Different blood-brain-barrier disruption profiles in multiple sclerosis, neuromyelitis optica spectrum disorders, and neuropsychiatric systemic lupus erythematosus.

AIM OF THE STUDY: To assess differences in BBB damage profiles by measuring serum levels of soluble vascular cell adhesion molecule-1 (sVCAM-1), soluble platelet endothelial cell adhesion molecule-1 (sPECAM-1), soluble intercellular adhesion molecule-1 (sICAM-1), and S100 calcium-binding protein B (S100B) in relapsing-remitting multiple sclerosis (RRMS), neuromyelitis optica spectrum disorders (NMOsd), and neuropsychiatric systemic lupus erythematosus (NPSLE) patients. CLINICAL RATIONALE FOR THE STUDY: Blood-brain-barrier (BBB) disruption is one of the key pathological processes involved in various demyelinating diseases of the central nervous system (CNS) and is associated with shedding of cell adhesion molecules and S100B into the serum compartment. Therefore, making an assessment of serum levels of the above-mentioned molecules could provide information about disease pathogenesis, severity of BBB disruption, and disease activity. MATERIAL AND METHODS: We recruited 42 RRMS, 19 NMOsd and 35 NPSLE patients. Subjects were treated with beta-interferons or glatiramer acetate (RRMS), oral steroids and/or azathioprine (NMOsd, NPSLE), other immunosuppressants (NPSLE), or antimalarials (NPSLE). The clinical condition of the patients was assessed using the Kurtzke Expanded Disability Status Scale for MS and NMOsd, and the Systemic Lupus Erythematosus Disease Activity Index for NPSLE. Serum levels of sVCAM-1, sPECAM-1, sICAM-1 and S100B were determined using enzyme-linked immunosorbent assay (ELISA). RESULTS: We found the lowest levels of sPECAM-1, sICAM-1 and S100B in sera from NMOsd patients. The highest levels of sPECAM-1 and sICAM-1 were observed in NPSLE, and in NPSLE and MS, respectively. There were no statistically significant differences in sVCAM-1 levels between the examined groups. In MS and NMOsd, there was a negative correlation between the EDSS score and the following molecules: sPECAM-1, sICAM-1 and S100B. CONCLUSIONS AND CLINICAL IMPLICATIONS: We conclude that there is a different profile of blood-brain-barrier disruption reflected by cell adhesion molecules shedding in the spectrum of autoimmune CNS disorders with disseminated white matter lesions. These molecules could become new biomarkers to be used in CNS demyelinating diseases differential diagnoses and monitoring disease activity, but further studies on larger groups of patients are necessary.

Drug survival of anakinra and canakinumab in monogenic autoinflammatory diseases: observational study from the International AIDA Registry.

OBJECTIVES: To investigate survival of IL-1 inhibitors in monogenic autoinflammatory disorders (mAID) through drug retention rate (DRR) and identify potential predictive factors of drug survival from a real-life perspective. PATIENTS AND METHODS: Multicentre retrospective study analysing patients affected by the most common mAID treated with anakinra or canakinumab. Survival curves were analysed with the Kaplan-Meier method. Statistical analysis included a Cox-proportional hazard model to detect factors responsible for drug discontinuation. RESULTS: Seventy-eight patients for a total of 102 treatment regimens were enrolled. The mean treatment duration was 29.59 months. The estimated DRR of IL-1 inhibitors at 12, 24 and 48 months of follow-up was 75.8%, 69.7% and 51.1%, respectively. Patients experiencing an adverse event had a significantly lower DRR (P=0.019). In contrast, no significant differences were observed between biologic-naïve patients and those previously treated with biologic drugs (P=0.985). Patients carrying high-penetrance mutations exhibited a significantly higher DRR compared with those with low-penetrance variants (P=0.015). Adverse events were the only variable associated with a higher hazard of treatment withdrawal [hazard ratio (HR) 2.573 (CI: 1.223, 5.411), P=0.013] on regression analysis. A significant glucorticoid-sparing effect was observed (P<0.0001). CONCLUSIONS: IL-1 inhibitors display an excellent long-term effectiveness in terms of DRR, and their survival is not influenced by the biologic line of treatment. They display a favourable safety profile, which deserves, however, a close monitoring given its impact on treatment continuation. Special attention should be paid to molecular diagnosis and mutation penetrance, as patients carrying low-penetrance variants are more likely to interrupt treatment.

Secondary immunodeficiencies with predominant antibody deficiency: multidisciplinary perspectives of Polish experts.

At present, secondary immune deficiencies have become a clinical problem, recognized in different specialties. The aim of this paper was to increase awareness and support the need for screening at-risk populations. Secondary immune deficiencies result in variety of conditions, but not all of them require immunoglobulin replacement therapy, as specific antibody response might be preserved. Moreover, the management of secondary immune deficiencies vary between countries and different medical disciplines. This literature review presents the most common causes and clinical presentation of secondary immunodeficiencies with predominant impaired antibody production. We present diagnostic guidelines for patients at-risk, with an emphasis on the role of prophylactic vaccination as a treatment and diagnostic tool. This review considers the specificity and disparities of the Polish healthcare system and ultimately, suggests that management teams should include a clinical immunologist experienced in the treatment of humoral immunodeficiencies.

Periodic fever, aphthous stomatitis, pharyngitis and cervical adenitis syndrome persisting to adulthood - an example of a diagnostic and therapeutic challenge.

Periodic fever, aphthous stomatitis, pharyngitis and cervical adenitis (PFAPA) syndrome is the most common cause of periodic fever in childhood. Reports of adult patients are sparse. In adults the clinical picture is more heterogeneous than in children, so PFAPA can be a real diagnostic challenge. Data regarding treatment efficacy and disease outcome are available mainly for children, whereas for adult patients they are limited and conflicting. Our aim is to increase the awareness about PFAPA among clinical practitioners. We present a case of PFAPA beginning in childhood and without resolution of symptoms in maturity. In our case the diagnostic delay was 15 years. We treated the patient with a prophylactic dose of colchicine. Colchicine helped to control flares and significantly improved the patient's quality of life. Periodic fever, aphthous stomatitis, pharyngitis and cervical adenitis in adults is a rare disease, but it should be included in the differential diagnosis of fever of unknown origin in adults.

Monogenic autoinflammatory diseases in adults - a challenge to rheumatologic practice at the onset of the Polish national programme of interleukin 1 inhibitor treatment.

Monogenic autoinflammatory diseases (AIDs, formerly known as hereditary periodic fever syndromes) cover a spectrum of diseases which lead to chronic or recurrent inflammation caused by activation of the innate immune system. The most common monogenic AID is familial Mediterranean fever. Monogenic autoinflammatory diseases are generally considered intracellular signalling defects. Some stereotypical knowledge may be misleading; e.g. monogenic AIDs are not exclusively found in children, family history is often negative, fever frequently is not a leading manifestation and frequency of attacks in adults is usually variable. Lack of genetic confirmation should not stop anti-inflammatory ex juvantibus therapy. The pattern of tissue injury in AIDs is basically different from that observed in autoimmunity. There is no autoaggression against organ-specific antigens, but substantial damage (amyloidosis, cachexia, premature cardiovascular disease) is secondary to long-lasting inflammation. The Polish national programme of anti-interleukin 1 treatment opens new possibilities for the treatment. However, monogenic AIDs are frequently misdiagnosed and more awareness is needed.

Determination of antibodies in everyday rheumatological practice.

Antibody determination is routinely used in everyday rheumatological practice. Its result repeatedly determines the diagnosis or exclusion of a particular disease. Antibodies are immunoglobulins, i.e. some of the most important proteins in the immune system, and have specific properties that we should know. In addition, there are a number of factors that can affect their concentration, including drugs commonly used in the treatment of rheumatic diseases. There are definite indications, when the total concentrations of individual classes of immunoglobulins should be initially determined and it should be evaluated whether the patient produces them at all or their production is impaired. In some cases, we should evaluate the levels of specific antibodies along with the total protein concentration and the γ-globulin fraction, in which the antibodies are contained. The article presents information on the most common mistakes made when performing these tests.

Biosimilar switching - current state of knowledge.

Evidence from over 10 years of clinical experience demonstrates that biosimilar medicines approved in the European Union can be used for all their registered indications as safely as their originators and with no negative impact on therapeutic efficacy. The debate on the use of biosimilars in rheumatology focuses specifically on the safety of switching between biosimilars and reference products. Studies conducted to date, including randomised double-blind and open-label extension trials, have not demonstrated any significant differences in therapeutic efficacy or safety between patients switched from one medicine to another and those who were continued on a single medicine. According to the latest recommendations for the use of biosimilars in rheumatic diseases, developed by an international task force in 2017, there is no clinical evidence that a single switch from an originator to a biosimilar medicine is associated with any significant risk for patient safety or reduction in therapeutic efficacy.

Treatment of rheumatic diseases and hepatitis B virus coinfection.

We often encounter rheumatological patients coinfected with hepatitis B in daily practice. In this paper, we will discuss the basic characteristics of the virus of hepatitis B, course of infection, the safety of rituximab, tocilizumab, abatacept treatment and therapeutic recommendations in management of patients with rheumatic diseases.

[Autoimmune connective tissue diseases and vaccination]. / Autoimmunizacyjne ukladowe choroby tkanki lacznej a szczepienia ochronne.

The idea that infectious agents can induce autoimmune diseases in genetically susceptible subjects has been a matter of discussion for years. Moreover, increased incidence of autoimmune diseases and introduction of prophylactic vaccinations from early childhood suggest that these two trends are linked. In the medical literature and even non-professional media, case reports or events temporally related to vaccination are reported. It raises the issue of vaccination safety. In everyday practice medical professionals, physicians, rheumatologists and other specialists will be asked their opinion of vaccination safety. The decision should be made according to evidence-based medicine and the current state of knowledge. The purpose of this paper is to discuss a potential mechanism which links infections, vaccinations and autoimmunity. We present an overview of published case reports, especially of systemic connective tissue diseases temporally related to vaccination and results from case-nested studies. As yet, no conclusive evidence supports a causal relationship between vaccination and autoimmune diseases. It has to be determined whether the performed studies are sufficiently sensitive to detect the link. The debate is ongoing, and new data may be required to explain the pathogenesis of autoimmunity. We would like to underscore the need for prophylactic vaccination in patients with autoimmune rheumatic diseases and to break down the myth that the vaccines are contraindicated in this target group.

[The Polish Task Force position statement on safety of biologic treatment with monoclonal antibodies and soluble receptors]. / Stanowisko Polskiej Grupy Ekspertów dotyczace bezpieczenstwa leczenia przeciwcialami monoklonalnymi i bialkami fuzyjnymi.

UNLABELLED: The introduction of biologic therapies for treatment in many fields of medicine such as rheumatology oncology, dermatology, hematology and allergology, became one of the most important achievements of the modem medicine. The first biological therapeutics have already reached patent expiration date and corresponding biosimilars were approved by EMA (European Medicine Agency) and FDA (Food and Drug Administration). Many more biosimilar products are currently under review for marketing authorization around the world. The approval of products similar, but not identical to already known innovative biologics, due to complexity of structure and manufacturing technology, stirs a lot of discussions regarding safety concerns related to differences in posttranslational processing and in immunogenicity between reference and biosimilar products, and relevance of these differences to the clinical practice. Critical issues involve extrapolation to different clinical indication, automatic substitution and switching. Despite EMA recommendation and advocacy for biosimilars, it is beyond this regulatory authority to establish definitive regulation for each EU member, which it is expected to be country related. The aim of the study was an attempt to define the stance regarding particular aspects of biological treatment conducted in Poland is undertaken. METHODS: The Task Force of 13 experts involved in various aspects of biologic therapies in Poland was established. A modified Delphi voting was performed to achieve consensus regarding the most important aspects of biologic treatment in Poland, with particular concern of biosimilars. RESULTS: Ten final statements were discussed and voted upon. The statements cover general aspects of biosimilars including expected cost-benefit ratios, extrapolation of clinical indications, interchange switching, patient information and requirement of patient consent. The state of post marketing pharmacovigilance of biologics (innovative ones as well as biosimilars) was also discussed. CONCLUSIONS: The Task Force agreed that introduction of biosimilars is an important achievement in the biological therapies, with potential for reduction of treatment cost and increased treatment availability. Experts also agree that the safety of biological treatment should be monitored more carefully in Poland. Other discussed issues sparked more questions. There is no consensus among experts as to the automatic interchangeability of biosimilar and their innovative biopharmaceuticals. However, the switching might be acceptable in clinical practice on the case by case basis. There is an unmet need in Poland to create registry collecting data sufficient for assessment of safety and efficacy of both biosimilars and reference products in accordance with the experience and principles introduced in the European countries.

Case report: VEXAS as an example of autoinflammatory syndrome in pulmonology clinical practice.

Lung involvement is not widely recognized as a complication of auto-inflammatory diseases. We present a broad approach to diagnose a severe form of autoinflammatory syndrome in an adult male patient. A 63-year-old Caucasian male presented with recurrent episodes of high fever, interstitial lung infiltration, and pleural effusion. Laboratory tests performed during the flares revealed lymphopenia and increased levels of C-reactive protein and ferritin. Broad diagnostic research on infections, connective tissue diseases, and malignancies yielded negative results. The patient's symptoms promptly resolved upon the administration of glucocorticoids; however, they reappeared when the prednisone dose was reduced. All attempts to administer immunomodulatory and immunosuppressive medications were ineffective. During follow-up, autoinflammatory syndrome was suspected; however, no pathological variants of monogenic autoinflammatory diseases were identified by genome-exome sequencing. The patient did not respond to interleukin 1 blockade with anakinra. He died due to multi-organ failure, and his condition remained unresolved until the first reported description of vacuole, E1 enzyme, X-linked, autoinflammatory, and somatic syndrome (VEXAS). We describe the diagnostic traps and reasoning process involved in establishing that the patient's symptoms were autoinflammatory in nature based on clinical symptoms, in addition to the proof of concept gained from genetic reevaluation and identification of pathogenic variants in the UBA1 gene. The aim of this review is to increase the awareness of VEXAS among pulmonologists. Genetic screening for UBA1 should be considered in patients with recurrent pneumonitis of unknown origin with elevated inflammatory markers and signs of cytopenia, especially if they require chronic steroids to control the disease. Respiratory manifestations are part of VEXAS; these may be dominant in the course of the disease and severe at presentation.

Anxiety in Polish adult patients with inborn errors of immunity: a cross-sectional study.

Background: Patients with inborn errors of immunity (IEI) experience recurrent infections, autoimmunity, and malignancies. Owing to repeated medical procedures, the need for constant treatment and surveillance, and the unpredictable course of the disease, patients with IEI are prone to develop mental health disorders, including anxiety. In this study, we aimed to assess the prevalence and level of anxiety symptoms in adult Polish patients with IEI and explore the determinants of anxiety in this group of patients. Methods: Data from 105 Polish patients with IEI were collected via the hospital anxiety and depression scale (HADS), brief illness perception questionnaire (B-IPQ), illness cognition questionnaire (ICQ), Pittsburgh sleep quality index (PSQI), and a questionnaire on general health and demographic data. For statistical analyses of data, the normality of distribution of quantitative data was assessed, and internal consistency of tests was investigated using Cronbach's alpha coefficient; moreover, we performed the analysis of correlations and between-group differences, and path analysis to explore causal relationships. Significance was considered at p < 0.050. Results: Thirty-eight (36.2%) patients had anxiety symptoms (HADS-A ≥ 8); 14 (13.3%) patients had severe anxiety (score ≥ 11), and 24 (22.9%) had moderate anxiety (score of 8-10). Patients with poor sleep quality, higher pain frequency, younger age, and no fixed income had higher anxiety scores than others. Emotional and cognitive representations of illness were positively correlated with anxiety levels. Intense anxiety was related to more negative illness perception, higher helplessness, lower illness acceptance, and lower perceived benefits. Discussion: Anxiety is common in patients with IEI. However, results indicate that it is not related to a more severe course of IEI or several comorbidities, whereas, pain frequency and poor sleep quality were identified to be important clinical factors for anxiety. Because anxiety was related to negative illness perception, psychological therapy may apply to this group of patients.

Trial of Cardiovascular Risk Factor Assessment and Transthoracic Echocardiography Results in Patients with Primary Antibody Deficiency.

The life expectancy and the risk of developing cardiovascular diseases in patients with inborn errors of immunity are systematically increasing. The aim of the study was to assess cardiovascular risk factors and to evaluate the heart in echocardiography in patients with primary antibody deficiency (PAD). Cardiac echography and selected cardiovascular risk factors, including body mass index, sedentary lifestyle, nicotine, glucose, C-reactive protein, lipid profile, uric acid level, certain chronic diseases, and glucocorticoid use, were analyzed in 94 patients >18 years of age with PAD. Of the patients,25.5% had a cardiovascular disease (mostly hypertension, 18%), 10.5% smoked, 17% were overweight, 14% were obese, and 15% were underweight. Abnormal blood pressure was found in 6.5% of the patients. Lipid metabolism disorders were found in 72.5% of in the studied cohort, increased total cholesterol (45.5%), non-high-density lipoprotein (HDL) (51%), low-density lipoprotein (LDL) (47%), and triglycerides (32%) were observed. Furthermore, 28.5% had a decrease in HDL and 9.5% had a history of hyperuricemia. The average number of risk factors was 5 ± 3 for the entire population and 4 ± 2 for those under 40 years of age. Elevated uric acid levels were found de novo in 4% of participants. In particular, 74.5% of the patients had never undergone an echocardiogram with a successful completion rate of 87% among those tested. Among them, 30% showed parameters within normal limits, primarily regurgitation (92.5%). New pathologies were identified in 28% of patients. Prevention in patients with PAD, aimed at reducing cardiovascular risk, should be a priority.

Orbital/ocular inflammatory involvement in VEXAS syndrome: Data from the international AIDA network VEXAS registry.

VEXAS syndrome is a recently described monogenic autoinflammatory disease capable of manifesting itself with a wide array of organs and tissues involvement. Orbital/ocular inflammatory manifestations are frequently described in VEXAS patients. The objective of this study is to further describe orbital/ocular conditions in VEXAS syndrome while investigating potential associations with other disease manifestations. In the present study, twenty-seven out of 59 (45.8 %) VEXAS patients showed an inflammatory orbital/ocular involvement during their clinical history. The most frequent orbital/ocular affections were represented by periorbital edema in 8 (13.6 %) cases, episcleritis in 5 (8.5 %) patients, scleritis in 5 (8.5 %) cases, uveitis in 4 (6.8 %) cases, conjunctivitis in 4 (6.8 %) cases, blepharitis in 3 (5.1 %) cases, orbital myositis in 2 (3.4 %) cases. A diagnosis of systemic immune-mediated disease was observed in 15 (55.6 %) cases, with relapsing polychondritis diagnosed in 12 patients. A significant association was observed between relapsing polychondritis and orbital/ocular involvement in VEXAS syndrome (Relative Risk: 2.37, 95 % C.I. 1.03-5.46, p = 0.048). Six deaths were observed in the whole cohort of patients after a median disease duration of 1.2 (IQR=5.35) years, 5 (83.3 %) of which showed orbital/ocular inflammatory involvement. In conclusion, this study confirms that orbital/ocular inflammatory involvement is a common finding in VEXAS patients, especially when relapsing polychondritis is diagnosed. This makes ophthalmologists a key figure in the diagnostic process of VEXAS syndrome. The high frequency of deaths observed in this study seems to suggest that patients with orbital/ocular involvement may require increased attention and more careful follow-up.

Dual-energy computed tomography as a lower radiation dose alternative to perfusion computed tomography in tumor viability assessment.

To present the utility of dual-energy computed tomography (DECT) in the assessment of angiogenesis of focal lesions as an example of a solitary pulmonary nodule (SPN). This prospective study comprised 28 patients with SPN who underwent DECT and perfusion computed tomography (CTP), according to a proprietary protocol. Two radiologists independently analyzed four perfusion parameters, namely blood flow (BF), blood volume (BV), the time to maximum of the tissue residue function (Tmax), permeability surface area product (PS) from CTP, in addition to the iodine concentration (IC) and normalized iodine concentration (NIC) of the SPN from DECT. We used the Pearson R correlation and interclass correlation coefficients (ICCs). Statistical significance was assumed at p < 0.05. The mean tumor size was 23.5 ± 6.5 mm. We observed good correlations between IC and BF (r = 0.78, p < 0.000) and NIC and BF (r = 0.71, p < 0.000) as well as between IC and BV (r = 0.73, p < 0.000) and NIC and BV (r = 0.73, p < 0.000) and poor correlation between IC and PS (r = 0.38, p = 0.044).There was no correlation between NIC and PS (r = 0.35, p = 0.064), IC content and Tmax (r = - 0.28, p = 0.147) and NIC and Tmax (r = - 0.21, p = 0.266). Inter-reader agreement on quantitative parameters at CTP (ICCPS = 0.97, ICCTmax = 0.96, ICCBV = 0.98, and ICCBF = 0.99) and DECT (ICCIC = 0.98) were excellent. The radiation dose was significantly lower in DECT than that in CTP (4.84 mSv vs. 9.07 mSv, respectively). DECT is useful for the functional assessment of oncological lesions with less exposure to radiation compared to perfusion computed tomography.

Increased Access to Immunoglobulin Replacement Therapy for Patients with Primary Immunodeficiency in Poland Based on Clinical Usage Data of Immunoglobulin G over a 5-Year Period.

Owing to the rising popularity and demand for immunoglobulins (IgG), obtaining supplies and rationalizing IgG use have become challenging. Herein, IgG consumption in Poland was analyzed through total IgG use and number of patients reported to the National Health Fund between 1 January 2016 and 31 December 2020. Total IgG used within 5 years increased by 27.48%, IgG use/1000 inhabitants/year was 23.13 g (2016) and 29.61 g (2020). In 2020, 35.5 % of IgG used was for neurological conditions, 25% for primary immunodeficiencies (PID), and 39.3% for all other indications. Within 5 years, 1,121,168.75 g IgG was used in PID; the use increased by 72%, from 783 in 2016 to 1153 patients in 2020. The proportion of patients who received subcutaneous immunoglobulin (SCIG) replacement therapy (IgRT) increased to 78% (2020). Within 5 years, 1,783,534.81 g IgG was used in neurological drug programs (+42.44%) and 2,327,513.88 g (+1.25%) outside neurological indications and outside PID. The annual IgG amount decreased in adult anesthesiology and intensive care (-46%), internal medicine (-55%), pneumonology (-50%), pediatric clinical immunology (-50%), and gynecology and obstetrics (-48%) and increased in dermatology (+178%), rheumatology (+103%), and clinical transplantation (+82%). IgG use significantly increased in Poland, mostly owing to PID. Subcutaneous IgG administration is currently the most common mode of IgRT in PID patients. An increase in SCIG administration may be expected for other indications. Implementing evidence-based clinical guidelines is key to prioritizing and rationalizing IgG use for immunomodulatory indications and secondary immune deficiencies.

Analysis of Leukocyte Subpopulations by Flow Cytometry during Hospitalization Depending on the Severity of COVID-19 Course.

The mechanisms underlying the immune response to coronavirus disease 2019 (COVID-19) and the recovery process have not been fully elucidated. The aim of the study was to analyze leukocyte subpopulations in patients at significant time points (at diagnosis, and 3 and 6 months after infection) selected according to the analysis of changes in the lungs by the CT classification system, considering the severity of the disease. The study groups consisted of severe and non-severe COVID-19 patients. There was a significant decrease in CD8+ T cells, NK and eosinophils, with an increasing percentage of neutrophils during hospitalization. We noticed lower levels of CD4 and CD8 T lymphocytes, eosinophils, basophils, and CD16+ monocytes and elevated neutrophil levels in severe patients relative to non-severe patients. Three months after infection, we observed higher levels of basophils, and after 6 months, higher CD4/CD8 ratios and T cell levels in the severe compared to non-severe group. Non-severe patients showed significant changes in the leukocyte populations studied at time of hospitalization and both within 3 months and 6 months of onset. The CT CSS classification with parameters of the flow cytometry method used for COVID-19 patients determined changes that proved useful in the initial evaluation of patients.

Points to Consider in Health Assessment of Adult Patients with Primary Antibody Deficiencies.

An improved recognition of inborn errors of immunity (IEI) is associated with an increase in life expectancy and a higher incidence of complications and related conditions. The aim of the study was to analyze factors enabling the primary prevention: BMI, smoking and selected laboratory tests (morphology with smear, creatinine, eGFR, total protein, albumin, ferritin, folic acid, vitamin B12, vitamin D3) included in the protocols of standard of care for adult patients with primary antibody deficiencies (PADs). The study included 94 participants ≥ 18 years old, diagnosed with PADs. Overweight was found in 17%, obesity in 14% and underweight in 15% of patients; 11.5% of patients smoked. Leukopenia was diagnosed in 16%, neutropenia in 8.5%, lymphopenia in 22.5% and thrombocytopenia in 14% of patients. A decreased concentration of hemoglobin was found in 32%, total protein in 19%, albumin in 17%, vitamin D3 in 52%, vitamin B12 in 6.5%, folic acid in 34% and ferritin in 26% of patients. Creatinine concentrations were elevated in 16% of patients, while in 20%, eGFR was reduced. Only a holistic assessment of comorbidities and complications of deficiency, as well as regular follow-up and lifestyle changes, can yield the best results in the long-term care of patients.

Axial spondyloarthritis in patients with recurrent fever attacks: data from the AIDA network registry for undifferentiated autoInflammatory diseases (USAIDs).

Beckground: Despite the recent advances in the field of autoinflammatory diseases, most patients with recurrent fever episodes do not have any defined diagnosis. The present study aims at describing a cohort of patients suffering from apparently unexplained recurrent fever, in whom non-radiographic axial spondylarthritis (SpA) represented the unique diagnosis identified after a complete clinical and radiologic assessment. Materials and methods: Patients' data were obtained from the international registry on Undifferentiated Systemic AutoInflammatory Diseases (USAIDs) developed by the AutoInflammatory Disease Alliance (AIDA) network. Results: A total of 54 patients with recurrent fever episodes were also affected by non-radiographic axial SpA according to the international classification criteria. SpA was diagnosed after the start of fever episodes in all cases; the mean age at the diagnosis of axial SpA was 39.9 ± 14.8 years with a diagnostic delay of 9.3 years. The highest body temperature reached during flares was 42°C, with a mean temperature of 38.8 ± 1.1°C. The most frequent manifestations associated to fever were: arthralgia in 33 (61.1%) cases, myalgia in 24 (44.4%) cases, arthritis in 22 (40.7%) cases, headache in 15 (27.8%) cases, diarrhea in 14 (25.9%) cases, abdominal pain in 13 (24.1%) cases, and skin rash in 12 (22.1%) cases. Twenty-four (44.4%) patients have taken daily or on-demand non-steroidal anti-inflammatory drugs (NSAIDs) and 31 (57.4%) patients have been treated with daily or on demand oral glucocorticoids. Colchicine was used in 28 (51.8%) patients, while other conventional disease modifying anti-rheumatic drugs (cDMARDs) were employed in 28 (51.8%) patients. Forty (74.1%) patients underwent anti-tumor necrosis factor (TNF) agents and 11 (20.4%) were treated with interleukin (IL)-1 inhibitors. The response to TNF inhibitors on recurrent fever episodes appeared more effective than that observed with anti-IL-1 agents; colchicine and other cDMARDs were more useful when combined with biotechnological agents. Conclusion: Signs and symptoms referring to axial SpA should be inquired in patients with apparently unexplained recurrent fever episodes. The specific treatment for axial SpA may lead to a remarkable improvement in the severity and/or frequency of fever episodes in patients with unexplained fevers and concomitant axial SpA.