Minor salivary gland inflammation in Devic’s disease and longitudinally extensive myelitis

Abstract

Devic's disease is often considered as a variant of multiple sclerosis (MS). However, evidence suggests that Devic's disease may be distinct from MS. Devic's disease can coexist with connective tissue diseases, particularly Sjögren's disease, but this association is rare with MS. Diagnosis of Sjögren's disease in patients with neurological symptoms is often difficult. During early stages of Sjögren's disease, patients may not fulfill all criteria for Sjögren's disease. A high percentage of patients with Sjögren's disease have inflammatory infiltrates in minor salivary glands, and this may be a reliable indicator of early or subclinical disease. We show high prevalence (80%) of salivary gland inflammation in Devic's disease and longitudinally extensive transverse myelitis (LETM). We diagnosed 16 patients with Devic's disease, and 2 of these satisfied criteria for Sjögren's disease as did 2 of 9 patients with LETM. Anti-SSA/B titers were infrequently elevated. Although most did not satisfy criteria for Sjögren's disease. 9 of 12 Devic's disease patients and 7 of 8 LETM patients had severe salivary gland inflammation. Thus: (1) patients with Devic's disease or with LETM who have positive labial biopsies but do not satisfy criteria for Sjögren's disease could have subclinical Sjögren's diseases. Alternatively, (2) as patients with Devic's disease have elevated titers of several autoantibodies, so there may exist a set of antibodies that react with antigens in minor salivary glands and cause inflammation. Minor salivary gland biopsy is more sensitive than anti-SSA/B serology in providing histological evidence for possible Sjögren's disease with CNS lesions.

Features of anti-aquaporin 4 antibody-seropositive Chinese patients with neuromyelitis optica spectrum optic neuritis

“…Coexisting autoimmune disorders, as well as sero-autoantibodies, were significantly more common in seropositive patients; SS and SLE were the most common CTDs and SSA and SSB were the most common autoantibodies in these patients. These findings are similar to previous studies which found that NMO could coexist with CTDs [43], particularly SS [44]; however, this association is rare in MS [45,46], as the prevalence of MS with SS ranges from 0 to 3.3 % [47]. Since AQP-4 Ab is a sensitive bio- CSF findings in NMO have been found to differ significantly from those of classical MS [48,49].…”

Neuromyelitis optica spectrum disorder in patients with connective tissue disease and myelitis

“…Definitive evidence for an association between NMO and SS has not yet been established, and mechanistic studies are needed to explain the potential connection between the 2 diseases. A recent study examined the prevalence of lymphocytic infiltration of labial salivary glands in patients with NMO or NMOSD without known CTD (21). Sixteen (80%) of 20 patients had a positive lip biopsy sample (focus score Ն1), but only 3 fulfilled established criteria for the diagnosis of SS.…”

“…It is of interest that AQP proteins are found in both of these areas (AQP-5 in salivary gland tissue and AQP-4 in CNS tissue). The AQP family of proteins shares significant structural homology, with approximately 50% of protein sequences shared between AQP-4 and AQP-5 (21). Therefore, epitope spreading represents a potential hypothesis to explain the development of autoimmunity against diverse organ systems in the subset of patients with concurrent SS and NMO/NMOSD.…”

Acute inflammatory myelopathies

“…Additional cases describing the co-occurrence of Sj€ ogren syndrome with NMO were reported prior to the general availability of the anti-AQP4 antibody assay (Mochizuki et al, 2000;Arabshahi et al, 2006;Gokcay et al, 2007). Subsequent to the commercial availability of the anti-AQP4 antibody test, multiple cases of Sj€ ogren syndrome-associated myelopathy have tested seropositive for the anti-AQP4 antibody (Hamnik et al, 2008;Javed et al, 2008;Sofat and Venables, 2008;Kim et al, 2009;Min et al, 2009;Wandinger et al, 2010;Kahlenberg, 2011). As with SLE, there appears to be overlap between NMO and Sj€ ogren syndrome.…”

“…That a minority of cases of Sj€ ogren syndrome-associated NMO tested seronegative for the NMO antibody is to be expected because the antibody, although highly specific, is not 100% sensitive for NMO (Javed et al, 2008;Chahin et al, 2009;Kim et al, 2009;Rabadi et al, 2010). As with SLE, the co-occurrence of these rare autoimmune diseases is unlikely to be due to chance.…”