TY - JOUR A1 - Froehlich, Matthias A1 - Zahner, Antonia A1 - Schmalzing, Marc A1 - Gernert, Michael A1 - Strunz, Patrick-Pascal A1 - Hueper, Sebastian A1 - Portegys, Jan A1 - Schwaneck, Eva Christina A1 - Gadeholt, Ottar A1 - Kübler, Andrea A1 - Hewig, Johannes A1 - Ziebell, Philipp T1 - Patient-reported outcomes provide evidence for increased depressive symptoms and increased mental impairment in giant cell arteritis JF - Frontiers in Medicine N2 - Objectives The spectrum of giant cell arteritis (GCA) and polymyalgia rheumatica (PMR) represents highly inflammatory rheumatic diseases. Patients mostly report severe physical impairment. Possible consequences for mental health have been scarcely studied. The aim of this study was to investigate psychological well-being in the context of GCA and PMR. Methods Cross-sectional study with N = 100 patients with GCA and/or PMR (GCA-PMR). Patient-reported outcomes (PROs) were measured using the Short Form 36 Version 2 (SF-36v2) and visual analog scale (VAS) assessment. Moreover, the Patient Health Questionnaire 9 (PHQ-9) was used in 35 of 100 patients to detect depression. To compare PROs with physician assessment, VAS was also rated from physician perspective. To assess a possible association with inflammation itself, serological parameters of inflammation (C-reactive protein [CRP], erythrocyte sedimentation rate [ESR]) were included. Results In all scales of the SF-36v2 except General Health (GH) and in the physical and mental sum score (PCS, MCS), a significant impairment compared to the German reference collective was evident (MCS: d = 0.533, p < 0.001). In the PHQ-9 categorization, 14 of the 35 (40%) showed evidence of major depression disorder. VAS Patient correlated significantly with PHQ-9 and SF-36 in all categories, while VAS Physician showed only correlations to physical categories and not in the mental dimensions. Regarding inflammatory parameters, linear regression showed CRP to be a complementary significant positive predictor of mental health subscale score, independent of pain. Conclusion PRO show a relevant impairment of mental health up to symptoms of major depression disorder. The degree of depressive symptoms is also distinctly associated with the serological inflammatory marker CRP. KW - giant cell arteritis KW - PRO KW - depression KW - mental impairment KW - SF-36 KW - PHQ-9 KW - VAS KW - polymyalgia rheumatica Y1 - 2023 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-319761 VL - 10 ER - TY - JOUR A1 - Guggenberger, Konstanze V. A1 - Vogt, Marius L. A1 - Song, Jae W. A1 - Weng, Andreas M. A1 - Fröhlich, Matthias A1 - Schmalzing, Marc A1 - Venhoff, Nils A1 - Hillenkamp, Jost A1 - Pham, Mirko A1 - Meckel, Stephan A1 - Bley, Thorsten A. T1 - Intraorbital findings in giant cell arteritis on black blood MRI JF - European Radiology N2 - Objective Blindness is a feared complication of giant cell arteritis (GCA). However, the spectrum of pathologic orbital imaging findings on magnetic resonance imaging (MRI) in GCA is not well understood. In this study, we assess inflammatory changes of intraorbital structures on black blood MRI (BB-MRI) in patients with GCA compared to age-matched controls. Methods In this multicenter case-control study, 106 subjects underwent BB-MRI. Fifty-six patients with clinically or histologically diagnosed GCA and 50 age-matched controls without clinical or laboratory evidence of vasculitis were included. All individuals were imaged on a 3-T MR scanner with a post-contrast compressed-sensing (CS) T1-weighted sampling perfection with application-optimized contrasts using different flip angle evolution (SPACE) BB-MRI sequence. Imaging results were correlated with available clinical symptoms. Results Eighteen of 56 GCA patients (32%) showed inflammatory changes of at least one of the intraorbital structures. The most common finding was enhancement of at least one of the optic nerve sheaths (N = 13, 72%). Vessel wall enhancement of the ophthalmic artery was unilateral in 8 and bilateral in 3 patients. Enhancement of the optic nerve was observed in one patient. There was no significant correlation between imaging features of inflammation and clinically reported orbital symptoms (p = 0.10). None of the age-matched control patients showed any inflammatory changes of intraorbital structures. Conclusions BB-MRI revealed inflammatory findings in the orbits in up to 32% of patients with GCA. Optic nerve sheath enhancement was the most common intraorbital inflammatory change on BB-MRI. MRI findings were independent of clinically reported orbital symptoms. Key Points • Up to 32% of GCA patients shows signs of inflammation of intraorbital structures on BB-MRI. • Enhancement of the optic nerve sheath is the most common intraorbital finding in GCA patients on BB-MRI. • Features of inflammation of intraorbital structures are independent of clinically reported symptoms. KW - giant cell arteritis KW - magnetic resonance imaging KW - orbit KW - ophthalmic artery KW - optic nerve Y1 - 2023 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-324978 VL - 33 IS - 4 ER - TY - JOUR A1 - Reiter, Theresa A1 - Demirbas, Senem A1 - Schmalzing, Marc A1 - Voelker, Wolfram A1 - Bauer, Wolfgang R. A1 - Güder, Gülmisal T1 - CMR detects extensive intracavitary thrombi as solitary clinical presentation of Antiphospholipid Syndrome: A case report JF - Clinical Case Reports N2 - Intracavitary thrombi are an important differential diagnosis of cardiac masses. Cardiac magnetic resonance imaging (CMR) allows their non-invasive characterization. This case highlights extensive cardiac thrombi detected by CMR as solitary presentation of antiphospholipid syndrome. KW - antiphospholipid syndrome KW - cardiac thrombi KW - CMR Y1 - 2022 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-312766 SN - 2050-0904 VL - 10 IS - 11 ER - TY - JOUR A1 - Gernert, Michael A1 - Schmalzing, Marc A1 - Tony, Hans-Peter A1 - Strunz, Patrick-Pascal A1 - Schwaneck, Eva Christina A1 - Fröhlich, Matthias T1 - Calprotectin (S100A8/S100A9) detects inflammatory activity in rheumatoid arthritis patients receiving tocilizumab therapy JF - Arthritis Research & Therapy N2 - Background Assessing serological inflammation is difficult in tocilizumab (TCZ)-treated rheumatoid arthritis (RA) patients, as standard inflammation parameters, like erythrocyte sedimentation rate (ESR) and C-reactive protein (CRP), are influenced by interleukin-6-receptor inhibition. Calprotectin in the serum, also named S100A8/S100A9, might be a more useful inflammation parameter in TCZ-treated patients. Methods Sixty-nine RA patients taking TCZ were included. Serum-calprotectin levels were assessed, as well as ESR, CRP, need for a change in disease-modifying anti-rheumatic drugs due to RA activity (= active RA), and the RA clinical disease activity score (CDAI). Forty-five RA patients taking tumor-necrosis factor-inhibitors (TNFi) were investigated for the same parameters. Results TCZ-treated patients with active RA had higher calprotectin values than not active RA patients (4155.5 [inter quartile range 1865.3–6068.3] vs 1040.0 [676.0–1638.0] ng/ml, P < 0.001). A calprotectin cut-off value of 1916.5 ng/ml resulted in a sensitivity and specificity of 80.0 %, respectively, for the detection of RA disease activity. Calprotectin values correlated with CDAI-scores (r = 0.228; P = 0.011). ESR and CRP were less suitable to detect RA activity in TCZ-treated patients. Also TNFi-treated patients with active RA had higher calprotectin values compared to not active RA (5422.0 [3749.0–8150.8] vs 1845.0 [832.0–2569.0] ng/ml, P < 0.001). The calprotectin value with the best sensitivity and specificity for detecting RA activity was 3690.5 ng/ml among TNFi-treated patients. Conclusion Calprotectin in the serum can be a useful inflammation parameter despite TCZ-treatment. KW - calprotectin KW - inflammation marker KW - c-reactive protein KW - tocilizumab KW - rheumatoid arthritis KW - S100A8/S100A9 Y1 - 2022 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-300523 VL - 24 IS - 1 ER - TY - JOUR A1 - Gernert, Michael A1 - Tony, Hans-Peter A1 - Schwanek, Eva Christina A1 - Gadeholt, Ottar A1 - Fröhlich, Matthias A1 - Portegys, Jan A1 - Strunz, Patrick-Pascal A1 - Schmalzing, Marc T1 - Lymphocyte subsets in the peripheral blood are disturbed in systemic sclerosis patients and can be changed by immunosuppressive medication JF - Rheumatology International N2 - Systemic sclerosis (SSc) is a severe chronic disease with a broad spectrum of clinical manifestations. SSc displays disturbed lymphocyte homeostasis. Immunosuppressive medications targeting T or B cells can improve disease manifestations. SSc clinical manifestations and immunosuppressive medication in itself can cause changes in lymphocyte subsets. The aim of this study was to investigate peripheral lymphocyte homeostasis in SSc with regards to the immunosuppression and to major organ involvement. 44 SSc patients and 19 healthy donors (HD) were included. Immunophenotyping of peripheral whole blood by fluorescence-activated cell sorting was performed. Cytokine secretions of stimulated B cell cultures were measured. SSc patients without immunosuppression compared to HD displayed lower γδ T cells, lower T helper cells (CD3+/CD4+), lower transitional B cells (CD19+/CD38++/CD10+/IgD+), lower pre-switched memory B cells (CD19+/CD27+/IgD+), and lower post-switched memory B cells (CD19+/CD27+/IgD-). There was no difference in the cytokine production of whole B cell cultures between SSc and HD. Within the SSc cohort, mycophenolate intake was associated with lower T helper cells and lower NK cells (CD56+/CD3-). The described differences in peripheral lymphocyte subsets between SSc and HD generate further insight in SSc pathogenesis. Lymphocyte changes under effective immunosuppression indicate how lymphocyte homeostasis in SSc might be restored. KW - mycophenolate KW - systemic sclerosis KW - scleroderma KW - memory B cells KW - B cell culture KW - cytokines KW - γδ T cells KW - immunophenotyping Y1 - 2022 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-266482 SN - 1437-160X VL - 42 IS - 8 ER - TY - JOUR A1 - Gernert, Michael A1 - Tony, Hans-Peter A1 - Fröhlich, Matthias A1 - Schwaneck, Eva Christina A1 - Schmalzing, Marc T1 - Immunosuppressive therapy after autologous hematopoietic stem cell transplantation in systemic sclerosis patients — high efficacy of Rituximab JF - Frontiers in Immunology N2 - Background Systemic sclerosis (SSc) patients often need immunosuppressive medication (IS) for disease control. If SSc is progressive despite IS, autologous hematopoietic stem cell transplantation (aHSCT) is a treatment option for selected SSc patients. aHSCT is effective with good available evidence, but not all patients achieve a treatment-free remission after aHSCT. Thus far, data about the need of IS after aHSCT in SSc is not published. The aim of this study was to investigate the use of IS after aHSCT, its efficacy, and the occurrence of severe adverse events (SAEs). Methods Twenty-seven patients with SSc who had undergone aHSCT were included in this single-center retrospective cohort study. Clinical data, including IS, SAEs, and lung function data, were collected. Results Sixteen of 27 (59.3%) patients received IS after aHSCT. Methotrexate, rituximab, mycophenolate, cyclophosphamide, and hydroxychloroquine were most commonly used. The main reason for starting IS was SSc progress. Nine patients received rituximab after aHSCT and showed an improvement in modified Rodnan skin score and a stabilization of lung function 2 years after rituximab. SAEs in patients with IS after aHSCT (50.0%) were not more common than in patients without IS (54.6%). SAEs were mostly due to SSc progress, secondary autoimmune diseases, or infections. Two deaths after aHSCT were transplantation related and three during long-term follow-up due to pulmonary arterial hypertension. Conclusion Disease progression and secondary autoimmune diseases may necessitate IS after aHSCT in SSc. Rituximab seems to be an efficacious treatment option in this setting. Long-term data on the safety of aHSCT is reassuring. KW - systemic sclerosis KW - scleroderma KW - autologous hematopoietic stem cell transplantation KW - immunosuppression KW - adverse events KW - rituximab Y1 - 2022 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-254345 SN - 1664-3224 VL - 12 ER - TY - JOUR A1 - Gernert, Michael A1 - Kiesel, Matthias A1 - Fröhlich, Matthias A1 - Renner, Regina A1 - Strunz, Patrick-Pascal A1 - Portegys, Jan A1 - Tony, Hans-Peter A1 - Schmalzing, Marc A1 - Schwaneck, Eva Christina T1 - High Prevalence of Genital Human Papillomavirus Infection in Patients With Primary Immunodeficiencies JF - Frontiers in Immunology N2 - Background Genital human papillomavirus (HPV)-infections are common in the general population and are responsible for relevant numbers of epithelial malignancies. Much data on the HPV-prevalence is available for secondary immunodeficiencies, especially for patients with human immunodeficiency virus (HIV)-infection. Little is known about the genital HPV-prevalence in patients with primary immunodeficiencies (PIDs). Methods We performed a cross-sectional study of patients with PIDs and took genital swabs from male and female patients, which were analyzed with polymerase chain reaction for the presence of HPV-DNA. Clinical and laboratory data was collected to identify risk factors. Results 28 PID patients were included in this study. 10 of 28 (35.7%) had HPV-DNA in their genital swabs. 6 patients had high-risk HPV-types (21.4%). Most patients had asymptomatic HPV-infections, as genital warts were rare (2 of 28 patients) and HPV-associated malignancy was absent. Differences in the HPV-positivity regarding clinical PID-diagnosis, duration of PID, age, sex, immunosuppression, immunoglobulin replacement, or circumcision in males were not present. HPV-positive PID patients had higher numbers of T cells (CD3\(^+\)), of cytotoxic T cells (CD3\(^+\)/CD8\(^+\)), of transitional B cells (CD19\(^+\)/CD38\(^{++}\)/CD10\(^+\)/IgD\(^+\)), and of plasmablasts (CD19\(^+\)/CD38\(^+\)/CD27\(^{++}\)/IgD\(^-\)) compared to HPV-negative. Conclusion PID patients exhibit a high rate of genital HPV-infections with a high rate of high-risk HPV-types. Regular screening for symptomatic genital HPV-infection and HPV-associated malignancy in PID patients seems recommendable. KW - human papillomavirus KW - primary immunodeficiency KW - inborn errors of immunity (IEIs) KW - common variable immunodeficiency (CVID) KW - genital warts Y1 - 2021 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-250273 SN - 1664-3224 VL - 12 ER - TY - JOUR A1 - Strunz, Patrick-Pascal A1 - Froehlich, Matthias A1 - Gernert, Michael A1 - Schwaneck, Eva Christina A1 - Fleischer, Anna A1 - Pecher, Ann-Christin A1 - Tony, Hans-Peter A1 - Henes, Joerg Christoph A1 - Schmalzing, Marc T1 - Immunological Adverse Events After Autologous Hematopoietic Stem Cell Transplantation in Systemic Sclerosis Patients JF - Frontiers in Immunology N2 - Autologous hematopoietic stem cell transplantation (aHSCT) represents an effective treatment for systemic sclerosis (SSc), but it also can cause immunological adverse events (iAEs). Therefore, we aimed to determine the frequency of iAEs [engraftment syndrome (ES) and secondary autoimmune disorder (sAD)] and to identify potential risk factors for their development in a retrospective analysis on 22 patients similarly transplanted due to SSc. While nine patients (41%) suffered from ESs, seven sADs occurred in six patients (27%). Patients who developed ES were older in our cohort (52.45 vs. 42.58 years, p = .0433, Cohen’s d = 0.86), and cardiac involvement by SSc was associated with development of ES (OR = 40.11, p = .0017). Patients with manifestation of sAD had a higher modified Rodnan skin score (mRSS) reduction after aHSCT (90.50% vs. 60.00%, p = .0064, r = .65). Thus, IAEs are common after aHSCT for SSc and can occur in different stages during and after aHSCT with characteristic clinical manifestations. Good cutaneous response after aHSCT might be considered as a risk factor for sAD, and higher age at aHSCT and cardiac involvement might be considered as risk factors for the development of ES. KW - scleroderma KW - fever KW - autoimmune disease KW - Grave’s disease KW - modified Rodnan skin score (mRSS) KW - risk factor analysis KW - engraftment syndrome KW - Sjögren’s syndrome Y1 - 2021 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-245574 SN - 1664-3224 VL - 12 ER - TY - JOUR A1 - Heim, Jana A1 - Almanzar, Giovanni A1 - Schmalzing, Marc A1 - Gernert, Michael A1 - Tony, Hans-Peter A1 - Prelog, Martina T1 - Induction of IL-9 in Peripheral Lymphocytes of Rheumatoid Arthritis Patients and Healthy Donors by Th17-Inducing Cytokine Conditions JF - Frontiers in Immunology N2 - IL-9-producing Th9 cells display a group of helper T cells with similarities to Th17 and Th2 T cells and have been shown to be involved in synovial inflammation in rheumatoid arthritis (RA) patients. So far, it is unclear which parameters drive Th9 differentiation in lymphocytes derived from RA patients compared to immunologically healthy individuals and whether autocrine mechanisms are able to enhance Th9 polarization. Further, parallel pathways of induction of IL-17-producing cells with Th9 phenotype have to be distinguished from exclusively Th9-inductive mechanisms. Thus, the present study aimed to determine the parameters of Th9 induction by simulation in a standardized inflammatory cytokine milieu.Peripheral naive and non-naive T cells of RA patients and healthy donors (HD) were cultured under Th9 and Th17-driving conditions and phenotypically analyzed by flow cytometry and molecular analysis.Our findings indicate a similar differentiation pathway of Th9 and Th17 cells and similar distributions of IL-9+ T cells in RA and HD regardless of Th9- or Th17-promoting cytokine milieus. Whereas the magnitude and direction of Th9- or Th17-polarization was about the same in RA and HD, IL-17+ CD4+ T cells were significantly stimulated by Th17-inducing conditions in HD. In conclusion, the results indicate that Th9- and Th17-inducing cytokine conditions mimicking autoimmune inflammation in RA may have similar stimulatory effects regarding polarization of peripheral naive and non-naive T cells into Th9 or Th17 cells. The results suggest that the differentiation of Th9 cells may be also induced by Th17-driving conditions. KW - Th9 KW - Th17 KW - interleukin-9 KW - rheumatoid arthritis KW - PU.1 Y1 - 2021 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-237838 SN - 1664-3224 VL - 12 ER - TY - JOUR A1 - Fröhlich, Matthias A1 - Serfling, Sebastian A1 - Higuchi, Takahiro A1 - Pomper, Martin G. A1 - Rowe, Steven P. A1 - Schmalzing, Marc A1 - Tony, Hans-Peter A1 - Gernert, Michael A1 - Strunz, Patrick-Pascal A1 - Portegys, Jan A1 - Schwaneck, Eva-Christina A1 - Gadeholt, Ottar A1 - Weich, Alexander A1 - Buck, Andreas K. A1 - Bley, Thorsten A. A1 - Guggenberger, Konstanze V. A1 - Werner, Rudolf A. T1 - Whole-Body [\(^{18}\)F]FDG PET/CT Can Alter Diagnosis in Patients with Suspected Rheumatic Disease JF - Diagnostics N2 - The 2-deoxy-d-[\(^{18}\)F]fluoro-D-glucose (FDG) positron emission tomography/computed tomography (PET/CT) is widely utilized to assess the vascular and articular inflammatory burden of patients with a suspected diagnosis of rheumatic disease. We aimed to elucidate the impact of [\(^{18}\)F]FDG PET/CT on change in initially suspected diagnosis in patients at the time of the scan. Thirty-four patients, who had undergone [\(^{18}\)F]FDG PET/CT, were enrolled and the initially suspected diagnosis prior to [18F]FDG PET/CT was compared to the final diagnosis. In addition, a semi-quantitative analysis including vessel wall-to-liver (VLR) and joint-to-liver (JLR) ratios was also conducted. Prior to [\(^{18}\)F]FDG PET/CT, 22/34 (64.7%) of patients did not have an established diagnosis, whereas in 7/34 (20.6%), polymyalgia rheumatica (PMR) was suspected, and in 5/34 (14.7%), giant cell arteritis (GCA) was suspected by the referring rheumatologists. After [\(^{18}\)F]FDG PET/CT, the diagnosis was GCA in 19/34 (55.9%), combined GCA and PMR (GCA + PMR) in 9/34 (26.5%) and PMR in the remaining 6/34 (17.6%). As such, [\(^{18}\)F]FDG PET/CT altered suspected diagnosis in 28/34 (82.4%), including in all unclear cases. VLR of patients whose final diagnosis was GCA tended to be significantly higher when compared to VLR in PMR (GCA, 1.01 ± 0.08 (95%CI, 0.95–1.1) vs. PMR, 0.92 ± 0.1 (95%CI, 0.85–0.99), p = 0.07), but not when compared to PMR + GCA (1.04 ± 0.14 (95%CI, 0.95–1.13), p = 1). JLR of individuals finally diagnosed with PMR (0.94 ± 0.16, (95%CI, 0.83–1.06)), however, was significantly increased relative to JLR in GCA (0.58 ± 0.04 (95%CI, 0.55–0.61)) and GCA + PMR (0.64 ± 0.09 (95%CI, 0.57–0.71); p < 0.0001, respectively). In individuals with a suspected diagnosis of rheumatic disease, an inflammatory-directed [\(^{18}\)F]FDG PET/CT can alter diagnosis in the majority of the cases, particularly in subjects who were referred because of diagnostic uncertainty. Semi-quantitative assessment may be helpful in establishing a final diagnosis of PMR, supporting the notion that a quantitative whole-body read-out may be useful in unclear cases. KW - giant cell arteritis KW - GCA KW - [18F]FDG PET/CT KW - vasculature KW - inflammation KW - polymyalgia rheumatica KW - PMR KW - vasculitis Y1 - 2021 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-250227 SN - 2075-4418 VL - 11 IS - 11 ER -