History Of Rheumatologic Disease Research Articles

Skeletal and muscular manifestations of post-COVID syndrome: literature review

The 2019 outbreak of a novel coronavirus infection in Wuhan City has resulted in a pandemic that has not only brought about global social change, but has also been a challenge for the entire medical community. The accumulation of material on this disease has revealed the multisystemic nature of internal organ damage with the development of new associated conditions, particularly those related to immunopathology and rheumatologic diseases. This review describes the literature on musculoskeletal symptoms during different periods of new-onset coronavirus infection (COVID-19). The paper defines the terms post-COVID syndrome and Long COVID, and describes clinical observations and the most common symptoms in adults and children. Clinical cases of joint syndrome are described in patients who have had a new coronavirus infection and no history of rheumatologic disease. Possible molecular pathogenesis of autoimmunity activation (cellular and humoral immune response as well as direct cytotoxic effect of the virus) both in acute period of coronavirus infection as well as during recuperation is also considered. Literature analysis of peculiarities of course of COVID-19 in patients with rheumatological diseases was carried out, in particular the risk of infection, its severe course and unfavourable outcome. In general, according to the analysis of the literature, musculoskeletal lesions occur more frequently between 3 and 10 weeks after the end of the acute stage of infection, most often manifested by muscle and joint pain, while the incidence of true reactive arthritis associated with COVID-19 is low. The pathogenesis of musculoskeletal damage requires further investigation and patients should be followed up for a longer period of time.

Musculoskeletal corticosteroid injection and risk of acute coronary syndrome: a case control study.

Musculoskeletal corticosteroid injection (CSI) is a frequently used treatment, considered safe with a low incidence of minor side effects. To investigate whether the incidence of acute coronary syndrome (ACS) is increased following corticosteroid injection for musculoskeletal conditions. Data were reviewed from 41,276 patients aged over 40 years and hospitalised with ACS between January 2015 and December 2019. Each ACS case was allocated up to 10 control patients from their primary care clinic, matched for age and sex. The cases and controls were reviewed for orthopaedic or rheumatological consultation including a CSI procedure and occurring prior to the hospital admission date. The incidence of CSI was compared between the case and control groups. Data from a total of 413,063 patients were reviewed, 41,276 ACS cases and 371,787 controls. The mean age was 68.1, standard deviation (SD) = 13.1, 69.4% male. In the week prior to their hospital admission, 118 ACS patients were treated with CSI compared with 495 patients in the control group; odds ratio (OR) = 1.95 (1.56-2.43). In total, 98% of CSI procedures were carried out by orthopaedic specialists. An association between ACS and prior CSI was strongest in the days immediately prior to hospitalisation: OR = 3.11 (2.10-4.61) for patients who were injected 1 day before ACS. The association between ACS and CSI declined with increasing time between injection and hospital admission: at 90 days OR = 1.08 (0.98-1.18). The association remained robust when cardiovascular risk factors, history of rheumatological disease, and other co-morbidity were taken into consideration. Musculoskeletal corticosteroid injection appears to substantially increase the risk of acute coronary syndrome.

Immune-related adverse effects of long-term PD-1/PD-L1 inhibtor treatment.

2661 Background: Immune-related adverse effects (irAE) are autoimmune-like toxicities caused by immune checkpoint inhibitor (ICI) treatment and often necessitate interventions such as corticosteroids, treatment interruptions/discontinuation, or hospital admission. Although ICI related irAEs are well described in literature, data on the toxicity profile associated with long-term ICI use remains limited. Since the optimal duration of therapy with ICI agents is currently unknown, it is crucial to assess the risks of long-term ICI use. Methods: This was a retrospective, observational, single-center study of adult oncology patients who received at least 1 year of programed death 1 (PD-1) inhibitor or programmed death ligand-1 (PD-L1) inhibitor treatment. The objective of this study was to characterize late-onset irAEs defined as greater than 1 year with long-term ICI treatment. Clinically significant irAEs were defined as those requiring corticosteroid treatment, hospital admission, treatment interruption or treatment discontinuation. This study included patients who received at least 1 year of nivolumab, pembrolizumab, atezolizumab or durvalumab between January 2016 and September 2021. Disease states included head and neck cancer, renal cell carcinoma, non-small cell lung cancer, and melanoma. Patients with concurrent exposure to other treatment such as chemotherapy, radiation, surgery, tyrosine kinase inhibitors and monoclonal antibodies while on ICI treatment were included in the study. Exclusion criteria included patients with treatment breaks of greater than 6 months, two malignancies undergoing active treatment, and treatment administration outside of the study center. Results: Of 282 patients assessed, 143 met study inclusion criteria. The median ICI treatment duration was 19 months (IQR 14-27). There was a 30% incidence of late-onset irAEs, of which 22% were clinically significant. Most late-onset irAEs were low in severity, as 45 (90%) were grade 1-2 and 5 (10%) were grade 3. The most common late-onset irAEs were pulmonary (8%) and gastrointestinal (7%). Univariate analysis suggests risk factors potentially associated with late-onset irAEs include concurrent exposure to additional therapies during ICI treatment and past medical history of rheumatologic disease. Conclusions: Although the optimal duration of ICI therapy is unknown, this study suggests that long-term ICI use was associated with a low but notable incidence of toxicities, of which most were low in severity. [Table: see text]

Ocular Findings Among Patients With Vitamin D Deficiency

ObjectiveThe aim of this study was to evaluate the ocular findings in patients with low vitamin D levels.MethodsAll patients who attended the Internal Medicine Clinic between March 2018 and February 2020 with vitamin low D levels but had been untreated for the same were included in our study. The exclusion criteria were as follows:history of intraocular surgery, trauma, steroid use, secondary glaucoma, and history of rheumatologic diseases. The patients were classified into three groups: group 1 had severe deficiency with vitamin D levels below 10 µg/L; group 2 had vitamin deficiency with levels of 10-20 µg/L; and group 3 had vitamin D insufficiency with levels of 20-30 µg/L. A comparison among groups was performed in terms of intraocular pressure (IOP), retinal nerve fiber layer (RNFL) thickness, central macular thickness (CMT), dry eyes, cataract, glaucoma, macular degeneration, and refractive error. The evaluation of statistical data was performed with the SPSS Statistics software version 22 (IBM, Armonk, NY).ResultsThere were a total of 98 patients and 196 eyes, who were classified into three groups. There were 41 patients in group 1, 45 in group 2, and 12 in group 3. Groups were similar in terms of age (p=0.25) and gender (p=0.46). The average age among the cohort was 51 ± 13.08 years; 65 (66.3%) of the patients were female and 33 (33.7%) were male. There was no statistically significant difference in terms of IOP (p=0.55), dry eyes (p=0.35), cataract (p=0.22), glaucoma (p=0.50), macular degeneration (p=0.64), and refractive error (p=0.46) among the groups. There was a statistically significant difference in CMT between group 1 and other groups (p=0.002 and p=0.002, respectively). Also, there was a statistically significant difference in RNFL thickness between group 1 and group 2 (p=0.01). When compared in terms of quadrants, a significant difference was found only with regard to the nasal quadrant.ConclusionBased on our findings, lower levels of 25-hydroxyvitamin D might be related to thinning in CMT. Regarding RNFL thickness, while there was a significant difference between groups 1 and 2, there was no difference between groups 1 and 3, and hence the association between lower levels of 25-hydroxyvitamin D and thinning in RNFL thickness could not be clearly established. Hence, we have assumed that lower levels of 25-hydroxyvitamin D might cause thinning in the macula and nasal quadrant of RNFL, and vitamin D deficiency might affect the nasal quadrant of RNFL primarily. Further long-term studies with a larger number of patients might clarify the relationship between vitamin D deficiency and the thinning in CMT, RNFL quadrants, and RNFL thickness.

Unilateral cyanosis on tongue as an unusual appearance in emergency department: a case report

Introduction: Unilateral and bilateral tongue cyanosis usually occurs due to the Raynaud syndrome and in the underlying severe types of vasculitis and rheumatology.Case Presentation: The present study was conducted on a 54-year-old woman who referred to the emergency department with complaints of sudden and painless discoloration of the left half of the tongue. The patient had no history of disease other than diabetes controlled with glibenclamide. Clinical examination of the head and neck revealed evidence of unilateral cyanosis in the left half of the tongue without pain, whose discoloration did not improve with warming of the tongue.Conclusion: Cyanosis in the emergency department can be managed appropriately by considering some parameters including history taking, history of cyanosis occurrence, history of cardiopulmonary disease, cold sensitivity and history of rheumatologic diseases, presence or absence of nail clubbing, arterial blood oxygen saturation and arterial blood gas test results. These parameters can be effective in designing a treatment regimen, while differentiating the causes of central from peripheral cyanosis.

The Relationship Between Serum Vitamin D Level and Systemic Lupus Erythematosus Activity

Background and aims: : Systemic lupus erythematosus (SLE) is an autoimmune disease which involves various organs. Vitamin D is an essential ingredient in regulating the immune system. This study aimed to investigate the relationship between vitamin D and the severity of lupus activity. Materials and Methods: This case-control study was carried out on 38 patients with lupus on the basis of the American College of Rheumatology (ACR) criteria and 44 healthy subjects with no history of rheumatologic disease. To measure the level of 25-hydroxy vitamin D, venous blood samples (5 cc) were taken from each participant and the activity of the lupus disease was measured by the Systemic Lupus Erythematosus Disease Activity Index (SLEDAI) scale. Finally, the chi-square test, independent sample t test, one-way ANOVA, and multiple linear regression analysis were used to measure multivariate effects. The level of significance was set to be P<0.05. Results: Thirty-five lupus patients and 40 healthy subjects were females (P=0.847). Vitamin D deficiency was observed in the case (42.1%) and control (11.4%) groups. The mean value of serum vitamin D3 level was 35.3 ng/mL in the control group, as well as 24.6 ng/mL and 21.3 ng/mL in patients with mild and severe SLE, respectively (P=0.024). Conclusion: In this study, high levels of 25-hydroxy vitamin D were observed among the healthy subjects compared to patients with SLE. Eventually, the level of vitamin D significantly decreased by increasing the severity of SLE activity.

Diagnostic value of Ultrasonography in the detection of Bone Erosions in patients with Rheumatoid Arthritis: a comparison with Conventional Radiography.

Objective:Rheumatoid arthritis (AR) is the most common systemic inflammatory disease of joints, with prevalence of 1% worldwide. Bone erosion (BE) is a central feature of rheumatoid arthritis and is associated with disease severity and poor functional outcome. Conventional Radiography (CR) and Ultrasonography (US) play an important role in the diagnosis of RA. The aim of this study was to compare the value of two methods in the detection of BE in AR patients.Methods:In this cross-sectional study, 111 patients with confirmed RA have been randomly selected and were studied. A checklist which includes demographic information such as age, gender, place of residence, history of smoking, education level and history of rheumatologic disease was completed for all patients, and then radiography and high-resolution US of dominant hands and wrists of metacarpophalangeal (MCP) joint were performed. Collected data was analysed by statistical methods in SPSS version 22.Results:The results of this study showed that there is no significant difference between these two methods in detection of BE. In age groups < 44 years old, US with 98% had more sensitivity than CR with 89%.Conclusion:Results showed that there is no significant difference in diagnostic value of US in bone erosion in patients with rheumatoid arthritis, in comparison with CR in terms of gender and diagnosis for the existence of erosions; however, in determining the amount of BE in age groups < 44 years old, US has better performance than CR.

Validation Of Medical Inpatient Venous Thrombosis Risk Assessment (MITH) Score

▪ IntroductionGovernmental agencies recommend risk assessment of venous thrombosis (VT) for medical inpatients at admission and provision of VT prophylaxis for moderate to high risk patients. While several risk factor models for predicting hospital-acquired VT have been proposed, none have been widely accepted and few have been prospectively validated. We sought to validate the recently published MITH VT risk assessment model in an independent cohort of medical inpatients (Zakai et al, Journal of Thrombosis and Haemostasis 2013). MethodsHospital-acquired VT and risk factors present at admission were collected from adult inpatients between June 2009 and April 2012 admitted to the medicine, medical intensive care, hematology/oncology, or cardiology services at Fletcher Allen Hospital (500 bed teaching hospital for the University of Vermont). Hospital-acquired VT was defined using VT discharge ICD-9 codes (flagged as not present on admission) and record of an imaging study that could diagnosis VT (such as duplex ultrasound, computed tomography angiography, or ventilation perfusions scan). Inpatients with VT ICD-9 codes flagged as present on admission were excluded. The sensitivity and specificity of the definition was confirmed by chart review of 30 cases of hospital-acquired VTE and 30 non-cases. Risk factors for hospital-acquired VT were captured using ICD-9 codes from the problem list, discharge codes, vital signs, and laboratory values at admission. The MITH score was calculated for each patient based on the points for each risk factor: history of heart failure = 5 pts, history of rheumatologic disease = 4 pts, history of fracture in past 3 months = 3 pts, history of cancer in past 12 months = 1 pt, tachycardia (HR>100 at admission) = 2pt, respiratory dysfunction (SpO2<90% at admission or intubated on hospital day 1) = 1 pt, white blood cell count >11 = 1 pt, platelet count >350 = 1 pt. The absolute rates of hospital-acquired VT for different cut points of the score were calculated and compared qualitatively to those previously published for the MITH score. ResultsThere were 120 hospital-acquired VT events complicating 20,334 medical admissions (5.9 cases per 1,000 hospital admissions). The sensitivity and specificity of our definition of hospital-acquired VT was 100% and 91%, respectively. The table presents the prevalence of the MITH score at various cut-offs in cases and non-cases as well as the incidence of VT. In the derivation of the MITH score, the rate of VT per 1000 admissions for a score <1, <2, or <3 was 1.0, 1.5, and 2.1 compared with 0.7, 1.8, and 2.2 VT per 1000 admissions for the validation cohort. The incidence of VTE in the derivation of the MITH score for a score ≥1, ≥2, and ≥3 was 6.0, 8.9, and 12.4 per 1000 admissions compared with 7.9, 9.0, and 10.3 per 1000 admissions in the validation cohort. ConclusionsWe have validated a previously published VT risk score for hospitalized medical patients in an independent population. Determination of a patient's risk of VT at admission using readily available clinical and laboratory data could allow physicians to make informed decisions about risks and benefits of DVT prophylaxis. Further work is required to determine at what level of risk pharmacologic VT prophylaxis is warranted in this patient population.TablePerformance of the MITH scoreMITH Scoren (%) of cases < scoren (%) of non-cases < scoreVT per 1000 admissions for < scoreVT per 1000 admissions for ≥ scoreCurrent AnalysisPredicted (95% CI) (Previously Published)Current AnalysisPredicted (95% CI) (Previously Published)14 (3.3%)5,582 (27.6%)0.71.0 (0.6, 1.8)7.96.0 (2.0, 17.7)216 (13.3%)8,710 (43.1%)1.81.5 (1.0, 2.3)9.08.9 (4.2, 18.8)326 (21.7%)11,189 (55.4%)2.22.1 (1.5, 3.0)10.312.4 (6.3, 24.5)440 (33.3%)12,995 (64.3%)3.12.9 (2.1, 4.1)11.015.5 (7.5, 31.8)550 (41.7%)14,096 (69.7%)3.53.3 (2.4, 4.8)11.317.3 (7.5, 39.0)667 (55.8%)16,447 (81.4%)4.14.4 (3.2, 5.9)13.934.5 (14.4, 80.4)779 (65.8%)17,786 (88.0%)4.44.7 (3.4, 6.3)16.666.6 (21.1, 191.0) Disclosures:No relevant conflicts of interest to declare.

Identifying Bleeding Risk In Medical Inpatients

IntroductionExpert guidelines and regulatory agencies recommend that all medical inpatients be assessed for venous thrombosis (VT) risk and pharmacologic prophylaxis provided to at-risk patients. However, anticoagulant prophylaxis may increase the risk of major bleeding in medical inpatients and the incidence and risk factors for major bleeding are not established. Our goal was to determine the rate of hospital-acquired major bleeding in medical inpatients and whether patients at increased risk of hospital-acquired VT were also at increased risk for hospital-acquired major bleeding. MethodsAll cases of hospital-acquired major bleeding on medical services (cardiology, hematology/oncology, intensive care, internal medicine) were identified at Fletcher Allen Health Care (500-bed teaching hospital for the University of Vermont) between June 2009 and April 2012. Major bleeding was defined as symptomatic bleeding in a critical area (intracranial, intraspinal, intraocular, retroperitoneal and peritoneal by ICD-9 discharge codes with the present on admission flag marked as ‘no') or any bleeding that caused a fall in hemoglobin of 2g/dL within 24 hours (assessed from the laboratory database after the patient had been admitted for 24 hours) and required a red blood cell transfusion. The sensitivity and specificity of the definition was confirmed by chart review of 20 cases of hospital-acquired major bleeding and 20 non-cases. Logistic regression was used to calculate odds ratios (OR) for major bleeding for age, use of anticoagulation, and risk factors for hospital-acquired VT contained in the Medical Inpatient Thrombosis (MITH) score (Table). The MITH score was calculated for each patient using data present on admission: history of heart failure = 5 points, history of rheumatologic disease = 4 points, history of fracture in past 3 months = 3 points, history of cancer in past 12 months = 1 point, tachycardia (HR>100 at admission) = 2 points, respiratory dysfunction (SpO2<90% at admission or intubated on hospital day 1) = 1 point, white blood cell count >11 x 103/µL = 1 points, platelet count >350 x 103/µL = 1 point). Major bleeding rate was calculated for MITH score using the following cut off points: 0-1, 2-5, ≥6. Results241 cases of major bleeding complicated 20,946 medical admissions (11.1 per 1000 admissions). The sensitivity and specificity of our definition of hospital-acquired major bleeding was 100% and 83%, respectively. Prophylactic anticoagulation ordered on admission was not associated with major bleeding (OR 1.1) but full anticoagulation on admission was associated with major bleeding (OR 1.4). Of the MITH score variables, respiratory dysfunction (OR 2.2), prior history of congestive heart failure (OR 2.2) and white cell count ≥11 x 103/µL (OR 2.0) on admission were associated with major bleeding (table 1). For MITH scores 0-1, 2-5, and ≥5, major bleeding occurred in 6, 11, and 19 per 1000 admissions, respectively. The corresponding incidence of hospital-acquired venous thrombosis for a MITH score of 0-1, 2-5, and ≥6 were 2, 7, and 14 per 1000 admissions. Hospital-acquired VT was strongly associated with major bleeding (OR 20.4; 95% CI 12.4, 33.7). ConclusionMajor bleeding is a more common complication of hospital admission than VT. Risk factors and an aggregate risk score for hospital-acquired VT were associated with the risk of major bleeding. Evidence-based models which assess both bleeding and thrombosis risk are urgently needed to help risk stratify medical patients for appropriate VT prophylaxis.TableAssociation of the MITH Thrombosis Risk Score Variables and Major BleedingRisk FactorOdds Ratio (95% Confidence Interval)Prophylactic-dose anticoagulation1.1 (0.8, 1.5)Full-dose Anticoagulation1.4 (1.0, 1.9)History of Congestive Heart Failure2.2 (1.7, 2.9)History of Rheumatologic or Inflammatory Disease1.1 (0.7, 1.8)Fracture in the past 3 monthsNo major bleeding cases with this risk factorHistory of Venous Thrombosis1.2 (0.8, 1.9)History of cancer in past 12 months1.3 (0.9, 1.7)Heart Rate ≥100 on admission1.1 (0.8, 1.5)Respiratory Dysfunction2.2 (1.6, 3.1)White Cell count ≥11 x 103/µL on admission2.0 (1.5-2.7)Platelet count ≥ 350 x 103/µL on admission1.3 (0.8, 2.1) Disclosures:No relevant conflicts of interest to declare.

Long-term chikungunya infection clinical manifestations after an outbreak in Italy: A prognostic cohort study

Following a Chikungunya (CHIKV) outbreak in Italy, a cohort study was conducted to describe the infection long-term clinical course and outcome. Persons identified through active and passive surveillance as confirmed or possible CHIKV cases during the outbreak were enrolled and interviewed by trained public health nurses, between 4-5 and 12-13 months following the acute stage. Patients reporting persistent clinical symptoms were evaluated by rheumatologists. Serum samples were obtained and anti-CHIKV specific IgG and IgM immune responses detected. Only confirmed cases who completed the follow-up were analysed. Out of 250 patients, 66.5% still reported myalgia, asthenia or arthralgia (most frequent sign) after 12 months. Functional ability, measured by the ROAD index, was more impaired for lower extremities (3.75; Inter Quartile Range - IQR 4.4), and the activities of daily living (average 4.2; IQR 5). Variables independently associated with the presence of joint pain at 12-13 months were increasing age, and history of rheumatologic diseases). Elderly, females, and persons with history of rheumatologic diseases had higher anti-CHIKV IgG titres at 12-13 months. This study confirms, in an unselected population, that the long-lasting burden of CHIKV infection is significant.

A Case of Periostitis Secondary to Voriconazole Therapy in a Heart Transplant Recipient

A 66-year-old man with a history of heart transplant for idiopathic dilated cardiomyopathy presented with progressive bone pain and myalgias. He has been on voriconazole for a pulmonary Aspergillus infection for 9 months. He had an elevated alkaline phosphatase of 280. There is no history of rheumatologic disease. Drug-induced periostitis has recently been reported in patients on long-term voriconazole therapy after lung transplantation for prophylaxis and treatment of Aspergillus infection. This case demonstrates the same phenomenon in a heart transplant patient. This patient's symptoms improved after discontinuation of voriconazole.

Quality of life is impaired in men with chronic prostatitis: the Chronic Prostatitis Collaborative Research Network.

Health-related quality of life (HRQOL) impairment may be a central component of chronic prostatitis for men afflicted with this condition. Our objective was to examine HRQOL, and factors associated with HRQOL, using both general and condition-specific instruments. Chronic Prostatitis Cohort (CPC) study. Six clinical research centers across the United States and Canada. Two hundred seventy-eight men with chronic prostatitis. The Short Form 12 (SF-12) Mental Component Summary (MCS) and Physical Component Summary (PCS), and the National Institutes of Health Chronic Prostatitis Symptom Index (NIH-CPSI) were measures used. CPC subjects' MCS scores (44.0 +/- 9.8) were lower than those observed in the most severe subgroups of patients with congestive heart failure and diabetes mellitus, and PCS scores (46.4+/-9.5) were worse than those among the general U.S. male population. Decreasing scores were seen in both domains with worsening symptom severity (P < .01). History of psychiatric disease and younger age were strongly associated with worse MCS scores, whereas history of rheumatologic disease was associated with worse PCS scores. Predictors of more severe NIH-CPSI scores included lower educational level and lower income; history of rheumatic disease was associated with higher scores. Men with chronic prostatitis experience impairment in the mental and physical domains of general HRQOL, as well as condition-specific HRQOL. To optimize the care of men with this condition, clinicians should consider administering HRQOL instruments to their patients to better understand the impact of the condition on patients' lives.

Iridocyclitis in black Americans: association with HLA B8 suggests an autoimmune aetiology.

Histocompatibility (HLA) testing was performed on a total of 171 black Americans, 129 controls, and 42 patients with iridocyclitis. None of the patients had a history of rheumatological disease. The phenotype frequency of HLA B8 was greatly increased among patients than the control group (exact p = 0.0010). Most striking was the almost identical phenotypic frequency of B27 found in patients and in the control group (exact p = 0.07087). No HLA DR antigen in the patient group was found to be significantly raised when compared with controls. The HLA B8 associated diseases was seen more in females, was bilateral and nongranulomatous, had no systemic disease associated with it, and left patients with visual handicap. The HLA B8 antigen has been associated with various entities of presumed autoimmune origin, and these data suggest that iridocyclitis, at least in blacks, may be of similar aetiology.