“Idiopathic” adhesive capsulitis is caused by reactivation of latent neurotrophic virus involving peripheral nerves around the shoulder capsule: A hypothesis

IF 0.8 4区 医学 Q3 MEDICINE, RESEARCH & EXPERIMENTAL Medical hypotheses Pub Date : 2025-02-22 DOI:10.1016/j.mehy.2025.111604
William Zhan Xia , Rosa Ezquerro Cortes , Kuen Foo Chin , Carlos Cobiella , Simon Lambert
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Abstract

The aetiology and pathogenesis of so-called “idiopathic” adhesive capsulitis (IAC), otherwise known as “frozen shoulder” is not well understood. The condition has been compared to the contracture of Dupuytren’s disease, but this appears to be unlikely, and the many modalities of treatment appear to incompletely address the associated symptoms while not affecting the underlying course of the disorder. It is a debilitating and intrusive condition with a characteristic lengthy duration, sharing features with other conditions characterized by initial hyperaemia with subsequent fibrosis. We hypothesize that IAC is caused by reactivation of latent neurotrophic viruses involving peripheral nerves in the shoulder capsule and synovium, predominantly affecting the distribution of branches of the lateral pectoral nerve in which sympathetic efferents from the stellate ganglion pass to the rotator interval of the shoulder. We postulate that IAC is a low-grade infection from reactivation of latent neurotropic herpesvirus or other viruses with similar biological behaviors. This is based on the observations of increased expression of neural markers in shoulder capsule in early IAC, the epidemiological and clinical similarities between IAC and herpes zoster, the recognition of diverse clinical presentations of herpes zoster induced brachial plexopathy, and finally the significant association between herpesvirus infection and idiopathic pulmonary fibrosis and fibrogenic cancers. An improved understanding on the aetiology of IAC may guide future research on identifying the exact pathogen(s), revealing the pathogenesis, facilitate early diagnosis and prognostication of the disease, and more importantly may potentially improve treatment outcomes (and cure the disease) with antiviral therapy or immunomodulation and possibly decrease the incidence of the condition with antiviral vaccine in susceptible subjects.
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“特发性”粘连性囊炎是由累及肩囊周围周围神经的潜在神经营养病毒的再激活引起的:一种假设
所谓的“特发性”粘连性囊炎(IAC)的病因和发病机制,也被称为“肩周炎”,目前尚不清楚。这种情况已被比作Dupuytren病的挛缩,但这似乎是不可能的,许多治疗方式似乎不能完全解决相关症状,而不影响疾病的潜在病程。它是一种使人衰弱和侵入性的疾病,其特征是持续时间长,与其他以初始充血和随后的纤维化为特征的疾病相同。我们假设IAC是由累及肩囊和滑膜周围神经的潜伏神经营养病毒的再激活引起的,主要影响胸外侧神经分支的分布,其中来自星状神经节的交感神经传出传递到肩部的旋转间隙。我们推测IAC是由潜伏性嗜神经疱疹病毒或其他具有类似生物学行为的病毒再激活引起的低级别感染。这是基于观察到IAC早期肩关节囊神经标志物的表达增加,IAC与带状疱疹的流行病学和临床相似性,认识到带状疱疹引起的臂丛病的多种临床表现,以及疱疹病毒感染与特发性肺纤维化和纤维源性癌症之间的显著关联。对IAC病因学的进一步了解可以指导未来的研究,以确定确切的病原体,揭示发病机制,促进疾病的早期诊断和预后,更重要的是可以通过抗病毒治疗或免疫调节改善治疗结果(治愈疾病),并可能降低使用抗病毒疫苗的易感受试者的发病率。
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来源期刊
Medical hypotheses
Medical hypotheses 医学-医学:研究与实验
CiteScore
10.60
自引率
2.10%
发文量
167
审稿时长
60 days
期刊介绍: Medical Hypotheses is a forum for ideas in medicine and related biomedical sciences. It will publish interesting and important theoretical papers that foster the diversity and debate upon which the scientific process thrives. The Aims and Scope of Medical Hypotheses are no different now from what was proposed by the founder of the journal, the late Dr David Horrobin. In his introduction to the first issue of the Journal, he asks ''what sorts of papers will be published in Medical Hypotheses? and goes on to answer ''Medical Hypotheses will publish papers which describe theories, ideas which have a great deal of observational support and some hypotheses where experimental support is yet fragmentary''. (Horrobin DF, 1975 Ideas in Biomedical Science: Reasons for the foundation of Medical Hypotheses. Medical Hypotheses Volume 1, Issue 1, January-February 1975, Pages 1-2.). Medical Hypotheses was therefore launched, and still exists today, to give novel, radical new ideas and speculations in medicine open-minded consideration, opening the field to radical hypotheses which would be rejected by most conventional journals. Papers in Medical Hypotheses take a standard scientific form in terms of style, structure and referencing. The journal therefore constitutes a bridge between cutting-edge theory and the mainstream of medical and scientific communication, which ideas must eventually enter if they are to be critiqued and tested against observations.
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