Maria Efenesia Baffa

Vitiligo is an autoimmune depigmenting disorder characterized by marked heterogeneity in therapeutic response, both between patients and among lesions within the same individual. While current therapies primarily target interferon-γ (IFN-γ)-driven inflammation, clinical outcomes remain variable and frequently incomplete, suggesting that additional lesion-specific biological factors contribute to repigmentation potential. In this narrative review, we propose the concept of repigmentation competence to describe the capacity of an individual lesion to achieve clinically meaningful repigmentation under therapy. We hypothesize that this competence emerges from the interaction of four interconnected biological axes: (i) cytokine network and immune memory, (ii) local immune regulation, (iii) regenerative capacity, and (iv) microenvironmental permissiveness. A targeted search of PubMed/MEDLINE and ClinicalTrials.gov up to March 2026 was conducted to identify translational studies, mechanistic models, and clinical trials relevant to these pathways. Evidence was synthesized thematically with emphasis on cytokine-mediated mechanisms and their interaction with regenerative and tissue-context processes. The IFN-γ/CXCL9/CXCL10 axis and tissue-resident memory T cells (TRM) represent the most clinically validated drivers of disease persistence, as demonstrated by the therapeutic efficacy of JAK inhibitors, although immune suppression alone often fails to achieve complete or durable repigmentation. In contrast, regulatory pathways involving PD-1/PD-L1 signaling, regulatory T cells (Tregs), IL-10, TGF-β, and IL-2–based strategies remain biologically compelling but only partially translated into effective therapies. Regenerative capacity has also emerged as an important determinant of treatment response, with growing evidence supporting the role of melanocyte stem cell niches, follicular regeneration, and Wnt/β-catenin signaling. Accordingly, regenerative approaches such as non-cultured epidermal cell suspension (NCES) are increasingly being integrated into combination therapeutic strategies. The lesional microenvironment remains the least therapeutically developed axis despite growing experimental evidence supporting its importance in melanocyte survival and migration. Collectively, these observations suggest that the variable efficacy of current therapies may reflect different combinations of lesion-specific biological constraints. The emerging benefit of combination strategies may therefore derive not simply from additive effects, but from the simultaneous engagement of multiple axes involved in repigmentation competence. Our review supports a shift from a predominantly drug-centered model toward a lesion-oriented framework integrating immune, regenerative, regulatory, and microenvironmental determinants of response.

Scleromyxoedema is a rare primary cutaneous mucinosis characterized by a generalized papular and sclerodermoid eruption and typically associated with monoclonal gammopathy. We report an 81-year-old man with Waldenström macroglobulinemia on zanobrutinib who presented with rapidly progressive upper-limb edema, waxy papules, and skin thickening. Histopathology showed diffuse dermal mucin deposition with fibroblast proliferation and fibrosis, consistent with scleromyxoedema. Therapeutic plasma exchange led to partial cutaneous improvement, but the patient subsequently developed fatal intestinal ischemia. This case highlights the characteristic features and potential severity of scleromyxoedema and contributes to the limited literature on therapeutic plasma exchange in this condition.

Background: Bullous pemphigoid is a chronic autoimmune blistering disease characterized by subepidermal blisters and caused by autoantibodies against BP180 and BP230. Although type 2 inflammation is considered relevant to its pathogenesis, the full spectrum of immune dysregulation in BP remains incompletely defined. Objectives: To comprehensively profile local and systemic inflammatory responses in BP and explore their potential associations with disease severity, clinical features and treatment outcomes. Methods: A total of 29 skin biopsies and 27 matched serum samples from patients with bullous pemphigoid, along with samples from 14 healthy controls, were analysed using the Olink Target 96 Inflammation panel. Analyses included principal component analysis, unsupervised clustering, differential expression, gene set enrichment and k‐means clustering to define molecular subgroups. Proteomic data were further compared with a publicly available single‐cell transcriptomic dataset from bullous pemphigoid skin for external validation. Results: Proteomic analysis revealed distinct inflammatory signatures in bullous pemphigoid skin and sera compared to controls, with 22 and 16 differentially expressed proteins, respectively. CCL13, IL‐6, OSM, TNFSF14 and CCL19 were significantly elevated in both compartments. Cutaneous CCL13, expressed mainly by keratinocytes, strongly correlated with the bullous pemphigoid disease activity index score and autoantibody titres. Two molecular skin clusters were identified, with one showing broader, predominantly type 2 inflammatory activation and significantly higher titres of BP180‐IgG antibodies. CCL13 was a major driver of cluster separation. Higher baseline serum IL22RA1 levels were observed in non‐responder patients at 1‐year follow‐up. Proteomic findings showed high concordance with transcriptomic data derived from publicly available single‐cell RNA sequencing of bullous pemphigoid lesional skin. Conclusions: CCL13 was among the most prominent inflammatory proteins identified in bullous pemphigoid. The emergence of two distinct skin proteomic clusters highlights a biological heterogeneity of bullous pemphigoid, indicating the need for endotype‐driven, personalized treatment strategies.

In our clinical case, the patient, affected by morphea, reported an excellent response to the administration of baricitinib 4 mg day–1, with rapid disappearance of itching and reduction of the erythematous-infiltrative component of the plaques, highlighting the important role of the JAK/STAT pathway in TGF-β-mediated profibrotic signalling.

This study reports the efficacy of tralokinumab in five patients with bullous pemphigoid.

Elephantiasis nostras verrucosa (ENV) is a rare and dramatic sequela of chronic nonfilarial lymphoedema. Here we would like to share a case of ENV that appeared as a late complication of limb amputation.

Citation: Pipitò C, Baffa ME, Maglie R, Senatore S, Antiga E. Post-Surgical Anti-BP230 Bullous Pemphigoid: A Rare Cause of Non-Healing Wound. Dermatol Pract Concept. 2024;14(1):e2024031. DOI: https://doi.org/10.5826/dpc.1401a31 Accepted: May 31, 2023; Published: January 2024 Copyright: ©2024 Pipitò et al. This is an open-access article distributed under the terms of the Creative Commons Attribution-NonCommercial License (BY-NC-4.0), https://creativecommons.org/licenses/by-nc/4.0/, which permits unrestricted noncommercial use, distribution, and reproduction in any medium, provided the original authors and source are credited. Funding: None. Competing interests: None. Authorship: All authors have contributed significantly to this publication. Corresponding author: Carlo Pipitò, Department of Health Sciences, Section of Dermatology, University of Florence, Hospital Piero Palagi, Viale Michelangiolo 41, 50125, Florence, Italy. E-mail: carlo.pipito@unifi.it This work is licensed under a Creative Commons Attribution-NonCommercial 4.0 International License.