zithromax and Arthritis--Rheumatoid

Topics: Adult; Anti-Bacterial Agents; Antibodies, Monoclonal, Humanized; Arthritis, Rheumatoid; Azithromycin; Bartonella henselae; Biopsy; Cat-Scratch Disease; Diagnosis, Differential; Humans; Lymph Nodes; Lymphatic Diseases; Male; Receptors, Interleukin-6; Treatment Outcome

To determine the feasibility, safety, and potential clinical efficacy of intravenous (IV) doxycycline therapy for rheumatoid arthritis (RA), as well as its possible effects on serum and urinary markers of collagen breakdown.. The exploratory trial was designed as a 16-week, single-center, randomized, double-blind, placebo-controlled trial. Eligible subjects with active seropositive or erosive RA were randomly allocated into 3 treatment groups: doxycycline 200 mg IV, azithromycin 250 mg orally, or placebo. The blinded IV study drug was administered once daily for the first 3 weeks by home self-infusion and then weekly for the next 8 weeks, concurrent with the blinded oral study drug at the prescribed doses. The primary end points were the change between baseline and week 4 in the tender joint count, erythrocyte sedimentation rate, and urinary excretion of pyridinoline.. The trial was stopped prematurely after enrollment of 31 patients. Three subjects were withdrawn because of worsening arthritis, and 1 patient was withdrawn when newly diagnosed with breast cancer. Infusion-related events occurred in 13 (42%) of 31 patients, but none were serious. There were 4 serious adverse events unrelated to the study drug, including a new diagnosis of breast cancer in 3 cases and hospitalization for abdominal pain in 1 case. No significant differences were observed across treatment groups in any of the 3 primary clinical end points.. Although IV doxycycline therapy was generally well-tolerated by patients in this trial, it did not show any evidence of reducing disease activity or collagen crosslink production.

Topics: Adult; Amino Acids; Anti-Bacterial Agents; Arthritis, Rheumatoid; Azithromycin; Collagen; Double-Blind Method; Doxycycline; Female; Humans; Injections, Intravenous; Male; Middle Aged; Patient Dropouts

Azithromycin is a macrolide antibiotic with anti-inflammatory properties. We aim to substantiate the treatment potential of azithromycin in rheumatoid arthritis.. Gene expression profiles were collected by RNA sequencing and the effects of azithromycin were assessed by in vitro and in vivo assays on the effects of azithromycin-mediated blockade of glucose-regulated protein 78 (GRP78). Anti-inflammatory activity of azithromycin was measured in fibroblast-like synoviocytes from rheumatoid arthritis patients and in collagen-induced arthritis in DBA/1 mice. Characterization of the binding of azithromycin to GRP78 was performed using drug affinity responsive target stability, proteomics and cellular thermal shift assays. Azithromycin-mediated inhibition of GRP78 and its relationship to its anti-arthritic activity was assessed.. Azithromycin reduced proinflammatory factor production, cell migration, invasion and chemoattraction and enhanced apoptosis, reducing the deleterious inflammatory response of rheumatoid arthritis fibroblast-like synoviocytes in vitro. Azithromycin ameliorated the severity of collagen-induced arthritis lesions as efficiently as the TNFα inhibitor etanercept. Transcriptional analyses suggested that azithromycin treatment impairs signalling cascades associated with cholesterol and lipid biosynthesis. GRP78 was identified as a novel target of azithromycin. Azithromycin-mediated activation of the unfolded protein response via the inhibition of GRP78 activity is required not only for inducing the expression of C/EBP-homologous protein (ChOP) but also for the activating sterol-regulatory element binding protein (SREBP) and its targeted genes involved in cholesterol and lipid biosynthetic processes. Furthermore, deletion of GRP78 abolished the anti-arthritic activity of azithromycin.. These findings indicate that azithromycin can used to treat rheumatoid arthritis.

Topics: Animals; Anti-Inflammatory Agents; Arthritis, Experimental; Arthritis, Rheumatoid; Azithromycin; Cells, Cultured; Fibroblasts; Glucose; Humans; Lipids; Mice; Mice, Inbred DBA; Synoviocytes; Unfolded Protein Response

Topics: Adolescent; Adult; Aged; Aged, 80 and over; Anti-Bacterial Agents; Antibodies, Monoclonal, Humanized; Antirheumatic Agents; Arthritis, Rheumatoid; Autoimmune Diseases; Azithromycin; Biological Products; COVID-19; COVID-19 Drug Treatment; Enzyme Inhibitors; Female; Glucocorticoids; Hospitalization; Humans; Hydroxychloroquine; Immunomodulation; Immunosuppressive Agents; Inflammatory Bowel Diseases; Intensive Care Units; Janus Kinase Inhibitors; Male; Middle Aged; Respiration, Artificial; Sarcoidosis; SARS-CoV-2; Surveys and Questionnaires; Tumor Necrosis Factor Inhibitors; Young Adult

Topics: Adult; Aged; Antirheumatic Agents; Antiviral Agents; Arthritis, Psoriatic; Arthritis, Rheumatoid; Azithromycin; Betacoronavirus; Cohort Studies; Coronavirus Infections; COVID-19; COVID-19 Drug Treatment; Drug Combinations; Female; Glucocorticoids; Humans; Hydroxychloroquine; Immunoglobulins, Intravenous; Immunologic Factors; Lopinavir; Lupus Erythematosus, Systemic; Male; Middle Aged; Pandemics; Pneumonia, Viral; Retrospective Studies; Rheumatic Diseases; Ritonavir; SARS-CoV-2; Severity of Illness Index; Spondylarthropathies

To describe clinical characteristics of patients with rheumatic and musculoskeletal diseases (RMDs) and immunosuppressive therapies with Coronavirus disease 2019 (COVID-19) at an academic rheumatology center in Madrid and to identify baseline variables associated with a severe infection requiring hospitalization.. We identified SARS-CoV-2 positive cases by polymerase chain reaction performed at our center within an updated RMDs database in our clinic. Additional RMDs patients were identified when they contacted the clinic because of a positive infection. Data extraction included diagnosis, demographics, immunosuppressive treatment, comorbidities, and laboratory tests. Comparisons between patients with or without hospitalization were performed. Multivariate logistic regression was used to analyze associations between baseline variables and need for hospitalization.. A total of 62 patients with COVID-19 and underlying RMDs were identified by April 24, 2020. Median age was 60.9 years, and 42% men. Forty-two patients required hospitalization; these were more frequently men, older and with comorbidities. There were no statistically significant between-group differences for rheumatologic diagnosis and for baseline use of immunosuppressive therapy except for glucocorticoids that were more frequent in hospitalized patients. Total deaths were 10 (16%) patients. In multivariate analysis, male sex (odds ratio [OR], 8.63; p = 0.018), previous lung disease (OR, 27.47; p = 0.042), and glucocorticoids use (> 5 mg/day) (OR, 9.95; p = 0.019) were significantly associated to hospitalization.. Neither specific RMD diagnoses or exposures to DMARDs were associated with increased odds of hospitalization. Being male, previous lung disease and exposure to glucocorticoids were associated with higher odds of hospitalization in RMDs patients.

Topics: Aged; Anti-Bacterial Agents; Antibodies, Monoclonal, Humanized; Antirheumatic Agents; Antiviral Agents; Arthritis, Psoriatic; Arthritis, Rheumatoid; Autoimmune Diseases; Azithromycin; Betacoronavirus; Comorbidity; Coronavirus Infections; COVID-19; COVID-19 Drug Treatment; Drug Combinations; Female; Glucocorticoids; Hospitalization; Humans; Hydroxychloroquine; Immunosuppressive Agents; Logistic Models; Lopinavir; Lung Diseases; Lupus Erythematosus, Systemic; Male; Middle Aged; Multivariate Analysis; Pandemics; Pneumonia, Viral; Retrospective Studies; Ritonavir; SARS-CoV-2; Severity of Illness Index; Sex Factors; Spain

Topics: Anti-Bacterial Agents; Anti-Infective Agents; Antimalarials; Arthritis, Rheumatoid; Azithromycin; Cardiovascular Diseases; COVID-19; COVID-19 Drug Treatment; Drug Therapy, Combination; Heart Disease Risk Factors; Humans; Hydroxychloroquine; Safety; SARS-CoV-2; Sulfasalazine; Time Factors

Tumor necrosis factor-alpha inhibitors are potent anti-rheumatic drugs, but there is evidence that the high level of immunosuppression they provide may also lead to a higher risk of infections. At our institution, 3 patients with inflammatory arthritis treated with tumor necrosis factor-alpha inhibitors developed mycobacterial soft tissue infections after routine hand surgery. All 3 patients required multiple surgical procedures, inpatient hospitalizations, and prolonged antibiotic multidrug therapy to clear the infections.

Topics: Aged; Antibodies, Monoclonal; Antirheumatic Agents; Arthritis, Psoriatic; Arthritis, Rheumatoid; Azithromycin; Etanercept; Female; Hand; Humans; Immunoglobulin G; Infliximab; Male; Methotrexate; Middle Aged; Mycobacterium Infections; Receptors, Tumor Necrosis Factor; Tenosynovitis; Trimethoprim, Sulfamethoxazole Drug Combination; Tumor Necrosis Factor-alpha

To date, few cases of human joint infection caused by the Mycobacterium terrae complex have been reported. Because M. terrae infection is a relatively uncommon problem, it can be mistaken for a noninfectious inflammatory joint condition. The most common presentation of M. terrae complex infection is tenosynovitis of the hand; infections in bones other than those of the hands are rarely reported. Here, we describe a patient with arthritis of the knee caused by M. terrae and review data from other cases reported in the medical literature.

Topics: Adult; Anti-Bacterial Agents; Arthritis, Rheumatoid; Azithromycin; Drug Therapy, Combination; Ethambutol; Humans; Male; Mycobacterium Infections, Nontuberculous; Nontuberculous Mycobacteria; Ofloxacin; Treatment Outcome

A 56-year-old man with a history of rheumatoid arthritis presented with a 2-day history of worsening pain in his left foot. Treatment with high-dose steroids was of no benefit, hence a diagnosis of septic arthritis was considered. However, the patient's condition deteriorated despite empirical antibiotic therapy. Following persistent investigation, the cause was identified as a fastidious Legionella longbeachae infection, and appropriate antibiotic therapy led to complete resolution of the sepsis. This emphasises the importance of considering infections with atypical organisms in patients on immunosuppressive therapy.

Topics: Arthritis, Rheumatoid; Aza Compounds; Azithromycin; Drug Therapy, Combination; Fluoroquinolones; Humans; Legionella longbeachae; Legionellosis; Male; Middle Aged; Moxifloxacin; Neutropenia; Osteomyelitis; Quinolines; Steroids

Topics: Aged, 80 and over; Anti-Bacterial Agents; Arthritis, Rheumatoid; Azithromycin; Drug Therapy, Combination; Ethambutol; Female; Glucocorticoids; Humans; Immunocompromised Host; Mycobacterium avium Complex; Mycobacterium avium-intracellulare Infection; Prednisone; Rifampin; Skin Diseases, Bacterial

Protein Arginine Deiminase 4 (PAD4) has emerged as a leading target for the development of a Rheumatoid Arthritis (RA) pharmaceutical. Herein, we describe the development of a novel screen for PAD4 inhibitors that is based on a PAD4-targeted Activity-Based Protein Profiling reagent, denoted Rhodamine-conjugated F-Amidine (RFA). This screen was validated by screening 10 Disease Modifying Anti-Rheumatic Drugs (DMARDs) and identified streptomycin, minocycline, and chlortetracycline as micromolar inhibitors of PAD4 activity.

Topics: Arthritis, Rheumatoid; Chlortetracycline; Combinatorial Chemistry Techniques; Enzyme Inhibitors; Fluorescent Dyes; Hydrolases; Minocycline; Models, Biological; Molecular Structure; Protein-Arginine Deiminase Type 4; Protein-Arginine Deiminases; Streptomycin; Tetracycline