Human T-Lymphotropic Virus Types I, II - HTLV I, II

Diagnosis

Indications for Testing

• Clinical presentation of adult T-cell leukemia/lymphoma (ATLL) or HTLV-I associated myelopathy (HAM) in patient with risk factors (eg, IV drug use, multiple sex partners, residence in endemic area) or undiagnosed myopathy or myelopathy
• ATLL subtypes and diagnostic criteria

Laboratory Testing

• Required evaluation for ATLL (according to Shimoyama criteria, 1991)
  • Peripheral blood smear – ATLL cells present
  • HTLV-I testing
  • HTLV-I antibody testing
    • HTLV-I and -II antibodies by EIA/Western blot is initial test
    • 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
    • Asymptomatic patients with HTLV-I antibodies
      • May be infected and should not donate blood
      • May not have ATLL or tropical spastic paraparesis (TSP) and may not develop ATLL, HAM, or TSP
    • Proviral loads correlate with infectivity
  • HTLV-I, II PCR – use to resolve untypable or indeterminate HTLV Western blot results when there is a strong suspicion of HTLV infection
• CSF studies
  • Protein – increased
  • Cell differential – lymphocytic pleocytosis
  • HTLV antibodies – positive
  • Oligoclonal bands – positive
• 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

• CT – recommend neck, thorax, abdomen, and pelvis to exclude extranodal disease
• Upper gastrointestinal endoscopy
• Central nervous system evaluation by CT/MRI if neurologic signs evident

Prognosis

• Poor prognosis risk factors
  • Serum LD elevated
  • Serum calcium elevated
  • Age ≥40
  • Three or more lesions
  • Additional – thrombocytopenia, eosinophilia, high IL5, p53 or p16 deletion

Differential Diagnosis

• HAM/TSP
  • Amyotrophic lateral sclerosis  
  • HIV
  • Multiple sclerosis
  • Myopathies
    • Inflammatory myopathies
    • Genetic myopathies
  • Myositis
  • Paraneoplastic syndromes
  • Polio
  • Parkinson disease
• ATLL
  • Acute lymphoblastic leukemia 
  • Acute myeloid leukemia 
  • Lymphoma
    • B-cell lymphoma
    • T/NK-cell lymphoma

Clinical Background

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 with HTLV-I-associated myelopathy (HAM).

Epidemiology

• Prevalence – 15-20 million infected with HTLV-I worldwide
  • Endemic in Japan, Caribbean countries, and sub-Saharan Africa
• Age – median is 50s
  • HAM/TSP – 30s-40s
• Sex
  • ATLL – M>F
  • HAM/TSP – M<F
• Transmission
  • Parenteral
  • Sexual
• Lifetime risk of disease if HTLV-I antibodies present is low
  • ATLL – 1-5% even in countries with high prevalence of HTLV-I (eg, Japan)
  • 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 subtype I
• HTLV and AIDS
  • HTLV-I does not cause AIDS
  • Antibodies of HTLV-I have no relationship to antibodies of human immunodeficiency virus 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)
• Suspicion of perinatal transmission
• 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 usually present 8-10 years before diagnosis
  • Prominent weakness of lower extremities with severe spasticity
    • Upper extremity weakness rare
    • Mild sensory impairment
    • Hyperreflex 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
    • Ichthyosis
    • Uveitis/keratoconjunctivitis
    • Sjögren syndrome, rheumatoid arthritis
    • Chronic alveolitis
    • Inclusion body myositis/polymyositis

Indications for Laboratory Testing

• Tests generally appear in the order most useful for common clinical situations
• Click on number for test-specific information in the ARUP Laboratory Test Directory

Click the plus sign to expand the table of additional tests.

Test Name and Number	Comments
Lactate Dehydrogenase, Serum or Plasma 0020006 Method: Quantitative Enzymatic
Calcium, Serum or Plasma 0020027 Method: Quantitative Spectrophotometry
Protein, Total, CSF 0020514 Method: Reflectance Spectrophotometry
Cell Count, CSF 0095018 Method: Cell Count/Differential
Oligoclonal Bands in CSF and Serum 0081135 Method: Qualitative Isoelectric Focusing/Electrophoresis

Diagnostic Algorithm

  Human T-Lymphotropic Virus Types I and II Testing Algorithm