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.

[AL amyloidosis mimicking IgG4-related disease: case report].

The article describes a unique clinical case of AL amyloidosis mimicking IgG4-related disease. Plasma cell dyscrasias can mimic clinical and laboratory manifestations of rheumatic diseases, which can lead to a delay in diagnosis and inappropriate therapy.

The efficacy of rituximab in the therapy of neuromyelitis optica in a patient with Sjogren's syndrome: case-report and literature review.

This case is the first description of the successful anti-B-cell therapy with rituximab in a patient with Sjogren's syndrome and neuromyelitis optica spectrum disorder in Russia. This article contains the literature data on clinical manifestations and methods of the diagnosis of neuromyelitis optica spectrum disorder. Furthermore, contemporary view on the pathogenesis of the combination of this disease with Sjogren's syndrome are presented here.

[Long-term follow-up of patients with refractory systemic lupus erythematosus during rituximab treatment].

AIM: To evaluate the impact of anti-B-cell therapy on the clinical and immunological parameters of systemic lupus erythematosus (SLE) activity, on the time course of changes in these parameters during long-term follow-up, and on the tolerability of repeated rituximab (RTM) therapy cycles. SUBJECTS AND METHODS: RTM was given to 97 patients with high activity of SLE refractory to treatment with glucocorticosteroids (GCS) and cytostatics. The follow-up lasted 18 (12-36) months. The most common clinical manifestations of SLE were lupus nephritis (LN) (62%) and skin (33%) and nervous system (22.7%) involvements. Clinical SLE activity was assessed applying the SLE disease activity index 2000 (SLEDAI2K); therapeutic effectiveness was evaluated using indicators, such as partial response (PR), complete response (CR) and exacerbation. The exacerbation was classified as moderate and severe using the Selena-Sledai Flare index (SFI). RESULTS: Depletion was identified in 78% of the patients with SLE immediately after RTM therapy. During 3.5 years of follow-up, the effect of RTM was seen in 82% of the patients after repeated RMT therapy cycles (CR 56% and PR 28%). Exacerbations were observed in a total of 24 (24.7%) patients; the exacerbation lasted 12 (12-24) months after RTM therapy: of them 17.5% with LN and 7.2% with extrahepatic manifestations of SLE (exacerbations occurred 12 (12-24) and 18 (6-48) months after RMT therapy). In 24 exacerbated patients, B cells recovered at 6 (3-12) months. A year after RMT therapy, a group of 35 patients who were observed to have complete B cell depletion achieved CR statistically significantly more frequently than a group of 20 patients who had B-cell recovery (65.7 and 30% respectively, p = 0.03). CR was observed significantly more often in patients after repeated RTM therapy cycles than those who had received only one RTM therapy cycle (p = 0.02). The long-term follow-up showed a reduction in SLEDAI2K, normalization of laboratory values, and a decrease in the daily dose of GCS. Most patients tolerated well both the first and repeated RTM therapy cycles. CONCLUSION: According to the results of the long-term follow-up, RTM therapy is a highly effective treatment option for SLE patients in whom the previous standard therapy with GCS and cytostatics was previously ineffective. The 3.5-year follow-up showed a good tolerability of RTM and revealed no increase in the risk of infectious complications or adverse reactions.

[Anti-C1q antibodies in patients with systemic lupus erythematosus treated by rituximab].

AIM: To determine the time course of changes in the blood levels of antibodies (Ab) to complement component C1q (a-C1q) in patients with systemic lupus erythematosus (SLE) during rituximab (RTM) therapy and the association with organ injuries in SLE. SUBJECTS AND METHODS: The study involved 41 patients (3 men and 38 women; their median age was 27.5 (range 22-36) years) with definite SLE. Their blood a-C1q levels were determined by enzyme immunoassay. The levels and detection rates of a-C1q were estimated in relation to organ injuries, the time course of RTM therapy-induced changes in a-C1q levels were determined. High-positive (> 30 U/ml), low-positive (10-30 U/ml), and negative (< or = 10 U/ml) a-C1q levels were found. RESULTS: A-C1q was detected in 19 (46.3%) patients with different clinical manifestations of SLE. The patients with renal diseases had high-positive levels of a-C1q statistically significantly more frequently than those without renal involvement (p = 0.04). Low-positive and negative a-C1q levels were found in 15 of 16 without nephritis. There was a statistically significant positive correlation of the concentration of a-C1q with Ab to double-stranded DNA (a-dsDNA), Ab to nucleosomes, the SLE Disease Activity Index 2000 (SLEDAI-2K), erythrocyturia, hematuria and a negative correlation between a-C1q and complement components C3 and C4. Just after one month of RTM therapy, the patients with nephritis were observed to have a statistically significant decrease in the levels of a-C1q (p = 0.002), which persisted 1 year after the treatment (p = 0.006). Nineteen patients with the higher baseline concentrations of a-C1q after RTM treatment showed a statistically significant decrease in the levels of a-C1q at 1-, 3-, 6-, and 12-month follow-up (p = 0.016, 0.02, 0.035, and 0.04, respectively) which was accompanied by the decreased SLEDAI-2K (p < 0.00004 at 1-, 3-, 6-, and 12-month follow-up). CONCLUSION: The high levels of a-C1q were found statistically significantly more often in the patients with lupus nephritis than in those with SLE without renal involvement. The level of a-C1q statistically significantly reduced after RTM therapy and remained within the normal range during a year.