Two challenging cases of anti-MDA-5 dermatomyositis with rapidly progressive interstitial lung disease.

Anti-MDA-5 dermatomyositis (DM) is a subtype of idiopathic inflammatory myopathy, commonly presenting as clinically amyopathic dermatomyositis. It is associated with rapidly progressive interstitial lung disease and a poor prognosis. Here, we present two cases of anti-MDA-5 DM and discuss the challenges associated with timely diagnosis, and the importance of early and aggressive treatment.

Assessing the effects of distinct biologic therapies on rheumatoid arthritis pain by nociceptive, neuropathic and nociplastic pain components: a randomised feasibility study.

BACKGROUND: Pain management is a major unmet need in people with rheumatoid arthritis (RA). Although many patients are treated with disease modifying anti-rheumatic drugs (DMARDS), including biologic therapies, many people with RA continue to experience significant pain. We aimed to determine whether performing a comprehensive pain evaluation is feasible in people with active RA receiving conventional DMARDs and biologic therapies. METHODS: The BIORA-PAIN feasibility study was an open-label, randomised trial, which recruited participants suitable for treatment with biologic therapy. The primary feasibility outcomes were recruitment, randomisation and retention of eligible participants. All participants underwent pain assessment for nociceptive, neuropathic and nociplastic pain during the 12-month study period, with quarterly assessments for VAS (Visual Analogue Scale) pain, painDETECT and QST (quantitative sensory testing). This trial was registered in clinicaltrials.gov NCT04255134. RESULTS: During the study period, 93 participants were screened of whom 25 were eligible: 13 were randomised to adalimumab and 12 to abatacept. Participant recruitment was lower than expected due to the COVID-19 pandemic. Pain assessments were practical in the clinical trial setting. An improvement was observed for VAS pain from baseline over 12 months, with a mean (SEM) of 3.7 (0.82) in the abatacept group and 2.3 (1.1) in the adalimumab group. There was a reduction in painDETECT and improvement in QST measures in both treatment groups during the study. Participant feedback included that some of the questionnaire-based pain assessments were lengthy and overlapped in their content. Adverse events were similar in both groups. There was one death due to COVID-19. CONCLUSIONS: This first-ever feasibility study of a randomised controlled trial assessing distinct modalities of pain in RA met its progression criteria. This study demonstrates that it is feasible to recruit and assess participants with active RA for specific modalities of pain, including nociceptive, neuropathic and nociplastic elements. Our data suggests that it is possible to stratify people for RA based on pain features. The differences in pain outcomes between abatacept and adalimumab treated groups warrant further investigation. TRIAL REGISTRATION: NCT04255134, Registered on Feb 5, 2020.

Treatment of gangrenous digit-threatening paraneoplastic acrocyanosis with vasodilator therapy.

A man in his 70s, with a recent diagnosis of transitional cell carcinoma of the bladder, reported a 2-month history of discolouration, pain and paraesthesia affecting his fingers. Clinical assessment noted peripheral acrocyanosis with areas of digital ulceration and gangrene. Following further work-up to evaluate potential causes, he was diagnosed with paraneoplastic acrocyanosis. He proceeded to undergo robotic cystoprostatectomy and received adjuvant chemotherapy for the management of his cancer. In parallel to the chemotherapy, vasodilatory therapy was administered as two courses of intravenous synthetic prostacyclin analogue iloprost along with sildenafil. This resulted in a significant improvement in digital pain and gangrene with healing of ulceration.

Lingual Raynaud's phenomenon: a rare presentation.

A woman in her mid-60s presented to transient ischaemic attack (TIA) clinic with a 3-year history of intermittent sensory changes and white discolouration affecting the left side of her tongue. Following extensive investigation, a provisional diagnosis of posterior circulation TIA was made, and the patient was commenced on clopidogrel therapy. Despite anti-platelet treatment, she continued to have identical episodic symptoms. She was referred to the rheumatology team for assessment of possible underlying autoimmune pathology. On rheumatology assessment, the patient reported colour changes on the tongue, associated with numbness, followed by paraesthesia of the affected area. A comprehensive assessment excluded secondary causes and a diagnosis of primary Raynaud's phenomenon of the tongue was made. The diagnosis of TIA was revoked. This case illustrates a rare presentation of a common condition and highlights the sensory symptoms which are associated with Raynaud's phenomenon.

The Utility of Myositis Specific Antibodies in Clinical Practice.

BACKGROUND: Fifteen myositis-specific antibodies have been described and characterized over the past 40 years. Approximately two thirds of patients with idiopathic inflammatory myositis have a myositis-specific antibody and only rarely more than one. Assays to detect them are now widely available within clinical practice. CONTENT: We describe the original description and clinical phenotype of the myositis-specific antibodies, forming the antisynthetase syndrome group, anti-MDA-5 and rapidly progressive interstitial lung disease, anti-SRP/HMGCR and necrotizing myositis, anti-TIF-1γ/NXP-2 and malignancy, anti-SAE and esophageal disease, and anti-Mi-2 and classic dermatomyositis skin disease. SUMMARY: Clinical practice is likely to be refined, with diagnosis and classification of the idiopathic inflammatory myositides based primarily on myositis-specific antibody, rather than directed by muscle histology or the broader clinical characteristics of polymyositis and dermatomyositis. All patients newly presenting with idiopathic inflammatory myositis should be routinely screened for myositis-specific antibodies. A positive result will usefully provide diagnostic and prognostic information, guide selection of therapy, and prompt surveillance for potential organ involvement and other features, such as cancer, throughout the disease course.

Lack of Effect of Propranolol on the Reconsolidation of Conditioned Fear Memory due to a Failure to Engage Memory Destabilisation.

The prospect of exploiting memory reconsolidation to treat mental health disorders has received great research interest, particularly following demonstrations that the ß-adrenergic receptor antagonist propranolol, which is safe for use in humans, can disrupt the reconsolidation of pavlovian conditioned fear memories. However, recent studies have failed to replicate the effects of propranolol on fear memory reconsolidation, and have questioned whether treatments based upon reconsolidation blockade would be robust enough for clinical translation. It remains possible, though, that studies reporting no effect of propranolol on memory reconsolidation could be due to a failure to engage the memory destabilisation process, which is necessary for the memory to become susceptible to disruption with amnestic agents. Demonstrating that memory destabilisation has not been engaged is challenging when only using behavioural measures, but there are molecular correlates of memory destabilisation that can be used to determine whether memory lability has been induced. Here, we attempted to replicate the classic finding that systemic administration of propranolol disrupts the reconsolidation of a pavlovian auditory fear memory. Following a failure to replicate, we manipulated the parameters of the memory reactivation session to enhance prediction error in an attempt to overcome the boundary conditions of reconsolidation. On finding no disruption of memory despite these manipulations, we examined the expression of the post-synaptic density protein Shank in the basolateral amygdala. Degradation of Shank has been shown to correlate with the induction of memory lability, but we found no effect on Shank expression, consistent with the lack of observed behavioural effects.

Post-Transplantation Diabetes Mellitus.

Solid organ transplantation (SOT) is an established therapeutic option for chronic disease resulting from end-stage organ dysfunction. Long-term use of immunosuppression is associated with post-transplantation diabetes mellitus (PTDM), placing patients at increased risk of infections, cardiovascular disease and mortality. The incidence rates for PTDM have varied from 10 to 40% between different studies. Diagnostic criteria have evolved over the years, as a greater understating of PTDM has been reached. There are differences in pathophysiology and clinical course of type 2 diabetes and PTDM. Hence, managing this condition can be a challenge for a diabetes physician, as there are several factors to consider when tailoring therapy for post-transplant patients to achieve better glycaemic as well as long-term transplant outcomes. This article is a detailed review of PTDM, examining the pathogenesis, diagnostic criteria and management in light of the current evidence. The therapeutic options are discussed in the context of their safety and potential drug-drug interactions with immunosuppressive agents.