Schnitzler's Syndrome-Diagnostic Experience, Approaches to Therapy, and Patient Management according to a Multicenter Russian Cohort.

The objectives of the study were 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. An observational retrospective study for a 10-year period (2012-2022) involved 17 patients with SchS who were admitted to the hospital or were observed on an outpatient basis (eight women and nine men). The diagnosis of all of them corresponded to the Strasbourg diagnostic criteria. The age of patients ranged from 25 to 81 years (Me 53[46; 56]). The age at the time of the onset of the disease ranged from 20 to 72 years (Me 46[39; 54]), the duration of the disease before diagnosis ranged from 1 to 35 years (Me 6.5[3; 6]), in three patients it exceeded 10 years, in the rest it ranged from 1 to 8 years. Infectious and lymphoproliferative diseases, monogenic AIDs (CAPS, TRAPS, and HIDS) were excluded from all patients at the prehospital stage. The referral diagnosis for all of them was Still 's disease in adults. Clinical manifestations of the disease in all patients included fatigue, lethargy, fatigue, rash, and fever. In all patients, skin elements were urticular and were accompanied by itching in 6 (37.5%) patients. Bone pain was observed in 12 (70.6%) patients; arthralgias, in 16 (94.1%); arthritis, in 9 (52.9%); myalgia, in 7 (41.2%); and weight loss, in 4 (23.5%). Lymphadenopathy was detected in 6 (35.3%) patients; enlarged liver, in 6 (35.3%); pericarditis, in 4 (23.5%); angioedema, in 6 (35.3); redness and dryness in the eyes, in 3 (17.6%); sore throat, in 2 (11.8%); abdominal pain, in 1 (5.9%), distal polyneuropathy, in 2 (11.8%); paraesthesia, in 1 (5.9%); and chondritis of the auricles, in 1 (5.9%). Monoclonal gammopathy was detected in all patients 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), and IgAλ (n = 1). Ben-Jones protein was not detected in any of them. All patients had an increased level of ESR and CRP. Before inclusion in the study, 16 patients received GCs (94.1%) with a temporary effect that disappeared with dose reduction or cancellation. Seven patients received cDMARDs, including methotrexate (5), hydroxychloroquine (2), and cyclophosphamide (1). All patients received NSAIDs and antihistamines, as well as biologics, including the anti-B-cell drug rituximab (1), monoclonal ABs to IgE omalizumab (2, 1 without effect and 1 with partial effect), IL-1i canakinumab (n = 10, 58.8%) subcutaneously once every 8 weeks, and anakinra (n = 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 patients. The duration of taking canakinumab at the time of analysis ranged from 7 months to 8 years. Against the background of treatment with IL-1i, 10 out of 11 (90.9%) patients received a complete response in terms of the clinical manifestations of the disease and a decrease in the level of ESR and CRP within a few days. In one patient, a partial response to the administration of anakinra was detected; however, after switching to canakinumab, the effect of treatment was finally lost. One patient received IL-6i for 8 months with an incomplete effect and a positive dynamics after switching to anakinra. Thus, anakinra was initially prescribed to four patients and changed to canakinumab in two of them; canakinumab was started as the first drug in seven patients. Treatment with anakinra was continued in two patients; with canakinumab, in nine patients. In one patient, due to the persistent absence of relapses, the interval between canakinumab injections was increased to 5 months without signs of reactivation; however, subsequently, against the background of stress and relapses of the disease, the intervals were reduced to 4 months. A healthy child was born by the same patient on the background of treatment. The tolerability of therapy was satisfactory in all patients, no SAEs were noted. SchS is a rare multifactorial/non-monogenic AID that should 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-1i is a highly effective and safe option in the treatment of such patients.

[Schnitzler syndrome: A review of literature, the authors' observation, and experience with the interleukin-1 inhibitor canakinumab]. / Sindrom Shnittslera: obzor literatury, sobstvennoe nabliudenie, opyt lecheniia ingibitorom interleikina-1 kanakinumabom.

The paper reviews the publications dealing with Schnitzler syndrome, a rare autoinflammatory disease, and describes the authors' own clinical observation. It describes the first Russian experience in successfully using the interleukin-1 inhibitor canakinumab to treat this disease.

[Serum calgranulin C is a highly sensitive autoinflammation activity indicator in patients with familial periodic fevers].

AIM: To determine the possibility of using the serum proinflammatory calcium-binding protein, or calgranulin C (S100A12), to assess activity and therapeutic efficiency in patients with periodic disease (PD) and other familial periodic fevers (FPFs). SUBJECTS AND METHODS: Thirty-five patients with PD and other FPDs, which were verified by molecular genetic study, were examined. In accordance with the disease activity, the patients were divided into 2 groups. The investigators determined the concentration of S100A12 by solid-phase enzyme immunoassay and that of other acute-phase inflammatory markers (erythrocyte sedimentation rate (ERT), neutrophil counts, and fibrinogen and C-reactive protein (CRP) concentrations). RESULTS: The serum concentration of S100A12 in the stage of disease activity was 466.7 (265.22--851.7) ng/ml, which was significantly higher than in remission (244.29 (118.93--409.85) ng/ml (p=0.000002). The highest S100A12 concentrations were noted in the patients with PD; these were 758.95 (434.80--1035.95) ng/ml; the S100A12 level in the majority of PD patients even during remission remained moderately higher. An investigation of the relationship of A100A12 to genetic variants found no differences between the patients homozygous for M694V and those with other genotypes (p=0.37). Estimation of the time course of therapy-induced changes in the serum S100A12 concentration revealed its considerable reduction (р=0.0018). However, normalization of S100A12 levels was not achieved in PD. The remaining increased S100A12 concentration in these patients may be suggestive of the activity of PD despite the absence of its clinical manifestations. S100A12 as a highly sensitive marker allows more exact evaluation of the anti-inflammatory effect of therapy. The S100A12 identification of the subclinical activity of autoinflammatory diseases made all the more important since traditional inflammatory markers, such as ERT, CRP, fibrinogen, and leukocyte counts, are less sensitive for these purposes. In our study, these markers were within the reference range in remission. No differences were found in the S100A12 levels between the groups with and without amyloidosis (p=0.62). CONCLUSION: S100A12 is a highly sensitive marker for the activity of autoinflammatory diseases and the efficiency of their therapy. The serum level of S100A12 in PD may be used to diagnose the subclinical activity of inflammation, which is of importance in monitoring the risk of amyloidosis.

[Analysis of one-year mortality of radically operated patients over 70 years with nonsmall cell lung cancer].

One-year lethality was studied in 613 patients older than 70 years who underwent surgery for lung cancer for the period of 1970-2002. During the first year after surgery 166 patients died (27.1%) and besides from the generalization of the disease - 92.2%, from other causes - 7.8%. The highest rate of one-year lethality was observed after pneumonectomy (39.4%), the lowest one - after lung margins resection (16.5%). It was found that the most important factor in one-year lethality rate was N2 lymph node status. Risk of dying from the generalization of the disease during the first year sharply increased in group of patients underwent extended and combined pneumonectomy (one-year lethality of 52.6% and 57.1%, respectively), pneumonectomy with N2 (56,0%), lobectomy in peripheral cancer with metastases of N2 level (63,6%), especially when the amount of the tumor was more than 5 cm (83.3%).

[The role of gap junction communication in metastatic B16 melanoma in C57BL mice].

The study is concerned with the effects of non-specific blocking gap junction communication with oleamide as well as genesis and spreading of melanoma B16 metastases to the lung in mice C57B1. The blocking exerted no distinct influence on primary tumorigenesis but had a marked effect on metastatic spread. Oleamide treatment during tumor growth led to an increase in area covered by metastases. A correlation was established between metastatic frequency and dosage: 1 mg/kg was followed by an upsurge in frequency of secondary lung tumors while 10 mg/kg--by a drop.

[Circadian features of carcinogenesis of the large intestine induced by 1,2-dimethylhydrazine in rats]. / Tsirkadiannye osobennosti kantserogeneza tolstoi kishki, indutsirovannogo 1,2-dimetilgidrazinom u krys.

The study was concerned with comparison of carcinogenesis induced in the rat large intestine by 5 single doses of 1,2-dimethylhydrazine (DMH) 21 mg/kg injected at different circadian stages--either at 10 a.m. or 10 p.m. Evening injections were followed by significant decrease in incidence (from 91 to 75%) and size of tumor (27.2-15.5 mm2). Also, there were relatively fewer large tumors in the evening series.

[Age and symptoms of Lyme disease]. / Vozrast i techenie laimskoi bolezni.

AIM: Comparison of clinical symptoms in Lyme disease (LD) in various age groups. MATERIAL AND METHODS: 150 patients with verified LD were divided into 4 age groups: under 15 years (group 1), 16-40 years (group 2), 41-60 years (group 3), over 60 years (group 4). Antibodies to Borrelia burgdorteri were detected with indirect immunofluorescence and Western blot. RESULTS: LD clinical symptoms differed in the age groups. Patients of group 1 had more prevalent infectious syndrome with fever but they had no radiculoneuritis and polyneuritis. Patients of group 2 more frequently suffered of carditis and secondary erythema. Groups 3 and 4 were characterized by infectious syndrome, secondary erythema and aseptic meningitis, joint lesions being more frequent in group 3, nervous system lesions--in group 4. CONCLUSION: Age peculiarities of LD symptoms are very important. In particular, joint syndrome is responsible for lingering course of LD.

The course of Lyme disease in different age groups.

Lyme disease is a multisystem infection affecting all age groups. In this study an attempt was made to determine whether the patient's age influences the course of the disease. One hundred and fifty patients with diagnosed Lyme disease were included in the study. Two serological methods were used to detect antibodies to Borrelia burgdorferi and to confirm the diagnosis: an indirect immunofluorescence assay (the Russian strain Ip-21) and Western blot. The course of Lyme disease did not differ from that seen in Europe and North America. However, a few clinical differences between groups were observed. In the first age group (0-15 years) the most common manifestation was flu-like symptoms with fever. Neither radiculoneuritis nor polyneuropathy was observed in this age group. Late manifestations were rare and the outcome of the disease was benign. The course of the disease in the second group (16-40 years) was most similar to that in childhood and the also outcome was similar. Carditis and erythema multiple were significantly more common in the second group (16-40 years) than in the other age groups. No differences were found between the third (41-60 years) and fourth (> than 60 years) group in the frequency of flu-like symptoms, erythema multiple and aseptic meningitis. However, the most important clinical sign in this group was involvement of the nervous system whereas in the third group this was joint damage. This feature deserves attention because, as a rule, the presence of an articular syndrome determines the prognosis of LD.