Long-Term Follow-Up of Lentigo Maligna Patients Treated with Imiquimod 5% Cream.

BACKGROUND The study investigated the long-term efficacy of imiquimod 5% cream for LM, with a focus on disease recurrence and the possible prognostic factors of disease-free survival (DFS) in a cohort, with long-term follow-up. METHODS Consecutive patients with histologically confirmed LM were included. Imiquimod 5% cream was applied until weeping erosion appeared on the LM-affected skin. The evaluation was performed through clinical examination and dermoscopy. RESULTS We analyzed 111 patients with LM (median age: 72 years, 61.3% women) with tumor clearance after imiquimod therapy, with a median follow-up of 8 years. The overall patient survival rates were 85.5% (95% confidence interval (CI): 78.5-92.6) and 70.4% (95% CI: 60.3-80.5) at 5 and 10 years, respectively. Among the 23 patients (20.1%) with relapse at follow-up, 17 (73.9%) were treated with surgery, five (21.7%) continued imiquimod therapy, and one (4.3%) underwent both surgery and radiotherapy. After adjustment for age and LM area in multivariable models, localization of LM in the nasal region was identified as a prognostic factor for DFS (HR = 2.66; 95% CI: 1.06-6.64). CONCLUSION If surgical excision is not possible due to the patients' age/comorbidities or critical cosmetic localization, imiquimod could provide optimal outcomes with an optimal risk of relapse for the management of LM

Tumor-Infiltrating Lymphocytes and Their Prognostic Value in Cutaneous Melanoma.

Recent breakthroughs in tumor immunotherapy such as immune checkpoint blockade (ICB) antibodies, have demonstrated the capacity of the immune system to fight cancer in a number of malignancies such as melanoma and lung cancer. The numbers, localization and phenotypes of tumor-infiltrating lymphocytes (TIL) are not only predictive of response to immunotherapy but also key modulators of disease progression. In this review, we focus on TIL profiling in cutaneous melanoma using histopathological approaches and highlight the observed prognostic value of the primary TIL subsets. The quantification of TIL in formalin-fixed tumor samples ranges from visual scoring of lymphocytic infiltrates in H&E to multiplex immunohistochemistry and immunofluorescence followed by enumeration using image analysis software. Nevertheless, TIL enumeration in the current literature primarily relies upon single marker immunohistochemistry analyses of major lymphocyte subsets such as conventional T cells (CD3, CD4, CD8), regulatory T cells (FOXP3) and B cells (CD20). We review key studies in the literature on associations between TIL subsets and patient survival. We also cover recent findings with respect to the existence of ectopic lymphoid aggregates found in the TME which are termed tertiary lymphoid structures (TLS) and are generally a positive prognostic feature. In addition to their prognostic significance, the existence of various TIL sub-populations has also been reported to predict a patient's response to ICB. Thus, the literature on the predictive potential of TIL subsets in melanoma patients receiving ICB has also been discussed. Finally, we describe recently developed state-of-the-art profiling approaches for tumor infiltrating immune cells such as digital pathology scoring algorithms (e.g., Immunoscore) and multiplex proteomics-based immunophenotyping platforms (e.g., imaging mass cytometry). Translating these novel technologies have the potential to revolutionize tumor immunopathology leading to altering our current understanding of cancer immunology and dramatically improving outcomes for patients

Canakinumab leads to rapid reduction of neutrophilic inflammation and long-lasting response in Schnitzler syndrome.

Interleukin-1 (IL-1)-blocking therapies are effective in reducing disease severity and inflammation in Schnitzler syndrome. Here, we present a patient with Schnitzler syndrome treated successfully using canakinumab for over 10 years. Complete clinical response was associated with a decrease in dermal neutrophil number and expression of the pro-inflammatory cytokines IL-1β, IL-8, and IL-17 as assessed by immunohistochemical studies

Dimethyl Fumarate Used as an Effective Treatment for Granuloma Annulare Disseminatum: An Immunohistochemical Case Study.

This investigation demonstrates the use of dimethyl fumarate (DMF) for the treatment of disseminated granuloma annulare (GAD), a rare and chronic inflammatory skin disease. In this case, progressive GAD was treated with DMF, resulting in significant improvement of skin lesions within 5 weeks and complete healing within 7 months. Clinical response was associated with a reduction in inflammatory cells, including both T cell subsets (CD4+ > CD8+), CD183+/CXCR3+ cells, Langerhans cells (CD1a+), myeloid DCs, M1- and M2-like macrophages and the activation marker HLA-DR in immunohistochemical analysis. These findings support the use of DMF as a promising treatment option for this rare skin condition

Skin hyperpigmentation index in melasma: A complementary method to classic scoring systems.

BACKGROUND Due to relapsing nature of melasma with significant impact on quality of life, an objective measurement score is warranted, especially to follow-up the patients with melasma and their therapy response in a quantitative and precise manner. AIMS To prove concordance of skin hyperpigmentation index (SHI) with well-established scores in melasma and demonstrate its superiority regarding inter-rater reliability. Development of SHI mapping for its integration in common scores. METHODS Calculation of SHI and common melasma scores by five dermatologists. Inter-rater reliability was assessed by intraclass correlation coefficient (ICC) and concordance by Kendall correlation coefficient. RESULTS Strong concordance of SHI with melasma area and severity index (MASI)-Darkness (0.48; 95% CI: 0.32, 0.63), melasma severity index (MSI)-Pigmentation (0.45; 95% CI: 0.26, 0.61), and melasma severity scale (MSS) (0.6; 95% CI: 0.42, 0.74). Using step function for mapping SHI into pigmentation scores showed an improvement of inter-rater reliability with a difference in (ICC of 0.22 for MASI-Darkness and 0.19 for MSI-Pigmentation), leading to an excellent agreement. CONCLUSION Skin hyperpigmentation index could be an important additional cost-and time-conserving assessment method, to follow-up the patients with melasma undergoing brightening therapies in clinical studies, as well as in routine clinical practice. It is in strong concordance with well-established scores but superior regarding inter-rater reliability

Case report: Area of focus of management of severe pityriasis rubra pilaris by dose optimization of adalimumab biosimilar in combination with acitretin and montelukast

Pityriasis rubra pilaris (PRP) is a rare inflammatory skin disorder characterized by hyperkeratotic follicular papules, orange-red scaling plaques with islands of sparing and palmoplantar keratoderma. While spontaneous resolution occurs in some cases, treatment can be challenging for others. The use of biologics in PRP management has gained attention in recent studies, although their high costs and potential side effects present limitations. We present a case of a 71-year-old patient with treatment-resistant PRP who showed significant improvement through optimized adalimumab treatment. Considering the emerging role of phospholipase A2 in PRP pathogenesis, montelukast was added, further enhancing the therapeutic response. By maintaining montelukast and prolonging the adalimumab interval to 3 and 4 weeks, effective dose optimization was achieved without PRP relapse. This case report highlights the potential for adalimumab dose optimization by shortening the initial treatment interval for increased effectiveness and lengthening the interval during the maintenance phase to conserve medication doses. Montelukast appears to assist in sustaining clinical outcomes during interval prolongation, necessitating further investigation through additional studies

European Dermatology Forum guidelines on topical photodynamic therapy 2019 Part 2: emerging indications – field cancerization, photorejuvenation and inflammatory/infective dermatoses

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Trajectories of humoral and cellular immunity and responses to a third dose of mRNA vaccines against SARS-CoV-2 in patients with a history of anti-CD20 therapy.

BACKGROUND The majority of patients with B-cell-depleting therapies show compromised vaccination-induced immune responses. Herein, we report on the trajectories of anti-SARS-CoV-2 immune responses in patients of the RituxiVac study compared with healthy volunteers and investigate the immunogenicity of a third vaccination in previously humoral non-responding patients. METHODS We investigated the humoral and cell-mediated immune response after SARS-CoV-2 messanger RNA vaccination in patients with a history with anti-CD20 therapies. Coprimary outcomes were antispike and SARS-CoV-2-stimulated interferon-γ concentrations in vaccine responders 4.3 months (median; IQR: 3.6-4.8 months) after first evaluation, and humoral and cell-mediated immunity (CMI) after a third vaccine dose in previous humoral non-responders. Immunity decay rates were compared using analysis of covariance in linear regression. RESULTS 5.6 months (IQR: 5.1-6.7) after the second vaccination, we detected antispike IgG in 88% (29/33) and CMI in 44% (14/32) of patients with a humoral response after two-dose vaccination compared with 92% (24/26) healthy volunteers with antispike IgG and 69% (11/16) with CMI 6.8 months after the second vaccination (IQR: 6.0-7.1). Decay rates of antibody concentrations were comparable between patients and controls (p=0.70). In two-dose non-responders, a third SARS-CoV-2 vaccine elicited humoral responses in 19% (6/32) and CMI in 32% (10/31) participants. CONCLUSION This study reveals comparable immunity decay rates between patients with anti-CD20 treatments and healthy volunteers, but inefficient humoral or CMI after a third SARS-CoV-2 vaccine in most two-dose humoral non-responders calling for individually tailored vaccination strategies in this population.Trial registration numberNCT04877496; ClinicalTrials.gov number

An insight to HTLV-1-associated myelopathy/tropical spastic paraparesis (HAM/TSP) pathogenesis; evidence from high-throughput data integration and meta-analysis

Background Human T-lymphotropic virus 1-associated myelopathy/tropical spastic paraparesis (HAM/TSP) is a progressive disease of the central nervous system that significantly affected spinal cord, nevertheless, the pathogenesis pathway and reliable biomarkers have not been well determined. This study aimed to employ high throughput meta-analysis to find major genes that are possibly involved in the pathogenesis of HAM/TSP. Results High-throughput statistical analyses identified 832, 49, and 22 differentially expressed genes for normal vs. ACs, normal vs. HAM/TSP, and ACs vs. HAM/TSP groups, respectively. The protein-protein interactions between DEGs were identified in STRING and further network analyses highlighted 24 and 6 hub genes for normal vs. HAM/TSP and ACs vs. HAM/TSP groups, respectively. Moreover, four biologically meaningful modules including 251 genes were identified for normal vs. ACs. Biological network analyses indicated the involvement of hub genes in many vital pathways like JAK-STAT signaling pathway, interferon, Interleukins, and immune pathways in the normal vs. HAM/TSP group and Metabolism of RNA, Viral mRNA Translation, Human T cell leukemia virus 1 infection, and Cell cycle in the normal vs. ACs group. Moreover, three major genes including STAT1, TAP1, and PSMB8 were identified by network analysis. Real-time PCR revealed the meaningful down-regulation of STAT1 in HAM/TSP samples than AC and normal samples (P = 0.01 and P = 0.02, respectively), up-regulation of PSMB8 in HAM/TSP samples than AC and normal samples (P = 0.04 and P = 0.01, respectively), and down-regulation of TAP1 in HAM/TSP samples than those in AC and normal samples (P = 0.008 and P = 0.02, respectively). No significant difference was found among three groups in terms of the percentage of T helper and cytotoxic T lymphocytes (P = 0.55 and P = 0.12). Conclusions High-throughput data integration disclosed novel hub genes involved in important pathways in virus infection and immune systems. The comprehensive studies are needed to improve our knowledge about the pathogenesis pathways and also biomarkers of complex diseases.Peer reviewe