Bioderma Congress Reports ESPD 2026

Reports written by Prof. Ivelina Yordanova (dermatologist, Bulgaria)

Speaker: Prof. Holm Schneider (professor of pediatrics and consultant pediatrician, Germany) 

Prof. Holm Schneider has been working as professor of pediatrics and consultant pediatrician at the University Hospital Erlangen, where he also heads the interdisciplinary Center for Ectodermal Dysplasias Erlangen, the German national reference center for ectodermal dysplasias and p63-associated disorders. Current research of his team is dedicated to novel therapeutic approaches to severe genodermatoses. Prof. Schneider pioneered the prenatal drug therapy of genetic diseases. 

He conducted numerous preclinical and investigator-initiated clinical studies focusing on congenital skin disorders and has been serving on medical advisory boards of various organizations. His research has been funded by the German Research Foundation and the Federal Ministry for Education and Research for 25 years. He has received numerous honors and awards, including the Gottron-Just Science Prize, the Gold medal of the Union of European Neonatal  and Perinatal Societies and the Care-for-Rare Science Award for outstanding scientific contributions.

Genetic deficiency of ectodysplasin A (EDA) causes X-linked hypohidrotic ectodermal dysplasia (XLHED), in which the development of sweat glands is irreversibly impaired -  an condition that can lead to life-threatening hyperthermia. During embryonic development, tissues and organs form in spatiotemporally defined successions of events until the organism has ac-quired its final shape. Many of these events, such as limb morphogenesis or the formation of sweat glands and other skin appendages,  can be irreversibly affected if specific signals are not provided at the appropriate time. For example, deficiency of EDA, which results from loss-of-function variants of the gene EDA, causes XLHED. When recombinant Fc-EDA (a fusion protein made up of the constant domain of IgG1 and the receptor-binding portion of EDA) or an antibody that activates the EDA receptor (EDAR) was administered repeatedly into the circulation of pregnant Eda-deficient mice, the disease phenotype of the pups was corrected, yet the dams (which were homozygous for the loss-of-function Eda allele) did not benefit fromtreatment. The same was true when Fc-EDA was delivered directly into the amniotic fluid surrounding Eda-deficient fetuses.In the second approach, a single dose was sufficient to correct the disease phenotype, and maternal drug exposure was negligible. Prof. Schneider present data supporting a critical role of the neonatal Fc receptor in drug uptake from amniotic fluid. This receptor mediates uptake of IgG from mother’s milk across the gut endothelium in rodents. 

He also report the sustained restoration of sweating ability in three human patients with XLHED in response to prenatal treatment with Fc-EDA.

The human sweat glands formed between gestational weeks 20 and 30. Direct intraamniotic administration of the drug (recombinant Fc-EDA) at the appropriate stages of development appeared to be a promising therapeutic approach. The amniotic fluid served as a reservoir of Fc-EDA: the size of the protein limit its diffusion from the amniotic cavity and allow its uptake from the fetal gut through the ingestion of amniotic fluid. The treated infants had a normal sweat-duct density on the soles of the feet, as well as normal pilocarpine-induced sweating at 6 months of age. Various body parts were repeatedly observed to be moist. Signs of positive effects on tooth development and salivary and meibomian glands have been observed in the treated infants, as compared with the phenotypes of their untreated affected siblings. Although the rate of amniocentesis-related miscarriage is only 0.11%, Fc-EDA was not delivered before week 26 of gestation. In summary, he identified a mechanism of drug uptake into fetuses, which resulted in effective treatment of a genetic disability. Prof. Schneider showed 20 male patients with XLHED in whom the drug was introduced at 25, 27 and 30 weeks of gestation. Combined with the ability to identify affected fetuses through noninvasive sonographic prenatal screening, the approach he describe represents a new means of protein-replacement therapy to correct XLHED. 

Reports written by Prof. Ivelina Yordanova (dermatologist, Bulgaria)

Speaker: Prof. Juliette Mazereeuw-Hautier (Professor of Dermatology, France)

Epidermal differentiation disorders (EDDs)

Epidermal differentiation disorders (EDDs) encompass inherited conditions characterized by abnormal epidermal differentiation, including nonsyndromic and syndromic subtypes with more extensive cutaneous involvement or palmoplantar keratoderma. Nonsyndromic EDDs (nEDDs) are defined as disorders that primarily affect large areas of skin and adnexal structures without alterations in extracutaneous tissues resulting from the underlying genetic change. 

To facilitate the development of targeted therapies and to provide clinicians with clearer therapeutic guidance, the authors have developed a new nomenclature for EDDs that includes the causative altered gene and the nEDD subgroup designation, sometimes with a clinical or histological descriptor or acronym. Historically, many nEDDs have been named on the basis of phenotypic characteristics or associations that are now considered outdated or inappropriate. For example, the term „harlequin ichthyosis“ evokes potentially stigmatizing images. Similarly, the word „ichthyosis“ is derived from the Greek ichthys, meaning fish, and the Greek hystrix, meaning porcupine. As a result, the clinical relevance of the previous classification, which included eponymous and/or descriptive titles, has diminished. In the new, gene-based classification, old terms considered pejorative, such as ichthyosis, vulgaris, hystrix and harlequin have been eliminated and eponyms have been replaced. Among the 53 genetically distinct nEDDs are conditions formerly known as autosomal recessive congenital ichthyosis, erythrokeratodermia variabilis et progressiva, Hailey–Hailey disease and Darier–White disease.

Hailey-Hailey disease

Hailey-Hailey disease is a rare genodermatosis described in 1939, with an autosomal dominant inheritance pattern, characterized by compromised adhesion between epidermal keratinocytes. It has an estimated prevalence of 1/50,000, with no gender or race predilection. It results from a heterozygous mutation in the ATP2C1 gene, which encodes the transmembrane protein hSPA1C, present in all tissues, with preferential expression in keratinocytes. Mutations in the ATP2C1 gene cause changes in the synthesis of junctional proteins, leading to acantholysis. It usually begins in adulthood, with isolated cases at the extremes of life. It manifests as vesico-bullous lesions mainly in the flexural areas, which develop into erosions and crusts. Chronic lesions may form vegetative or verrucous plaques. 

Pruritus, a burning feeling and pain are common. It evolves with periods of remission and exacerbation, generally triggered by humidity, friction, heat, trauma and secondary infections. The diagnosis is based on clinical and histopathological criteria: marked suprabasal acantholysis, loosely joined keratinocytes, giving the appearance of a “dilapidated brick wall”, with a few dyskeratotic cells. The acantholysis affects the epidermis and spares the adnexal epithelia, which helps in the differential diagnosis with pemphigus vulgaris. Direct immunofluorescence is negative. The main differential diagnoses are Darier disease, pemphigus vegetans, intertrigo, contact dermatitis, and inverse psoriasis. There is no cure and the treatment is challenging, including measures to control heat, sweat and friction, topical medications (corticosteroids, calcineurin inhibitors, antibiotics), systemic medications (antibiotics, corticosteroids, immunosuppressants, retinoids and immunobiologicals) and procedures such as botulinum toxin, laser and surgery. There is a lack of controlled clinical trials to support the choice of the best treatment. There are reports of controversial responses after using etanercept (anti-TNFα) with weekly doses between 25 and 50 mg. However, most reports claim against any positive effect of anti-TNFα in HHD. Recently, the use of dupilumab (anti-interleukins 4 and 13) as treatment for HHD was reported. Prof. Mazereeuw-Hautier showed results of systemic treatment with Dupilumab in 20 patients with Morbus Hailey-Hailey, which led to a significant reduction in skin inflammation after 6 months. She also showed treatment of patients diagnosed with Pachyonychia congenita with the local JAK-kinase inhibitor Roxulitinib, as well as systemic treatment with oral Erlotinib.

Darier disease

Darier disease is caused by mutation in the ATP2A2 gene. This disrupts the SERCA2 pump and leads to impaired calcium homeostasis in the keratinocytes and decreased cell-cell adhesion. Darier disease presents with brownish papules mainly in the seborrheic and intertriginous areas, with a keratotic surface. These may coalesce into macerated lesions.

Typical nail changes in Darier disease include red and white longitudinal streaks ending in V-shaped notches at the free margin of the nail plates. Acrokeratosis verruciformis as well as bullous, hemorrhagic, comedonic and linear/segmental types are clinical variants of Darier disease. Darier disease is frequently associated with neuropsychiatric disorders. Acute exacerbation may be caused by superinfection with Staphylococcus aureus or herpes simplex virus. Histology in Darier disease is characterized by pronounced dyskeratosis. Keratolysis as well as antiseptic treatment to avoid superinfection are essential. Topical corticosteroids are used. Among systemic treatments, the best body of data is available for acitretin. Ablative therapies (dermabrasion, CO2 laser, Er:YAG laser) are effective but limited by the size of the areas that can be treated. In Padua, Prof. Mazereeuw-Hautier showed results of a new systemic treatment of a 25-year-old patient with Darier disease, treated for 2 months with MEK kinase inhibitor Tramatinib,  with  positive effect. She explained that this is a new pathogenetic therapy for this disease, introduced thanks to the understanding that in Darier disease, we have a disruption of keratinocyte expression due to hyperactivation of MEK and ERK - the pathogenetic pathways.

Reports written by Prof. Ivelina Yordanova (dermatologist, Bulgaria)

Speaker: Prof. Francesco Zulian (Paediatric Rheumatology Unit, Department of Women’s and Children’s Health, Padua)

Prof. Francesco Zulian is an Associate Professor of Pediatrics at the University of Padua where he graduated from Medical School, trained in Pediatrics and specialized in Pediatric (USA 1991) and Adult Rheumatology.  Since 1992 he is the Chief of the Pediatric Rheumatology Unit at the University of Padova. From 2001-2009 he acted as Chairman of the Juvenile Scleroderma Working Group of PRES (Pediatric Rheumatology European Society) and from 2006-2009, of the Italian Society of Pediatric Rheumatology. Prof. Zulian’s main research interests are in Scleroderma syndromes, Kawasaki disease, Juvenile Idiopathic Arthritis (JIA), Joint Hypermobile Syndromes and JIA- related chronic uveitis. He has around 150 publications in International peer-reviewed Journals (h Index 46) and has acted also as editorial reviewer for many of them. 

Localized scleroderma (LS)

Localized scleroderma (LS) is a complex disease characterized by a mixture of inflammation and fibrosis of the skin that, especially in the pediatric population, also affects extracutaneous tissues ranging from muscle to the central nervous system. Although developmental origins have been hypothesized, evidence points to LS as a systemic autoimmune disorder, as there is a strong correlation to family history of autoimmune disease, the presence of shared HLA types with rheumatoid arthritis, high frequency of auto-antibodies, and elevated circulating chemokines and cytokines associated with T-helper cell, IFNγ, and other inflammatory pathways. 

This inflammatory phenotype of the peripheral blood is reflected in the skin via microarray, RNA Sequencing and tissue staining. Research is underway to identify the key players in the pathogenesis of LS, but close approximation of inflammatory lymphocytic and macrophage infiltrate with collagen and fibroblasts deposition supports the notion that LS is a disease of inflammatory driven fibrosis. The immune system is dynamic and undergoes changes during childhood, and we speculate on how the immune system in childhood could potentially contribute to some of the differences in LS between children and adults. Interestingly, the immune phenotype in pediatric LS resembles to some extent the healthy adult cellular phenotype, possibly supporting accelerated maturation of the immune system in LS. Localized scleroderma (LS) is the most common form of pediatric scleroderma, a disease whose histologic pathology involves inflammation and fibrosis, similar to that of systemic sclerosis (SSc), although the clinical phenotypes are markedly different. The mean age of pediatric LS disease onset is 6.4–8.7 years, with the disease more prevalent in Caucasians. Females are more commonly affected than males (2.3 4:1 ratio). LS can present in several different patterns (subtypes) depending on depth and distribution of lesions, including circumscribed morphea (plaque lesions), linear scleroderma of the trunk/limb or head (band-like lesion), generalized morphea (multiple plaque lesions), pansclerotic morphea, or a combination of two or more of these subtypes (mixed morphea). Twenty to 70% of juvenile LS patients have been reported to have extracutaneous involvement, with higher frequencies reported in prospective studies. The most common type of extracutaneous involvement is musculoskeletal, which includes joint, tendon, muscle, and bone issues. Joint and tendon issues include arthralgia, arthritis, joint contractures, some of which require corrective surgeries. Muscle involvement includes myalgia, myositis, and muscle atrophy. While treatment strategies effective for most patients have been identified, there is a major need for additional treatment options and strategies. Thirty percent of LS patients may fail to respond to initial standard immunosuppressive treatment, and 15–53% of patients can relapse following treatment. 

Active disease can persist for decades. Failure to achieve remission and relapsing disease are both associated with poorer outcome. Identifying optimal treatment strategies for LS will require comparative effectiveness studies; the feasibility of this approach was demonstrated by a recent pilot study of three standardized methotrexate based regimens. Because treatment is focused on controlling inflammation, sensitive monitoring of disease activity is essential for conducting such trials. A recent study identified specific lesion features for tracking disease activity that are likely to improve the sensitivity and specificity of existing clinical measures. Future work may lead to development of a weighted clinical activity measure to further improve an ability to identify relative differences in treatment efficacies. The identification of biomarkers that facilitate monitoring activity level and/or help identify response to specific treatments will enable to work toward personalized medicine for these patients. Prof. Francesco Zulian introduced the terms Localised scleroderma severity index (LoSSI) and LoSCAT score for assessment of the disease and effect of treatment.