Inflammatory manifestations of HTLV-1 and their therapeutic options

Abstract

Human T lymphotropic virus type 1 (HTLV-1) is one of the most intriguing retroviruses infecting humans. Most commonly, infection remains undetected, since it does not cause obvious harm, yet in 4–9% of patients, this infection can be devastating, causing adult T-cell leukemia/lymphoma and/or HTLV-1 associated myelopathy/tropical spastic paraparesis (HAM/TSP). This review concentrates on all inflammatory aspects of HTLV-1 infection: HAM/TSP, HTLV-1 associated uveitis, HTLV-1 associated conjunctivitis, sicca syndrome and interstitial keratitis, HTLV-1 associated Sjögren’s syndrome, Hashimoto’s thyroiditis and Graves’ disease, HTLV-1 associated pulmonary disease, infective dermatitis associated with HTLV-1, HTLV-1 associated inflammatory myositis and HTLV-1 associated arthritis. With the exception of HAM/TSP treatment, studies of these conditions are sparse and even for HAM/TSP, the level of evidence is limited. While control or elimination of infection remains a goal, most therapy beyond symptomatic management is directed at the immune response to HTLV-1.

Keywords::

• arthritis
• Graves’
• HAID
• HAM/TSP
• Hashimoto
• HAU
• HTLV
• infective dermatitis
• inflammation
• keratitis
• polymyositis
• Sjögren’s
• thyroiditis
• uveitis

Acknowledgement

The authors would like to thank P Roberts for creating the figures for this manuscript.

Financial & competing interests disclosure

GP Taylor is supported by the Imperial NIHR Biomedical Research Centre. P Roberts acted as the authors’ medical illustrator and was reimbursed by F Martin’s research funds. The authors have no other relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript apart from those disclosed.

No writing assistance was utilized in the production of this manuscript.

Key issues

• Human T lymphotropic virus type 1 (HTLV-1) causes chronic inflammation in many different types of human tissue.

• Local and systemic host versus pathogen interaction drive inflammation.

• HTLV-1 associated myelopathy/tropical spastic paraparesis is the most commonly reported HTLV-1 associated inflammatory disease (HAID), affecting disproportionately women of older age.

• HTLV-1 proviral DNA level, HBZ protein expression and its low antigenicity play a role in driving inflammation.

• There is currently no evidence-based treatment to prevent HAID from developing or progressing.

• Worldwide, corticosteroids are most commonly prescribed in HAID, although no randomized controlled trial to date has shown its efficacy.

• International collaborations and large enough state-of-the-art randomized controlled trials are needed to discover efficient novel and/or repurposed treatment for HAID.

Notes