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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.
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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.
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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.
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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.
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Linfoma Cutâneo de Células T , Micose Fungoide , Síndrome de Sézary , Neoplasias Cutâneas , Humanos , Citocinas/genética , Neoplasias Cutâneas/tratamento farmacológico , Neoplasias Cutâneas/etiologia , Linfoma Cutâneo de Células T/tratamento farmacológico , Linfoma Cutâneo de Células T/patologia , Micose Fungoide/patologia , Síndrome de Sézary/terapia , Síndrome de Sézary/genética , Interferon gama , Microambiente TumoralRESUMO
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.
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Transplante de Coração , Neoplasias Hematológicas , Neoplasias Cutâneas , Transplantados , Humanos , Transplante de Coração/efeitos adversos , Neoplasias Hematológicas/complicações , Tolerância Imunológica , Terapia de Imunossupressão/efeitos adversos , Neoplasias Cutâneas/diagnóstico , Neoplasias Cutâneas/epidemiologia , Neoplasias Cutâneas/etiologiaRESUMO
BACKGROUND: The mechanisms involved in mycosis fungoides, and Sezary Syndrome progression are largely unknown. Over the last decade the interest in immune system contrast of neoplasm has grown owing to the introduction of immunotherapy. PD-1 and its ligand (PD-L1) are the target of several immunotherapy treatment. In the literature reports on the expression of PD-1 and PD-L1 have provided contrasting results. METHODS: In our analysis we investigated PD-1 expression in neoplastic cells and in tumor infiltrating lymphocytes (TILs) as well as PD-L1 expression in tumor cells and in tumor associated macrophages (TAMs). PD-L1 and PD-1 positive cells were counted in 5 high-power fields (HPF) and scored as the average number of positive neoplastic cells/TILs/TAMs per HPF. RESULTS: From databases of two institutions (Bologna and Florence) thirty-five patients corresponding to 43 biopsies were retrieved. In seven instances sequential biopsies were present. No statistically significant expression was observed comparing early to advanced stages by analysing PD-1 by tumor cells and TILs and of PD-L1 by tumor cells and TAMs. CONCLUSIONS: Our results corroborate that PD-1 and PD-L1 expression is not stage-dependent in mycosis fungoides and Sezary syndrome. However, PD-1 and PD-L1 expression in affected patients provides a rationale to schedule anti PD-1/PD-L1 drugs.
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Antígeno B7-H1 , Micose Fungoide , Receptor de Morte Celular Programada 1 , Síndrome de Sézary , Neoplasias Cutâneas , Antígeno B7-H1/genética , Humanos , Linfócitos do Interstício Tumoral , Micose Fungoide/metabolismo , Receptor de Morte Celular Programada 1/genética , Síndrome de Sézary/metabolismo , Neoplasias Cutâneas/metabolismoRESUMO
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.
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Anticorpos Monoclonais , Psoríase , Anticorpos Monoclonais/farmacologia , Anticorpos Monoclonais/uso terapêutico , Terapia Biológica , Humanos , Rim/efeitos dos fármacos , Rim/patologia , Rim/fisiologia , Psoríase/diagnóstico , Psoríase/tratamento farmacológico , Índice de Gravidade de Doença , Resultado do TratamentoRESUMO
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.
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Dermatite Esfoliativa , Linfoma Cutâneo de Células T , Psoríase , Síndrome de Sézary , Neoplasias Cutâneas , Dermatite Esfoliativa/diagnóstico , Feminino , Humanos , Linfoma Cutâneo de Células T/complicações , Masculino , Psoríase/complicações , Síndrome de Sézary/complicaçõesRESUMO
BACKGROUND: Mycosis fungoides (MF) and Sezary Syndrome (SS) are the most common cutaneous T-cell lymphomas. It has been hypothesized that the interaction between the immune system, cutaneous cells, and neoplastic elements may play a role in MF/SS pathogenesis and progression. METHODS: This paper aims to revise in a narrative way our current knowledge of the microenvironment's role in MF/SS. RESULTS AND CONCLUSIONS: Literature data support a possible implication of microenvironment cells in MF/SS pathogenesis and progression, opening up new therapeutic avenues.
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Progressão da Doença , Micose Fungoide/patologia , Micose Fungoide/terapia , Síndrome de Sézary/patologia , Síndrome de Sézary/terapia , Neoplasias Cutâneas/patologia , Neoplasias Cutâneas/terapia , Microambiente Tumoral , Animais , HumanosRESUMO
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.
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Líquen Escleroso e Atrófico , Vitiligo , Líquen Escleroso Vulvar , Criança , Feminino , Humanos , Líquen Escleroso e Atrófico/complicações , Líquen Escleroso e Atrófico/diagnóstico , Estudos Observacionais como Assunto , Pele , Vitiligo/diagnóstico , Líquen Escleroso Vulvar/diagnósticoRESUMO
Primary cutaneous T-cell lymphomas (PCTCL) are the most common types of cutaneous lymphomas, with Mycosis fungoides as the most frequent subtype. Besides early stages which usually have a good prognosis, advanced stages remain a great therapeutic challenge with low survival rates. To date, none of the currently available therapeutic options have significantly improved the outcomes of advanced cutaneous lymphomas. Recent studies have demonstrated that immune-checkpoint molecules, such as PD-1 and CTLA-4, play part in the proliferation pathways of neoplastic T-cells, as well as in other tumors. Hence, the potential role of immune-checkpoint-inhibitors in treating cutaneous lymphomas has been investigated in the last years. Herein, we outline the current knowledge regarding the role of immune-checkpoint molecules in PCTCL, their signaling pathways, microenvironment and therapeutic inhibition rationale. Moreover, we review the published data on immunotherapies in PCTCL and summarize the currently ongoing clinical trials in this field.