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3.13eP Hydroxychloroquine skeletal muscle toxicity in a referral biopsy cohort: light microscopic and ultrastructural features
Abstract   Peer reviewed

3.13eP Hydroxychloroquine skeletal muscle toxicity in a referral biopsy cohort: light microscopic and ultrastructural features

Osorio Lopes Abath Neto, Erica Fossee, Melissa Mejia-Bautista, Kathryn Eschbacher and Steven Moore
Neuromuscular disorders : NMD, Vol.67(Suppl 1), 106980
09/29/2026
DOI: 10.1016/j.nmd.2026.106980

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Abstract

Hydroxychloroquine (HCQ) skeletal muscle toxicity is suggested in biopsy evaluations by demonstrating vacuolar pathology on light microscopy (LM) and curvilinear bodies on electron microscopy (EM), but recognition may be complicated by variable histopathologic expression and limited sampling. We analyzed a cohort of 17 skeletal muscle biopsies from HCQ-treated patients, all demonstrating curvilinear bodies on EM. The median age was 56 years (range 20-76). There was a female predominance (13/17). Overt vacuolar pathology was observed by LM in 7/17 cases; subtle or rare vacuoles were seen in 6/17; and no vacuolar changes were present in 4/17. Additional LM features included myonecrosis and regeneration (9/17), nuclear internalization (8/17), and COX-negative fibers in excess of expected for age (4/17). Lymphocytic infiltrates were present in a minority of cases (4/17). On EM, all cases showed curvilinear bodies, frequently accompanied by autophagic vacuoles (15/17) and myeloid bodies (9/17). Based on integrated diagnostic reports, 10/17 biopsies were interpreted as HCQ-predominant myopathy, while 6/17 showed overlapping pathology including neurogenic atrophy or features of inflammatory, necrotizing, or mitochondrial myopathy. One case was most consistent with inclusion body myositis with associated HCQ-related ultrastructural changes. These findings show that HCQ toxicity is often an ultrastructural diagnosis, with LM pathology ranging from classic vacuolar myopathy to minimal or nonspecific abnormalities. Moreover, the ultrastructural changes of HCQ toxicity frequently coexist with other pathologic processes, which can complicate biopsy interpretation. The absence of overt vacuolar changes on LM should not exclude consideration of HCQ toxicity when exposure is known; EM evaluation is important in this setting.

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