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1.
Dermatology ; : 1-11, 2021 Sep 02.
Artigo em Inglês | MEDLINE | ID: mdl-34474409

RESUMO

BACKGROUND: Hidradenitis suppurativa (HS) is a chronic, inflammatory, recurrent, debilitating skin disease of the hair follicle that usually occurs after puberty with painful, deep-seated, inflamed nodules and sinus tracts in the apocrine gland-bearing areas of the body, most commonly the axillae and inguinal and anogenital regions, with a relevant impact on patients' quality of life (QoL). OBJECTIVE: To evaluate how the burden of HS disease impacts on patient well-being and working activities in a large Italian population over a period of 9 months. METHODS: A multicenter, prospective, epidemiologic cohort study was conducted in adult Italian patients with HS. HS severity was assessed through Hurley stage and HS Physician's Global Assessment (HS-PGA), clinical improvement by HS Clinical Response (HiSCR) and partial response, and disease burden through QoL questionnaires (HIDRAdisk, Skindex-16, Dermatology Life Quality Index [DLQI]), and Work Productivity and Activity Impairment - General Health (WPAI:GH). RESULTS: A total of 308 patients (56.2% women; mean age 35.2 ± 12.9 years) were enrolled in 27 dermatologic clinics. Men were older (37.4 years vs. 33.5), more smoking addicted (74.1% vs. 60.1%), and alcohol consumer (34.1% vs. 13.9%), while more women were obese (34.10% vs. 22.22%). At baseline, most patients had a Hurley severity stage of 2 (43.9%), a moderate HS-PGA score (57.1%), and poor QoL (HIDRAdisk: 65.7 ± 23.3, Skindex-16: 60.3 ± 26.9, and DLQI: 10.8 ± 8.1). Patients with more severe disease showed worse QoL. Mean values for the variables related to HS severity decreased during the study period. The achievement of HiSCR and partial response increased during the study. CONCLUSION: This study offers insight into the disease burden of HS in an Italian population. Our results underline the impact of QoL evaluation, also with the use of the HIDRAdisk, in clinical routine as a support to validated severity clinical and instrumental indexes for a "360-degree" assessment of HS patient's burden of disease.

2.
Nat Commun ; 12(1): 5006, 2021 08 18.
Artigo em Inglês | MEDLINE | ID: mdl-34408135

RESUMO

Obesity is a strong risk factor for cancer progression, posing obesity-related cancer as one of the leading causes of death. Nevertheless, the molecular mechanisms that endow cancer cells with metastatic properties in patients affected by obesity remain unexplored.Here, we show that IL-6 and HGF, secreted by tumor neighboring visceral adipose stromal cells (V-ASCs), expand the metastatic colorectal (CR) cancer cell compartment (CD44v6 + ), which in turn secretes neurotrophins such as NGF and NT-3, and recruits adipose stem cells within tumor mass. Visceral adipose-derived factors promote vasculogenesis and the onset of metastatic dissemination by activation of STAT3, which inhibits miR-200a and enhances ZEB2 expression, effectively reprogramming CRC cells into a highly metastatic phenotype. Notably, obesity-associated tumor microenvironment provokes a transition in the transcriptomic expression profile of cells derived from the epithelial consensus molecular subtype (CMS2) CRC patients towards a mesenchymal subtype (CMS4). STAT3 pathway inhibition reduces ZEB2 expression and abrogates the metastatic growth sustained by adipose-released proteins. Together, our data suggest that targeting adipose factors in colorectal cancer patients with obesity may represent a therapeutic strategy for preventing metastatic disease.


Assuntos
Tecido Adiposo/citologia , Reprogramação Celular , Neoplasias do Colo/fisiopatologia , Células-Tronco Neoplásicas/citologia , Nicho de Células-Tronco , Tecido Adiposo/metabolismo , Animais , Neoplasias do Colo/genética , Neoplasias do Colo/metabolismo , Neoplasias do Colo/patologia , Fator de Crescimento de Hepatócito/genética , Fator de Crescimento de Hepatócito/metabolismo , Humanos , Interleucina-6/genética , Interleucina-6/metabolismo , Masculino , Camundongos , Camundongos SCID , MicroRNAs/genética , MicroRNAs/metabolismo , Metástase Neoplásica , Células-Tronco/citologia , Células-Tronco/metabolismo , Homeobox 2 de Ligação a E-box com Dedos de Zinco/genética , Homeobox 2 de Ligação a E-box com Dedos de Zinco/metabolismo
3.
Skinmed ; 19(3): 189-196, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34303389

RESUMO

The current medical treatments of androgenetic alopecia (AGA) have hardly achieved a satisfying clinical improvement. Biologic regenerative therapies, such as platelet-rich plasma (PRP) injections in the scalp, have been proposed recently. This multidisciplinary prospective study aims to explore the efficacy and safety of autologous PRP injections into the scalp of patients with AGA. Fifty-four patients with AGA (35 men and 19 women) were enrolled. Non-activated autologous PRP was injected into the androgen-related areas of the scalp. The study protocol consisted of three sessions of injections at 3-month interval. The effects were assessed by means of noninvasive methods. Safety profile, patient satisfaction, and Dermatology Life Quality Index were assessed. Increase in hair thickness was observed 1 month after the first PRP injection, and hair loss reduction was found after 3 months. In most patients, the improvement was progressively evident until the 12th month. Hair growth/production showed differences between women and men. The safety profile was satisfactory. This study confirms that PRP injections are effective in reducing thinning of the scalp hair and suggests more efficacy in women.

4.
Allergy ; 76(6): 1813-1824, 2021 06.
Artigo em Inglês | MEDLINE | ID: mdl-34152613

RESUMO

BACKGROUND: Few and small studies have described the management of immunomodulant/immunosuppressive therapies or phototherapy in atopic dermatitis (AD) patients during coronavirus disease 2019 (COVID-19) pandemic. METHODS: A national registry, named DA-COVID-19 and involving 35 Italian dermatology units, was established in order to evaluate the impact of COVID-19 pandemic on the management of adult AD patients treated with systemic immunomodulant/immunosuppressive medications or phototherapy. Demographic and clinical data were obtained at different timepoints by teledermatology during COVID-19 pandemic, when regular visits were not allowed due to sanitary restrictions. Disease severity was assessed by both physician- and patient-reported assessment scores evaluating itch intensity, sleep disturbances, and AD severity. RESULTS: A total of 1831 patients were included, with 1580/1831 (86.3%) continuing therapy during pandemic. Most patients were treated with dupilumab (86.1%, 1576/1831) that was interrupted in only 9.9% (156/1576) of cases, while systemic immunosuppressive compounds were more frequently withdrawn. Treatment interruption was due to decision of the patient, general practitioner, or dermatologist in 39.9% (114/286), 5.6% (16/286), and 30.1% (86/286) of cases, respectively. Fear of increased susceptibility to SARS-CoV-2 infection (24.8%, 71/286) was one of the main causes of interruption. Sixteen patients (0.9%) resulted positive to SARS-CoV-2 infection; 3 of them (0.2%) were hospitalized but no cases of COVID-related death occurred. CONCLUSIONS: Most AD patients continued systemic treatments during COVID pandemic and lockdown period, without high impact on disease control, particularly dupilumab-treated patients.


Assuntos
COVID-19 , Dermatite Atópica , Adulto , Controle de Doenças Transmissíveis , Dermatite Atópica/tratamento farmacológico , Dermatite Atópica/epidemiologia , Humanos , Itália/epidemiologia , Pandemias , Sistema de Registros , SARS-CoV-2
5.
Wien Med Wochenschr ; 2021 Jun 29.
Artigo em Inglês | MEDLINE | ID: mdl-34185217

RESUMO

BACKGROUND: It is generally acknowledged that the first morphological change of hidradenitis suppurativa/acne inversa (HS/AI) consists of infundibular plugging of the folliculosebaceous apocrine apparatus, which is followed by acute and chronic inflammation, cysts with sinus formation, and fibrosis. Alternatively, it has been hypothesized that HS/AI is primarily a neutrophilic autoinflammatory disease and that the follicular plugging typical of this disease is secondary to inflammation. OBJECTIVE: To review the sequence of the changes that mark the disease development, we have performed a histopathologic study on the surgical material from a series of axillary and inguinal/perineal cases. METHODS: The histologic material from surgery on Hurley's second and third stage HS/AI was retrieved and collected with the patients' clinical images. The virtually uninvolved skin peripheral to the lesions was studied together with the main inflammatory foci on vertical sections stained with hematoxylin-eosin and immunohistochemistry for the follicle sheaths. RESULTS: The fully developed lesions showed acute and chronic, suppurative and granulomatous inflammation overlapping fibrosis, cysts, and sinuses. Instead, the skin adjacent to florid inflammation showed plugging and dysmorphic alterations of the hair follicles associated with immunopathological changes of the inner root sheath keratin expression. CONCLUSION: Our observations coincide with the classical pathological studies on the progressive changes of HS/AI; however, in our specimens, the virtually normal skin peripheral to the fully developed lesions show seemingly initial follicular changes that suggest development error. This finding would support the hypothesis of combined mutation-induced epithelial differentiative defects and immunological derangement in HS/AI pathogenesis.

6.
Gut ; 2021 Jan 12.
Artigo em Inglês | MEDLINE | ID: mdl-33436496

RESUMO

OBJECTIVE: Cancer stem cells are responsible for tumour spreading and relapse. Human epidermal growth factor receptor 2 (HER2) expression is a negative prognostic factor in colorectal cancer (CRC) and a potential target in tumours carrying the gene amplification. Our aim was to define the expression of HER2 in colorectal cancer stem cells (CR-CSCs) and its possible role as therapeutic target in CRC resistant to anti- epidermal growth factor receptor (EGFR) therapy. DESIGN: A collection of primary sphere cell cultures obtained from 60 CRC specimens was used to generate CR-CSC mouse avatars to preclinically validate therapeutic options. We also made use of the ChIP-seq analysis for transcriptional evaluation of HER2 activation and global RNA-seq to identify the mechanisms underlying therapy resistance. RESULTS: Here we show that in CD44v6-positive CR-CSCs, high HER2 expression levels are associated with an activation of the phosphatidylinositol 3-kinase (PI3K)/AKT pathway, which promotes the acetylation at the regulatory elements of the Erbb2 gene. HER2 targeting in combination with phosphatidylinositol 3-kinase (PI3K) and mitogen-activated protein kinase kinase (MEK) inhibitors induces CR-CSC death and regression of tumour xenografts, including those carrying Kras and Pik3ca mutation. Requirement for the triple targeting is due to the presence of cancer-associated fibroblasts, which release cytokines able to confer CR-CSC resistance to PI3K/AKT inhibitors. In contrast, targeting of PI3K/AKT as monotherapy is sufficient to kill liver-disseminating CR-CSCs in a model of adjuvant therapy. CONCLUSIONS: While PI3K targeting kills liver-colonising CR-CSCs, the concomitant inhibition of PI3K, HER2 and MEK is required to induce regression of tumours resistant to anti-EGFR therapies. These data may provide a rationale for designing clinical trials in the adjuvant and metastatic setting.

7.
Expert Opin Biol Ther ; 21(2): 271-277, 2021 02.
Artigo em Inglês | MEDLINE | ID: mdl-33216643

RESUMO

Background: The susceptibility of patients with chronic plaque psoriasis and the risks or benefits related to the use of biological therapies for COVID-19 are unknown. Few data about prevalence, clinical course and outcomes of COVID-19 among psoriatic patients were reported. The aims of this study were 1) to assess the prevalence and severity of COVID-19 in psoriatic patients treated with biologic agents during the first phase of the emergency (22 February to 22 April 2020) in Italy, and 2) to report the clinical outcomes of patients who have been exposed to individuals with confirmed SARS-CoV-2 infection. Methods: Patients with moderate-to-severe chronic plaque psoriasis, aged ≥18 years and undergoing treatment with biologic agents as of 22 February 2020, were eligible to be included in PSO-BIO-COVID study. Demographic and clinical characteristics of patients using any biologic for psoriasis treatment between 22 February and 22 April 2020 were registered. Results: A total of 12,807 psoriatic patients were included in the PSO-BIO-COVID study. In this cohort 26 patients (0.2%) had a swab confirmation of SARS-CoV-2 infection. Eleven patients required hospitalization and two died. Conclusion: The incidence of COVID-19 observed in our cohort of psoriatic patients (0.2%) is similar to that seen in the general population (0.31%) in Italy. However, the course of the disease was mild in most patients. Biological therapies may likely lessen 'cytokine storm' of COVID-19, which sometimes lead to multiple organ failure, ARDS, and death.


Assuntos
Produtos Biológicos/uso terapêutico , Terapia Biológica/métodos , COVID-19/epidemiologia , Psoríase/tratamento farmacológico , Adulto , Idoso , Idoso de 80 Anos ou mais , Produtos Biológicos/farmacologia , COVID-19/diagnóstico , Doença Crônica , Estudos de Coortes , Feminino , Humanos , Incidência , Interleucina-17/antagonistas & inibidores , Itália/epidemiologia , Masculino , Pessoa de Meia-Idade , Pandemias , Psoríase/diagnóstico , Psoríase/epidemiologia , Receptores de Interleucina/antagonistas & inibidores , Medição de Risco/métodos , Fator de Necrose Tumoral alfa/antagonistas & inibidores , Adulto Jovem
11.
Oncogene ; 39(5): 987-1003, 2020 01.
Artigo em Inglês | MEDLINE | ID: mdl-31591478

RESUMO

Despite intense research and clinical efforts, patients affected by advanced colorectal cancer (CRC) have still a poor prognosis. The discovery of colorectal (CR) cancer stem cell (CSC) as the cell compartment responsible for tumor initiation and propagation may provide new opportunities for the development of new therapeutic strategies. Given the reduced sensitivity of CR-CSCs to chemotherapy and the ability of bone morphogenetic proteins (BMP) to promote colonic stem cell differentiation, we aimed to investigate whether an enhanced variant of BMP7 (BMP7v) could sensitize to chemotherapy-resistant CRC cells and tumors. Thirty-five primary human cultures enriched in CR-CSCs, including four from chemoresistant metastatic lesions, were used for in vitro studies and to generate CR-CSC-based mouse avatars to evaluate tumor growth and progression upon treatment with BMP7v alone or in combination with standard therapy or PI3K inhibitors. BMP7v treatment promotes CR-CSC differentiation and recapitulates the cell differentiation-related gene expression profile by suppressing Wnt pathway activity and reducing mesenchymal traits and survival of CR-CSCs. Moreover, in CR-CSC-based mouse avatars, BMP7v exerts an antiangiogenic effect and sensitizes tumor cells to standard chemotherapy regardless of the mutational, MSI, and CMS profiles. Of note, tumor harboring PIK3CA mutations were affected to a lower extent by the combination of BMP7v and chemotherapy. However, the addition of a PI3K inhibitor to the BMP7v-based combination potentiates PIK3CA-mutant tumor drug response and reduces the metastatic lesion size. These data suggest that BMP7v treatment may represent a useful antiangiogenic and prodifferentiation agent, which renders CSCs sensitive to both standard and targeted therapies.


Assuntos
Proteína Morfogenética Óssea 7/genética , Proteína Morfogenética Óssea 7/farmacologia , Neoplasias Colorretais/patologia , Mutação , Animais , Antineoplásicos/farmacologia , Diferenciação Celular/efeitos dos fármacos , Linhagem Celular Tumoral , Neoplasias Colorretais/tratamento farmacológico , Humanos , Camundongos , Células-Tronco Neoplásicas/efeitos dos fármacos , Células-Tronco Neoplásicas/patologia , Inibidores de Fosfoinositídeo-3 Quinase/farmacologia , Ensaios Antitumorais Modelo de Xenoenxerto
12.
Dermatol Ther ; 32(5): e13021, 2019 09.
Artigo em Inglês | MEDLINE | ID: mdl-31306540

RESUMO

Psoriasis impacts the quality of life (QoL) by disrupting overall health and social life. Thus, the use of a QoL evaluation item is crucial in assessing a therapeutic regimen. Also, faster improvements in QoL lead to better patient compliance, but very few studies compare psoriasis traditional and biologic therapies timing. To evaluate how much different systemic therapies improve disease severity and QoL, a retrospective analysis was performed on 56 patients. Subjects were administered different drugs and their vital statistics, psoriasis area severity index (PASI) and PSOdisk were collected at baseline and after 30 days. We found a moderate correlation between PASI and PSOdisk score with (r): .62. In terms of clinical scores improvement after 30 days, Ustekinumab turned out to be the fastest therapy available, while cyclosporine, among the systemic therapies available, appeared as highly competitive if not better than other biologic therapies.


Assuntos
Adalimumab/uso terapêutico , Terapia Biológica/métodos , Ciclosporina/uso terapêutico , Psoríase/terapia , Qualidade de Vida , Ustekinumab/uso terapêutico , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Anti-Inflamatórios/uso terapêutico , Fármacos Dermatológicos/uso terapêutico , Feminino , Seguimentos , Humanos , Masculino , Pessoa de Meia-Idade , Psoríase/diagnóstico , Psoríase/psicologia , Estudos Retrospectivos , Índice de Gravidade de Doença , Pele/patologia , Inquéritos e Questionários , Fatores de Tempo , Resultado do Tratamento , Adulto Jovem
14.
J Dermatolog Treat ; 29(sup1): 21-24, 2018.
Artigo em Inglês | MEDLINE | ID: mdl-30273068

RESUMO

Nail involvement is frequent in patients with psoriasis, especially those with psoriatic arthritis (PsA), and can significantly impair quality of life (QoL). It is typically difficult to treat compared with skin lesions, although several conventional treatment options are available. The aim of this article is to describe our experience in the treatment of nail psoriasis with secukinumab in a case series. Fifteen patients (11 males and 4 females), with moderate-severe plaque psoriasis and nail psoriasis, eligible for systemic therapy, and received secukinumab. The Psoriasis Area and Severity Index (PASI) and body surface area (BSA) assessed cutaneous severity. Nail Psoriasis Severity Index (NAPSI) was used to evaluate nail involvement. Starting from 6 weeks after initiation of treatment with secukinumab 300 mg, a clinically significant response was observed, with progressive reduction of both skin and nail disease indexes. Average reduction of PASI was 75%, of BSA 70%, and of NAPSI 50%, at week 6. At week 12, NAPSI reduction was by 80%, of PASI 90%, and of BSA 97%. Effective treatment of both skin and nail psoriasis was obtained with secukinumab, a new approach to psoriatic patients resistant to topical therapy.


Assuntos
Anticorpos Monoclonais/uso terapêutico , Doenças da Unha/tratamento farmacológico , Psoríase/tratamento farmacológico , Adulto , Anticorpos Monoclonais Humanizados , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Doenças da Unha/etiologia , Psoríase/complicações , Qualidade de Vida , Índice de Gravidade de Doença , Resultado do Tratamento
15.
Med Lav ; 108(2): 123-129, 2017 04 21.
Artigo em Inglês | MEDLINE | ID: mdl-28446739

RESUMO

BACKGROUND: Leishmaniasis is a widespread infectious disease, but there is not much information about its prevalence in high risk occupational categories. OBJECTIVES: The aim of this study is to assess the prevalence of Leishmania immunological positivity in human skin tissues collected from subjects living in Western Sicily, with suspected cutaneous Leishmania infection, in order to explore the risk possibly related to occupation. METHODS: 318 consecutive subjects (M/F ratio=1.0, mean age=40±25.4 years), attending the Dermatology Department of the University of Palermo Hospital from 2013 to 2015, without any previous history of Leishmania infection and performing various occupations, were included. Parasite isolation and PCR-RT test on skin scrapings were performed to evaluate the immunological status; all data were analyzed by the chi square test, comparing all positive results from the different provinces. RESULTS: 81 (50.9%) out of 159 females and 79 (49.7%) out of 159 males were found PCR-RT positive to Leishmania infantum, with a higher risk in the Agrigento district (p<0.001) and in subjects living in rural areas (p=0.0038), regardless of the type of work performed. The observed animal leishmaniasis prevalence in the same areas shows the endemic status of the disease in Sicily. CONCLUSIONS: Although based on a relatively small sample, our study shows that cutaneous leishmaniasis represents a health care problem with a medical and social impact in Western Sicily. An active surveillance system and the establishment of diagnosis and treatment centres could be useful in controlling this public health problem.


Assuntos
Leishmaniose Cutânea/epidemiologia , Ocupações/estatística & dados numéricos , Adolescente , Adulto , Idoso , Criança , Estudos Transversais , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Prevalência , Sicília/epidemiologia , Adulto Jovem
18.
Int J Dermatol ; 54(7): 795-9, 2015 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-25660724

RESUMO

BACKGROUND: Avian mite dermatitis is a skin disease caused in mammals by the incidental bites of blood-sucking mites which customarily parasitize wild and domestic birds. It manifests in the form of pruritic, erythematous, or urticarial papules, with a central sting mark, in skin regions normally covered by clothing. The species mainly implicated in human bite cases are Dermanyssus gallinae, Ornithonyssus sylviarum and, less frequently, Ornithonyssus bursa. The latter is mainly a tropical and subtropical mite and its - presumably transitory - presence has been recorded only once in Europe, in migratory birds. CASE REPORT: We report a case of avian mite dermatitis in a 70-year-old man, an owner of chickens, who lived in Sicily, an island in southern Italy. He presented with an itching, erythematous, papular eruption. Numerous mites were seen racing across his skin. The precise identification of O. bursa was based on the morphology of its plates and chelicerae and on the arrangement of its setae. CONCLUSIONS: Not only does this paper report the first European case of human infestation with O. bursa, it provides evidence that this alien species has settled and spread in the Old Continent. It may have been flown in from a small focus reported in Danish migratory birds in the 1980s or may have been accidentally introduced into Italy through the importation of infested poultry from South America. Such occurrences may have unpredictable epidemiological and ecological consequences. More comprehensive veterinary inspection of imported birds is desirable.


Assuntos
Galinhas/parasitologia , Dermatite/parasitologia , Infestações por Ácaros/complicações , Infestações por Ácaros/parasitologia , Doenças das Aves Domésticas/parasitologia , Idoso , Animais , Humanos , Espécies Introduzidas , Masculino , Infestações por Ácaros/veterinária , Ácaros , Sicília
19.
J Dermatolog Treat ; 26(1): 67-72, 2015 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-24521072

RESUMO

UNLABELLED: What is known and objective: Pemphigus is a severe, potentially life-threatening autoimmune blistering disease. The use of corticosteroids has dramatically improved the prognosis and changed its course. However, current morbidity of pemphigus is largely iatrogenic, caused by side effects of the long-term, high-dose corticosteroid therapy that is necessary to sustain disease control. In order to minimize side effects, a range of corticosteroid-sparing immunosuppressive agents have been introduced, including mycophenolate mofetil (MMF) and enteric-coated mycophenolate sodium (EC-MPS). A systematic review was performed to evaluate the effectiveness of MMF and EC-MPS in the treatment of pemphigus vulgaris and pemphigus foliaceus. METHODS: A retrospective literature search was conducted through multiple electronic databases (PubMed, Medline, The Cochrane database of systematic reviews) for reports on the use of mycophenolic acid (MPA) in the treatment of pemphigus vulgaris and pemphigus foliaceus. RESULTS: Sixteen studies with a total of 239 patients have evaluated the treatment of pemphigus vulgaris and pemphigus foliac;eus with MPA. The majority of patients had refractory disease treated with corticosteroids as monotherapy or associated to adjuvant agents. DISCUSSION: The results of this review suggest that MPA, as MMF or EC-MPS, may be a promising adjuvant or alternative therapy for the treatment of pemphigus vulgaris and pemphigus foliaceus. It appears safe, at least in the medium term and its adverse events seem to be dose dependent. WHAT IS NEW AND CONCLUSION: The use of mycophenolate is first-line adjuvant therapy in the treatment of pemphigus vulgaris and pemphigus foliaceus.


Assuntos
Imunossupressores/uso terapêutico , Ácido Micofenólico/análogos & derivados , Pênfigo/tratamento farmacológico , Fármacos Dermatológicos/administração & dosagem , Fármacos Dermatológicos/uso terapêutico , Quimioterapia Combinada , Glucocorticoides/administração & dosagem , Glucocorticoides/uso terapêutico , Humanos , Imunossupressores/administração & dosagem , Ácido Micofenólico/administração & dosagem , Ácido Micofenólico/uso terapêutico , Pênfigo/patologia , Prognóstico , Resultado do Tratamento
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