10-year follow-up of patients with rheumatoid arthritis and secondary Sjögren's syndrome or sicca symptoms in daily clinical practice.

OBJECTIVES: To evaluate the presence of sicca symptoms and secondary Sjögren's syndrome (SS) and the association with clinical characteristics, functional tests and patient-reported outcomes in patients with rheumatoid arthritis (RA) at baseline and after 10 years of follow-up. METHODS: A cohort of RA patients was evaluated in 2008 and re-evaluated in 2018 with respect to sicca symptoms, presence of secondary SS according to AECG classification criteria, disease activity of RA and patient-reported outcomes. Patient characteristics were compared between the RA-non-sicca, RA-sicca and RA-SS groups. RESULTS: Of the original 2008 cohort of 96 RA patients, 32 (33%) had sicca symptoms and 6 (6.3%) secondary SS. Of the 36 patients who agreed to be re-evaluated in 2018, 6 (17%) had sicca symptoms and 2 (6%) developed secondary SS. In the majority of patients, sicca symptoms were reversible while the functional tests of salivary and lacrimal glands significantly decreased. 67% of RA-sicca patients had no sicca complaints at the second screening, while only two RA-sicca patients developed secondary SS. RA-SS patients and, to a slightly lesser extent, RA-sicca patients had significantly higher RA disease activity (DAS-28), lower lacrimal (Schirmer's test) and salivary gland function, more limitations in daily activities (HAQ), worse health-related quality of life (RAND-36), more fatigue (MFI) and more patient symptoms (ESSPRI) compared to RA-non-sicca patients. CONCLUSIONS: Secondary SS was found in a minor subset of the RA patients. Sicca symptoms of the eyes or mouth were more frequent, but their presence varied over time. Higher RA disease activity was associated with SS and sicca symptoms. These patients had lower gland function and worse patient-reported outcomes.

Serum immunoglobulin free light chains are sensitive biomarkers for monitoring disease activity and treatment response in primary Sjögren's syndrome.

Objectives: Serum immunoglobulin free light chains (FLCs) are frequently elevated in B-cell-mediated autoimmune diseases, including primary SS (pSS). The objective of this study was to assess if serum FLCs can contribute to classification, mucosa-associated lymphoid tissue (MALT) lymphoma detection, monitoring of disease activity and treatment response in pSS. Methods: Serum samples of 100 consecutive patients suspected of pSS were included. Forty-five patients fulfilled ACR-EULAR criteria for pSS. Additionally, samples of 17 pSS patients with MALT lymphoma and longitudinal samples of pSS patients treated with rituximab (n = 20), placebo (n = 10) or abatacept (n = 15) were included. Serum FLCκ/FLCλ was measured by nephelometry or turbidimetry. Results: At diagnosis, FLCκ and FLCλ serum levels were significantly higher in pSS compared with non-SS sicca patients. The FLCκ/FLCλ ratio was abnormal in 11% of pSS patients. In established MALT-pSS patients, without recent rituximab treatment (n = 12), 50% had abnormal FLCκ/FLCλ ratios. FLC measurement had no additional value for pSS classification, compared with IgG and anti-SSA. FLC levels correlated significantly with systemic disease activity, assessed by EULAR SS Disease Activity Index (ESSDAI) and clinical ESSDAI, both cross-sectionally and longitudinally following treatment. Treatment with rituximab or abatacept significantly lowered FLC levels. FLCs show a large sensitivity to change and relative changes induced by treatment were higher compared with IgG. Conclusion: Serum FLCs are elevated in pSS, and abnormal FLCκ/FLCλ ratios may be indicative for the presence of MALT lymhoma. FLC levels can be used as a biomarker for systemic disease activity and monitoring treatment responses. FLCs are sensitive to change and have more favorable kinetics than IgG.

Detailed Analysis of the Articular Domain in Patients with Primary Sjögren Syndrome.

OBJECTIVE: We used the 28-joint Disease Activity Score (DAS28) and the European League Against Rheumatism Sjögren's Syndrome Disease Activity Index (ESSDAI) articular domain to assess the effect of rituximab (RTX) and abatacept (ABA) on articular involvement in primary Sjögren syndrome (pSS). METHODS: Patients with pSS treated with RTX (n = 18) or ABA (n = 13) and having a DAS28 erythrocyte sedimentation rate (ESR)/C-reactive protein (CRP) level ≥ 3.2 at baseline were selected. Generalized estimating equations were used to analyze the DAS28 and ESSDAI articular domain over time. RESULTS: In the RTX group, DAS28-ESR/CRP decreased significantly up to 48 weeks. In the ABA group, DAS28-ESR/CRP decreased significantly up to 24 weeks. DAS28 correlated significantly with ESSDAI articular domain. CONCLUSION: DAS28 is useful to evaluate the effect of biologicals on articular involvement in patients with pSS.

Physical fatigue characterises patient experience of primary Sjögren's syndrome.

OBJECTIVES: Besides ocular and oral dryness, fatigue is a major symptom in patients with primary Sjögren's syndrome (pSS). Our aim was to investigate the importance of fatigue in relation to other symptoms experienced as well as to evaluate the effect of rituximab treatment on fatigue in pSS patients with active disease. METHODS: This analysis was based on data from our open-label rituximab study in 28 pSS patients. Symptoms of dryness, physical fatigue, pain, and mental fatigue were scored on 0-10 scales (according to ESSPRI). Systemic disease activity was assessed with ESSDAI. RESULTS: At baseline, 24 (86%) patients rated physical fatigue as the complaint most eligible for improvement (median importance of 10), followed by pain, dryness, and mental fatigue. After rituximab treatment, physical fatigue showed maximum improvement of 2.5 points and 31% in median values at group level, and 10 (36%) patients reached physical fatigue score<5 representing patient-acceptable symptom state (PASS). In comparison, systemic disease activity improved 5.5 points and 73% at group level, and 22 (79%) patients reached ESSDAI<5 representing low disease activity. GEE analysis over time revealed that physical fatigue was significantly associated with absolute number of B cells, dryness and mental fatigue, but not with ESSDAI, IgG levels and IgM-RF. CONCLUSIONS: Physical fatigue characterises patient experience of pSS. Rituximab treatment resulted in significant improvement of patient-reported symptoms. However, the large majority of patients still experienced physical fatigue at an unsatisfactory level, above the cut-off value for PASS. Therefore, attention for optimal management of this prominent symptom is warranted.

Purulent lupus panniculitis unmasked by FDG-PET/CT scan: A case report.

RATIONALE: Lupus panniculitis (LP) is a unique variant of cutaneous lupus erythematosus. Clinical manifestations are typically mild and include erythema, nodules, and small ulcers. In certain cases, diagnosing LP may be challenging. Skin overlying the typical subcutaneous inflammation may appear normal, and bacterial superinfections of the skin sometimes mask the underlying LP. It has been suggested that a computed tomography (CT) scan may help to identify obscure LP lesions. Here, we report a case of a 54-year-old woman with an unusually severe form of LP, in which the full disease extent was only revealed by a fluorodeoxyglucose positron emission tomography (FDG-PET)/CT scan. PATIENT CONCERNS/DIAGNOSES/INTERVENTIONS/OUTCOMES: Our patient initially presented with a bacterial infection of the skin. After initial improvement with antibiotic treatment, new erythematous lesions and sterile subcutaneous pus collections developed. An FDG-PET/CT scan revealed extensive subcutaneous inflammation at sites that had appeared normal during physical examination and on CT scan. As the subcutaneous lesions showed a remarkably linear pattern on FDG-PET/CT scan, the patient was suspected of having LP. After confirmation of this diagnosis by a deep-skin biopsy, our patient was treated with systemic glucocorticoids. Eventually, our patient succumbed to complications of LP and its treatment. LESSONS: Our case demonstrates that clinical manifestations of LP are not always mild and that timely diagnosis is needed. Furthermore, we show that obscure LP lesions are more readily identified on an FDG-PET/CT scan than CT scan.

Safety of treatments for primary Sjögren's syndrome.

INTRODUCTION: Primary Sjögren's syndrome (pSS) is a disabling auto-immune disease, affecting exocrine glands and several organs. AREAS COVERED: In this review we analyze the safety of therapies used in pSS. Symptomatic treatment is widely applied due to the good supportive effect and good safety profile. Systemic stimulation of tears and saliva can be successful in pSS. However, cumbersome adverse events can influence the tolerability of this therapy. Evidence for the effectiveness of synthetic DMARDs therapies in pSS is limited, while there is a risk of adverse events. Several studies on biologic DMARD treatment of pSS patients have shown promising efficacy and safety results. EXPERT OPINION: The safety of symptomatic treatment of pSS is very good. However, systemic therapy is necessary to achieve long-term relieve and prevention of organ-damage. Synthetic DMARDs have not shown much efficacy in earlier studies, and their benefits do not weigh up to the possible harms, while biologic DMARDs show promising results regarding efficacy and cause mostly mild adverse events. Many questions remain unanswered regarding safety of DMARDs in pSS. There is a need for well designed studies, in which safety should be evaluated in a uniform manner to be able to compare the results between studies.

Sjögren's syndrome in older patients: aetiology, diagnosis and management.

Sjögren's syndrome (SS) is a systemic autoimmune disease, characterized by chronic inflammation of exocrine glands that results in development of xerostomia and keratoconjunctivitis sicca. The disease activity of SS is not restricted to exocrine glands, and many other organs and organ systems can be involved. Diagnosis of SS in the elderly population can be challenging because xerostomia, dry eyes, symptoms of fatigue, weight loss and muscle pain are also common features of old age. Delay between clinical onset and diagnosis of SS in the elderly may be due to the shared features of SS and old age. The 2002 revised American-European Consensus Group (AECG) classification criteria for SS are the preferred tool used to confirm diagnosis of SS, but recently alternative criteria have been put forward by the American College of Rheumatology (ACR). The AECG criteria set combines subjective symptoms of dry eyes and dry mouth with objective signs of keratoconjunctivitis sicca, salivary gland dysfunction and histopathological (salivary gland biopsy) and serological (autoantibodies against SSA/Ro and SSB/La antigens) features. Treatment of SS in the elderly does not differ from that in younger patients. The aims of the treatment of SS are to control glandular and extraglandular manifestations, to prevent damage to organ systems and loss of function, and to decrease morbidity and mortality. Treatment of the elderly can be complicated by co-morbidities, an increased rate of adverse events related to therapeutic agents, and polypharmacy. Therefore, careful follow-up of the treatment is required.