Australian rheumatologists' perception of autologous haemopoietic stem cell transplantation for the treatment of systemic sclerosis: a cross-sectional survey.

BACKGROUND: Autologous haemopoietic stem cell transplantation (AHSCT) is an effective treatment for systemic sclerosis (SSc); however, treatment-related toxicity remains a key issue. AIMS: To investigate the perceptions of rheumatologists on the use of AHSCT for SSc. METHODS: Australian rheumatologists were asked for their opinion on the role of AHSCT, the indications for treatment and the barriers to the use of AHSCT for SSc. A secondary analysis assessed what factors influenced the perception of AHSCT. RESULTS: A total of 77.8% rheumatologists agreed or strongly agreed with the statement that AHSCT is an accepted treatment for SSc. While 65.1% agreed or strongly agreed that treatment-associated mortality was a significant barrier to referral for AHSCT, only 15.2% agreed or strongly agreed that this risk was unacceptable. Progressive lung or skin disease, or lack of response to other therapies, were considered the main referral criteria. A total of 92.0% of respondents agreed or strongly agreed that reduction of treatment toxicity would increase their likelihood to refer patients for AHSCT. Rheumatologists who were aware of the correct evidence base were more likely to consider AHSCT an acceptable treatment for SSc (4.21 ± 0.7 vs 3.64 ± 0.9, P = 0.007). Rheumatologists desire improved patient selection criteria and access to treatment. CONCLUSION: In this national survey of rheumatologists, AHSCT is considered an accepted therapy. However, concern about toxicity remains a potential barrier to patient referral. Access, studies to refine patient selection and development of AHSCT protocols that improve safety were identified as key areas of need.

Cardiotoxicity in autologous haematopoietic stem cell transplantation for systemic sclerosis.

Autologous haematopoietic stem cell transplantation is now well-established as an effective treatment for severe systemic sclerosis with clear demonstration of favourable end-organ and survival outcomes. Treatment-related cardiotoxicity remains the predominant safety concern and contraindicates autologous haematopoietic stem cell transplantation in patients with severe cardiopulmonary disease. In this review, we describe the cardiovascular outcomes of autologous haematopoietic stem cell transplantation recipients, discuss the potential mechanisms of cardiotoxicity and propose future mitigating strategies.

A mitochondrial cytopathy presenting with persistent troponin elevation: case report.

Background: Mitochondrial diseases represent an important potential cause of cardiomyopathy and should be considered in patients presenting with multisystem manifestations. Timely diagnosis of a mitochondrial disorder is needed as it can have reproductive implications for the offspring of the proband. Case Summary: We describe a case of undifferentiated rising and persistent troponin elevation in a 70-year-old female with only mild heart failure symptoms and signs. An eventual diagnosis of a mitochondrial cytopathy was made after genetic testing, striated muscle, and endomyocardial biopsy. Multidisciplinary involvement was vital in securing the ultimate diagnosis and is a key lesson from this case. On follow up, with institution of heart failure therapy including cardiac resynchronisation device therapy there was improvement in exercise tolerance and symptoms. Discussion: For discussion is the investigation of undifferentiated cardiomyopathies and consideration of mitochondrial disorders as an important diagnosis to exclude prior to diagnosis as an idiopathic cardiomyopathy.

Disseminated Mycobacterium chelonae infection complicating rheumatoid arthritis: A case report and review of the literature.

INTRODUCTION: Rheumatoid arthritis (RA) may predispose patients to opportunistic infections-either from innate immune dysregulation, or as a result of immunosuppressant use to treat the RA. Particularly concerning opportunistic infections are those caused by non-tuberculous mycobacterial (NTM) organisms, the incidence of which has been increasing in epidemiological studies. Despite this, guidelines on the management of patients with RA who develop NTM infections are scarce, particularly with respect to immunosuppressant regimen modulation and duration of antibiotic therapy. CASE REPORT: Herein, we present a case of disseminated Mycobacterium chelonae infection, manifesting as arthralgia and cutaneous nodules. DISCUSSION: In addition, a review of the literature was conducted to Preferred Reporting Items for Systemic Reviews and Meta-Analyses guidelines to identify similar cases in the literature-revealing that all RA-associated M. Chelonae infections occurred in immunosuppressed patients (the majority with corticosteroids or tumor necrosis factor inhibitors), and considerable heterogeneity in management approaches. Further research regarding risk factors, preventative approaches and best management of such NTM infections in vulnerable patients with RA is required in order to establish consensus guidelines and consistency.

Effect of Therapeutic Plasma Exchange on Itraconazole Pharmacokinetics: A Case Study.

ABSTRACT: The authors present the case of a 34-year-old male patient who underwent therapeutic plasma exchange (TPE) for amyopathic dermatomyositis. Immunosuppression resulted in Aspergillus lentulus pulmonary infection , requiring treatment with super bioavailable-itraconazole. Therapeutic itraconazole concentrations were attained after 2 weeks of treatment after dose adjustments. Interestingly, a substantial reduction in plasma itraconazole concentration was observed during TPE, which was attributed to an insufficient delay between the dosing of itraconazole and TPE initiation. Furthermore, there was an increase in plasma concentration post-TPE, which presumably reflects the redistribution of itraconazole from peripheral compartments back into plasma. This was confirmed by sampling of the TPE plasmapheresate, which revealed that changes in plasma concentration overestimated itraconazole clearance. These findings highlight that the pharmacokinetics of itraconazole are altered during TPE, which should be considered when timing drug administration and obtaining plasma concentrations.

Voriconazole-Associated Periostitis: New Insights into Pathophysiology and Management.

Voriconazole-associated periostitis (VAP) is an underrecognized and unpredictable side effect of long-term voriconazole therapy. We report two cases of VAP occurring in the post-transplant setting: a 68-year-old lung transplant recipient who required ongoing voriconazole therapy, in whom urinary alkalinization was used to promote fluoride excretion and minimize voriconazole-related skeletal toxicity, and a 68-year-old stem-cell transplant recipient with a high voriconazole dose requirement, identified on pharmacogenomic testing to be a CYP2C19 ultrarapid metabolizer, the dominant enzyme in voriconazole metabolism. This is the first reported case of pharmacogenomic profiling in VAP and may explain the variability in individual susceptibility to this uncommon adverse effect. Our findings provide new insights into both the management and underlying pathophysiology of VAP. © 2021 The Authors. JBMR Plus published by Wiley Periodicals LLC on behalf of American Society for Bone and Mineral Research.

Assessing the role for nailfold videocapillaroscopy in interstitial lung disease classfication: a systematic review and meta-analysis.

OBJECTIVES: The nailfold videocapillaroscopy (NVC) has been known to assist with interstitial lung disease (ILD) classification. However, evidence on its diagnostic efficacy is limited, particularly in some connective tissue disease-related interstitial lung diseases (CTD-ILD), and in interstitial pneumonia with autoimmune features (IPAF). This study aimed to address this limitation by conducting a meta-analysis on the efficacy of the NVC in ILD subgroups of CTD-ILD, IPAF and idiopathic pulmonary fibrosis (IPF). METHODS: MEDLINE, EMBASE, CENTRAL were screened from inception to December 2020 according to Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines. Studies that report prevalence of nailfold abnormalities (NVC+) in CTD-ILD, IPAF and IPF cohorts were included. Data were presented as prevalence ratio (PR) with 95% CI using a random-effects model. Quality of evidence was assessed using GRADE criteria. RESULTS: Twenty-one studies were eligible. Prevalence of NVC+ was highest in CTD-ILD; PR (95 CI%) 80.4% (74.3%, 85.3%), followed by IPAF; 27.4% (10.9%, 53.7%), and IPF; 13.8% (5.7%, 29.9%). Late scleroderma pattern was the most prevalent nailfold pattern; 40.4% (28.1%, 54.1%) in our CTD-ILD cohort. Quality of evidence was low for CTD-ILD, IPAF and IPF cohorts, moderate for the late scleroderma pattern cohort. CONCLUSION: NVC can increase the diagnostic accuracy of ILD when used in a multi-disciplinary setting, and appears to have greatest utility in CTD-ILD, followed by IPAF and IPF. The Late Scleroderma Pattern was the most frequent nailfold capillary pattern in SSc-ILD. Future research will allow for greater understanding of the prognostic value of the NVC in ILD.

Eosinophilic annular erythema: a subset of Wells' syndrome or a distinct entity?

A 52-year-old woman with a 6-year history of a persistent non-pruritic cutaneous annular eruption, forming polycyclic and arcuate plaques that commenced as erythematous papules and nodules, is presented. Lethargy and arthralgia were associated symptoms. We have followed this patient for the last 3 years, and during this period she has continued to have a florid annular eruption of unknown cause. Laboratory tests, including an eosinophil count, examination of stool samples for parasites, and a computed tomography scan of the chest, abdomen and pelvis, failed to detect any abnormalities. Skin biopsies demonstrated a superficial to deep cellular infiltrate consisting of numerous eosinophils, with lymphocytes and isolated neutrophils. Eosinophilic dust, flame figures and granulomatous inflammation were not seen. In addition, strands of mucin were present through the dermis, and prominent basal vacuolar change was evident at the dermoepidermal junction; these features may represent new findings that help define a distinct form of eosinophilic annular erythema.

Clinical use of anti-TNF-alpha biological agents--a guide for GPs.

BACKGROUND: Tumour necrosis factor-alpha (TNF-alpha) inhibitors are a new class of injectable drugs, under the umbrella term 'biological agents', now available for the treatment of rheumatoid arthritis and other chronic inflammatory conditions including juvenile idiopathic arthritis, Crohn disease, psoriasis and psoriatic arthritis. OBJECTIVE: The aim of this review is to provide an overview of TNF-alpha inhibitors and highlight the key practical issues of relevance to general practitioners. DISCUSSION: TNF-alpha inhibitors may have a potent effect in reducing inflammation and possibly inducing remission where conventional disease modifying drugs have failed to do so. These drugs are associated with an increased risk of infection as well as other potentially serious side effects. Their use is restricted to the relevant specialist prescribing the drug and are only available on the Pharmaceutical Benefits Scheme under strict prescribing criteria. The role of the GP is critical in identifying patients suitable for referral to consider commencing treatment and in monitoring patients on long term therapy.