Osteoporosis therapy in patients with inflammatory rheumatic diseases and osteonecrosis of the jaw.

BACKGROUND AND OBJECTIVES: The aim of the present study was to assess the prevalence of medication-related osteonecrosis of the jaw (MRONJ) in osteoporosis patients suffering from inflammatory rheumatic diseases, as well as to assess the prevalence of relevant dental, behavioral, and medical risk factors for MRONJ. MATERIALS AND METHODS: A total of 198 patients with inflammatory rheumatic diseases and osteoporosis therapy were recruited from a tertiary rheumatological/immunological referral center between June 2015 and September 2016. They were assessed using a structured interview. A maxillofacial surgeon later examined patients complaining of possible symptoms of osteonecrosis. In cases of osteonecrosis, dental records were obtained and evaluated. Preventive measures taken and dental as well as other clinical risk factors were evaluated. RESULTS: Of the 198 patients, three suffered from osteonecrosis of the jaw, none of whom had any history of malignant disease or radiation therapy, resulting in a prevalence of 1.5%. Of these three patients, only one was given bisphosphonates intravenously (i.v.), whereas all three had been treated orally. All three diagnoses of MRONJ had been previously known to the patients and their maxillofacial surgeons. Two of the patients had rheumatoid arthritis, and one patient suffered from large vessel vasculitis. Long anti-osteoporotic treatment duration, low functional status, and low bone density of the femur were significantly associated with MRONJ development. CONCLUSION: Inflammatory rheumatic diseases constitute a risk factor for MRONJ in patients treated with bisphosphonates for osteoporosis. Patients should be counseled accordingly and should be offered dental screening and regular dental check-ups.

T cells, natural killer cells, and γδT cells in a large patient cohort with rheumatoid arthritis: influence of age and anti-rheumatic therapy.

Objective: The aim of this cohort study was to evaluate the distribution of natural killer (NK) cells and T-cell subsets, including γδT cells, in the peripheral blood of patients with rheumatoid arthritis (RA) in a large real-life patient cohort, taking into account the patients' demographics, disease characteristics, and anti-rheumatic therapy.Method: The study recruited 508 RA patients between November 2013 and August 2015. Lymphocyte differentiation using eight-colour flow cytometry (fluorescence-activated cell sorting) of the peripheral blood was performed for all patients. Clinical data, including age, gender, disease duration, serostatus, disease activity, antibody status, immunosuppressive therapy including use of different biological disease-modifying anti-rheumatic drugs (bDMARDs) and conventional synthetic DMARDs, were retrospectively assessed using electronic patient files. Multivariate regression analysis was performed to assess the effect of these variables on T-cell, NK-cell, and γδT-cell counts.Results: The median patient age was 61.0 years and 74.1% were female. The median disease duration of RA was 12.0 years. Median Disease Activity Score based on 28-joint count was 2.8 and 56.3% were treated with bDMARDs. There were no differences in immunosuppressive therapy between different age groups. While rituximab, abatacept, and tocilizumab had no influence on lymphocyte subdifferentiation, tumour necrosis factor (TNF) inhibitors and age significantly influenced the numbers of T cells, T-helper cells, T-NK cells, NK cells, and γδT cells.Conclusion: Age and TNF-inhibition therapy influence lymphocyte subdifferentiation in patients with RA. It may be prudent to use age- and therapy-adjusted standard values for lymphocyte subsets during clinical trials and treatment of RA.

Addition or removal of concomitant methotrexate alters adalimumab effectiveness in rheumatoid arthritis but not psoriatic arthritis.

Objective: Randomized trials have shown that concomitant methotrexate (MTX) augments the effectiveness of tumour necrosis factor (TNF) inhibitors in rheumatoid arthritis (RA), but its benefit in psoriatic arthritis (PsA) has not been demonstrated. The goal of this study was to examine whether the impact of concomitant MTX on therapeutic outcomes in patients with PsA was similar to its effects in RA. Methods: We used data from highly comparable and concurrent observational studies of patients with PsA (N = 1424) or RA (N = 3148) who initiated adalimumab therapy during routine clinical care. The 28-joint Disease Activity Score (DAS28) and patient-reported pain scores were evaluated in patients who received 24 months of continuous treatment with adalimumab monotherapy or adalimumab + MTX and in patients who initiated or stopped concomitant MTX during ongoing adalimumab therapy. Results: Twenty-four months of continuous treatment with adalimumab + MTX was superior to adalimumab monotherapy in RA patients, while no significant difference was observed in patients with PsA. RA patients who added MTX during the study showed significant individual improvements in DAS28 and pain scores at 6 months after the change in therapy, while those who removed MTX had slight increases in disease activity. In contrast, in patients with PsA, neither initiation nor removal of MTX during continuous adalimumab therapy had a significant effect on therapeutic outcomes. Conclusion: Addition of MTX to adalimumab confers further therapeutic benefit in patients with RA, but not in those with PsA, suggesting differences in MTX effects in these two patient populations. Clinicaltrials.gov NCT01078090, NCT01077258, NCT01111240.

[Recurrent infections of the upper aerodigestive tract in patients with primary immunodeficiency]. / Rezidivierende Infektionen bei Patienten mit primären Immundefekten im oberen Aerodigestivtrakt.

BACKGROUND: Primary immunodeficiency is a rare disease of humoral and cellular immune defense, which can lead to severe and recurrent infections of different organs. The diagnosis of this disease is often difficult, and its early identification is necessary for adequate treatment and control. OBJECTIVE: This study aimed to analyze ear, nose, and throat (ENT) infections in adults and children with a primary immunodeficiency. We attempted to characterize possible warning signs that should trigger an immunologic diagnostic workup. MATERIALS AND METHODS: The current study comprised a retrospective case series of patients with primary immunodeficiencies. The type of immunodeficiency and the number of ENT infections were recorded. RESULTS: A total of 85 Patients were included in the study. 56 patients (66%) had an acute exacerbation of chronic rhinosinusitis (n = 28), cervical lymphadenitis (n = 16), acute tonsillitis (n = 14), and acute otitis media (n = 6). Reporting detailed information about the frequencies and dates of infections was not possible, due to the retrospective nature of the analysis. CONCLUSION: The prevalence of ENT infections in patients with a primary immunodeficiency is increased compared to the normal population. For the ENT specialist, these findings underline the necessity of including primary immunodeficiency in the differential diagnosis and initiating targeted diagnostic methods where indicated. Interdisciplinary collaboration with rheumatologists and immunologists is highly recommended, particularly for pediatric patients.

Power-Doppler perfusion phenotype in RA patients is dependent on anti-citrullinated peptide antibody status, not on rheumatoid factor.

It is not known whether there are any consistent non-serological differences between seropositive and seronegative rheumatoid arthritis, and if any, whether they depend upon rheumatoid factor (RF), anti-citrullinated peptide antibodies (ACPA), or both. In a pilot study, we showed that the two forms could be differentiated using power-Doppler sonography (PDS), and that the difference is ACPA dependent. This extended study explored whether the previous findings could be confirmed. 103 patients 51 ACPA positive (ACPA +), 52 ACPA negative (ACPA -) with active wrist arthritis were examined using PDS. By means of a temporal image series, pulsatility was evaluated over a 3-5-s period, maximum and minimum perfusion signal were determined using a computer program counting the number of coloured pixels for each frame. Maxima (Pmax) and minima (Pmin) were determined, and the standardized peak-to-peak amplitude sA was calculated (sA = (Pmax - Pmin)/Pmax). This parameter was then compared for ACPA + and ACPA- patients. In addition, a multivariate regression was performed, to determine which factors influence sA. sA differed significantly between ACPA + and ACPA- patients [20% (13-26) vs. 41% (32-57), p < 0. 0001]. In the multivariate analysis, age (t = 2.5, p = 0.02) and ACPA status (t = - 4.8, p < 0.0001) were independent predictors of sA. PDS perfusion patterns are different in seropositive and seronegative RA. The difference appears to be ACPA, not RF dependent. This suggests that the underlying pathophysiological process is different in ACPA-positive and ACPA-negative RA.