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.

Multicentric Castlemans disease. Symptoms, diagnostics and therapy.

Castleman disease (CD) describes a group of heterogeneous hematologic disorders with characteristic histopathological features. CD can present with unicentric (UCD) or multicentric (MCD) regions of lymph node enlargement. Some cases of MCD are caused by human herpesvirus-8 (HHV-8), whereas others are HHV-8-negative/idiopathic (iMCD). Treatment of iMCD is challenging, and outcomes can be poor. In this paper, we briefly report about symptoms of iMCD and about the International, evidencebased consensus diagnostic criteria for HHV-8-negative/idiopathic multicentric Castleman disease and International evidence based consensus treatment guidelines for idiopathic multicentric Castleman disease.

IgG4-related disease. Clinical manifestation differential diagnosis and recent International Diagnostic Criteria for IgG4-related disease.

Immunoglobulin G4- related disease (IgG4-RD) is a rare systemic fibro-inflammatory disorder. Autoimmune pancreatitis is the most frequent manifestation of IgG4-RD. However, IgG4-RD can affect any organ such as salivary glands, orbits, retroperitoneum, prostate and many others. Recent research enabled a clear clinical and histopathological description of IgG4-RD and in 2019 four Clinical phenotypes of IgG4-related disease were described. Diagnosis is based on morphological examination with typical findings of lymphoplasmocellular inflammation, storiform fibrosis and obliterative phlebitis in IgG4-RD biopsies and the tissue invading plasma cells largely produce IgG4. Elevated serum IgG4 levels are found in many but not all patients. New diagnostic criteria for IgG4-RD have been published recently in 2019 and 2021. This review summarizes current knowledge on pathophysiology, clinical manifestations, diagnosis and differential diagnosis of IgG4-RD from the point of view 2022 and in next article brings overview of the IgG4-RD therapy.

Langerhans cell histiocytosis (LCH). Overview of symptoms of LCH, which may lead the patients to any of these medical specialists.

Langerhans cell histiocytosis (LCH) is a rare condition with incidence in adults 1-2/1 million, wherein Langerhans cells proliferate abnormally, adversely impacting organs including most frequently bones, skin, lungs, pituitary gland, lymph nodes, gums and other organs. The LCH course varies widely among patients from a self-limiting condition, to one that progresses. But LCH only very rarely culminates in death. To aim of this text is to review all possible symptoms and manifestations of this disease.

Therapy of immunoglonuline IgG4 related disease (IgG4-RD).

Immunoglobulin IgG4 related disease (IgG4-RD) is a heterogeneous disorder with multi-organ involvement recognised as a separate entity at the beginning of this century only. Evolving therapy is reviewed in this paper. Glucocorticoids are first choice drug but long administration of glucocorticoids is connected with many adverse effects. In case of combination glucocorticoids and immunosuppressive agents lower doses of glucocorticoids are needed, the response rate is higher and therapy is better tolerated. Rituximab is drug, that is possible use as monotherapy or in combination with glucocorticoids and immunosuppressive drugs. Only one study compared two immunosuporessive drugs, mycophenolate mofetil and cyclophosphamide. The response rated was similar but remissions were longer after glucocorticoids with cyclophosphamide then glucocorticoids with mycofenolat mofetil. No other comparative study of combination of various imunossupressive drugs with glucocorticoids was published. Rituximab has high number (90 %) of response rate in monotherapy, but can be used in combination with glucocorticoids and immunosuppressives. Rituximab is now preferred and recommended for maintenance therapy administered in 6-month interval. In case of advanced disease, we prefer therefore combination of rituximab, cyclofosphamide and dexamethasone for initial therapy followed by maintenance with rituximab in 6 months interval. There are two new drugs under investigation abatacept and dupilimab with promising results. Although we have very intensive therapies for good results of therapy early diagnosis before irreversible fibrotic changes in IgG4-RD involved organs is still needed.

Arterial Spin Labeling is a Useful MRI Method for Presurgical Evaluation in MRI-Negative Focal Epilepsy.

Arterial spin labeling (ASL) is an MRI technique measuring brain perfusion using magnetically labeled blood as a tracer. The clinical utility of ASL for presurgical evaluation in non-lesional epilepsy as compared with the quantitative analysis of interictal [18F] fluorodeoxyglucose PET (FDG-PET) was studied. In 10 patients (4 female; median age 29 years) who underwent a complete presurgical evaluation followed by surgical resection, the presurgical FDG-PET and ASL scans were compared with the resection masks using asymmetry index (AI) maps. The positive predictive value (PPV) and sensitivity (SEN), were calculated from the number of voxels inside the mask (true positive), and outside the mask (false positive). The comparison of the PPVs showed better PPV in 6 patients using ASL and in 2 patients with PET. SEN was better in 4 patients using ASL and in 5 patients with PET. According to the Wilcoxon signed rank test for PPV (p = 0.74) and for SEN (p = 0.43), these methods have similar predictive power. ASL is a useful method for presurgical evaluation in non-lesional epilepsy. The main benefits of ASL over PET are that it avoids radiation exposure for patients, and it offers lower costs, higher availability, and better time efficiency.

Preoperative Chemoradiotherapy for Gastroesophageal Junction Adenocarcinoma Modified by PET/CT: Results of Virtual Planning Study.

Background and Objectives: The treatment of gastroesophageal junction (GEJ) adenocarcinoma consists of either perioperative chemotherapy or preoperative chemoradiotherapy. Radiotherapy (RT) in the neoadjuvant setting is associated with a higher probability of resections with negative margins (R0) and better tumor regression rate, which might be enhanced by incrementing RT dose with potential impact on treatment results. This virtual planning study demonstrates the feasibility of increasing the dose to GEJ tumor and involved nodes using PET/CT imaging. Materials and Methods: 16 patients from the chemoradiotherapy arm of the phase II GastroPET study were treated by a prescribed dose of 45.0 Gray (Gy) in 25 fractions. PET/CT was performed before treatment. The prescribed dose was virtually boosted on PET/CT-positive areas to 54.0 Gy by 9 Gy in 5 fractions. Dose-volume histograms (DVH) were compared, and normal tissue complication (NTCP) modeling was performed for both dose schedules. Results: DVHs were exceeded in mean heart dose in one case for 45.0 Gy and two cases for 54.0 Gy, peritoneal space volume criterion V45Gy < 195 ccm in three cases for 54.0 Gy and V15Gy < 825 ccm in one case for both dose schedules. The left lung volume of 25 Gy isodose exceeded 10% in most cases for both schedules. The NTCP values for the heart, spine, liver, kidneys and intestines were zero for both schemes. An increase in NTCP value was for lungs (median 3.15% vs. 4.05% for 25 × 1.8 Gy and 25 + 5 × 1.8 Gy, respectively, p = 0.013) and peritoneal space (median values for 25 × 1.8 Gy and 25 + 5 × 1.8 Gy were 3.3% and 14.25%, respectively, p < 0.001). Conclusion: Boosting PET/CT-positive areas in RT of GEJ tumors is feasible, but prospective trials are needed.

68Ga-DOTATOC.

The radiopharmaceutical 68Ga-DOTATOC represents the latest radiopharmaceutical in the diagnosis of a neuroendocrine tumor with somatostatin receptor overexpression. Technological and economic difficulties of preparing and quality control of the radiopharmaceutical limit its use to specialised departments. Background of the department with rich experience with radiopharmaceuticals for positron emission tomography allows handling more difficult 68Ga-radiopharmacy and may increase and improve the care of oncology patients.

Therapy of 3 patients with Erdhiem-Chester disease with cladribin or cladribin in combination with cyclophosphamide. Case report and review of the therapy.

Three adult patients with confirmed Erdheim-Chester disease (ECD) are followed at our department. Cladribine in monotherapy or in combination with cyclophosphamide were used for first line therapy. The median number of cycles of cladribine or cladribine and cyclophosphamide was 7 (range 6-8). In two cases complete response was achieved, in one case this therapy achieved no response. The duration of response is in one case 11 years, in second case the follow up is too short for evaluation of response duration. In case of no-response to cladribine and cyclophosphamide stabilisation of disease was achieved with anakinra. The tolerance was good without any toxicity grade II and higher. Cladribin and cyclophosphamide is one option for treatment of Erdheim-Chester disease.

Unicentric Castlemans disease. Symptoms, diagnostics and therapy.

Castleman disease (CD) includes a group of rare and heterogeneous disorders with characteristic lymph node histopathological abnormalities. CD can occur in a single lymph node station, which is referred to as unicentric CD (UCD). CD can also involve multicentric lymphadenopathy and inflammatory symptoms - multicentric Castleman disease. The first-ever diagnostic and treatment guidelines were recently developed for UCD and published 2020. Complete surgical resection is often curative and is therefore the preferred first-line therapy, if possible. The management of unresectable UCD is more challenging. Existing evidence supports that asymptomatic unresectable UCD may be observed. The anti-interleukin-6 monoclonal antibody siltuximab should be considered for unresectable UCD patients with an inflammatory syndrome. Unresectable UCD that is symptomatic because of compression of vital neighbouring structures may be rendered amenable to resection by medical therapy (rituximab, steroids), radiotherapy, or embolization. In this article, we report about the symptoms of this disease and about the diagnostics recommendation published in the International, evidence-based consensus diagnostic criteria for HHV-8-negative/ idiopathic multicentric Castleman disease and about the therapeutic recommendation published in International evidence-based consensus diagnostic and treatment guidelines for unicentric Castleman disease published in the year 2020.

Transformation of IgM-MGUS into Waldenström´s macroglobulinemia in two of six patients treated for Schnitzler´s syndrome.

Transformation of IgM-MGUS into Waldenström´s macroglobulinemia in two of six patients treated for Schnitzler´s syndrome Schnitzler´s syndrome is a very rare, adult-onset, apparently acquired autoinflammatory disease. Chronic urticarial rash and symptoms of systemic inflammation including fever, arthralgia and bone pain with the presence of monoclonal immunoglobulin M (IgM), rarely IgG, are among hallmarks of the disease. We performed a retrospective study of 6 patients (5 men, 1 woman) diagnosed with Schnitzler´s syndrome fulfilling the Strasbourg criteria who had been treated at our centre in the University Hospital Brno from 2007 to 2021. Median age at diagnosis was 54 (45-67) years, median follow up was 8 (3-14) years. All 6 patients had IgM κ monoclonal gammopathy, increased CRP and/or erythrocyte sedimentation rate and arthralgia or bone pain, 4 patients suffered from fever, three had leucocytosis 10 × 109/L and lymphadenopathy was found in one patient. 18FDG-PET/CT scan with low-dose total body CT became a part of the initial baseline assessment in 5 patients with suspected Schnitzler´s syndrome, while Na18F-PET/CT was used in one patient to confirm the presence of osteosclerotic leasions as a criterion of the disease. All patients had osteosclerotic or hyperostotic bone lesions detected by low-dose CT examination, with increased 18FDG uptake in illiac and femoral bone marrow. The patient with Na18F-PET/CT scan revealed intensive abnormal tracer uptake with Na18F-PET/CT being more sensitive for detection of osteosclerotic lesions in Schnitzler´s syndrome than 18FDG-PET/CT. All patients were treated with daily subcutaneous anakinra without any adverse events, with excellent clinical results. We observed complete disappearance of urticaria and other symptoms persisting during years of anakinra administration. IgM-MGUS transformed into Waldenström´s macroglobulinemia in two of six patients, but only one patient developed symptoms requiring RBD (Rituximab, Bendamustin, and Dexamethasone) treatment, which induced almost complete remission of the disease. Successful RBD therapy enabled to prolong intervals of maintenance anakinra from 24 to 48 hours with almost complete control of urticarial rash and other symptoms. We suggest close monitoring of patients with Schnitzler´s syndrome to early capture potential transformation into Waldenström´s macroglobulinemia with succesful treatment of both conditions.

Complete remission of necrobiotic xanthogranuloma after disappearance of monoclonal immunoglobulin induced by bortezomib, lenalidomid and dexamethasone.

Necrobiotic xanthogranuloma (NXG) is a rare chronic condition, belonging to the group non-Langerhans cell histiocytoses, which is relevant due to the possibility of extracutaneous involvement and association with systemic diseases, particularly monoclonal gammopathy, MGUS and multiple myeloma. The case reported here NXG was diagnosed after 1 years of evolution in patient with asymptomatic multiple myeloma. After treatment with bortezomib, lenalidomid and dexamethasone, there was evident abrupt decrease of monoclonal immunoglobulin to not measurable level (complete remission of multiple myeloma) and in the same time was evident disappearance of cutaneous and hepatic lesions of NXG on FDG-PET/CT. The etiopathogenetic association of monoclonal immunoglobulin with NXG is documented in this case report with disappearance of NXG in the time of disappearance of monoclonal immunoglobulin.

The effect of oral and nasal breathing on the deposition of inhaled particles in upper and tracheobronchial airways.

The inhalation route has a substantial influence on the fate of inhaled particles. An outbreak of infectious diseases such as COVID-19, influenza or tuberculosis depends on the site of deposition of the inhaled pathogens. But the knowledge of respiratory deposition is important also for occupational safety or targeted delivery of inhaled pharmaceuticals. Simulations utilizing computational fluid dynamics are becoming available to a wide spectrum of users and they can undoubtedly bring detailed predictions of regional deposition of particles. However, if those simulations are to be trusted, they must be validated by experimental data. This article presents simulations and experiments performed on a geometry of airways which is available to other users and thus those results can be used for intercomparison between different research groups. In particular, three hypotheses were tested. First: Oral breathing and combined breathing are equivalent in terms of particle deposition in TB airways, as the pressure resistance of the nasal cavity is so high that the inhaled aerosol flows mostly through the oral cavity in both cases. Second: The influence of the inhalation route (nasal, oral or combined) on the regional distribution of the deposited particles downstream of the trachea is negligible. Third: Simulations can accurately and credibly predict deposition hotspots. The maximum spatial resolution of predicted deposition achievable by current methods was searched for. The simulations were performed using large-eddy simulation, the flow measurements were done by laser Doppler anemometry and the deposition has been measured by positron emission tomography in a realistic replica of human airways. Limitations and sources of uncertainties of the experimental methods were identified. The results confirmed that the high-pressure resistance of the nasal cavity leads to practically identical velocity profiles, even above the glottis for the mouth, and combined mouth and nose breathing. The distribution of deposited particles downstream of the trachea was not influenced by the inhalation route. The carina of the first bifurcation was not among the main deposition hotspots regardless of the inhalation route or flow rate. On the other hand, the deposition hotspots were identified by both CFD and experiments in the second bifurcation in both lungs, and to a lesser extent also in both the third bifurcations in the left lung.

Numerous cold arousals and rare arousal cascades as a hibernation strategy in European Myotis bats.

Hibernating bats optimise the duration of torpor bouts and arousals in relation to hibernaculum microclimatic conditions and fat reserves. Clustering has significant physiological and ecological benefits, promoting successful hibernation of individuals. Such aggregations may help maintain optimal temperatures, allowing better energy utilisation than in solitarily bats. However, aroused bats in a cluster could conceivably disturb those still hibernating, starting an energy-demanding arousal process. Our study was conducted over two winters in two different hibernacula (cave and mine) in the Czech Republic, where Greater mouse-eared bats (Myotis myotis) have previously been diagnosed with white-nose syndrome. In 118 arousal episodes we recorded 193 individual arousals in which a warming phase was observed, 135 (69.9%) being cold arousals, where bats ceased increasing their body temperatures at ≤ 10 °C. The remaining arousals were standard normothermic arousals, where body (fur) surface temperatures reached > 20 °C. Cold arousals occurred during the mid- and late hibernation periods, suggesting they were a response to disturbance by a neighbour in the same cluster. Arousal cascades, where bats aroused in series, were rare (12.7%) and reached a maximum in mid-January. Our data suggest that Myotis bats prolong their torpor bouts using numerous cold arousals but few arousal cascades. Upon arrival of a bat, the clustered bats show tolerance to disturbing by conspecifics.

Systemic inflammatory response with high CRP values as the dominant symptom of multiple myeloma.

A man aged 60 years was examined for intense inflammatory response, night sweats, subfebrile and later febrile temperatures and a weight loss of 18 kg in 7 months. CRP was 270 mg / l, i.e. more than 20 times the upper limit of the physiological range. Reactive leukocytosis (10 × 109/l), thrombocytosis (530 × 109/l), increased fibrinogen (greater than 7 g/l), and anemia with hemoglobin of 80 g/l were present. No infection or systemic autoimmune disease has been proven. The patient had normal renal function and had no osteolytic deposits detectable by FDG-PET/CT. The procalcitonin level was not elevated. The bone marrow examination revealed a 30-40% infiltration of proplasmacyte type with admixture of plasmablasts, expressing light chains λ. Monoclonal immunoglobulin IgA λ was at a low concentration of about 8 g/l and the ratio of free light chains κ/λ was 0.13. The extent of bone marrow infiltration and anemia met the criteria for the diagnosis of symptomatic multiple myeloma. Following initiation of the combination therapy using thalidomide, bortezomib and dexamethasone, the maximum decrease in the concentrations of monoclonal immunoglobulin, free light chains and CRP was observed already after the first 2 cycles of treatment. Later, during the following two 2 cycles, the disease began to progress again. The patient underwent successful stem cell collection after the application of cyclophosphamide 2.5 g/m 2 and leukocyte growth factor (G-CSF), and high-dose chemotherapy (melphalan 200 mg/m 2) with the support of stem cell transplantation. At 2 months following high-dose chemotherapy, CRP levels of the physiological range decreased, the blood count was normalized, and monoclonal immunoglobulin was not detectable. Conclusion: The chronic inflammatory response may be due to plasmocytary bone marrow infiltration even if there are no other symptoms of multiple myel-oma present, except for anemia which, however, also involves the inflammatory reaction. In this case, the systemic inflammatory reaction with high CRP levels signalled aggressive behaviour of the disease. Key words: CRP - multiple myeloma - procalcitonin - systemic inflammatory response.

Predictive value of preoperative statistical parametric mapping of regional glucose metabolism in mesial temporal lobe epilepsy with hippocampal sclerosis.

OBJECTIVE: This study was designed to use statistical parametric mapping of interictal positron-emission tomography using [18F]Fluorodeoxyglucose (FDG-PET) to compare the brain metabolisms of patients with mesial temporal lobe epilepsy (MTLE)/hippocampal sclerosis and controls. Another aim of this study was to analyze the potential differences among patients in terms of epilepsy duration, side of hippocampal sclerosis, histopathological findings, insult in their history, and postoperative outcomes. METHODS: We analyzed FDG-PET scans from 49 patients with MTLE/hippocampal sclerosis and 24 control subjects. We analyzed the differences in regional glucose metabolism between the patients and the control group and within the patient group using multiple variables. RESULTS: We observed widespread hypometabolism in the patient group in comparison with the control group in temporal and extratemporal areas on the epileptogenic side (ES). On the nonepileptogenic side (NES), we observed the most hypometabolism in the thalamus and the anterior and middle cingulate gyrus. In the group of patients with more severe hippocampal sclerosis, we observed statistically significant hypometabolism in the insula on the ES. In patients with poor postoperative outcomes, we found statistically significant hypometabolism in the insula on the ES and the temporal pole (TP) on the NES. Patients with any insult in their history showed hypermetabolism in the TP on both sides. CONCLUSION: Our study showed that there are widespread changes in metabolism in patients with MTLE in comparison to controls, either inside or outside the temporal lobe. There are significant differences among these patients in terms of postoperative outcomes, degree of hippocampal sclerosis, and insults in their history.

[Polymyalgia rheumatica]. / Polymyalgia rheumatica.

Polymyalgia rheumatica is the most frequent inflammatory disease of people over 50 years of age. It mainly affects the Caucasian race and roughly 2-3 times as many women. From the viewpoint of etiology, polymyalgia rheumatica is a complex disease. Involved in its origin is genetic predisposition, factors of age and outer environment. 16-21 % of patients with polymyalgia rheumatica may at the same time have symptoms of giant cell arteritis. Diagnosis is made primarily on the basis of clinical symptoms and it is supported by the presence of laboratory signs of inflammation. There is no specific diagnostic test available for diagnosing polymyalgia rheumatica. In recent time modern imaging devices, e.g. ultrasonography or positron emission tomography, can be used in diagnosing the disease. In the past a number of diagnostic and classification criteria were established which may be used in diagnosing of polymyalgia rheumatica in general practice. The differential diagnostics of the disease is extensive. Before the treatment commencement it is necessary to rule out the presence of another disease with manifestations simulating polymyalgia rheumatica. The treatment strategy should draw on the current EULAR/ACR Recommendations for the treatment of polymyalgia rheumatica issued in 2015.Key words: polymyalgia rheumatica - positron emission tomography - prognosis - treatment - ultrasonography.

Radiotherapy of Glioblastoma 15 Years after the Landmark Stupp's Trial: More Controversies than Standards?

BACKGROUND: The current standard of care of glioblastoma, the most common primary brain tumor in adults, has remained unchanged for over a decade. Nevertheless, some improvements in patient outcomes have occurred as a consequence of modern surgery, improved radiotherapy and up-to-date management of toxicity. Patients from control arms (receiving standard concurrent chemoradiotherapy and adjuvant chemotherapy with temozolomide) of recent clinical trials achieve better outcomes compared to the median survival of 14.6 months reported in Stupp's landmark clinical trial in 2005. The approach to radiotherapy that emerged from Stupp's trial, which continues to be a basis for the current standard of care, is no longer applicable and there is a need to develop updated guidelines for radiotherapy within the daily clinical practice that address or at least acknowledge existing controversies in the planning of radiotherapy.The goal of this review is to provoke critical thinking about potentially controversial aspects in the radiotherapy of glioblastoma, including among others the issue of target definitions, simultaneously integrated boost technique, and hippocampal sparing. CONCLUSIONS: In conjunction with new treatment approaches such as tumor-treating fields (TTF) and immunotherapy, the role of adjuvant radiotherapy will be further defined. The personalized approach in daily radiotherapy practice is enabled with modern radiotherapy systems.

[Remission of steroid-resistant Stills disease treated with anakinra, evidenced by FDG-PET/CT examination: case report]. / Remise steroid-rezistentní Stillovy nemoci pri lécbe anakinrou dokumentovaná FDG-PET/CT vysetrením: kazuistika.

After elimination of infectious causes, neoplastic causes and the systemic autoimmune disease of connective tissue, a patient with high fevers over 39 °C was diagnosed with Stills disease. High doses of prednisone led to resolution of symptoms, however after reducing the doses of prednisone to 15 mg, high fevers over 39 °C returned, as well as joint pains. The high doses of prednisone led to decompensation of diabetes mellitus even with 4 daily insulin dosages. Therefore it was proceeded to regular subcutaneous administration of anakinra once a day. Anakinra enabled the reduction of prednisone to as much as the currently administered 2.5 mg a day, but it has not so far allowed for removing glucocorticoids from the treatment completely. Activity of the disease is shown by the findings within the FDG-PET/CT examination. At the time of maximum activity of the disease there was distinct lymphadenopathy with pathological accumulation of FDG visible as well as increased accumulation of FDG in the hematopoietic bone marrow. As the disease activity decreased, the size of nodules regressed and FDG accumulation in both the lymphatic nodes and bone marrow declined. FDG-PET/CT is a suitable method for monitoring the activity of Stills disease.Key words: anakinra - Adult-onset Stills disease.

[Remission of the disease associated/related with immunoglobulin IgG4 accompanied by multiple lymphadenopathy after treatment with rituximab and dexamethasone: a case report]. / Remise "the disease associated/related with immunoglobulin IgG4" provázeného mnohocetnou lymfadenopatií po lécbe rituximabem a dexametazonem: kazuistika.

A disease associated with immunoglobulin IgG4 is a rare unit with very variable symptoms. We describe the course and treatment of the disease in a patient who presented with multiple lymphadenopathy and infiltrates in the area of the retroperitoneum and pelvis and signs of chronic sclerosing pancreatitis. The disease was clinically manifested by a significant loss of weight, but also by a loss of perception of taste and smell. The diagnosis was made based on a high amount of IgG4 expressing plasma cells in the sampled tissue and an increased concentration of immunoglobulins of type IgG and mainly subclass IG4. Rituximab in 475 mg/m2 dose was used in the treatment, the initial four doses of rituximab were administered at 14-day intervals, always with a one-off administration of a 40 mg dose of dexamethasone. According to FDG-PET/CT, only partial remission of the disease was reached after 4 applications of rituximab and dexamethasone. The patient recovered its sense of smell and taste. In another 4 cycles ritu-ximab was administered on day 1 of a 28-day cycle. On days 1 and 15 of the cycle dexamethasone at 40 mg and cyclophosphamide at 600 mg were administered by intravenous infusion. After the completion of 8 cycles of treatment based on rituximab and dexamethasone and with cyclophosphamide added in the second half of the treatment, the control FDG-PET/CT examination proved the complete remission. Before the treatment commencement the concentration of the subclass of immunoglobulin IgG4 was equal to 51.0 g/l, after the completion of the aforementioned treatment it dropped to 3.5 g/l. The patient tolerated the treatment without any adverse effects. Ritu-ximab, dexamethasone and cyclophosphamide induced the complete remission of this disease.Key words: IgG4-associated/releated disease - rituximab.