Human T-lymphotropic virus

Background

Microbiology

• Single-stranded negative-sense RNA virus in the Retroviridae family, genus Deltaretrovirus
• Four types:
  • HTLV-1, cause of adult T-cell leukemia-lymphoma and HTLV-associated myelopathy
  • HTLV-2, cause of HTLV-associated myelopathy
  • HTLV-3 and HTLV-4 are rare

Epidemiology

• HTLV-1 endemic to central Africa, the Caribbean basin, parts of South America, and southwestern Japan
• HTLV-2 endemic to indigenous people in the Americas, and Central African pygmies, as well as injection drug users in North America and Europe
• Transmitted sexually, parenterally (blood-borne), and vertically (mother-to-child, primarily through breastfeeding)
• Seroprevalence increases with age and is higher in women than men

Clinical Manifestations

Syndrome	HTLV-1	HTLV-2
Children
Infective dermatitis	yes	no
Lymphadenopathy	yes	yes
Adults
Adult T-cell leukemia-lymphoma	yes	no
HTLV-associated myelopathy	yes	yes
Infective dermatitis	yes	no
Polymyositis	possibly	unknown
Uveitis	yes	unknown
HTLV-associated arthritis	possibly	possibly
Sjögren syndrome	possibly	unknown
Strongyloidiasis	possibly	unknown
Pulmonary infiltrative pneumonitis	possibly	possibly
Invasive cervical cancer	possibly	unknown

Adult T-cell Leukemia-Lymphoma (ATL)

• Associated with HTLV-1, with a lifetime risk of 2 to 4% and latent period to 30 to 50 years
• Aggressive T-cell leukemia or lymphoma with four subtypes
  • Smoldering (5%), with ≥5% abnormal T-cells but otherwise normal differential, ± skin lesions ± pulmonary involvement
  • Chronic (19%), with lymphocytosis ≥4 and T-cells >3.5, ± lymphadenopathy/organomegaly/skin lesions/pulmonary involvement
  • Lymphoma/leukemia (19%), with lymphadenopathy without lymphocytosis; poor prognosis (median 10 months)
  • Acute (57%), with increased leukemic T cells and worsening clinical picture including hypercalcemia; poor prognosis (median 6 months)
• Presents with lymphadenopathy, hepatosplenomegaly, hypercalcemia, skin lesions, lytic bone lesions, and abnormal peripheral blood film with lymphocytosis and "flower cells"
• Skin findings can be either localized or diffuse as papules, nodules, plaques, erythematous patches, and diffuse erythroderma

HTLV-Associated Myelopathy

• Also called tropical spastic paraparesis
• Associated with HTLV-1 and -2, with lifetime prevalence of 4%
• Thought to be caused by an autoimmune response from HTLV-1 antibodies due to molecular mimicry
• Chronic progressive demyelinating disease affecting white matter and spinal cord
  • Unexplained central neurological disease with loss of pyramidal tract
  • Stiff gait progressing to spasticity and weakness, back pain, urinary incontinence, and impotence
  • Can have parasthesias and burning sensation
  • Impaired vibration sense
  • Hyperreflexia with clonus and upgoing plantar reflexes
• Usually insidious onset, but can be acute
• MRI may be normal or show atrophy of the spinal cord and non-specific brain lesions
• CSF can have mild lymphocytosis and mild protein elevation, including oligoclonal bands

Other Syndromes

HTLV-1

• Other neurological abnormalities, including sensory neuropathy, gait abnormality, bladder dysfunction, erectile dysfunction, amyotrophic lateral sclerosis, mild cognitive deficit, and motor neuropathy
• Infective dermatitis, which occurs in children who experience failure to thrive, eczema, and Gram-positive infections
• Polymyositis (HTLV-1-associated inflammatory myopathy of skeletal muscle)
• Large joint polyarthropathy
• Uveitis
• Infiltrative pneumonitis
• Chronic lympadenopathy
• Strongyloides hyperinfection
• Crusted scabies

HTLV-2

• Rarely, HAM and other neurological abnormalities

Differential Diagnosis

HTLV-Associated Myelopathy

• Multiple sclerosis, which should have a more waxing-waning course
• Spinal cord tumour
• Toxic neuropathy
• Malnutrition
• HIV
• Syphilis

Management

• Monitoring for signs or symptoms of leukemia, lymphoma, and neurological disease
• Management of ATL per Hematologi-Oncology service