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Clinical Manifestations of HTLV-1 Infection
Abstract & Commentary
By Dean L. Winslow, MD, FACP, FIDSA, Chief, Division of AIDS Medicine, Santa Clara Valley Medical Center; Clinical Professor of Medicine, Stanford University School of Medicine, Section Editor, HIV, is Associate Editor for Infectious Disease Alert.
Source: Caskey MF, et al. Clinical manifestations associated with HTLV type 1 infection: A cross-sectional study. AIDS Res Hum Retroviruses 2007; 23: 365-371.
Synopsis: A cross-sectional study of 115 HTLV-1 infected Brazilian blood donors without myelopathy and 115 age — and sex-matched seronegative controls was performed. Compared with controls, HTLV-1 infected donors were more likely to report arm or leg weakness, hand or foot numbness, arthralgias, nocturia, erectile dysfunction or to have gingivitis, periodontitis and dry oral mucosa.
This was a retrospective small case control study that looked at 115 HTLV-1 infected patients from the state of Bahia in Northeastern Brazil who were originally found to be HTLV-1 infected at the time of blood donation and were later followed in a special clinic. Patients with HTLV-1 associated myelopathy/tropical spastic paraparesis (HAM/TSP) were excluded. 115 age and sex matched controls were recruited from one of the 3 major blood banks in the region and were HTLV-1 negative. All subjects completed a standardized questionnaire and HTLV-1 patients underwent examination by a dentist and one of 3 neurologists. The controls were evaluated at the blood bank by an internist. Matched univariate odds ratios (ORs) were calculated using logistic regression analysis. No adjustment was made for multiple comparisons.
Cases were found to be more often black or mulatto and significantly more likely to have a lower educational level than controls. Using adjustment for income level a few symptoms appeared to be associated with HTLV-1 infection including hand and foot numbness, arm and leg weakness, arthralgia, gingival bleeding, dry eyes, and erectile dysfunction. Interestingly, physical findings of weakness or hyperreflexia or objective evidence of synovitis were not seen more frequently in cases vs. controls. However, gingivitis, periodontitis, and dry mucosa were observed more frequently in cases.
HTLV-1 infects a significant proportion of the populations in certain areas of the world including the Caribbean, South America, Western sub-Saharan Africa, southern Japan, and New Guinea. While infection is endemic in these areas, only 3-5% of HTLV-1 infected individuals ever show manifestations of disease over the course of a lifetime. The best known of these manifestations include adult T-cell leukemia/lymphoma (ATL- which almost certainly represents a direct oncogenic effect of the retrovirus and usually takes several decades to develop) and HAM/TSP (which has been shown to develop in as short of time as 18 weeks after infection and may represent an autoimmune response to infection). Other fairly well-established associations include infective dermatitis and persistent lymphadenopathy in children as well as infective dermatitis, polymyositis, and uveitis in adults. A variety of "possible" associated clinical manifestations include arthritis, Sjögren's Syndrome, and nonspecific pneumonitis.
This small study purports to show possible associations between HTLV-1 infection and a number of fairly vague symptoms and nonspecific physical findings. The findings are intriguing in that on superficial examination the data appear to support an association between HTLV-1 infection and vague neurologic symptoms which could possibly represent either early or "forme fruste" HAM/TSP. Unfortunately the design of the study makes interpretation of the findings difficult. This includes the fact that neither the patients nor the examining physicians were blinded as to HTLV-1 status, the patients were already seeking care in a special clinic, and different physicians were performing the examinations; all of whom had knowledge of the patients' serostatus. In addition, the small numbers of controls selected (while matched for age and sex) were clearly different from the patients in terms of race, educational and socioeconomic status. Numerous studies from North America, Great Britain, and Europe have shown significantly greater burden of nonspecific symptoms as well as disease in people from lower socioeconomic status.
If you are studying for the board examinations, if there is a question regarding clinical manifestations of HTLV-1 infection, I feel the only definite "correct" answers remain ATL and HAM/TSP.