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

• The aetiology of idiopathic adhesive capsulitis (IAC) remains enigmatic. • Neurotropic viral infections cause characteristic pain and target tissue injury . • The epidemiology of IAC suggests a similar pathogenesis to herpes zoster infection . • The neuroanatomy of the shoulder capsule and synovium suggest these are a potential target for infection. • HERVs and reactivation of latent herpes infection may be relevant to IAC. 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.