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G Ital Dermatol Venereol ; 155(3): 346-348, 2020 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-32635708


During the Middle Ages, leprosy sufferers could not live in the city and were forced outside the walls. In the centuries, the Genoese area dedicated several hospitals to lepers, such as S. Lazzaro and Pammatone Hospital, a small leprosarium in the Tigullio area and San Martino Hospital from 1935. The first doctor who recognized to cure leprosy in Genoa was Goffredo, who later was also nominated rector of the community. In the early 1900's, Radaeli promoted the construction of a leprosarium behind the San Martino hospital. In 1936 Giuseppe Mariani was known for using the leprosarium to hide Italian Jews during deportation to the extermination camps. Later, Professor Aldo Baccaredda-Boy instituted the graduate school in "Leprosy and Tropical Dermatology", continued by professor Enrico Nunzi until 1990. The leprosarium was then transformed into the Department of Tropical Dermatology and finally into the Operative Unit of Social Dermatology, a national reference center.

Hospitais de Dermatologia Sanitária de Patologia Tropical/história , Hanseníase/história , Médicos/história , História do Século XV , História do Século XVI , História do Século XVII , História do Século XVIII , História do Século XIX , História do Século XX , História do Século XXI , História Medieval , Humanos , Itália , II Guerra Mundial
J Biol Chem ; 294(12): 4520-4528, 2019 03 22.
Artigo em Inglês | MEDLINE | ID: mdl-30692201


Pemphigus vulgaris (PV) is a potentially lethal mucocutaneous blistering disease characterized by IgG autoantibodies (AuAbs) binding to epidermal keratinocytes and inducing this devastating disease. Here, we observed that non-desmoglein (Dsg) AuAbs in the sera of patients with Dsg1/3 AuAb-negative acute PV are pathogenic, because IgGs from these individuals induced skin blistering in neonatal mice caused by suprabasal acantholysis. Serum levels of AuAbs to desmocollin 3 (Dsc3), M3 muscarinic acetylcholine receptor (M3AR), and secretory pathway Ca2+/Mn2+-ATPase isoform 1 (SPCA1) correlated with the disease stage of PV. Moreover, AuAb absorption on recombinant Dsc3, M3AR, or SPCA1 both prevented skin blistering in the passive transfer of AuAbs model of PV in BALB/c mice and significantly decreased the extent of acantholysis in a neonatal mouse skin explant model. Although acantholytic activities of each of these immunoaffinity-purified AuAbs could not induce a PV-like phenotype, their mixture produced a synergistic effect manifested by a positive Nikolskiy sign in the skin of neonatal mice. The downstream signaling of all pathogenic non-Dsg AuAbs involved p38 mitogen-activated protein kinase (MAPK)-mediated phosphorylation and elevation of cytochrome c release and caspase 9 activity. Anti-Dsc3 and anti-SPCA1 AuAbs also activated SRC proto-oncogene, nonreceptor tyrosine kinase (SRC). Of note, although a constellation of non-Dsg AuAbs apparently disrupted epidermal integrity, elimination of a single pathogenic AuAb could prevent keratinocyte detachment and blistering. Therefore, anti-Dsg1/3 AuAb-free PV can be a model for elucidating the roles of non-Dsg antigen-specific AuAbs in the physiological regulation of keratinocyte cell-cell adhesion and blister development.

Desmogleína 1/imunologia , Desmogleína 3/imunologia , Pênfigo/imunologia , Animais , Animais Recém-Nascidos , Autoanticorpos/sangue , Autoanticorpos/imunologia , Autoanticorpos/isolamento & purificação , ATPases Transportadoras de Cálcio/imunologia , Cromatografia de Afinidade/métodos , Humanos , Queratinócitos/enzimologia , Queratinócitos/metabolismo , Camundongos , Camundongos Endogâmicos BALB C , Pênfigo/patologia , Proto-Oncogene Mas
Exp Dermatol ; 27(12): 1322-1327, 2018 12.
Artigo em Inglês | MEDLINE | ID: mdl-30218612


Cutaneous deposition of eosinophil degranulation proteins is a major feature of eosinophil-rich cutaneous diseases including bullous pemphigoid (BP). We sought to better understand the effect of two of these proteins - eosinophil cationic protein (ECP) and eosinophil-derived neurotoxin (EDN), on human keratinocytes using the Het-1A cell line. To evaluate expression of key cytokines and chemokines observed in BP as well as metal metalloprotease 9 (MMP9), we performed qPCR and in-cell Western assays on cells treated with either ECP or EDN. We further evaluated the effect of ECP and EDN on keratinocyte survival, generation of reactive oxygen species (ROS) and apoptosis. Lastly, we assessed ECP and EDN's ability to induce keratinocyte detachment from provisional matrix. Treatment of keratinocytes with ECP and EDN resulted in significant increases in IL-5, eotaxin-1 and CCL5 (RANTES) expression at both mRNA and protein levels, but not IL-17 or IL-31. ECP and EDN also upregulate MMP9 production. Inhibiting MMP9, we confirmed that keratinocyte expression of IL-5, eotaxin-1 and RANTES was independent from MMP9. Both ECP and EDN were cytotoxic to keratinocytes, inducing ROS formation and apoptosis through a mitochondrion-dependent pathway as evidenced by results of terminal deoxynucleotidyl transferase dUTP nick-end labelling (TUNEL) and cytochrome c release assays, respectively. ECP but not EDN led to significant keratinocyte detachment from provisional matrix. These findings demonstrate that the pathogenic effects of ECP and EDN in BP may result from their direct action on keratinocytes, and as such may became a target for future therapies in eosinophil-rich cutaneous diseases.

Proteína Catiônica de Eosinófilo/metabolismo , Neurotoxina Derivada de Eosinófilo/metabolismo , Eosinófilos/metabolismo , Queratinócitos/metabolismo , Apoptose , Linhagem Celular , Sobrevivência Celular , Quimiocina CCL11/metabolismo , Quimiocina CCL5/metabolismo , Proteína Catiônica de Eosinófilo/farmacologia , Neurotoxina Derivada de Eosinófilo/farmacologia , Regulação da Expressão Gênica , Humanos , Interleucina-17/metabolismo , Interleucina-5/metabolismo , Interleucinas/metabolismo , Queratinócitos/efeitos dos fármacos , Metaloproteinase 9 da Matriz/metabolismo , Espécies Reativas de Oxigênio/metabolismo
JAMA Dermatol ; 153(11): 1137-1141, 2017 11 01.
Artigo em Inglês | MEDLINE | ID: mdl-28854309


Importance: Pneumocystis pneumonia (PCP) is a potentially lethal opportunistic infection that primary prophylaxis can help prevent. The risk of prophylactic therapy must be weighed against the incidence of PCP in the patient population. Prophylaxis most frequently involves trimethoprim-sulfamethoxazole, with second-line therapies, including atovaquone, dapsone, and pentamide. The indication for prophylaxis in immunocompromised patients without HIV is less well defined. Previously, an incidence of at least 3.5% has been proposed as a cutoff to justify prophylaxis. Objective: To assess the incidence of PCP in patients with autoimmune blistering diseases receiving no routine prophylaxis. Design, Setting, and Participants: This was a retrospective analysis of patient medical records to determine the incidence of PCP infections. The multicenter study was performed at tertiary care centers that provide care for patients with autoimmune blistering disease in Germany, Italy, Singapore, Israel, and the Netherlands. Patients had a confirmed diagnosis of pemphigus vulgaris/foliaceus, bullous pemphigoid, epidermolysis bullosa acquisita, mucous membrane pemphigoid/cicatricial pemphigoid, or anti-p200 pemphigoid. Main Outcomes and Measures: To determine the incidence of PCP defined as patients with the International Classification of Diseases, Ninth Revision (ICD-9), code 136.3, for PCP, or free text documentation of PCP occurring based on characteristic radiographic findings with elevated lactate dehydrogenase, or hospitalization for pneumonia with bronchioalveolar lavage demonstrating Pneumocystis jiroveci on confirmatory stains. Results: A total of 801 patients with autoimmune blistering diseases were included in this study; their mean (SD) age was 66.5 (17.6) years, and a total of 465 (58%) were female. Only 1 patient developed PCP, resulting in an incidence rate of 0.1%. This incidence significantly fell below the recommended threshold of 3.5% (0.1% vs 3.5%, χ21 = 27.0; P < .001). This incidence was significantly lower than the previously reported incidence of PCP in all immunosuppressed dermatologic patients (0.1% vs 1.3%; χ21 = 8.2; P = .004). Conclusions and Relevance: Routine Pneumocystis prophylaxis for patients with autoimmune blistering diseases does not seem to be warranted. Patients with autoimmune blistering disease seem to have a lower risk of PCP than the general population of immunosuppressed dermatology patients. Risks of routine prophylaxis include hyperkalemia, hypoglycemia, photosensitivity, thrombocytopenia, and more rare adverse reactions.

Doenças Autoimunes/epidemiologia , Imunossupressores/administração & dosagem , Pneumocystis carinii/isolamento & purificação , Pneumonia por Pneumocystis/epidemiologia , Dermatopatias Vesiculobolhosas/epidemiologia , Idoso , Idoso de 80 Anos ou mais , Doenças Autoimunes/fisiopatologia , Lavagem Broncoalveolar , Feminino , Seguimentos , Hospitalização/estatística & dados numéricos , Humanos , Incidência , Masculino , Pessoa de Meia-Idade , Estudos Retrospectivos , Dermatopatias Vesiculobolhosas/fisiopatologia
G Ital Dermatol Venereol ; 152(5): 418-423, 2017 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-26889725


BACKGROUND: The aim of this study was to investigate the role of Demodex folliculorum (DF), Helicobacter pylori (HP), and small intestine bacterial overgrowth (SIBO) in the development of rosacea. METHODS: A case-control study including 60 patients with rosacea and 40 healthy controls was performed. All the patients underwent standardized skin surface biopsy to investigate DF, urea breath test for HP and lactulose breath test and glucose breath test for SIBO. Etiological therapy was started in the following order: acaricidal treatment, antibiotics for SIBO and HP. These exams were repeated after 3 years. Statistical analysis was performed. RESULTS: As regards the 88 patients who completed the entire follow-up, DF positivity was found in 47.7% of the patients, SIBO in 25.0%, and HP in 21.6%. SIBO significantly prevailed in papulopustular rosacea, while HP in erythrosis. At the 6-month follow up, the 61% of patients were in remission. After 3 years, 18% of patients dropped out, while the remaining patients repeated all the investigations. The majority of patients were still in remission and negative for HP while only 5 were positive for DF and 4 for SIBO. CONCLUSIONS: SIBO was the most relevant factor in papulopustular rosacea. Its treatment was crucial in improvement and in maintaining the clinical remission.

Síndrome da Alça Cega/complicações , Infecções por Helicobacter/complicações , Infestações por Ácaros/complicações , Rosácea/etiologia , Acaricidas/uso terapêutico , Adolescente , Adulto , Idoso , Animais , Antibacterianos/uso terapêutico , Biópsia , Síndrome da Alça Cega/diagnóstico , Síndrome da Alça Cega/epidemiologia , Testes Respiratórios , Estudos de Casos e Controles , Feminino , Seguimentos , Infecções por Helicobacter/diagnóstico , Infecções por Helicobacter/epidemiologia , Helicobacter pylori/isolamento & purificação , Humanos , Masculino , Pessoa de Meia-Idade , Infestações por Ácaros/diagnóstico , Infestações por Ácaros/epidemiologia , Rosácea/microbiologia , Rosácea/parasitologia , Adulto Jovem
Int J Dermatol ; 54(10): e389-93, 2015 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-26147127


BACKGROUND: Remitting seronegative symmetrical synovitis with pitting edema (RS3PE) is a rare syndrome consisting of acute symmetrical tenosynovitis of the hands and wrists associated with pain and marked pitting edema of the dorsum of the hands or the feet. Persistent rheumatoid factor seronegativity and elevated acute phase reactants are the rule, while radiographic findings are characterized by the absence of bony erosions. The syndrome has occasionally been associated with a wide range of diseases including solid and hematological malignancies, polymyalgia rheumatica, and other inflammatory rheumatic diseases. METHODS: Two patients with skin eruption on hands and feet associated with arthromyalgias have been investigated to confirm diagnosis of RS3PE and to detect comorbidities. A revision of all the possible medical conditions correlated to RS3PE has been performed. RESULTS: We report two cases of RS3PE associated with Parvovirus B19 infection/reactivation. There are very few reports on the association between RS3PE and infectious agents, and in only one case the syndrome has been correlated to parvovirus infection. CONCLUSIONS: We want to underline the importance for patients with RS3PE to be seen by dermatologists who should become familiar with this syndrome and remark that Parvovirus B19 infection may be a potential cause of RS3PE.

Edema/diagnóstico , Doenças do Pé/diagnóstico , Infecções por Parvoviridae/diagnóstico , Tenossinovite/diagnóstico , Adulto , Tornozelo , Proteína C-Reativa/metabolismo , Comorbidade , Doenças do Pé/virologia , Humanos , Masculino , Pessoa de Meia-Idade , Parvovirus B19 Humano , Fator Reumatoide/sangue , Síndrome , Tenossinovite/sangue , Tenossinovite/virologia , Punho