Neurological complications of herpes zoster in adult patients receiving Janus kinase inhibitors: a systematic review

Authors

  • Luh Putu Indah Wahyuningtyas Mangusada Regional Hospital, Badung, Bali, Indonesia
  • Tjokorde Istri Amrita Rosvanti Department of Dermatology and Venerology, Mangusada Regional Hospital, Badung, Bali, Indonesia
  • Anak Agung Ari Agung Kayika Silayukti Department of Dermatology and Venerology, Mangusada Regional Hospital, Badung, Bali, Indonesia
  • Anak Agung Istri Saraswati Dewi Department of Dermatology and Venerology, Mangusada Regional Hospital, Badung, Bali, Indonesia
  • Made Hermina Laksmi Department of Dermatology and Venerology, Mangusada Regional Hospital, Badung, Bali, Indonesia

DOI:

https://doi.org/10.18203/issn.2455-4529.IntJResDermatol20262846

Keywords:

Herpes zoster, Janus kinase inhibitor, Tofacitinib, Post-herpetic neuralgia, Neurological complications

Abstract

Herpes zoster (HZ) is a recognized infectious adverse event among adult patients receiving Janus kinase (JAK) inhibitors. Although most cases are cutaneous, neurological complications such as post-herpetic neuralgia (PHN), meningitis, and encephalitis may cause substantial morbidity. This systematic review was conducted at the Dermatology and Venereology Department, Mangusada Regional Hospital, Badung, Bali, Indonesia. PubMed, Cochrane Library, and ScienceDirect were searched from 1 May to 15 May 2026 using terms related to HZ, neurological complications, and JAK inhibitors. Eligible studies included clinical trial safety analyses, observational studies, pharmacovigilance studies, and case reports. Seven studies were included and synthesized narratively because of clinical and methodological heterogeneity. Seven studies were included. Evidence consisted of one matched cohort study, one case report, three tofacitinib clinical safety analyses, one ruxolitinib cream safety analysis, and one pharmacovigilance study. Tofacitinib accounted for most systemic JAK inhibitor evidence. In ulcerative colitis studies, HZ occurred in 5.6-8.2% of tofacitinib-treated patients, with PHN reported in 0.3% and one case of HZ encephalitis/meningitis. In rheumatoid arthritis, PHN occurred after first HZ events in 6.9% of patients. A case report described severe HZ meningitis after tofacitinib, with residual visual loss and facial nerve paralysis. Ruxolitinib cream was associated with rare HZ and isolated PHN. Pharmacovigilance data detected PHN signals for tofacitinib, ruxolitinib, and baricitinib. Clinicians should anticipate HZ risk during JAK inhibitor therapy and promptly evaluate neurological symptoms.

 

References

Forbes HJ, Bhaskaran K, Grint D, Hu VH, Langan SM, McDonald HI, et al. Incidence of acute complications of herpes zoster among immunocompetent adults in England: a matched cohort study using routine health data. Br J Dermatol. 2021;184(6):1077-84. DOI: https://doi.org/10.1111/bjd.19687

Nagel MA, Niemeyer CS, Bubak AN. Central nervous system infections produced by varicella zoster virus. Curr Opin Infect Dis. 2020;33(3):273-8. DOI: https://doi.org/10.1097/QCO.0000000000000647

Yun H, Yang S, Chen L, Xie F, Winthrop K, Baddley JW, et al. Risk of Herpes Zoster in Autoimmune and Inflammatory Diseases: Implications for Vaccination. Arthrit Rheumatol. 2016;68(9):2328–37. DOI: https://doi.org/10.1002/art.39670

Nash P, Kerschbaumer A, Dörner T, Dougados M, Fleischmann RM, Geissler K, et al. Points to consider for the treatment of immune-mediated inflammatory diseases with Janus kinase inhibitors: a consensus statement. Ann Rheumatic Dis. 2021;80(1):71-87. DOI: https://doi.org/10.1136/annrheumdis-2020-218398

Winthrop KL, Vermeire S, Long MD, Panés J, Ng SC, Kulisek N, et al. Long-term Risk of Herpes Zoster Infection in Patients With Ulcerative Colitis Receiving Tofacitinib. Inflammatory Bowel Diseases. 2023;29(1):85-96. DOI: https://doi.org/10.1093/ibd/izac063

Winthrop KL, Melmed GY, Vermeire S, Long MD, Chan G, Pedersen RD, et al. Herpes Zoster Infection in Patients with Ulcerative Colitis Receiving Tofacitinib. Inflammatory Bowel Diseases. 2018;24(10):2258-65. DOI: https://doi.org/10.1093/ibd/izy131

Winthrop KL, Curtis JR, Yamaoka K, Lee EB, Hirose T, Rivas JL, et al. Clinical Management of Herpes Zoster in Patients with Rheumatoid Arthritis or Psoriatic Arthritis Receiving Tofacitinib Treatment. Rheumatol Ther. 2022;9(1):243-63. DOI: https://doi.org/10.1007/s40744-021-00390-0

Nakamura Y, Honda D, Takizawa N, Fujita Y. Herpes zoster meningitis in a rheumatoid arthritis patient treated with tofacitinib. BMJ Case Rep. 2022;15(3):e247276. DOI: https://doi.org/10.1136/bcr-2021-247276

Park S, Kim MK, Park SB, Kim DH, Byun YJ, Choi SA. Neurological Adverse Events Associated with the Use of Janus Kinase Inhibitors: A Pharmacovigilance Study Based on Vigibase. Pharmaceuticals. 2025;18(3):394. DOI: https://doi.org/10.3390/ph18030394

Rosmarin D, Pandya AG, Passeron T, Forman SB, Zdybski J, Amster M, et al. Long-Term Integrated Safety Summary of Ruxolitinib Cream in Phase 3 Clinical Trials of Patients with Vitiligo. Dermatol Ther (Heidelb). 2025;15(12):3703-16. DOI: https://doi.org/10.1007/s13555-025-01555-3

Moens U, Macdonald A. Effect of the Large and Small T-Antigens of Human Polyomaviruses on Signaling Pathways. IJMS. 2019;20(16):3914. DOI: https://doi.org/10.3390/ijms20163914

Gilden D, Cohrs RJ, Mahalingam R, Nagel MA. Varicella zoster virus vasculopathies: diverse clinical manifestations, laboratory features, pathogenesis, and treatment. The Lancet Neurol. 2009;8(8):731-40. DOI: https://doi.org/10.1016/S1474-4422(09)70134-6

Marra F, Lo E, Kalashnikov V, Richardson K. Risk of Herpes Zoster in Individuals on Biologics, Disease-Modifying Antirheumatic Drugs, and/or Corticosteroids for Autoimmune Diseases: A Systematic Review and Meta-Analysis. Open Forum Infect Dis. 2016;3(4):ofw205. DOI: https://doi.org/10.1093/ofid/ofw205

Dooling KL, Guo A, Patel M, Lee GM, Moore K, Belongia EA, et al. Recommendations of the Advisory Committee on Immunization Practices for use of herpes zoster vaccines. Am J Transplant. 2018;18(3):756-62. DOI: https://doi.org/10.1111/ajt.14683

15. Lal H, Cunningham AL, Godeaux O, Chlibek R, Diez-Domingo J, Hwang SJ, et al. Efficacy of an Adjuvanted Herpes Zoster Subunit Vaccine in Older Adults. N Engl J Med. 2015;372(22):2087-96. DOI: https://doi.org/10.1056/NEJMoa1501184

Winthrop KL, Nash P, Yamaoka K, Mysler E, Khan N, Camp HS, et al. Incidence and risk factors for herpes zoster in patients with rheumatoid arthritis receiving upadacitinib: a pooled analysis of six phase III clinical trials. Ann Rheum Dis. 2022;81(2):206-13. DOI: https://doi.org/10.1136/annrheumdis-2021-220822

Genovese MC, Smolen JS, Takeuchi T, Burmester G, Brinker D, Rooney TP, et al. Safety profile of baricitinib for the treatment of rheumatoid arthritis over a median of 3 years of treatment: an updated integrated safety analysis. Lancet Rheumatol. 2020;2(6):e347-57. DOI: https://doi.org/10.1016/S2665-9913(20)30032-1

Cohen SB, Tanaka Y, Mariette X, Curtis JR, Lee EB, Nash P, et al. Long-term safety of tofacitinib up to 9.5 years: a comprehensive integrated analysis of the rheumatoid arthritis clinical development programme. RMD Open. 2020;6(3):e001395. DOI: https://doi.org/10.1136/rmdopen-2020-001395

Anderson TC, Masters NB, Guo A, Shepersky L, Leidner AJ, Lee GM, et al. Use of recombinant zoster vaccine in immunocompromised adults aged 19 years or older: recommendations of the Advisory Committee on Immunization Practices-United States, 2022. MMWR Morb Mortal Wkly Rep. 2022;71(3):80-4. DOI: https://doi.org/10.15585/mmwr.mm7103a2

Chen YJ, Chen YM, Huang WN, Chen HH, Liao TL, Chen JP, et al. Herpes zoster in rheumatoid arthritis patients receiving tofacitinib: a single-center experience from Taiwan. Medicine (Baltimore). 2020;99(41):e22504. DOI: https://doi.org/10.1097/MD.0000000000022504

Downloads

Published

2026-08-21

How to Cite

Wahyuningtyas, L. P. I., Rosvanti, T. I. A., Silayukti, A. A. A. A. K., Dewi, A. A. I. S., & Laksmi, M. H. (2026). Neurological complications of herpes zoster in adult patients receiving Janus kinase inhibitors: a systematic review. International Journal of Research in Dermatology, 12(5), 471–480. https://doi.org/10.18203/issn.2455-4529.IntJResDermatol20262846

Issue

Section

Systematic Reviews