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Rosai-Dorfman disease, also known as sinus histiocytosis with massive lymphadenopathy (SHML), is a rare subtype of reactive histiocytosis which is seldom associated with Hodgkin's and non-Hodgkin's lymphomas. To date, the coexistence in the same patient of extra nodal SHML and primary cutaneous B-cell lymphoma (PCBCL) has been reported in the literature, as metachronous diagnosis in the anatomical area of the original PCBCL or synchronous occurrence in the same lesions. However, no data have been published as for synchronous occurrence of the two pathological entities in distinct anatomical sites. Herein, we report the first ever described synchronous occurrence of PCBCL and SHML, detected in distinct lesions, affecting the same patient. The complete resolution of the patient's PCBCL after rituximab treatment and the concomitant regression of SHML suggest that this clinically benign reactive histiocytic proliferation, potentially triggered by the lymphoma microenvironment itself, may take place not only in the site of the PCBCL lesion, but also in other distant areas not directly affected by the primary cutaneous lymphoma.
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Histiocitose Sinusal , Linfoma de Células B , Linfoma não Hodgkin , Linfoma , Dermatopatias , Humanos , Histiocitose Sinusal/patologia , Linfoma não Hodgkin/complicações , Dermatopatias/complicações , Linfoma de Células B/diagnóstico , Microambiente TumoralRESUMO
BACKGROUND: There is limited epidemiological evidence on outcomes associated with dupilumab exposure during pregnancy; monitoring pregnancy outcomes in large populations is required. OBJECTIVE: To investigate the potential association between exposure to dupilumab in pregnant women with atopic dermatitis and any adverse pregnancy, neonatal, congenital and post-partum outcomes. METHODS: We performed a multicentre retrospective cohort study across 19 Italian tertiary referral hospital. Childbearing women were eligible if aged 18-49 years and carried out the pregnancy between 1 October 2018 and 1 September 2022. RESULTS: We retrospectively screened records of 5062 patients receiving dupilumab regardless of age and gender, identifying 951 female atopic dermatitis patients of childbearing age, 29 of whom had been exposed to the drug during pregnancy (3%). The median duration of dupilumab treatment prior to conception was 22.5 weeks (range: 3-118). The median time of exposure to the drug during pregnancy was 6 weeks (range: 2-24). All the documented pregnancies were unplanned, and the drug was discontinued in all cases once pregnancy status was reported. The comparison of the study cohort and the control group found no significant drug-associated risk for adverse pregnancy, congenital, neonatal or post-partum outcomes. The absence of a statistically significant effect of exposure on the event was confirmed by bivariate analysis and multivariate analysis adjusted for other confounding factors. CONCLUSIONS: This cohort of pregnant patients exposed to dupilumab adds to the existing evidence concerning the safety of biologic agents in pregnancy. No safety issues were identified regarding the primary outcome assessed. In clinical practice, these data provide reassurance in case of dupilumab exposure during the first trimester. However, the continuous use of dupilumab throughout pregnancy warrants further research.
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BACKGROUND: Biologics targeting IL-23 and IL-17 show efficacy and safety in the treatment of moderate-to-severe psoriasis. OBJECTIVE: To investigate drug survival in patients with psoriasis treated with biologics. PATIENTS AND METHODS: We performed a comparative evaluation of the achievement of PASI 90 and PASI ≤ 3 at 16, 28, and 52 weeks along with a DS (drug survival) analysis with IL-17 and IL-23 inhibitors brodalumab, ixekizumab, secukinumab, risankizumab, tildrakizumab, and guselkumab on 1,057 patients. RESULTS: IL-17 inhibitors showed a faster achievement of PASI 90 and PASI ≤ 3 with significant superiority over IL-23 inhibitors at week 16 (p < 0.001; 56% vs. 42% and 70% vs. 59%, respectively). A difference was shown in favor of IL-23 inhibitors regarding DS (p < 0.001), which was 88% at 24 months vs. 75% for IL-17 inhibitors. In multivariate analysis, IL-23 inhibitors (HR 0.54 CI 0.37-0.78, p = 0.001), and male sex (HR 0.57 CI 0.42-0.76, p < 0.001) were all associated with a lower probability of drug interruption. Risankizumab (HR 0.42 CI 0.26-0.69, p = 0.001), guselkumab (HR 0.49 CI 0.24-0.99, p = 0.046), and male sex (HR 0.57 CI 0.43-0.77, p < 0.001) were associated with a lower probability of drug interruption than secukinumab. CONCLUSIONS: IL-23 inhibitors showed the best performance on DS. Overall, the most effective class was IL-17 inhibitors considering the short-term effectiveness, but long-term effectiveness is in favor of anti-IL-23.
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Anticorpos Monoclonais Humanizados , Anticorpos Monoclonais , Produtos Biológicos , Psoríase , Humanos , Masculino , Interleucina-17 , Resultado do Tratamento , Produtos Biológicos/uso terapêutico , Psoríase/tratamento farmacológico , Índice de Gravidade de Doença , Interleucina-23/uso terapêuticoRESUMO
BACKGROUND: Alcohol abuse is correlated with the onset and worsening of psoriasis, but its effects, as for smoking, on biological therapies are still poorly investigated. MATERIALS AND METHODS: This study aimed to determine the prevalence of alcohol abuse and other discretionary habits (such as smoking and sedentary lifestyle) in patients with psoriasis treated with topicals, conventional systemic and biologic therapies. The second objective is to investigate the impact of discretionary habits, focusing on alcohol abuse, on the response to biological therapy. To identify alcohol dependence, the CAGE questionnaire was distributed among patients of our clinic. RESULTS: 305 patients were included with 18% at high risk of alcohol abuse. Clinically, guttate psoriasis and psoriatic arthritis were more common in patients at higher risk of alcohol abuse. Furthermore, patients with an alcohol problem who started biological therapy reported a higher PASI than those who drank less. None of the considered variables seemed to correlate with discontinuation of medication or with lower achievement of the analyzed outcomes (PASI100, PASI90, and PASI≤3). There was a stronger association between alcohol dependence and patients receiving conventional therapy than with patients receiving biologics. CONCLUSIONS: The efficacy of biologicals did not seem to be impacted by alcohol consumption, smoking, or sedentary lifestyle.
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Dupilumab effectiveness and safety in treating moderate-to-severe atopic dermatitis (AD) have been demonstrated in open-label studies up to 4 years. Evidence about long-term psychological outcome is lacking. This study evaluates the long-term psychological outcome of moderate-to-severe AD patients continuously treated with Dupilumab up to 3 years. A prospective observational real-life study was conducted at an Italian tertiary centre from January 2019 to September 2022. Measures of disease severity and psychological outcomes were assessed at baseline, after 4, 8, 12, 24 and 36 months. A total of 382 moderate-to-severe AD patients were included. After 36 months, EASI-75 and EASI-90 were achieved by 91.8% and 77.2% of participants. Significant improvement (p < 0.001; ω2 = 0.18-0.84) in objective and patient-reported measures of disease severity and in the psychological condition were observed after 4 months of treatment and maintained up to 36 months. Longitudinal analysis of interactions of demographic and clinical features found subgroups of patients who did not reported psychological improvement over the study period notwithstanding the positive clinical response. Long-term improvement in the psychological outcome of moderate-to-severe AD patients continuously treated with Dupilumab is confirmed up to 3 years, supporting its wide use in this population. Between-subject differences in the psychological outcome irrespective of clinical response observed in this study foster the biopsychosocial approach in the clinical management of these patients.
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Dermatite Atópica , Humanos , Dermatite Atópica/tratamento farmacológico , Dermatite Atópica/induzido quimicamente , Resultado do Tratamento , Índice de Gravidade de Doença , Anticorpos Monoclonais Humanizados/uso terapêutico , Método Duplo-CegoRESUMO
BACKGROUND: The COVID-19 pandemic-related health crisis has imposed measures aimed at reducing the overcrowding of health facilities, by developing telemedicine and by forcing many sexually transmitted infection (STI) clinics to book appointments by telephone. In this work, we evaluate the performance of the nursing telephone triage system, introduced in the major STI center in Northwest Italy, for the adequacy of clinical pathways for of symptomatic STI patients. METHODS: From January to March 2021, all symptomatic patients wishing to access the CeMuSS center first underwent nurse-led telephone triage. Symptoms suggestive of STIs were further classified into four syndromic presentations: cutaneous neoformations, genital and oral ulcers, anogenital discharge, and finally other dermatological manifestations. All other clinical pictures were properly managed and eventually referred to other centers and not considered in the analysis. During the following medical examinations, the concordance between presumptive syndromic diagnosis and confirmed clinical diagnosis were recorded. Cohen k test was used to assess concordance. RESULTS: According to the Cohen k test, a good concordance between telephone presumptive diagnoses and medical clinical assessment was found (73.79% with a k = 0.611), whereas only a scarcely acceptable concordance between expected and real waiting time was established (75.51%, k = 0.34). CONCLUSIONS: Concordance between nursing syndromic diagnosis and syndromic medically confirmed diagnosis is good from a clinical point of view but there is a limitation when considering a public health perspective. An optimal training of nurses may improve the method of telephone triage. For future ongoing emergencies, the implementation of telemedicine with accurate patient management systems is mandatory.
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COVID-19 , Saúde Sexual , Infecções Sexualmente Transmissíveis , Humanos , COVID-19/diagnóstico , COVID-19/epidemiologia , Triagem/métodos , Projetos Piloto , Pandemias , Infecções Sexualmente Transmissíveis/diagnóstico , Infecções Sexualmente Transmissíveis/epidemiologia , Telefone , HospitaisRESUMO
Adalimumab is the only biological drug approved to date for the treatment of moderate and/or severe hidradenitis suppurativa. Adverse events reported during therapy include paradoxical psoriasiform reactions. No guidelines are currently available for the management of this clinical condition. The aim of this paper is to describe the incidence and clinical features of paradoxical psoriasiform eruptions occurring during treatment with adalimumab in patients with hidradenitis suppurativa and to report real-life experience in management and the possible role of other biologic agents for the treatment of both conditions.
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Produtos Biológicos , Hidradenite Supurativa , Psoríase , Humanos , Adalimumab , Hidradenite Supurativa/tratamento farmacológico , Hidradenite Supurativa/induzido quimicamente , Produtos Biológicos/uso terapêutico , Psoríase/tratamento farmacológico , Psoríase/induzido quimicamente , Fatores Biológicos/uso terapêuticoRESUMO
Dupilumab is the first biological agent approved for treatment of moderate-to-severe atopic dermatitis (AD). Evidence of Dupilumab effectiveness on psychological outcomes beyond 16 weeks of treatment from real-life settings is lacking. To evaluate the effectiveness of Dupilumab treatment up to 32 weeks, focusing health-related quality of life and psychological outcome of patients with moderate-to-severe AD. An observational prospective cohort study was conducted in a real-life setting at an Italian tertiary centre. Assessment of outcome measures was carried out at baseline, after 16 and 32 weeks of treatment. A total of 171 patients were included. EASI-75 and EASI-90 were achieved in 85% and 60% of the participants, respectively, after 16 weeks, and in 89.6% and 69.8% after 32 weeks of treatment. Significant improvements (p < 0.001; r = 0.57-0.95) were found after 16 weeks for each outcome considered, including clinician and patient-reported measures of AD severity and scales of health-related quality of life and psychological morbidity, and maintained up to 32 weeks. Further analysis revealed that patients' quality of life was more associated with the subjective perception of disease severity rather than objective measures and suggested a possible different response to treatment based on the age of AD onset. Dupilumab was confirmed to be rapid, effective and safe in patients with moderate-to-severe AD. Its positive impact on psychological outcomes up to 32 weeks was ascertained here, adding new evidence on the need to consider subjective factors affecting patients' perception of disease severity in evaluating the response to treatment.
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Dermatite Atópica , Anticorpos Monoclonais Humanizados , Ansiedade/tratamento farmacológico , Depressão/tratamento farmacológico , Dermatite Atópica/diagnóstico , Dermatite Atópica/tratamento farmacológico , Dermatite Atópica/psicologia , Método Duplo-Cego , Humanos , Estudos Prospectivos , Qualidade de Vida , Índice de Gravidade de Doença , Resultado do TratamentoRESUMO
Nail psoriasis is a chronic nail disorder that commonly affects psoriatic patients causing severe distress despite the limited body surface area. Treatments for nail psoriasis are limited, as nails are often difficult to treat with topical therapies, and among different systemic agents responses are unpredictable. We carried out a prospective study in order to analyze the effectiveness and tolerability of topical cyclosporine hydrogel ointment in nail psoriasis. Three patients, for a total of 44 nails, were treated with topical cyclosporine hydrogel ointment. All nails were evaluated, before starting the treatment, every 28 days and after 12 weeks of therapy, by the same dermatologists, through clinical and onychoscopic evaluations. The patients were also asked to assess on the compliance with product use. Complete response (CR) was observed in 2 of 3 patients; a partial response (PR) was observed in the other patient. Overall, 24 of 44 nails had CR and 20 had a PR. Cyclosporine hydrogel ointment has shown efficacy and safety in the treatment of nail psoriasis. The product has also been shown to be stable in composition, easy to apply and not discomfortable for the patient.
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Fármacos Dermatológicos , Doenças da Unha , Psoríase , Humanos , Ciclosporina , Pomadas/uso terapêutico , Estudos Prospectivos , Hidrogéis/uso terapêutico , Doenças da Unha/diagnóstico , Doenças da Unha/tratamento farmacológico , Doenças da Unha/etiologia , Psoríase/diagnóstico , Psoríase/tratamento farmacológico , Psoríase/complicaçõesRESUMO
Guselkumab is an IL-23 inhibitor that has been demonstrated to be effective and safe for the treatment of moderate-to-severe plaque psoriasis in clinical trials. The data pool relating to the use of guselkumab in a real-life setting is still lacking. To evaluate the efficacy and safety of guselkumab in a real-life setting, focusing on predictors of early clinical response, a single-center prospective study was conducted enrolling patients with moderate-to-severe psoriasis. The clinical data relating to the efficacy and safety of the drug were acquired at initiation of treatment and at all subsequent clinical follow-ups: the primary endpoint was PASI90 and PASI100 response at week 12, 24, and 48. Out of the total cohort of 74 patients, 62 (83.8) reached a 48-week follow-up 64 (87.8%) reached a 24-week follow-up, while 72 (97.3%) a 12-week follow-up. Treatment with guselkumab reduced the mean PASI from the initial 11 ± 6.3 to 2.5 ± 3.1 at 12 weeks, to 1.2 ± 1.8 at 24 weeks, and to 0.8 ± 1.6 at 48 weeks. At week 12, a PASI 90 and PASI 100 response was achieved by 44.4% and 23.6% of patients, respectively. After 24 weeks, 63% of patients reported a PASI 90 while 46.1% achieved PASI 100. Previous treatment with one or more other biologics did not impact significantly on the achievement of the PASI 90 and 100 at any endpoints analyzed. We reported no difference between bio-naïve and non-naïve patients in the response to guselkumab, high safety, and efficacy was showed in both populations.
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Produtos Biológicos , Psoríase , Anticorpos Monoclonais/uso terapêutico , Anticorpos Monoclonais Humanizados , Produtos Biológicos/uso terapêutico , Humanos , Interleucina-23 , Estudos Prospectivos , Psoríase/diagnóstico , Psoríase/tratamento farmacológico , Índice de Gravidade de Doença , Resultado do TratamentoRESUMO
Risankizumab has been recently approved for moderate-to-severe plaque psoriasis; however, real-life studies are scarce. Analysis of possible predictor factors of treatment response are limited to body mass index (BMI) and previous biologic experience. Our objectives were to evaluate the effectiveness and safety of Risankizumab and to investigate on possible predictor factors response. We retrospectively analyzed 166 patients from two centers in Italy who undergone Risankizumab for psoriasis. The proportion of patients achieving a 100%, 90%, 75% of improvement in Psoriasis Area Severity Index (PASI) and PASI <3 were collected at weeks 16, 28, 40, and 52. Study population was analyzed in subgroups to investigate possible predictors of response to Risankizumab since week 40. At the time of analysis 165, 103, 30, and 11 patients had completed 16, 28, 40, and 52 weeks of treatment, respectively. The mean PASI score decreased from 12.5 ± 5.1 at baseline to 1.9 ± 2.4 at week 16. Similar reductions were observed when considering PASI <3, PASI 75, PASI 90, and PASI 100. Previous biologics failure, different smoking habits, obesity, and joint involvement resulted in a lower response to risankizumab. In particular, significant differences in mean PASI at any time-points was observed between psoriatic arthritis (PSA) and non-PSA patients: 2.7 versus 1.7 (p = 0.036), 1.9 versus 0.4 (p = 0.006), and 4.1 versus 0.5 (p = 0.016) at 16, 28, and 40 weeks, respectively. No difference in response to risankizumab occurred in the case of involvement of difficult-to-treat areas. In this population, Risankizumab was effective and safe. Smoking habits, joint involvement, obese status, and previous biologic experience may negatively affect treatment response, while difficult body sites involvement have minor impact.
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Artrite Psoriásica , Psoríase , Anticorpos Monoclonais , Método Duplo-Cego , Humanos , Psoríase/diagnóstico , Psoríase/tratamento farmacológico , Estudos Retrospectivos , Índice de Gravidade de Doença , Resultado do TratamentoRESUMO
Immunotherapy and target therapy have revolutionized treatment of stage III/IV melanoma. Both treatments show a favorable toxicity profile even if cutaneous adverse events (AEs) are frequent (30%-40% of cases). This is a retrospective single center cohort study that included patients with stage IV or inoperable stage III metastatic melanoma (AJCC 8th) who received BRAFi + MEKi therapy or immunotherapy with Checkpoint inhibitors. All cutaneous AEs were ascertained by a dermatologist based on clinical and histological findings. The primary outcome was to provide a detailed clinical dermatological classification of cutaneous adverse events and an evaluation of the incidence of skin toxicity in the two arms of therapy (immunotherapy and target therapy). A total of 286 patients with stages III-IV metastatic melanoma were included: 146 received immunotherapy and 140 target therapy. In the immunotherapy cohort, 63 (43.1%) cutaneous reactions were observed while 33 skin reactions (23.6%) were identified in patients treated with target therapy. All the skin toxicities observed were grade I, excepted four cases: an erythema multiforme-like eruption, a grade III psoriasis and two grade III maculopapular rashes. Immunotherapy in older age resulted statistically related to skin toxicities (p = 0.011), meanly in metastatic setting (p = 0.011). Cumulative incidence of skin toxicities was 65.63% in immunotherapy cohort (p = 0.001). Also multivariate logistic regression shows a significant association between skin adverse events and immunotherapy (odds ratio [OR] = 0.50; 95% confidence interval [CI]: 0.29-0.85, p: 0.01) and between cutaneous AEs and metastatic setting (OR = 1.97; 95% CI: 1.04-3.74, p: 0.04). We have also shown that as the age of initiation of therapy increases the probability of developing skin toxicity grows. However, stratifying by type of therapies the effect of age persists only in immunotherapy (OD: 1.04; CI: 1.01-1.06; p: 0.04) while for target therapy age does not affect the onset of skin toxicity (OD 1.01; CI 0.98-1.04; p = 0.42). No differences were shown between patients on target therapy and immunotherapy regarding gender. Patients were also evaluated regarding concomitant therapies and seems that Levotyroxine may be involved in AEs during immunotherapy treatment. More studies are needed to deepen this aspect, also considering the medical history and diverse drug associations. Cutaneous adverse events are characterized by heterogeneous manifestations, are more often seen in patients on immunotherapy and dermatologists can play a crucial role in multidisciplinary care.
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Efeitos Colaterais e Reações Adversas Relacionados a Medicamentos , Melanoma , Dermatopatias , Neoplasias Cutâneas , Estudos de Coortes , Efeitos Colaterais e Reações Adversas Relacionados a Medicamentos/etiologia , Humanos , Fatores Imunológicos/uso terapêutico , Imunoterapia/efeitos adversos , Imunoterapia/métodos , Melanoma/tratamento farmacológico , Melanoma/patologia , Estudos Retrospectivos , Dermatopatias/etiologia , Neoplasias Cutâneas/tratamento farmacológico , Neoplasias Cutâneas/etiologia , Melanoma Maligno CutâneoRESUMO
Psoriatic patients with latent tuberculosis infection and properly treated active tuberculosis need careful management when prescribing modern biological drugs. Although data and guidelines regarding tumour necrosis factor-α inhibitors advise caution and initiation of prophylactic therapy in patients with latent tuberculosis infection, the same indications do not seem to find equal force for interleukin (IL)-23 and IL-17 inhibitors. In order to evaluate the risk of reactivation in patients with latent tuberculosis infection or properly treated active tuberculosis, an observational retrospective study was conducted on the population referred to our centre at Dermatologic Clinic of University of Turin, Italy. In the last 10 years at the clinic 19 psoriatic patients were found to be at risk of tuberculosis reactivation: 10 patients were QuantiFERON- TB-positive at baseline, 2 became positive during treatment, 6 reported prior tuberculous infection, and 1 was QuantiFERON-TB-negative at baseline and developed disseminated tuberculosis during treatment with anti-tumour necrosis factor-α. Overall, 10.5% of this group of patients developed active tuberculosis; however, stratifying by biologic therapy, zero cases were observed among patients treated with anti-IL-17, -23, or -12/23 over a relatively long follow-up (48.1 months) A review of the available literature following our experience confirms the increased risk of tuberculosis reactivation with tumour necrosis factor-α inhibitors. Concerning anti-IL-23 and IL-17 drugs, available data showed high safety in patients at risk of tuberculosis reactivation. Screening of patients who should be taking IL-17 and IL-23 inhibitors is recommended for public health purposes. In case of a positive result with these therapies, consulting with an infectious diseases specialist is suggested in order to weigh up the risks and benefits of prophylactic treatment.
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Tuberculose Latente , Psoríase , Tuberculose , Humanos , Terapia Biológica , Tuberculose Latente/induzido quimicamente , Tuberculose Latente/diagnóstico , Tuberculose Latente/epidemiologia , Necrose , Estudos Observacionais como Assunto , Psoríase/diagnóstico , Psoríase/tratamento farmacológico , Estudos Retrospectivos , Centros de Atenção Terciária , Teste Tuberculínico , Tuberculose/prevenção & controle , Fator de Necrose Tumoral alfaRESUMO
Melanoma is one of the most aggressive skin cancers. The 5-year survival rate of stage III melanoma patients ranges from 93% (IIIA) to 32% (IIID) with a high risk of recurrence after complete surgery. The introduction of target and immune therapies has dramatically improved the overall survival, but the identification of patients with a high risk of relapse who will benefit from adjuvant therapy and the determination of the best treatment choice remain crucial. Currently, patient prognosis is based on clinico-pathological features, highlighting the urgent need of predictive and prognostic markers to improve patient management. In recent years, many groups have focused their attention on identifying molecular biomarkers with prognostic and predictive potential. In this review, we examined the main candidate biomarkers reported in the literature.
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Melanoma/genética , Melanoma/patologia , Melanoma/terapia , Biomarcadores , Biomarcadores Farmacológicos , DNA Tumoral Circulante/genética , Humanos , MicroRNAs/genética , Estadiamento de Neoplasias/métodos , Prognóstico , Proteínas Proto-Oncogênicas B-raf/genética , Neoplasias Cutâneas/patologia , Taxa de Sobrevida , Melanoma Maligno CutâneoRESUMO
Dupilumab is an IgG4 human monoclonal antibody licensed for the treatment of moderate-to-severe atopic dermatitis. Despite evidence suggesting that T helper type two cytokines can modulate HIV-1 replication and anti-HIV-specific immune responses, impacting on viral reservoirs, HIV-positive patients under immunomodulating therapy have been excluded from clinical trials. We report a 47-year-old HIV-positive man with late-onset severe atopic dermatitis, treated with dupilumab and followed up for 27 months. Improvements in skin lesions and quality of life were observed after four months. Blood tests showed normalization of IgE levels, with the clinical condition remaining stable at a 27- month follow-up. We gathered 16 other cases reported in the literature of HIV-positive patients treated with dupilumab, with no, or few adverse reactions, for which it is unclear if dupilumab should be held accountable. With our case and literature review, we aim to shed light on dupilumab efficacy, safety, and tolerability among HIV-positive patients suffering from atopic dermatitis. In this regard, future research should focus on the effective role, underlying mechanisms, and efficacy of dupilumab in HIV-positive patients and HIV-positivity could be questioned as a valid exclusion criterion for clinical trials.