Neurologic complications of HTLV-1: a review / Complicações neurológicas do HTLV: uma revisão HTLV-1

The human T-cell lymphotropic virus type 1 (HTLV-1) is a retrovirus that infects about 20 million people worldwide and causes immune-mediated diseases of the nervous system. The classical neurological presentation of HTLV-1 infection is the so-called HTLV-1-associated myelopathy/tropical spastic paraparesis (HAM/TSP). However, HAM/ TSP is not the only neurological outcome that can result from HTLV-1 infection. In this Review it is made an update on the many aspects of this important neurological condition, the HTLV-1 neurological complex.

O vírus linfotrópico de células T humanas tipo 1 (HTLV-1) é um retrovírus que infecta cerca de 20 milhões de pessoas em todo o mundo e causa doenças imunomediadas do sistema nervoso. A apresentação neurológica clássica da infecção pelo HTLV-1 é a chamada paraparesia espástica tropical / mielopatia associada ao HTLV-1 (HAM/TSP). HAM / TSP,no entanto, não é o único desfecho neurológico que pode resultar da infecção pelo HTLV-1. Nesta revisão, é feita uma atualização sobre vários aspectos desta importante condição neurológica, o complexo neurológico do HTLV-1.

Flower cells of tropical descent: a challenging case of adult T-cell leukemia/lymphoma.

BACKGROUND: Adult T-cell leukemia/lymphoma (ATLL) is an aggressive disease associated with human T-lymphotropic virus type 1 infection, with a very high prevalence in tropical areas but exceptionally rare in Europe and Western countries. CASE PRESENTATION: We describe a challenging case of ATLL in a young male patient with Brazilian origin and adopted as a child by an Italian family, presenting to our clinic with atypical T-lymphocytosis and life-threatening lung infections. CONCLUSIONS: Diagnosis of ATLL outside of endemic areas can be difficult, requiring a high index of clinical suspicion with careful evaluation of the patient's clinical history. Prognosis is affected by disease stage at presentation and degree of immunosuppression. Few effective treatments are available, although new molecular insights have highlighted the role of host immune response and immune checkpoint blockade inhibitors, given the overexpression of PD-L1 on lymphoma cells and on microenvironment cells.

Impacto da infecção por HTLV-1 nas manifestações clínicas e no tratamento de pacientes com estrongiloidíase / Impact of HTLV-1 infection on clinical presentations and treatment of strongyloidiasis patients

A estrongiloidíase é uma enfermidade que acomete cerca de 100 milhões de pessoas em todo mundo. Essa parasitose apresenta alta prevalência e tem maior gravidade clínica entre indivíduos imunossuprimidos, principalmente aqueles portadores do vírus linfotrópico de células T humana tipo 1 (HTLV). Este fato torna a coinfecção por esse vírus em pacientes parasitados por Strongyloides stercoralis um grave problema de saúde pública. O presente estudo teve por objetivo revisar os estudos sobre coinfecção por HTLV/S. stercoralis. Foi realizada busca eletrônica completa de dados disponíveis sobre a coinfecção entre o vírus e S. stercoralis. As publicações foram capturadas a partir das bases de dados PubMed e SciELO, sendo utilizados os seguintes descritores "vírus linfotrópico de células T humanas tipo 1", "HTLV-1", "S. stercoralis" e "estrongiloidiase". A infecção por HTLV em pacientes parasitados representa fator de risco para o desenvolvimento de estrongiloidíase grave e, nesses indivíduos, o tratamento recomendado deve ser realizado e monitorado para garantir o sucesso terapêutico.(AU)

Strongyloidiasis is a disease that affects approximately 100 million people worldwide. This parasitosis is highly prevalent and more clinically severe among immunosuppressed individuals, particularly those with Human T-lymphotropic virus 1 (HTLV-1). This fact makes the co-infection with this virus in patients parasitized by Strongyloides stercoralis a serious public health problem. The present study aimed at reviewing the studies of co-infection with HTLV/S. stercoralis. A complete electronic search for available data about the co-infection of the virusand S. stercoralis was performed. The publications were obtained from the databases PubMed and SciELO, with the following descriptors being used: "Human T-lymphotropic Virus type 1, "HTLV-1", S. stercoralis, and "strongyloidiasis". The infection with HTLV in infected patients is a risk factor for the development of severe strongyloidiasis, and for these individuals the recommended treatment should be performed and monitored to ensure therapeutic success.(AU)

Treatment of strongyloidiasis in HTLV-1 and Strongyloides stercoralis coinfected patients is associated with increased TNFα and decreased soluble IL2 receptor levels.

BACKGROUND: Human T cell lymphotropic virus type 1 (HTLV-1) infection has been associated with recurrent and disseminated strongyloidiasis and adult T cell leukemia/lymphoma (ATLL). METHODS: We compared immunological aspects and markers for ATLL in HTLV-1 patients with or without strongyloidiasis, and evaluated the influence of Strongyloides stercoralis treatment on the immune response and clinical outcomes of HTLV-1 infection. RESULTS: Levels of TNFα and IFNγ were lower in patients coinfected with HTLV-1 and S. stercoralis than in patients with HTLV-1 only (p < 0.05), and there was an increase in TNFα levels after anthelmintic treatment. Levels of sIL-2R were higher in patients with HTLV-1 coinfected with S. stercoralis and anthelmintic treatment decreased sIL-2R levels (p < 0.05). The one patient who developed ATLL was coinfected with S. stercoralis. CONCLUSION: These data show that helminthic infection has a modulatory role in HTLV-1 infection and that S. stercoralis may be a cofactor in the development of ATLL.

Therapeutic strategies in HTLV-I-associated myelopathy/tropical spastic paraparesis (HAM/TSP).

Human T lymphotropic virus type I (HTLV-I)-associated myelopathy/tropical spastic paraparesis (HAM/TSP) is chronic progressive myelopathy characterized by bilateral pyramidal tracts involvement with sphincteric disturbances. HTLV-I infects approximately 10-20 million people worldwide. There are large endemic areas in southern Japan, the Caribbean, Central and South America, the Middle East, Melanesia, and equatorial regions of Africa. Since the primary neuropathological feature of HAM/TSP is chronic inflammation caused by HTLV-I infection in the spinal cord, various treatments focusing on immunomodulatory or anti-viral effects were performed for HAM/TSP patients until now. However, there are still many of problems, such as insufficient effects, side effects and expensive costs in long-term treatments, etc., in these treatments. Therefore, an ideal therapeutic strategy against HAM/TSP is still not established yet. Although only a small proportion of HTLV-I-infected individuals develops HAM/TSP, neurological symptoms are certainly progressive once myelopathy develops, leading to deterioration of the quality of life. Therefore, we now need the therapeutic regimens to protect the development, or be able to commence the treatments as soon as possible after the development safely and inexpensively even in long-term course or lifelong course of treatment. As HTLV-I-infected CD4(+) T cells are the first responders in the immunopathogenesis of HAM/TSP, the ideal treatment is the elimination of HTLV-I-infected cells from the peripheral blood. In this article, we will review the therapeutic strategies against HAM/TSP up to now and will introduce our new therapeutic approach focusing on the targeting of HTLV-I-infected cells in HAM/TSP patients.

Onset of opportunistic infections in patients co-infected by HTLV-1 and HIV-1, with high CD4+ cells count

We reported two cases of patients with coinfection by human immunodeficiency virus (HIV) type 1 and human T-cell lymphotropic virus (HTLV) type I who developed opportunistic infections despite of relatively high CD4+ cells count. These cases showed clinical evidence to consider an earlier antiretroviral treatment for coinfected patientes regardless CD4+ cells counts.

Onset of opportunistic infections in patients co-infected by HTLV-1 and HIV-1, with high CD4+ cells count.

We reported two cases of patients with coinfection by human immunodeficiency virus (HIV) type 1 and human T-cell lymphotropic virus (HTLV) type I who developed opportunistic infections despite of relatively high CD4+ cells count. These cases showed clinical evidence to consider an earlier antiretroviral treatment for coinfected patientes regardless CD4+ cells counts.

[Exfoliative erythroderma and infective dermatitis in an infant infected with human T-lymphotropic virus type I (HTLV I)]. / Eritrodermia exfoliativa y dermatitis infecciosa en un lactante infectado por el virus linfotrópico humano-I (HTLV-I).

We report a HTLV-I positive infant, whose infection was confirmed by polymerase chain reaction. The infant presented with an acute, severe, generalized eczema, exfoliation and severe erythroderma that yielded to an acute proteic malnutrition and frequent staphylococcal infections, unresponsive to treatment, since the second month of life. Immunodeficiencies from other origin and other causes of erythroderma were ruled out. The histopathology studies and clinical course yielded to the diagnosis of infective dermatitis associated to HTLV-I. A review of the literature is performed.

Eritrodermia exfoliativa y dermatitis infecciosa en un lactante infectado por el virus linfotrópico humano-I (HTLV-I) / Exfoliative erythroderma and infective dermatitis in an infant infected with human T-lymphotropic virus type I (HTLV I)

We report a HTLV-I positive infant, whose infection was confirmed by polymerase chain reaction. The infant presented with an acute, severe, generalized eczema, exfoliation and severe erythroderma that yielded to an acute proteic malnutrition and frequent staphyloccocal infections, unresponsive to treatment, since the second month of life. Immunodeficiencies from other origin and other causes of erythroderma were ruled out. The histopathology studies and clinical course yielded to the diagnosis of infective dermatitis associated to HTLV-I. A review of the literature is performed.

Se presenta un niño infectado por virus HTLV-I por vía vertical, confirmado por reacción de polimerasa en cadena, quien, a partir del segundo mes de vida, presentó un cuadro de eccema agudo severo generalizado, que llegó a la eritrodermia y exfoliación masiva, provocando una desnutrición proteica aguda e infecciones repetidas por Staphylococcus aureus, de difícil manejo. Se descartaron inmunodeficiencias de otro origen, así como otras causas de eritrodermia. Posteriormente, de acuerdo con la evolución clínica y con las biopsias, se interpretó el cuadro como una dermatitis infecciosa asociada a HTLV-I. Se revisa la literatura en relación a la infección por HTLV-I.

Adult-onset infective dermatitis associated with HTLV-I. Clinical and immunopathological aspects of two cases.

Infective dermatitis associated with HTLV-I (IDH) is a chronic, infected childhood eczema. Two adult-onset cases of IDH were studied, one of which was associated with HAM/TSP. The patients were submitted to dermatological, neurological and pathological examination. Immunohistochemical studies were made using CD3, CD4, CD8, CD20, CD79a, and CD57 antibodies. Cytotoxic granules were investigated using granzyme B, perforin, and TIA. The patients presented infected erythematous, scaly lesions with mild itching and a good response to sulfamethoxazole/ trimethoprim. A differential diagnosis with atopic dermatitis (AD) and seborrheic dermatitis (SD) was made, based on: the distinctive morphology and distribution of the lesions, presence of exudative and infected lesions, and mild pruritus. The inflammatory infiltrate was composed predominantly of CD8+ lymphocytes that did not present cytotoxic granules. We concluded that IDH can begin in adulthood and may be associated with HAM/TSP. The immunohistochemical findings were different from those observed in AD and SD.

Multiple clinical manifestation of HTLV1 infection in a single patient

HTLV-1 infection is endemic in the Caribbean and several publications have reported the clinical disease entities seen in this population of patients. This case report is an account of a patient admitted to Kingstown General Hospital, St Vincent and the Grenadines, who had severe infective dermatitis, tropical spastic paraparesis (TSP) and Non-Hodgkin's Lymphoma (NHL). As far as we are aware, all three diseases have not been described in a single patient

Multiple clinical manifestation of HTLV1 infection in a single patient.

HTLV-1 infection is endemic in the Caribbean and several publications have reported the clinical disease entities seen in this population of patients. This case report is an account of a patient admitted to Kingstown General Hospital, St Vincent and the Grenadines, who had severe infective dermatitis, tropical spastic paraparesis (TSP) and Non-Hodgkin's Lymphoma (NHL). As far as we are aware, all three diseases have not been described in a single patient.

HTLV-I Associated infective dermatitis may be an indolent HTLV-I associated lymphoma

When present for a first time blood donation, a 28-year-old Brazilian white female reported a pruritic eczema of the scalp and retroauricular areas since childhood that had been frequently infected. Her mother had been diagnosed as having HTLV-I-associated myelopathy (HAM), and the patient was found to be a human T-lymphotropic virus type-I (HTLV-I) carrier. The patient had been breast-fed for 6 months. The patient had a complete examination, and a biopsy was taken from eczema in the retroauricular area. The byopsy indicated chronic lymphohistiocytic dermatitis with no abnormal lymphocystes. Eleven months later, the patient had an infliltration in the skin of the retroauricular area and a new biopsy revealed atypical lymphocytes. Nested polymerase chain reaction (PCR) was positive for HTLV-I and immunohistochemistry of the tissue at this time confirmed adult T-cell leukemia/lymphoma (ATLL). Retrospective immunohistochemistry showed that the first fragment submitted from the biopsy 11 months before was also compatible with the diagnosis of ATLL. This case fulfilled all major criteria for diagnosis of HTLV-I-associated infective dermatitis (HTLV-I-ID). We postulate that the patient has indolent ATLL associated with HTLV-I infective dermatitis since childhood. We recommended that tissue immunohistochemistry analysis be done in any patient with HTLV-associated infective dermatitis.

Linfoma cutáneo con compromiso pulmonar / Cutaneous lymphoma with pulmonary complication

Paciente varón de 31 años sin patología previa, que comenzó con cuadro de dermatitis, que no respondió a tratamiento esteroidal, generalizándose. Se realizó biopsia de piel informándose linfoma de células T; presentó masas pulmonares que se biopsiaron por broncoscopía en la que también apareció linfoma de células T. Dentro del estudio se confirmó serología positiva a HTLV-I. Se realizó quimioterapia, produciéndose neumotórax por necrosis de masas tumorales, que no se operó. Sobrevive por más de 33 meses con quimioterapia y aún está en control. Se comenta la asociación entre linfoma T e infección con virus HTLV-I y la situación actual en Chile de esta condición

Efecto del núcleo CMP forte en 46 pacientes con paraparesia espástica progresiva: estudio randomizado y ciego / Effect of CMP forte nucleus in 46 patients with progressive spastic paraparesis: randomized and blind study

Idiopatic or HTLV-1 associated progressive spastic paraparesis does not have a clear etiology or treatment. To assess the effects of a medication containing cytidinmonophosphate, uridintriphosphate and vitamin B 12 in the treatment of progressive spastic. Patients with the disease were randomly assigned to receive the Nucleus CMP forte (containing dysodic cytidinmonophosphate 5 mg,trisodic uridintriphosphate 3 mg and hydroxicobalamin 2 mg) tid or placebo during 6 months. Gait, spasticity, degree of neurogenic bladder and somatosensitive evoked potentials were assessed during treatment. Forty six patients aged 25 to 79 years old were studied, 24 were female and 29 HTLV-1 positive. Twenty two were treated with the drug and the rest with placebo. Gait and spasticity improved in 7 of 22 patients receiving the drug and 1 of 24 receiving placebo (p<0.05). Neurogenic bladder improved in 10 of 22 receiving the drug and 4 patients treated with the drug and in two of seven treated with placebo. The medication caused a modest improvement in patients with progressive spastic paraparesis and was free of side effects

Clinical characteristics of HTLV-1 associated dermato-polymyositis. Seven cases from Martinique.

Myositis linked to HTLV-1 is unfrequent. Over a period of 8 years, 14 patients with inflammatory myopathy were diagnosed in Martinique. Seven were seropositive for HTLV 1 antibody; the clinical and pathological data of whom are presented herein. Five patients presented with polymyositis, two with dermatomyositis. All seven patients had extra-muscular clinical features including neuropathy (4/7) and myelopathy (6/7), resulting in a quite peculiar clinical picture. Muscle biopsy showed a neurogenic process combined with myositic changes in 3/7 patients. Corticotherapy led to dramatic improvement in only one case, but with no sustained effect. HTLV 1 may be considered the etiological agent of this form of dermato-polymyositis, characterized by a clearly distinctive clinico-pathological picture, and a poor response to corticotherapy. As in the case of tropical spastic paraparesis/HTLV 1 associated myelopathy, careful assessment of non-steroidal therapy is now warranted.