Human T-cell lymphotropic virus type I (HTLV-I) is etiologically associated with adult T-cell leukemia/lymphoma (ATLL); tropical spastic paraparesis (TSP), a demyelinating neurological disorder; and HTLV-I-associated myelopathy (HAM). Two types of HTLV testing are available - antibody and molecular testing.
Tabs Content Clinical Overview Diagnosis
Indications for Testing
Adult T-cell leukemia/lymphoma (ATLL)
Fatigue, rash, lymphadenopathy, accompanied by lymphocytosis, hypercalcemia, and elevated lactate dehydrogenase (LDH)
Human T-lymphotropic virus type I (HTLV-I)-associated myelopathy/tropical spastic paresis (HAM/TSP)
Muscle pain, stiffness, and weakness (myalgias and myopathy)
Changes in bowel and/or bladder function
Other neurological signs and symptoms including peripheral paresthesias and dysesthesias, hyperreflexia, tremor, deafness, changes in vision
Criteria for Diagnosis
ATLL subtypes and diagnostic criteria (Gonçalves, 2010)
Laboratory Testing
Required evaluation for ATLL (Shimoyama, 1991)
Peripheral blood smear – ATLL cells present
HTLV-I testing
HTLV-I and -II antibodies by enzyme immunoassay (EIA)/Western blot
Initial testing
HTLV-II antibodies significantly cross-react to HTLV-I antigens
Populations such as parenteral drug abusers infected with HTLV-II may test positive for HTLV-I antibodies due to antibody cross-reactivity
No evidence to suggest HTLV-II causes human disease
Asymptomatic patients with HTLV-I antibodies
May be infected and should not donate blood
Often do not have ATLL or TSP and may not develop ATLL, HAM, or TSP
Repeat Western blot testing for indeterminate results – 2 weeks and/or 3 months after initial testing
HTLV-I, II polymerase chain reaction (PCR) – use to resolve untypable HTLV Western blot results when there is a strong suspicion of HTLV infection
Cerebrospinal fluid (CSF) studies
Protein – increased
Cell differential – lymphocytic pleocytosis
HTLV antibodies – positive
Oligoclonal bands – positive
IgG index – high
Bone marrow exam – generally not required
Histology
If diagnosis not obtained by above, perform lesion biopsy (if present)
Immunophenotyping
Minimum testing should include CD3, CD4, CD7, CD8, and CD25
Most ATLL cells lack CD7, CD52 with diminished CD3
CD4+ T-cells express CD2, CD5, CD25, CD45RO, CD29
CD7 and CD26 negative and CD3 expression diminished
Imaging Studies
Computed tomography (CT) – recommend neck, thorax, abdomen, and pelvis to exclude extranodal disease
Upper gastrointestinal endoscopy
Central nervous system evaluation by CT/magnetic resonance imaging (MRI) if neurologic signs evident
Prognosis
Poor prognosis risk factors
Serum LDH elevated
Serum calcium elevated
Age ≥40
Three or more lesions
Additional – thrombocytopenia , eosinophilia , high IL5, p53 or p16 deletion
Differential Diagnosis
HAM/TSP
Infectious
Multiple sclerosis Neurodegenerative
Amyotrophic lateral sclerosis
Friedreich ataxia
Myopathic
Paraneoplastic syndromes Inflammatory diseases
Malignant
Bony or epidural metastases
Primary intra/extra dural tumor
Nutritional
ATLL
Background
Epidemiology
Prevalence
15-20 million infected with HTLV-I worldwide
Endemic in Japan, Caribbean countries, Papua New Guinea, and sub-Saharan Africa
Age
ATLL – mean 60 years
HAM/TSP – 40s-50s
Sex
Transmission
Parenteral
Sexual
Breastfeeding
Lifetime risk of disease in presence of HTLV-I antibodies is low
ATLL – men have increased risk for progression compared to women
HAM/TSP – 0.5-4%
Organism
HTLV-I and HTLV-II are human type C retroviruses
Several subtypes exist that are geographically specific
HTLV-I – six subtypes (A-F)
Single-stranded RNA virus
Majority of human infections caused by HTLV-I
HTLV and AIDS
HTLV-I does not cause AIDS
Antibodies of HTLV-I have no relationship to antibodies of HIV type I (HIV-I)
Antibodies to HTLV-I do not imply excess risk for AIDS
HTLV-I virus is only remotely related to HIV-I, the AIDS virus
HTLV-I and HTLV-II are transmitted similarly to HIV-I and HIV-II
Individuals with HTLV-I or HTLV-II may be coinfected with HIV due to common risk factors (eg, sexual contact, IV drug use)
Risk Factors
Cellular blood products – most efficient mode of transmission
Breast milk – 20% of children of infected mothers will also become infected
Sexual contact – associated with unprotected sex, multiple partners, presence of genital sores, sex exchanged for drugs or money
Sharing of contaminated needles and syringes (eg, IV drug use)
HTLV-I positive mother – perinatal transmission may occur
Poverty
Clinical Presentation
ATLL
4 types – acute, chronic, smoldering, lymphoma
Acute ATLL most common
Rapidly fatal without treatment
Pulmonary complications, opportunistic infections, sepsis
Uncontrolled hypercalcemia may occur
TSP and HAM
Slowly progressive spastic paraparesis – disease is usually present 8-10 years before diagnosis
Prominent weakness of lower extremities with severe spasticity
Upper extremity weakness rare
Mild sensory impairment
Hyperreflexia is often present
Neuropathic pain is common in advanced stage
Bladder/bowel/sexual dysfunction later in disease – urinary tract infections, lithiasis, chronic pyelonephritis, chronic renal failure
Other associated diseases
ARUP Lab Tests
Screen for antibodies to HTLV-I and -II
Assay should not be used for blood donor screening, associated reentry protocols, or for screening human cell, tissues, and cellular and tissue-based products
Resolve untypable HTLV Western blot results when there is a strong suspicion of HTLV infection
Confirm antibody test results for a positive screening test (HTLV-I/II)
Assay should not be used for blood donor screening, associated reentry protocols, or for screening human cell, tissues, and cellular and tissue-based products
Aid in evaluation of hematopoietic neoplasms (ie, leukemia, lymphoma)
Specimens include bone marrow, whole blood, tissue, or fluid
Monitor therapy in patients with established diagnosis of hematopoietic neoplasms
Markers selected based on provided clinical history and/or previous test results
Use for assessment of multiple sclerosis
Detect unique IgG oligoclonal bands in CSF in conjunction with a matched serum specimen
Preferred test is oligoclonal band profile testing
Preferred test is oligoclonal band profile testing
Index test aids in workup of suspected multiple sclerosis
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Morrison BJ, Labo N, Miley WJ, Whitby D. Serodiagnosis for tumor viruses. Semin Oncol. 2015; 42(2): 191-206. PubMed
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Shimoyama M. Diagnostic criteria and classification of clinical subtypes of adult T-cell leukaemia-lymphoma. A report from the Lymphoma Study Group (1984-87). Br J Haematol. 1991; 79(3): 428-37. PubMed
Taylor G. Molecular aspects of HTLV-I infection and adult T-cell leukaemia/lymphoma. J Clin Pathol. 2007; 60(12): 1392-6. PubMed
Testing Algorithms Related Topics Last Update: November 2019
