title: Curvilinear bodies are associated with adverse effects on muscle function but not with hydroxychloroquine dosing.
abstract: The clinical significance of curvilinear bodies (CB) seen in association with hydroxychloroquine (HCQ) therapy is uncertain. Patients with CB on muscle biopsy performed between 2006 and the present were identified, and their clinical features including body mass index and cumulative HCQ dose were recorded. A control group of 16 patients with idiopathic inflammatory myositis (IIM) on HCQ at time of biopsy but without evidence of CB was identified. Nineteen patients with CB were identified; details were available for 18. Among patients with CB, 7/18 also had IIM. Seven out of ten patients with CB who did not have IIM or MHCI/II expression had proximal weakness; 7/11 had raised serum creatinine kinase (CK) levels. There was no difference in body weight (p = 0.47), body mass index (p = 0.93), cumulative HCQ dose (p = 0.52) or cumulative dose adjusted for body weight (p = 0.39) or body mass index (p = 0.32) between patients with CB and controls. Patients with CB had lower median CK levels than controls (p = 0.034). Weakness was present in 12/17 patients and 12/16 controls (p = 1.0). Concurrent proton-pump inhibitors were co-prescribed in 12/18 (67 %) patients with CB and in 6/16 (38 %) controls (p = 0.17). Development of CB does not appear to be related to cumulative HCQ dose or body weight. Patients with CB frequently have muscle weakness in the absence of MHC1 expression suggesting a role for non-immune mechanisms of muscle injury. A high proportion of patients with CB are co-prescribed proton-pump inhibitors raising the possibility that co-prescription of both agents may disrupt lysosomal function and adversely affect muscle function.
authors.affiliation: University of Adelaide, North Tce, Adelaide, SA, 5000, Australia.
authors.forename: Thomas
authors.initials: T
authors.lastname: Khoo
authors.affiliation: Anatomical Pathology, SA Pathology, Adelaide, SA, 5000, Australia.
authors.forename: Sophia
authors.initials: S
authors.lastname: Otto
authors.affiliation: Anatomical Pathology, SA Pathology, Adelaide, SA, 5000, Australia.
authors.forename: Caroline
authors.initials: C
authors.lastname: Smith
authors.affiliation: Anatomical Pathology, SA Pathology, Adelaide, SA, 5000, Australia.
authors.forename: Barbara
authors.initials: B
authors.lastname: Koszyca
authors.affiliation: Rheumatology Department, The Queen Elizabeth Hospital, 28 Woodville Rd, Woodville South, SA, 5011, Australia.
authors.forename: Sue
authors.initials: S
authors.lastname: Lester
authors.affiliation: University of Adelaide, North Tce, Adelaide, SA, 5000, Australia.
authors.forename: Peter
authors.initials: P
authors.lastname: Blumbergs
authors.affiliation: University of Adelaide, North Tce, Adelaide, SA, 5000, Australia. vidya.limaye@sa.gov.au.|Rheumatology Department, Royal Adelaide Hospital, North Tce, Adelaide, SA, 5000, Australia. vidya.limaye@sa.gov.au.
authors.forename: Vidya
authors.initials: V
authors.lastname: Limaye
mesh_terms: D018501:Antirheumatic Agents / Q000009:adverse effects* / Q000627:therapeutic use; D016208:Databases, Factual; D006801:Humans; D006886:Hydroxychloroquine / Q000009:adverse effects* / Q000627:therapeutic use; D018908:Muscle Weakness / Q000139:chemically induced* / Q000473:pathology; D018482:Muscle, Skeletal / Q000473:pathology*; D009220:Myositis / Q000188:drug therapy* / Q000473:pathology
chemical_list: D018501:Antirheumatic Agents; D006886:Hydroxychloroquine
keywords: Curvilinear bodies; Hydroxychloroquine; Inflammatory myositis; Muscle biopsy