Management of Rheumatic Diseases During Pregnancy and Breastfeeding: Position Paper of the Working Group for Obstetrics and Prenatal Medicine in the German Society for Gynecology and Obstetrics e. V. (AGG - Section Maternal Diseases in Pregnancy).

Purpose These recommendations issued by the AGG (Section Maternal Diseases in Pregnancy) were developed as a rapid orientation on maternal rheumatic diseases for counselling and disease management in pregnancy and breastfeeding. Methods The standard literature, consensus and position papers, guidelines and recommendations by other specialist associations were evaluated by a task force of the Section and summarized in these recommendations following a joint consensus process. Recommendations This paper provides an orientating overview of the physiology, pathophysiology and definitions of rheumatic diseases which is relevant for gynecologists and obstetricians. The recommendations focus on the maternal, fetal and neonatal diagnostic workup in cases with underlying maternal rheumatic disease.

18F-FDG PET/MRI compared with clinical and serological markers for monitoring disease activity in patients with aortitis and chronic periaortitis.

OBJECTIVES: We compared the diagnostic value of fully integrated 18F-FDG PET/MRI to that of clinical and serological markers for monitoring disease activity in patients with aortitis/chronic periaortitis (A/CPA) during immunosuppressive therapy. METHODS: Patients positive for A/CPA at the initial and at least 2 consecutive PET/MRI studies were included for retrospective analysis. Imaging (qualitative and quantitative analysis), clinical, and serologic (C-reactive protein, erythrocyte sedimentation rate) assessments were determined at each visit, and their findings compared. Differences in various PET/MRI parameters, clinical symptoms, and serologic markers during therapy between first and second visits were tested for statistical significance. Spearman's rank correlation coefficient was calculated to relate imaging to serologic marker changes between the first 2 visits. RESULTS: Serial assessments were performed in 12 patients with A/CPA, over 34 visits. PET/MRI suggested active disease in 22/34 (64.7%) studies, whereas clinical assessment and serological analysis were positive in only 18/34 (52.9%) and 17/34 (50%) cases, respectively. Disease activity assessment differed between PET/MRI, and clinical and serological markers, in 8/34 (23.5%) and 9/34 (26.5%) cases, respectively. Imaging and serologic parameters (p < 0.009) and clinical symptoms (p = 0.063) predominantly improved at the second visit. Changes from the first to the second visit were not correlated between PET/MRI and serologic markers. CONCLUSIONS: Fully integrated 18F-FDG PET/MRI provides a comprehensive imaging approach with data on vascular/perivascular inflammation that is complementary to clinical and laboratory assessments. This highlights the potential value of imaging-based disease activity monitoring, which might have a crucial impact on clinical management in patients with A/CPA.

Mortality prediction in stable hemodialysis patients is refined by YKL-40, a 40-kDa glycoprotein associated with inflammation.

Chronic inflammation contributes to increased mortality in hemodialysis (HD) patients. YKL-40 is a novel marker of inflammation, tissue remodeling, and highly expressed in macrophages inside vascular lesions. Elevated levels of YKL-40 have been reported for HD patients but how it integrates into the proinflammatory mediator network as a predictor of mortality remains elusive. We studied serum YKL-40, Interleukin-6 (IL-6), high-sensitivity C-reactive protein, monocyte chemotactic protein-1 (MCP-1), and interferon-gamma induced protein-10 (IP-10) in 475 chronic hemodialysis patients. Patients were followed for mortality for a median of 37 [interquartile range: 25-49] months and checked for interrelation of the measured mediators. To plot cumulative incidence functions, patients were stratified into terciles per YKL-40, IL-6, MCP-1, and IP-10 levels. Multivariable Cox regression models were built to examine associations of YKL-40, IP-10, and MCP-1 with all-cause and cause-specific mortality. Net reclassification improvement was calculated for the final models containing YKL-40 and IL-6. Increased YKL-40 was independently associated with age, IP-10, and IL-6 serum levels. After adjustment for demographic and laboratory parameters, comorbidities, and IL-6, only YKL-40 significantly improved risk prediction for all-cause (hazard ratio 1.4; 95% confidence interval 1.1-1.8) and cardiovascular mortality (hazard ratio 1.5; 95% confidence interval 1.03-2.2). Thus, in contrast to other biomarkers of aberrant macrophage activation, YKL-40 reflects inflammatory activity, which is not covered by IL-6. Mechanistic and prospective studies are needed to test for causal involvement of YKL-40 and whether it might qualify as a therapeutic target.

Rapidly progressive intracranial artery stenosis in primary antiphospholipid syndrome.

Antiphospholipid antibody syndrome (APS) is usually a disease of young adults. In elderly stroke patients APS was not associated with progressive intracerebral stenosis in the past. Here, we report a 65-year-old patient who presented with recurrent ischemic strokes associated with progressive stenosis of the right middle cerebral artery. Antiphospholipid antibodies were detected and treatment with plasma exchange, tapered steroids, and anticoagulants was successful. This case demonstrates that APS should be considered also in elderly stroke patients. This is of particular relevance since APS confers a significant risk to angioplasty and stenting procedures which therefore should be avoided in APS.

Diagnostic utility of Acoustic Radiation Force Impulse (ARFI) imaging in primary Sjoegren`s syndrome.

OBJECTIVES: The purpose of the study was to assess the diagnostic utility of acoustic radiation force impulse (ARFI) imaging in primary Sjögren's syndrome (pSS). METHODS: One hundred fifty-seven patients with sicca symptoms and/or salivary gland swelling were included. Sicca symptoms, Schirmer test, unstimulated whole saliva (UWS), SS-A/B antibodies, and histology were assessed according to American-European Consensus group (AECG) criteria. All patients underwent high-resolution ultrasound and ARFI imaging of the parotid (PG) and submandibular glands (SMG). RESULTS: Seventy patients were classified as having pSS. The remaining 87 patients suffered from idiopathic sicca (n = 24), rheumatoid arthritis (n = 12), sarcoidosis (n = 9), cutaneous/systemic lupus erythematosus (n = 7), scleroderma (n = 2), dermatomyositis (n = 1), HBV/HCV (n = 2), and panarteritis nodosa (n = 1), and disorders in 29 patients were classified as not otherwise specified. ARFI values of the PG were significantly higher in the pSS versus non-pSS groups (2.86 ± 0.07 m/s vs. 2.15 ± 0.11 m/s, p < 0.0001). ARFI imaging demonstrated diagnostic sensitivity and specificity of 81 % and 67 %, respectively. CONCLUSIONS: In addition to histology, ARFI imaging was the most important diagnostic tool for identifying early pSS. KEY POINTS: • Early stages in Sjögren's syndrome become apparent with major salivary gland enlargements. • Schirmer and unstimulated whole saliva tests demonstrated insufficient sensitivity/specificity for early-stage diagnosis. • Acoustic radiation force impulse imaging is a reliable tool for diagnosing early disease stages.

Imaging large vessel vasculitis with fully integrated PET/MRI: a pilot study.

PURPOSE: The aim of this study was to evaluate the feasibility of hybrid [(18)F]fluorodeoxyglucose (FDG) positron emission tomography (PET)/MRI in patients with large vessel vasculitis (LVV) by comparing visual and quantitative parameters to that of PET/CT. Furthermore, the value of PET/MRI in disease activity and extent of LVV was assessed. METHODS: A total of 16 [(18)F]FDG PET/MRI and 12 [(18)F]-FDG PET/CT examinations were performed in 12 patients with LVV. MRI of the vessel wall by T1-weighted and T2-weighted sequences was used for anatomical localization of FDG uptake and identification of morphological changes associated with LVV. In addition, contrast-enhanced (CE) magnetic resonance angiography (MRA) was performed. The vascular FDG uptake in the vasculitis group was compared to a reference group of 16 patients using a four-point visual score. Visual scores and quantitative parameters [maximum standardized uptake value (SUVmax) and target to background ratio (TBR)] were compared between PET/MRI and PET/CT. Furthermore, correlations between C-reactive protein (CRP) and quantitative PET results, as well the extent of vasculitis in PET, MRI/CE-MRA and combined PET/MRI, were analysed. RESULTS: TBRs, SUVmax values and visual scores correlated well between PET/MRI and PET/CT (r = 0.92, r = 0.91; r = 0.84, p < 0.05). There was no significant difference between both modalities concerning SUVmax measurements and visual scores. In PET/MRI, PET alone revealed abnormal FDG uptake in 86 vascular regions. MRI/CE-MRA indicated 49 vessel segments with morphological changes related to vasculitis, leading to a total number of 95 vasculitis regions in combination with PET. Strong and significant correlations between CRP and disease extent in PET alone (r = 0.75, p = 0.0067) and PET/MRI (r = 0.92, p < 0.0001) in contrast to MRI/CE-MRA only were observed. Regarding disease activity, no significant correlations were seen between quantitative PET results and CRP, although there was a trend towards significance (r = 0.55, p = 0.0651). PET/MRI also showed active LVV in 15/16 examinations. CONCLUSION: Hybrid PET/MRI is feasible in LVV and holds promise for precisely determining disease extent and disease activity.

Clinical aspects of granulomatosis with polyangiitis affecting the head and neck.

There are many controversies in head and neck granulomatosis with polyangiitis (HN-GPA). Diagnostic/therapeutic regimens vary due to limited knowledge about the special properties of HN-GPA. 28 patients were diagnosed with GPA accordingly. Anti-neutrophil-cytoplasmatic-antibody (ANCA), anti-peroxidase-antibody (anti-PR3) and biopsies were performed for all patients and set into clinical context. 14 patients had sinonasal symptoms. Otological (n = 8) and laryngeal (n = 2) symptoms were usually associated with complex disease activity. Pulmonary and/or renal impairment was present in 14 patients at the time of diagnosis and developed in a further nine patients within 1 year. 21 patients with systemic disease displayed elevated ANCA/anti-PR3. In contrast, those with persistent isolated HN manifestations (n = 6) lacked auto-antibodies. These patients underwent multiple biopsies to diagnose GPA. Interestingly, five patients without clinical HN manifestations but elevated auto-antibodies were identified by nasal "blind" biopsy. Clinical examination, auto-antibody testing, and histology are effective diagnostic tools in HN-GPA. Histological diagnosis remains the gold standard in patients with persistent isolated head and neck manifestations but missing auto-antibodies. Based on our findings, we suggest early and sufficient systemic therapy for all HN-GPA. Nasal mucosal "blind" biopsy should be performed in patients with elevated auto-antibodies but lacking clinical head and neck manifestations.

Fluorescence-aided tomographic imaging of synovitis in the human finger.

PURPOSE: To propose and evaluate indocyanine green (ICG)-enhanced tomographic optical imaging for detection and characterization of synovitis in affected finger joints of patients with rheumatoid arthritis and differentiation from healthy joints in comparison to 3-T magnetic resonance (MR) imaging. MATERIALS AND METHODS: This prospective pilot study was approved by the institutional ethics committee. Six arthritic proximal interphalangeal (PIP) joints in six patients (five women and one man; mean age ± standard deviation, 62.6 years ± 13.3) with clinically determined rheumatoid arthritis and six healthy PIP joints from six volunteers (four women and two men; mean age, 41.5 years ± 20.2) were examined with an ICG-enhanced fluorescence molecular tomography (FMT) system and 3-T MR imaging as the standard of reference. The degree of inflammation was graded semiquantitatively on a four-point ordinate scale according to the Outcome Measures in Rheumatology Clinical Trials Rheumatoid Arthritis MR Imaging Score, or OMERACT RAMRIS. FMT reconstructions were coregistered with the MR images. Groups were compared by using a two-sided t test, and a weighted κ coefficient was used for comparing FMT and MR imaging semiquantitative scores, as well as assessing intrareader agreement. RESULTS: FMT was used to detect synovitis in all arthritic joints. The reconstructed FMT signal correlated with MR imaging findings in intensity and spatial, transverse profile. Semiquantitative scoring of FMT correlated well with MR imaging findings (weighted κ coefficient = 0.90). The reconstructed quantitative FMT signal, denoting synovial hyperperfusion, was used to differentiate between synovitis and healthy joints (healthy joints, 1.25 ± 0.59; arthritic joints, 3.13 ± 1.03; P < .001). CONCLUSION: FMT enhanced with ICG provided depth-resolved imaging of synovitis in PIP joints. FMT may help detect synovitis in patients with rheumatoid arthritis.

Haemostasis in chronic kidney disease.

The coagulation system has gained much interest again as new anticoagulatory substances have been introduced into clinical practice. Especially patients with renal failure are likely candidates for such a therapy as they often experience significant comorbidity including cardiovascular diseases that require anticoagulation. Patients with renal failure on new anticoagulants have experienced excessive bleeding which can be related to a changed pharmacokinetic profile of the compounds. However, the coagulation system itself, even without any interference with coagulation modifying drugs, is already profoundly changed during renal failure. Coagulation disorders with either episodes of severe bleeding or thrombosis represent an important cause for the morbidity and mortality of such patients. The underlying reasons for these coagulation disorders involve the changed interaction of different components of the coagulation system such as the coagulation cascade, the platelets and the vessel wall in the metabolic conditions of renal failure. Recent work provides evidence that new factors such as microparticles (MPs) can influence the coagulation system in patients with renal insufficiency through their potent procoagulatory effects. Interestingly, MPs may also contain microRNAs thus inhibiting the function of platelets, resulting in bleeding episodes. This review comprises the findings on the complex pathophysiology of coagulation disorders including new factors such as MPs and microRNAs in patients with renal insufficiency.

Head and neck sarcoidosis, from wait and see to tumor necrosis factor alpha therapy: a pilot study.

BACKGROUND: To suggest treatment modalities with respect to the specific requirements of head and neck sarcoidosis. METHODS: Head and neck sarcoidosis was diagnosed in 31 patients. Treatment regimes comprised wait and see, corticosteroid-pulse, stable-dose corticosteroids, or adalimumab. RESULTS: In all, 21 patients had isolated head and neck sarcoidosis and a further 8 patients showed concomitant pulmonary sarcoidosis. Two patients with pulmonary sarcoidosis developed subsequent head and neck manifestation. Most patients with isolated head and neck sarcoidosis did not receive systemic therapy. None exhibited relapsing disease. Three patients with head and neck manifestation underwent corticosteroid pulse. Complete remission (CR) was detected for all after 5 months. Six patients were treated with stable-dose corticosteroids. Five of 6 showed CR after 12 months and 1 of 6 patients partial remission (PR) after 24 months. Five of 6 patients exhibited relapses. Two patients underwent adalimumab therapy and showed PR after 65 or CR after 26 months, respectively. CONCLUSIONS: Most patients with head and neck sarcoidosis did not require systemic therapy. We suggest corticosteroid-pulse therapy for patients with severe head and neck manifestation. Adalimumab might be potent for nonresponder.

Kidney transplant after preexisting posterior reversible encephalopathy syndrome induced by Goodpasture's syndrome.

Posterior reversible encephalopathy syndrome is characterized by varying neurologic symptoms associated with brain vasogenic edema. Posterior reversible encephalopathy syndrome can be associated with severe hypertension (eg, in eclampsia or HELLP syndrome), but it also has been observed without hypertension and in several clinical conditions including infections and autoimmune disorders. The literature offers several reports of posterior reversible encephalopathy syndrome detected or induced after bone-marrow and solid-organ transplant, or induction by immunosuppression. We describe what is, to the best of our knowledge, the first case of man who successfully underwent a kidney transplant with preexisting posterior reversible encephalopathy syndrome induced by Goodpasture's syndrome.