Case report: Variability in clinical manifestations within a family with incontinentia pigmenti.

Diagnosing skin diseases in children can be a complex interdisciplinary problem. Incontinentia pigmenti (IP), also known as Bloch-Sulzberger syndrome, is a rare hereditary genodermatosis related to a mutation in the IKBKG gene. We present a family case of IP described from the perspective of various specialists, including dermatologists, oncologists, geneticists, dentists, and trichologists. The peculiarity of this case is the development of squamous cell carcinoma (SCC) on the shin of a 10-year-old female patient with IP. The patient had a positive family history: her mother and two sisters also displayed clinical manifestations of IP with involvement of skin, teeth and hair. The presence of exons 4-10 deletion in the IKBKG gene in all affected females was confirmed by detailed genetic evaluation using long-range PCR, and also high degree of X-chromosome inactivation skewing was demonstrated. The family underwent a comprehensive examination and was followed up for 2 years with successful symptomatic treatment of dermatologic manifestations. Recommendations were also made regarding dental and hair problems. By the end of the follow-up period, patients had stabilized, with the exception of a 36-year-old mother who developed generalized morphea. The study demonstrates the varying expressiveness of clinical symptoms among family members and emphasizes the importance of timely diagnosis for effective management of patients with IP.

Disease burden, clinical management and unmet treatment need of patients with moderate to severe atopic dermatitis; consensus statements, insights and practices from CERTADE (Central/Eastern EU, Russia, Turkiye AD Experts) Delphi panel.

Background: There is limited insight into the current disease burden and everyday clinical management of moderate-to- severe AD in Poland, Czechia, Russia, and Turkiye. Therefore, this study aimed to get information-driven insights regarding the current disease burden and clinical management of patients with moderate-to-severe AD with common and differentiating aspects of the patient journey and establish a consensus. Methods: In this modified 2-round Delphi panel, 133 questions were asked in total to 27 dermatologists. A consensus was achieved when 70% of the panel members strongly agreed or agreed (or strongly disagreed or disagreed) with an item. Statements with <40% agreement dropped from the Delphi rounds and were not repeated. Results: The results state that AD has a significant impact on the quality of life for both patients and their families with social and economic consequences in these countries. While there were significant dissimilarities regarding the current treatment approach by preference order and treatment duration among participants, there was also a high percentage of consensus on literature and guideline-based statements. Current topical therapies and the immune response modifiers were not found to be sufficient by panelists to cover the therapeutic needs of patients with moderate-to-severe AD. Moreover, panelists highlighted the significant burden of adverse events with the off-label use of currently available immunosuppressants. Conclusions: These results underlined that there is a significant disease burden with an unmet treatment need for patients with moderate-to-severe AD in Poland, Czechia, Russia, and Turkiye.

Disease burden, clinical management and unmet treatment need of patients with moderate to severe alopecia areata; consensus statements, insights, and practices from CERTAAE (Central/Eastern EU, Russia, Türkiye AA experts) Delphi panel.

Objectives: This study aims to update the understanding of Alopecia Areata (AA) in Poland, Czechia, Russia, and Türkiye, focusing on the disease burden, clinical management, and patient journey. It seeks to establish a consensus on optimal management strategies for AA in these regions. Methods: A modified 2-round Delphi panel was conveyed with 23 Dermatologists (Russia; 4, Türkiye; 7, Poland; 6, and Czechia; 6). The Delphi questionnaire consisted of 61 statements and 43 questions designed to obtain an overall understanding of the perception and acceptance of available information regarding the care of patients with alopecia areata. Results: The study revealed that moderate-to-severe AA significantly impacts patients' and their families' QoL, consistent with previous studies. AA was found to cause more substantial impairment when additional lesions appeared in visible areas besides the scalp. Work and productivity impairment were notably higher in adults with moderate-to-severe AA. Diagnostic consensus highlighted the importance of skin biopsies and trichoscopy, while the need for more practical severity scoring systems was emphasized. Current treatments, including topical therapies, corticosteroids, and systemic immune modifiers, were deemed insufficient, highlighting the unmet medical need. Conclusion: The Delphi study underscores a significant disease burden and unmet medical needs in patients with moderate-to-severe AA. It highlights the necessity of access to novel treatments and further research to develop more effective therapies with a tolerable safety profile. The findings align with global research, emphasizing the psychosocial impact of AA and the need for standardized, effective treatment protocols.

Mesenchymal stromal cell therapy alone does not lead to complete restoration of skin parameters in diabetic foot patients within a 3-year follow-up period.

Introduction: Mesenchymal stromal cells (MSCs) administration is an effective option for the treatment of diabetic foot ulcers (DFUs). However, to date, studies assessing long-term outcomes and evaluating skin parameters after cell-based therapy are lacking. We presented the clinical outcomes of 3 patients, treated for DFUs with the bone marrow MSCs 3 years earlier. Methods: Ultrasound examination was used to compare collagen density and epidermal thickness in areas of healed ulcers in comparison with non-affected skin used as a control. Ultrasound and dermatoscopy were used to exclude neoplasm formation, to assess scar contracture and wound recurrence. Results: In all patients, no ulcer recurrence was detected, which was lower than the expected 60% rate of re-ulceration in diabetic patients in a 3-year period (OD [odds ratio] = 0.095, P = 0.12). No neoplasm formation, no contracture of hypertrophic scar, and adjacent tissue were registered. Collagen ultrasound density was decreased by 57% (P = 0.053) and epidermal thickness was increased by 72% (P = 0.01) in the area of healed ulcers in all patients. Conclusion: MSCs therapy alone did not result in the complete restoration of the skin parameters within a 3-year period. MSCs may represent important adjuvant to the therapy, however, other novel approaches are required to achieve better results.

Mental stress in atopic dermatitis--neuronal plasticity and the cholinergic system are affected in atopic dermatitis and in response to acute experimental mental stress in a randomized controlled pilot study.

RATIONALE: In mouse models for atopic dermatitis (AD) hypothalamus pituitary adrenal axis (HPA) dysfunction and neuropeptide-dependent neurogenic inflammation explain stress-aggravated flares to some extent. Lately, cholinergic signaling has emerged as a link between innate and adaptive immunity as well as stress responses in chronic inflammatory diseases. Here we aim to determine in humans the impact of acute stress on neuro-immune interaction as well as on the non-neuronal cholinergic system (NNCS). METHODS: Skin biopsies were obtained from 22 individuals (AD patients and matched healthy control subjects) before and after the Trier social stress test (TSST). To assess neuro-immune interaction, nerve fiber (NF)-density, NF-mast cell contacts and mast cell activation were determined by immunohistomorphometry. To evaluate NNCS effects, expression of secreted mammal Ly-6/urokinase-type plasminogen activator receptor-related protein (SLURP) 1 and 2 (endogenous nicotinic acetylcholine receptor ligands) and their main corresponding receptors were assessed by quantitative RT-PCR. RESULTS: With respect to neuro-immune interaction we found higher numbers of NGF+ dermal NF in lesional compared to non-lesional AD but lower numbers of Gap43+ growing NF at baseline. Mast cell-NF contacts correlated with SCORAD and itch in lesional skin. With respect to the NNCS, nicotinic acetylcholine receptor α7 (α7nAChR) mRNA was significantly lower in lesional AD skin at baseline. After TSST, PGP 9.5+ NF numbers dropped in lesional AD as did their contacts with mast cells. NGF+ NF now correlated with SCORAD and mast cell-NF contacts with itch in non-lesional skin. At the same time, SLURP-2 levels increased in lesional AD skin. CONCLUSIONS: In humans chronic inflammatory and highly acute psycho-emotional stress interact to modulate cutaneous neuro-immune communication and NNCS marker expression. These findings may have consequences for understanding and treatment of chronic inflammatory diseases in the future.