Role of Human Leukocyte Antigen Class II in Antibody-Mediated Skin Disorders.

HLA class II molecules are key factors determining susceptibility to autoimmune disorders, and their role in immune-mediated skin conditions such as psoriasis has been extensively investigated. However, there is currently little understanding of their role in antibody-mediated skin diseases such as autoimmune blistering disorders. We researched the available literature using PubMed to narratively review the current knowledge on HLA associations in antibody-mediated blistering skin pathologies. Our results summarized the risk alleles that are identified in the literature, together with certain known protective alleles: in the pemphigus group, alleles HLA-DQB1*0503 and HLA-DRB1*0402 are most commonly associated with disease; in the pemphigoid group, the most studied allele is HLA-DQB1*0301; in epidermolysis bullosa acquisita, few genetic studies are available; in dermatitis herpetiformis, the association with haplotypes HLA-DQ2 and HLA-DQ8 is strongly established; finally, in linear IgA bullous disease, specific HLA alleles may be responsible for pediatric presentations. Our current pathogenic understanding of this group of disorders assigns a key role to predisposing HLA class II alleles that are able to bind disease autoantigens and therefore stimulate antigen-specific autoreactive T cells. The latter engage B lymphocytes that will produce pathogenic autoantibodies. The distribution of HLA alleles and their disease associations are variable across demographics, and an in-depth pathogenetic understanding is needed to support associations between HLA alleles and disease phenotypes. Additionally, in a personalized medicine approach, the identification of HLA alleles associated with the risk of disease may become clinically relevant in identifying susceptible subjects that should avoid exposure to known triggers, such as medication, when possible.

Role of IL-4 and IL-13 in Cutaneous T Cell Lymphoma.

The interleukins IL-4 and IL-13 are increasingly recognized contributors to the pathogenesis of cutaneous T cell lymphomas (CTCLs), and their role in disease-associated pruritus is accepted. The prevailing Th2 profile in advanced CTCL underscores the significance of understanding IL-4/IL-13 expression dynamics from the early stages of disease, as a shift from Th1 to Th2 may explain CTCL progression. Targeted agents blocking key cytokines of type 2 immunity are established therapeutics in atopic disorders and have a promising therapeutic potential in CTCL, given their involvement in cutaneous symptoms and their contribution to the pathogenesis of disease. IL-4, IL-13, and IL-31 are implicated in pruritus, offering therapeutic targets with dupilumab, tralokinumab, lebrikizumab, and nemolizumab. This review analyzes current knowledge on the IL-4/IL-13 axis in mycosis fungoides and Sezary syndrome, the most common types of CTCL, examining existing literature on the pathogenetic implications with a focus on investigational treatments. Clinical trials and case reports are required to shed light on novel uses of medications in various diseases, and ongoing research into the role of IL-4/IL-13 axis blockers in CTCL therapy might not only improve the management of disease-related pruritus but also provide in-depth insights on the pathophysiologic mechanisms of CTCL.

Skin Hypopigmentation in Hematology Disorders.

Hypopigmentation disorders pose significant diagnostic challenges in dermatology, sometimes reflecting underlying hematological conditions. This review explores the clinical presentations related to hypopigmentation in hematological disorders, focusing on vitiligo, morphea, and syndromic albinism. Vitiligo, an autoimmune disorder targeting melanocytes, involves interactions between genetic polymorphisms and immune responses, particularly regarding CD8+ T cells and IFN-γ. Drug-induced vitiligo, notably by immune checkpoint inhibitors and small-molecule targeted anticancer therapies, underscores the importance of immune dysregulation. Morphea, an inflammatory skin disorder, may signal hematological involvement, as seen in deep morphea and post-radiotherapy lesions. Syndromic albinism, linked to various genetic mutations affecting melanin production, often presents with hematologic abnormalities. Treatment approaches focus on targeting the immune pathways specific to the condition, and when that is not possible, managing symptoms. Understanding these dermatological manifestations is crucial for the timely diagnosis and management of hematological disorders.

Cutaneous Lymphoma and Antibody-Directed Therapies.

The introduction of monoclonal antibodies such as rituximab to the treatment of cancer has greatly advanced the treatment scenario in onco-hematology. However, the response to these agents may be limited by insufficient efficacy or resistance. Antibody-drug conjugates are an attractive strategy to deliver payloads of toxicity or radiation with high selectivity toward malignant targets and limited unwanted effects. Primary cutaneous lymphomas are a heterogeneous group of disorders and a current area of unmet need in dermato-oncology due to the limited options available for advanced cases. This review briefly summarizes our current understanding of T and B cell lymphomagenesis, with a focus on recognized molecular alterations that may provide investigative therapeutic targets. The authors reviewed antibody-directed therapies investigated in the setting of lymphoma: this term includes a broad spectrum of approaches, from antibody-drug conjugates such as brentuximab vedotin, to bi-specific antibodies, antibody combinations, antibody-conjugated nanotherapeutics, radioimmunotherapy and, finally, photoimmunotherapy with specific antibody-photoadsorber conjugates, as an attractive strategy in development for the future management of cutaneous lymphoma.

Complete remission of primary cutaneous anaplastic large cell lymphoma after a short course of brentuximab vedotin.

Primary cutaneous anaplastic large cell lymphoma (PCALCL) is a rare CD30+ lymphoproliferative disorder characterized by the development of lesions ranging from papules to large tumors. Most cases present as localized disease, however multifocal and generalized involvement of the skin can occur. Several treatments have been proposed for PCALCL; however a highly effective standard approach to multifocal disease has not yet been elucidated. The disease expression of CD30 antigen in at least 75% of the tumor makes it an optimal target for immunotherapy. The current study presents a case of a 62-year-old male referred to the University of Padua Dermatology Clinic complaining about nodular and ulcerated lesions involving the frontal area and scalp that were 8 cm in diameter. Doses of 180 mg brentuximab vedotin (BV), which is an antibody drug conjugate binding CD30 antigen, were administered every 21 days. A 75% decrease in dimensions after the first infusion and a complete remission after the second was observed. Disease response appeared to be dose-related and adverse reactions, in particular peripheral neuropathy, may be an effect of cumulative toxicity, meaning that treatment cycle reduction should be considered. Based on the present results, A high dose, short course of BV is recommended as a cost-effective approach for PCALCL. However, further studies are required to assess the efficacy and other potential advantages of this therapeutic regimen.