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1.
Arch Dermatol Res ; 2022 Jan 15.
Artigo em Inglês | MEDLINE | ID: mdl-35032198

RESUMO

The timing pattern in which dipeptidyl-peptidase IV inhibitors (DPP4i) confer the risk of bullous pemphigoid (BP) is unknown. To investigate the odds of BP following exposure to DPP4i and to perform a duration-response analysis evaluating the risk of BP in relation to the duration of exposure to the culprit drug. A population-based nested case-control study was performed comparing diabetic patients with BP (n = 1458) with age-, sex- and ethnicity-matched diabetic control subjects (n = 6051) with respect to the prevalence of exposure to DPP4i. Adjusted odds ratios (ORs) were estimated by logistic regression. Overall exposure to DPP4i was associated with an 80% increase in the odds of subsequent BP (OR, 1.81; 95% CI, 1.46-2.08; P < 0.001). In an intraclass analysis, the odds of BP were increased in association with vildagliptin (OR, 3.40; 95% CI, 2.69-4.29; P < 0.001) and sitagliptin (OR, 1.56; 95% CI, 1.33-1.84; P < 0.001). In a duration-response analysis, the highest likelihood of BP was found 1-2 years after commencing the drug (OR, 2.66; 95% CI, 1.97-3.59; P < 0.001). The odds of BP were increased across all time periods and retained its statistical significance even ≥ 6 years after the drug initiation (OR, 1.44; 95% CI, 1.09-1.91; P = 0.011). Relative to other diabetic patients with BP, patients with DPP4i-associated BP were more likely to be admitted to inpatient dermatologic wards (OR, 1.66; 95% CI, 1.30-2.13; P < 0.001) and had higher mean(SD) numbers of outpatient dermatologist visits (14.7[14.8] vs. 12.3[13.2], respectively; P = 0.006). DPP4i should be suspected as a predisposing factor for BP even numerous years after the drug initiation.

2.
Pharmaceuticals (Basel) ; 15(1)2022 Jan 14.
Artigo em Inglês | MEDLINE | ID: mdl-35056153

RESUMO

Since psoriasis (PsO) is a chronic inflammatory disease, patients may experience a drug failure also with very effective drugs (i.e., secukinumab) and, consequently, dermatologists have two therapeutic options: switching or perform a combination therapy (rescue therapy) to save the drug that had decreased its efficacy. At the moment no studies focused on combination/rescue therapy of secukinumab, so we performed a 52-weeks multicenter retrospective observational study that involved 40 subjects with plaque psoriasis that experienced a secondary failure and were treated with combination therapy (ciclosporin (n = 11), MTX (n = 15), NB-UVB (n = 7) and apremilast (n = 7)). After 16 weeks of rescue/combination therapy, PASI and a DLQI varied respectively from 8 [7.0-9.0] and 13 [12.0-15.0], to 3 [2.8-4.0] and 3 [2.0-3.3]), suggesting a significant improvement of daily functionality and quality of life. Results were maintained at 52 weeks. No side effects were experienced during the study. Secukinumab remains a safety and effective drug for PsO patients also in the IL-23 and JAK inhibitors era. The rescue therapy is a valid therapeutic option in case of secukinumab secondary failure.

3.
Front Oncol ; 11: 737399, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34868928

RESUMO

Introduction: Among white people, the incidence of cutaneous malignant melanoma (CMM) has been increasing steadily for several decades. Meanwhile, there has also been a significant improvement in 5-year survival among patients with melanoma. This population-based cohort study investigates the five-year melanoma-specific survival (MSS) for all melanoma cases recorded in 2015 in the Veneto Tumor Registry (North-Est Italian Region), taking both demographic and clinical-pathological variables into consideration. Methods: The cumulative melanoma-specific survival probabilities were calculated with the Kaplan-Meier method, applying different sociodemographic and clinical-pathological variables. Cox's proportional hazards model was fitted to the data to assess the association between independent variables and MSS, and also overall survival (OS), calculating the hazard ratios (HR) relative to a reference condition, and adjusting for sex, age, site of tumor, histotype, melanoma ulceration, mitotic count, tumor-infiltrating lymphocytes (TIL), and stage at diagnosis. Results: Compared with stage I melanoma, the risk of death was increased for stage II (HR 3.31, 95% CI: 0.94-11.76, p=0.064), almost ten times higher for stage III (HR 10.51, 95% CI: 3.16-35.02, p<0.001), and more than a hundred times higher for stage IV (HR 117.17, 95% CI: 25.30-542.62, p<0.001). Among the other variables included in the model, the presence of mitoses and histological subtype emerged as independent risk factors for death. Conclusions: The multivariable analysis disclosed that older age, tumor site, histotype, mitotic count, and tumor stage were independently associated with a higher risk of death. Data on survival by clinical and morphological characteristics could be useful in modelling, planning, and managing the most appropriate treatment and follow-up for patients with CMM.

4.
Dermatol Ther ; : e15275, 2021 Dec 19.
Artigo em Inglês | MEDLINE | ID: mdl-34923732

RESUMO

Tetracycline-class antibiotics are frequently prescribed by dermatologists, commonly for acne vulgaris. Gastrointestinal absorption of first and second-generation tetracycline-class antibiotics, including doxycycline and minocycline, may be reduced by co-administration with food, resulting in potentially lower clinical efficacy. Development of novel compounds and formulations that are not impacted by diet could improve compliance, absorption, and effectiveness among patients. The objective of this study is to investigate weight-based dosing protocols and the impact of food intake, including high-fat meals, on the absorption, and clinical efficacy of sarecycline, a novel oral narrow-spectrum third-generation tetracycline-class antibiotic approved by the Food and Drug Administration for acne vulgaris treatment. Data from 12 clinical studies were analyzed using population pharmacokinetic modeling, exposure-response modeling and pharmacodynamics to evaluate sarecycline dosing recommendations. The extent of exposure is estimated to decrease by 21.7% following co-administration of a sarecycline tablet with a high-fat meal. Based on the PopPK-PD model, this is equivalent to a decrease in efficacy of 0.9 inflammatory lesions, which is not clinically meaningful. Sarecycline can be administered using weight-based dosing with or without food. Co-administration with high-fat food has a limited impact on clinical efficacy. The pharmacokinetics of oral sarecycline may provide added convenience and support ease of use and improved compliance for acne vulgaris patients.

5.
Medicina (Kaunas) ; 57(11)2021 Nov 11.
Artigo em Inglês | MEDLINE | ID: mdl-34833446

RESUMO

Background and Objectives: Epidemiologic data show significant differences in melanoma incidence and outcomes between sexes. The role of hormonal receptors in the pathogenesis of melanocytic lesions remains unclear, thus we performed this study aiming to assess estrogen receptors expression in different melanocytic lesions. Materials and Methods: We performed a cross-sectional study that included 73 consecutively excised melanocytic lesions. Estrogen receptor alpha (ERα), beta (ERß), and G-protein coupled estrogen receptor (GPER) expression was analyzed in melanocytes and keratinocytes of common nevi, dysplastic nevi, melanoma, healthy skin margin, and in sebaceous and sweat gland cells. Results: ERß expression was higher in dysplastic nevi margin melanocytes compared to common nevi (p = 0.046) and in dysplastic nevi keratinocytes compared to melanoma keratinocytes (p = 0.021). ERß expression was significantly higher in margin melanocytes compared to melanoma melanocytes (p = 0.009). No difference in ERß expression was shown between melanocytes of three types of lesions. GPER expression was higher in nuclei and cytoplasm of dysplastic nevi (p = 0.02 and p = 0.036 respectively) and at the margin compared to melanoma. GPER expression was lower in sebaceous glands of tissue surrounding common nevi (p = 0.025) compared to dysplastic nevi. GPER expression was higher in skin margin tissue melanocytes (p = 0.016 nuclear, p = 0.029 cytoplasmic) compared to melanoma melanocytes. There were no differences in ERα expression between the melanocytic lesions. Conclusion: Further large-scale studies are warranted to investigate the potential role of ERß and GPER in the pathogenesis of melanocytic lesions.


Assuntos
Síndrome do Nevo Displásico , Melanoma , Nevo , Neoplasias Cutâneas , Estudos Transversais , Síndrome do Nevo Displásico/genética , Receptor alfa de Estrogênio/genética , Receptor alfa de Estrogênio/metabolismo , Estrogênios , Proteínas de Ligação ao GTP , Humanos , Melanoma/genética , Receptores de Estrogênio , Neoplasias Cutâneas/genética
6.
Artigo em Inglês | MEDLINE | ID: mdl-34769816

RESUMO

Multiple chemical sensitivity (MCS) is a multisystem, recurrent, environmental disorder that flares in response to different exposures (i.e., pesticides, solvents, toxic metals and molds) under the threshold limit value (TLV) calculated for age and gender in the general population. MCS is a syndrome characterized by cutaneous, allergic, gastrointestinal, rheumatological, endocrinological, cardiological and neurological signs and symptoms. We performed a systematic review of the literature to summarize the current clinical and therapeutic evidence and then oriented an eDelphi consensus. Four main research domains were identified (diagnosis, treatment, hospitalization and emergency) and discussed by 10 experts and an MCS patient. Thus, the first Italian MCS consensus had the double aim: (a) to improve MCS knowledge among healthcare workers and patients by standardizing the clinical and therapeutic management to MCS patients; and (b) to improve and shed light on MCS misconceptions not supported by evidence-based medicine (EBM).


Assuntos
Hipersensibilidade , Sensibilidade Química Múltipla , Consenso , Humanos , Itália/epidemiologia , Sensibilidade Química Múltipla/diagnóstico , Sensibilidade Química Múltipla/epidemiologia , Sensibilidade Química Múltipla/terapia , Solventes
7.
J Am Acad Dermatol ; 2021 Oct 23.
Artigo em Inglês | MEDLINE | ID: mdl-34695527

RESUMO

BACKGROUND: Limited data on dermatoscopy of nodular/plaque-type T-/B-cell primary cutaneous lymphomas (PCLs) is available. OBJECTIVE: To describe dermatoscopic features of nodular/plaque-type PCLs, comparing them with those of clinical mimickers (pseudolymphomas, tumors, and inflammatory lesions) and investigating possible differences according to histologic subtypes. METHODS: Participants were invited to join this retrospective, multicenter case-control study by submitting histologically/immunohistochemically confirmed instances of nodular/plaque-type PCLs and controls. Standardized assessments of the dermatoscopic images and comparative analyses were performed. RESULTS: A total of 261 lesions were included (121 PCLs and 140 controls). Orange structureless areas were the strongest PCL dermatoscopic predictor on multivariate analysis compared with tumors and noninfiltrative inflammatory dermatoses. On the other hand, a positive association was found between PCLs and either unfocused linear vessels with branches or focal white structureless areas compared with infiltrative inflammatory dermatoses, whereas white lines were predictive of PCLs over pseudolymphomas. Differences in the vascular pattern were also seen between B- and T-cell PCLs and among B-cell PCL subtypes. LIMITATIONS: Retrospective design and the lack of a dermatoscopic-pathologic correlation analysis. CONCLUSION: Nodular/plaque-type PCLs display dermatoscopic clues, which may partially vary according to histologic subtype and whose diagnostic relevance depends on the considered clinical differential diagnoses.

8.
Photodiagnosis Photodyn Ther ; : 102598, 2021 Oct 23.
Artigo em Inglês | MEDLINE | ID: mdl-34699984

RESUMO

BACKGROUND: Antimicrobial photodynamic therapy (aPDT) is being used in endodontics to improve orthograde root canal disinfection as an adjunct to standard treatments. Conversely, evidence concerning the application of aPDT in retrograde endodontic surgery is limited. Thus, the aim of the present study was to provide additional data regarding the use of aPDT in the surgical endodontic treatment of periapical lesions. METHODS: A total of 25 consecutive patients presenting teeth with periapical radiolucency eventually associated with clinical signs and symptoms of apical periodontitis were included. Following access flap completion, osteotomy, mechanical debridement, root apical third resection, and preparation of the root-end cavity, aPDT was applied to decontaminate the surgical site using phenothiazine chloride dye at a concentration of 10 mg/mL and irradiation with a hand-held 100-mW diode laser with a wavelength of 660 ± 10 nm. At the latest follow-up visit, healing was evaluated as successful, uncertain, or failure according to well-established clinical and radiological criteria. RESULTS: Overall, 31 periapical lesions were treated with aPDT. Healing proceeded uneventfully. The mean follow-up time was 36.19 months, with times ranging from 12 to 85 months. A total of 25 (80.65%) cases were classified as successful, 5 (16.13%) as uncertain, and only one (3.22%) as failure. Irrespective of the treatment outcome, all treated teeth were still functional, with no symptoms reported by the patients. CONCLUSION: aPDT as an adjunctive treatment modality in the surgical endodontic treatment of periapical lesions showed promising medium-term results associated with preservation of all diseased teeth.

9.
Nutrients ; 13(9)2021 Aug 25.
Artigo em Inglês | MEDLINE | ID: mdl-34578812

RESUMO

Vegans and vegetarians often consume foods containing photosensitizers capable of triggering phytophotodermatitis. The potential effect of vegan and vegetarian diets on the response of psoriatic patients undergoing phototherapy is not well characterized. We assessed clinical outcomes of vegan, vegetarian and omnivore adult psoriatic patients undergoing band ultraviolet B phototherapy (NB-UVB). In this multicenter prospective observational study, we enrolled 119 adult, psoriatic patients, of whom 40 were omnivores, 41 were vegetarians and 38 were vegans, with phototherapy indication. After determining the minimum erythemal dose (MED), we performed NB-UVB sessions for 8 weeks. The first irradiation dosage was 70.00% of the MED, then increased by 20.00% (no erythema) or by 10.00% (presence of erythema) until a maximum single dose of 3 J/cm2 was reached and constantly maintained. All the enrolled patients completed the 8 weeks of therapy. Severe erythema was present in 16 (42.11%) vegans, 7 (17.07%) vegetarians and 4 (10.00%) omnivores (p < 0.01). MED was lowest among vegans (21.18 ± 4.85 J/m2), followed by vegetarians (28.90 ± 6.66 J/m2) and omnivores (33.63 ± 4.53 J/m2, p < 0.01). Patients with severe erythema were more likely to have a high furocumarin intake (OR 5.67, 95% CI 3.74-8.61, p < 0.01). Vegans consumed the highest amount of furocumarin-rich foods. A model examining erythema, adjusted for gender, age, skin type, MED, phototherapy type, number of phototherapies and furocumarin intake, confirmed that vegans had a lower number of treatments. Vegans had more frequent severe erythema from NB-UVB, even after adjustment of the phototherapy protocol for their lower MED. Assessing diet information and adapting the protocol for vegan patients may be prudent.


Assuntos
Dermatite Fototóxica/etiologia , Dieta/efeitos adversos , Fármacos Fotossensibilizantes/efeitos adversos , Fototerapia/métodos , Psoríase/terapia , Adulto , Dieta/métodos , Dieta Vegana/efeitos adversos , Dieta Vegana/métodos , Dieta Vegetariana/efeitos adversos , Dieta Vegetariana/métodos , Feminino , Humanos , Itália , Masculino , Fármacos Fotossensibilizantes/administração & dosagem , Estudos Prospectivos
10.
PLoS One ; 16(8): e0255716, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34358260

RESUMO

BACKGROUND: Checkpoint inhibitors have revolutionized advanced melanoma care; however, their cutaneous side effects have not been definitively elucidated. OBJECTIVE: To identify the prevalence of cutaneous toxicity in patients with melanoma treated with immune checkpoint inhibitors as monotherapy and/or in combination with chemotherapy and/or radiotherapy. MATERIALS AND METHODS: We performed a systematic review and meta-analysis, which encompassed both clinical trials and observational studies describing the dermatological toxicities in patients treated with immune checkpoint inhibitors. The protocol was registered in the International Prospective Register of Systematic Review under the number CRD42018091915. The searches were performed using the CINAHL, Cochrane CENTRAL, LILACS, LIVIVO, PubMed, Scopus, and Web of Science databases. The methodological quality of the studies was evaluated with the JBI Critical Appraisal Checklist for Studies Reporting Prevalence Data. RESULTS: A total of 9,802 articles were identified in the databases. The final sample comprised 39 studies. The evaluated drugs were ipilimumab, tremelimumab, pembrolizumab, and nivolumab. The results suggest that the most prevalent side effect was grade 1 and 2 pruritus (24%), followed by grade 1 and 2 rash (21%) and grade 1 and 2 vitiligo (10%). CONCLUSION: The most prevalent side effects in patients treated with checkpoint inhibitors are pruritus, rash, and vitiligo, and they are rated mostly as grades 1 and 2 adverse events. Remarkably, vitiligo is most commonly found in patients treated with PD-1 inhibitors.

11.
Dermatol Ther ; 34(5): e15077, 2021 09.
Artigo em Inglês | MEDLINE | ID: mdl-34333823

RESUMO

Topical treatment is the mainstay for mild or moderate psoriasis, but patients are generally little satisfied. Calcipotriol/betamethasone dipropionate (Cal/BD) cutaneous foam has shown to improve signs and symptoms in plaque psoriasis patients. This study assessed patient's satisfaction with Cal/BD foam in a real-life Italian dermatological clinical practice. A multicenter, 4-week observational prospective cohort study enrolled, in 17 Italian dermatology clinics, adult patients with plaque psoriasis on the body and/or scalp. Treatment satisfaction was assessed by 9-item Treatment Satisfaction Questionnaire for Medication (TSQM-9), preference over previous treatments by Patient Preference Questionnaire (PPQ), and change in disease state by Psoriasis Area Severity Index (PASI). Overall 256 patients were eligible, with a mean (SD) age of 55.6 (15.4) years, 59.4% were males. Psoriasis severity was mild in 52.0% of patients, moderate in 43.3%, and severe in 4.7%. Scalp involvement was present in 36.7% of patients. Previous antipsoriatic treatments had been received by 80.5% of patients. TSQM-9 median (25th-75th percentile) scores were 83.3 (66.7-88.9) for effectiveness, 77.8 (66.7-88.9) for convenience, and 78.6 (64.3-92.9) for global satisfaction. Mean (SD) PASI value decreased from 7.3 (4.8) to 2.1 (2.7) after 4 weeks. More than 90% of patients previously treated for psoriasis evaluated the Cal/BD foam more effective, easier to use and better tolerated compared to previous topical treatments at PPQ. This observational study provides real-life evidence of a high level of satisfaction with effectiveness and convenience of the Cal/BD foam in a cohort of plaque psoriasis patients, with an objective improvement in PASI.


Assuntos
Fármacos Dermatológicos , Psoríase , Adulto , Betametasona/análogos & derivados , Calcitriol/análogos & derivados , Fármacos Dermatológicos/efeitos adversos , Combinação de Medicamentos , Humanos , Masculino , Pessoa de Meia-Idade , Satisfação do Paciente , Estudos Prospectivos , Psoríase/diagnóstico , Psoríase/tratamento farmacológico , Resultado do Tratamento
12.
Immunol Res ; 69(6): 533-540, 2021 12.
Artigo em Inglês | MEDLINE | ID: mdl-34409549

RESUMO

Despite some common pathogenic themes, the association of hidradenitis suppurativa (HS) and rheumatoid arthritis (RA) has been poorly investigated. We aimed to evaluate the bidirectional association between HS and RA. A population-based study was conducted to compare HS patients (n = 6779) with age-, sex- and ethnicity-matched control subjects (n = 33,260) with regard to the incidence of new-onset and the prevalence of preexisting RA. Adjusted hazard ratios (HRs) and adjusted odds ratios (ORs) were estimated. The prevalence of preexisting RA was greater among patients with HS relative to controls (0.5% vs 0.3%. respectively; p = 0.019). The odds of being diagnosed with HS were 1.6-fold higher in patients with a history of RA (fully-adjusted OR, 1.66; 95% CI, 1.11-2.49; p = 0.014). The incidence rate of new-onset RA was estimated at 4.3 (95% CI, 2.5-6.8) and 2.4 (95% CI, 1.8-3.2) cases per 10,000 person-years among patients with HS and controls, respectively. The risk of RA was comparable between patients with HS and controls (fully-adjusted HR, 1.45; 95% CI, 0.77-2.72; p = 0.249). Compared to other patients with HS, those with HS and comorbid RA were older, had a higher prevalence of diabetes mellitus, hypertension, and hyperlipidemia, and had a comparable risk of all-cause mortality. In conclusions, a preexisting diagnosis of RA predisposes individuals to develop HS. Clinicians managing patients with HS and RA should be aware of this association. Further research is required to delineate the underlying pathomechanism of this observation.

13.
Dermatol Ther ; 34(5): e15088, 2021 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-34355846

RESUMO

During this pandemic, dermatological infusion centers were partially unavailable, suspended or even reconverted to guest COVID-19 patients, consequently infliximab (IFX) infusions became challenging for their both logistic arrangement and also for patients' COVID-19 phobia. This 48 weeks follow-up retrospective observational study included 37 PsO patients that underwent IFX SB2 during pandemic in two primary dermatological referral centers. In 23 (62.1%) we had to switch from IFX to other biologics, not motivated by adverse reactions, contraindication or even loss of response but only to pandemic related conditions. Nine patients underwent interclass switching and 15 underwent intraclass switching; interestingly 2 patients that underwent adalimumab SB-5 switched back to IFX. Interclass switching was privileged in elder patients and smokers. All patients at week 48 achieved PASI 100. Intra- and interclass switchings are both safe and effective strategies in psoriatic patients with COVID-19 phobia and/or difficulties to undergo infliximab infusions.


Assuntos
COVID-19 , Pandemias , Adalimumab , Idoso , Humanos , Infliximab/efeitos adversos , Estudos Retrospectivos , SARS-CoV-2 , Resultado do Tratamento
14.
Australas J Dermatol ; 62(3): 336-341, 2021 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-34076886

RESUMO

BACKGROUND: The question of whether solid malignancies (SMs) are associated with pyoderma gangrenosum (PG) remains to be conclusively answered. OBJECTIVE: To evaluate the risk of SM among patients with PG and the odds of PG after a diagnosis of SM. METHODS: A population-based retrospective cohort study was conducted to study the risk for SM in patients with PG (n = 302) as compared with age-, sex- and ethnicity-matched control subjects (n = 1799). A case-control design was used to estimate the odds of PG in those with a preexisting history of SM. RESULTS: The prevalence of a preexisting SM was comparable in patients with PG and controls (7.5% vs. 8.8%, respectively; P = 0.490). The odds of having PG following a diagnosis of a SM was not statistically increased (OR, 0.85; 95% CI, 0.53-1.36). The incidence of SM was 6.8 (95% CI, 3.5-12.2) and 7.9 (95% CI, 6.1-10.1) per 1000 person-years among patients with PG and controls, respectively. Patients with PG were not more likely to develop SM as compared to controls (HR, 0.86; 95% CI, 0.44-1.69). Patients with a dual diagnosis of PG and SM were older and had more frequent comorbid conditions and increased mortality. CONCLUSIONS: SM is not associated with provoking PG, and patients with PG are not at an increased risk of developing SM. A thorough routine screening for SM in patients with new-onset PG is an unnecessary approach based on the study findings.

15.
Am J Clin Dermatol ; 22(5): 709-718, 2021 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-34060006

RESUMO

BACKGROUND: The impact of immune-related conditions on the outcomes of coronavirus disease 2019 (COVID-19) is poorly understood. Determinants of COVID-19 outcomes among patients with psoriasis are yet to be established. OBJECTIVE: Th objective of this study was to characterize a large cohort of patients with psoriasis with COVID-19 and to identify predictors of COVID-19-associated hospitalization and mortality. METHODS: A population-based nested case-control study was performed using the computerized database of Clalit Health Services, Israel. Multivariable logistic regression was used to estimate odds ratios (ORs) and 95% confidence (CIs) of predictors for COVID-19-associated hospitalization and mortality. RESULTS: The study population included 3151 patients with psoriasis who tested positive for COVID-19. Subclinical COVID-19 infection occurred in 2818 (89.4%) of the patients while 122 (3.9%), 71 (2.3%), 123 (3.9%), and 16 (0.5%) of the patients experienced a mild, moderate, severe, and critical disease, respectively. Overall, 332 (10.5%) patients were hospitalized and 50 (1.6%) patients died because of COVID-19 complications. Intake of methotrexate independently predicted COVID-19-associated hospitalization (adjusted OR 2.30; 95% CI 1.11-4.78; p = 0.025). Use of biologic agents was not associated with COVID-19-associated hospitalization (OR 0.75; 95% CI 0.32-1.73; p = 0.491) or mortality (OR 0.85; 95% CI 0.12-6.21; p = 0.870). Older age, the presence of comorbid cardiovascular diseases, metabolic syndrome, chronic obstructive pulmonary disease, and chronic renal failure independently predicted both COVID-19-associated hospitalization and mortality. CONCLUSIONS: The use of oral methotrexate was associated with an increased odds of COVID-associated hospitalization, whereas the use of biologic drugs was not associated with worse outcomes of COVID-19 among patients with psoriasis.


Assuntos
Produtos Biológicos/uso terapêutico , COVID-19/mortalidade , Hospitalização/estatística & dados numéricos , Imunossupressores/uso terapêutico , Metotrexato/uso terapêutico , Psoríase/tratamento farmacológico , Adolescente , Adulto , Fatores Etários , Idoso , Idoso de 80 Anos ou mais , Estudos de Casos e Controles , Criança , Pré-Escolar , Comorbidade , Feminino , Humanos , Lactente , Masculino , Pessoa de Meia-Idade , Psoríase/epidemiologia , Fatores de Risco , SARS-CoV-2 , Adulto Jovem
16.
Dermatitis ; 32(1S): S45-S52, 2021 Oct 01.
Artigo em Inglês | MEDLINE | ID: mdl-34138775

RESUMO

BACKGROUND: The burden of coronavirus disease 2019 (COVID-19) among patients with atopic dermatitis (AD) is poorly understood. OBJECTIVES: The aims of the study were to characterize a large cohort of COVID-19-positive adult patients with AD and to identify predictors of COVID-19-associated hospitalization and mortality. METHODS: A population-based nested case-control study was performed. Multivariable logistic regression was used to evaluate odds ratios and 95% confidence intervals of predictors for COVID-19-associated hospitalization and mortality. RESULTS: Of 78,073 adult patients with AD, 3618 (4.6%) tested positive for COVID-19. Subclinical COVID-19 infection occurred in 3368 (93.1%) of COVID-19-positive patients, whereas 123 (3.4%), 46 (1.3%), 55 (1.5%), and 26 (0.7%) patients developed a mild, moderate, severe, and critical disease, respectively. Altogether, 250 patients (6.0%) were hospitalized, and 40 patients (1.1%) died because of COVID-19 complications. Coronavirus disease 2019-associated hospitalization was independently associated with the intake of extended courses of systemic corticosteroids (adjusted odds ratio, 1.96; 95% confidence interval, 1.23-3.14; P = 0.005). None of AD-related variables independently predicted COVID-19-associated mortality. The presence of comorbid metabolic syndrome, chronic obstructive pulmonary disease, chronic renal failure, and depression projected both COVID-19-associated hospitalization and mortality. CONCLUSIONS: Prolonged systemic corticosteroids during the pandemic are associated with increased odds of COVID-19-associated hospitalization and should be avoided in patients with AD.


Assuntos
COVID-19/complicações , COVID-19/mortalidade , Efeitos Psicossociais da Doença , Dermatite Atópica/complicações , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , COVID-19/diagnóstico , Estudos de Casos e Controles , Estudos de Coortes , Dermatite Atópica/epidemiologia , Dermatite Atópica/terapia , Feminino , Hospitalização , Humanos , Modelos Logísticos , Masculino , Pessoa de Meia-Idade , Razão de Chances , Taxa de Sobrevida , Adulto Jovem
17.
Dermatol Ther ; 34(4): e15003, 2021 07.
Artigo em Inglês | MEDLINE | ID: mdl-34033207

RESUMO

The risk of coronavirus disease 2019 (COVID-19) and its complications among patients with psoriasis treated by tumor necrosis factor inhibitors (TNFis) remains to be decisively delineated. We aimed to assess the risk of COVID-19 infection, COVID-19-associated hospitalization, and mortality among Israeli patients with psoriasis treated by TNFi relative to other systemic agents. A population-based cohort study was conducted to compare psoriasis patients treated by TNFi (n = 1943), with those treated by methotrexate (n = 1929), ustekinumab (n = 348), and acitretin (n = 1892) regarding COVID-19 outcomes. Risk of investigated outcomes was assessed using uni- and multi-variate Cox regression analyses. The incidence rate of COVID-19, COVID-19-associated hospitalization, and mortality in the TNFi group was 35.8 (95% CI, 26.1-47.9), 0.8 (95% CI, 0.0-4.2), and 0.0 per 1000 person-years, respectively. Exposure to TNFi was associated with a comparable risk of COVID-19 infection [adjusted hazard ration (HR) for TNFi vs methotrexate: 1.07 (95% CI, 0.67-1.71); TNFi vs ustekinumab: 1.07 (95% CI, 0.48-2.40); TNFi vs acitretin: 0.98 (95% CI, 0.61-1.57)]. TNFi was associated with a decreased risk of COVID-19-associated hospitalization relative to methotrexate (adjusted HR, 0.10; 95% CI, 0.01-0.82) and ustekinumab (adjusted HR, 0.04; 95% CI, 0.00-0.64), but not to acitretin (adjusted HR, 1.00; 95% CI, 0.16-6.16). No significant difference in COVID-19-associated mortality was found between the four different groups. TNFi was associated with a decreased risk of admissions due to COVID-19. Our findings substantiate the continuation of TNFi treatment during the pandemic. TNFi may be positively considered in patients with moderate-to-severe psoriasis warranting systemic treatment during the pandemic.


Assuntos
Antirreumáticos , COVID-19 , Psoríase , Antirreumáticos/uso terapêutico , Estudos de Coortes , Hospitalização , Humanos , Psoríase/diagnóstico , Psoríase/tratamento farmacológico , Psoríase/epidemiologia , SARS-CoV-2 , Inibidores do Fator de Necrose Tumoral , Fator de Necrose Tumoral alfa
18.
Front Immunol ; 12: 635018, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-33936047

RESUMO

Objective: Bacterial and viral infectious triggers are linked to spondyloarthritis (SpA) including psoriatic arthritis (PsA) development, likely via dendritic cell activation. We investigated spinal entheseal plasmacytoid dendritic cells (pDCs) toll-like receptor (TLR)-7 and 9 activation and therapeutic modulation, including JAK inhibition. We also investigated if COVID-19 infection, a potent TLR-7 stimulator triggered PsA flares. Methods: Normal entheseal pDCs were characterized and stimulated with imiquimod and CpG oligodeoxynucleotides (ODN) to evaluate TNF and IFNα production. NanoString gene expression assay of total pDCs RNA was performed pre- and post- ODN stimulation. Pharmacological inhibition of induced IFNα protein was performed with Tofacitinib and PDE4 inhibition. The impact of SARS-CoV2 viral infection on PsA flares was evaluated. Results: CD45+HLA-DR+CD123+CD303+CD11c- entheseal pDCs were more numerous than blood pDCs (1.9 ± 0.8% vs 0.2 ± 0.07% of CD45+ cells, p=0.008) and showed inducible IFNα and TNF protein following ODN/imiquimod stimulation and were the sole entheseal IFNα producers. NanoString data identified 11 significantly upregulated differentially expressed genes (DEGs) including TNF in stimulated pDCs. Canonical pathway analysis revealed activation of dendritic cell maturation, NF-κB signaling, toll-like receptor signaling and JAK/STAT signaling pathways following ODN stimulation. Both tofacitinib and PDE4i strongly attenuated ODN induced IFNα. DAPSA scores elevations occurred in 18 PsA cases with SARS-CoV2 infection (9.7 ± 4 pre-infection and 35.3 ± 7.5 during infection). Conclusion: Entheseal pDCs link microbes to TNF/IFNα production. SARS-CoV-2 infection is associated with PsA Flares and JAK inhibition suppressed activated entheseal plasmacytoid dendritic Type-1 interferon responses as pointers towards a novel mechanism of PsA and SpA-related arthropathy.


Assuntos
Artrite Psoriásica/complicações , COVID-19/complicações , Células Dendríticas/metabolismo , Interferon-alfa/metabolismo , Janus Quinases/antagonistas & inibidores , Adjuvantes Imunológicos/farmacologia , Adulto , Idoso , COVID-19/genética , COVID-19/metabolismo , Biologia Computacional , Nucleotídeo Cíclico Fosfodiesterase do Tipo 4/metabolismo , Células Dendríticas/efeitos dos fármacos , Feminino , Regulação da Expressão Gênica/efeitos dos fármacos , Regulação da Expressão Gênica/genética , Humanos , Imiquimode/farmacologia , Janus Quinases/metabolismo , Masculino , Pessoa de Meia-Idade , NF-kappa B/metabolismo , Oligonucleotídeos/farmacologia , Inibidores da Fosfodiesterase 4/farmacologia , Piperidinas/farmacologia , Inibidores de Proteínas Quinases/farmacologia , Pirimidinas/farmacologia , Transdução de Sinais/efeitos dos fármacos , Transdução de Sinais/genética , Receptor 7 Toll-Like/metabolismo , Receptor Toll-Like 9/metabolismo , Transcriptoma , Fator de Necrose Tumoral alfa/metabolismo
19.
Artigo em Inglês | MEDLINE | ID: mdl-33982550

RESUMO

INTRODUCTION: Narrow band ultraviolet B (NB-UVB) and psoralen-ultraviolet A (PUVA) remain inexpensive and effective anti-psoriatic therapies adopted worldwide with different frequency protocols. We aimed to systematically assess the evidence on the effects of different frequency protocols of phototherapy in treating psoriasis. EVIDENCE ACQUISITION: We used the following terms, namely "photochemotherapy", "phototherapy", "psoriasis", "UVB", "UVA" and "ultraviolet therapy", to search the Cochrane Controlled Register of Trials, MEDLINE and Embase databases on August 1, 2019. We organized results using a PRISM diagram and analyzed bias risks with RoB-2 tool. EVIDENCE SYNTHESIS: We included five randomized controlled trials (RCTs) on oral PUVA and three RCTs on NB-UVB. The five studies on PUVA included a total of 1452 patients with plaque psoriasis and did not find any significant difference in efficacy comparing two- vs. three- vs. four times weekly protocols. The three studies on NB-UVB included a total of 248 patients with plaque psoriasis. No differences in efficacy were reported in comparing different frequencies in delivering NB-UVB, namely twice vs. thrice weekly, twice vs. four times weekly, and thrice- vs. five times weekly protocols. Although protocols with higher treatments frequency per week achieved clearance faster than lower frequency ones, but they did not differ in terms of efficacy. CONCLUSIONS: PUVA and NB-UVB remain an effective anti-psoriatic treatment; however further studies are needed to elucidate which protocol may be more effective in different skin phototypes.

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