Persisting sicca complaints in sarcoidosis.

Background: Sarcoidosis is a systemic inflammatory disease that is characterized by non-caseating granulomas. Besides the lung as classical site of involvement, extrapulmonary manifestations are common, for example cervical lymph nodes or the salivary glands. The aim of this investigation is the analysis of the long-term course of glandular symptoms with a focus on persisting sicca symptoms. Materials and methods: All patients with the diagnosis of sarcoidosis over a period of 20 years in the departments of otorhinolaryngology, nephrology and pneumology were identified. In addition to clinical examinations and functional evaluation of the salivary glands, a sonographic examination of the salivary glands was carried out. Results: A total of 76 patients were included in the study (age 35.1 ± 21.6 years). At baseline, 32 out of 76 patients were suffering from xerostomia, 36 from dry eyes. While other salivary gland symptoms, such as gland enlargement, pain or facial nerve impairment, dissolved during the further course of the disease, xerostomia was still present in 29 and dry eyes in 35 out of 76 patients at the time of follow-up (which took place on average after 88.2 months). Conclusion: Sicca symptoms persist in patients with the diagnosis of sarcoidosis, while other salivary gland symptoms completely dissolve during the further course of the disease. This development appears to be independent of the type of therapy and should be considered during the follow-up of these patients, since sicca symptoms can cause further ocular, oral and dental damage.

Fluorescence optical imaging and 3T-MRI for detection of synovitis in patients with rheumatoid arthritis in comparison to a composite standard of reference.

OBJECTIVES: To address whether Indocyanine Green (ICG) enhanced fluorescence optical imaging (FOI) is more sensitive than magnetic resonance imaging (MRI) in the detection of synovitis of the wrist and finger joints in rheumatoid arthritis and to analyze the performance of FOI depending on the grade of synovitis. METHODS: Twenty patients with highly active rheumatoid arthritis (mean DAS28-ESR 5.25±1.0) and thirteen healthy volunteers underwent clinical examination, FOI and contrast-enhanced 3T-MRI. Joints were rated by three independent readers semiquantitatively (grade 0-3: no, low, moderate and high grade synovitis) and compared to a semiquantitative composite standard of reference (cSOR, grade 0-3) that incorporated clinical parameters, FOI and MRI results. RESULTS: 2.868 evaluations in 956 joints were performed. FOI had an overall sensitivity of 57.3% and a specificity of 92.1%, whereas MRI had a sensitivity of 89.2% and a specificity of 92.6%. The sensitivity of FOI increased with the degree of synovitis to 65.0% for moderate and severe synovitis (specificity 88.1%) and 76,3% for severe synovitis (specificity 80.5%). The performance of FOI decreased with the degree of synovitis with false negative results predominantly for mild (156/343, 45.5%) and moderate (160/343, 46.6%) synovitis and false positive FOI evaluations predominantly based on weak (grade 1) signals (133/163, 81,6%). CONCLUSION: FOI has a lower sensitivity than 3T-MRI in the detection of synovitis of the hand and finger joints. The diagnostic performance of FOI decreases with the degree of synovitis and with the strength of FOI signals.

Head and neck giant cell arteritis: an autoimmune disease with many faces.

CONCLUSION: A high rate of infrequent presentations of giant cell arteritis were seen in the ENT department and should be anticipated as a differential diagnosis in every older patient with odynophagia with high CRP values without cause in thorough ENT examination. OBJECTIVE: To describe the clinical manifestation of head and neck giant cell arteritis and to derive a diagnostic pathway covering atypical cases. METHOD: Single-center, retrospective analysis of cases with GCA in the head and neck region (HN-GCA) (2002-2012) to describe the clinical presentation and to derive a diagnostic pathway covering manifestations presenting to an ENT department. RESULTS: Sixty-five patients were newly diagnosed with HN-GCA in the department of otolaryngology, ophthalmology and neurology. The most frequent symptoms were loss of vision (83%) and new onset headache (63%). Eight patients (12%) presented with infrequent manifestations, predominantly in the department of otorhinolaryngology. The most common atypical presentation (50%) was odynophagia in conjunction with high CRP values misleading to an infectious cause and delaying diagnosis. A diagnostic pathway for GCA was derived based on the ACR classification criteria and the clinical findings.

Biomarkers in Autoimmune Salivary Gland Disorders: A Review.

Salivary glands are frequent sites of manifestations of autoimmune disorders in the head and neck. Sjögren syndrome, sarcoidosis, granulomatosis with polyangiitis, and IgG4-related sialadenitis represent the most important autoimmune salivary gland disorders. Due to the lack of specific symptoms, diagnosis of these conditions remains a challenge. Diagnosis is usually based on classification criteria involving clinical tests, histopathological evaluation, and serological examinations. Depending on the disease, biomarkers are of different value and have to be interpreted carefully. In Sjögren syndrome, antibodies against Ro/SS-A and La/SS-B are essential and part of established classification criteria. In sarcoidosis, biomarkers such as angiotensin-converting enzyme, serum amyloid A, adenosine deaminase, and soluble interleukin-2 receptor are not suitable to confirm a diagnosis due to low sensitivity and specificity, but allow a differentiation between active and inactive disease. In patients with suspected granulomatosis with polyangiitis, positivity for anti-neutrophil cytoplasmic antibodies (ANCA) allows a diagnosis without histopathological confirmation in selected cases. In the head and neck, limited manifestations are common, in which less patients are positive for ANCA and histopathological confirmation is required. Diagnosis of IgG4-related sialadenitis solely based on elevated IgG4 serum levels is not possible. The concentration of blood plasmablasts is reported to have a higher diagnostic value.

Disease activity and vascular involvement in retroperitoneal fibrosis: first experience with fully integrated 18F-fluorodeoxyglucose positron emission tomography/magnetic resonance imaging compared to clinical and laboratory parameters.

OBJECTIVES: The aim of this study was to evaluate the value of fully integrated [18F]-FDG PET/MRI in the assessment of retroperitoneal fibrosis with regard to disease activity, extent and vascular involvement compared to clinical and laboratory parameters. METHODS: Seventeen [18F]-FDG PET/MRI examinations were performed in fourteen patients. Qualitative (visual 4-point scale) and quantitative PET parameters (maximum standardised uptake value, SUVmax; target-background ratio, TBR) as well as RF thickness and volume were correlated to clinical and inflammatory parameters and compared between therapy-naïve patients and patients under immunosuppression. Evidence for associated large-vessel vasculitis was examined. Magnetic resonance angiography (MRA) was performed to detect aneurysms or stenoses. RESULTS: Clinical parameters, C-reactive protein (CRP) and erythrocyte sedimentation rate (ESR) only incompletely displayed inflammatory activity and did not correlate with PET/MRI parameters. In 29% (4/17) resp. 50% (8/16) of PET/MRI examinations active disease was detected although CRP resp. ESR were in the normal range. SUVmax, TBR and volume of the retroperitoneal mass differed significantly between therapy-naïve patients and patients under therapy (SUVmax p=0.004, TBR p=0.015, volume p=0.015), whereas thickness of the retroperitoneal mass did not (p=0.406). Large-vessel vasculitis was detected in 21% (3/14) and aortic aneurysms in 14% (2/14) of patients. Vasculitis occurred apart from the site of RF in two patients. CONCLUSIONS: Whole body hybrid [18F]-FDG-PET/MRI is superior to clinical and inflammatory parameters in disease activity assessment of RF. There may be substantial disease activity despite inflammatory parameters in the normal range. Associated large-vessel vasculitis and aneurysms may occur apart from the site of RF.

Sonoelastographic Modalities in the Evaluation of Salivary Gland Characteristics in Sjögren's Syndrome.

The purpose of this study was to investigate salivary tissue assessment with various sonoelastographic modalities (real-time tissue elastography, Virtual Touch imaging and quantification) in patients with Sjögren's syndrome as compared with an appropriate control group. The sonoelastographic modalities were evaluated in 50 patients with primary Sjögren's syndrome (pSS). Patients underwent high-resolution ultrasonography of the submandibular and parotid glands. Results of B-mode, real-time tissue elastography, Virtual Touch imaging-each graded with the appropriate scoring system-and Virtual Touch quantification were compared with those for 50 patients with sicca symptoms who did not fulfill the American-European consensus group criteria. In B-mode, 34 of 50 parotid glands in patients with pSS and 8 of 50 in the control group had abnormal findings (p < 0.001). Compared with 9 of 50 control patients, 38 of 50 patients with pSS had abnormal findings in submandibular gland B-mode (p < 0.001). With real-time tissue elastography, there was a trend toward higher scores for parotid glands in the pSS group (p = 0.238), whereas scores for submandibular glands in the control group were higher (p = 0.107). Virtual Touch imaging did not indicate any difference (p = 0.647 and p = 0.658). In Virtual Touch quantification, values for parotid (mean: 2.99 m/s) and submandibular glands (mean: 2.54 m/s) in the pSS group were higher than those for parotid (mean: 2.16 m/s) and submandibular (mean: 2.04 m/s) glands in the control group (p < 0.001 and p = 0.008). Glandular stiffness, measured by Virtual Touch quantification, was significantly higher in patients with Sjögrens syndrome than in patients with sicca symptoms.

Spotlight on rituximab in the treatment of antineutrophil cytoplasmic antibody-associated vasculitis: current perspectives.

A 54-year-old patient presented to his general practitioner because of strong muscle pain in both thighs. Inflammatory parameters (CRP 16.3 mg/dL) and white blood cells (15 g/L) were elevated. The patient reported a weight loss of 10 kg in 4 weeks. There was no fever or any other specific symptoms. Urine dipstick examination and computed tomography of the chest were unremarkable. Because of increasing symptoms, the patient was referred to our department. Magnetic resonance tomography showed diffuse inflammatory changes of the muscles of both thighs. Neurological examination and electrophysiology revealed axonal sensorimotor neuropathy and ground-glass opacities of both lungs had occurred. Serum creatinine increased to 229 µmol/L within a few days, with proteinuria of 3.3 g/g creatinine. Kidney biopsy showed diffuse pauci-immune proliferative glomerulonephritis. Proteinase 3-specific antineutrophil cytoplasmic antibodies were markedly increased. Birmingham Vasculitis Activity Score was 35. Within 2 days, serum creatinine further increased to 495 µmol/L. Plasma exchange, high-dose glucocorticosteroids, and hemodialysis were started. The patient received cyclophosphamide 1 g twice and rituximab 375 mg/m(2) four times according to the RITUXVAS protocol. Despite ongoing therapy, hemodialysis could not be withdrawn and had to be continued over 3 weeks until diuresis normalized. Glucocorticosteroids were tapered to 20 mg after 2 months, and serum creatinine was 133 µmol/L. However, nephritic urinary sediment reappeared. Another dose of 1 g cyclophosphamide was given, and glucocorticosteroids were raised for another 4 weeks. After 6 months, the daily prednisolone dose was able to be tapered to 5 mg. Serum creatinine was 124 µmol/L, proteinuria further decreased to 382 mg/g creatinine, and the Birmingham Vasculitis Activity Score was 0. Maintenance therapy with rituximab 375 mg/m(2) every 6 months was started. At the last visit after 8 months, the patient was still in remission, with only minor persistent dysesthesia of the left foot and a persistent serum creatinine of 133 µmol/L.

Synovitis in patients with early inflammatory arthritis monitored with quantitative analysis of dynamic contrast-enhanced optical imaging and MR imaging.

PURPOSE: To evaluate quantitative perfusion measurements of dynamic indocyanine green (ICG)-enhanced optical imaging for monitoring synovitis in the hands of patients with inflammatory arthritis compared with dynamic contrast-enhanced (DCE) magnetic resonance (MR) imaging and clinical outcome. MATERIALS AND METHODS: This study was approved by the ethics committee at the institution. Individual joints (n = 840) in the hands and wrists of 28 patients (14 women; mean age, 53.3 years) with inflammatory arthritis were examined at three different time points: before start of therapy and 12 and 24 weeks after start of therapy or therapy escalation. Treatment response was assessed by using clinical measures (simple disease activity index [SDAI]), ICG-enhanced optical imaging, and DCE MR imaging. Dynamic images were obtained for optical imaging and DCE MR imaging. The rate of early enhancement (REE) of the perfusion curves of each joint was calculated by using in-house developed software. Correlation coefficients were estimated to evaluate the associations of changes of imaging parameters and SDAI change. RESULTS: Quantitative perfusion measurements with optical imaging and MR imaging correctly identified patients who responded (n = 18) and did not respond to therapy (n = 10), as determined by SDAI. The difference of REE after 24 weeks of treatment compared with baseline in responders was significantly reduced in optical imaging and MR imaging (optical imaging: mean, -21.5%; MR imaging: mean, -41.0%; P < .001 for both), while in nonresponders it was increased (optical imaging: mean, 10.8%; P = .075; MR imaging: mean, 8.7%; P = .03). The REE of optical imaging significantly correlated with MR imaging (ρ = 0.80; P < .001) and SDAI (ρ = 0.61; P < .001). CONCLUSION: Quantitative analysis of contrast-enhanced optical imaging allows for potential therapeutic monitoring of synovitis in patients with inflammatory arthritis.

Using TNF-alpha antagonist adalimumab for treatment for multisystem sarcoidosis: a case study.

We report the usage of the TNF-alpha antagonist adalimumab in patients with progressive multisystem sarcoidosis. Three patients with multisystem sarcoidosis (MSS) were treated with adalimumab for 12 months. All three patients were quickly responded to adalimumab and experienced a nearly complete regression of the symptoms that lead to an intensive immunosuppression. However, some accompanying symptoms of sarcoidosis, such as splenomegalia, did not respond. One patient suffered 18 months later a new unspecified abdominal lymphadenopathy. TNF-alpha antagonists can be helpful agents in the treatment for MSS. However, the experience with TNF-alpha antagonists in patients with sarcoidosis is still limited. Multicenter trials and a comparison of the different agents are needed to validate the safety and efficacy in these patients. Optimal dosage, duration of therapy and long-term toxicity of anti-TNF therapy in patients with refractory sarcoidosis are yet to be determined in prospective trials.

Treatment of relapsing polychondritis with the TNF-alpha antagonist adalimumab.

Relapsing polychondritis (RP) is a rare immune-mediated disease which is associated with inflammation in cartilaginous tissue throughout the body. Especially, the cartilaginous structures of ear, respiratory tract, nose, and joints are affected. Around 30% of the cases are associated with other diseases especially systemic vasculitis. Onset of RP is most likely between the ages of 40-60 years. This case reports the often disguised and similar symptoms of RP to Wegner's granulomatosis and the challenge of diagnosis. The relative rarity of RP has not permitted clinical trials to determine the efficacy and safety of different therapies. Current treatment is largely empiric and based on case reports. In this case, we successfully used a treatment with the TNF-alpha antagonist adalimumab.

Relapsing polychondritis: An autoimmune disease with many faces.

Relapsing polychondritis (RPC) is a rare immune mediated disease which is associated with inflammation in cartilaginous tissue throughout the body. Especially the cartilaginous structures of ear, nose, joints and respiratory tract are affected. In around 30% of the cases an association with other diseases especially systemic vasculitis or myelodysplatic syndrome can be detected. The relative rarity of RPC has not permitted clinical trials to determine the efficacy and safety of therapy strategies. Often the medication in current use is largely empiric and based on case reports. Therefore different immunosuppressants such as cyclophosphamide, azathioprine, cyclosporine, mycophenolate mofetil and also new approaches like tumor necrosis factor alpha blockers (TNF-alpha antagonists) have been used for the treatment of severe manifestations of RPC with varying degrees of efficacy. This review gives a close look to clinical manifestation, diagnosis and also therapy options of RPC.

Autologous blood donation in cardiac surgery: reduction of allogeneic blood transfusion and cost-effectiveness.

OBJECTIVE: The purpose of this study was to assess transfusion requirements in patients undergoing cardiac surgery with and without autologous blood donation and to calculate the costs of predonation from the hospital perspective. DESIGN: Observational study. SETTING: Single university hospital. PARTICIPANTS: Four thousand three hundred twenty-five patients undergoing elective cardiac surgery with and without autologous blood donation. INTERVENTIONS: Eight hundred forty-nine patients (20%) underwent autologous blood donation, whereas 3,476 (80%) did not. Perioperative allogeneic blood transfusion was recorded as the primary endpoint. To avoid selection bias, patients were stratified according to their preoperative risk score. A decision model was derived from acquired data for the optimization of autologous blood donation. MEASUREMENTS AND MAIN RESULTS: Allogeneic blood transfusion rate was 13% in patients with predonation versus 48% without predonation (p < 0.05). This difference remained statistically significant even after risk stratification. The predonation of 1, 2, or 3 units reduced the probability of receiving allogeneic blood to 24%, 14%, and 9%, respectively. An efficient program of predonation within the department of anesthesiology allowed keeping the costs of predonation low. Decision-tree analysis revealed that predonation of 2 autologous units of blood saved the most allogeneic blood for the smallest increase in costs. Incremental cost for male patients predonating 2 units was dollars 33 (US), whereas for females predonation could be done at no extra cost in comparison to patients without predonation. CONCLUSION: Autologous blood donation significantly reduces allogeneic blood requirement in cardiac surgery. If adjusted for diagnosis and gender, autologous blood donation is a cost-effective alternative to reduce allogeneic blood consumption.