Examining the safety of relaxed drug monitoring for methotrexate in response to the COVID-19 pandemic.

Objectives: This is a retrospective study that set out to assess the safety, feasibility and cost savings of temporary relaxed blood test monitoring for patients on MTX under the rheumatology service that was rolled out during the coronavirus pandemic. Methods: This is a single-centre study that reviewed the blood tests of all patients who received an MTX prescription from the trust between December 2019 and November 2020. After the application of inclusion and exclusion criteria, the blood testing intervals and findings were analysed and collated. The cost of the blood tests was obtained from the laboratory. Results: A total of 1194 patients were identified as having received an MTX prescription. After applying inclusion and exclusion criteria, 462 patients were included. Of these, 395 (85%) patients had a blood test within the standard 3-month schedule and 67 had blood tests within the relaxed blood monitoring schedule. Six patients had an abnormality identified on their blood tests, but no harm was caused by any of these abnormalities. The intervention resulted in a cost savings of at least £1187 from the blood test costs alone. Conclusion: MTX is a widely used steroid-sparing agent that requires regular blood test monitoring to reduce adverse outcomes for patients. During extraordinary circumstances such as a pandemic, relaxing the interval between monitoring blood tests in stable patients is a feasible intervention. A relaxed monitoring blood test interval for a set period is safe, achievable and cost effective.

Inflammatory myopathy occurring shortly after severe acute respiratory syndrome coronavirus 2 vaccination: two case reports.

BACKGROUND: Vaccination remains the cornerstone approach to exiting the current global coronavirus disease 2019 pandemic caused by severe acute respiratory syndrome coronavirus 2. The novel messenger ribonucleic acid vaccines offer a high level of protection and are widely used throughout the world. With more people receiving the vaccines, better understanding of their relative safety can be reached. In this report, we describe two patients who developed inflammatory myopathy within 48 hours of receiving the Pfizer BNT162b2 vaccine. CASE PRESENTATION: Patient A, a 55-year-old South East Asian woman, presented with a 6-week history of pruritic facial and torso rash and a 1-week history of worsening proximal myopathy. Her rash first developed 2 days after receiving the first dose of BNT162b2 vaccine. Patient B, a 72-year-old Caucasian woman, presented with a 2-week history of proximal myopathy a day after receiving the second dose of BNT162b2 vaccine. Both patients had elevated creatine kinase on admission. Patient A tested positive for anti-Mi-2a antibody and anti-Ro-52 antibody, while Patient B was positive for anti-fibrillarin antibody. Magnetic resonance imaging subsequently confirmed generalized acute muscle inflammation and subcutaneous inflammation consistent with inflammatory myositis. Both patients did not have a previous history or family history of autoimmune disease. Patients A and B were diagnosed with dermatomyositis and inflammatory myositis, respectively. They were initially treated with pulsed intravenous methylprednisolone followed by oral prednisolone. However, as their conditions were resistant to corticosteroids, both eventually received and responded well to intravenous immunoglobulin therapy. CONCLUSION: There are previously reported cases of severe acute respiratory syndrome coronavirus 2-induced and other vaccine-related inflammatory myopathies. However, the precise mechanisms are not elucidated. Without more evidence and convincing pathophysiology, it is not possible to conclude that our patients developed inflammatory myopathy because of the vaccine. However, the timing of the disease onset and the lack of previous history raise an important question of this novel messenger ribonucleic acid therapy.

Cutaneous Polyarteritis Nodosa Presenting Atypically with Severe Pharyngeal Ulceration.

Polyarteritis nodosa (PAN) is a multisystem, necrotising vasculitis of small- and medium-sized arteries with a predilection for the visceral vessels. Cutaneous PAN is a rare variant with symptomatic vasculitis limited to the skin, typically presenting as nodular lesions on the extremities with a propensity to ulcerate. We describe a rare case of histologically confirmed cutaneous PAN presenting in a 55-year-old Ghanaian woman with severe oropharyngeal ulceration. This was associated with dysphagia and significant weight loss. Oesophagoduodenoscopy showed that the ulceration extended throughout the oropharynx. Systemic polyarteritis nodosa was ruled out with magnetic resonance angiography. Our patient was treated successfully with corticosteroids and methotrexate. This case suggests that cutaneous PAN should be considered in the differential diagnosis of patients with oropharyngeal ulceration and that histological assessment is pivotal in establishing the diagnosis early in order to instigate appropriate therapy.

A case of IgG4oligoarthritis mimicking psoriatic arthritis.

IgG4-related disease (IgG4-RD) is a rare but rapidly emerging immune-mediated fibroinflammatory condition that can affect almost any organ. It is typically associated with involvement of organs such as lymph nodes, submandibular glands, orbits, periaortic region and pancreas. However, IgG4-RD presenting primarily as an inflammatory arthritis is much less recognised. We present a rare case of IgG4-RD mimicking psoriatic arthritis. In spite of normal circulating IgG4 plasma levels, a clinical index of suspicion was required to obtain a histopathological diagnosis. The patient's aggressive arthritis disease did not initially respond to typical disease- modifying agents such as methotrexate. Instead, we report a dramatic response to B cell depletion with rituximab. It is important to emphasise this case as a rare presentation of a rare disease. IgG4-RD is a rapidly emerging condition and the diagnosis should be considered when the alternatives do not seem to fit.

Tocilizumab in refractory rheumatoid arthritis: long-term efficacy, safety, and tolerability beyond 2 years.

OBJECTIVES: To evaluate the long-term efficacy and safety of tocilizumab (TCZ) in clinical patients with rheumatoid arthritis (RA) refractory to synthetic disease-modifying antirheumatic drugs, anti-tumor necrosis factor agents, and B-cell depletion therapy with rituximab (RTX). METHODS: We conducted a single-center retrospective study of 22 patients with RA treated with TCZ. We collected data including demographics and medication histories. We recorded clinical parameters including tender joint counts and swollen joint counts, and laboratory parameters including inflammatory makers and lipid profiles over regular intervals of TCZ treatment. RESULTS: In all, 22 patients with RA were included, 20 of whom were female. The median age at the first dose of TCZ was 62 years (range: 35-75 years). The mean duration of the disease from diagnosis with RA to May 2015 was 15.7 years (range: 6-30 years). A total of 15 out of 22 patients remained on TCZ at the end of the study, and in all, there was an improvement in markers of disease activity following initiating TCZ. The effect was sustained for a mean of 35 months (SD±15.5 months, range: 9-72 months). Of the 17 patients who failed to respond to RTX previously, 12 patients remained on TCZ. In all, eight out of 22 patients developed adverse events, five of whom discontinued TCZ. In contrast to previously documented short-term data, TCZ did not result in a statistically significant (P<0.05) long-term deterioration in lipid profile for any of the lipid parameters measured in our cohort (mean ± SD at initiation of TCZ to most recent follow-up: total cholesterol 5.25±1.05 to 5.28±0.77 mmol/L, high-density lipoprotein 1.72±0.54 to 1.67±0.43 mmol/L, low-density lipoprotein 3.05±0.98 to 2.98±0.81 mmol/L, and cholesterol to high-density lipoprotein ratio 3.41±1.23 to 3.40±1.22). CONCLUSION: The efficacy of TCZ in patients with RA refractory to disease-modifying drugs, including anti-tumor necrosis factor blockade and RTX, is sustained over 3 years. TCZ confers a good safety profile in the long term even in patients who previously developed adverse events to other rheumatic drugs. In the long run, there is no statistically significant deterioration in lipid profile during treatment with TCZ.

Regulation of mitochondrial structure and function by the F1Fo-ATPase inhibitor protein, IF1.

When mitochondrial respiration is compromised, the F(1)F(o)-ATP synthase reverses and consumes ATP, serving to maintain the mitochondrial membrane potential (Delta psi(m)). This process is mitigated by IF(1). As little is known of the cell biology of IF(1), we have investigated the functional consequences of varying IF(1) expression. We report that, (1) during inhibition of respiration, IF(1) conserves ATP at the expense of Delta psi(m); (2) overexpression of IF(1) is protective against ischemic injury; (3) relative IF(1) expression level varies between tissues and cell types and dictates the response to inhibition of mitochondrial respiration; (4) the density of mitochondrial cristae is increased by IF(1) overexpression and decreased by IF(1) suppression; and (5) IF(1) overexpression increases the formation of dimeric ATP synthase complexes and increases F(1)F(o)-ATP synthase activity. Thus, IF(1) regulates mitochondrial function and structure under both physiological and pathological conditions.