Human T Cell Lymphotropic Virus (HTLV)

Key Features

• Retroviruses, types 1 and 2, that infect CD4 and CD8 T cells, respectively

• HTLV-1 infection

  • Associated with HTLV-1 adult T cell lymphoma/leukemia (ATL) and HTLV-1 associated myelopathy/tropical spastic paraparesis (HAM/TSP)

  • Infects approximately 20 million individuals worldwide

  • Endemic in southern Japan, Caribbean, much of the sub-Saharan Africa, South America, Eastern Europe, Oceania

• HTLV-2 is mainly found in native populations of South (1–58%), Central (8–10%) and North America (2–13%), as well as African pygmies tribes

• Virus is transmitted horizontally (sex), vertically (intrauterine, peripartum, and prolonged breast-feeding), and parenterally (injection drug use and blood transfusion)

• Transmission via organ transplant has been reported

• Disease may flare when biologic agents are used for rheumatoid conditions

Clinical Findings

• ATL presents with

  • Diffuse lymphadenopathy

  • Maculopapular skin lesions

  • Bronchoalveolar disorder

  • Organomegaly

  • Lytic bone lesions

  • Hypercalcemia

• Opportunistic infections, such as Pneumocystis jirovecii pneumonia and cryptococcal meningitis, are common

• HTLV-1 seropositivity is associated with

  • Increased risk of tuberculosis and Strongyloides stercoralis hyperinfection

  • Crusted scabies

  • Infective dermatitis

• HTLV positivity is associated with erythrocytosis, lymphocytosis (HTLV-2) and with thrombocytosis (HTLV-1).

• HTLV-2 appears to cause a myelopathy that is milder and slower to progress than HAM

• HTLV-1/HIV coinfection is associated both with higher CD4 counts and a higher risk of HAM

• Inflammatory states associated with HTLV-1 infection include

  • Arthropathy

  • Recurrent facial palsies

  • Polymyositis

  • Uveitis

  • Sicca

  • Sjögren syndrome

  • Vasculitis

  • Cryoglobulinemia

  • Infiltrative pneumonitis

  • Ichthyosis

• Bronchioloalveolar carcinoma is increased in frequency in the presence of HTLV-1

• HAM characterized by

  • Progressive motor weakness

  • Symmetric spastic paraparesis

  • Bilateral facial palsies

  • Falls

  • Nociceptive low back pain

  • Paraplegia with hyperreflexia

  • Bladder and sexual disorders (eg, dyspareunia, erectile dysfunction), sensory disturbances, constipation

Diagnosis

• The peripheral smear can show atypical lymphoid cells with basophilic cytoplasm and convoluted nuclei (flower cells)

• The diagnostic standard is evidence of clonal integration of the proviral DNA genome into tumor cell

• Identification of HTLV-1 antibodies supports the diagnosis

• An HTLV-1 provirus load in peripheral blood mononuclear cells and CSF cells, and an HTLV-1 mRNA load are proposed as markers of HAM risk and progression

• Serum neopterin levels may indicate disease activity

Treatment

• No vaccine or antiviral therapy currently exists for the prevention and treatment of HTLV infections

• Management of ATL consists mainly of

  • Chemotherapy (such as CHOP and EPOCH regimens), followed by allogeneic stem cell transplantation

  • Immunotherapies are increasingly used, including

    • Monoclonal antibodies (eg, the anti-CCR4 inhibitor mogamulizumab, anti-CD25 agents)

    • SYK/JAK (spleen tyrosine kinase/Janus kinase) inhibitors (eg, cerdulatinib and ruxolitinib)

    • PD-1/immune checkpoint inhibitors (eg, nivolumab)

• A chemotherapy regimen in Japan using eight different agents shows a higher response rate than traditional biweekly CHOP (40% vs 25%)

• Combination therapy with interferon-alpha has been used with success. A therapeutic vaccine is in early clinical trials

• Prophylaxis against infections is needed in ATL because patients show a profound immunodeficiency

• HAM treated with corticosteroids

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