Nishikai, M, Akiya, K, Tojo, T et al. · British journal of rheumatology · 1996 · DOI
This study looked at whether some people diagnosed with ME/CFS who also experience dry eyes and mouth might actually have a related condition called Sjögren's syndrome. Researchers tested one-third of ME/CFS patients with these dry symptoms against several official diagnostic criteria for Sjögren's syndrome and found they met the criteria. However, these patients tested negative for the antibodies typically found in Sjögren's syndrome, making them an unusual variant of the disease.
This finding is important because it suggests that some ME/CFS patients may have an overlooked or misdiagnosed autoimmune condition that could inform treatment approaches. Identifying potential Sjögren's syndrome in ME/CFS populations may help clinicians recognize secondary conditions and improve symptom management. Understanding disease overlap expands the biological framework for understanding ME/CFS heterogeneity.
This study does not prove that Sjögren's syndrome causes ME/CFS or vice versa—it only identifies overlap between conditions in a subset of patients. The seronegative nature of these cases means they differ from typical Sjögren's syndrome, so findings may not apply to classical SS populations. The cross-sectional design cannot establish whether sicca symptoms preceded CFS diagnosis or developed secondarily.
About the PEM badge: “PEM required” means post-exertional malaise was an explicit required diagnostic criterion for participant inclusion in this study — not that PEM was studied, observed, or discussed. Studies using criteria that do not require PEM (e.g. Fukuda, Oxford) are tagged “PEM not required”. How the atlas works →
The first block is for the primary paper and is the citation you should use in research work. The atlas-snapshot line only applies if you are specifically referring to this atlas’s reading of the paper on the date shown.
Primary citation
Nishikai, M, Akiya, K, Tojo, T, Onoda, N, Tani, M, & Shimizu, K (1996). 'Seronegative' Sjögren's syndrome manifested as a subset of chronic fatigue syndrome.. British journal of rheumatology. https://doi.org/10.1093/rheumatology/35.5.471
BibTeX
@article{mecfsatlas-nishikai-1996-seronegative-gren,
author = {Nishikai, M and Akiya, K and Tojo, T and Onoda, N and Tani, M and Shimizu, K},
title = {'Seronegative' Sjögren's syndrome manifested as a subset of chronic fatigue syndrome.},
journal = {British journal of rheumatology},
year = {1996},
doi = {10.1093/rheumatology/35.5.471},
note = {PubMed: 8646439},
url = {https://www.mecfsatlas.com/evidence/nishikai-1996-seronegative-gren},
}Atlas snapshot reference
ME/CFS Atlas. Generator v1 / Scanner v1.4 / policy v0.1. Accessed 2026-05-30. https://www.mecfsatlas.com/evidence/nishikai-1996-seronegative-gren
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