doi: medRxiv preprint NOTE: This preprint reports new research that has not been certified by peer review and should not be used to guide clinical practice.

Background Primary Sjögren Syndrome (pSS) is an autoimmune disorder characterized by a chronic lymphocytic and plasmacellular infiltration of exocrine glands and extraglandular features including both peripheral nervous system and central nervous system involvement. However, the diagnosis of pSS with neurologic involvement is sometimes difficult and specially central nervous system manifestations have been rarely described. Objectives To perform an observational retrospective cross-sectional case–control study to evaluate prevalence, clinical patterns and outcomes of neurological involvement in a cohort of pSS patients followed up in a single centre. Methods A total of 91 pSS patients (88 females, 3 male) with a mean age 47,6 years, diagnosed according to the 2002 criteria proposed by the American–European Consensus Group, were evaluated for neurological involvement after exclusion of secondary causes. Demographic, clinical, immunological data were compared between patients with and without neurological involvement. Neuroimaging data and peripheral nerve conduction study with quantitative sensory testing were also analysed. Results Neurological involvement was detected in 24 (26, 4%) patients (all females). The mean age at disease onset and neurological onset were 41,8 and 47,9 years, respectively. Neurologic involvement frequently preceded the diagnosis of pSS in 10 (42%) patients. Fifty (n=12) patients had peripheral system involvement (PNS), 46% (n=11) patients had CNS disorders and 4% (n=1) patients had both PNS and CNS involvement. In patients with PNS involvement, pure sensory neuropathy (small fiber neuropathy confirmed by quantitative sensory testing and sural neuropathy) occurred most frequently (n=5), followed by cranial nerve involvement affecting trigeminal, facial, or trochlear nerves (n=4). Multiple mononeuropathy (n=1), sensorimotor polyneuropathy (n=1), autonomic neuropathy (n=1) and myasthenia gravis (n=1), were also observed. In patients with CNS disorders, headache with MRI abnormalities compatible with inflammatory disease (n=3) occurred most frequently. Spinal cord involvement (n=2), seizures (n=2), motor and sensory deficit (n=2), movement disorders (n=2), aseptic meningitis (n=1) were the other manifestations observed. Cognitive dysfunction was observed in 3 of these patients. Headache was reported in nine patients other than the three mentioned above. The Raynaud’s phenomenon was more common in these patients (p=0, 04).The frequency of constitutional symptoms (such as fever and fatigue) and lung involvement was significantly higher (p<0,05) in pSS with neurological involvement than in pSS without neurological involvement and the articular symptoms were significantly less frequent (p<0,05) in pSS with neurological involvement. There was no statisticalsignificance in other factors parameters between the two groups. The neurologic outcome was good in 58% (n=14) patients. Conclusions Our results showed that neurological complications were present in 26, 4% of all patients with pSS. In other...

Systemic lupus erythematosus (SLE) is a chronic autoimmune disease of unknown origin, in which both genetic and environmental factors are involved. One such environmental factor is vitamin D, a vital hormone that plays a specific function in the immune system homeostasis, acting through a nuclear receptor (VDR) expressed in all immune cells. Several polymorphisms of the gene that encodes this receptor have been described. Though inconsistently, these polymorphisms have been associated with clinical manifestations and SLE development.The aim of this study was to determine the possible association between VDR gene polymorphisms (BsmI, ApaI, TaqI e FokI) and SLE susceptibility and severity, in a cohort of lupus patients from the north of Portugal.A total of 170 patients (F = 155, M = 15; age = 45 ± 13.4 years) with SLE (diagnosed according the American College of Rheumatology criteria) with at least five years of disease evolution and followed in the Autoimmune Disease Clinical Immunology Unit of Centro Hospitalar do Porto were studied. Patients and 192 ethnicity-matched controls were genotyped for BsmI (rs1544410), ApaI (rs7975232), TaqI (rs731236) and FokI (rs2228570) polymorphisms by TaqMan allelic discrimination assay. Disease severity was assessed by SLICC damage score, number of affected organs, number of severe flares and pharmacological history.SLE patients with the CT genotype of FokI polymorphism have a higher SLICC value (p = 0.031). The same result was observed for the group of patients with the TT genotype of TaqI polymorphism (p = 0.046). No differences were observed in VDR genotype between patients and controls. Also, we observed that the other clinical features analysed were not influenced by VDR polymorphisms.Our study confirms a possible role of VDR gene polymorphisms in SLE. A positive association was found between VDR polymorphisms and SLE severity (chronic damage). The presence of CT genotype of FokI and TT genotype of TaqI seems to confer a worse prognosis and may constitute a risk factor for higher long-term cumulative damage in SLE patients.

Diffuse alveolar hemorrhage (DAH) is a rare but potentially catastrophic manifestation with a high mortality. Among rheumatologic diseases, it occurs most frequently in patients with systemic lupus erythematosus (SLE) and systemic vasculitis. Despite new diagnostic tools and therapies, it remains a diagnostic and therapeutic challenge. The aim of this work was to characterize the SLE patients with an episode of alveolar hemorrhage followed in our Clinical Immunology Unit (CIU). A retrospective chart review was carried out for all patients with SLE followed in CIU between 1984 and the end of 2013. We reviewed the following data: demographic characteristics, clinical and laboratory data, radiologic investigations, histologic studies, treatment, and outcome. We identified 10 episodes of DAH, corresponding to seven patients, all female. These represent 1.6% of SLE patients followed in our Unit. The age at DAH attack was 42.75 ± 18.9 years. The average time between diagnosis of SLE and the onset of DAH was 7.1 years. Three patients had the diagnosis of SLE and the DAH attack at the same time. Disease activity according to SLEDAI was high, ranging from 15 to 41. All patients were treated with methylprednisolone, 37.5% cyclophosphamide and 28.6% plasmapheresis. The overall mortality rate was 28.6%.