Severe atopic dermatitis in early infancy: characteristics, challenges and new perspectives in clinical practice.

Atopic dermatitis (AD) is the most common skin disease in infants and children with a prevalence of 10% in the first two years of life. In this age group up to 15% are severely affected. "Children are not little adults" - this applies in particular to infants with severe atopic dermatitis. Age-specific clinical aspects (psychosocial, neurocognitive, morphological) of the disease require an adjusted disease management. Considering recent approval of systemic treatment options, early identification of infants and children with severe and early persistent disease is of particular importance also in view of possible prevention of atopic comorbidity. As several inborn errors of immunity (IEI) share features of the atopic phenotype, it is essential for clinicians to distinguish signs of immunodeficiency from severe AD. Here, we describe a practical approach on the basis of clinical history and key dermatological and laboratory findings. Furthermore, this paper is aimed at providing an update on general management of severe AD in early infancy, including recommendations for systemic treatment.

A new era of atopic eczema research: Advances and highlights.

Atopic eczema (AE) is an inflammatory skin disease with involvement of genetic, immunological and environmental factors. One hallmark of AE is a skin barrier disruption on multiple, highly interconnected levels: filaggrin mutations, increased skin pH and a microbiome dysbiosis towards Staphylococcus aureus overgrowth are observed in addition to an abnormal type 2 immune response. Extrinsic factors seem to play a major role in the development of AE. As AE is a first step in the atopic march, its prevention and appropriate treatment are essential. Although standard therapy remains topical treatment, powerful systemic treatment options emerged in the last years. However, thorough endotyping of the individual patients is still required for ideal precision medicine approaches in future. Therefore, novel microbial and immunological biomarkers were described recently for the prediction of disease development and treatment response. This review summarizes the current state of the art in AE research.

[Diagnostics of alpha-gal syndrome : Current standards, pitfalls and perspectives]. / Diagnostik des α­Gal-Syndroms : Aktuelle Standards, Fallstricke und Perspektiven.

α-Gal syndrome results from sensitization to the carbohydrate epitope galactose-α-1,3-galactose (α­gal). The allergen occurs in mammalian meat and innards, but also in other foods and medical products of animal origin. Allergic reactions generally occur delayed after allergen intake with a latency period, depending on the individual tolerance threshold and the influence of cofactors. Details in the patient's medical history can help to establish the suspected diagnosis of α­gal syndrome. Confirmation of the diagnosis requires the expertise of specialists, experienced with the implementation and interpretation of in vitro and in vivo diagnostic tests. Whereas skin prick testing with commercial whole-meat extracts often does not provide reliable results, allergen-specific IgE (α-gal) is generally detectable in affected patients. Cell-based tests such as the basophil activation test are currently only employed in an experimental setting. To evaluate, whether a sensitization is clinically relevant, an in-patient oral food challenge should be performed, using for example cooked pork or porcine kidney in addition to suspected cofactors.

Wells syndrome.

A rare eosinophilic dermatosis, Wells syndrome, also referred to as eosinophilic cellulitis, is characterized by great clinical variability. Typical findings include infiltrated erythematous plaques arising on the extremities. Lesions initially resemble erysipelas/cellulitis, however, they do not improve with antibiotic treatment. Eosinophilic cellulitis is a diagnosis of exclusion that may only be made over the course of the disease, taking into account clinical and characteristic histological findings (flame figures). Although multiple potential triggers have been proposed, the exact etiology remains unresolved. Involvement of abnormal Th2 cells, IL-5, and activated eosinophilic granulocytes suggest a nonspecific hypersensitivity response to exogenous or endogenous stimuli. Corticosteroids may have a beneficial effect on the chronic, recurrent course frequently observed. The disease is often self-limiting, healing without sequelae. Given that transitions to hematological and oncological disorders have been observed, patients should be closely followed up.

Wells-Syndrom.

Das Wells-Syndrom, auch als eosinophile Zellulitis bezeichnet, ist eine seltene, sporadisch auftretende eosinophile Dermatose mit polymorphem klinischem Bild. Als typisch gelten entzündliche Erytheme oder Plaques an den Extremitäten, die initial als Erysipel imponieren können, unter antimikrobieller Behandlung aber persistieren. Die eosinophile Zellulitis ist eine Ausschlussdiagnose, die in Zusammenschau von klinischem Befund und charakteristischem histologischem Bild (Flammenfiguren) nur im Verlauf gestellt werden kann. Mit einer Vielzahl möglicher Triggerfaktoren ist die Ätiologie nicht geklärt. Die Beteiligung abnormer Th2-Zellen, des Zytokins IL-5 und aktivierter eosinophiler Granulozyten lässt eine unspezifische Hypersensitivitätsreaktion auf exo- und endogene Stimuli vermuten. Die häufiger vorkommenden chronisch- rezidivierenden Formen lassen sich durch Glukokortikoide günstig beeinflussen. Der Verlauf ist meist selbstlimitierend, ohne Residuen. Aufgrund von Übergängen in hämatoonkologische Erkrankungen sind Verlaufskontrollen angezeigt.

Cancer predisposing syndromes in childhood and adolescence pose several challenges necessitating interdisciplinary care in dedicated programs.

Introduction: Genetic disposition is a major etiologic factor in childhood cancer. More than 100 cancer predisposing syndromes (CPS) are known. Surveillance protocols seek to mitigate morbidity and mortality. To implement recommendations in patient care and to ascertain that the constant gain of knowledge forces its way into practice specific pediatric CPS programs were established. Patients and methods: We retrospectively analyzed data on children, adolescents, and young adults referred to our pediatric CPS program between October 1, 2021, and March 31, 2023. Follow-up ended on December 31, 2023. Results: We identified 67 patients (30 male, 36 female, 1 non-binary, median age 9.5 years). Thirty-five patients were referred for CPS surveillance, 32 for features suspicious of a CPS including café-au-lait macules (n = 10), overgrowth (n = 9), other specific symptoms (n = 4), cancer suspicious of a CPS (n = 6), and rare neoplasms (n = 3). CPS was confirmed by clinical criteria in 6 patients and genetic testing in 7 (of 13). In addition, 6 clinically unaffected at-risk relatives were identified carrying a cancer predisposing pathogenic variant. A total of 48 patients were eventually diagnosed with CPS, surveillance recommendations were on record for 45. Of those, 8 patients did not keep their appointments for various reasons. Surveillance revealed neoplasms (n = 2) and metachronous tumors (n = 4) by clinical (n = 2), radiological examination (n = 2), and endoscopy (n = 2). Psychosocial counselling was utilized by 16 (of 45; 35.6%) families. Conclusions: The diverse pediatric CPSs pose several challenges necessitating interdisciplinary care in specified CPS programs. To ultimately improve outcome including psychosocial well-being joint clinical and research efforts are necessary.