A deep look into the storm: Israeli multi-center experience of coronavirus disease 2019 (COVID-19) in patients with autoimmune inflammatory rheumatic diseases before and after vaccinations.

Objective: We aimed to characterize the course of COVID-19 in autoimmune inflammatory rheumatic disease (AIIRD) patients in Israel, taking into consideration several remarkable aspects, including the outcomes of the different outbreaks, the effect of vaccination campaigns, and AIIRD activity post-recovery. Methods: We established a national registry of AIIRD patients diagnosed with COVID-19, including demographic data, AIIRD diagnosis, duration and systemic involvement, comorbidities, date of COVID-19 diagnosis, clinical course, and dates of vaccinations. COVID-19 was diagnosed by a positive SARS-CoV-2 polymerase chain reaction. Results: Israel experienced 4 outbreaks of COVID-19 until 30.11.2021. The first three outbreaks (1.3.2020 - 30.4.2021) comprised 298 AIIRD patients. 64.9% had a mild disease and 24.2% had a severe course; 161 (53.3%) patients were hospitalized, 27 (8.9%) died. The 4th outbreak (delta variant), starting 6 months after the beginning of the vaccination campaign comprised 110 patients. Despite similar demographic and clinical characteristics, a smaller proportion of AIIRD patients had negative outcomes as compared to the first 3 outbreaks, with regards to severity (16 patients,14.5%), hospitalization (29 patients, 26.4%) and death (7 patients, 6.4%). COVID-19 did not seem to influence the AIIRD activity 1-3 months post-recovery. Conclusions: COVID-19 is more severe and has an increased mortality in active AIIRD patients with systemic involvement, older age and comorbidities. Vaccination with 3 doses of the mRNA vaccine against SARS-CoV-2 protected from severe COVID-19, hospitalization and death during the 4th outbreak. The pattern of spread of COVID-19 in AIIRD patients was similar to the general population.

Ruxolitinib for Refractory Macrophage Activation Syndrome Complicating Adult-Onset Still's Disease.

Macrophage activation syndrome is the most frequent life-threatening complication of adult-onset Still's disease. This is a nearly fatal case of a young patient, which has been refractory to corticoste- roids, anakinra, tocilizumab, cyclosporine A, and etoposide, but eventually responded miraculously to salvage therapy with ruxolitinib. We review recent pertinent data related to the therapeutic value of ruxolitinib for macrophage activation syndrome triggered by adult-onset Still's disease.

All-cause hospitalizations in systemic lupus erythematosus from a single medical center in Israel.

OBJECTIVE: Clinical features of systemic lupus erythematosus (SLE) have been described from different geographical regions in the world. The aim of this study was to obtain local and contemporary data on all-cause hospitalizations of SLE patients in an Israeli Medical Center. METHODS: This is a retrospective observational single-center study. Revision of medical records of hospitalized lupus patients during 5-year period (January 2012-December 2016) was performed. RESULTS: A total of 61 lupus patients and 138 hospitalizations were identified. Female-to-male ratio was 9:1. Average age was 42.5 years. Average disease duration was 14.58 years. Mean SLICC/ACR damage index was 0.75. The majority of patients were treated with lupus medications (47, 77%). The most common lupus medications were hydroxychloroquine (40, 65.5%), prednisone (25, 40.9%), and azathioprine (9, 14.75%). The most common reasons for hospitalization were disease flare (28, 20.3%), pregnancy and labor (26, 18.9%), and infection (19, 13.8%). The average length of hospitalization for all patients was 6.65 days. No fetal morbidity was recorded, and there was one event of maternal morbidity. There were no cases of acute coronary events. There were six ICU admissions (4.35%). Two admissions (1.45%) were complicated by hospital-acquired infection. Three patients died (2.17%) during hospital stay. CONCLUSIONS: This survey from a single Israeli medical center revealed low rates of pregnancy complications, coronary events, and nosocomial infections in hospitalized lupus patients. Further studies are required to determine whether these findings reflect local disease expression or it may remark global trend of decrease in lupus complications.

The impact of concomitant fibromyalgia on visual analogue scales of pain, fatigue and function in patients with various rheumatic disorders.

OBJECTIVES: To evaluate the impact of concomitant fibromyalgia on the rating of pain, fatigue, and dysfunction, in patients with various rheumatic disorders. METHODS: A cross-sectional study was carried out in a hospital-based rheumatology unit. Standard clinical and laboratory data were obtained and all patients completed questionnaires on pain, fatigue, and daily function. The rate of concomitant fibromyalgia was estimated using the 1990 American College of Rheumatology (ACR) classification criteria for fibromyalgia and the analysis concentrated on visual analogue scales (VAS). RESULTS: Six hundred and eighteen visits of 383 patients with inflammatory as well as non-inflammatory rheumatic disorders were analyzed. Concomitant fibromyalgia was noted in 74 patients (23% of the cohort). Patients with rheumatic diseases and concomitant fibromyalgia had significantly higher mean VAS scores for pain, fatigue, and function (79±17, 81±18, 80±18, respectively) as compared to patients who had no features of fibromyalgia (47±28, 50±29, 44±30 respectively; all p values <0.001). The scores reported by patients with rheumatic diseases and concomitant fibromyalgia were similar to the scores obtained from patients with primary FM. CONCLUSIONS: Concomitant FM is common both among patients with inflammatory and patients with non inflammatory rheumatic disorders. Concomitant FM has a remarkable impact on the severity of symptoms and, moreover, patients with concomitant FM exhibit extreme and significantly distinct levels of pain and fatigue which is as severe as that reported by patients with primary FM. It seems that fibromyalgic features dominate and become the main cause of morbidity in rheumatological patients with concomitant FM.

Visual Analogue Scales of Pain, Fatigue and Function in Patients with Various Rheumatic Disorders Receiving Standard Care.

BACKGROUND: Pain, fatigue and functional disability are common key outcomes in most rheumatologic disorders. While many studies have assessed the outcomes of specific disease states, few have compared the outcomes of various rheumatic diseases. OBJECTIVES: To assess how the intensity and rating of pain, fatigue and functional disability vary among groups of patients with various rheumatic disorders receiving standard care. METHODS: In a cross-sectional study conducted in a hospital-based rheumatology unit, standard clinical and laboratory data were obtained and all patients filled out questionnaires on pain, fatigue and daily function. The analysis concentrated on visual analogue scales (VAS) using specific statistical methods. RESULTS: A total of 618 visits of 383 patients with inflammatory as well as non-inflammatory rheumatic disorders were analyzed. Fibromyalgia patients had significantly higher VAS scores compared to all other groups. On the other hand, patients with polymyalgia rheumatica demonstrated significantly lower VAS scores compared to all other groups of patients. Patients with psoriatic arthritis also demonstrated relatively low VAS scores. VAS scores were lower in patients with inflammatory disorders as compared to patients with non-inflammatory disorders. CONCLUSIONS: Our results suggest a spectrum of outcome intensity in various rheumatic disorders receiving standard care, ranging from fibromyalgia patients who report distinctive severity to patients with inflammatory disorders who are doing relatively well as compared to patients with non-inflammatory disorders. The findings emphasize the need to explore the underlying mechanisms of pain and fatigue in patients with non-inflammatory rheumatic disorders.

Increased ERK and JNK activation and decreased ERK/JNK ratio are associated with long-term organ damage in patients with systemic lupus erythematosus.

OBJECTIVE: The activities of two mitogen-activated protein kinases (MAPKs), extracellular signal-regulated kinase (ERK) and c-Jun N-terminal kinase (JNK), correlate with disease severity in SLE patients. Whether they are also associated with long-term organ damage is unknown. The aim of the present work was to determine whether impaired expression and activity of ERK and JNK correlate with long-term damage in SLE. METHODS: The expression of ERK and JNK and their phosphorylated active forms was determined by western blot analysis four times during the first year of follow-up in peripheral blood mononuclear cells from 36 SLE patients. A correlation analysis was performed between ERK and JNK expression and longterm organ damage estimated by the SLICC/ARC Damage Index (SDI) 4 years later. RESULTS: Mean levels of ERK and JNK activities during the first year correlated with long-term organ damage severity (r = 0.38 and r = 0.35, respectively; P = 0.05). Overall JNK expression increased with the severity of chronic damage (P = 0.01; P = 0.05 for SDI score 2 and 3, respectively). In contrast, overall ERK expression significantly decreased in patients with maximal organ damage (SDI score 3) compared with patients with an SDI score of 2 (P = 0.03). The ERK/JNK ratio decreased by approximately 40% and 30% in patients with an SDI score of 3 as compared with patients without organ damage and healthy controls, respectively. CONCLUSION: These results demonstrate that early activation of ERK and JNK along with decreased overall ERK expression and reduced ERK/JNK ratio may predict the severity of long-term organ damage in SLE patients.

Anti-neutrophil antibody associated vasculitis in systemic sclerosis.

OBJECTIVES: To report 3 cases ANCA-associated vasculitis (AAV) that developed in patients suffering from systemic sclerosis (SSc) and to review previously reported cases. METHODS: We describe 3 patients diagnosed with SSc who developed severe AAV that presented as crescentic glomerulonephritis (GN) and/or alveolar hemorrhage. A retrospective review of the literature was performed using the PubMed database. RESULTS: The first patient presented with rapidly progressive renal failure and then with 2 episodes of massive alveolar hemorrhage. She was partially refractory to treatment with corticosteroids and cyclophosphamide but responded promptly to treatment with rituximab. The second patient suffered from 2 episodes of fulminant alveolar hemorrhage; the first responded to intravenous corticosteroids, but the second was fatal despite aggressive immune suppression with corticosteroids and cyclophosphamide. The third patient presented with a clinical picture compatible with scleroderma renal crisis (SRC) but was later diagnosed with crescentic GN and subsequently died from probable alveolar hemorrhage. Thirty-seven cases of AAV in SSc patients have been described in the English literature. Clinical manifestations include rapidly progressive GN, alveolar hemorrhage, limb ischemia, and vasculitic skin rash. In contrast to SRC that usually develops early in the course of SSc, ANCA-associated GN in SSc patients occurred later, after several years of illness. Hypertension, microangiopathic hemolytic anemia, and thrombocytopenia that are the hallmark of SRC were observed only in a minority of AAV cases. Almost all cases of AAV in SSc were positive for MPO-ANCA. CONCLUSIONS: AAV in the setting of SSc is a diagnostic challenge. Differential diagnosis from SRC is crucial as treatment approach for these conditions completely differs. High doses of corticosteroids and immune suppression are advocated in severe AAV. In resistant cases, treatment with rituximab may be considered.

Can fibromyalgia be associated with whiplash injury? A 3-year follow-up study.

The objective of this study is to assess the long-term outcome and natural history of a cohort of patients with whiplash injury regarding the development of fibromyalgia. Of the 153 patients who were admitted to the emergency room after whiplash injury in 2004, 126 were reassessed 3 years later. Also, 33 of 53 patients from the original control group of hospitalized patients with fractures were reevaluated. Patients were interviewed by phone and by written forms using a detailed questionnaire. Patients who complained of musculoskeletal symptoms were invited and examined. The study group included 68 men and 58 women, with a mean age of 50.1 ± 9.7. The control group included 19 men and 14 women with a mean age of 44.2 ± 10.3. Follow-up period did not differ significantly between the groups 38.3 ± 2.3 vs. 36.4 ± 4.2 months. At the end of the follow-up period, three patients in the study group compared with one patient in the control group were diagnosed as having fibromyalgia; all of them were women. The rate of new onset widespread pain increased with time in both groups. Symptoms of dizziness, headaches, fatigue and sleep disturbances improved, as well as the quality of life (QOL) and the Fibromyalgia Impact Questionnaire (FIQ) scores. Insurance claims continued to be more prevalent in the control group. The results of this extended follow-up study confirm previous short-term results showing that whiplash injury and road accident trauma are not associated with an increased risk of fibromyalgia.

Neck injury and fibromyalgia-- are they really associated?

OBJECTIVE: To investigate whether whiplash injury may be a trigger for the onset of fibromyalgia (FM). METHODS: One hundred fifty-three patients presenting to the emergency room with the diagnosis of whiplash injury were examined. The control group included 53 patients hospitalized with fractures of the limbs, spine, and ribs due to road accident. The study and control groups were interviewed shortly after presenting and then followed prospectively. Patients complaining of musculoskeletal symptoms during followup were examined and a count of 18 tender points was conducted. FM was diagnosed if the patient fulfilled currently accepted 1990 American College of Rheumatology criteria. RESULTS: The mean followup period for the study and control groups was 14.5 months (range 12-18) and 9 months (range 6-14), respectively. There were no differences between the groups with regard to age, sex, marital, education, or employment status. During the followup period only one patient in the study group and no patients in the control group developed signs and symptoms of FM. Three patients in the study group (2%) and 15 patients in the control group (16%) filed insurance claims; none was associated with FM. CONCLUSION: Whiplash injury and road accident trauma were not associated with an increased rate of FM after more than 14.5 months of followup.

The effect of balneotherapy on osteoarthritis. Is an intermittent regimen effective?

Background: Balneotherapy is used as a treatment modality for various musculoskeletal disorders. The aim of this study was to evaluate the effectiveness of intermittent balneotherapy in patients with knee osteoarthritis (OA). Methods: Seventy-two patients with knee OA were included in the study. Patients were divided into two groups: group A (48 patients) was given intermittent once weekly treatment for 6 weeks; group B (24 patients) served as a control group. Evaluation was done prior to study entry, at weeks 4 and 6, and 4 weeks following completion of treatment (week 10). Assessment included global pain score (VAS), WOMAC index, Lequesne's functional index, patients' and physician's disease severity score, and NSAID/analgesic consumption. Results: Following balneotherapy, a statistically significant improvement, determined by the reduction in the mean changes of most outcome parameters (VAS, WOMAC, and Lequesne's index), was noted in group A at weeks 4 and 6 and was sustained 4 weeks after cessation of treatment (week 10). Significant improvement in both physician's and patients' disease severity scores, as well as a reduction in analgesic and NSAID consumption, were also noted in group A. No improvement was found in the control group in any of the tested parameters. Conclusions: Intermittent balneotherapy appears to be effective in the treatment of knee OA.