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

  • Periodontitis

  • 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

• Studies from Brazil show that a subset of patients with chronic inflammation and HTLV-1 infections

  • May be asymptomatic

  • Are recognized as having an "intermediate syndrome" that may progress to full blown myelopathy

• 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, although considerable research in Japan on the use of the viral product tax in immunotherapy remains underway

• ATL managed with chemotherapy, with allogeneic stem cell transplantation and use of monoclonal antibodies

  • Mogamulizumab, an anti-CCR4 inhibitor

  • Anti-CD25 agents

  • Cerdulatinib, a dual SYK/JAK [spleen tyrosine kinase/Janus kinase] inhibitor

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

• Combination therapy with ...