Inflammatory Arthralgia Research Articles

Omalizumab-Induced Arthralgias in a Patient with Chronic Idiopathic Urticaria

Background: Omalizumab (Xolair) is a recombinant DNA-derived humanized IgG1 κ monoclonal antibody that selectively binds to the high-affinity IgE receptor on the surface of mast cells and basophils, limiting release of mediators of the allergic response. It is the first monoclonal antibody approved for the treatment of refractory chronic idiopathic urticaria in patients over the age of 12 and has been shown to result in clinically significant improvement of itching and wheal formation in these patients. Rarely, inflammatory arthralgias can be a severe side effect of omalizumab. Clinical Case: We report a case of a 38-year-old female patient with chronic idiopathic urticaria who responded well on a therapeutic dosage of omalizumab, but subsequently developed severe inflammatory arthralgias. We decreased her dosage and added methotrexate for complete resolution of her urticarial and arthritic symptoms. Conclusion: In patients with concern for medication-induced inflammatory arthralgias, physicians should consider reducing or discontinuing omalizumab with consideration of patient goals for the treatment of chronic idiopathic urticaria. This article highlights the occurrence of inflammatory arthralgias as a side effect of omalizumab, the importance of eliciting patient goals and preferences for treatment, and proposes a solution to manage these arthralgias while appropriately treating symptoms in patients with chronic idiopathic urticaria.

Polyglandular Syndrome type III in a young patient: case report

Introduction: Autoimmune polyglandular syndromes (APS) are rare diseases defined by the coexistence of at least two autoimmune endocrine diseases. Objective: To describe a case of type III polyglandular syndrome in a young patient. Case report: Female, 37 years old, with hypothyroidism, presented with a weight loss of 9 kg, daily vomiting, asthenia, fatigue, and postprandial fullness for 3 months. He also reported arthritis in his wrists, shoulders, and hips. In laboratory tests, macrocytic and hyperchromic anemia associated with leukopenia, as well as hypovitaminosis B12, was observed. Pernicious anemia was investigated as the cause of this deficiency. Upper digestive endoscopy showed moderate gastritis – histopathological with gastric atrophy, positive anti-intrinsic factor antibody. Due to inflammatory arthralgia, ANA was requested, with an associated positive anti-dsDNA result of 1:80. In the EULAR/2019 diagnostic criteria for Systemic Lupus Erythematosus (SLE), she presented 14 points, thus she was diagnosed with SLE, and hydroxychloroquine (HXC) was started. Conclusion: SPA is rare, mainly in association with non-glandular autoimmunity, following an early diagnosis.

Interstitial Lung Disease Phenotypes and Predictive Risk Factors in Primary Sjögren's Syndrome.

Background/Objectives: The prevalence of Interstitial Lung Disease (ILD) and risk factors for its development in patients with primary Sjögren's syndrome (pSS) are still debated, possibly due to the existence of heterogeneous pSS-related ILD phenotypes. The aims of this study were: 1. To investigate the prevalence and predictive factors for ILD development in a single-center pSS cohort; 2. To characterize different pSS-ILD phenotypes. Methods: Clinical, laboratory and imaging data of pSS patients attending our center from January 2019 to September 2023 were retrospectively analyzed. ILD presence was confirmed on HRCT. Results: Forty-three out of 474 enrolled pSS patients presented ILD (M:F = 6:37), accounting for an overall ILD prevalence of 9.1%. In 19 cases, ILD was the first manifestation of pSS (ILD-onset), while in 24 ILD was diagnosed after pSS (ILD-incident). Compared to ILD-onset, ILD-incident patients more often presented pSS-related hematologic abnormalities (p = 0.012), cutaneous involvement (p = 0.027), inflammatory arthralgias (p = 0.026), C4 hypocomplementemia (p = 0.012) and positive RF (p = 0.031). On the other hand, ILD-onset patients were significantly older at pSS diagnosis (p = 0.008) and presented more severe fibrosis on HRCT (p = 0.008). On the univariate analysis, higher ESSDAI (p = 0.011), Raynaud's phenomenon (p = 0.009), anti-Ro52 (p = 0.031), hypergammaglobulinemia (p = 0.011), Rheumatoid Factor (RF) (p = 0.038) and C4 hypocomplementemia (p = 0.044) at baseline were associated to ILD development during follow-up. On the multivariate analysis, the ESSDAI at baseline (p = 0.05) and Raynaud's phenomenon (p = 0.013) at baseline were the only independent predictors of ILD development. Conclusions: ILD is a relatively common and clinically heterogenous pSS manifestation. Elevated disease activity at pSS onset is a risk factor for ILD development, prompting careful follow-up and intriguingly suggesting that immunomodulatory therapies may prevent ILD.

Arthralgia in psoriasis vulgaris - sometimes it's worth taking a second look

The 71-year-old patient reported long-standing inflammatory arthralgia due to psoriasis vulgaris. Therapy with methotrexate led to elevated liver values; the symptoms persisted under treatment with the TNFα inhibitor adalimumab. Using arthrosonography and MRI, a predominantly periarticular inflammatory pattern on the wrists, metacarpophalangeal joints and proximal interphalangeal joints could be objectified without post-inflammatory stigmata of psoriatic arthritis. Laboratory diagnostics revealed an elevated anti-HCV titer with a high viral load consistent with a florid hepatitis C. A predominantly extrahepatic hepatitis C with associated periarthritis was diagnosed. With combined, interferon-free antiviral therapy, arthralgia suspended completely. Hepatitis C can appear through extrahepatic manifestations in the form of periarticular inflammation. Suspicious inflammatory arthralgias in psoriasis vulgaris are not conterminous with the diagnosis of psoriatic arthritis and should be evaluated by a professional rheumatologist.

Efficacy and safety of TRPV1-related preparations in the treatment of inflammatory arthralgia.

Currently, medications for the treatment of inflammatory arthralgia are limited. The role and safety of transient receptor potential vanilloid subtype 1 (TRPV1)-related preparations in reducing inflammatory arthralgia have not yet been fully established. Thus, we aimed to review the efficacy and safety of TRPV1-related preparations for the treatment of inflammatory arthralgia. We searched PubMed, Web of Science, Cochrane, and Embase databases for relevant studies, and the primary outcome was pain score (VAS, PI, NRS, and WOMAC). Six randomized controlled trials involving 481 patients were analyzed. Patients with inflammatory arthralgia who received TRPV1-related preparations had lower pain scores after treatment than those who received placebo or nonsteroidal anti-inflammatory agents (standardized mean difference = -0.525; 95% confidence interval [CI], -0.789 to -0.261; P < .001). There was no significant difference in the incidence of total adverse reactions between the TRPV1-related preparations and control groups (relative risk = 1.225; 95% CI, 0.685 to 2.191; P = .494). TRPV1-related preparations are clinically safe and effective in the treatment of inflammatory arthralgia and are superior to placebo or nonsteroidal drugs. This may be the preferred treatment for patients with inflammatory arthralgia.

Development of an ultrasound set for early diagnosis of rheumatoid arthritis: First steps

Introduction/ObjectiveEarly diagnosis of rheumatoid arthritis (RA) can improve the prognosis of the disease by reducing joint destruction and achieving a better rate of remission. Musculoskeletal ultrasound (US) has become a potent tool to detect synovitis and erosions. However, until now, there has been a lack of consensus on the US scoring system to help in diagnosing RA early. The purpose of our study was to elaborate a US set suitable for classifying RA patients with inflammatory arthralgia or expressing synovitis and who did not satisfy ACR/EULAR criteria, called “USSRA” (UltraSound Set for Rheumatoid Arthritis). Materials and methodsA multistep study was conducted. A preliminary set of joints, tendons, and erosions to include in the USSRA were identified through a deep literature screening. The final step of this study was the validation of the final set by international experts in US using a Delphi process. ResultsThe preliminary set included 20 joints, 16 tendons, and 8 erosion sites for assessment. After the Delphi process, the changes were to add an assessment of two additional wrist joints and remove one. As for the tendons, two sites were removed from the final set. No changes were proposed for the section erosions. The elementary lesions and scoring system were clarified. The final USSRA forms include 18 joints, 12 tendons, and 8 sites of erosion. ConclusionThe USSRA is a novel diagnostic tool proposed for detecting early RA in routine practice. The next step will be to assess the reliability of this set in a patient-based exercise.

Peripheral neuropathies during systemic diseases: Part I (connective tissue diseases and granulomatosis)

Systemic diseases (connective disease, granulomatosis) may be associated with peripheral neuropathies. The diagnosis can be complex when the neuropathy is the presenting manifestation of the disease, requiring close collaboration between neurologists and internists. Conversely, when the systemic disease is already known, the main question remaining is its imputability in the neuropathy. Regardless of the situation, the positive diagnosis of neuropathy is based on a systematic and rigorous electro-clinical investigation, specifying the topography, the evolution and the mechanism of the nerve damage. Certain imaging examinations, such as nerve and/or plexus MRI, or other more invasive examinations (skin biopsy, neuromuscular biopsy) enable to specify the topography and the mechanism of the injury. The imputability of the neuropathy in the course of a known systemic disease is based mainly on its electro-clinical pattern, on which the alternatives diagnoses depend. In the case of an inaugural neuropathy, a set of arguments orients the diagnosis, including the underlying terrain (young subject), possible associated systemic manifestations (inflammatory arthralgias, polyadenopathy), results of first-line laboratory tests (lymphopenia, hyper-gammaglobulinemia, hypocomplementemia), autoantibodies (antinuclear, anti-native DNA, anti-SSA/B) and sometimes invasive examinations (neuromuscular biopsy).

Rheumatic Diseases Development in Patients Treated by Anti-PD1 Immune Checkpoint Inhibitors: A Single-Centre Descriptive Study.

The introduction of the so-called immune checkpoint inhibitors (ICIs) substantially changed the history of cancer therapy. On the other hand, they can induce the development of rheumatic immune-related adverse events (Rh-irAEs). In the scenario of a joint oncology/rheumatology outpatient clinic, we conducted a single-centre descriptive study to define from a laboratory, clinical and therapeutic point of view, rheumatic conditions developed during anti-PD1 treatment. The study included 32 patients (M/F 16/16, median age 69, IQR 16.5). According to the international classification criteria, eight patients could be classified as affected by Rheumatoid Arthritis, one by Psoriatic Arthritis, six by Polymyalgia Rheumatica, five by systemic connective tissue diseases (two systemic lupus erythematosus, two Sjögren's syndrome, one undifferentiated connective tissue disease). The remaining patients were diagnosed as having undifferentiated arthritis or inflammatory arthralgia. The median interval between ICIs starting and the onset of symptoms was 14 weeks (IQR 19.75). Moving to treatment, the longitudinal observation revealed that all RA, PsA and CTD patients required the introduction of treatment with DMARDs. In conclusion, the growing use of ICIs in a real-life setting confirmed the possible development of different rheumatological conditions, further emphasising the need for shared oncology/rheumatology management.

87 Intracerebral inflammatory pseudotumor in Behçet’s disease: a pediatric case report

IntroductionBehçet's disease is a chronic, relapsing, multisystem vasculitis. The diagnosis is essentially clinical, due to the absence of specific biological criteria, which remains very difficult to establish in pediatric age because of often insidious or atypical disease onset. The association of Pseudo Inflammatory Non-Specific Tumors (PTINS) and Behcet's disease (BD) is exceptionally reported. We report the case of a 12-year-old boy with Behçet's disease who presented with an inflammatory pseudotumor during the course of his disease.Methods and resultsA 12-year-old boy, from Batna (Algeria), with no relevant past medical history, admitted in 2010 for the management of a venous thrombosis of the right lower limb without any obvious cause and which responded well to anticoagulant treatment.A year later, the child was readmitted for polymorphic clinical signs made up of joint damage (inflammatory arthralgia of the large joints), digestive (glairo-bloody diarrhea) and ocular (decreased visual acuity) and skin and mucous membranes (oral-genital apthosis and erythema nodosum of the 4 limbs).Lab work-up showed significant inflammatory syndrome with erythrocyte sedimentation rate (ESR) of 100 mm at the first h, C-reactive protein (CRP) up to 400 mg/l and thrombocytosis (700 000–900 000 elements/mm2). HLA B51 was negative.The patient was treated with Colchicine, Steroids, and Aspirin with partial response. Subsequently, a treatment with azathioprine was started, with clinical improvement (despite occasional digestive crises) but with persistent biologic inflammation.In 2012 the patient presented with a unilateral decrease in visual acuity. A CT scan was performed showing an intracranial tumor compressing the right optic nerve with all the criteria of a malignant tumor (rupture of the cortex, increase in volume on 2 successive CT scans). A transsphenoidal biopsy of the mass revealed a non-specific inflammation. Biological treatment with anti-TNF alpha (Infliximab) was associated with a spectacular tumor regression, allowing retrospectively the diagnosis of an inflammatory granulomatous lesion related to Behçet's disease rather than a malignant tumor. The outcomes were favorable with clinical and biological improvement for the first time since the onset of the disease.ConclusionBehcet is rare in the pediatric age group and it is difficult to diagnose. Nonspecific inflammatory pseudotumors can be associated with Behçet's disease and constitute a real diagnostic and therapeutic challenge.Disclosure of InterestNone declared

Erosive arthritis in systemic lupus erythematosus: application of cluster analysis.

In the present study, we applied cluster analysis (CA) in SLE patients with joint involvement to identify which disease subset most commonly develops erosive damage. We collected clinical and laboratory data of SLE patients with a clinical history of joint involvement (arthritis/arthralgia). Ultrasonographic assessment was performed at level of MCPs and PIPs joints, to identify erosive arthritis, defined as the presence of erosions in at least one joint. Moreover, we detected RF, ACPA anti-CarP, and Dkk1 serum levels. We applied an unsupervised hierarchical CA to identify the aggregation of patients into different subgroups sharing common characteristics in terms of clinical and laboratory phenotypes. CA included 112 SLE patients (M/F 6/106; median age 45 years, IQR 17; median disease duration 96 months, IQR 165). Arthritis was observed in 82 patients (73.2%) and inflammatory arthralgia in 30 (26.8%). US-detected erosive arthritis was observed in 29 patients (25.9%). CA on clinical and laboratory features allowed the identification of four main clusters: in particular erosive arthritis was located in a cluster including renal and neuropsychiatric involvement, serositis, positivity for ACPA, anti-Carp, anti-Sm, anti-RNP, detectable levels of Dkk1. The application of CA made it possible to better characterise SLE phenotype including erosive arthritis. In particular, feature-driven CA leads to the identification of a more aggressive disease, due to a common pathogenic mechanism.

Systemic lupus erythematosus and antiphospholipid syndrome after COVID-19 vaccination. A case report.

IntroductionCOVID-19 vaccines have some adverse effects, mostly mild. However, by presenting an immunological challenge to the individual, they could infrequently trigger immune-mediated diseases.Case reportWe report the case of a 42-year-old woman, with no previous medical history, who received the first dose of vaccine against COVID-19 and developed inflammatory arthralgias, associated with sudden onset dyspnea and hypoxemia. Pulmonary thromboembolism was documented and the diagnosis of systemic lupus erythematosus (SLE) and secondary antiphospholipid syndrome (APS) was suspected. Autoantibodies were measured confirming this suspicion. After a few days, she presented a massive pericardial effusion with cardiac tamponade that required surgical management. She received treatment with hydroxychloroquine, corticosteroids and anticoagulation with improvement of all symptoms.DiscussionThere is controversy regarding the potential of COVID-19 vaccines to induce autoimmunity. Studies addressing the safety of using these vaccines have reported the occurrence of mild local and systemic reactions, most frequently in young adults. So far there are few reports of patients who have developed autoimmune or autoinflammatory diseases after getting vaccinated with any of the COVID-19 vaccines. To the best of our knowledge, to date this is one of the first cases of new-onset SLE and secondary APS after COVID-19 vaccination.

Antineutrophil cytoplasmic antibody-associated vasculitis in presence of positive antiphospholipid antibody: a case report\xa0

BackgroundAntineutrophil cytoplasmic antibody-associated vasculitis is dominated by inflammatory occlusion of small vessels, causing tissue ischemia in various organs. This disorder has rarely been associated with vasculopathy, such as antiphospholipid syndrome.Case presentationWe report a case of a 48-year-old Persian male presenting with distal digital gangrene along with inflammatory arthralgia. High titers of anti-proteinase 3 and antiphospholipid antibodies (anticardiolipin antibody) were detected in laboratory evaluation. Therefore, a diagnosis of antineutrophil cytoplasmic antibody-associated vasculitis and antiphospholipid syndrome was made and treated with anticoagulant along with monthly pulses of cyclophosphamide and a daily dose of 1 mg/kg prednisolone.ConclusionOur case, along with other reports, illustrates that these two entities can coexist. Therefore, monitoring antiphospholipid antibodies in patients with antineutrophil cytoplasmic antibody-associated vasculitis with or without clinical evidence of any thrombosis and ruling out thrombosis in cases that do not respond to proper treatment of vasculitis may be relevant to prevent irreversible or fatal organ damage.

A rare variant of chronic inflammatory demyelinating polyneuropathy with autonomic dysfunction

A young hypothyroid female with history of chronic inflammatory small joint arthralgias presenting with distal sensory motor symptoms of 8 weeks duration and prominent disturbances of bladder sensations was found to have symmetric motor and distal large fibre sensory loss and blunting of perineal sensations. On evaluation was found to have a normal nerve conduction study at presentation and imaging showing hypertrophic and enhancing cervical and lumbosacral nerve roots with a positive marker of mixed connective tissue disorder on ANA profile, fitting into a diagnosis of Chronic Immune Sensorimotor Polyradiculopathy in the background of a connective tissue disorder.

Risk Factors for Developing Rheumatoid Arthritis in Patients With Undifferentiated Arthritis and Inflammatory Arthralgia.

Currently, there is an increasing interest in treating patients at risk of rheumatoid arthritis (RA) to prevent the development of this chronic disease. In this sense, research has focused attention on the early identification of predictive factors of this disease. Autoantibodies and markers of systemic inflammation can be present before clinical arthritis and RA development. So, the phase of inflammatory arthralgia preceding clinical arthritis is an important part of the window of opportunity and, starting treatment might prevent progression to chronic arthritis. Additionally, the early diagnosis and treatment initiation, in patients with inflammatory arthritis at risk of persistence and/or erosive progression, are fundamental because may allow optimal clinical responses, better chances of achieving sustained remission, preventing irreversible organ damage and optimizing long-term outcomes. This review aims to give an overview of clinical risk factors for developing RA, both in suspected arthralgia and in undifferentiated arthritis. Besides taking into consideration the role of serological markers (immunological and acute phase reactants) and clinical features assessed at consultation such as: articular affection and patient's clinical perception. Other features as sociodemographic and environmental factors (lifestyle habits, microbiota, periodontal disease among others), have been included in this revision to give an insight on strategies to prevent development of RA and/or to treat it in early stages.

Recommendations for the pragmatic use of ultrasound in rheumatoid arthritis by the GEISPER French group.

To develop recommendations for the appropriate use of ultrasound in the management of rheumatoid arthritis (RA) in routine practice based on data from the literature and of experts opinion. Based on a systematic literature review, a scientific committee decided on themes and relevant questions to draw up an initial draft of recommendations. These recommendations were submitted to a group of experts in ultrasound in rheumatic and musculoskeletal diseases using a Delphi method, which produced preliminary recommendations. These were submitted to an expanded group of ultrasound experts for relevance, comprehensibility and comprehensiveness. The level of agreement of the experts were recorded during a face-to-face meeting. Following two rounds of the Delphi, a consensus was reached on three overarching principles, including definitions of joints, tendons and articular sites to be examined, and 10 recommendations. These recommendations underline the benefit of ultrasound for the diagnosis of RA in cases of inflammatory arthralgia or undifferentiated arthritis as well as in assessing the extent of initial structural and inflammatory damage. They also define the role of ultrasound during follow-up or when considering treatment reduction once clinical remission has been achieved. Lastly, they illustrate the utility of ultrasound in facilitating technical procedures. These 10 consensus-based recommendations should harmonize and optimize clinical practice and thus improve the management of RA patients.

Contribution of Ultrasonography of Hands and Wrists in Early Rheumatoid Arthritis.

Early diagnosis and management of rheumatoid arthritis (RA) have improved the outcome of patients. In the last decade, musculoskeletal Ultrasonography (MSUS) had demonstrated its superiority over clinical examination in detecting synovitis in RA. We conducted this present study in order to assess the added value of MSUS in diagnosing early RA. A cross-sectional study was conducted, including one hundred patients diagnosed RA based on the physician's opinion and presenting with inflammatory arthralgia or swollen joints for more than 6 weeks and less than 2 years. Patients underwent clinical, laboratory, and radiographic examination. MSUS was performed by a radiologist blinded to clinical findings assessing 22 joints of hands. A US ACR/EULAR 2010 score was calculated by replacing the swollen joints of hands with those expressing synovitis in Greyscale US. Agreement between clinical and US ACR/EULAR score was assessed. Among the 2200 joints scanned by the US, synovitis was detected in 81% of patients, an intra-articular effusion in 36% patients, and PD signals in 51% of patients. Flexor tenosynovitis was present in 55% of patients and extensor tenosynovitis in 59% of patients. Synovitis and PD signals were more often detected in wrists. PD mode was found to be correlated with CRP results (r=0,302, p=0,023). The MSUS assessment has demonstrated synovitis on 71% (N=22) patients who were free of swollen joints on clinical examination. Through 13 patients expressing monoarthritis at clinical examination, 69% (N=9) patients were reclassified with oligo or polyarthritis. By adding US data, a further 13 patients accomplished the ACR/EULAR score. A good level of agreement was found between clinical and US ACR/EULAR criteria (k=0,684, p=0,001). MSUS is an inexpensive and accessible examination tool, which should be considered in patients in the onset of an inflammatory rheumatic disease in order to benefit of the window of opportunity and reach remission.

Apremilast in Refractory Behçet's Syndrome: A Multicenter Observational Study.

ObjectiveMucocutaneous and joint disorders are the most common manifestations in Behçet’s syndrome (BS) and are frequently clustered in the so-called minor forms of BS. There remains a need for safe and effective treatment for joint lesions in BS. We report the long-term safety and effectiveness of apremilast in refractory joint and mucocutaneous manifestations of BS.MethodsFrench nationwide multicenter study including 50 BS patients with either active joint and/or mucocutaneous manifestations resistant to colchicine and/or DMARDs. Patients received apremilast 30 mg twice a day. Primary effectiveness endpoint was the proportion of patients with complete response (CR) of articular symptoms at month 6 (M6), defined as resolution of inflammatory arthralgia and arthritis, with joint count equal to zero.ResultsAt inclusion, the median tender and swollen joint count was of 4 [2-6] and 2 [1-2], respectively. The proportion of CR in joint disease at M6 was 65% (n = 15/23), and 17% (n = 4/23) were partial responders. CR of oral and genital ulcers, and pseudofolliculitis at M6 was 73% (n = 24/33), 94% (n = 16/17) and 71% (n = 10/14), respectively. The overall response at M6 was 74% for the entire cohort and 70% for the mucocutaneous-articular cluster (n = 27). The median Behçet’s syndrome activity score significantly decreased during study period [50 (40–60) vs. 20 (0–40); p <0.0001]. After a median follow-up of 11 [6-13] months, 27 (54%) patients were still on apremilast. Reasons for apremilast withdrawal included adverse events (n = 15, 30%) and treatment failure (n = 8, 16%). Thirty-three (66%) patients experienced adverse events, mostly diarrhea (n = 19, 38%), nausea (n = 17, 34%) and headache (n = 16, 32%).ConclusionApremilast seems effective in BS-related articular disease refractory to colchicine and DMARDs. Discontinuation rates were significantly higher than that reported in clinical trials.

Associations between serum antibodies to periodontal pathogens and preclinical phases of rheumatoid arthritis.

To examine whether serum antibodies against selected periodontal pathogens are associated with early symptoms of RA development in healthy individuals at risk of developing the disease. Within an ongoing study cohort of first-degree relatives of patients with RA (RA-FDRs), we selected four groups corresponding to specific preclinical phases of RA development (n = 201). (i) RA-FDR controls without signs and symptoms of arthritis nor RA-related autoimmunity (n = 51); (ii) RA-FDRs with RA-related autoimmunity (n = 51); (iii) RA-FDRs with inflammatory arthralgias without clinical arthritis (n = 51); and (iv) RA-FDRs who have presented at least one swollen joint ('unclassified arthritis') (n = 48). Groups were matched for smoking, age, sex and shared epitope status. The primary outcome was IgG serum levels against five selected periodontal pathogens and one commensal oral species assessed using validated-in-house ELISA assays. Associations between IgG measurements and preclinical phases of RA development were examined using Kruskal-Wallis or Mann-Whitney tests (α = 0.05). None of the IgGs directed against individual periodontal pathogens significantly differed between the four groups of RA-FDRs. Further analyses of cumulated IgG levels into bacterial clusters representative of periodontal infections revealed significantly higher IgG titres against periodontopathogens in anti-citrullinated protein antibodies (ACPA)-positive RA-FDRs (P = 0.015). Current smoking displayed a marked trend towards reduced IgG titres against periodontopathogens. Our results do not suggest an association between serum IgG titres against individual periodontal pathogens and specific preclinical phases of RA development. However, associations between cumulative IgG titres against periodontopathogens and the presence of ACPAs suggest a synergistic contribution of periodontopathogens to ACPA development.

Emergence of Different Autoimmune Diseases Including a Behçet's disease in a Sibling After tick bites. Remarkable cure of Behcet's disease by a Combination of Antibiotics and Hydroxychloroquine

We report therein the onset of three chronic diseases: Behcet's disease, fibromyalgia and rheumatoid arthritis in three sisters after tick bites. Only Behcet's disease was treated in our department. After failure of the initial treatment including colchicine and corticoids, the patient recovered within a prolonged antibiotic therapy time period of 18 months. A 23-year-old female patient was admitted to hospital in the Infectious Diseases Department as she presented with headache, diffuse inflammatory arthromyalgia, abdominal pain and cutaneous folliculitis, and for the umpteenth time for several past years, meningeal syndrome recurrence. The physical examination was unremarkable. The biological test assessment was normal, as were the ophthalmological and cerebral MRI examinations. The patient’s HLA B5 test was negative. The upper digestive fibroscopy shown digestive ulcerations. The diagnosis of Behcet's disease was made on the following: inflammatory arthralgias, digestive ulcerations, folliculitis lesions; recurrent bipolar aphthosis was found at patient’s interview. The patient was given prednisone 0.5 mg/kg/day and colchicine 1 mg/day. The evolution was characterized by an initial improvement of clinical symptoms followed by further iterative recurrence as soon as the corticosteroid doses were reduced. Upon resuming the interview with the patient’ s mother, clinical symptoms began at the age of 9 years old by the occurrence of a voluminous cutaneous erythema following multiple tick bites. One month later the patient presented with subacute lymphocytic meningitis, which was treated as tuberculosis meningitis without relevant bacteriological evidence. On the same day, the patient's two sisters were also bitten by ticks. A few weeks later on, one of them developed osteomyelitis of the tibia, which was operated on. The bacteriological examination result was negative, the histological examination showed non-specific osteomyelitis. Subsequently, she developed various multiple functional complaints that led to the diagnosis of fibromyalgia. Her other sister concomitantly developed seronegative rheumatoid arthritis. The diagnosis of chronic post-tick bite syndrome was suspected despite the negativity of the Lyme serology. The patient significantly improved thanks to high-dose of intravenous penicillin G, despite an initial exacerbation during the first month of treatment, which could be interpreted as confirmation of an infectious process (Jarisch-Herxheimer reaction). Corticosteroids and colchicine were discontinued ; the patient was given doxycycline for a total duration of 18 months. Antibiotic therapy was associated with hydroxychloroquine, the same way as reported for therapy of chronic Q fever and some types of Lyme disease [1]. In 2004, the patient was in complete remission of Behcet's disease. Ten years later, no recurrence has been observed.

Immune-related adverse events in patients with solid-organ tumours treated with immunotherapy: a 3-year study of 102 cases from a single centre

Immune checkpoint blockade therapy (ICBT) increases the anti-tumoural function of the immune system, but it can also induce immune-related adverse events (irAEs). Our aim was to assess the irAEs due to ICBT in patients from a single centre of Northern Spain. We set up an observational study of patients treated in monotherapy with ICBT targeted against cytotoxic T-lymphocyte antigen 4 (CTLA-4), programmed cell death 1 (PD-1) or its ligand (PD-L1) for solid organ tumours. All patients were followed up in a single University Hospital from March 2015 to September 2018. We studied 102 patients (63 men/39 women); mean age 60.6±9.7 years, with lung (n=63), melanoma (n=21), kidney (n=11), gastric (n=3), colon (n=3) or bladder (n=1) cancer. Only 7 patients had a previous diagnosis of an immune-mediated disease, specifically: psoriasis (n=2), psoriatic arthritis (n=1), systemic lupus erythematosus (n=1), spondyloarthitis (n=1), rheumatoid arthritis (n=1) and cutaneous lupus (n=1). One of the following ICBT was administered: nivolumab (n=52), pembrolizumab (n=35), atezolizumab (n=10) and ipilimumab (n=5). After a mean follow-up time of 14.4±7.7 months since ICBT onset, 87 (85.3%) patients had experienced irAEs, mostly gastrointestinal, thyroid and musculskeletal manifestations including inflammatory arthralgia (n= 8), arthritis (n= 6) and myositis (n=2). ICBT was discontinued in 41 patients but it was reintroduced in 30 of them after resolution of the adverse event, with a good tolerance in all cases. Thirty-six (41.4%) of the 87 patients required specific treatment (prednisone, levothyroxine, and thiamazol) for the irAEs. irAEs are frequent in patients undergoing ICBT. Almost half of the patients that have irAEs require treatment. Musculoskeletal manifestations are not uncommon.