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.

Elongated linear vessels simulating branching vessels and diffuse structureless orange areas as prominent dermoscopic features of diffuse flat facial and extrafacial granuloma faciale: A case series.

Dermoscopy can be an important help for the diagnosis of skin cancers and inflammatory cutaneous diseases. The list of the dermoscopic features reported in granuloma faciale is wide and includes vascular and non-vascular features. We report here three cases of diffuse flat facial and extrafacial granuloma faciale that exhibited elongated linear vessels simulating branching vessels and diffuse structureless orange areas. The differential diagnosis between flat-type granuloma faciale, basal cell carcinoma and cutaneous sarcoidosis can be extremely difficult, making histology mandatory before any treatment.

Ablative CO2-Assisted Laser for Topical Drug Delivery in Nail Psoriasis: A Systematic Review.

Background: Nail psoriasis poses challenges for effective treatment, and topical drug delivery through the nail plate is limited. A novel approach to address this challenge involves the use of ablative fractional laser as a pretreatment strategy to enhance topical drug delivery for nail psoriasis. Summary: This systematic review, conducted in accordance with PRISMA guidelines, involved an extensive literature search across PubMed/MEDLINE, EMBASE, and the Cochrane Library up to July 2023. The primary focus was on exploring studies that investigated the application of ablative laser technology to augment drug delivery for nail psoriasis. Key Messages: (1) The review included seven randomized controlled trials, all examining the combination of fractional CO2 laser with topical treatments. These trials demonstrated varying degrees of improvement in nail psoriasis. (2) Patients undergoing laser treatment reported experiencing moderate levels of pain, effectively managed through the application of topical anesthesia. (3) Commonly observed side effects included erythema, swelling, and crusting, with the Koebner phenomenon being a rare occurrence. (4) Notably, patient satisfaction levels with the combined approach of laser and topical treatments were consistently high. In conclusion, the utilization of ablative CO2-assisted laser pretreatment, when used in conjunction with topical therapy, appears to be both effective and well-tolerated for the treatment of nail psoriasis. However, the establishment of optimal parameters and treatment intervals for fractional laser therapy remains an area for further research. Standardized studies are imperative to identify the most effective strategy for enhancing topical drug delivery in the context of nail psoriasis treatment.

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.

Is It Time to Reconsider Rituximab Dosing Regimens for Pemphigus Vulgaris?

Rituximab is currently approved for patients affected by moderate-to-severe pemphigus vulgaris, a severe autoimmune blistering skin disease that can be life-threatening. The standard rituximab dosing regimens, originally established for B-cell non-Hodgkin's lymphomas, have been recognized to exceed the effective dose required for inducing B-cell depletion, considering that the B-cell burden in pemphigus vulgaris is considerably lower than in lymphoproliferative disorders. We herein report our experience with very ultra-low-dose rituximab in two patients affected by pemphigus vulgaris.

A critical evaluation of suitability of tralokinumab for treatment of moderate-to-severe atopic dermatitis in adolescents and adults.

INTRODUCTION: Atopic dermatitis (AD) is a chronic, intensely pruritic disease associated with significant patient burden. Recent advancements in AD pathogenesis have expanded its therapeutics pipeline. Tralokinumab is a fully human monoclonal antibody that binds specifically Interleukin (IL)-13, inhibiting the downstream IL-13 signaling. Phase 3 clinical trials and some real-world studies showed that tralokinumab, as monotherapy or in combination with topical corticosteroids, is efficacious and safe in adult patients with moderate-to-severe AD. Similar results were reported in a phase 3 trial in adolescents (aged ≥12 years). AREAS COVERED: We review the role of IL-13 in AD and discuss the value of tralokinumab for treating moderate-to-severe AD, comparing efficacy and safety results derived from clinical trials and real-life data. EXPERT OPINION: The role of IL-13 in AD supports a targeted therapeutic approach. Tralokinumab has proven efficacious and well-tolerated in a large proportion of patients confirming its value for treating moderate-to-severe AD from age 12 years onwards; it quickly improves itching and can maintain a high-level of response over time; it can be administered with flexible dosing schedules. Future studies will further clarify the role of IL-13 pathway and which patients would be best suited to tralokinumab, shifting AD treatment into an era of precision medicine.

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.

Paraviral bullous eruption in a 7-year-old child during acute Epstein-Barr virus infection: A case report.

We present the case of a child developing widespread vesicle-bullous lesions during an acute and symptomatic Epstein-Barr Virus infection. Antibody serology, biopsy, and direct immunofluorescence allowed the diagnosis of a paraviral bullous eruption. To our knowledge, this is the first report of bullous eruption following Epstein-Barr virus infection in childhood.

Neoplastic and Autoimmune Comorbidities in Patients with Primary Cutaneous B-Cell Lymphoma.

Primary cutaneous B-cell lymphomas (PCBCLs) constitute a rare subset of non-Hodgkin lymphoma (NHL), with distinctive clinical and biological characteristics. The risk of autoimmune or neoplastic comorbidities in subjects with NHL has been extensively reported in the literature, but the data available are not directly applicable to PCBCLs. The aim of our study was to determine the frequency of relevant medical conditions, with a primary focus on autoimmune and neoplastic disorders, in subjects with PCBCL. We performed a retrospective observational study involving 56 patients diagnosed histologically with PCBCL and 54 sex- and age-matched controls. Our results show a statistically significant association for neoplastic comorbidities in general (41.1% vs. 22.2%, p = 0.034) and hematological malignancies specifically (19.6% vs. 1.9%, p = 0.0041) with PCBCL compared to controls. We did not highlight a statistically significant difference in the frequency of autoimmune comorbidities (21.4% vs. 9.3%, p = 0.1128) and of chronic viral hepatitis (7.1% vs. 0, p = 0.1184). Finally, type 2 diabetes (19.6% vs. 1.9%, p = 0.0041) was significantly associated with PCBCL. Our preliminary data supporting the association between PCBCLs and neoplastic disorders suggest that altered immune surveillance may be a common predisposing mechanism.

Altitude Effect on Cutaneous Melanoma Epidemiology in the Veneto Region (Northern Italy): A Pilot Study.

The incidence of cutaneous melanoma has been increasing in the last decades among the fair-skinned population. Despite its complex and multifactorial etiology, the exposure to ultraviolet radiation (UVR) is the most consistent modifiable risk factor for melanoma. Several factors influence the amount of UVR reaching the Earth's surface. Our study aimed to explore the relationship between melanoma and altitude in an area with mixed geographic morphology, such as the Veneto region (Italy). We included 2752 melanoma patients who were referred to our centers between 1998 and 2014. Demographics, histological and clinical data, and survival information were extracted from a prospectively maintained local database. Head/neck and acral melanoma were more common in patients from the hills and the mountains, while limb and trunk melanoma were more common in patients living in plain and coastal areas. Breslow thickness, ulceration and mitotic rate impaired with increased altitude. However, the geographical area of origin was not associated with overall or disease-free survival. The geographical area of origin of melanoma patients and the "coast-plain-hill gradient" could help to estimate the influence of different sun exposure and to explain the importance of vitamin D levels in skin-cancer control.

Merkel Cell Carcinoma: Evaluation of the Clinico-Pathological Characteristics, Treatment Strategies and Prognostic Factors in a Monocentric Retrospective Series (n=143).

BACKGROUND: Merkel cell carcinoma (MCC) is a rare neuroendocrine tumor of the skin. The incidence of the disease has undergone a significant increase in recent years, which is caused by an increase in the average age of the population and in the use of immunosuppressive therapies. MCC is an aggressive pathology, which metastasizes early to the lymph nodes. These characteristics impose an accurate diagnostic analysis of the regional lymph node district with radiography, clinical examination and sentinel node biopsy. In recent years, there has been a breakthrough in the treatment of the advanced pathology thanks to the introduction of monoclonal antibodies acting on the PD-1/PD-L1 axis. This study aimed to describe the clinico-pathological characteristics, treatment strategies and prognostic factors of MCC. METHODS: A retrospective cohort study was conducted involving 143 consecutive patients who were diagnosed and/or treated for MCC. These patients were referred to the Veneto Institute of Oncology IOV-IRCCS and to the University Hospital of Padua (a third-level center) in the period between December 1991 and January 2020. In the majority of cases, diagnosis took place at the IOV. However, some patients were diagnosed elsewhere and subsequently referred to the IOV for a review of the diagnosis or to begin specific therapeutic regimens. RESULTS: 143 patients, with an average age of 71 years, were affected mainly with autoimmune and neoplastic comorbidities. Our analysis has shown that age, autoimmune comorbidities and the use of therapy with immunomodulating drugs (which include corticosteroids, statins and beta-blockers) are associated with a negative prognosis. In this sense, male sex is also a negative prognostic factor. CONCLUSIONS: Autoimmune and neoplastic comorbidities were frequent in the studied population. The use of drugs with immunomodulatory effects was also found to be a common feature of the population under examination. The use of this type of medication is considered a negative prognostic factor. The relevance of a multidisciplinary approach to the patient with MCC is confirmed, with the aim of assessing the risks and benefits related to the use of immunomodulating therapy in the individual patient.