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.

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.

Acute ulceronecrotic adverse reaction to potassium hydroxide 5% solution in the treatment of molluscum contagiosum.

Molluscum contagiosum is a common childhood condition, and although it is self-limited, treatments are often prescribed. Several medications are available, but there is no consensus regarding the optimal choice in the pediatric population. We report a child who underwent potassium hydroxide 5% treatment resulting in superficial diffuse erosions caused by the inappropriate application. This underlines the importance of parent education before use of this medication with well-known caustic properties.

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.

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.

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.

Role of Rituximab in the Treatment of Pemphigus Vulgaris: Patient Selection and Acceptability.

Anti-CD20 monoclonal antibody rituximab is an approved adjuvant treatment, in combination with oral corticosteroids, for patients with pemphigus vulgaris, a severe and potentially life-threatening autoimmune blistering skin disorder. Updated approaches to the management of pemphigus vulgaris support rituximab as a first-line adjuvant treatment to induce remission early in the course of disease; however, its feasibility in the clinical setting is often reduced by a series of limitations, including high cost of this biological drug, physician and patient concern for the risk of adverse reactions, and uncertainty regarding the optimum dosing and schedule of administration. The standard approved rituximab dosages, which are derived from lymphoma protocols, have been recognized to exceed the effective dose required for inducing B cell depletion, since the B cell burden in pemphigus vulgaris is much lower than in lymphoproliferative disorders. To overcome these limitations, recent research has investigated alternative regimens of rituximab, using lower doses of the drug. Moreover, differences in patient and disease characteristics that are highlighted in the literature strongly suggest that therapy should be tailored individually on a case-by-case basis: personalized treatment schedules may be necessary to optimize response to treatment and tolerability in different subjects, with the possibility of repeated infusions for severe forms and in case of relapse. Finally, low-dose regimens of rituximab were suggested to be favorable during the COVID-19 pandemic by providing a lesser degree of immune cell depletion while retaining a sufficient response. In conclusion, the current literature suggests that lower-dose regimens of rituximab are not only tolerable and cost-effective but may also be associated with a positive response in pemphigus vulgaris, comparable to that achieved with higher doses especially in early disease. Further evidence from rigorous clinical trials will be required to optimize lower-dose regimens of RTX and establish their position within the treatment scenario of pemphigus vulgaris.

Psoriasis and Diabetes, a Dangerous Association: Evaluation of Insulin Resistance, Lipid Abnormalities, and Cardiovascular Risk Biomarkers.

Aims: Psoriasis is an immune-mediated dermatosis with cardio-metabolic comorbidities. The aim of this study was to assess insulin-resistance, lipid abnormalities, and cardiovascular risk biomarkers in psoriatic patients with or without type 2 diabetes mellitus (T2DM). Methods and materials: We enrolled 425 patients: 86 psoriatics, 69 psoriatics with T2DM, 120 T2DM patients, and 150 healthy subjects. We measured the Psoriasis Area and Severity Index (PASI), body mass index (BMI), insulin-resistance parameters [glycosylated hemoglobin (HbA1c), fasting plasma glucose (FPG), fasting plasma insulin (FPI), and with homeostasis model assessment index (HOMA index)], lipidic panel, plasminogen activator inhibitor-1 (PAI-1), homocysteine, soluble adhesion molecules, matrix metalloproteinase, and adipocytokines. Results: FPG, HbA1c, and HOMA-IR were higher in diabetics with psoriasis (p < 0.0001) than in psoriatics. FPI levels were higher in diabetics with psoriasis than in diabetics and psoriatics (p < 0.0001), and higher in psoriatics than controls (p < 0.0001). Psoriatics and diabetics with psoriasis showed higher triglyceride and LDL-C levels (p < 0.0001) than diabetics. Homocysteine was higher in psoriatics and diabetics with psoriasis (p < 0.0001) than in diabetics. PAI-1 was higher in diabetics with psoriasis than diabetics (p < 0.01). sICAM-1 and sVCAM-1 were higher in diabetics with psoriasis than diabetics (p < 0.001 and p < 0.01) and psoriatics (p < 0.001 and p < 0.0001). Visfatin and resistin were lower in psoriatics (p < 0.0001) and in diabetics with psoriasis (p < 0.001 and p < 0.0001, respectively) than diabetics. Conclusions: A limitation of this study is that there is a significant difference in mean age between controls and other study groups: the lack of matching between case and control groups may interfere with the external validity of the study findings. Despite this, the study highlights a pathogenetic link between psoriasis, considered a pre-diabetic condition, and diabetes. Insulin-resistance seems to be the keystone of psoriasis comorbidities. Psoriasis reinforces diabetes, causing a greater cardiometabolic risk.