Primary Cutaneous CD4+ Small/Medium T-Cell Lymphoproliferative Disorders (SMPLPD), demographical, clinical, therapeutic and prognostic aspects: a retrospective monocentric analysis.

Primary Cutaneous CD4+ Small/Medium T-Cell Lymphoproliferative Disorders (SMPLPD), also known as PCS-TCLPD, represent a rare group of hematologic diseases primarily affecting the skin. In this retrospective single-centre case series study, we aimed to investigate the demographic, clinical, therapeutic, and prognostic aspects of SMPLPD. We collected data from cases diagnosed between 2010 and the present, employing histopathological and immunohistochemical methods following WHO criteria. We included 22 patients with a median age of 61.50 years and median time between clinical onset and diagnosis of 3.00 months. Surgical excision with conservative margins was the primary choice, showing clinical remission in 17 cases, while non-surgical treatments, including radiotherapy, high-potency steroid treatment and ablative laser, achieved clinical remission in four cases. Clinical presentations varied, but the most common one was a single violaceous nodule/papule on upper body parts. In conclusion, our single-centre case series provides valuable insights into SMPLPD, highlighting the effectiveness of surgical treatments and the potential of non-surgical ones. Even if controversial, the benign nature of SMPLPD emphasizes the importance of achieving tumour clearance with acceptable aesthetic outcomes.

Biological therapy in patients with psoriasis: What we know about the effects on renal function.

Psoriasis is a chronic inflammatory dermatosis affecting 2%-3% of the general population. The link between psoriasis and renal dysfunction has been investigated, demonstrating a common pro-inflammatory pathogenesis. This study is aimed at evaluating renal function in patients with moderate-to-severe chronic plaque psoriasis treated with biological therapy. We analyzed 92 patients, correlating PASI and serum creatinine levels at baseline, after 6 months and after 1 year of continuous treatment with biological therapy. Data were analyzed using paired t-test and the linear mixed model for PASI and serum creatinine levels correlation, whereas the analysis of variances (ANOVA) was used for creatinine levels assessment between the baseline, the 6-months and, 1-year later evaluation. We observed a significant mean decrease in comparing serum creatinine levels after 1 year of biological therapy (p < 0.001). Interestingly, PASI reduction is correlated with creatinine decrease, and the renal function improvement is greater when complete psoriasis remission is attained. Our data suggest that a drop in systemic inflammation, secondary to biological therapy administration, might improve renal function. Future research is needed to confirm and expand our findings.

Head and neck dermatitis, a subtype of atopic dermatitis induced by Malassezia spp: Clinical aspects and treatment outcomes in adolescent and adult patients.

BACKGROUND AND OBJECTIVES: Head and neck dermatitis (HND) is a clinical variant of atopic dermatitis (AD), presenting in adolescence or adulthood and characterized by involvement of the head, neck, and superior part of the trunk. The role of Malassezia spp has been advocated in the pathogenesis of HND, and antifungal agents represent the treatment of choice. METHODS: A retrospective single-center study was performed to define the clinical features and treatment response of HND among adolescent and adult patients. RESULTS: Thirty-one patients were identified, 17 with "adolescent-onset" and 14 with "adult-onset" HND. Adolescent-onset HND positively correlated with a past history of AD and presented with exclusive head and neck involvement (P < .05). Adult-onset HND was associated with concomitant widespread atopic eczema, involving the flexural areas of the upper and lower limbs, trunk, nipples, or hands (P < .05). A positive response to itraconazole in combination with topical treatments was observed in both groups. CONCLUSIONS: This study delineates two HND clinical phenotypes: adolescent vs adult onset. Different characteristics were observed in terms of relationship to AD and eczema localization. A history of AD in childhood and presentation with exclusive involvement of head and neck regions was observed predominantly in the adolescent-onset form, while adult-onset HND often occurred in association with diffuse dermatitis and a past history of AD was less frequent than in the adolescent group. The study is limited by the single-center retrospective nature, which may lead to diagnostic and selection biases, and the small cohort of patients.

Vulvar vitiligo and lichen sclerosus in children: A clinical challenge.

Vulvar vitiligo (VV) and vulvar lichen sclerosus (VLS), both feature skin and mucosal hypo-/depigmentation. The aim of this study was to describe the clinical and dermoscopic features of VV and VLS in the pediatric population, providing diagnostic clues, and to define their association. We performed a systematic literature review of the clinical and dermoscopic features of pediatric VV and VLS. An observational study was conducted on children affected by VLS associated with VV, referred to the Dermatology Unit of the Sant'Orsola Polyclinic in Bologna, Italy. Medical history, age at diagnosis, ethnicity, clinical and dermoscopic features, and symptoms were recorded for all patients. 124 cases of VLS and 10 cases of VV were reviewed. Clinical manifestations included hypo-/depigmented patches in both conditions, while ecchymosis/purpura and fissures/erosion were observed in VLS. Symptoms including pruritus, pain, or burning were reported only by VLS patients. In our study five patients with VLS associated with VV were retrieved. Clinical features included well-demarcated depigmented patches in VV and translucent areas, erythema, ecchymoses/purpura, and labial fusion in VLS. Dermoscopy showed white structureless areas with a whipped cream-like appearance, linear or dotted vessels, white chrysalis-like structures, erosion and red-purpuric blotches in VLS and reduced pigment network or pigment absence, intralesional spots of residual pigmentation and telangiectasias in VV. Symptoms were present in all patients. Both VV and VLS show hypo-/depigmented patches. In the presence of associated symptoms, possible VLS should be investigated with clinical and dermoscopic examination to achieve a prompt diagnosis.

Cutaneous adverse-events in patients treated with Ibrutinib.

Ibrutinib is a Burton tyrosine kinase inhibitor (BTKi) approved for the treatment of several hematologic malignancies. Analyze skin adverse events (SAE). All the patients treated with Ibrutinib featuring cutaneous adverse events were selected. Twenty five patients were retrieved with a median interval between Ibrutinib start and SAE time of onset of 120 days. Most common SAE observed involved hairs and nails. Eczematous reaction and leucocytoclastic vasculitis were also detected. One patient had a long-history Ibrutinib treatment and experienced numerous cutaneous adverse events. Infective disease such as superficial mycosis and impetigo were rarely present in our series. Despite the development of cutaneous SAE, all the patients continued their concomitant drugs without the onset of any further SAE. Our data suggest Ibrutinib-associated rash should be distinguished in early and late events and a careful dermatologic management of patients should be scheduled.

The Role of Cytokines in Cutaneous T Cell Lymphoma: A Focus on the State of the Art and Possible Therapeutic Targets.

Cutaneous T cell lymphomas (CTCLs), encompassing mycosis fungoides (MF) and Sézary syndrome (SS), present a complex landscape influenced by cytokines and cellular responses. In this work, the intricate relationship between these inflammatory proteins and disease pathogenesis is examined, focusing on what is known at the clinical and therapeutic levels regarding the most well-known inflammatory mediators. An in-depth look is given to their possible alterations caused by novel immunomodulatory drugs and how they may alter disease progression. From this narrative review of the actual scientific landscape, Interferon-gamma (IFN-γ) emerges as a central player, demonstrating a dual role in both promoting and inhibiting cancer immunity, but the work navigates through all the major interleukins known in inflammatory environments. Immunotherapeutic perspectives are elucidated, highlighting the crucial role of the cutaneous microenvironment in shaping dysfunctional cell trafficking, antitumor immunity, and angiogenesis in MF, showcasing advancements in understanding and targeting the immune phenotype in CTCL. In summary, this manuscript aims to comprehensively explore the multifaceted aspects of CTCL, from the immunopathogenesis and cytokine dynamics centred around TNF-α and IFN-γ to evolving therapeutic modalities. Including all the major known and studied cytokines in this analysis broadens our understanding of the intricate interplay influencing CTCL, paving the way for improved management of this complex lymphoma.

A Narrative Review of the State of the Art of CCR4-Based Therapies in Cutaneous T-Cell Lymphomas: Focus on Mogamulizumab and Future Treatments.

The CCR4 receptor is a pivotal target in cutaneous T-cell lymphoma (CTCL) therapy due to its role in impairing immune responses against malignant T-cells and expression profiles. Monoclonal antibodies like mogamulizumab effectively bind to CCR4, reducing tumour burden and enhancing patient outcomes by inhibiting the receptor's interaction with ligands, thereby hindering malignant T-cell migration and survival. Combining CCR4 antibodies with chemotherapy, radiation, and other drugs is being explored for synergistic effects. Additionally, small-molecular inhibitors, old pharmacological agents interacting with CCR4, and CAR-T therapies are under investigation. Challenges include drug resistance, off-target effects, and patient selection, addressed through ongoing trials refining protocols and identifying biomarkers. Despite advancements, real-life data for most of the emerging treatments are needed to temper expectations. In conclusion, CCR4-targeted therapies show promise for CTCL management, but challenges persist. Continued research aims to optimise treatments, enhance outcomes, and transform CTCL management. This review aims to elucidate the biological rationale and the several agents under various stages of development and clinical evaluation with the actual known data.

Biologics and small molecules treatment for moderate-to-severe atopic dermatitis patients with comorbid conditions and special populations: an Italian perspective.

This comprehensive review offers a detailed look at atopic dermatitis (AD) treatment in Italy, focusing primarily on the use of biologics and small molecules. In response to advancing knowledge of AD's causes and treatments, there's a global need for updated guidelines to provide physicians with a more comprehensive clinical perspective, facilitating personalized treatment strategies. Dupilumab, a groundbreaking biologic, gained approval as a significant milestone. Clinical trials demonstrated its ability to significantly reduce AD severity scores, with an impressive 37% of patients achieving clear or nearly clear skin within just 16 weeks of treatment. Real-world studies further support its efficacy across various age groups, including the elderly, with a safety profile akin to that of younger adults. Tralokinumab, a more recent approval, shows promise in clinical trials, particularly among younger populations. However, its real-world application, especially in older individuals, lacks comprehensive data. Janus Kinases inhibitors like Upadacitinib, Baricitinib, and Abrocitinib hold substantial potential for AD treatment. Nevertheless, data remains limited for patients over 75, with older adults perceived to carry a higher risk profile. Integrated safety analyses revealed individuals aged 60 and above experiencing major adverse cardiovascular events and malignancies, underscoring the need for cautious consideration. While these therapies offer promise, especially among younger patients, further research is essential to determine their safety and efficacy in various populations, including pediatric, geriatric, and those with comorbidities. Biologics and small molecules are improving AD treatment, as shown in this review.

New insights into the oncological risk in heart transplant recipients: could skin tumors represent a marker of increased risk for solid neoplasm?

BACKGROUND: Solid organ transplant recipients are at increased risk for skin cancers due to immune-suppressive therapies. However, little is known about the risk and the characteristics of neoplasms in heart transplant recipients (HTRs). The aim of this study is to delineate the incidence of different skin tumors in HTRs and to correlate it with the incidence of other malignancies, including solid tumors and hematological neoplasms. METHODS: Patients who underwent to HTRs between January 1991 and November 2021 were retrieved. Clinical data on immunosuppressive therapies, skin tumors, solid and hematological neoplasms were obtained. HTRs with skin tumors were included in group A, while patients with no evidence of skin tumors during the follow-up were included in group B. RESULTS: One hundred and eight patients were retrieved. A significant increase in solid tumors was observed in group A, while no significant difference in hematological neoplasms was detected between the two groups. CONCLUSIONS: HTRs with skin tumors showed a significantly higher incidence of solid neoplasms. In most of the cases the skin tumor preceded the onset of the solid neoplasm, suggesting that the skin tumor could represent a 'marker' of immunosuppression eventually leading to the development of an internal malignancy.

Erythroderma: psoriasis or lymphoma? A diagnostic challenge and therapeutic pitfall.

BACKGROUND: Psoriasis and lymphoma risk is widely debated, but few is known about misdiagnosis risk between erythrodermic psoriasis and lymphoma. In fact, erythroderma might represent a clinical presentation of psoriasis, cutaneous T-cell lymphomas and skin dissemination of systemic lymphomas. METHODS: All patients referred to psoriasis outpatient service with a diagnosis of erythrodermic psoriasis were re-examined. Among them, all the patients with a subsequent lymphoma diagnosis were included. For each patient data concerning age, gender, age at erythroderma onset, age at lymphoma diagnosis, immune-suppressive therapy, type of lymphoma and relative stage, lymphoma treatment and outcome were obtained. RESULTS: Twenty-five patients (15 females and 10 males) with a diagnosis of erythrodermic psoriasis were retrieved. Among them, 9 patients (5 males and 4 females) were affected by erythrodermic lymphoma, including 4 patients with Sèzary Syndrome, 3 with mycosis fungoides, and 2 with peripheral T-cell lymphoma not otherwise specified. Prior to lymphoma diagnosis all the patients (9/9) received cyclosporine, two (2/9) of them methotrexate, one (1/9) azatioprine, and two (2/9) systemic corticosteroids. The prognosis of our patients was poor, due to immune-suppressive drugs administration in patients with undiagnosed lymphoma. The only exception was one (1/9) patient with Sèzary Syndrome still alive with disease after 120 months of follow-up. CONCLUSIONS: In case of patients with erythroderma, multiple skin biopsies and specific peripheral blood studies like flow cytometry and T-cell receptor gene rearrangement analysis are required in order to avoid misdiagnosis risk between psoriasis and lymphoma.