HTLV-1 proviral load in infective dermatitis associated with HTLV-1 does not increase after the development of HTLV-1-associated myelopathy/tropical spastic paraparesis and does not decrease after IDH remission.

INTRODUCTION: Infective dermatitis associated with HTLV-1 (IDH) is a recurrent eczema which affects children vertically infected with HTLV-1. In Bahia, Brazil, we recently reported that 47% of IDH patients also develop juvenile HTLV-1-associated myelopathy/tropical spastic paraparesis (HAM/TSP), a progressive disabling disorder which is typically reported in adult HTLV-1 carriers. IDH may also predispose to adult T-cell leukemia/lymphoma, a neoplasm associated with HTLV-1. The factors relating to the development of HTLV-1-associated juvenile diseases have not yet been defined. HTLV-1 proviral load (PVL) is one of the main parameters related to the development of HTLV-1 associated diseases in adults. In the current study, we investigated the role of PVL in IDH and juvenile HAM/TSP. METHODOLOGY/PRINCIPAL FINDINGS: This is a cohort study that included fifty-nine HTLV-1 infected children and adolescents, comprising 16 asymptomatic carriers, 18 IDH patients, 20 patients with IDH and HAM/TSP (IDH/HAM/TSP) and five with HAM/TSP. These patients were followed-up for up to 14 years (median of 8 years). We found that PVL in IDH and IDH/HAM/TSP patients were similarly higher than PVL in juvenile asymptomatic carriers (p<0.0001). In those IDH patients who developed HAM/TSP during follow-up, PVL levels did not vary significantly. HAM/TSP development did not occur in those IDH patients who presented high levels of PVL. IDH remission was associated with an increase of PVL. Inter-individual differences in PVL were observed within all groups. However, intra-individual PVL did not fluctuate significantly during follow-up. CONCLUSIONS/SIGNIFICANCE: High PVL in IDH patients was not necessary indicative of progression to HAM/TSP. PVL did not decrease after IDH remission. The maintenance of high PVL after remission could favor early development of ATL. Therefore, IDH patients would have to be followed-up even after remission of IDH and for a long period of time.

Early Juvenile Human T-cell Lymphotropic Virus Type-1-Associated Myelopathy/Tropical Spastic Paraparesis: Study of 25 Patients.

Background: Human T-cell lymphotropic virus type-1 (HTLV-1) may cause severe diseases such as HTLV-1-associated myelopathy/tropical spastic paraparesis (HAM/TSP) and infective dermatitis associated with HTLV-1 (IDH). The clinical characteristics and progression of 25 early onset HAM/TSP associated or not to IDH were described. Methods: Following-up 37 IDH patients with neurological examinations, 54% developed HAM/TSP. To these cases were added 5 cases of juvenile HAM/TSP. The patients were HTLV-1+ and were submitted to dermatological and neurological examinations. Diagnosis of HAM/TSP was performed according to Osame et al (1990) and Castro-Costa et al (2006) criteria. Results: Twenty-one patients were classified as definite HAM/TSP by both criteria, 3 as probable HAM/TSP by Osame et al, and another as probable HAM/TSP according to Castro-Costa et al Median age at onset of neurological manifestations was 9 years for the IDH/HAM/TSP group and 16 years for the HAM/TSP group (P = .045). In 12 patients, the onset of neurological manifestations occurred when they were less than 10 years of age. In the group IDH/HAM/TSP, the neurological symptoms always begun during the period of activity of IDH. The progression of HAM/TSP evaluated in 17 cases was heterogeneous, and 3 had rapid progressive course. Conclusions: The juvenile HAM/TSP may occur very early and also presents marked female predominance. Progression of IDH to HAM/TSP before 19 years of age is frequent (54%). Rapid progressive form may also occur in early HAM/TSP. As juvenile IDH and HAM/TSP are due to vertical transmission through breastfeeding, it is very important to avoid this pathway of infection.

Clustering of HTLV-1 associated myelopathy/tropical spastic paraparesis (HAM/TSP) and infective dermatitis associated with HTLV-1 (IDH) in Salvador, Bahia, Brazil.

Fifteen families with clustering of infective dermatitis associated with HTLV-1 (IDH) and/or HTLV-1 associated myelopathy/tropical spastic paraparesis (HAM/TSP) were observed among 28 families of IDH index cases, 93% of them occurring in two generations. With the exception of two mothers of children with IDH, all the mothers with HAM/TSP had at least one child with HAM/TSP. This is the first report of such clustering involving many families.

Infective dermatitis associated with human T-cell lymphotropic virus type 1: evaluation of 42 cases observed in Bahia, Brazil.

BACKGROUND: Infective dermatitis associated with human T-cell lymphotropic virus type 1 (HTLV-1; IDH) is a chronic recurrent eczema affecting HTLV-1-infected children. The epidemiological and dermatological characteristics of IDH are described, and their principal diagnostic criteria are reevaluated. METHODS: Forty-two patients were included: 40 patients serologically positive for HTLV-1 and 2 seronegative patients who tested positive in polymerase chain reaction (PCR) assays. RESULTS: The mean age at onset of the disease was 2.6 ± 2.4 years (range, 2 months-11 years). The mean duration of breast-feeding was 24.2 months. The lesions were erythematous, scaly, and crusted, always affecting the scalp and retroauricular regions. Crusting of the nostrils was observed in 64.3% of the patients. Of the 36 patients followed up, 23 had the active disease. The age at which IDH disappeared in the others was 10-20 years. CONCLUSIONS: The onset of IDH may occur earlier than reported in the literature. The scalp and retroauricular regions are always affected, and lesions are invariably present in ≥3 areas. Crusting of the nostrils cannot be considered an obligatory factor for the diagnosis of IDH. The recurring nature of IDH was a characteristic found in all cases. Patients with classic IDH lesions who are serologically negative should be investigated by PCR. Therefore, the indispensable criteria for diagnosis are (1) presence of erythematous-scaly, exudative, and crusted lesions involving ≥3 areas, including the scalp and retroauricular regions; (2) recurring nature of the lesions; and (3) a finding of HTLV-1 infection by serology or molecular biology.

Flower cells in patients with infective dermatitis associated with HTLV-1.

BACKGROUND: Infective dermatitis associated with HTLV-1 (IDH) is a severe childhood form of eczema that may progress to adult T-cell leukemia/lymphoma (ATL). OBJECTIVE: In this study, the presence of clinical and laboratory parameters suggestive of ATL was evaluated in a cohort of 30 patients with IDH. STUDY DESIGN: Over a period of 33 months, the patients were submitted to three-monthly clinical evaluations, routine laboratory exams, full blood count and blood smears, and to six-monthly blood sampling for HTLV-1 proviral load determination. HTLV-1 proviral load was quantified using real-time TaqMan PCR assay. RESULTS: Abnormal cells (Ably) were found in the peripheral blood smears of nine patients (30%), flower cells being detected in five of these cases (16.6%). The presence of Ably and flower cells was not associated with a higher proviral load in those patients. CONCLUSIONS: This is the first report on the presence of flower cells in HTLV-1-infected children and adolescents. Furthermore, these cells have not previously been reported in IDH patients. The cases with flower cells probably represent precursory ATL cases, these patients being at a greater risk of developing ATL.

Early sequential development of infective dermatitis, human T cell lymphotropic virus type 1-associated myelopathy, and adult T cell leukemia/lymphoma.

We describe a patient with human T cell lymphotropic virus type 1 (HTLV-1)-associated infective dermatitis who developed HTLV-1-associated myelopathy/tropical spastic paraparesis and adult T cell leukemia/lymphoma at 16 years of age. Long inverse polymerase chain reaction was used to demonstrate monoclonal integration of proviral DNA in the lymphomatous skin lesion.

Manifestations of the human T-cell lymphotropic virus type I infection in childhood and adolescence.

OBJECTIVES: To review the literature on diseases linked with infection by human T-cell lymphotropic virus type I (HTLV-I) in childhood and adolescence, with focus on clinical aspects, diagnosis, pathogenesis, progression and treatment. SOURCES: Medical literature published during the last 20 years identified using PubMed and MEDLINE and from specialized medical books, with emphasis on infective dermatitis associated with HTLV-I (IDH), on the juvenile form of HTLV-associated myelopathy/tropical spastic paraparesis (HAM/TSP), on adult T-cell leukemia/lymphoma (ATL) and on HTLV-I-associated uveitis. Keywords used to search databases were: HTLV-I-associated infective dermatitis, HTLV-I-associated myelopathy/tropical spastic paraparesis, adult T-cell leukemia/lymphoma, HTLV-I-associated uveitis. SUMMARY OF THE FINDINGS: IDH is a chronic, relapsing and infected dermatitis of childhood which always involves the scalp and which may progress to HAM/TSP and ATL. HAM/TSP is a chronic and incapacitating myelopathy of adults. There are 17 well-documented cases of HAM/TSP in children and adolescents in the literature, 12 of whom are patients with IDH. In contrast with the adult form of the disease, the juvenile form is rapid and progressive. ATL is a type of T-cell leukemia/lymphoma that affects adults and is generally fatal. Eleven of the 24 published reports of ATL in children and adolescents were diagnosed in Brazil. CONCLUSIONS: These diseases are likely to be more common in childhood and adolescence than the literature would suggest. It is advisable that serological testing be performed for HTLV-I in children and adolescents suffering from chronic and relapsing eczema, with signs and symptoms of myelopathy or with a diagnosis of T-cell leukemia/lymphoma. It is important that pediatricians know how to recognize the pediatric manifestations of this infection in order to correctly diagnose them and offer their patients appropriate guidance and treatment.

Manifestations of the human T-cell lymphotropic virus type I infection in childhood and adolescence

OBJETIVOS: Revisão da literatura sobre doenças relacionadas à infecção pelo vírus linfotrópico de células T humanas (HTLV-I) na infância e adolescência, focalizando clínica, diagnóstico, patogênese, evolução e tratamento. FONTES DOS DADOS: Literatura médica dos últimos 20 anos utilizando PubMed e MEDLINE e livros médicos especializados, com ênfase na dermatite infecciosa associada ao HTLV-I (DIH), na forma infanto-juvenil da mielopatia associada ao HTLV/paraparesia espástica tropical (HAM/TSP), na leucemia/linfoma de células T do adulto (ATL) e na uveíte associada ao HTLV-I. Palavras-chave usadas na pesquisa: dermatite infecciosa associada ao HTLV-I, mielopatia associada ao HTLV/paraparesia espástica tropical, leucemia/linfoma de células T do adulto, uveíte associada ao HTLV-I. SíNTESE DOS ACHADOS: A DIH é uma dermatite crônica, recidivante e infectada da infância que sempre envolve o couro cabeludo e que pode evoluir para HAM/TSP e ATL. A HAM/TSP é uma mielopatia crônica e incapacitante do adulto. Há 17 casos infanto-juvenis de HAM/TSP bem documentados na literatura, 12 dos quais em pacientes com DIH. Ao contrário da doença no adulto, essa forma é rapidamente progressiva. A ATL é uma leucemia/linfoma T do adulto, geralmente fatal. De 24 casos infanto-juvenis de ATL da literatura, 11 foram diagnosticados no Brasil. CONCLUSÕES: Essas doenças devem ser mais freqüentes na infância e adolescência do que indica a literatura. É aconselhável fazer sorologia para o HTLV-I em crianças e adolescentes com eczema crônico e recidivante, com sintomas e sinais de mielopatia ou com diagnóstico de leucemia/linfoma de células T. É importante que os pediatras saibam reconhecer as manifestações pediátricas dessa infecção para diagnosticá-las corretamente, propiciando aos pacientes orientação e tratamento adequados.

OBJECTIVES: To review the literature on diseases linked with infection by human T-cell lymphotropic virus type I (HTLV-I) in childhood and adolescence, with focus on clinical aspects, diagnosis, pathogenesis, progression and treatment. SOURCES: Medical literature published during the last 20 years identified using PubMed and MEDLINE and from specialized medical books, with emphasis on infective dermatitis associated with HTLV-I (IDH), on the juvenile form of HTLV-associated myelopathy/tropical spastic paraparesis (HAM/TSP), on adult T-cell leukemia/lymphoma (ATL) and on HTLV-I-associated uveitis. Keywords used to search databases were: HTLV-I-associated infective dermatitis, HTLV-I-associated myelopathy/tropical spastic paraparesis, adult T-cell leukemia/lymphoma, HTLV-I-associated uveitis. SUMMARY OF THE FINDINGS: IDH is a chronic, relapsing and infected dermatitis of childhood which always involves the scalp and which may progress to HAM/TSP and ATL. HAM/TSP is a chronic and incapacitating myelopathy of adults. There are 17 well-documented cases of HAM/TSP in children and adolescents in the literature, 12 of whom are patients with IDH. In contrast with the adult form of the disease, the juvenile form is rapid and progressive. ATL is a type of T-cell leukemia/lymphoma that affects adults and is generally fatal. Eleven of the 24 published reports of ATL in children and adolescents were diagnosed in Brazil. CONCLUSIONS: These diseases are likely to be more common in childhood and adolescence than the literature would suggest. It is advisable that serological testing be performed for HTLV-I in children and adolescents suffering from chronic and relapsing eczema, with signs and symptoms of myelopathy or with a diagnosis of T-cell leukemia/lymphoma. It is important that pediatricians know how to recognize the pediatric manifestations of this infection in order to correctly diagnose them and offer their patients appropriate guidance and treatment.

Infective dermatitis and human T cell lymphotropic virus type 1-associated myelopathy/tropical spastic paraparesis in childhood and adolescence.

BACKGROUND: Human T cell lymphotropic virus type 1 (HTLV-1)-associated infective dermatitis (IDH) is a chronic and recurrent eczema occurring during childhood and adolescence. HTLV-1-associated myelopathy/tropical spastic paraparesis (HAM/TSP) is a chronic myelopathy of adulthood, presenting with slowly progressive spastic paraparesis and sphincter dysfunction with mild sensory involvement. There are few reports describing an association between IDH and HAM/TSP. The objective of this study was to evaluate the occurrence of HAM/TSP in patients with IDH and in seropositive members of their families and to determine the blood levels of antibodies against HTLV-1 in patients with HAM/TSP. METHODS: Twenty patients with IDH and their seropositive mothers and siblings underwent clinical, neurological, and laboratory evaluations. The diagnosis of HAM/TSP was made in accordance with the World Health Organization criteria. RESULTS: Nine individuals had HAM/TSP (6 of the patients with IDH, 2 mothers, and 1 seropositive brother). In 3 families, > 1 individual had HAM/TSP. The serum antibody titers of the patients with HAM/TSP varied from 1 : 3.125 to 1 : 78.125. CONCLUSIONS: A strong association was observed between IDH and HAM/TSP. The familial clustering of both diseases suggests a genetic background. Serological screening for HTLV-1 in children with symptoms of myelopathy is essential in areas where HTLV-1 is endemic.