Successful therapy of retroperitoneal fibrosis due to IgG4-related disease with rituximab, cyclophosphamide and glucocorticoids followed by maintenance therapy wit ritutixmab.

Idiopathic retroperitoneal fibrosis (IRF) is a rare condition characterized by the development of a peri-aortic and peri-iliac tissue showing chronic inflammatory infiltrates and pronounced fibrosis. Ureteral entrapment with consequent obstructive uropathy is one of the most common complications, which can lead to acute renal failure and, in the long term, to varying degrees of chronic kidney disease. Common symptoms at onset include lower back, abdominal or flank pain, and constitutional symptoms such as malaise, fever, and anorexia and weight loss. Pain is frequently referred to the hip, to the groin and to the lateral regions of the leg, with nocturnal exacerbations, and typically does not modify with position. We report a case of 56 year-old male with recurrent lower back pain and lower abdominal pain. Contrast-enhanced computed tomography and was suggestive of retroperitoneal fibrosis and unilateral ureteral occlusion. Histologic examination with immunohistochemical staining for IgG4 demonstrate IgG4-related retroperitoneal fibrosis. Therapy was started with prednison 1 mg/kg, but the tolerance of this dose was poor. Therefore the therapy was switched to combination of rituximab 375 mg/ m2 on day 1, cyclophosphamide 300 mg/m2 mg infusion and dexamethasone 20 mg total dose infusion on day 1 and 15 in 28 days cycle. FDG-PET/CT control in fourth month showed residual accumulation of FDG in retroperitoneal fibrotic mass, and therefore the therapy was prolonged to 8 month. The subjective symptoms of this diseases disappeared in the 8th month. Then the maintenance therapy, administration of rituximab in 6 month interval, was started. The activity of this disease be further evaluated by FDG-PET/CT imagination. Glucocorticoids are considered the cornerstone of therapy. The use of other immunosuppressive agents, including cyclophosphamide, azathioprine, methotrexate, mycophenolate mofetil and biological agents such as rituximab, tocilizumab and infliximab and sirolimus have been reported as a valuable option mostly in case reports, cases series and small studies. This agents allowed to reduce cumulative dose of glucocorticoids and its adverse effects. Therefore in our patients we preferred combination of rituximab cyclophosphamide s dexamethasone with lover dose of prednisonem. This combination is preferable for patients who cannot tolerate glucocorticoids or who are likely to suffer from significant glucocorticoids -related toxicity.

Successful treatment of SAPHO syndrome (chronic nonbacterial osteomyelitis and acne) with anakinra and denosumab. Case report and review of therapy.

SAPHO is an acronym derived from capital letters of Synovitis, Acne, Pustulosis, Hyperostosis, and Osteitis (SAPHO). SAPHO syndrome is an umbrella term covering a constellation of bone lesions and skin manifestations. A 40-year-old male complained about his jaw and back pain, swelling of multiple joints and weight loss accompanied by physical deterioration and acne type skin lesions. Laboratory tests revealed abnormal elevation of inflammatory markers. Imaging studies illustrated multiple osteolytic bone lesions and paraosseal infiltrates. According to the set of criteria diagnosis of SAPHO syndrome was stated. The patient was treated with glucocorticoids and non-steroidal anti-inflammatory drugs (NSAIDs), but only high dose dexamethasone and prednisone were effective. Daily subcutaneous administration of anakinra at the dose of 100 mg was initiated due to limited response to more classical therapies. Because of planned mandibular osteosynthesis initiation of denosumab was preferred before bisphosphonates. Therapeutic response was confirmed by FDG-PET/MR after 5 months of anakinra and denosumab therapy, showing decreased accumulation of FDG in periosteal and paraosseal infiltrates. Inflammatory markers significantly decreased, bone pain deferred but skin manifestation receded only partially. Therefore the response was evaluated as partial remission.

PET/CT imaging in polymyalgia rheumatica: praepubic 18F-FDG uptake correlates with pectineus and adductor longus muscles enthesitis and with tenosynovitis.

BACKGROUND: The role of 18F-fluorodeoxyglucose positron emission computed tomography (18F-FDG PET/CT) is increasing in the diagnosis of polymyalgia rheumatica (PMR), one of the most common inflammatory rheumatic diseases. In addition to other locations, increased 18F-FDG accumulation has been detected in the praepubic region in some patients. However, a deeper description and pathophysiological explanation of this increased praepubic accumulation has been lacking. The aim of the presented study is to confirm a decrease in praepubic 18F-FDG accumulation in response to therapy and to describe potential correlations to other 18F-FDG PET/CT scan characteristics during the course of disease. As a secondary objective, we describe the pathological aspects of the observed praepubic 18F-FDG uptake. PATIENTS AND METHODS: A retrospective review of patients with newly suspected PMR undergoing baseline and follow up 18F-FDG PET/CT between February 2010 and March 2016 is given. Those with a visually detected presence of praepubic 18F-FDG accumulation were further analysed. The uptake was assessed visually and also semi-quantitatively in the defined region of interest by calculation of target-to-liver ratios. Other regions typical for PMR were systematically described as well (shoulders, hips, sternoclavicular joints, ischiogluteal bursae, spinous interspaces). RESULTS: Twenty-three out of 89 screened patients (26%) presented with initial praepubic 18F-FDG PET/CT positivity, 15 of whom also underwent follow up 18F-FDG PET/CT examination. Five out of 15 patients presented with increased 18F-FDG accumulation in large arteries as a sign of giant cell arteritis. During follow up examination, decrease in 18F-FDG accumulation caused by therapeutic intervention was observed in all evaluated locations in all analysed patients and no new positivity was indicated, including periarticular, extraarticular tissues or target large vessels. Praepubical accumulation of 18F-FDG was diminished in all patients (15/15, 100%) after treatment with steroids. CONCLUSIONS: Increased praepubic 18F-FDG uptake in patients with PMR is relatively common and this region should be systematically evaluated during differential diagnosis of rheumatic and malignant disease. Praepubic inflammation is probably related to enthesitis and tenosynovitis at the origin of pectineus and adductor longus muscles ventrally from the pubis.

Significance of F-18 FDG PET/MRI in the search for the etiology of inflammation of unclear origin and fever of unknown origin.

PURPOSE: To evaluate the contribution of F-18 FDG-PET/MRI in the search for the etiology of the inflammation of unknown origin (IUO) and fever of unknown origin (FUO). MATERIAL AND METHODS: The study included 104 patients who underwent F-18 FDG-PET/MRI for IUO or FUO. The sensitivity, specificity, predictive values of the PET/MRI findings in relation to the final diagnosis of IUO/FUO were evaluated. A five-point Likert scale was used to semiquantitatively assess the probability of the cause of IUO/FUO based on PET/MRI finding. Furthermore, clinical (fever, arthralgia, weight loss, night sweats, age) and laboratory (C-reactive protein, leukocytes) parameters were monitored and compared with the true positivity rate of PET/MRI. RESULTS: In patients with definitively identified etiology of FUO and IUO, FDG-PET/MRI achieved a sensitivity of 96 %, specificity of 82 %, and positive and negative predictive values of 92 and 90 %. The cause of the IUO was determined in 71 patients (68.3 %). In 33 (31.7 %) patients, the etiology of IUO/FUO remained unknown, while in 25 (75.8 %) of them the symptoms resolved spontaneously and in 8 (24.2 %) patients they persisted without explanation even after 12 months of the follow-up. The most significant parameter in relation to subsequent PET/MRI finding was increased level of CRP, which was present in 96 % of true positive PET/MRI and normal CRP level was present in 56 % of true negative PET/MRI. CONCLUSION: Based on this study, FDG-PET/MRI is a suitable alternative for the investigation of IUO/FUO, this imaging technique has a very high sensitivity and negative predictive value.

Idiopathic retroperitoneal fibrosis: an unusual cause of low back pain.

Retroperitoneal fibrosis (RPF) is a rare inflammatory disease which is characterized by the development of a fibrous process that surrounds the major vessels and organs located within the retroperitoneum. About two thirds of all cases of RPF are idiopathic and are thought to be immunological in origin. Diagnosis of RPF should be considered in patients with unexplained abdominal and low back pain and retroperitoneal lesions. We present a case report of a 59-year-old white male with idiopathic RPF with history of low back pain and weight loss as only symptoms and treated by tamoxifen, corticosteroids, and insertion of JJ endoureteric catheters due to the obstruction of the upper urinary tract.

18F-FDG PET/CT in polymyalgia rheumatica-a pictorial review.

Polymyalgia rheumatica (PMR) is one of the inflammatory rheumatic diseases that can potentially be detected by positron emission tomography/CT. High fluorine-18 fludeoxyglucose (18F-FDG) accumulation around the shoulders, sternoclavicular and hip joints are the most common pre-treatment features of patients with PMR. Another common sign is increased 18F-FDG uptake in extra-articular regions between columnal spinous processes, near ischial tuberosities and in the praepubic area. Some patients also present with high 18F-FDG uptake in main arteries, corresponding to the characteristics of giant cell arteritis. It is possible to observe a decrease or even a disappearance of 18F-FDG uptake after effective therapy, an event which may be useful for the monitoring of treatment as well as for detection of PMR relapse.

Various forms of (18)F-FDG PET and PET/CT findings in patients with polymyalgia rheumatica.

AIM: Polymyalgia rheumatica (PMR) is a disease presenting with pain and stiffness, mainly in shoulders, hip joints and neck. Laboratory markers of inflammation may bolster diagnosis. PMR afflicts patients over 50 years old, predominantly women, and may also accompany giant cell arteritis. PATIENTS AND METHODS: 67 patients, who fullfiled Healey´s criteria for PMR in the period between 2004 and 2013 and had positive FDG PET (PET/CT) findings were retrospectively evaluated. FDG uptake was assessed in large arteries, proximal joints (shoulders, hips and sternoclavicular joints), in extraarticular synovial structures (interspinous, ischiogluteal and praepubic bursae). RESULTS: Articular/periarticular involvement (A) was detected in 59/67 (88.1%) patients and extrarticular synovial involvement (E) in 51/67 (76.1%) patients either individually or in combinations. Vascular involvement (V) was detected in 27/67 (40.3%) patients only in combination with articular (A) and/or extraarticular synovial (E) involvement. These combinations were: A+E involvement in 30/67 (44.8%) patients, A+V involvement in 8/67 (11.9%) patients, E+V involvement in 6/67 (9%) patients and A+E+V in 13/67 (19.4%) patients. CONCLUSIONS: PMR presents by articular/periarticular synovitis, extraarticular synovitis and can be accompanied by giant cell arteritis. All types of involvement have their distinct FDG PET (PET/CT) finding, which can be seen either individually or in any of their 4 combinations. FDG PET (PET/CT) examination seems to be an advantageous one-step examination for detecting different variants of PMR, for assessing extent and severity and also for excluding occult malignancy.

Upsampling from aorta and aortic branches: PET/CT hybrid imaging identified 18F-FDG hypermetabolism in inflamed temporal and occipital arteries.

Temporal arteries are typically below detectable levels of PET scanners, which repeatedly showed to be limiting in finding increased F-FDG accumulation even in histologically proven cases of giant cell arteritis. In 2010, Gaemperli and coworkers showed metabolic active inflammation in temporal arteries in an experimental study using PET with [C]-PK11195 combined with CT angiography. Herein, we present the case where an increased accumulation of routinely used tracer F-FDG can be identified directly in temporal and occipital arteries and even in smaller branches using a common hybrid PET/CT scanner if a brain acquisition protocol is applied.

Association of the -1082 G/A promoter polymorphism of interleukin-10 gene with the autoantibodies production in patients with rheumatoid arthritis.

Interleukin-10 (IL-10) is an immunoregulatory cytokine, usually considered to mediate the downregulation of the inflammatory response in rheumatoid arthritis (RA). Some effects of IL-10 are not anti-inflammatory; for example, the activation of B cells to promote autoantibody production. Allelic polymorphisms located in the promoter region of the IL-10 gene may contribute to the regulation of autoantibodies production. To examine the putative association between the -1082 G/A polymorphism in the promoter region of the IL-10 gene and the susceptibility to disease onset and severity of RA, a total of 144 patients with RA diagnosed according to the revised criteria of the American College of Rheumatology for RA were consecutively recruited into the study. Radiographic progression of RA was scored according to the Sharp/van der Heijde method. Serum levels of rheumatoid factors (RFs) were measured by enzyme-linked immunosorbent assay. Polymerase chain reaction amplification was used for the analysis of the promoter polymorphism of the IL-10 gene. We observed significant differences in genotype distribution of the -1082 G/A polymorphism between IgM RF, IgA RF, and IgG RF positive/negative subgroups of RA patients, with higher prevalence of the GG genotype within IgM RF (Pg = 0.006), IgA RF (Pg = 0.05), and IgG RF (Pg = 0.007) negative RA patients. Results obtained in this study provide the evidence of an association between the -1082 G/A polymorphism in the IL-10 gene promoter and the production of RFs in RA patients.