Adult-onset Still’s disease complicated by Guillain-Barré syndrome

Guillain-Barré syndrome (GBS) is an acute polyneuropathy with a variable degree of weakness that reaches its maximal severity within 4 weeks. The disease is mostly preceded by an infection and generally runs a monophasic course. Both intravenous immunoglobulin (IVIg) and plasma exchange (PE) are effective in GBS. Rather surprisingly, steroids alone are ineffective. Mainly for practical reasons, IVIg usually is the preferred treatment. GBS can be subdivided in the acute inflammatory demyelinating polyneuropathy (AIDP), the most frequent form in the western world; acute motor axonal neuropathy (AMAN), most frequent in Asia and Japan; and in Miller-Fisher syndrome (MFS). Additionally, overlap syndromes exist (GBS-MFS overlap). About 10% of GBS patients have a secondary deterioration within the first 8 weeks after start of IVIg. Such a treatment-related fluctuation (TRF) requires repeated IVIg treatment. About 5% of patients initially diagnosed with GBS turn out to have chronic inflammatory demyelinating polyradiculoneuropathy (CIDP) with acute onset (A-CIDP). It is yet unknown whether GBS patients who remain able to walk ('mildly affected GBS patients'), or patients with MFS, also benefit from IVIg. Despite current treatment, GBS remains a severe disease, as about 25% of patients require artificial ventilation during a period of days to months, about 20% of patients are still unable to walk after 6 months and 3-10% of patients die. Additionally, many patients have pain, fatigue or other residual complaints that may persist for months or years. Pain can also be very confusing in making the diagnosis, especially when it precedes the onset of weakness. Advances in prognostic modelling resulted in the development of a simple prognostic scale that predicts the chance for artificial ventilation, already at admission; and in an outcome scale that can be used to determine the chance to be able to walk unaided after 1, 3 or 6 months. GBS patients with a poor prognosis potentially might benefit from a more intensified treatment. A larger increase in serum IgG levels after standard IVIg treatment (0.4 g/kg/day for 5 consecutive days) seems to be related with an improved outcome after GBS. This was one of the reasons to start the second course IVIg trial (SID-GBS trial) in GBS patients with a poor prognosis. This study is currently going on. The international GBS outcome study (IGOS) is a new worldwide prognostic study that aims to get further insight in the (immune)pathophysiology and outcome of GBS, both in children and adults. Hopefully these and other studies will further help to improve the understanding and especially the outcome in patients with GBS.

Previous studies have revealed that several micro-organisms, especially DNA viruses, have been associated with adult-onset Still's disease (AOSD). However, there are no studies on the relationship between the presence of viral infections in AOSD patients with disease occurrence and reactivation. In the present study, we aimed to investigate the presence of antibodies against virus, virus DNA load and nucleic acid sensors in AOSD patients. Anti-viral antibodies were measured by enzyme-linked immunosorbent assay (ELISA) in plasma samples from 100 AOSD patients and 70 healthy controls (HCs). The copy number of cytomegalovirus (CMV) DNA in 100 AOSD patients was detected by PCR. The expression levels of nucleic acid sensors interferon gamma-inducible protein 16 (IFI16) and absent in melanoma 2 (AIM2) in peripheral blood mononuclear cell (PBMC) and skin from AOSD patients and HCs were analyzed by PCR and immunohistochemistry. The levels of antibodies against CMV were significantly higher in AOSD patients compared to HCs. Moreover, the level of anti-CMV IgM antibody was significantly increased in patients with fever, sore throat, arthralgia and rash. CMV DNA was found in plasma of AOSD patients with disease new-onset and relapse. Furthermore, the copy number of CMV DNA significantly increased in patients with fever, sore throat, arthralgia and rash. And the significant associations of the CMV DNA level with the levels of leukocytes, erythrocyte sedimentation rate (ESR), C-reactive protein (CRP) and tumor necrosis factor-α (TNF-α) were observed. Moreover, we found an upregulation of cytoplasmic DNA-sensing receptor IFI16 and AIM2 in PBMC and skin from AOSD patients. In conclusion, our results showed that CMV infection may play a role in the initiation or amplification of inflammatory responses in AOSD.