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1.
An Bras Dermatol ; 97(2): 231-235, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-34996656

RESUMO

Patients with lepromatous or borderline leprosy may present two types of vasculonecrotic reactions: Lucio's phenomenon (LP) and necrotic erythema nodosum leprosum (nENL). These are serious conditions, which mostly lead to life-threatening infectious and thrombotic complications. The authors report the case of a patient with leprosy recurrence associated with an atypical type II reaction with LP characteristics on histopathology.


Assuntos
Eritema Nodoso , Hanseníase Dimorfa , Hanseníase Virchowiana , Hanseníase Multibacilar , Hanseníase , Eritema Nodoso/patologia , Humanos , Hanseníase/complicações , Hanseníase Virchowiana/complicações , Hanseníase Virchowiana/patologia , Hanseníase Multibacilar/complicações , Necrose
2.
Am J Trop Med Hyg ; 106(1): 51-53, 2021 10 18.
Artigo em Inglês | MEDLINE | ID: mdl-34662871

RESUMO

Erythema nodosum leprosum (ENL), or type 2 lepra reaction, presents with crops of evanescent, tender erythematous nodules accompanied by fever, arthralgia, malaise and organ-specific manifestations and is seen in borderline and lepromatous leprosy. The drugs approved for ENL include nonsteroidal anti-inflammatory drugs, systemic steroids, thalidomide and clofazimine. The management of ENL is challenging because long-term steroid use leads to steroid dependence. The present patient had severe steroid recalcitrant ENL with vesicular and pustular lesions mimicking Sweet's syndrome and was treated effectively with a low-dose thalidomide regimen (100 mg/d) as opposed to high dose (400 mg/d) recommended in literature. We discuss the patho-mechanics and clinical utility of a low-dose thalidomide regimen as an effective treatment option for ENL.


Assuntos
Eritema Nodoso/tratamento farmacológico , Hanseníase Virchowiana/tratamento farmacológico , Talidomida , Adulto , Diagnóstico Diferencial , Eritema Nodoso/diagnóstico , Eritema Nodoso/patologia , Feminino , Humanos , Hansenostáticos/uso terapêutico , Hanseníase Virchowiana/diagnóstico , Hanseníase Virchowiana/patologia , Esteroides/administração & dosagem , Esteroides/uso terapêutico , Síndrome de Sweet/diagnóstico , Síndrome de Sweet/patologia , Talidomida/administração & dosagem , Talidomida/uso terapêutico
3.
Am J Dermatopathol ; 43(10): 700-706, 2021 Oct 01.
Artigo em Inglês | MEDLINE | ID: mdl-33264135

RESUMO

ABSTRACT: Erythema nodosum leprosum (ENL) occurs as an immunological complication of multibacillary leprosy (MBL). The pathogenesis of ENL is long considered to be a T-cell-mediated process. The role of B cells and plasma cells in ENL is not well described in the literature. Therefore, we investigated the B-cell and plasma cell infiltrates in the skin biopsies of biopsy-proven cases of ENL by immunohistochemistry and image morphometry and compared the result with paucibacillary leprosy and MBL. Moreover, we sought a correlation of the B-cell and plasma cell infiltrates with different clinical, hematological, histopathological, and bacteriological parameters as well as the T-cell subsets in the skin biopsies. Our study highlighted a significant reduction in the number of B cells from paucibacillary leprosy to MBL to ENL, although there was no significant variation in the plasma cell infiltrate. The plasma cell infiltrate correlated with absolute neutrophilia in the blood and the presence of eosinophils in the ENL lesions. Both B cells and plasma cells positively correlated with CD4-positive T-helper cells and the CD8-positive cytotoxic T cells. Besides, the B cells also correlated positively with the CD3-positive pan T cells in the biopsy and negatively correlated with the T-regulatory:T-cell ratio. Our results suggested the role of B cells and plasma cells even at the tissue level in the pathobiogenesis of ENL.


Assuntos
Linfócitos B/patologia , Eritema Nodoso/patologia , Hanseníase Virchowiana/patologia , Plasmócitos/patologia , Adolescente , Adulto , Idoso , Antígenos CD20/metabolismo , Linfócitos B/metabolismo , Contagem de Células Sanguíneas , Criança , Pré-Escolar , Eosinófilos/patologia , Eritema Nodoso/sangue , Eritema Nodoso/imunologia , Feminino , Humanos , Imuno-Histoquímica , Lactente , Hanseníase Virchowiana/sangue , Hanseníase Virchowiana/imunologia , Hanseníase Paucibacilar/imunologia , Hanseníase Paucibacilar/patologia , Masculino , Pessoa de Meia-Idade , Neutrófilos , Plasmócitos/metabolismo , Sindecana-1/metabolismo , Linfócitos T Citotóxicos/patologia , Linfócitos T Auxiliares-Indutores/patologia , Linfócitos T Reguladores/patologia , Adulto Jovem
4.
Rev Chilena Infectol ; 38(5): 707-712, 2021 10.
Artigo em Espanhol | MEDLINE | ID: mdl-35506839

RESUMO

Leprosy or Hansen's disease is one of the classic neglected diseases that still persists in Peru. The infection is caused by Mycobacterium leprae. The disease varies in a wide range of manifestations from tuberculoid (paucibacillary) to lepromatous (multibacillary) leprosy. We present the case of a 55-year-old man, farmer and wood extractor, from the Peruvian Amazon with old infiltrating cutaneous lesions on the face, neck, thorax, abdomen and extremities. The smear and biopsy examinations confirm the presence of acid-alcohol-resistant bacilli compatible with leprosy. It is concluded, with a long delay, it was a case of nodular lepromatous leprosy. He received therapy with rifampicin, dapsone and clofamizine for two years with slow progressive improvement; however, he presented an erythema nodosum leprosum (type 2 reaction) with response to corticosteroids and thalidomide.


Assuntos
Eritema Nodoso , Hanseníase Virchowiana , Hanseníase , Diagnóstico Tardio , Eritema Nodoso/diagnóstico , Eritema Nodoso/tratamento farmacológico , Eritema Nodoso/patologia , Humanos , Hanseníase Virchowiana/diagnóstico , Hanseníase Virchowiana/tratamento farmacológico , Masculino , Pessoa de Meia-Idade , Peru
5.
Dermatol Online J ; 26(9)2020 Sep 15.
Artigo em Inglês | MEDLINE | ID: mdl-33054941

RESUMO

Lepromatous leprosy is associated with a high bacillary load and poor cellular immune response. Early dermatologic manifestations include erythematous macules, papules, nodules, and plaques with a symmetrical distribution. Leprosy also shows two major reaction states including type I (reversal reaction) and type II (vasculitis). These reactions are usually seen in some patients who are undergoing treatment. Herein, we report an interesting patient with lepromatous leprosy who presented with skin lesions of type II reaction without receiving any anti-leprosy treatment and surprisingly showed a type I reaction eight months after the beginning of the treatment.


Assuntos
Eritema Nodoso/patologia , Hansenostáticos/uso terapêutico , Hanseníase Virchowiana/patologia , Clofazimina/uso terapêutico , Dapsona/uso terapêutico , Progressão da Doença , Quimioterapia Combinada , Eritema Nodoso/tratamento farmacológico , Humanos , Hanseníase Virchowiana/tratamento farmacológico , Masculino , Pessoa de Meia-Idade , Rifampina/uso terapêutico , Resultado do Tratamento
7.
Int J Mycobacteriol ; 9(2): 226-228, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32474551

RESUMO

Erythema multiforme (EM)-like erythema nodosum leprosum (ENL) is a rare atypical presentation, and its late appearance after the completion of multidrug therapy (MDT) is unusual. We describe the case of a lepromatous leprosy patient who after the completion of MDT presented to us with late EM-like ENL and was found to be resistant to rifampicin. We discuss the implications of this finding and the potential role of resistant bacilli in causing reactions with atypical presentations.


Assuntos
Quimioterapia Combinada/efeitos adversos , Hansenostáticos/uso terapêutico , Hanseníase/diagnóstico , Hanseníase/tratamento farmacológico , Rifampina/uso terapêutico , Adulto , Farmacorresistência Bacteriana/genética , Eritema Multiforme/diagnóstico , Eritema Multiforme/patologia , Eritema Nodoso/diagnóstico , Eritema Nodoso/patologia , Humanos , Masculino , Mycobacterium lepraemurium/efeitos dos fármacos , Mycobacterium lepraemurium/genética , Rifampina/farmacologia , Fatores de Tempo
8.
J Investig Med High Impact Case Rep ; 8: 2324709620927884, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32462938

RESUMO

The distinction between persistent infection and immunologic reactions in leprosy is often difficult but critically important since their management is different. We present the case of a 51-year-old Vietnamese female who presented in 2015 with areas of erythema and skin infiltration on face and chest, as well as edema on her hands and feet. Skin biopsy was consistent with lepromatous leprosy. She was treated with rifampin, clarithromycin, and levofloxacin for 2 years. Her lower extremity edema was attributed to type 2 immunological reaction for which she was started on prednisone and methotrexate, but she was lost to follow-up for 19 months. She presented with new skin lesions and pain on her extremities. New biopsies revealed an intense neutrophilic infiltrate in the dermis and acid-fast bacilli focally within cutaneous nerve twigs. As compared with the initial biopsy, the inflammatory infiltrates were diminished and the bacilli had a degenerating appearance. These findings were consistent with type 2 immunological reaction. The patient was treated with thalidomide with improvement in the appearance of the skin lesions. A follow-up biopsy showed lack of neutrophilic infiltrates and decreased number of bacilli. This case illustrates the importance of differentiating between persistent infection and immunologic reactions in leprosy. Clinicians should be aware of these complications. A high index of suspicion and accurate interpretation of skin biopsy results are essential for appropriate diagnosis.


Assuntos
Eritema Nodoso/etiologia , Hanseníase Virchowiana/tratamento farmacológico , Hanseníase Virchowiana/patologia , Pele/patologia , Biópsia , Edema/etiologia , Eritema Nodoso/patologia , Feminino , Humanos , Hansenostáticos/uso terapêutico , Hanseníase Virchowiana/classificação , Hanseníase Virchowiana/imunologia , Pessoa de Meia-Idade , Prednisona/uso terapêutico
9.
Int J Dermatol ; 59(7): 856-861, 2020 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-32358972

RESUMO

BACKGROUND: Leprosy can cause acute reactions, which may be type 1 (reverse reaction) or type 2 (erythema nodosum leprosum - ENL). ENL has been classified as mild, moderate, or severe. In order to standardize the classification, the Erythema Nodosum Leprosum International Study (ENLIST) Group has developed an objective scale, the ENLIST ENL Severity Scale (EESS), which was the first validated severity scale of ENL in the world. The goal of the study was to describe the sociodemographic and clinical characteristics of patients with ENL attending a tertiary hospital in Piauí, Brazil, classifying them according to the EESS. METHODS: A descriptive cross-sectional observational study was conducted on 26 patients recruited sequentially from May 2017 to February 2018. Their data were statistically analyzed and compared against each other through a structured questionnaire. RESULTS: According to the score obtained in the scale, the patients were divided into two groups: mild ENL and moderate/severe ENL. The extent and number of nodules were related to the severity of the cases, and these data were statistically significant. The majority of the patients were male, between the ages of 31 and 49 years old, with low educational level, and residents in the urban area. CONCLUSIONS: This was the first study to use EESS in Brazil. This scale is easy to apply and allows for the enhancement of treatment protocols. The study also showed a correlation between the number and extension of nodules and the severity of the condition.


Assuntos
Eritema Nodoso/epidemiologia , Hanseníase Virchowiana/epidemiologia , Índice de Gravidade de Doença , Adolescente , Adulto , Brasil/epidemiologia , Estudos Transversais , Escolaridade , Eritema Nodoso/complicações , Eritema Nodoso/patologia , Feminino , Febre/microbiologia , Humanos , Hanseníase Virchowiana/complicações , Hanseníase Virchowiana/patologia , Masculino , Pessoa de Meia-Idade , Dor/microbiologia , Prevalência , Fatores Sexuais , Inquéritos e Questionários , População Urbana , Adulto Jovem
11.
Pharmacogenomics ; 20(7): 503-516, 2019 05.
Artigo em Inglês | MEDLINE | ID: mdl-31124417

RESUMO

Aim: To evaluate the effects of gene polymorphisms in the treatment of erythema nodosum leprosum with prednisone/thalidomide. Patients & methods: A total of 152 patients from different regions of Brazil were included. Generalized estimating equation was used to evaluate the influence of polymorphisms and haplotypes on the drug dose variation throughout the treatment. Results: An association between the genotype tuberculoid of polymorphism ABCB1 3435C>T (rs1045642; p = 0.02) and prednisone dose was found in the recessive model. An association between the haplotypes 1031T/-863C/-857C/-308A/-238G (p = 0.006) and 1031T/-863C/-857T/-308A/-238G (p = 0.040) of the TNF gene and the CYP2C19*2 polymorphism were also identified, in relation to thalidomide dosage variation over the course of treatment. Conclusion: This work presents the first pharmacogenetic report of association between gene polymorphisms and erythema nodosum leprosum treatment with prednisone/thalidomide.


Assuntos
Citocromo P-450 CYP2C19/genética , Eritema Nodoso/tratamento farmacológico , Fator de Necrose Tumoral alfa/genética , Subfamília B de Transportador de Cassetes de Ligação de ATP/genética , Adulto , Brasil/epidemiologia , Relação Dose-Resposta a Droga , Eritema Nodoso/genética , Eritema Nodoso/patologia , Feminino , Estudos de Associação Genética , Predisposição Genética para Doença , Genótipo , Haplótipos/genética , Humanos , Masculino , Polimorfismo Genético , Prednisona/administração & dosagem , Prednisona/efeitos adversos , Receptores de Glucocorticoides/genética , Talidomida/administração & dosagem , Talidomida/efeitos adversos
12.
Int J Mycobacteriol ; 8(1): 29-34, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-30860176

RESUMO

Background: Erythema nodosum leprosum (ENL) classically presents with tender, coppery, evanescent nodules along with constitutional features and visceral involvement. However, uncommon morphological variants of ENL-like erythema nodosum necroticans, erythema multiforme (EM)-like ENL, Sweet's syndrome (SS)-like ENL, Lucio phenomenon, and reactive perforating type of ENL have also been described in the literature. The primary objective of this study was to describe the clinical features of the severe and uncommon morphological variants of ENL. Methods: This was an observational case series with retrospective review of records of all ENL patients with ulceronecrotic lesions admitted in the Department of Dermato-venereo-leprology of a tertiary health center of central India over a period of 2 years. Results: Eighteen patients were included, all of whom had ulceronecrotic lesions. Four out of them had EM like ENL, two had SS-like presentation, and one of them had annular bullous lesions over old infiltrated plaques of leprosy. Conclusions: Uncommon variants of ENL can be very commonly misdiagnosed in patients, especially in those who have not been previously diagnosed with leprosy. Hence, a high index of suspicion is required in such cases to avoid delay in the diagnosis and resulting morbidity.


Assuntos
Eritema Nodoso/diagnóstico , Eritema Nodoso/patologia , Hanseníase Virchowiana/diagnóstico , Hanseníase Virchowiana/patologia , Úlcera/etiologia , Adolescente , Adulto , Idoso , Criança , Feminino , Humanos , Índia , Masculino , Pessoa de Meia-Idade , Necrose/etiologia , Necrose/patologia , Estudos Retrospectivos , Centros de Atenção Terciária , Úlcera/patologia , Adulto Jovem
13.
QJM ; 112(6): 429-435, 2019 Jun 01.
Artigo em Inglês | MEDLINE | ID: mdl-30778548

RESUMO

BACKGROUND: Histoid leprosy is a subtype of leprosy with distinct clinical presentation and histologic features. It accounts for <4% of leprosy cases. The exact location of histoid leprosy along the immune spectrum and its relation to other subtypes is unclear. AIM: To evaluate the local immune phenomenon which define histoid leprosy. DESIGN: Parallel skin biopsies from histoid lesions and from unremarkable skin in patients with histoid leprosy were evaluated and the histologic findings compared. METHODS: Formalin fixed, paraffin embedded tissue sections from lesional and non-lesional biopsies were assessed for changes in epidermis and dermis; type and extent of infiltrate, presence or absence of pseudocapsule and associated reactions. Bacillary index was evaluated using Wade Fite stain for lepra bacilli. RESULTS: Amongst 208 leprosy cases, six cases of histoid leprosy were identified (2.88%). The cases showed presence of nodules, patches and plaques overlying clinically unremarkable skin. Fourteen skin biopsies were evaluated of which the lesional biopsies showed equal proportion of fusocellular, fusocellular epithelioid and fusocellular-vacuolated histology. A greater circumscription was noted in lesional biopsies; however the cellular content of the infiltrate was similar in lesional and non-lesional biopsies. A case of erythema nodosum leprosum in histoid leprosy was also seen. CONCLUSIONS: Ours is the first study comparing normal and lesional skin in histoid leprosy. Though the histoid lesions appear to have a derivation from lepromatous leprosy, the local histologic and clinical alterations may be a result of heightened local immunity or reactive local modifying factors.


Assuntos
Eritema Nodoso/diagnóstico , Eritema Nodoso/patologia , Hanseníase Virchowiana/diagnóstico , Hanseníase Virchowiana/patologia , Adulto , Idoso , Feminino , Humanos , Imuno-Histoquímica , Índia , Masculino , Pessoa de Meia-Idade , Pele/patologia
14.
Am J Trop Med Hyg ; 100(2): 377-385, 2019 02.
Artigo em Inglês | MEDLINE | ID: mdl-30652669

RESUMO

Type 2 reaction (T2R) or erythema nodosum leprosum (ENL), a sudden episode of acute inflammation predominantly affecting lepromatous leprosy patients (LL), characterized by a reduced cellular immune response. This possibly indicates a close relationship between the onset of T2R and the altered frequency, and functional activity of T lymphocytes, particularly of memory subsets. This study performed ex vivo and in vitro characterizations of T cell blood subpopulations from LL patients with or without T2R. In addition, the evaluation of activity of these subpopulations was performed by analyzing the frequency of these cells producing IFN-γ, TNF, and IL-10 by flow cytometry. Furthermore, the expression of transcription factors, for the differentiation of T cells, were analyzed by quantitative real-time polymerase chain reaction. Our results showed an increased frequency of CD8+/TNF+ effector memory T cells (TEM) among T2Rs. Moreover, there was evidence of a reduced frequency of CD4 and CD8+ IFN-γ-producing cells in T2R, and a reduced expression of STAT4 and TBX21. Finally, a significant and positive correlation between bacteriological index (BI) of T2R patients and CD4+/TNF+ and CD4+/IFN-γ+ T cells was observed. Thus, negative correlation between BI and the frequency of CD4+/IL-10+ T cells was noted. These results suggest that CD8+/TNF+ TEM are primarily responsible for the transient alteration in the immune response to Mycobacterium leprae in ENL patients. Thus, our study improves our understanding of pathogenic mechanisms and might suggest new therapeutic approaches for leprosy.


Assuntos
Linfócitos T CD4-Positivos/imunologia , Linfócitos T CD8-Positivos/imunologia , Eritema Nodoso/imunologia , Hanseníase Virchowiana/imunologia , Mycobacterium leprae/patogenicidade , Fator de Necrose Tumoral alfa/imunologia , Adolescente , Adulto , Idoso , Linfócitos T CD4-Positivos/microbiologia , Linfócitos T CD8-Positivos/microbiologia , Estudos de Casos e Controles , Eritema Nodoso/genética , Eritema Nodoso/patologia , Feminino , Regulação da Expressão Gênica , Interações Hospedeiro-Patógeno/genética , Interações Hospedeiro-Patógeno/imunologia , Humanos , Memória Imunológica , Imunofenotipagem , Interferon gama/genética , Interferon gama/imunologia , Interleucina-10/genética , Interleucina-10/imunologia , Hanseníase Virchowiana/genética , Hanseníase Virchowiana/patologia , Masculino , Pessoa de Meia-Idade , Mycobacterium leprae/crescimento & desenvolvimento , Mycobacterium leprae/imunologia , Cultura Primária de Células , Fator de Transcrição STAT4/genética , Fator de Transcrição STAT4/imunologia , Transdução de Sinais , Proteínas com Domínio T/genética , Proteínas com Domínio T/imunologia , Fator de Necrose Tumoral alfa/genética
16.
Int J Mycobacteriol ; 7(2): 191-194, 2018.
Artigo em Inglês | MEDLINE | ID: mdl-29900900

RESUMO

Erythema nodosum leprosum (ENL) is characterized by tender erythematous nodules, accompanied by fever, malaise, arthralgia, and systemic complications. Atypical clinical manifestations have been reported such as pustular, bullous, ulceration; livedo reticularis; erythema multiforme-like reaction; and Sweet's syndrome (SS)-like presentation. We reported a case of ENL reaction presenting as SS-like reaction in a borderline lepromatous leprosy patient.


Assuntos
Eritema Nodoso/diagnóstico , Hanseníase Dimorfa/diagnóstico , Hanseníase Virchowiana/diagnóstico , Síndrome de Sweet/diagnóstico , Adulto , Eritema Nodoso/microbiologia , Eritema Nodoso/patologia , Humanos , Hanseníase Dimorfa/microbiologia , Hanseníase Dimorfa/patologia , Hanseníase Virchowiana/microbiologia , Hanseníase Virchowiana/patologia , Masculino , Mycobacterium leprae/genética , Mycobacterium leprae/isolamento & purificação , Síndrome de Sweet/microbiologia , Síndrome de Sweet/patologia
17.
Int J Mycobacteriol ; 7(1): 97-100, 2018.
Artigo em Inglês | MEDLINE | ID: mdl-29516895

RESUMO

Type 2 leprosy reactions commonly known as erythema nodosum leprosum, but various clinical manifestations of type 2 leprosy reaction were exist. The highlight of this case series was to report various atypical clinical manifestations of type 2 leprosy reaction such as reactive perforating leprosy, erythema multiforme-like reaction, and sweet's syndrome (SS)-like reaction.


Assuntos
Eritema Nodoso/patologia , Hanseníase Dimorfa/patologia , Hanseníase Virchowiana/patologia , Síndrome de Sweet/patologia , Adulto , Feminino , Humanos , Hansenostáticos/uso terapêutico , Hanseníase Dimorfa/tratamento farmacológico , Hanseníase Virchowiana/tratamento farmacológico , Masculino
20.
J Infect Dis ; 216(12): 1635-1643, 2017 12 19.
Artigo em Inglês | MEDLINE | ID: mdl-29272525

RESUMO

Background: Leprosy, the leading infectious cause of disability worldwide, remains a major public health challenge in the most severely affected countries despite the sharp decline in new cases in recent years. The search for biomarkers is essential to achieve a better understanding of the molecular and cellular mechanisms underlying the disease. Methods: Pentraxin-3 (PTX3) analyses of sera from 87 leprosy patients with or without reactions were conducted via enzyme-linked immunosorbent assay. In situ identification of PTX3 in skin lesion was confirmed by quantitative reverse-transcription polymerase chain reaction, immunohistochemistry, and immunofluorescence assays. Results: We found that PTX3 serum levels were higher in multibacillary patients when evaluated before the onset of acute erythema nodosum leprosum (ENL) and persistently elevated during reaction. Thalidomide treatment reduced PTX3 in the serum 7 days after starting treatment. In situ analyses have also demonstrated enhancement of PTX3 in ENL lesions and showed that treatment with thalidomide reduced its expression and the prominent neutrophilic infiltrate, a hallmark of the disease. Conclusions: In summary, our study provides in vivo evidence that PTX3 is enhanced during ENL but not in reversal reaction and provides a new molecular target in ENL pathogenesis.


Assuntos
Biomarcadores/análise , Proteína C-Reativa/análise , Eritema Nodoso/diagnóstico , Eritema Nodoso/patologia , Hanseníase Virchowiana/diagnóstico , Hanseníase Virchowiana/patologia , Componente Amiloide P Sérico/análise , Adolescente , Adulto , Idoso , Proteína C-Reativa/genética , Estudos de Casos e Controles , Criança , Ensaio de Imunoadsorção Enzimática , Feminino , Imunofluorescência , Humanos , Imuno-Histoquímica , Hansenostáticos/administração & dosagem , Masculino , Pessoa de Meia-Idade , Reação em Cadeia da Polimerase em Tempo Real , Reação em Cadeia da Polimerase Via Transcriptase Reversa , Componente Amiloide P Sérico/genética , Pele/patologia , Talidomida/administração & dosagem , Adulto Jovem
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