a family history of DD	[20]
Acantholytic dyskeratotic acanthoma	Focal acantholytic dyskeratosis, often well‐circumscribed and with acanthosis	Solitary lesion, benign neoplastic nature, trunk/extremities	[102]
Papular acantholytic dyskeratosis of the genitocrural region	Acantholytic dyskeratosis	Location‐specific (genitocrural); clinical features differ	[103]
Pityriasis Rubra Pilaris (PRP)	Mild psoriasiform changes, checkerboard‐type parakeratosis with variable acantholytic dyskeratosis	More prominent psoriasiform changes; distinct checkerboard pattern of parakeratosis	[104]
Pemphigus (e.g. vulgaris)	Acantholysis, sometimes with dyskeratosis	Presence of desmoglein 1 or 3 antibodies, as can be confirmed via direct immunofluorescence (tissue‐bound), indirect immunofluorescence, or ELISA for desmoglein 1 and 3 antibodies (circulating)	[99, 105]

NEW CLASSIFICATION OF EPIDERMAL DIFFERENTIATION DISORDERS

The updated classification of epidermal differentiation disorders (EDDs) ¹⁰⁶ represents a major step toward a coherent and gene‐based framework, distinguishing nonsyndromic (nEDD), syndromic (sEDD) and palmoplantar (pEDD) forms. ¹⁰⁷ , ¹⁰⁸ , ¹⁰⁹ Disorders are now named by the affected gene followed by the EDD designation and, when useful, a clinical descriptor. DD has recently been included in this group. While DD has traditionally been regarded as a non‐syndromic EDD, emerging evidence supports discussion about changing its classification to syndromic EDD in the future. A fruitful and ongoing discussion continues within the field regarding the syndromic versus non‐syndromic nature of DD. ¹⁰⁷ , ¹¹⁰

MANAGEMENT

Management strategy

Management of patients with DD is elaborated in Table 9.

TABLE 9.

Management of patient with DD.

Explanation of disease	Potential multisystem involvement (Table 1) Inheritance: autosomal dominant; family‐specific features; penetrance—complete, phenotype—variable; family consultation/genetic consultation and prenatal testing and procedures if available
Triggers to avoid	Sweating (heat, exercise)—friction (tight clothing) UV/Sun exposure Infections Stress
Social/Occupational advice	Indoor or low‐heat environments recommended—avoid physically strenuous jobs that induce sweating or require prolonged sun exposure Referral to support group	DD support group—Decoding Dariers https://decodingdariers.com/https://linktr.ee/decodingdariers
Preventive skin care	Bleach baths—antiseptic soaps Regular moisturizing Botulinum toxin	Bleach baths (e.g. diluted sodium hypochlorite 2–3 times per week for 5–10 min)
Topical therapy	Emollients‐Topical corticosteroids (short‐term) Topical antibiotics (for bacterial infection) Topical retinoids (e.g. adapalene, tretinoin, tazarotene) Keratolytics (e.g. salicylic acid, urea) Topical non‐steroidal anti‐inflammatory (e.g. diclofenac)	Topical retinoids can be irritating so should be used with caution
Systemic drug therapy a	Oral retinoids (e.g. acitretin 0.2–0.7 mg/kg/day, isotretinoin 0.5‐1 mg/kg/day, alitretinoin 10‐30 mg/day; may consider dosing on alternate days) a Antibiotics 111 , 112 , 113 or antivirals for secondary infections Antihistamines for itch 114 Naltrexone 115 : from 1.5 mg/day to 6 mg/day is reported in the literature but the authors' experience is of 3 mg/day Doxycycline 100 mg once to twice daily Biologics, dose according to label (anti‐IL‐17, anti‐IL‐23, IL‐4R) 41 , 47 , 48 , 49 Small molecule inhibitors (apremilast) 116	Low‐dose oral retinoids for moderate/severe disease as maintenance treatment
Other	Botulinum toxin 117 Photodynamic therapy 118 , 119 , 120 , 121 , 122 , 123 Lasers 124 , 125 , 126 , 127 , 128 , 129 , 130 , 131 , 132 Low‐dose superficial radiation therapy (SRT) 133 , 134 , 135 , 136 , 137 Electron beam therapy 133 , 137 Surgery 138 , 139 , 140 , 141 , 142 Dermabrasion 143
Specialist referrals	Based on symptoms: Psychology/Psychiatry Oral Medicine Gynaecology/Urology Ophthalmology Neurology

Note: None of these treatments were assessed in double blind placebo controlled trials, all are based on case reports/series and the authors' experience. In bold are the authors' recommendations.

^a Various dosages are reported in the literature and any dose adjustments may be made at the clinician's discretion.

There is no curative therapy for DD. Its chronic, relapsing course makes treatment challenging, with current options primarily focused on symptomatic relief and treatment of pain and secondary infection (commonly bacterial and viral). ⁴⁸ Various treatments have been reported in the literature (primarily as case reports and case series) with varying degrees of response and a likely publication bias towards successful case outcomes rather than failed interventions. Treatment aims to reduce inflammation, keratinization, decrease pathogenic bacterial colonization and bacterial and herpetic infections. The treatment should be tailored according to the type of lesion (Table 2). Treatment of vegetative plaques, comedonal lesions, keratoderma and bullae necessitates a different management than treatment of classical keratotic papules and plaques, adding to the challenge of reaching consensus on treatment guidelines. In DD, seasonal variation, particularly in humid or high‐UV regions, necessitates flexible treatment strategies, with more intensive therapy often required during flare‐prone seasons. Bacterial dysbiosis significantly contributes to skin disease severity. Therefore, preventive strategies aimed at reducing pathogenic bacterial colonization, such as antimicrobial washes or dilute bleach baths, constitute an essential component of management in most patients.

Antiseptics

To reduce pathogenic bacterial colonization, control odour and prevent flares, the use of antiseptics is recommended. In the authors' experience, the following measures may be helpful: for localized disease, antiseptic soaks or compresses of diluted bleach or diluted vinegar can be used; for widespread disease, dilute bleach baths (e.g. 0.005% sodium hypochlorite, equivalent to 1 mL of household bleach per litre of water or approximately ½ cup per full 20‐gallon bathtub) are preferred. Although dilute bleach baths are well studied in atopic dermatitis, ¹⁴⁴ their efficacy in DD is undocumented. We suggest 5–10 min baths two to three times per week as a preventive measure, and daily baths during flares, particularly when crusting is present.

Botulinum toxin injection

Botulinum toxin injections, particularly in areas prone to friction and sweating such as intertriginous zones (e.g. axillae, groin), have been reported to improve skin lesions, likely via reduced eccrine secretions. ¹¹⁷ This is also supported by the authors' experience.

Oral immunomodulatory and anti‐proliferative therapies

Oral retinoids remain the preferred first‐line therapy for widespread severe disease due to their effect on epidermal differentiation and keratinocyte turnover. ¹⁴⁵ In the largest published series, they proved to be beneficial in 91% of patients but adverse effects are common, ⁵⁵ , ¹⁴⁶ , ¹⁴⁷ , ¹⁴⁸ , ¹⁴⁹ , ¹⁵⁰ , ¹⁵¹ , ¹⁵² relapse after withdrawal of retinoids is frequent and teratogenic risk is high. In women of child‐bearing age, isotretinoin is preferred over other retinoids due to its shorter half‐life, while maintaining comparable efficacy. Retinoids need to be stopped if considering pregnancy or becoming pregnant unexpectedly. Most patients respond well to low‐dose systemic retinoids (e.g. acitretin, isotretinoin and alitretinoin on alternate days or 3 times per week). It is advised to start with a low dose and monitor the patient's mental health and mood during treatment with retinoids, although the association with psychological side effects remains controversial. Beyond retinoids, doxycycline has been used with success, including maintenance on a low dose. ¹¹¹ , ¹¹² , ¹¹³ Low‐dose naltrexone, an opioid receptor antagonist with unclear effects in the skin, has shown anecdotal benefit in DD. ¹¹⁵ Apremilast, a phosphodiesterase‐4 (PDE4) inhibitor approved for psoriasis, has also demonstrated clinical improvement in case reports. ¹¹⁶

Biologics

Recent insights into the potential immunological contributors to DD have prompted exploration of targeted biologic therapies. Growing evidence supports a role for immune dysregulation in DD, particularly an IL‐17/IL‐23 skewed Th17 response. This has opened the door for the off‐label use of biologics traditionally used in psoriasis. Significant improvement in cutaneous lesions and symptoms such as pruritus and malodor following treatment with guselkumab (anti‐IL‐23A) or secukinumab (anti‐IL‐17A) was found during a 1‐year period. ⁴¹ Consistent with this, tissue analysis revealed elevated Th17 cell infiltration in lesional DD skin. Biologics were well tolerated with no serious side effects or infections observed ⁴⁸ although the risk of immunosuppression/immunomodulation should be taken into account in patients with dysbiosis of skin and increased incidence of cutaneous bacterial and viral infection, as in DD. Additionally, type 2 inflammation may also contribute to DD in certain patients. A 2024 case series demonstrated sustained efficacy of IL‐4 inhibitor dupilumab and IL‐13 inhibitor tralokinumab. ⁴⁹ Cytokine profiling of lesional skin using qPCR (polymerase chain reaction) may help personalize treatment in DD while minimizing side effects. It remains unclear whether the inflammatory signatures in DD are primarily responsible for its pathology or are secondary to skin barrier breakdown and dysbiosis. Moreover, larger prospective multicentre studies are needed to test the safety and efficacy of biologics in this rare condition in a less biased manner. ⁴⁸

MEK inhibitors

Zaver et al. identified hyperactivation of the MAPK/ERK pathway in SERCA2‐deficient keratinocytes using a CRISPR‐modified organotypic epidermal model of DD, proposing MEK inhibition as a potential therapeutic strategy. ³⁹ Building on this mechanistic rationale, a case report by Soto‐García et al. ⁴⁰ described a dramatic response to oral trametinib in a young adult male with severe DD refractory to multiple systemic therapies, including secukinumab. Interestingly, paradoxical overactivation of the MAPK pathway has also been associated with Grover disease ¹⁵³ and can cause Darier‐like disease in patients taking BRAF inhibitors, ¹⁵⁴ which may explain the shared histopathological features between these two diseases.

Radiotherapy

Radiotherapy is an option in selected recalcitrant cases of DD, particularly when lesions are localized or resistant to systemic treatments. Grenz ray therapy, delivering low‐penetration ultrasoft radiation (~2 mm), has achieved long‐term remission in DD with tolerable side effects. However, concerns about carcinogenesis and long‐term toxicity necessitate cautious use and informed consent. ¹⁵⁵ Similarly, electron beam therapy ¹³³ and superficial X‐ray therapy have shown efficacy even at low doses. ¹⁵⁶

Procedures

With regard to procedural treatments, in the authors' experience, gentle dermabrasion may offer relief for localized, thick or function‐limiting plaques, and outcomes range from improvement to long remissions. ¹³⁸ , ¹³⁹ , ¹⁴⁰ , ¹⁴¹ , ¹⁴² , ¹⁴³ Successful DD lesion treatment has also been reported with cryotherapy, carbon dioxide laser and photodynamic therapy. ¹⁵⁷

Genetic counselling

When DD is suspected or confirmed, patients should be referred for genetic counselling, including DNA analysis when available, to identify pathogenic variants in the ATP2A2 gene. Identification of the specific pathogenic variants can inform family studies and reproductive planning. For families with a known pathogenic variant, prenatal diagnostic options such as chorionic villus sampling (10–13 weeks), amniocentesis (15–18 weeks) or preimplantation genetic diagnosis can be discussed.

In summary, treatment of DD is evolving from symptom‐directed approaches towards targeted therapy informed by molecular pathology.

FUTURE PERSPECTIVES AND UNMET NEEDS

DD remains a complex genodermatosis, posing challenges for patients, clinicians and researchers. Key unmet needs include the lack of standardized diagnostic criteria and validated severity assessment tools, limiting recognition and comparability of outcomes. These gaps are being addressed through ongoing projects and collaborations by the DDITF and the ERN, working together to advance care and research for this rare disorder.

As a monogenic disorder thought to be a haplo‐insufficiency, DD is theoretically amenable to gene therapy approaches, though pharmacologic rather than curative, such as a modified HSV vector recently FDA‐approved for dystrophic epidermolysis bullosa. ⁴² , ⁷⁹ , ¹⁵⁸ However, effectiveness of such topical gene therapy would be limited to the cutaneous manifestations. ¹⁵⁹ , ¹⁶⁰ CRISPR‐based DNA editing of pathogenic variants has been FDA‐approved for sickle cell disease, but the application of such technology to a large tissue with rapid turnover like the epidermis presents a therapeutic challenge.

Better knowledge of the genotype–phenotype relationship in DD may help predict the clinical course and optimize the management and counselling of DD patients.

Another critical gap is the limited understanding of systemic inflammation, neuroinflammation and immune dysregulation in DD aspects that may be essential for identifying new treatment targets and personalizing patient management. ⁴¹ , ⁴³ , ⁴⁴ , ⁴⁵ , ⁵²

We hope that our recent foundation of the DDITF, uniting experts from 25 countries, will serve as a catalyst for advancing both the clinical and scientific understanding of this complex disorder. Through global collaboration, the development of standardized assessment tools and coordinated research efforts, the task force aims to uncover new and clinically meaningful aspects of DD, refine its classification and ultimately enhance patient care and outcomes. We invite dermatologists worldwide with a special interest and experience in DD to join the DDITF in this collective effort. For those interested in contributing, please contact us at darierdiseaseitf@gmail.com.

DD research holds promise not only for improving patient care but also for advancing fundamental scientific understanding of both cutaneous and extracutaneous manifestations of DD. It may serve as a unique ‘micro‐laboratory’ for exploring the genetic basis of neuropsychiatric disorders, which remain poorly understood. Ultimately, the study of rare diseases such as Darier disease will continue to help uncover the underlying principles that inform our understanding of more prevalent disorders . ¹⁶¹

AUTHOR CONTRIBUTIONS

Roni Pircha Dodiuk‐Gad, Sofia Labbouz, Alexander Navarini and Alain Hovnanian contributed to the conceptualization, methodology, data curation, supervision and writing of the original draft. All other authors (Grace Xiong, Dedee Frances Murrell, Simon M. Mueller, Khaled Ezzedine, Nessa Aghazadeh Mohandesi, Ahmed Salem Aldhaheri, Nissim Asayag, Eulalia Baselga, Chen Nadler, Keith Choate, Chia‐Yu Chu, John Robert Edminister, Emmanuella Guenova, Melis Gönülal, Antoni Gostynski, Ankan Gupta, Lalit Kumar Gupta, Juliette Mazereeuw Hautier, Wolfram Hoetzenecker, Peter Itin, Marek Jankowski, Akiharu Kubo, Haur Yueh Lee, Julia Scott Lehman, Anfisa Lepekhova, Márta Medvecz, Jemima E. Mellerio, Verena Moosbrugger‐Martinz, Amy S. Paller, Dóra Plázár, Amadeu José Rodrigues Queiróz, Josep Riera‐Monroig, Ralph Rosa, Matthias Schmuth, Maella Severino Freire, Itzhak Shabat, Jonathan Shapiro, Cory L. Simpson, Diego Soto‐García, Alexander J. Stratigos, Gianluca Abel Tadini, Takuya Takeichi, Kaushal K. Verma, Jakob D. Wikström, Alexander Zink and Michael Ziv) contributed to writing the original draft and to conceptualization. The manuscript was developed through an extensive collaborative process. Multiple structured online meetings were held to present and discuss key aspects of DD and to reach consensus on the scope and structure of the article. Sections were assigned according to individual areas of expertise. Drafts underwent multiple rounds of consolidation, editing and harmonization, with iterative redistribution to all co‐authors. All authors critically reviewed the integrated manuscript, contributed revisions and approved the final version prior to submission.

FUNDING INFORMATION

The authors have nothing to report.

CONFLICT OF INTEREST STATEMENT

Dr. Labbouz declared no conflict of interest. Dr. Hovnanian declared no conflict of interest. Dr. Murrell declared no conflict of interest. Dr. Mueller has served as a consultant for Sanofi Aventis, Galderma, Janssen‐Cilag, Leo Pharma, Incyte, Novartis, UCB. Dr. Ezzedine declared no conflict of interest. Dr. Aghazadeh Mohandesi declared no conflict of interest. Dr. Aldhaheri declared no conflict of interest. Dr. Asayag declared no conflict of interest. Dr. Baselga holds a leadership role in ERN‐SKIN IPPK. Dr. Chen declared no conflict of interest. Dr. Choate has served as an investigator for AbbVie, Janssen, Boehringer Ingelheim and Biocryst. He is a consultant for Palvella and Resvita. Dr. Chu declared no conflict of interest. Dr. Edminister has received grants from Foundation for Ichtyosis and Related Skin Types, and Dermatology Foundation and served as a consultant for Priovant Therapeutics. Dr. Guenova has received funds from the Swiss National Science Foundation. Dr. Gönülal declared no conflict of interest. Dr. Gostynski has served as a consultant for AbbVie, Pfizer, Sanofi, Galderma, Leo Pharma, UCB; has received honoraria for lectures from UCB and AbbVie; and support for attending meetings from USB. He holds stock or stock options in Sanofi, UCB, Pfizer, BioCryst. Dr. A. Gupta declared no conflict of interest. Dr. K. Gupta declared no conflict of interest. Dr. Mazereeuw‐Hautier declared no conflict of interest. Dr. Hoetzenecker declared no conflict of interest. Dr. Itin declared no conflict of interest. Dr. Jankowski declared no conflict of interest. Dr. Kubo declared no conflict of interest. Dr. Lee has served as an investigator for Novartis, Pfizer, Amgen; and in the data safety monitoring board for Johnson & Johnson. He has received honorarium for lectures from GA2LEN Adcare Meeting‐Atopic Dermatitis and support for attending meetings from Sanofi. Dr. Lehman declared no conflict of interest. Dr. Lepekhova declared no conflict of interest. Dr. Medvecz declared no conflict of interest. Dr. Mellerio declared no conflict of interest. Dr. Moosbrugger‐Martinz declared no conflict of interest. Dr. Paller has served as an investigator for AbbVie, Biomendics, Dermavant, Eli Lilly, Incyte, Johnson & Johnson Innovative Medicine, Moonlake, Regeneron, TWI, UCB; as a consultant for Abeona, Arcutis, BioCryst, Boehringer‐Ingelheim, Castle Creek, Chiesi, Dermavant, Johnson & Johnson Innovative Medicine, Krystal, LEO, Lilly, L'Oréal, MoonLake Immunotherapeutics, Peltheos, Quoin, Regeneron, and Sanofi; and in the data safety monitoring board for AbbVie, Abeona, Biocryst, Daiichi Sankyo and Galderma. Dr. Plázár declared no conflict of interest. Dr. Rodrigues Queiróz declared no conflict of interest. Dr. Riera‐Monroig has served as a consultant for AbbVie, Almirall, Galenicum, Johnson&Johnson, Leo Pharma, Lilly, Novartis, UCB and received honoraria for lectures from AbbVie, Almirall, Bristol‐Mayers Squibb, Galenicum, Johnson&Johnson, Leo Pharma, Lilly, Novartis, UCB; and support for attending meetings from AbbVie, Almirall, Boehringer Ingelheim, Galenicum, Johnson&Johnson, Leo Pharma, Lilly, Novartis, UCB, ISDIN, La Roche‐Posay, Sanofi. Dr. de Rosa declared no conflict of interest. Dr. Schmuth declared no conflict of interest. Dr. Severino‐Freire has served in the data safety monitoring board for AbbVie and Lilly and received payments for expert testimony from AbbVie. Dr. Shabat declared no conflict of interest. Dr. Shapiro declared no conflict of interest. Dr. Simpson has served as an investigator for Leo Foundation, Foundation for Ichtyosis and Related Skin Types, as a consultant for Mitsubishi‐Tanabe Pharma America and Argenx. He holds a leadership role in Society for Investigative Dermatology. Dr. Soto‐Garcia declared no conflict of interest. Dr. Stratigos has served as an investigator for AbbVie, Lilly, L'Oréal, Leo Pharma, Pfizer, UCB. He has received honoraria for lectures from Sanofi, Genesis Pharma, Regeneron. Dr. Tadini declared no conflict of interest. Dr. Takeichi declared no conflict of interest. Dr. Verma has served as a consultant for AIIMS New Delhi. Dr. Wikström declared no conflict of interest. Ms. Xiong declared no conflict of interest. Dr. Zink declared no conflict of interest. Dr. Ziv declared no conflict of interest. Dr. Navarini has served as a consultant and received honoraria for lectures from AbbVie, Almirall, Amgen, Biomed, Bristol‐Myers Squibb, Boehringer Ingelheim, Lilly, Galderma, Incyte Biosciences, Janssen Cilag, LEO Pharma, Louis Widmer, Merz Pharma, MSD, Novartis, Pfizer, Pierre Fabre Pharma, Sanofi Aventis, Takeda, UCB; and in the data safety monitoring board for Novartis. Dr. Dodiuk‐Gad served as a consultant for Sol‐Gel Technologies Ltd. and Mitsubishi Tanabe Pharma America.

ETHICAL APPROVAL

Not applicable.

ETHICS STATEMENT

The patients in this manuscript have given written informedconsent to publication of their case details.

Labbouz S, Hovnanian A, Xiong G, Murrell DF, Mueller SM, Ezzedine K, et al. Darier disease—A review highlighting new insights from the Darier Disease International Task Force. J Eur Acad Dermatol Venereol. 2026;40:1626–1647. 10.1111/jdv.70483

DATA AVAILABILITY STATEMENT

Data sharing not applicable to this article as no datasets were generated or analysed during the current study.