Ciprofloxacin-Induced Anaphylactic Reaction Followed by Negative Provocation Test in Response to Levofloxacin: A Case Report.

Fluoroquinolones are a commonly prescribed class of antibiotics due to their broad spectrum of antimicrobial activity, favorable pharmacokinetic properties, ability to switch from parenteral to oral administration, and global availability. After beta-lactams, they are the second most common antibiotic class associated with drug allergies. The mechanism of fluoroquinolone-induced hypersensitivity reactions has not yet been fully understood, so the true incidence of hypersensitivity reactions remains unknown. Cross-reactivity between fluoroquinolones has been the subject of conflicting and limited clinical research. Due to their similar chemical structure, some argue for close cross-reactivity within the group. However, recent studies have produced contradictory results. We present the case of a young patient who had an anaphylactic reaction to ciprofloxacin but was tolerant to levofloxacin, as determined via a skin prick test followed by a drug provocation test. Our findings support the notion that there is little cross-reactivity between fluoroquinolones. Consequently, exposure to another fluoroquinolone in a hospital setting may be beneficial, particularly for patients who lack adequate antibiotic alternatives. However, additional research on this subject is required.

Safe and Efficient Use of Tocilizumab in Rheumatoid Arthritis Patient on Maintenance Hemodialysis: A Case Report.

Background: Rheumatoid arthritis (RA) is a chronic systemic autoimmune and inflammatory disease. Conventional synthetic and biologic disease-modifying antirheumatic drugs (DMARDs), Janus kinase inhibitors, and rituximab are used to treat the disease. There are no recommendations or guidelines for the treatment of patients with both inflammatory arthritis and end-stage renal disease (ESRD), despite the safety and efficacy of the mentioned drugs. The anti-interleukin-6 receptor antibody tocilizumab (TCZ) has not been used as a long-term therapy for hemodialysis (HD) patients with RA, except in a few case reports. Case Description: We present the case of a 41-year-old patient with RA and ESRD on maintenance HD due to type 1 diabetes-related complications. Due to high RA disease activity, the patient was not a suitable candidate for a kidney transplant. Because TCZ is used to treat both RA and kidney transplant rejection, therapy with a full dose of TCZ was administered. The patient has achieved sustained clinical remission (for the past four years) with no adverse events reported. Conclusions: Herein, we present the safe and effective use of TCZ in an RA patient on HD who is also a candidate for kidney transplant. Consequently, TCZ could be the treatment of choice for RA patients with ESRD who have not achieved disease control (low activity or remission) with conventional synthetic DMARDs. Clinical studies are required to evaluate the efficacy and safety of biologic DMARDs and Janus kinase inhibitors in patients with both inflammatory arthritis and ESRD.

Perimyocarditis as First Manifestation of Systemic Lupus Erythematosus Successfully Treated with Heart Failure and Immunosuppressive Therapy.

Systemic lupus erythematosus (SLE) myocarditis is presumed to be rare, but associated with adverse outcomes. If SLE diagnosis has not previously been established, its clinical presentation is often unspecific and difficult to recognize. Furthermore, there is a lack of data in the scientific literature regarding myocarditis and its treatment in systemic immune-mediated diseases, leading to its late recognition and undertreatment. We present the case of a young woman whose first lupus manifestations included acute perimyocarditis, among other symptoms and signs that provided clues to the diagnosis of SLE. Transthoracic and speckle tracking echocardiography were helpful in detecting early abnormalities in the myocardial wall thickness and contractility while waiting for cardiac magnetic resonance. Since the patient presented with acute decompensated heart failure (HF), HF treatment was promptly started in parallel with immunosuppressive therapy, with a good response. In the treatment of myocarditis with heart failure, we were guided by the clinical signs, echocardiographic findings, biomarkers of myocardial stress, necrosis, and systemic inflammation, as well as markers of SLE disease activity.

Rituximab, Intravitreal Bevacizumab and Laser Photocoagulation for Treatment of Macrophage Activation Syndrome and Retinal Vasculitis in Lupus: A Case Report.

Systemic lupus erythematosus (SLE) most commonly manifests as mild to moderate disease with severe manifestations such as diffuse alveolar hemorrhage, central nervous system vasculitis, macrophage activation syndrome (MAS) or retinal vasculitis (RV) with visual disturbances occurring in a significantly smaller proportion of patients, most of whom have a poor outcome. Macrophage activation syndrome and RV are insufficiently early and rarely recognized presentations of lupus-consequently there are still no treatment recommendations. Here we present the course of diagnosis and treatment of a patient with an SLE flare that resulted in both life-threatening disease (MAS) and vision-threatening disease (RV). The patient was successfully treated with systemic immunosuppressives, a high dose of glucocorticoids and rituximab (RTX), in parallel with intraocular therapy, intravitreal bevacizumab (BEV) and laser photocoagulation.

DRUG-INDUCED HYPERSENSITIVITY SYNDROME CAUSED BY LAMOTRIGINE, A CASE REPORT.

Drug reaction with eosinophilia and systemic symptoms (DRESS) syndrome, also known as drug-induced hypersensitivity syndrome (DIHS), is an under-recognized and potentially life-threatening hypersensitivity reaction associated with a variety of medications, many of them anti-epileptics. Patients with DRESS syndrome typically present with rash, swelling, fever, and systemic manifestations. We report a case of a patient admitted to out hospital after the administration of an anticonvulsive drug lamotrigine. She was presented with high fever, rash, face oedema and elevated liver enzymes. At admission, all previous medications were discontinued, systemic corticosteroid therapy was administered, and the patient was monitored for signs of clinical recovery. This case report suggests that in patients presenting with skin rash and systemic abnormalities after a recent change in medications, physicians should consider DRESS syndrome as a possible diagnosis and switch to a more aggressive therapy if removal of the offending agent does not result in clinical improvement. Early diagnosis can reduce the risk of complications and the mortality rate.

Preventive CCL2/CCR2 Axis Blockade Suppresses Osteoclast Activity in a Mouse Model of Rheumatoid Arthritis by Reducing Homing of CCR2hi Osteoclast Progenitors to the Affected Bone.

Detailed characterization of medullary and extramedullary reservoirs of osteoclast progenitors (OCPs) is required to understand the pathophysiology of increased periarticular and systemic bone resorption in arthritis. In this study, we focused on identifying the OCP population specifically induced by arthritis and the role of circulatory OCPs in inflammatory bone loss. In addition, we determined the relevant chemokine axis responsible for their migration, and targeted the attraction signal to reduce bone resorption in murine collagen-induced arthritis (CIA). OCPs were expanded in periarticular as well as circulatory compartment of arthritic mice, particularly the CCR2hi subset. This subset demonstrated enhanced osteoclastogenic activity in arthritis, whereas its migratory potential was susceptible to CCR2 blockade in vitro. Intravascular compartment of the periarticular area contained increased frequency of OCPs with the ability to home to the arthritic bone, as demonstrated in vivo by intravascular staining and adoptive transfer of splenic LysMcre/Ai9 tdTomato-expressing cells. Simultaneously, CCL2 levels were increased locally and systemically in arthritic mice. Mouse cohorts were treated with the small-molecule inhibitor (SMI) of CCR2 alone or in combination with methotrexate (MTX). Preventive CCR2/CCL2 axis blockade in vivo reduced bone resorption and OCP frequency, whereas combining with MTX treatment also decreased disease clinical score, number of active osteoclasts, and OCP differentiation potential. In conclusion, our study characterized the functional properties of two distinct OCP subsets in CIA, based on their CCR2 expression levels, implying that the CCR2hi circulatory-like subset is specifically induced by arthritis. Signaling through the CCL2/CCR2 axis contributes to OCP homing in the inflamed joints and to their increased osteoclastogenic potential. Therefore, addition of CCL2/CCR2 blockade early in the course of arthritis is a promising approach to reduce bone pathology.

FasL (rs763110) gene polymorphism is not associated with susceptibility to rheumatoid arthritis in Croatian population.

AIM: To investigate the association of FasL gene polymorphism (rs763110) with rheumatoid arthritis occurrence, disease activity, and tumor necrosis factor-α (TNF-α) plasma concentration in Croatian patients, and to conduct an updated meta-analysis. METHODS: This cross-sectional study enrolled 81 patients with rheumatoid arthritis and 94 control patients. After the assessment of the Disease Activity Score (DAS)-28, blood was taken for analysis. DNA was isolated from the whole blood to determine FasL polymorphism (rs763110) by polymerase chain reaction. Protein levels of TNF-α were determined with ELISA. After a detailed literature search, we conducted an updated meta-analysis using the Review Manager 5 software. RESULTS: Rheumatoid arthritis patients had significantly higher TNF-α concentration in plasma (1.65 [1.2-2.42] pg/mL) than controls (0.99 [0.77-1.35] pg/mL, P<0.001). The FasL rs763110 polymorphism was not associated with rheumatoid arthritis occurrence in either codominant, dominant, recessive, overdominant, or log additive model. Furthermore, the rs763110 genotype was not associated with DAS 28 score or TNF-α concentration. After we added our results to an updated meta-analysis, the significant association previously reported for Western Eurasians was abolished. CONCLUSION: Our data suggest that the association between FasL rs763110 polymorphism and RA susceptibility in Western Eurasians observed in previous studies might be overestimated and should be limited to the population of Southwestern Asia until further investigations are performed.

Combined manual and automated immunophenotypisation identified disease-specific peripheral blood immune subpopulations in rheumatoid arthritis, ankylosing spondylitis and psoriatic arthritis.

OBJECTIVES: Rheumatoid arthritis (RA), ankylosing spondylitis (AS) and psoriatic arthritis (PsA) are associated with abnormal immune cell functions. We combined manual and automated profiling in subpopulations of T-cells, B-cells and monocytes, in parallel to functional testing and clinical correlation. METHODS: Using flow cytometry, we analysed the expression of CCR4, CCR6 and CXCR5 on helper and cyotoxic T-cells, CD32B and CD86 on naïve and memory B-cells, and CCR1, CCR2, CCR4 and CXCR4 on monocytes in chronic high-disease activity patients to identify peripheral blood subpopulations. Cell activation, proliferative capability and osteoclastogenic effects were tested in vitro. Comparison with synovial compartment, clinical data and anti-TNF treatment were added to peripheral blood analysis. RESULTS: PsA had lower double-negative T-cell frequency, while RA had lower double-positive T-cell frequency and expanded Th1-like and cytotoxic T-cell subsets. CD32B expression was increased on naïve and memory B-cells in AS and associated with disease activity. CCR6+ and CXCR5+ cytotoxic T-cells and CD32B+ naïve and memory B-cells were highly enriched within the synovial compartment. T-cells and B-cells from AS exhibited enhanced activation and proliferation in vitro, whereas T-cell conditioned medium from RA produced an increased osteoclastogenic effect. CCR1 and CXCR4 were upregulated on osteoclastogenic monocyte subsets of RA, AS and PsA patients. Bioinformatic Citrus analysis identified additional T-cell, B-cell and monocyte clusters specifically associated with each disease. CONCLUSIONS: By combining manual and automated data analysis, our study revealed several disease-specific immune cell subpopulations, particularly cytotoxic T-cell subsets in RA and memory B-cell subsets in AS, which may serve as an indicator of active disease or possible therapeutic target.