Primary Sjögren's syndrome independently promotes premature subclinical atherosclerosis.

OBJECTIVES: Cardiovascular comorbidities are common in patients with autoimmune diseases. This study investigates the extent of subclinical atherosclerosis in patients with primary Sjögren's syndrome (pSS). Correlations with clinical factors such as organ involvement (OI) or disease activity were analysed and oxLDL antibodies (oxLDL ab) were measured as potential biomarkers of vascular damage. METHODS: Patients with pSS were consecutively included from the rheumatology outpatient clinic. Age- and sex-matched controls were recruited (2:1 ratio). Data collection was performed by a standardised questionnaire and Doppler ultrasound to evaluate the plaque extent and carotid intima-media thickness (cIMT). Propensity score matching included all cardiovascular risk (CVR) factors and corresponding laboratory markers. RESULTS: Data were available for 299 participants (199 pSS/100 controls), aged 59.4 years (50.6-65.0), 19.1% male. After matching, the pSS cohort had greater cIMT (p<0.001) and plaque extent (OR=1.82; 95% CI 1.14 to 2.95). Subgroup analyses of patients with pSS revealed that OI was associated with increased cIMT (p=0.025) and increased plaque occurrence compared with patients without OI (OR=1.74; 95% CI 1.02 to 3.01). OxLDL ab tended to be lower in patients with plaque (p=0.052). Correlations of higher Oxidized Low Density Lipoprotein (oxLDL) ab with EULAR Sjögren's Syndrome Disease Activity Index (p<0.001) and anti-Sjögren's-syndrome-related antigen A autoantibodies (SSA/Ro antibodies) (p=0.026) were observed. CONCLUSIONS: Subclinical atherosclerosis occurs earlier and more severely in patients with pSS. The difference in cIMT between pSS and controls seems mainly driven by patients with OI, suggesting that this subgroup is particularly at risk. OxLDL ab might protect against atherosclerotic progression in patients with pSS. CVR stratification and preventive medications such as Hydroxymethylglutaryl-CoA (HMG-CoA) reductase inhibitors should be discussed and further longitudinal studies are needed.

[Update on Sjögren's syndrome : Diagnostics, treatment, and challenges]. / Update Sjögren-Syndrom : Diagnostik, Therapie und Fallstricke.

Sjögren's syndrome (SjS) is the most common connective tissue disease with a prevalence of 1:200. Predominantly affecting women, SjS is associated with destruction of the exocrine glands, leading to xerophthalmia and xerostomia. In over 50% of patients, there are also extraglandular manifestations, leading to multiple organ manifestations including polyneuropathies and interstitial lung disease as well as symptoms such as fatigue and arthralgia. Diagnostic procedures include biomarkers, in particular anti-SS-A/Ro antibodies, histology of salivary glands, and salivary gland sonography. There are currently no licensed immunosuppressive drugs for SjS, so current treatment is often based on off-label use of drugs. The European League Against Rheumatism (EULAR) has recently published treatment recommendations based on the prevailing organ manifestations. Several promising controlled trials with novel compounds and concepts are currently in progress.

Sjögren's syndrome with and without neurological involvement.

OBJECTIVE: Neurological manifestations of Sjögren's syndrome can be severe but also treatment-responsive. We aimed to systematically evaluate neurological manifestations of primary Sjögren's syndrome and find clinical features allowing sufficient identification of affected patients (pSSN) among those with Sjögren's syndrome without neurological involvement (pSS). METHODS: Para-/clinical features of patients with primary Sjögren's syndrome (2016 ACR/EULAR classification criteria) were compared between pSSN and pSS. At our university-based center, patients with suggestive neurological symptoms undergo screening for Sjögren's syndrome, and newly diagnosed pSS patients are thoroughly evaluated for neurologic involvement. pSSN disease activity was rated by the Neurological Involvement of Sjögren's Syndrome Disease Activity Score (NISSDAI). RESULTS: 512 patients treated for pSS/pSSN at our site between 04/2018 and 07/2022 were included (238 pSSN patients [46%] vs. 274 pSS patients [54%], cross-sectional design). Independent predictors of neurological involvement in Sjögren's syndrome were male sex [p < 0.001], older age at disease onset [p < 0.0001], hospitalization at first presentation [p < 0.001], lower IgG levels [p = 0.04] and higher eosinophil values (treatment-naïve) [p = 0.02]. Univariate regression additionally showed older age at diagnosis [p < 0.001], lower prevalence of rheumatoid factor [p = 0.001], SSA(Ro)/SSB(La) antibodies [p = 0.03; p < 0.001], higher white blood cell count [p = 0.02] and CK levels [p = 0.02] (treatment-naïve) in pSSN. INTERPRETATION: Patients with pSSN had different clinical characteristics than patients with pSS and represented a large proportion of the cohort. Our data suggest that neurological involvement in Sjögren's syndrome has been underestimated. Intensified screening for neurologic involvement should be included in the diagnostic algorithm for Sjögren's syndrome, especially in males of older age and with severe disease course requiring hospitalization.

Clinical and paraclinical features of small fiber neuropathy in Sjögren's syndrome.

Sjögren's syndrome is a potentially treatable cause of Small Fiber Neuropathy (SFN)-a condition that severely affects patients' quality of life. We therefore aimed to characterize patients with SFN and Sjögren's syndrome to raise awareness of this disease and facilitate its early recognition as an essential step for appropriate treatment. In 97 SFN patients (median age 48 years, 77% female), we studied the clinical features associated with Sjögren's syndrome compared to the idiopathic SFN subtype. According to the current ACR/EULAR classification criteria (Shiboski et al., Ann Rheum Dis 76:9-16, 2017), 24/97 individuals (25%, median age 48.5 years, 75% female) were diagnosed with Sjögren's syndrome. We did not observe any differences in SFN-defining sensory plus symptoms. Furthermore, intraepidermal nerve fiber densities (IENFD) were significantly lower in patients with SFN and Sjögren's syndrome (mean 2.6 ± 1.2/mm) compared to patients with idiopathic SFN (mean 3.2 ± 1.5/mm; p = 0.048). There were no significant group differences when analyzing cerebrospinal fluid (CSF) parameters. We conclude that Sjögren's syndrome-associated SFN is difficult to distinguish from idiopathic forms based on initial clinical symptoms and CSF results. However, lower IENFD values in patients with Sjögren's syndrome-associated SFN might indicate a distinct different pathomechanism in this entity compared to idiopathic SFN.

Work situation of rheumatologists and residents in times of COVID-19 : Findings from a survey in Germany.

BACKGROUND AND OBJECTIVE: The work situation is an important dimension of professional life and wellbeing, and a policy lever to strengthen recruitment and retention. This study aims to explore the work situation of physicians and residents in internal medical rheumatology, considering the impact of the coronavirus pandemic COVID-19. METHODS: A questionnaire-based online survey was conducted in early 2021 at the Hannover Medical School, supported by the German Society of Rheumatology. Target groups were all rheumatology physicians and residents in Germany. The main areas of investigation included work hours, task delegation, and collaboration; workload and mental health issues; discrimination and sexual harassment experiences; and the impact of COVID-19. Descriptive statistical analysis was performed for the standardized items and qualitative content analysis for the free-text information. RESULTS: The respondents (n = 101) expressed positive attitudes towards cooperation and task delegation to medical assistants, especially those specialized in rheumatology, while attitudes towards cooperation with GPs pointed to blockades. There was a strong mismatch between actual and desired work hours both in the group of women and in the group of men. 81% rated their workload as high or very high; every sixth rheumatologist has suffered from stress or burnout syndromes at least once in the past. Experiences of gender discrimination and sexual harassment/violence were frequently reported, mostly by women. COVID-19 was an amplifier of stress, with major stressors being digitalization and increased demand for communication and patient education. CONCLUSION: There is an urgent need to improve the work situation of rheumatologists and reduce stress and mental health risks.

Primary antibody deficiency-associated arthritis shares features with spondyloarthritis and enteropathic arthritis.

OBJECTIVE: The clinical spectrum of primary antibody deficiencies (PADs) and especially common variable immunodeficiency (CVID) includes various autoimmune disorders. We studied the prevalence and the features of articular rheumatic disease in a cohort of patient with PADs. METHODS: In this retrospective cohort study, complete clinical data of 268 patients with PADs, mainly consisting of patients with CVID, visiting the immunology outpatient clinic of a German tertiary hospital between 2018 and 2021 were collected. Those included case history, physical examination, laboratory as well as radiological findings. RESULTS: Inflammatory arthritis was diagnosed in 16.4% of studied patients and was significantly more common among patients with PAD-associated enteropathy (OR 13.39, p=0.0001), splenomegaly (OR 6.09, p=0.0001) or atopic diseases (OR 3.31, p=0.021). Given HLA-B27 status, the involvement of the axial skeleton and the presence of features, such as anterior uveitis, inflammatory bowel disease, psoriasis and/or dactylitis, 75% of studied patients fulfilled the Assessment of Spondyloarthritis International Society classification criteria. CONCLUSION: PAD-associated arthritis frequently shares features with spondyloarthritis (SpA) and enteropathic arthritis. The latter may suggest the interconnected pathomechanisms of inflammatory arthritis in SpA and PADs.

Saliva Free Light Chains in Patients with Neuro-Sjögren.

Background: Sjögren's syndrome (SS) is an autoimmune disease characterized by sicca symptoms and various extra-glandular manifestations. The diagnosis of SS requires sicca symptoms, anti-SSA(Ro)-antibody positivity, and/or pathological focus scores on a minor salivary gland biopsy. Previous studies have investigated different biomarkers in order to avoid invasive diagnostic procedures. It was found that kappa and lambda free light chains (KFLC and LFLC) in saliva are specific for SS. Methods: FLC concentrations in saliva and serum were determined in 130 patients-50 with SS and neurological involvement (Neuro-Sjögren) and 80 neurological controls. The EULAR SS disease activity index and patient reported index (ESSPRI) were determined in patients with SS. Results: Patients with SS revealed increased pain and decreased saliva production according to the ESSPRI and Saxon test, respectively, with increasing FLC concentrations in the saliva. No significant differences in serum and salivary protein concentrations were observed between patients with SS and controls. Conclusion: KFLC and LFLC concentrations in saliva are not suitable to distinguish patients with Neuro-Sjögren and neurological control subjects, thus a diagnostic biopsy is still required. The association of salivary KFLC and LFLC concentrations with saliva production and ESSPRI pain score suggests a complex relationship between dryness and pain in patients with SS.

Trigeminal Nerve Affection in Patients with Neuro-Sjögren Detected by Corneal Confocal Microscopy.

BACKGROUND: Patients with Sjögren's syndrome and polyneuropathy more frequently develop cranial nerve affection when compared to patients with chronic inflammatory demyelinating polyneuropathy (CIDP). We therefore aimed to analyze trigeminal corneal nerve fibre characteristics in both patient groups. METHODS: A total of 26 patients with Sjögren's syndrome associated neuropathy and 29 patients with CIDP were recruited at our university hospital and compared to 6 healthy controls. Dry eye symptoms and signs were assessed via clinical examination and the Ocular Disease Surface Index questionnaire. Trigeminal corneal nerve fibres were analyzed via corneal confocal microscopy (CCM) as a non-invasive in vivo microscopy. RESULTS: CCM revealed significantly reduced corneal nerve fibre density and corneal nerve fibre main branch density in the Neuro-Sjögren group when compared with healthy controls. There were no significant group differences between the Neuro-Sjögren and the CIDP group for any of the microscopic parameters. Dry eye assessment showed similarly reduced scores for both patient groups, while healthy controls showed better results for objective dry eye signs. There was no correlation between microscopic parameters of the corneal confocal microscopy and parameters of dry eye assessment. CONCLUSIONS: Our data revealed trigeminal corneal nerve affection in patients with neuropathy associated with Sjögren's syndrome and patients with CIDP detected by CCM. No difference was found between both neuropathy groups indicating that CCM is not able to distinguish between both entities.

Premature stroke and cardiovascular risk in primary Sjögren's syndrome.

Introduction: Primary Sjögren's syndrome (pSS) is associated with an increased prevalence of traditional risk factors and cardiovascular diseases (CVDs). The study aimed to identify specific risk factors for CVD in pSS patients. Methods: PSS patients with and without CVD were compared. All patients fulfilled the EULAR/ACR classification criteria. Patients with CVD presented at least one of the following manifestations: myocardial infarction, transient ischemic attacks, ischemic or hemorrhagic stroke, peripheral artery disease, coronary artery disease, and carotid plaques. Data were collected by a standardized protocol and review of medical records. Results: 61/312 (19.6%) pSS patients presented with CVD. Traditional risk factors such as hypertension, hypercholesterinemia and diabetes (p < 0.05), pSS manifestations, in particular vasculitis (p = 0.033) and Raynaud's phenomenon (p = 0.018) were associated with CVD. Among patients with ischemic events (28/312, 9%), particularly cerebrovascular disease (n = 12/28, 42.9%), correlations with increased EULAR Sjögren's Syndrome Disease Activity Index (ESSDAI) (p = 0.039) and EULAR Sjögren's Syndrome Patient Reported Index (ESSPRI) (p = 0.048) were observed. Age at first cerebrovascular event was 55.2 [48.9-69.6] years. Multivariate analysis confirmed hypertension [odds ratio (OR) 3.7, 95% confidence interval (CI) 1.87-7.18, p < 0.001], hypercholesterinemia (OR 3.1, 95% CI 1.63-5.72, p < 0.001), male gender (OR 0.4, 95% CI 0.17-0.78, p = 0.009), Raynaud's phenomenon (OR 2.5, 95% CI 1.28-4.82, p = 0.007), and CNS involvement (OR 2.7, 95% CI 1.00-7.15, p = 0.048) as independent CVD predictors. Conclusion: Raynaud's phenomen as well as vasculitis and high ESSDAI have shown a significant association to CVD. PSS patients with cerebrovascular events were younger than expected. Knowledge about risk factors may help clinicians to identify pSS patients at risk for CVD. After diagnosis of pSS, patients should be screened for risk factors such as hypertension and receive appropriate therapy to prevent or at least reduce sequelae such as infarction. However, further investigations are necessary in order to achieve a reliable risk stratification for these patients.

[Care of rheumatology patients during the lockdown in early 2020 : Telemedicine, delegation, patient satisfaction and vaccination behavior]. / Versorgung von rheumatologischen Patienten während des Lockdowns im Frühjahr 2020 : Telemedizin, Delegation, Patientenzufriedenheit und Impfverhalten.

BACKGROUND: Telemedicine was implemented in outpatient care during the lockdown between March and May 2020. The aim of the study was to assess patients from a private practice and the university outpatient department with respect to patient satisfaction with telemedicine, COVID-19 worries and vaccination behavior and to compare the teleconsultation by a medical assistant for rheumatology (RFA) and a physician. METHODS: Patients with rheumatoid arthritis, psoriatric arthropathy or spondylarthritis without treatment modifications since the previous presentation were offered a telemedical replacement appointment within the framework of this study in the case of appointment cancellation by the treating center. Participants were randomized to a telemedicine appointment by a physician or an RFA (RFA university only). The patient history was carried out by telephone and standardized using a questionnaire. The disease activity was determined using the modified clinical disease activity score (CDAI) and the BASDAI. Subsequently, all patients received a pseudonymized evaluation questionnaire. RESULTS: In total 112/116 (96%) patients participated. Of these 88/112 (79%) returned the questionnaire. The RFAs conducted 19/112 (17%) of the telephone calls. The treatment was modified in 19/112 (17%) patients. Concerns about contracting COVID-19 correlated with high disease activity (p = 0.031) including the presence of painful joints (p = 0.001) and high pain levels (VAS ≥7, p = 0.009). These patients would have also cancelled their appointment themselves (p = 0.015). Patient satisfaction with the consultation was good (mean 4.3/5.0 modified FAPI) independent of the institution, the duration of the consultation and the consultation partner. Patients with a high pain intensity were the least satisfied (p = 0.036). Only 42/100 (38.2%) of the patients had been vaccinated against pneumococci and 59/100 (53.6%) against influenza. CONCLUSION: Telemedical care within the framework of a telephone consultation is well-suited for selected patients. With respect to patient satisfaction the delegation of a telemedical consultation to an RFA is possible. There is a need for improvement with respect to the vaccination behavior.

[Health workforce development in rheumatology : A mapping exercise and wake-up call for health policy]. / Fachkräfteentwicklung in der Rheumatologie : Ein berufsstruktureller Überblick und gesundheitspolitischer Weckruf.

BACKGROUND AND OBJECTIVE: Health workforce shortage in German rheumatology has been identified as a healthcare service and delivery problem. Health policy has increased staffing targets, yet effective intervention strategies are lacking. This research aimed to systematically map the rheumatology workforce to improve the evidence for interventions and explore possibilities for more effective health workforce management. METHODS: The WHO National Health Workforce Accounts provided a conceptual framework for the mapping exercise. Four major sets of indicators were selected, comprising staffing levels, health labor market flows, composition and education/training. A comparison of age groups and time series was applied to explore trends. Public statistics and other secondary sources served our analysis using descriptive methodology. RESULTS: In Germany there are 1076 physicians specialized in internal medical rheumatology. Absolute numbers have nearly doubled (91%) since 2000 but with a strong demographic bias. Between 2000 and 2019 numbers markedly increased in the group aged 50 years and older but only by 9% in the younger group under 50 years; since 2010 the group aged 40-50 years even faces a decrease. In 2019, the absolute numbers of rheumatologists in retirement age exceeded those aged 40 years and under. Since 2015 an expanding workforce trend has overall flattened but this was strongest in the hospital sector; the numbers in resident training did not show any relevant growth. CONCLUSION: Health workforce trends reveal that an available number of rheumatologists cannot meet new health policy planning targets. There is a need for effective health workforce management, focusing on innovation in resident training, improved task delegation and gender equality.

Nerve ultrasound findings in Sjögren's syndrome-associated neuropathy.

BACKGROUND AND PURPOSE: The phenotype of Sjögren's syndrome-associated neuropathy has been better characterized in recent years. However, Sjögren's syndrome-associated neuropathy remains an underdiagnosed entity with only few insights considering the pathomechanisms of nerve damage. Nerve ultrasound has proven to be a useful and efficient tool in detecting nerve damage of autoimmune origin. We, therefore, aimed to evaluate this method for Sjögren's syndrome-associated neuropathy. METHODS: Patients with Sjögren's syndrome and clinical signs of neuropathy underwent sonographic examination of both median and ulnar nerves. Nerve thickening was classified for cross-sectional areas of >12 mm² at the median nerve and for >10 mm² at the ulnar nerve. Fascicle thickening was documented for cross-sectional areas ≥5 mm² at the median and ≥3 mm² at the ulnar nerve. RESULTS: Forty-three patients were included in the analysis (median age 60 years [interquartile range 53-73 years], female rate 60%). 31/43 patients (72%) showed abnormalities on nerve ultrasound, while nerve thickening was found more frequently than fascicle thickening (90% vs. 52% of patients with sonographic abnormalities, respectively). Abnormal findings were observed more frequently at the median nerve and in proximal localization. Abnormal findings on nerve conduction studies were evident in 36/43 patients (84%). Nerve conduction studies revealed a tendency of demyelinating nerve damage patterns being associated with abnormal findings on nerve ultrasound. CONCLUSIONS: In addition to nerve conduction studies, nerve ultrasound may have a supporting role in the diagnosis of Sjögren's syndrome-associated neuropathy. Also, our data support an immune-mediated inflammatory demyelinating pathogenesis of Sjögren's syndrome-associated neuropathy.

CIDP associated with Sjögren's syndrome.

BACKGROUND: This study addresses the challenging characterisation and differentiation of CIDP versus CIDP in association with Sjögren's syndrome to facilitate the process in clinical routine. METHODS: Patients with both CIDP and Sjögren's syndrome and CIDP without Sjögren's syndrome were compared concerning relevant differences in clinical, laboratory and electrophysiological findings. 154 patients who fulfilled the diagnostic EFNS/PNS criteria for CIDP were included in the analysis. 54 of these patients additionally fulfilled the ACR/EULAR classification criteria for Sjögren's syndrome. RESULTS: The frequency of female patients was higher in patients with CIDP and Sjögren's syndrome (52%) versus CIDP patients without Sjögren's syndrome (28%). Furthermore, the occurrence of cranial nerve impairment was significantly higher in patients with Sjögren's syndrome (39% versus 14%). There were no significant group differences in the evaluation of initial symptoms, severity of disability judged by INCAT disability scale score, presence or distribution of sensory deficits, limb weakness and the presence of ataxia, pain or dysautonomia, CSF laboratory or electrophysiological findings. CONCLUSIONS: In conclusion, our data indicate that cranial nerve impairment and female gender might represent red flags for an additional Sjögren's syndrome in patients with CIDP. The patterns of clinical disabilities and electrophysiological findings due to peripheral nerve damage are similar in both CIDP entities.

Multimodal Assessment and Characterization of Sicca Syndrome.

Background: Sicca syndrome represents a heterogeneous group of conditions, such as Sjögren syndrome, causing xerophthalmiaand xerostomia. This study characterizes in depth patients with Sicca syndrome and evaluates salivary gland ultrasound (SGUS). Methods: Principal component analysis and hierarchical clustering of clinical parameters, such as ESSPRI, ESSDAI and laboratory data, were performed on all referrals for assessment of Sicca symptoms between October 2018 and March 2021. SGUS and labial gland biopsies were compared across groups. Results: A total of 583 patients were assessed. Objective dryness was confirmed in 73% of the patients. Cluster analysis identified 3 groups with post-hoc analysis confirming distinct phenotypes: Somatic Group (283/583; 49%) with more frequent symptoms but limited objective dryness; Dry Without Autoimmune Features (DAFneg, 206/584; 35%), and Dry With Autoimmune Features (DAFpos, 94/584;16%). DAFpos patients had highest autoantibody titers (anti-SSA(Ro) 240 vs. 3.6 vs. 3.8; p < 0.001), most extra-glandular manifestations (p < 0.001), and highest median SGUS Score (DAFpos: 8 [IQR 4-10] vs. SG: 2 [1-4] vs. DAFneg 4 [2-5]; p < 0.001). No tangible correlation with primary Sjögren syndrome criteria was observed. Discussion: SGUS score correlated with a subset of patients with Sjögren syndrome, identified in the DAFpos cluster. This study highlights heterogeneity within sicca and, indeed, Sjögren syndrome, highlighting the need for further studies.

Salivary Gland Ultrasonography in Sjögren's Syndrome: A European Multicenter Reliability Exercise for the HarmonicSS Project.

Objectives: Salivary gland ultrasonography (SGUS) is increasingly applied for the management of primary Sjögren's syndrome (pSS). This study aims to: (i) compare the reliability between two SGUS scores; (ii) test the reliability among sonographers with different levels of experience. Methods: In the reliability exercise, two four-grade semi-quantitative SGUS scoring systems, namely De Vita et al. and OMERACT, were tested. The sonographers involved in work-package 7 of the HarmonicSS project from nine countries in Europe were invited to participate. Different levels of sonographers were identified on the basis of their SGUS experience and of the knowledge of the tested scores. A dedicated atlas was used as support for SGUS scoring. Results: Twenty sonographers participated in the two rounds of the reliability exercise. The intra-rater reliability for both scores was almost perfect, with a Light's kappa of 0.86 for the De Vita et al. score and 0.87 for the OMERACT score. The inter-rater reliability for the De Vita et al. and the OMERACT score was substantial with Light's Kappa of 0.75 and 0.77, respectively. Furthermore, no significant difference was noticed among sonographers with different levels of experience. Conclusion: The two tested SGUS scores are reliable for the evaluation of major salivary glands in pSS, and even less-expert sonographers could be reliable if adequately instructed.

Strategic Anti-SARS-CoV-2 Serology Testing in a Low Prevalence Setting: The COVID-19 Contact (CoCo) Study in Healthcare Professionals.

BACKGROUND: Serology testing is explored for epidemiological research and to inform individuals after suspected infection. During the coronavirus disease 2019 (COVID-19) pandemic, frontline healthcare professionals (HCP) may be at particular risk for infection. No longitudinal data on functional seroconversion in HCP in regions with low COVID-19 prevalence and low pre-test probability exist. METHODS: In a large German university hospital, we performed weekly questionnaire assessments and anti-severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) immunoglobulin G (IgG) measurements with various commercial tests, a novel surrogate virus neutralisation test, and a neutralisation assay using live SARS-CoV-2. RESULTS: From baseline to week 6, 1080 screening measurements for anti-SARS CoV-2 (S1) IgG from 217 frontline HCP (65% female) were performed. Overall, 75.6% of HCP reported at least one symptom of respiratory infection. Self-perceived infection probability declined over time (from mean 20.1% at baseline to 12.4% in week 6, p < 0.001). In sera of convalescent patients with PCR-confirmed COVID-19, we measured high anti-SARS-CoV-2 IgG levels, obtained highly concordant results from enzyme-linked immunosorbent assays (ELISA) using e.g. the spike 1 (S1) protein domain and the nucleocapsid protein (NCP) as targets, and confirmed antiviral neutralisation. However, in HCP the cumulative incidence for anti-SARS-CoV-2 (S1) IgG was 1.86% for positive and 0.93% for equivocal positive results over the study period of 6 weeks. Except for one HCP, none of the eight initial positive results were confirmed by alternative serology tests or showed in vitro neutralisation against live SARS-CoV-2. The only true seroconversion occurred without symptoms and mounted strong functional humoral immunity. Thus, the confirmed cumulative incidence for neutralizing anti-SARS-CoV-2 IgG was 0.47%. CONCLUSION: When assessing anti-SARS-CoV-2 immune status in individuals with low pre-test probability, we suggest confirming positive results from single measurements by alternative serology tests or functional assays. Our data highlight the need for a methodical serology screening approach in regions with low SARS-CoV-2 infection rates. TRIAL REGISTRATION: The study is registered at DRKS00021152.

Recurrent Life-threatening Pneumonitis in a 37-Year-Old Woman.

CASE PRESENTATION: A 37-year-old previously healthy and athletic woman presented to the ED in October 2018 with acute-onset high fever, dyspnea, and productive cough. Chest radiograph showed bilateral infiltrates that correlated with multifocal ground glass opacities in a thoracic CT scan (Fig 1). The patient was severely hypoxemic and required intensive care and oxygen administration via a high-flow nasal cannula. On admission, leucocyte counts were 23.3 k/µL; platelet counts were 518 k/µL; hemoglobin level was 12 g/dL; C-reactive protein was 83 mg/L, and procalcitonin was 0.7 µg/L. An auto-antibody panel that included antinuclear antibodies, extractable nuclear antigen (including anti-centromere-antibodies), antineutrophil cytoplasmic antibodies, and myositis- and granulocyte macrophage colony-stimulating factor-antibodies was negative, as was the rheumatoid factor. Immunoglobulins that included IgG1-4 and IgA and renal function were normal. Sicca symptoms like xerophthalmia and xerostomia were negated. The patient fully recovered after empiric administration of antibiotics and glucocorticoids (initially 500 mg methylprednisolone daily over 3 days with consecutive tapering).

Lung Involvement in Primary Sjögren's Syndrome-An Under-Diagnosed Entity.

Interstitial lung disease (ILD) represents a frequent extra-glandular manifestation of primary Sjögren's Syndrome (pSS). Limited published data regarding phenotyping and treatment exists. Advances in managing specific ILD phenotypes have not been comprehensively explored in patients with coexisting pSS. This retrospective study aimed to phenotype lung diseases occurring in a well-described pSS-ILD cohort and describe treatment course and outcomes. Between April 2018 and February 2020, all pSS patients attending our Outpatient clinic were screened for possible lung involvement. Clinical, laboratory and high-resolution computed tomography (HRCT) findings were analyzed. Patients were classified according to HRCT findings into five groups: usual interstitial pneumonia (UIP), non-specific interstitial pneumonia (NSIP), desquamative interstitial pneumonia (DIP), combined pulmonary fibrosis and emphysema (CPFE), and non-specific-ILD. Lung involvement was confirmed in 31/268 pSS patients (13%). One-third (10/31) of pSS-ILD patients were Ro/SSA antibody negative. ILD at pSS diagnosis was present in 19/31 (61%) patients. The commonest phenotype was UIP n = 13 (43%), followed by NSIP n = 9 (29%), DIP n = 2 (6 %), CPFE n = 2 (6 %), and non-specific-ILD n = 5 (16%). Forced vital capacity (FVC) and carbon monoxide diffusion capacity (DLCO) appeared lower in UIP and DIP, without reaching a significant difference. Treatment focused universally on intensified immunosuppression, with 13/31 patients (42%) receiving cyclophosphamide. No anti-fibrotic treatments were used. Median follow-up was 38.2 [12.4-119.6] months. Lung involvement in pSS is heterogeneous. Better phenotyping and tailored treatment may improve outcomes and requires further evaluation in larger prospective studies.