Antonio Carlos Martins Guedes

Epidemiology, Treatment, and Prevention of Human T-Cell Leukemia Virus Type 1-Associated Diseases

SUMMARY Human T-cell leukemia virus type 1 (HTLV-1), the first human retrovirus to be discovered, is present in diverse regions of the world, where its infection is usually neglected in health care settings and by public health authorities. Since it is usually asymptomatic in the beginning of the infection and disease typically manifests later in life, silent transmission occurs, which is associated with sexual relations, breastfeeding, and blood transfusions. There are no prospects of vaccines, and screening of blood banks and in prenatal care settings is not universal. Therefore, its transmission is active in many areas such as parts of Africa, South and Central America, the Caribbean region, Asia, and Melanesia. It causes serious diseases in humans, including adult T-cell leukemia/lymphoma (ATL) and an incapacitating neurological disease (HTLV-associated myelopathy/tropical spastic paraparesis [HAM/TSP]) besides other afflictions such as uveitis, rheumatic syndromes, and predisposition to helminthic and bacterial infections, among others. These diseases are not curable as yet, and current treatments as well as new perspectives are discussed in the present review.

Infecção e doença pelos vírus linfotrópicos humanos de células T (HTLV-I/II) no Brasil

HTLV-I/II infection is present in all regions of Brazil, but its prevalence varies according to the geographical area, being higher in Bahia, Pernambuco and Pará. It has been estimated that Brazil has the highest absolute number of infected individuals in the world. Blood donors screening and research conducted with special groups (indigenous population of Brazil, IV drug users and pregnant women) are the major sources of information about these viruses in our Country. HTLV-I causes adult T cell leukemia/lymphoma (ATLL), HTLV associated myelopathy/tropical spastic paraparesis (HAM/TSP), HTLV associated uveitis (HAU), dermatological and immunological abnormalities. HTLV-II is not consistently associated with any disease. Diagnosis is established using screening (enzymatic assays, agglutination) and confirmatory (Western blot, PCR) tests. The viruses are transmitted by blood and contaminated needles, by sexual relations and from mother to child, especially by breast feeding. Prevention efforts should focus on education of positive blood donors, infected mothers and IV drug users.

Dermatological Findings in 3 Generations of a Family with a High Prevalence of Human T Cell Lymphotropic Virus Type 1 Infection in Brazil

BACKGROUND Dermatologic manifestations are quite common in patients with adult T cell leukemia and lymphoma and patients with myelopathy and/or tropical spastic paraparesis associated with human T cell lymphotropic virus type 1 (HTLV-1). The aim of this study was to investigate dermatological findings presented by 30 members of a Brazilian family, half of whom are infected with HTLV-1 (as confirmed by enzyme-linked immunosorbent assay and Western blot). METHODS The subjects underwent dermatologic examination and laboratory assessment, which included the search for the HTLV-1 genome in peripheral blood mononuclear cells (PBMCs) by qualitative and semiquantitative polymerase chain reaction (PCR) and in skin samples by nested qualitative PCR and immunofluorescence assay. RESULTS We found that cases of xerotic dermatological alterations, including 3 cases of acquired ichthyosis, were more frequent among the infected patients (7 cases vs. none among the uninfected individuals; P=.0063). Other lesions observed in this group included impetigo, scabies, epidermal nevus, herpes zoster scar, rosacea, and juvenile acne. One HTLV-1-infected individual presented with concurrently acquired ichthyosis, impetigo, scabies, dermatophytosis, and seborrheic dermatitis. The PCR performed on PBMCs and skin samples from 24 patients confirmed the serological results in all cases. Additionally, the HTLV-1 proviral load was higher in patients with >1 skin lesion. Finally, HTLV-1 could be identified in the skin by immunofluorescence assay, which, by use of PCR as the gold standard, showed a sensitivity and specificity of 61.5% and 100%, respectively. CONCLUSIONS Altogether, these clinical and laboratory findings point to an HTLV-1 tropism toward the skin, even in HTLV-1 carriers without adult T cell leukemia/lymphoma or HTLV-1-associated myelopathy and/or tropical spastic paraparesis.

Lesões dermatológicas em pacientes infectados pelo vírus linfotrópico humano de células T do tipo 1 (HTLV-1)

Human T-cell Lymphotropic virus type I (HTLV-1) was the first human retrovirus described. Some time after its discovery a group of diseases were related to this virus, such as, adult T-cell leukemia lymphoma (ATLL), HTLV-1 associated myelopathy/tropical spastic paraparesis (HAM/TSP) and HTLV-1 associated uveitis (HAU). In the nineties, HTLV-1 was associated to a severe eczema of children, called infective dermatitis (ID). Since then, several other skin manifestations have been observed in HTLV-1-infected individuals, particularly in patients with ATLL or HAM/TSP. However, according to some reports, dermatologic lesions are also common in asymptomatic HTLV-1 carriers. Besides ID, all other skin lesions reported are nonspecific. The aim of this review is to outline the dermatologic manifestations reported in HTLV-1 infected patients, emphasizing the clinical and epidemiological value of these findings.

Isolation of Leishmania sp. from aqueous humor of a patient with cutaneous disseminated leishmaniasis and bilateral iridocyclitis (preliminary report)

The authors report an uncommon case of leishmaniasis with disseminated cutaneous lesions, systemic manifestations and ocular involvement, the latter being characterized by bilateral nongranulomatous iridocyclitis. The severity of the ophthalmologic lesions and its unresponsiveness to therapy (in spite of satisfactory regression of both systemic and cutaneous manifestations) lead to a needle aspiration of the anterior eye chamber content. From this material Leishmania sp was isolated. To our knowledge this is the first time that Leishmania has been shown into the ocular globe.

Increased Prevalence of Human T Cell Lymphotropic Virus Type 1 in Patients Attending a Brazilian Dermatology Clinic

Brazil may have the highest absolute number of individuals infected by human T cell lymphotropic virus type 1 (HTLV-1). It has been suggested that the prevalence of HTLV-1 is increased in patients with skin diseases. This study shows a higher prevalence of this infection in 1,229 patients attending a Brazilian dermatology clinic (0.7%) when compared to blood donors (0.22%). Of note, one additional patient tested positive for HTLV-2. The main skin diseases described in HTLV-1 seropositives were vitiligo (2 cases), dermatophytosis (2 cases), and leprosy (2 cases). A 23-year-old woman received a diagnosis of infectious dermatitis.

Identification of Leishmania chagasi from skin in Leishmania/HIV co-infection: a case report

A case of HIV/Leishmania co-infection presenting both visceral and cutaneous manifestations is reported. Leishmania infection was confirmed by conventional methods (parasitological approach and serology) and by PCR. Leishmania chagasi isolated from the skin lesion was characterized by enzyme electrophoresis and by restriction fragment length polymorphism of the internal transcribed spacer of the ribosomal gene.

Immunological profile of HTLV-1-infected patients associated with infectious or autoimmune dermatological disorders.

In the present study, the frequency, the activation and the cytokine and chemokine profile of HTLV-1 carriers with or without dermatological lesions were thoroughly described and compared. The results indicated that HTLV-1-infected patients with dermatological lesions have distinct frequency and activation status when compared to asymptomatic carriers. Alterations in the CD4+HLA-DR+, CD8+ T cell, macrophage-like and NKT subsets as well as in the serum chemokines CCL5, CXCL8, CXCL9 and CXCL10 were observed in the HTLV-1-infected group with skin lesions. Additionally, HTLV-1 carriers with dermatological skin lesions showed more frequently high proviral load as compared to asymptomatic carriers. The elevated proviral load in HTLV-1 patients with infectious skin lesions correlated significantly with TNF-α/IL-10 ratio, while the same significant correlation was found for the IL-12/IL-10 ratio and the high proviral load in HTLV-1-infected patients with autoimmune skin lesions. All in all, these results suggest a distinct and unique immunological profile in the peripheral blood of HTLV-1-infected patients with skin disorders, and the different nature of skin lesion observed in these patients may be an outcome of a distinct unbalance of the systemic inflammatory response upon HTLV-1 infection.

Increased expression of 2′5′oligoadenylate synthetase and double-stranded RNA dependent protein kinase messenger RNAs on affected skin of systemic sclerosis patients

Scleroderma or systemic sclerosis (SSc) is an autoimmune disorder of unknown aetiology characterized by excessive collagen synthesis and subsequent deposition on the skin and various internal organs. Interferons (IFNs) are well-known immunomodulators and inhibitors of collagen production. However, IFN therapy has been implicated in the development or exacerbation of several autoimmune diseases, including SSc. We analyzed the expression of several interferon-stimulated genes (ISGs) in affected skin of SSc patients (skin tissue and cultured skin fibroblasts). A set of ISGs (PKR, 2′5′OAS, M×A, and 6–16) was analyzed by real-time PCR using RNA extracted from cultured skin fibroblasts and skin tissue of normal individuals and SSc patients. Both normal and SSc affected skin cultured fibroblasts were sensitive to the IFN treatment and presented similar levels of all ISGs tested. However, PKR and 2′5′OAS mRNA expression levels were significantly higher in the affected skin tissue of SSc patients when compared to normal controls. These data suggest that the IFN system plays a role in the pathogenesis of SSc.

Basal Activation of Type I Interferons (Alpha2 and Beta) and 2'5'OAS Genes: Insights into Differential Expression Profiles of Interferon System Components in Systemic Sclerosis.

Objective. Systemic sclerosis (SSc) is a complex autoimmune disease in which interferons (IFNs) may play an essential role. We hypothesized that type I and III IFNs may be found in increased levels in patients and be responsible for SSc autoimmune status. Methods. Type I and III IFN and ISG basal expression profiles were measured by qPCR using RNA from PBMCs of patients and controls . Results. Type I IFNs are increased in SSc patients, while no induction of type III IFNs was detected. This induction cannot be related to IRF7, since no upregulation of this gene was seen on patients. Of the ISGs tested, 2′5′OAS levels were increased in patients, while 6–16 and MxA levels were not. Conclusions. While there is no indication of type III IFN induction, increased levels of type I IFNs may lead to abnormal regulation of ISGs that can be responsible for immune system alterations described for SSc.