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Anti-HMGCR myopathy overlaps with dermatomyositis-like rash: a distinct subtype of idiopathic inflammatory myopathy

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Abstract

Objective

To characterize the clinical and pathological features of anti-HMGCR myopathy.

Methods

The presence of anti-HMGCR antibody in the serum of 227 patients with idiopathic inflammatory myopathy (IIM) and 100 healthy control individuals was assessed by ELISA. All ELISA positive samples were retested by indirect immunofluorescence assay (IIFA) on HEK293 cells. The clinical findings, muscle pathological features, and treatment outcomes of patients with anti-HMGCR myopathy, along with comparisons between anti-HMGCR myopathy with and without dermatomyositis (DM)-like skin rashes, and among MSA-based subgroups were analyzed.

Results

We established an optimized ELISA cutoff for anti-HMGCR antibody positivity as ≥ 5.28 U. The overall concordance between ELISA and IIFA was 96.83%. Twenty-one out of 227 IIM patients were anti-HMGCR-positive by both assays. Of these 21 patients, 9 had DM-like skin rashes, and 16 showed remarkable muscle inflammation; 5 patients were juvenile-onset, and 2 received statin treatment. The muscle biopsies from these patients demonstrated variable muscle necrosis and T cell infiltration. Most anti-HMGCR-positive patients achieved favorable outcomes following prednisone and additional immunotherapies. The anti-HMGCR myopathy patients with DM-like rashes, compared to those without DM-like rashes, were younger and had a shorter disease duration.

Conclusions

Optimization of cutoff of anti-HMGCR antibody assays with confirmation by alternative assays can result in higher sensitivity and specificity. DM-like skin rashes and lymphocytic infiltrates were not rare in patients with anti-HMGCR myopathy. These findings suggest that while anti-HMGCR myopathy may overlap with DM-like rash, it is pathologically different from classic DM, and should be considered a distinct subgroup of IIM.

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Data availability

All data relevant to the study are either included in the article or will be shared at the request of any qualified investigator.

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Acknowledgements

The authors thank Inova Diagnostics for providing HMGCR ELISA kits and thank all the patients and healthy controls included in this study.

Funding

This work was supported by the Taishan Scholars Program of Shandong Province, the National Nature Science Foundation of China (No.81701238), 20 policy supported projects of collaborative innovation and achievement transformation in universities and research institutes of Jinan (2019GXRC050), Shandong Provincial Natural Science Foundation (Grant Number ZR2020QH167), Innovative Research Project of Undergraduate Clinical Medicine Teaching of Qilu Hospital, Shandong University (Grant Number 2019QLJY13), Qingdao Technology Program for Health and Welfare (20-3-4-42-nsh), Qingdao Applied Basic Research Source Innovation Plan (19-6-2-78-cg), and Qingdao Key Health Discipline Development Fund.

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Author notes

  1. Ying Hou and Kai Shao have contributed equally to this work.

Authors and Affiliations

  1. Research Institute of Neuromuscular and Neurodegenerative Diseases and Department of Neurology, Qilu Hospital, Cheeloo College of Medicine, Shandong University, No. 107 West Wenhua Road, Jinan, Shandong, China

    Ying Hou, Tingjun Dai, Wei Li, Yuying Zhao, Duoling Li & Chuanzhu Yan

  2. Department of Central Laboratory and Mitochondrial Medicine Laboratory, Qilu Hospital (Qingdao), Cheeloo College of Medicine, Shandong University, Qingdao, China

    Kai Shao & Chuanzhu Yan

  3. Key Laboratory of the Ministry of Education for Medicinal Resources and Natural Pharmaceutical Chemistry, National Engineering Laboratory for Resource Development of Endangered Crude Drugs in Northwest of China, College of Life Sciences, Shaanxi Normal University, Xian, China

    Yaping Yan

  4. Neuropathology Section, Department of Pathology and Molecular Medicine, McMaster University, Hamilton, ON, Canada

    Jian-Qiang Lu

  5. Inova Diagnostics, San Diego, CA, USA

    Gary L. Norman

  6. Brain Science Research Institute, Shandong University, Jinan, China

    Chuanzhu Yan

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  1. Ying Hou
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Contributions

YH and KS contributed equally to this work. CY designed and conceptualized study. YH and KS analyzed the data and drafted the manuscript. KS, YY, and GN tested antibodies. CY, YH, TD, WL, YZ, and DL, major role in the acquisition of data. CY, JL, and GN interpreted the data and revised the manuscript.

Corresponding author

Correspondence to Chuanzhu Yan.

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The study was performed in accordance with the Declaration of Helsinki and approved by the Ethics Committee of Qilu Hospital (Qingdao), Shandong University, China (KYLL-qdql2020019).

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All patients or their guardian gave their written informed consent for participation in the study and further publications.

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Hou, Y., Shao, K., Yan, Y. et al. Anti-HMGCR myopathy overlaps with dermatomyositis-like rash: a distinct subtype of idiopathic inflammatory myopathy. J Neurol 269, 280–293 (2022). https://doi.org/10.1007/s00415-021-10621-7

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