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.

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.

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.

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.

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.

Aggressive systemic mastocytosis with diffuse bone marrow 18F-FDG uptake.

Mastocytosis is a clonal hematopoietic disorder characterized by proliferation of abnormal mast cells in various organs including the skin, digestive system, lymph nodes, and bone marrow. We report on a 75-year-old woman presenting with abdominal pain, vomiting, diarrhoea, myalgia, and weight loss. Abdominal CT showed hepatosplenomegaly with heterogeneous splenic parenchyma, lymphadenopathy, and osteopenia with areas of osteosclerosis but no primary tumour. An 18F-FDG PET/CT revealed an overall low metabolic activity of the lesions with a diffuse bone marrow involvement raising suspicion of a haematological neoplasm. Subsequently, bone marrow and peripheral blood examinations confirmed the diagnosis of aggressive systemic mastocytosis.

Epithelioid hemangioendothelioma on PET/CT scan.

BACKGROUND: At present, lung cancer ranks among the most frequent malignant diseases. However, according to literature data, mesenchymal lung tumors are very rare, representing less than 0.5% of all malignant lung tumours. Epithelioid hemangioendothelioma of the lungs belongs to this group of uncommon entities. CASE REPORT: We present a case of a 45-year-old male with a history of increasing dyspnoea and abdominal and back pains, developing over the past several months. Vertebral lesions were found on imaging studies. PET/ CT following 18F-fluorodeoxyglucose administration (FDG) showed a large FDG-positive malignant infiltration affecting the thorax, abdominal cavity, and bones. The extension and other characteristics of the mass on PET/ CT did not correspond to any of the common oncologic diseases. With its spread in a plaque-like form predominantly in the right hemithorax and on the surface of the liver, the disease closely resembled malignant mesothelioma. The primary tumour origin could not be clearly identified on PET/ CT scans but they allowed us to choose a suitable site to obtain tissue for pathologic examination. Based on a CT-guided bone bio-psy of the 7th right rib, the dia-gnosis was concluded as epithelioid hemangioendothelioma. Despite an early initiation of systemic treatment, the patient succumbed to the disease only 15 days after the dia-gnosis, due to superior vena cava syndrome and progressive pleural effusion leading to respiratory insufficiency. CONCLUSIONS: Given the extremely low prevalence of epithelioid hemangioendothelioma and its heterogeneous manifestation, it is impossible to base the dia-gnosis solely on disease symptoms, laboratory findings, and imaging modalities. In this respect, pathologic examination has a crucial role. For the same reason, there is a lack of recommendations for the standard-of-care systemic therapy of metastatic disease.

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.

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.

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.

In silico study of pseudoprogression in glioblastoma: collaboration of radiologists and radiation oncologists in the estimation of extent of high dose RT region.

BACKGROUND AND AIM: Oncologists play a vital role in the interpretation of radiographic results in glioblastoma patients. Molecular pathology and information on radiation treatment protocols among others are all important for accurate interpretation of radiology images. One important issue that may arise in interpreting such images is the phenomenon of tumor "pseudoprogression"; oncologists need to be able to distinguish this effect from true disease progression.Exact knowledge about the location of high-dose radiotherapy region is needed for valid determination of pseudoprogression according to RANO (Response Assessment in Neuro-Oncology) criteria in neurooncology. The aim of the present study was to evaluate the radiologists' understanding of a radiotherapy high-dose region in routine clinical practice since radiation oncologists do not always report 3-dimensional isodoses when ordering follow up imaging. METHODS: Eight glioblastoma patients who underwent postresection radiotherapy were included in this study. Four radiologists worked with their pre-radiotherapy planning MR, however, they were blinded to RT target volumes which were defined by radiation oncologists according to current guidelines. The aim was to draw target volume for high dose RT fields (that is the region, where they would consider that there may be a pseudoprogression in future MRI scans). Many different indices describing structure differences were analyzed in comparison with original per-protocol RT target volumes. RESULTS: The median volume for RT high dose field was 277 ccm (range 218 to 401 ccm) as defined per protocol by radiation oncologist and 87 ccm (range 32-338) as defined by radiologists (median difference of paired difference 31%, range 15-112%). The Median Dice index of similarity was 0.46 (range 0.14 - 0.78), the median Hausdorff distance 25 mm. CONCLUSION: Continuing effort to improve education on specific procedures in RT and in radiology as well as automatic tools for exporting RT targets is needed in order to increase specificity and sensitivity in response evaluation.

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.

[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.

[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.

[Indeterminate cell histiocytosis - disappearance of skin infiltration following electron beam therapy and an application of 2-chlorodeoxyadenosine: case report]. / Histiocytóza z indeterminovaných bunek - vymizení kozní infiltrace po ozárení elektronovým svazkem a aplikace 2-chlorodeoxyadenozinu: kazuistika.

Indeterminate cell histiocytosis is a rare disease belonging to the group of malignant histiocytic diseases. The disease predominantly affects the skin. The disease appeared in the described patient at the age of 80 years. Morphs began to develop on the skin and rapidly spread over the whole body including the face. Only the hands and feet were left uncovered. The patients skin samples were taken from 2 sites for histological examination. The resulting conclusion was indeterminate cell histiocytosis. The treatment we chose was analogous to the procedures for Langerhans cell histiocytosis. We chose PUVA phototherapy as the first-line treatment. This treatment is frequently efficient for skin forms of Langerhans cell histiocytosis. In the described case, however, PUVA phototherapy did not influence the disease activity at all. As the second-line treatment, we used low-energy electron beam irradiation in the total dose of 36.2 Gy. This treatment had a positive impact, morphs began to diminish and slowly disappear from the skin. But they have not disappeared completely, therefore we assessed the treatment effect of the radiotherapy itself as partial remission of the disease. Within the third-line treatment, we used 2-chlorodeoxyadenosine in a dose of 5 mg/m2/per day, administered via subcutaneous injection over 5 consecutive days in monthly intervals. There were three cycles of this treatment administered overall. The treatment with 2-chlorodeoxyadenosine was tolerated without any adverse effects. The patient aged 82 years was only administered 3 cycles of 2-chlorodeoxyadenosine. When after the 3rd cycle the skin was free from any pathological morphs and only some pigmentation spots remained, we finished the treatment. The skin expressions of indeterminate cell histiocytosis completely disappeared after electron beam irradiation and the following administration of 3 cycles of 2-chlorodeoxyadenosine. The remission was short, however, after 6 months the disease recurred and the treatment is planned to resume. We assume the disease regresses following administration of 2-chlorodeoxyadenosine, but more than 3 treatment cycles will probably be needed to reach a longer-term response.Key words: electron beam irradiation - indeterminate cell histiocytosis - 2-chlorodeoxyadenosine.

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.

[Evaluation of five years of treatment of Erdheim-Chester disease with anakinra: case report and overview of literature]. / Hodnocení petileté lécby Erdheimovy-Chesterovy nemoci anakinrou - kazuistika a prehled literatury.

Erdheim-Chester disease is a histiocytic neoplasm of diseases from the group of non-Langerhans-cell histiocytoses, formed by infiltrates of foamy histiocytes. These pathological histiocytes produce pro-inflammatory cytokines. Therefore Erdheim-Chester disease is called inflammatory histiocytary neoplasm. The disease is accompanied by clinical symptoms of systemic inflammatory response, i.e. B symptoms. Imaging examinations detect typical osteosclerotic changes affecting diaphyses and metaphyses of the lower long bones and fibrotic changes which affect the aorta wall and the vessels leading from it. Also characteristic are perirenal fibrotic changes spreading in the retroperitoneum. They can cause serious complications - hydronephrosis with all its consequences. The therapy for this disease was not satisfactory in the previous years. Conventional chemotherapy or glucocorticoids do not bring any substantial and long-term improvement. Considering cytostatic drugs, only 2-chlorodeoxyadenosine (cladribine) is effective, though not in all patients. We have only reached complete remission through 2-chlorodeoxyadenosine in one of our two patients, which now lasts more than 5 years, while cladribine in the same patient did effect the reduction of infiltrates into the CNS, but it did not achieve abatement of the disease activity in other locations as shown by PET/CT with the application of the radio-pharmaceutical fluorodeoxyglucose (FDG). Another effective medicine for patients with Erdheim-Chester disease is interferon α. However its long-term administration is associated with multiple adverse effects and so we did not test it in the described patient. The introduction of anakinra, the interleukin-1 receptor blocker, to therapy brought a new hope for these patients. We are describing the patient who has been treated with anakinra for more than 5 years. The patient applies 1 ampoule of 100 mg subcutaneously per day. This treatment completely removed systemic B symptoms, relieved bone pains and attained normalization of all findings that signalled systemic inflammatory response. The treatment effect is regularly checked by CT imaging of the abdomen and by FDG-PET/CT examinations. The retroperitoneal fibrotic changes gradually regressed during the 5 years of anakinra treatment, as documented by the pictures in the text. Low-dose CT imaging which was part of the PET/CT examination, identified many osteosclerotic lesions in the skeleton, mainly in the legs, with an increased accumulation of 18F-fluorodeoxyglucose (FDG). Osteosclerotic lesions remain well visible at repeated examinations. Still during the course of the 5-year period the FDG accumulation in them decreased, as shown by the pictures in the text. Anakinra treatment has a character of maintenance therapy. The BRAFV600E mutation was not proven in the described patient, therefore we did not test vemurafenib treatment. CONCLUSION: anakinra effected regression of fibrotic changes in the retroperitoneum and disappearance of B symptoms as well as decrease in FDG accumulation at FDG-PET/CT examination.Key words: anakinra - Erdheim-Chester disease - cladribine - retroperitoneal fibrosis - vemurafenib.

[Schnitzlers SyndromeDifferential diagnostics, an overview of therapeutic options and description of 5 cases treated with anakinra]. / Schnitzlerové syndromDiferenciální diagnostika, prehled lécebných mozností a popis 5 prípadu lécených anakinrou.

Schnitzlers syndrome is an acquired auto-inflammatory disease of still unclear origin. The Strasbourg criteria were adopted (non-infectious fever, chronic urticaria, changes in the bone structure, leukocytosis and higher values of inflammatory markers - CRP and presence of monoclonal immunoglobulin mostly of type IgM, very rarely of IgG) to establish this diagnosis. The first-choice therapy for this disease is the blocking of interleukin-1 effects. In practice, the interleukin-1 receptor antagonist, anakinra, is the most commonly used. Currently reports also appear of the use of other medicines blocking the effect of interleukin-1, namely canakinumab and rilonacept. We have been treating 5 patients with anakinra (108, 72, 33, 32 and 1 months) on a long-term basis. In all the patients, we commenced administration of anakinra in a dose of 100 mg once a day. As a result of 100 mg being administered once a day, all symptoms went away completely in 4 patients, while they receded by about 75 % in 1 patient, without disappearing completely. This patient needs an increased dose of 2 ampoules per day on the days of spontaneously intensified medical ailments. After one year of treatment it turned out for one of the four patients whose symptoms had completely disappeared when administered the 100mg daily dose, that he only needed the respective dose of anakinra at 48-hour intervals. However this patient does not tolerate further extension of the intervals between dose administrations. We have not recorded any adverse effects of anakinra in the course of the treatment, and no decline in the efficiency of anakinra has been observed: it acts as effectively now as it did at the beginning of the treatment. The text discusses the differential diagnostics of the Schnitzler syndrome.Key words: anakinra - auto-inflammatory diseases - canakinumab - fever of unknown origin - FUO - interleukin 1 - cryopyrin-associated autoinflammatory syndrome (CAPS) - monoclonal gammopathy - rilonacept - Schnitzlers Syndrome - Adult Stills disease.

[Sinus histiocytosis with massive lymphadenopathy: FDG-PET/CT documented partial remission after treatment with 2-chlorodeoxyadenosine]. / Sinusová histiocytóza s masivní lymfadenopatií: FDG-PET/CT dokumentovaná parciální remise po lécbe 2-chlorodeoxyadenozinem.

UNLABELLED: Sinus histiocytosis with massive lymphadenopathy (Rosai-Dorfman disease) is a very rare disease belonging to a group of histiocytoses (more precisely non-Langerhans cell histiocytoses). Rosai-Dorfman disease is characterised by the presence of atypical histiocytic cells in the sinuses of lymph nodes or in the extranodal lymphoid tissue, absorbing lymphocytes and plasma cells. The structure and function of the absorbed cells is not impaired and they can leave histiocytes as viable cells. This effect is called emperipolesis, whereas ingestion of cells with their destruction is called phagocytosis. In our text we describe a patient with this disease located, characteristically, in supraclavicular lymph nodes, but also in mediastinal lymph nodes. Along with lymphadenopathy skin alterations appeared which were both clinically and histologically described as eczema dermatitis. At the same time as lymphadenopathy also strong headaches started which the patient had never suffered before. Within the first-line treatment prednisone was administered, but no effect was achieved. 2-chlorodeoxyadenosine in 5 mg/m2 s. c. dose was used in the second-line treatment, for 5 successive days in monthly intervals. There were four cycles of this treatment administered overall. Therapy was tolerated without any manifestations of toxicity. Already after the 1st cycle skin alterations as well as headaches entirely disappeared. To assess the effect of treatment the PET/CT examination with 18F-fluorodeoxyglucose (FDG-PET/CT) was made. After 4 cycles of treatment the mediastinal lymph nodes diminished to a physiological size and the accumulation of fluorodeoxyglucose in them was assessed as physiological. Lymphadenopathy in the neck area also significantly diminished by 50-75 % and the accumulation of fluorodeoxyglucose was reduced as well, though it did not reach the norm. Therefore we evaluate the effect of treatment as a partial remission with complete disappearance of skin alterations and headaches. The cause of the eczema and headaches has not been clarified, however considering the same time of their arising and then disappearance after the application of 2-chlorodeoxyadenosine the causal connection with Rosai-Dorfman disease is likely. KEY WORDS: Castlemans disease - lenalidomide - Rosai-Dorfman disease - rituximab - sinus lymphadenopathy with massive lymphadenopathy - thalidomide - 2-chlorodeoxyadenosine.