May 04, 2012
Years published: 2008, 2012
NORD gratefully acknowledges Marco A. Lima, MD, PhD, Researcher, Instituto de e Pesquisa Clinica Evandro Chagas/FIOCRUZ, Rio de Janeiro, Brazil, for the preparation of this report.
HTLV-I was first isolated in 1980 from a patient originally thought to have a cutaneous lymphoma. It became clear that it was a distinct form of lymphoma, which was designated as acute T-cell leukemia/ lymphoma (ATL). Some years later, different groups in Martinique and Japan described an association between a chronic disease of the spinal cord and HTLV-I infection, which was later named HTLV-I associated myelopathy/tropical spastic paraparesis (HAM/TSP). Since then, several other conditions have been linked to HTLV infection.
It is estimated that between 10 and 20 million people are infected by HTLV-I in the world. Only 0.25-2% of the infected individuals will develop a progressive neurologic disease named HTLV-I associated myelopathy/tropical spastic paraparesis (HAM/TSP). Approximately 2-5% of HTLV-I carriers will develop ATL. More rarely, HTLV-I may lead to arthropathy, uveitis (inflammation of the eye), pneumonitis and thyroid problems. Areas of the world that are endemic to the HTLV-1 virus are the Caribbean, southern Japan, equatorial Africa, Middle East, South America, and Melanesia.
HAM/TSP usually has an insidious onset and chronic evolution. Initial symptoms are subtle and include gait problems, unexplained falls, low back pain, constipation, urinary urgency/incontinence and numbness or pain in the lower limbs. Over the years, progressive leg weakness ensues followed by the exacerbation of the urinary and sensory symptoms. The prognosis of the neurological disability is variable. While some patients are still ambulatory after one or two decades of disease, others may be confined to a wheelchair months after onset of disease.
HTLV-I-induced ATL has four different subtypes: acute, lymphomatous, chronic and smoldering. Each of them has a distinct clinical picture and evolution. A combination of skin and bone lesions, pulmonary infiltrates, elevation of serum calcium, enlargement of the liver, spleen and lymph nodes, and opportunistic infections may be present.
The transmission of HIV (the virus responsible for AIDS) and HTLV-Type I infection are similar. Infection can occur by sexual contact with an infected individual, through sharing of contaminated needles and syringes by intravenous drug users, or as the result of a transfusion of contaminated blood. Mother to child transmission may happen through perinatal exposure or most often through breast-feeding. The intrauterine transmission is very rare.
The cause of HAM/TSP has not been completely understood to date, since most infected individuals will never develop any symptoms or signs of disease. Theories include a direct effect of the virus on the central nervous system or an autoimmune process. In ATL, there is a disordered clonal expansion of blood cells called CD4+ T lymphocytes, which are infected by the virus.
Populations in the endemic areas around the world, including the Caribbean, southern Japan, equatorial Africa, Middle East, South America and Melanesia, are at a higher risk as are immigrants from such areas. Women are infected at a 2:1 proportion.
ATL is more common in patients who acquired HTLV-I infection during the perinatal period, with men having a threefold higher risk when compared to women. The latency between infection and development of symptoms is longer than 20 years in most ATL cases. HAM/TSP usually develops in the fourth or fifth decades but onset at extremes of age is observed. The latency period of HAM/TSP is shorter than in ATL, and women are more affected.
The diagnosis of HTLV-I infection is usually made by detection of antibodies against the virus in the blood or cerebrospinal fluid. In some cases, techniques that detect HTLV-I genome in infected cells may be necessary.
Concerning HAM/TSP, many HTLV-I infected individuals remain asymptomatic throughout their lives, beyond the positive laboratory findings of HTLV-I infection. Thus, it is necessary to rule out the presence of typical symptoms and exclusion of other disorders than can present in the same way (other infections, vitamin deficiencies, genetic disorders and compression of the spinal cord).
ATL is diagnosed based on the clinical picture, evidence of HTLV-I integration into host cells, peripheral blood analysis and biopsy of affected sites. Atypical lymphocytes named flower cells may be present on examination of blood smears. Elevation of serum calcium (hypercalcemia) is common.
In endemic areas, screening of candidate blood donors decreases the number of new infections in the population. Screening pregnant women and avoiding breastfeeding can reduce maternal transmission. Condom use offers protection against sexual transmission.
Several drugs have been used in the treatment of HAM/TSP including Interferon, danazol, high dose vitamin C, azatioprine, antivirals employed in treatment of HIV infection (zidovudine and lamivudine), valproic acid among others, but results were disappointing. High dose steroids might provide transient improvement in early stages of disease.
Although there is no specific treatment to date, relief of symptoms is a crucial aspect of the care of affected individuals. Spasticity (stiffness) can be treated with relaxant drugs (diazepam, baclofen), botulinic toxin injection and physical therapy. Anticholinergic drugs or urinary catheters are effective for urinary incontinence/urgency. Stool-softeners and laxants are commonly used for constipation.
The treatment of pain and other sensory symptoms such as tingling sensation (paresthesias) is dictated by their quality and severity and may include anti- inflammatory, antidepressants and antiepileptic drugs. Coordinated efforts of a team of specialists consisted of neurologists, infectious disease specialists, urologists, physical therapists and other healthcare professionals are usually necessary for comprehensive care.
Treatment of ATL includes the combination of interferon and zidovudine, intensive chemotherapy and allogenic haematopoietic stem cell transplantation. Prognosis depends on the ATL subtype. While chronic subtype has a relatively good prognosis, the median survival in acute subtype is less than one year in most series.
Information on current clinical trials is posted on the Internet at www.clinicaltrials.gov. All studies receiving U.S. government funding, and some supported by private industry, are posted on this government web site
For information about clinical trials being conducted at the NIH Clinical Center in Bethesda, MD, contact the NIH Patient Recruitment Office:
Tollfree: (800) 411-1222
TTY: (866) 411-1010
For information about clinical trials sponsored by private sources, contact:
Recent studies have examined the role of new approaches such as targeted therapy against surface molecule on ATLL cells, retinoid derivatives, and the proteasome inhibitor bortezomib but their efficacy remains to be established.
Contact for additional information about research into and treatment for HTLV Type 1 and II:
Marco A. Lima, MD, PhD
Instituto de e Pesquisa Clinica Evandro Chagas-FIOCRUZ
Rio de Janeiro, Brazil, 21040-900
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