Antiphospholipid syndrome, thrombosis, and vaccination in the COVID-19 pandemic.

Thrombosis is one of the many signs of antiphospholipid syndrome (APS) and COVID-19 infection. Although the mechanisms contributing to thrombosis in APS and COVID-19 are relatively similar, this remains an open subject. Even now (when the COVID-19 pandemic has subsided), there is no conclusive solution to APS and COVID-19 co-occurrence. The presence of newly generated antiphospholipid antibodies (aPLs) in COVID-19 infection may or may not be connected to the diagnosis of APS. The prevalence of aPLs is substantial in severe COVID-19 but not related to thrombosis or a worse outcome. Adequate monitoring of antibody positivity over time is recommended for APL diagnosis. On the other hand, thrombosis and thrombocytopenia can rarely occur with vaccination with mRNA vaccines. Some studies have shown that COVID-19 immunization is well tolerated among APS patients who are triple-positive for aPL, which may comfort patients and referring physicians and lessen hesitation in unvaccinated APS/aPL-positive patients. In this narrative review, we will give an overview of the interaction between aPL-APS-COVID-19-thrombosis and related diagnostic insights learned during the pandemic.

Rituximab as the first-line therapy in anti-synthetase syndrome-related interstitial lung disease.

Anti-synthetase syndrome (ASS) is an idiopathic inflammatory myopathy (IIM). In comparison to interstitial lung disease (ILD) in polymyositis and dermatomyositis (PM/DM), ILD in ASS is more frequent, has a more aggressive phenotype, a greater involvement of the lungs, and a more rapid onset of pulmonary symptoms. Continuous declines in predicted forced vital capacity (FVC) and dyspnea were the main features of patients who developed end-stage ILD. The severity of ASS at diagnosis dictates when and which immunosuppressant will be started. There is an experience for the usage of RTX in the first, second, and subsequent lines, as well as for reintroduction and salvage therapies. Not all ASS patients will develop severe illness and require intense immunosuppression. Some features associated with poor prognosis include older age, acute or subacute onset, lack of response to steroids, and lower baseline values for FVC and DLCO. Here we hypothesize that RTX should be the first line of treatment for high-risk ILD in ASS to preserve lung function and then maintenance therapy should be continued with the same or another drug depending on the recovery of lung function.

Anti-programmed death-1 inhibitor nivolumab-induced immune-related adverse events: hepatitis, renal insufficiency, myositis, vitiligo, and hypothyroidism: a case-based review.

Nivolumab (NIVO) is a monoclonal antibody used to treat renal cell cancer. It is an anti-programmed death-1 (anti-PD-1) inhibitor, enhancing the tumor-targeted immune response of T lymphocytes, resulting in immune-mediated adverse events (AEs). We present five immunological AEs in a single patient treated with NIVO. A 68-year-old male patient with metastatic renal cell carcinoma and right-sided nephrectomy received NIVO after pazopanib and sunitinib treatment. Two and a half months after starting NIVO, hepatocellular enzymes and creatinine were elevated. Concomitantly, the patient noticed hypopigmentation of the hand skin and a change in voice and speech. Due to hepatitis, he has been treated with dexamethasone 16 mg daily for 22 days, after which hypothyroidism and increased creatine kinase were found without muscle pain and functional impairment. Dexamethasone was continued, and a rapid decline in all parameters except thyroid-stimulating hormone (TSH) and vitiligo was observed. Myositis was initially considered a part of hypothyroidism and elevated renal parameters due to hypohydration. The rapid regression on glucocorticoid treatment and a longer time for creatinine normalization than expected with hydration were noticed. Nivolumab likely induced those side effects as assessed by Naranjo Adverse Drug Reaction Probability Scale. The literature review shows that the consequences of PD-1 inhibition are not uniform. Side effects of checkpoint inhibitors should be monitored carefully in the early and later treatment schedules evaluating subclinical manifestations like myositis and worsening of kidney parameters. Early administered higher doses of glucocorticoids can stop drug toxicity and reverse-induced tissue damage.

Treatment of rheumatoid arthritis with conventional, targeted and biological disease-modifying antirheumatic drugs in the setting of liver injury and non-alcoholic fatty liver disease.

Increased incidence of liver diseases emphasizes greater caution in prescribing antirheumatic drugs due to their hepatotoxicity. A transient elevation of transaminases to autoimmune hepatitis and acute liver failure has been described. For every 10 cases of alanine aminotransferase (ALT) elevation in a clinical trial, it is estimated that one case of more severe liver injury will develop once the investigated drug is widely available. Biologic disease-modifying antirheumatic drugs (bDMARDs) and targeted synthetic (tsDMARDs) are less likely to cause liver damage. However, various manifestations, from a transient elevation of transaminases to autoimmune hepatitis and acute liver failure, have been described. Research on non-alcoholic fatty liver disease (NAFLD) has provided insight into a pre-existing liver disease that may be worsen by medication. Diabetes and obesity could be an additional burden in drug-induced liver injury (DILI). In the intertwining of the inflammatory and metabolic pathways, the most important cytokines are IL-6 and TNF alpha, which are also the cornerstone of biological treatment for rheumatoid arthritis. This narrative review evaluates the complexity and prevention of DILI in RA and treatment options involving biological therapy and tsDMARDs.

Bone Phenotyping Approaches in Human, Mice and Zebrafish - Expert Overview of the EU Cost Action GEMSTONE ("GEnomics of MusculoSkeletal traits TranslatiOnal NEtwork").

A synoptic overview of scientific methods applied in bone and associated research fields across species has yet to be published. Experts from the EU Cost Action GEMSTONE ("GEnomics of MusculoSkeletal Traits translational Network") Working Group 2 present an overview of the routine techniques as well as clinical and research approaches employed to characterize bone phenotypes in humans and selected animal models (mice and zebrafish) of health and disease. The goal is consolidation of knowledge and a map for future research. This expert paper provides a comprehensive overview of state-of-the-art technologies to investigate bone properties in humans and animals - including their strengths and weaknesses. New research methodologies are outlined and future strategies are discussed to combine phenotypic with rapidly developing -omics data in order to advance musculoskeletal research and move towards "personalised medicine".

The multifactorial origin of posterior reversible encephalopathy syndrome in cyclophosphamide-treated lupus patients.

The cyclophosphamide as a predisposing factor for Posterior Reversible Encephalopathy Syndrome (PRES) and therapeutic option for systemic lupus erythematosus (SLE) is still confusing. The first and only case of PRES, probably induced by cyclophosphamide, in Croatia followed by the findings of 36 SLE patients diagnosed with PRES after treatment with cyclophosphamide worldwide are described. An 18-year-old Caucasian female patient with a 1-year history of SLE was admitted to the hospital due to lupus nephritis and acute arthritis. After the second dose of cyclophosphamide was administered, according to the Euro-lupus protocol, the patient presented with a grand mal status epilepticus. The differential diagnosis of neurolupus, cerebrovascular insult, and infection were excluded. The MRI findings showed brain changes in corresponding to PRES. The treatment consisted of antihypertensives, antiepileptics, antiedema therapy, mechanical ventilation, and avoiding further cyclophosphamide use. A Naranjo Adverse Drug Reaction Probability Scale total score of five and a probable reaction related to drug therapy (cyclophosphamide, PRES) was confirmed. In this systematic review, along with cyclophosphamide use, the main predisposing factors involved in PRES occurrence in SLE patients were active SLE and renal involvement. Due to the high number of simultaneously involved predisposing factors (max. six) and their overlapping effect, it is still not possible to clearly establish the role of every factor on PRES onset. The use of cyclophosphamide, as a contributing factor for PRES onset, should be carefully assessed, based on clinicians' experience and knowledge, in the setting of active SLE.

[Clinical manifestations, diagnosis and treatment of patients with temporal arteritis in Clinical Hospital Center Rijeka]. / Klinicka ocitovanja, dijagnoza i lijecenje pacijenata s temporalnim arteritisom u Klinickome bolnickom centru Rijeka.

Temporal arteritis is middle and large vessel vasculitis, that affects parts of carotid arteries. First symptoms are headache, weakness and tiredness. Later occur scalp sensitivity, lack of pulse and temporal nodes, visual disturbances, and claudications of jaw and limbs. Diagnosis is based on clinical symptoms, laboratory findings, and biopsy of the temporal artery. First choice for treatment are glucocorticoids. The aim of the study was to show the clinical characteristics, laboratory findings, treatment and its side effects in patients with temporal arteritis in KBC Rijeka, using retrospective analysis. During the analyzed period 18 patients with an average age of 73 years were treated. 100% of patients had headache as a symptom, 78% weakness, fatigue and fever, 61% scalp sensitivity, 56% vision problems, 39% claudication, 27% nodes in the field of temporal artery, and 23% dizziness. In 62% of patients the diagnosis was confirmed by biopsy of the temporal artery. The initial therapy for all patients were glucocorticoids. Steroid side effects occurred in 67% of treated.