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Background: Acute Kidney Injury (AKI) complicates a substantial part of patients with COVID-19. Direct viral penetration of renal cells through the Angiotensin Converting Enzyme 2 receptor, and indirect damage by the aberrant inflammatory response characteristic of COVID-19 are likely mechanisms. Nevertheless, other common respiratory viruses such as Influenza and Respiratory Syncytial Virus (RSV) are also associated with AKI. Methods: We retrospectively compared the incidence, risk factors and outcomes of AKI among patients who were admitted to a tertiary hospital because of infection with COVID-19, influenza (A + B) or RSV. Results: We collected data of 2593 patients hospitalized with COVID-19, 2041 patients with influenza and 429 with RSV. Patients affected by RSV were older, had more comorbidities and presented with higher rates of AKI at admission and within 7 days (11.7% vs. 13.3% vs. 18% for COVID-19, influenza and RSV, respectively p = 0.001). Nevertheless, patients hospitalized with COVID-19 had higher mortality (18% with COVID-19 vs. 8.6% and 13.5% for influenza and RSV, respectively P < 0.001) and higher need of mechanical ventilation (12.4% vs. 6.5% vs.8.2% for COVID-19, influenza and RSV, respectively, P = 0.002). High ferritin levels and low oxygen saturation were independent risk factors for severe AKI only in the COVID-19 group. AKI in the first 48 h of admission and in the first 7 days of hospitalization were strong independent risk factors for adverse outcome in all groups. Conclusion: Despite many reports of direct kidney injury by SARS-COV-2, AKI was less in patients with COVID-19 compared to influenza and RSV patients. AKI was a prognostic marker for adverse outcome across all viruses. Graphical abstract:

To study the prevalence of fibromyalgia (FM) in the general population according to a 2016 modification of the American College of Rheumatology criteria (FM 2016) and the Analgesic, Anesthetic, and Addiction Clinical Trial Translations Innovations Opportunities and Networks–American Pain Society pain taxonomy criteria (AAPT), and to compare diagnostic and clinical variables between the criteria sets. We studied 2,531 randomly selected subjects from the German general population in 2019. Pain regions from the Michigan Body Map were fitted to the FM 2016 and the AAPT criteria, and criteria symptom items were derived from validated questionnaires assessing somatic and psychological symptom burden and disability. We determined FM criteria prevalence and criteria‐related scales including widespread and multisite pain (MSP) and symptom scales, and measured symptom burden and disability. According to the FM 2016 criteria, the prevalence of FM was 3.4% (n = 75 subjects; 95% confidence interval [95% CI] 2.7, 4.3) compared with 5.7% (n = 130 subjects; 95% CI 4.8, 6.8) for the AAPT criteria; κ = 0.65. Compared with AAPT‐positive subjects, FM 2016–positive subjects had higher MSP, Widespread Pain Index score, Polysymptomatic Distress Scale scores, Symptom Severity Scores, and psychological symptom burden. Physician‐diagnosed FM was reported by 1.1% of the subjects. Of these, 44.0% met the FM 2016 criteria, and 47.5% met the AAPT criteria. The prevalence of FM in the German general population is 73% greater using the AAPT criteria than the FM 2016 criteria. The AAPT criteria select individuals with less symptom severity and fewer pain sites. The FM 2016 criteria, but not the AAPT criteria, provide a general severity measure for FM.

Objective.To investigate the relation of physical (non-psychological) comorbidity and multimorbidity to quantitative measures of fibromyalgia (FM) and musculoskeletal pain.Methods.We studied 12,215 patients in a research databank with quantitative measures of FM-related variables (FMV) that included binary determinations of FM and widespread pain (WSP), and constituent variables of FM diagnosis that included the WSP index (WPI), the symptom severity score (SSS), and the polysymptomatic distress scale (PSD). We assessed self-reported comorbid conditions and covariates that included age, sex, body mass index, hypertension, smoking history, and total household income. We used nearest-neighbor matching and regression adjustment treatment effects models to measure the effect of comorbidities on FMV.Results.We found a positive association between FMV and the probability of having each comorbid condition. Patients with ≥ 1 comorbidities had PSD, WPI, and SSS increases of 3.0 (95% CI 2.7–3.3), 1.8 (95% CI 1.6–2.0), and 1.2 (95% CI 1.1–1.3) units, respectively, and an increase in FM prevalence from 20.4% to 32.6%. As the number of comorbid conditions present increased from 1 to 4 or more, PSD, WPI, SSS, and FM percent increased stepwise. For patients with ≥ 4 conditions, the predicted prevalence of FM was 55.2%.Conclusion.FM and FMV are associated with an increase in the number of comorbidities, and the association can be measured quantitatively. However, the association of WSP and FM may be an effect of definitions of WSP and FM, because comorbidity increases are also present with subsyndromal levels of both conditions.

To evaluate the prevalence of sacroiliitis, the radiographic hallmark of inflammatory spondyloarthropathy, among patients diagnosed with fibromyalgia syndrome (FMS), using the current Assessment of SpondyloArthritis International Society (ASAS) criteria and magnetic resonance imaging. Patients experiencing FMS (American College of Rheumatology 1990 criteria) were interviewed regarding the presence of spondyloarthritis (SpA) features and underwent HLA–B27 testing, C‐reactive protein (CRP) level measurement, and magnetic resonance imaging examinations of the sacroiliac joints. FMS severity was assessed by the Fibromyalgia Impact Questionnaire and the Short Form 36 health survey. SpA severity was assessed by the Bath Ankylosing Spondylitis Disease Activity Index. Sacroiliitis was demonstrated among 8 patients (8.1%) and ASAS criteria for diagnosis of axial SpA were met in 10 patients (10.2%). Imaging changes suggestive of inflammatory involvement (e.g., erosions and subchondral sclerosis) were demonstrated in 15 patients (17%) and 22 patients (25%), respectively. The diagnosis of axial SpA was positively correlated with increased CRP level and with physical role limitation at recruitment. Imaging changes suggestive of axial SpA were common among patients with a diagnosis of FMS. These findings suggest that FMS may mask an underlying axial SpA, a diagnosis with important therapeutic implications. Physicians involved in the management of FMS should remain vigilant to the possibility of underlying inflammatory disorders and actively search for such comorbidities.

Objective.In 2016, a revised version of the 2010 American College of Rheumatology fibromyalgia (FM) criteria and the 2011 self-report (survey) FM criteria were published. The 2016 criteria preserved the distinction between physician and patient criteria, but made the individual criteria items identical, added a “generalized pain” criterion, and changed ascertainment and scoring methods, among other changes. In this study, we evaluated diagnostic differences relating to 2016 changes.Methods.We used the National Data Bank for Rheumatic Diseases and evaluated 16,987 participants with painful rheumatic disorders using the 2011 and 2016 methodologies.Results.There were 4731 patients (27.9%) who satisfied the 2011 criteria and 4077 (24.0%) the 2016 revision. This resulted in agreement in 96.2% of cases and disagreement in 3.9%. All disagreements occurred in the 4731 2011-positive cases who failed to meet the 2016 criteria. This result came about because 654 (13.8%) of the 2011-positive cases failed to meet the new generalized pain requirement. When using the approximate polysymptomatic distress diagnostic method, diagnostic misclassification ranged between 7% and 13%.Conclusion.The 2016 FM criteria further refined and increased the usefulness of symptom-based diagnosis of FM by excluding patients with regional pain syndromes. However, these changes, useful as they are, underscore the social construction of symptom-based diagnosis and the inherent limitations in reliability and validity associated with FM criteria.

Treating chronic pain is a complex challenge. While textbooks and medical education classically categorize pain as originating from peripheral (nociceptive), neuropathic, or centralized origins, in real life each and every patient may present a combination of various pain sources, types, and mechanisms. Moreover, individual patients may evolve and develop differing types of pain throughout their clinical follow-up, further emphasizing the necessity to maintain clinical diligence during the evaluation and follow-up of these patients. Rational treatment of patients suffering from chronic pain must attempt at deconstructing complex pain cases, identifying variegate pain generators, and targeting them with appropriate interventions, while incorporating both pharmacological and non-pharmacological strategies, rather than focusing on the total pain level, which represents an integral of all pain types.

Fibromyalgia syndrome (FMS), a condition characterized by chronic widespread pain and tenderness, is a complex condition considered to represent a paradigm of centralized pain. FMS has demonstrated a clear familial aggregation, and hence it is considered to have a genetic background. Multiple candidate-gene studies have been conducted in this field, focusing on target genes that play a role in the transmission and processing of pain. While many of these have focused in the past on markers related to neurotransmitter systems such as catecholamines (catechol-O-methyltransferase (COMT)) and serotonin, novel target genes have recently emerged. In addition, genome-wide sequencing scanning (genome-wide association study (GWAS)) is increasingly being harnessed for the study of chronic pain, including FMS. Micro RNAs are another novel field of research related to posttranscriptional inhibition of gene expression, which are currently regarding the pathogenesis of FMS.

Objective.To describe the Israeli experience of treating adult-onset Still’s disease (AOSD) with tocilizumab (TCZ).Methods.Israeli rheumatologists who treated AOSD with TCZ filled in questionnaires on symptoms, number of tender and swollen joints, erythrocyte sedimentation rate (ESR), C-reactive protein (CRP), and dosage of prednisone at initial TCZ administration, after 6 months, and at the end of followup.Results.Nine male and 6 female patients, aged 33 ± 12 years, mean disease duration 9 years (range: 1–25) were identified. They had used a mean of 3.6 disease-modifying drugs, including 10 patients with tumor necrosis factor blockers. Intravenous TCZ 8 mg/kg was administered every 4 weeks (12 patients) or every 2 weeks (3 patients). All patients completed at least 6 months of treatment. The mean followup period was 15.7 ± 9 months. At the onset of therapy, despite the use of prednisone (27.6 ± 26.3 mg/d), all patients reported joint pain. Fever was reported in 9 patients, rash in 7, pleuritis in 3, and hepatitis in 2 before TCZ use, with mean ESR and CRP levels of 60 ± 28 mm/h and 11.6 ± 15 mg/dl, respectively. After 6 months of treatment and at the end of followup, the number of tender and swollen joints, the ESR and CRP levels, and the prednisone dosage decreased significantly. Only 2 patients still complained of mild arthralgias, and none reported systemic symptoms at the end of followup.Conclusion.TCZ 8 mg/kg was extremely efficacious in treating adult patients with refractory Still’s disease. Both TCZ and interleukin 1 blockade should be considered in the treatment algorithm of AOSD. Randomized controlled studies are needed to validate these findings.

Background Fibromyalgia syndrome (FMS), the prototypical central pain augmentation syndrome, is characterized by widespread pain and tenderness. Although patients referred to tertiary care pain clinics are recognized as suffering from chronic pain, they are generally considered to have pain attributable to discrete peripheral, nociceptive, or neuropathic etiology. The purpose of the current study was to assess the prevalence of FMS among consecutive patients referred to a tertiary pain clinic and to evaluate the contribution of central pain to the clinical impact upon such patients.Methods Eighty-five consecutive patients (38 were male, and 47 were female) attending a pain clinic were assessed for the presence of FMS. The presence of FMS was determined according to the 1990 American College of Rheumatology (ACR) classification criteria. Quality of life and physical functioning were assessed, utilizing a structured questionnaire.Results The ACR criteria for the classification of FMS were fulfilled by 41.2% of patients. Patients fulfilling FMS criteria ranked significantly lower on all domains of the SF-36, including general health, physical functioning, role limitation due to physical and emotional problems, vitality, social functioning, bodily pain, and mental health. Composite physical and mental health scores were significantly lower among patients fulfilling ACR FMS criteria. Patients fulfilling the ACR criteria for FMS felt significantly more tenderness, based on the mean number of tender points and the mean tenderness threshold, when compared with patients not fulfilling the ACR FMS criteria.Conclusions A significant proportion of patients referred to a tertiary pain clinic were found to fulfill the ACR criteria for classification of FMS and thus exhibit an important element of central pain. Central pain augmentation should be actively searched for and therapeutically addressed in the evaluation and management of all patients with chronic pain.

Importance of the field:Fibromyalgia syndrome (FMS) is currently perceived by rheumatologists and pain physicians alike as representing the classic condition of central sensitization. This term has come to denote a condition in which chronic, widespread pain is attributed mainly to an increase in the processing and handling of pain by the CNS. Thus, effective treatment of the pain of FMS must be directed at the function of the CNS. Over recent years, the pharmacological industry has focused increasing attention on this syndrome, leading to the recent approval of three first medications specifically indicated in the treatment of FMS (i.e., pregabalin, duloxetine and milnacipran). Nonetheless, treatment of FMS remains challenging and in many cases incompletely successful. Issues with drug compliance and side effects, as well as limitations of intrinsic effectiveness, hamper the outcome in many cases. Thus, FMS continues to pose a significantly unmet medical need.Areas covered in this review:In the current review, we attempt to update readers on novel developments in the FMS over the last 2 years. We include a discussion of the various pharmacological classes of medications which appear to be of promising potential in this area, including sodium oxybate, dopamine agonists, naltrexone, novel anticonvulsive medications, synthetic cannabinoids, NMDA antagonists and others.What the reader will gain:Readers of this review will gain a glimpse into upcoming pharmacological directions in the management of FMS as well as attain an understanding of the mechanisms and pathophysiological pathways which are currently considered targets for drug development in FMS.Take home message:Following the introduction of three medications specifically indicated in the management of FMS over the last 4 years, additional research is actively leading towards the introduction of new drugs aimed at improving symptoms related to pain and sleep in FMS. Physicians involved in the treatment of FMS patients are required to keep up-to-date on these promising avenues of progress and to be ready to incorporate them into clinical use.

Background: Fibromyalgia syndrome (FMS) is a disorder characterized by widespread pain, tenderness, and fatigue. High prevalence marks the syndrome which is considered to reflect altered central pain processing. Fibromyalgia syndrome runs a chronic, non-progressive course, extracting high price owing to impaired quality of life, restricted vocational capacity, and increased health care utilization. Objective: To review current and emerging trends in the treatment of FMS. Methods: A rigorous search of published literature, abstract presentations, and industry provided data was performed. Results/conclusion: The recent FDA approval of pregabalin as a first specific medication for FMS may herald a new era for the development of medications with higher specificity and efficacy for this hitherto frustrating condition.

Fibromyalgia is characterized by widespread pain and tenderness, and has a significant familial component. The etiology of fibromyalgia remains unclear, but genetic factors seem to have a significant role, and are influenced by environmental factors. Research over the past two decades has demonstrated that genetic polymorphisms in the serotoninergic, dopaminergic and catecholaminergic systems of pain transmission and processing are involved in the etiology of fibromyalgia, but additional candidates continue to emerge. Fibromyalgia is thought to belong to the group of affective spectrum disorders, which include related psychiatric and medical disorders. As the concept of affective spectrum disorders continues to evolve, progress in the understanding of the genetic basis of related functional disorders, such as irritable bowel syndrome and post-traumatic-stress disorder, is aiding our understanding of the genetic basis of fibromyalgia.

The clinical field of rheumatology utilizes numerous medications which are either structurally derived from antibiotic compounds or are actually originally track - record proven anti - infective agents adapted for use in this field. Though in many cases, exemplified by rheumatoid arthritis, a presumed infectious etiology brought about the introduction of these drugs into rheumatology, subsequent research has often failed to demonstrate an infectious agent; nevertheless such originally anti - infectious agents as hydroxychloroquine and sulfasalazine have gained a place in the rheumatologic armamentarium. This sequence of events implies that in many cases anti - infective agents posses anti - inflammatory or immuno - modulatory qualities not directly linked to their potential capacity to kill foreign pathogens. More recently agents such as cyclosporine and tacrolimus, both of antibiotic structure, have been developed specifically for their immuno - modulatory effects. This review covers the main events in the development of anti - infective agents for rheumatology and attempts to clarify the often enigmatic relationship between these two seemingly unrelated fields.

Acute herpes-zoster infection is a painful dermatomal lesion that can be manifested by a wide array of neurologic symptoms. We present a 55-year-old female with non-Hodgkin's lymphoma, who developed a left sciatic pain involving the S2.4roots. Two weeks later, the patient developed fever and vesicular rash over the left gluteal area. Herpes-zoster infection was diagnosed and confirmed by the presence of immunoglobulin M (IgM) antibodies against varicella-zoster. The pain and rash resolved, after treatment with acyclovir. In the appropriate clinical setting, sacral herpes-zoster infection ought to be considered in the differential diagnosis of new-onset sciatic pain.

Background. Fibromyalgia syndrome (FMS), a chronic widespread pain disorder, has been associated with various models of stress, including those that are workplace-related. In a previous study, we have documented the significantly increased prevalence of FMS among schoolteachers, as well as correlating symptoms with stressful workplace-related factors. In the current study, we have focused on the specific population of kindergarten teachers and attempted to document both the prevalence of FMS symptoms among this group and the association with stress and symptoms of posttrauma. Methods. All participants in the study were working as kindergarten teachers in Israel at the time of the study. Participants responded to a questionnaire documenting FMS symptom, which included the widespread pain index (WPI) and symptom severity scale (SSS), which together constitute the suggested American College of Rheumatology (ACR) FMS diagnostic criteria. Additional items on the questionnaire documented work motivation and performance, the occurrence of workplace-related stressful events, and the presence of posttraumatic symptoms. Results. 242 participants were recruited to the current study, including 239 (98.8%) females and 3 (1.2%) males. 62 individuals (25.6%) were found to fulfill ACR FMS criteria. Significant differences in work performance were found between teachers fulfilling FMS criteria compared with those not fulfilling criteria. Thus, FMS-positive teachers reported significantly higher rates of missing workdays, leaving work early, and a lower quality of interaction with children in the kindergarten and with peers and supervisors. Motivation to work was also significantly lower among these individuals. The widespread pain index (WPI) and symptom severity scale (SSS), which together constitute the components of the FMS diagnostic criteria, were positively correlated with both stress and posttraumatic symptoms. In addition, widespread pain, disordered sleep, difficulty with concentration, and other FMS symptoms were strongly correlated with many specific stressful factors at the workplace, including the number of children in the kindergarten, interaction with parents, lack of optimal physical conditions in the classrooms, and various demands on behalf of the educational system. Conclusion. FMS symptoms were found to be highly prevalent among Israeli kindergarten teachers, at a rate that greatly exceeds the prevalence in the general Israeli population. Stressful work-related events appear to be positively associated with the occurrence of FMS symptoms and may serve as triggers for their development. Healthcare professionals treating individuals engaged in this occupation should be vigilant for the occurrence of symptoms that are clinically associated with FMS and overlapping functional disorders.

FMS patients demonstrate an altered profile of chemokines relative to healthy controls (HC). Eotaxin-2 is a potent chemoattractant distributed in a variety of tissues. The aim of the study was to compare serum levels of eotaxin-2 between FMS patients and HC and to examine a potential correlation between eotaxin-2 levels and clinical parameters of FMS. Methods. 50 patients with FMS and 15 HC were recruited. Data on the severity of FMS symptoms and depression were collected. Serum levels of eotaxin-2 (ELISA) were determined in all participants. High-sensitive CRP (hs-CRP) was measured in the FMS group. Results. The FMS cohort included predominantly females (84%), mean age of 49, and mean disease duration of 6 years. FMS patients exhibited significantly higher eotaxin-2 levels (pg/ml) versus HC: 833 (±384) versus 622 (±149), p=0.04. Mean hs-CRP level among FMS patients was 4.8 ± 6 mg/l, a value not indicative of acute inflammation. No correlation was found between eotaxin-2 and hs-CRP levels. No correlation was found between eotaxin-2 and severity measures of FMS or depression. Conclusion. Eotaxin-2 does not appear to be a candidate for a disease activity biomarker in FMS. Further research is warranted into the role of this chemokine in the pathophysiology of the FMS.

Objective. The association between Fibromyalgia Syndrome (FMS) and childhood maltreatment and adversity has frequently been proposed but limited data exists regarding the transcultural nature of this association. Methods. 75 Israeli FMS patients and 23 Rheumatoid Arthritis (RA) patients were compared. Childhood maltreatment was assessed by the Childhood Trauma Questionnaire (CTQ) and potential depressive and anxiety disorders were assessed by the Patient Health Questionnaire-4. FMS severity was assessed by the Widespread Pain Index (WPI), the Symptom Severity Score (SSS), and the FIQ. PTSD was diagnosed according to the DSM IV. RA severity was assessed by the RA Disease Activity Index. Health status was assessed by the SF-36. Results. Similar to reports in other countries, high levels of self-reported childhood adversity were reported by Israeli FMS patients. PTSD was significantly more common among FMS patients compared with RA patients, as well as childhood emotional abuse and physical and emotional neglect. Levels of depression and anxiety were significantly higher among FMS patients. Conclusion. The study demonstrated the cross cultural association between FMS and childhood maltreatment, including neglect, emotional abuse, and PTSD. Significant differences were demonstrated between FMS patients and patients suffering from RA, a model of an inflammatory chronic rheumatic disease.

BACKGROUND: Leptin, an adipocyte-produced cytokine, interacts with various hormones, including those of the hypothalamic-pituitary-adrenal axis. Fibromyalgia is a syndrome characterized by widespread pain accompanied by tenderness. The pathogenesis involves a disturbance in pain processing and transmission by the central nervous system, leading to a general increase in pain perception.OBJECTIVES: To analyze potential changes in leptin levels among female fibromyalgia patients compared with healthy controls, and to evaluate the changes in leptin levels during treatment.METHODS: Sixteen female fibromyalgia patients were recruited. Patients underwent clinical evaluation, physical examination, including manual dolorimetry, and were evaluated regarding quality of life, pain, fatigue, anxiety and depression. Plasma leptin levels were determined by ELISA. Patients were offered standard treatment for fibromyalgia. Clinical evaluation and leptin determination were repeated after three months.RESULTS: No significant difference was observed between leptin levels among fibromyalgia patients and controls; no significant correlation was observed between leptin levels and clinical parameters reflecting fibromyalgia severity; and no significant change was observed in leptin levels over three months of treatment. These results did not change after adjustment of leptin levels for body mass index values.CONCLUSIONS: The results of the present study do not support the existence of a significant relationship between leptin and fibromyalgia pathogenesis. Increasing the sample size or examining the interaction between leptin and additional hormones/mediators of metabolism and body weight control may yet uncover significant information in this field.