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The aim – to present the experience of diagnosis, management, and therapy with IL-1 inhibitors in patients with Schnitzler’s syndrome (SchS) according to a multicenter Russian cohort.Materials and methods. In an observational retrospective study for a 10-year period (2012–2022), 17 patients with SchS who were admitted to the hospital or were observed on an outpatient basis, among them 8 women, 9 men, were included in the study. The diagnosis of all corresponded to the Strasbourg diagnostic criteria.Results. The age of patients ranged from 25 to 81 years (Me 53 [46; 56] years). The age at the time of the onset of the disease ranged from 20 to 72 years (Me 46 [39; 54] years), the duration of the disease before diagnosis ranged from 1 to 35 years (Me 6.5 [3; 6] years), in 3 it exceeded 10 years, in the rest it ranged from 1 to 8 years. Infectious and lymphoproliferative diseases, monogenic AIDS (CAPS, TRAPS, HIDS) were excluded from all patients at the prehospital stage. The guiding diagnosis for all was Still’s disease in adults. Clinical manifestations of the disease included: fatigue, lethargy, fatigue, rash and fever in all, skin elements were urticular in all, accompanied by itching in 6 (37.5%). Bone pain had 12 (70.6%), arthralgia – 16 (94.1%), arthritis – 9 (52.9%), myalgia – 7 (41.2%), weight loss in 4 (23.5%). Lymphadenopathy (6), enlarged liver (6), pericarditis (4), angioedema (6), redness and dryness in the eyes (3), sore throat (2), abdominal pain (1), distal polyneuropathy (2), paraesthesia (1), chondritis of the auricles were less common (1). Monoclonal gammopathy was detected in all with a secretion level of 2.9–15.1 g/l: IgMk (n=10 (64.7%)), less often IgMλ (n=2), IgGk (n=2), IgGλ (n=1), IgAλ (n=1). Ben-Jones protein was not detected in any of them. All patients had an increase in the level of ESR, CRP. 16 patients before inclusion in the study received GC (94.1%) with a temporary effect and its escape with dose reduction or cancellation, DMARD – 7, among them methotrexate (5), hydroxychloroquine (2), cyclophosphamide (1), also NSAIDs and antihistamines in all, biological drugs: anti-B-cell the drug rituximab (1), monoclonal AT to IgE – omalizumab in 2 (1 – without effect, 1 – partial effect). 11 patients were prescribed IL-1: canakinumab – 9 (52.9%) subcutaneously once every 8 weeks, anakinra – 4 (23.5%) subcutaneously daily. The duration of taking anakinra, which was prescribed in the test mode, ranged from 1 week to 2.5 months with a further switch to canakinumab in 3. The duration of taking canakinumab at the time of analysis ranged from 7 months to 8 years. Against the background of treatment with IL-1, 10 out of 11 (90.9%) received a complete response from the clinical manifestations of the disease and a decrease in the level of ESR and CRP within a few days. In 1 patient, a partial response was received to the administration of anakinra, and when switching to canakinumab, the effect of treatment was finally lost. 1 patient received IL-6 for 8 months with incomplete effect and transition to IL-1 with positive dynamics. In 1 patient, due to the persistent absence of relapses, the interval between canakinumab injections was increased to 5 months without signs of reactivation, but subsequently, against the background of stress and relapses of the disease, the intervals were reduced to 4 months. A healthy child was born in the same patient on the background of treatment. The tolerability of therapy was satisfactory in all patients, no SAE was noted.Conclusion. SchS is a rare multifactorial/non–monogenic AID that needs to be differentiated from a number of rheumatic diseases and other AIDS. The onset in adulthood, the presence of recurrent urticarial rashes in combination with fever and other manifestations of a systemic inflammatory response are indications for examination for monoclonal secretion. The use of short- or long-acting IL-1 is a highly effective and safe option in the treatment of such patients.

This study was performed in real clinical practice settings. Our paper describes two case studies which show the difficulty of differential diagnosis of monoclonal gammopathies, multiple myeloma associated with AL-amyloidosis and primary AL-amyloidosis.

Objective. To describe the difficulties of diagnosis of Waldenström macroglobulinemia in a patient with atypical clinical picture.Materials and methods. Patient K., 57 years old, came in outpatient department with complaints of unilateral increase in submandibular lymph nodes on the right, discomfort in the nasopharynx, cough without sputum, increased fatigue. During the examination she was consulted by: an infectious disease specialist, otolaryngologist, surgeon, dentist, phthisiologist, hematologist and oncologist consulted her. To confirm the diagnosis conducted diagnostic activities: dynamic assessment of laboratory parameters, examination program cancer search (including multislice computed tomography and magnetic resonance imaging of various areas), with the exception of tuberculosis, monogenically study proteins in the blood and urine tests, biopsy of the ileum, immunohistochemistry trepanobiopsy.Results. During the 4‑year examination in the patient’s blood, an M-gradient in the gamma zone was detected, monoclonal immunoglobulin М-κ 19.3 g / l, Bens-Jones-κ protein in urine (daily proteinuria 0.45 g) was detected during immunofixation. In the myelogram at the light-optical level, the number of cell elements was significantly reduced with a pronounced lymphoid proliferation of 40 %, the granulocytic series and erythropoiesis were relatively narrowed, and plasma cells 6 %. Immunomorphological picture trepanobiopsy our patient based on the data of laboratory methods of research corresponds to the defeat of the bone marrow in Waldenström’s disease-κ, secretion of M-paraprotein. An important feature that allowed to go on the right path of diagnosis was almost pathognomonic for tumor lymphoproliferation, detection of Bens-Jones protein in the urine, which was absent in the onset of the disease.Conclusion. This clinical case is interesting not only by the complexity of the diagnosis of macroglobulinemia of Waldenström in General, but also by the atypical, erased clinical disease in our patient.

This article describes a rare case of necrotic xanthogranuloma in a 46-year-old patient who presented with the development of periorbital xanthelasms, progressive bilateral sensorineural hearing loss and bilateral vestibulopathy, followed by multiple myeloma and amyloidosis. For several years, the patient underwent standard rehabilitation for chronic sensorineural hearing loss and was fitted with a hearing aid. During hospitalisation for exacerbation of chronic bronchitis, monoclonal gammopathy was identified, and later, after careful examination and repeated biopsies, necrotic xanthogranuloma, multiple myeloma and AL-amyloidosis were confirmed. Targeted immunochemotherapy resulted in improvement of hearing and significant recovery of the vestibuloocular reflex bilaterally.

POEMS-syndrome (P — polyneuropathy, O — organomegaly, E — endocrinopathy, M — M-protein, S — skin) in 64-year old patient isdescribed in the article. The clinical picture was marked by such symptoms, as polyneuropathy, multiple myeloma, organomegaly (hepatosplenomegaly), endocrinopathy (diabetes), skin changes (redness and induration of the dermis in the neck), fever, hypoproteinemia, edema, weight loss, thrombocytosis. Bone-destructive syndrome was absent. In myelogram 18 % of the cells with signs of some plasmatic anaplasia were found. In blood, low level of paraprotein secretion Aλ, increased β2-microglobulin was fixed. A course of therapy with prednisolone and alkeranom was accompanied by slight positive effect. However, a second course was interrupted in the third day due to worsening of concomitant cardiac disease (ischemic heart disease in combination with hypertension). Last episode of recurrent of pulmonary edema occurred fatal. Autopsy study was not conducted. This observation illustrates the need for more rigorous examination (myelogram, immunochemical study of blood and urine) in the presence of clinical signs of POEMS-syndrome for the timely diagnosis of the underlying disease and its treatment.

Surowiec Agnieszka, Wołowiec Łukasz, Kochański Bartosz, Kałużna Anna, Kałużny Krystian, Krakowska Alicja, Zukow Walery. Niewydolność nerek w przebiegu szpiczaka mnogiego = Renal failure in multiple myeloma. Journal of Education, Health and Sport. 2016;6(1):262-270. eISSN 2391-8306. DOI http://dx.doi.org/10.5281/zenodo.45356 http://ojs.ukw.edu.pl/index.php/johs/article/view/3346 https://pbn.nauka.gov.pl/works/710506 The journal has had 7 points in Ministry of Science and Higher Education parametric evaluation. Part B item 755 (23.12.2015). 755 Journal of Education, Health and Sport eISSN 2391-8306 7 © The Author (s) 2016; This article is published with open access at Licensee Open Journal Systems of Kazimierz Wielki University in Bydgoszcz, Poland Open Access. This article is distributed under the terms of the Creative Commons Attribution Noncommercial License which permits any noncommercial use, distribution, and reproduction in any medium, provided the original author(s) and source are credited. This is an open access article licensed under the terms of the Creative Commons Attribution Non Commercial License (http://creativecommons.org/licenses/by-nc/4.0/) which permits unrestricted, non commercial use, distribution and reproduction in any medium, provided the work is properly cited. This is an open access article licensed under the terms of the Creative Commons Attribution Non Commercial License (http://creativecommons.org/licenses/by-nc/4.0/) which permits unrestricted, non commercial use, distribution and reproduction in any medium, provided the work is properly cited. The authors declare that there is no conflict of interests regarding the publication of this paper. Received: 01.01.2016. Revised 12.01.2016. Accepted: 31.01.2016. Niewydolność nerek w przebiegu szpiczaka mnogiego Renal failure in multiple myeloma Agnieszka Surowiec1,Łukasz Wołowiec2, Bartosz Kochański3, Anna Kałużna3, Krystian Kałużny3, Alicja Krakowska3,Walery Zukow4 1Studenckie Koło Naukowe Diagnostyki i Terapii Niewydolności Serca, II Katedra Kardiologii, Wydział Nauk o Zdrowiu, Uniwersytet Mikołaja Kopernika w Toruniu 2II Katedra Kardiologii, Wydział Nauk o Zdrowiu, Uniwersytet Mikołaja Kopernika w Toruniu 3Katedra i Klinika Rehabilitacji, Wydział Nauk o Zdrowiu, Uniwersytet Mikołaja Kopernika w Toruniu 4Instytut Kultury Fizycznej, Wydział Kultury Fizycznej, Zdrowia i Turystyki, Uniwersytet Kazimierza Wielkiego w Bydgoszczy Streszczenie Pierwszą manifestacją kliniczną szpiczaka mnogiego (MM) może być niewydolność nerek (z ang. renal failure RF). Podwyższone stężenie kreatyniny w surowicy jest już często obecne w momencie rozpoznania choroby aż u 20-50% pacjentów z MM. MM charakteryzuje się proliferacją monoklonalnych komórek plazmatycznych, wytwarzających białko M i rozwija się etapami. W pierwszym etapie komórki B stają się nieśmiertelne z powodu translokacji chromosomalnej w locus ciężkiego łańcucha immunoglobulinowego. Rokowanie u pacjentów z kreatyniny w surowicy> 2,0 mg/dl. Ponadto, pacjenci z niewydolnością nerek są często eliminowani z agresywnych czy też wysokodawkowych protokołów chemioterapeutycznych ze względu na ich toksyczność. Abstract One of the first symptoms of multiple myeloma (MM) can be renal insufficiency (RI). Elevated concentration of serum creatinine states is already present at the time of diagnosis in 20–50% of patients with MM. MM is characterised by monoclonal proliferation of plasma cells which are producing monoclonal immunoglobulin (M protein). The disease develops in many stages. In the first stage the cells B becomes immortal due to chromosomes translocation in the immunoglobuline heavy chain locus. The prognosis for patients with a serum creatinine >2.0 mg/dL is very bad. Moreover, patients with renal failure are often excluded from aggressive or high-dose chemotherapy protocols because of an expected higher toxicity rate. Słowa kluczowe: szpiczak mnogi, gammapatia monoklonalna, niewydolność nerek. Keywords: multiple myeloma, monoclonal gammopathy, renal failure.

Monoclonal gammopathy (MG) is not only the state preceding of hematological neoplasms, but also associated with non - hematological diseases, in particular kidney damage., Aim: To assess the diagnostic value of "Freelite" methods in addition to electrophoresis (EF) and immunofixation (IF) of serum and urine proteins for detecting MG in patients with kidney diseases., Materials and Methods: 87 patients with kidney damage, in which MG was established using the method of electrophoresis of serum proteins (EF), immunofixation (IF) and the method of free light chains determination - FLC "Freelite" were selected. The diagnostic value of three - component serum panel was compared with EF and IF., Results and Discussion: AL-amyloidosis with kidney involvement was diagnosed in 41% patients, cryoglobulinemic glomerulonephritis (cryo GN) - in 18%, chronic glomerulonephritis (CGN) - in 35%, also there was small number of patients with light chain disease and cast - nephropathy. Determination of MG using EP was possible only in 38 (44%). Adding to the serum electrophoretic methods instead of the "Freelite" method, the urine EF and IF reduced the number of missed patients with monoclonal gammopathy from 24 (27%) to 11 (13%), including in the subgroup of patients with AL-amyloidosis but did not reach the sensitivity of the three - component serum screening panel. In 10 (11.5%) MG was represented only by intact mIg with one type of light chain, either κ or λ. Most often - in 25% of patients, intact monoclonal gammopathy was observed in HCV (+) cryo GN. A combination of intact mIgM, mIgG or mIgA with mFLC, was detected in 37 (42.5%). In almost half (46%) of the patients, only mFLC was detected - an abnormal κ/λ ratio., Conclusion: The serum screening panel EF + IF + "Freelite" spreads the low - grade monoclonal gammopathy recognition (MGUS) and should be included in the algorithm of examining patients with kidney disease.

The content of free light chains of immunoglobulins kappa and lambda and also ratio of their concentrations in blood serum are important diagnostic and prognostic markers in case of monoclonal gammopathy. The technique FreelightTM based on nephelometric detection of free light chains using polyclonal antibodies is one of common modes of detection of free light chains. The actual study was carried out with purpose of validating of national test-system for detection of level of free light chains in blood serum using technique of enzyme-linked immunosorbent assay. The samples of blood serum were taken from 89 healthy donors and 165 patients with monoclonal gammopathy. To detect the level of free light chains enzyme-linked immunosorbent assay testsystem "Polygnost" was used based on application of monoclonal a ntibodies. The number of analytical characteristics of reagents set was determined including limit of detection and range of linearity. The limit of detection of free light chains using enzymelinked immunosorbent assay test-system was two times lower than claimed by manufacturer of nephelometric set "FreelightTM". Hence, analytical characteristics of enzyme-linked immunosorbent assay set make it possible to detect the level of free light chains within range of standard values. The reference limits were established concerning concentration of free light chains kappa (3.25-15.81 mkg/ml), free light chains lambda (3.23-28.05 mkg/ml) and their ratio (0.3-1.9) in blood serum that factually matched the recommended intervals for "FreelightTM" set. In patients with monoclonal gammopathy the level of free light chains was reliably higher (p<0.01) as compared with control group of healthy donors. In case of paraproteinemia reliable alteration (p<0.01) of ratio free light chains kappa/free light chains lambda was observed in comparison with control group. The results of actual study testify that national enzyme-linked immunosorbent assay set has good analytical and diagnostic characteristics and it can be used in laboratory practice., Competing Interests: The authors declare no conflict of interest.