Survival differences in rheumatoid arthritis interstitial lung disease and idiopathic pulmonary fibrosis may be explained by delays in presentation: results from multivariate analysis in a monocentric UK study.

Rheumatoid arthritis-associated interstitial lung disease (RA-ILD) has a better prognosis compared to idiopathic pulmonary fibrosis (IPF). Recent data suggest that antifibrotics are effective in slowing progression across both groups. Hence, we designed this study to investigate the similarities and differences between these groups of patients. This is a retrospective cohort study examining baseline data, progression and outcomes in patients with RA-ILD and IPF prior to antifibrotic use in the Coventry ILD database. Ethics approval was obtained from the University Hospital Coventry and Warwickshire NHS Trust. Statistical analysis was performed using R software and Cox's proportional hazards technique was used for survival analysis. We identified 131 cases, including 49 patients with IPF, 34 patients with RA-ILD and 48 patients with other forms of idiopathic interstitial pneumonia. At baseline, there were significant differences in the groups with RA-ILD patients being significantly younger (65.7 vs 72.4 years), had preserved lung volumes (FVC 95% vs 84.7%) and higher gas transfer (61.5% vs 48.2%) compared to IPF patients. 5-year survival was better for RA-ILD compared to IPF (87.5% vs 40.4%, p = 0.0042). Univariate analysis revealed gas transfer, FVC, age, sex and phenotype (IPF or RA-ILD) were all significant predictors, but multivariate analysis revealed that gas transfer and age were both significantly associated with prognosis, whereas sex, FVC or phenotype were not significant. This study suggests that the difference between RA-ILD and IPF prognosis may be due to demographics and early diagnosis rather than the diseases behaving differently. This has important management implications.

Four-factor risk score for the prediction of interstitial lung disease in rheumatoid arthritis.

OBJECTIVE: Interstitial lung disease (ILD) is one of the commonest systemic complications in patients with rheumatoid arthritis (RA) and carries a significant morbidity and mortality burden. We aimed to identify key variables to risk-stratify RA patients in order to identify those at increased risk of developing ILD. We propose a probability score based on the identification of these variables. METHODS: A retrospective, multicentre study using clinical data collected between 2010 and 2020, across 20 centres. RESULTS: A total of 430 RA (210 with ILD confirmed on high-resolution computed tomography (HRCT)) patients were evaluated. We explored several independent variables for the risk of developing ILD in RA and found that the key significant variables were smoking (past or present), older age and positive rheumatoid factor/anti-cyclic citrullinated peptide. Multivariate logistic regression models were used to form a scoring system for categorising patients into high and low risk on a scale of 0-9 points and a cut-off score of 5, based on the area under the receiver operating characteristic curve of 0.76 (CI 95% 0.71-0.82). This yielded a sensitivity of 86% and a specificity of 58%. High-risk patients should be considered for investigation with HRCT and monitored closely. CONCLUSION: We have proposed a new model for identifying RA patients at risk of developing ILD. This approach identified four simple clinical variables: age, anti-cyclic citrullinated peptide antibodies, Rheumatoid factor and smoking, which allowed development of a predictive scoring system for the presence of ILD in patients with RA.

Role of Temporal artery biopsy in a sequential Giant Cell Arteritis fast-track pathway: a 5-year prospective study.

BACKGROUND: Increasing number of centres are establishing sequential fast track pathways (FTP) for management of giant cell arteritis (GCA), with temporal artery ultrasound (US) replacing temporal artery biopsy (TAB) as the first investigational method. Biopsy is performed as second investigation, when US is negative/inconclusive. This study investigates the role of TAB in a sequential GCA-FTP and its utility in those with negative/inconclusive US. METHODS: Prospective study of patients referred for TAB as part of Coventry sequential GCA-FTP May 2014-June 2019. Analysis included sensitivity and specificity of TAB, impact of arterial specimen length and duration of treatment with corticosteroids on sensitivity of TAB and the clinical predictors for a positive biopsy. RESULTS: A total of 1149 patients with suspected GCA were referred to this GCA-FTP, with 109 (9.5%) referred for TAB. Overall sensitivity of TAB was 47% (specificity: 100%) and in patients with negative/inconclusive US sensitivity was 39% (specificity:100%). Post-fixation arterial specimen length <15 mm showed lower sensitivity (14%), which increased to 52% when specimen length was ≥15 mm. Sensitivity of TAB was highest in first 7 (60%) to 10 days (59%) from starting corticosteroids. Predictors of positive biopsy using univariate logistic regression analysis were jaw claudication (OR = 5.40; p = 0.0057), elevated erythrocyte sedimentation rate (OR = 5.50; p = 0.013) and elevated C-reactive protein (OR = 23.7; p = 0.0043). CONCLUSION: This is the first study to look at the role of TAB in a sequential GCA-FTP. Biopsy plays an important role in GCA-FTP, when US is negative/inconclusive. Sensitivity of TAB improved when specimen length was ≥15 mm and performed within 10 days of commencing corticosteroids.

Patient perceptions of co-morbidities in inflammatory arthritis.

OBJECTIVE: Longer life expectancy has resulted in people living with an increasing number of co-morbidities. The average individual with inflammatory arthritis has two co-morbidities, which contribute to higher mortality, poorer functional outcomes and increased health-care utilization and cost. A number of studies have investigated the prevalence of co-morbidities, whereas this study was designed to look at patient perspectives. METHODS: The study comprised two parts: a patient questionnaire and an interview. Individuals with physician-verified inflammatory arthritis along with one or more Charlson co-morbidities were invited to participate. In-depth data were obtained by interviews with 12 willing participants. RESULTS: One hundred and forty-six individuals were recruited; 50 (35%) had one co-morbidity, 69 (48%) had two and 25 (17%) had more than four co-morbidities. Seventy-seven individuals (53%) reported that co-morbidities affected their health as much as their arthritis, and 82 (56%) reported dependence on others for activities of daily living. Lack of education was highlighted by 106 (73%) participants. Qualitative data provided further support for the challenges, with participants highlighting the lack of time to discuss complex or multiple problems, with no-one coordinating their care. This, in turn, led to polypharmacy and insufficient discussion around drug and disease interactions, complications and self-help measures. CONCLUSION: This study highlights the challenges for individuals with inflammatory arthritis who suffer with multiple co-morbidities. The challenges result from limited resources or support within the current health-care environments. Individuals highlighted the poor quality of life, which is multifactorial, and the need for better educational strategies and coordination of care to improve outcomes.

Anti-tumour necrosis factor treatment for the prevention of ischaemic events in patients with deficiency of adenosine deaminase 2 (DADA2).

OBJECTIVE: To evaluate the impact of anti-Tumour Necrosis Factor-α (anti-TNF) treatment on the occurrence of vasculitic ischaemic events in patients with deficiency of adenosine deaminase 2 (DADA2). METHODS: A retrospective analysis of DADA2 patients referred from six centres to Great Ormond Street Hospital for Children was conducted. Ischaemic events, vasculitic disease activity, biochemical, immunological, and radiological features were compared, before and after anti-TNF treatment. RESULTS: A total of 31 patients with genetically confirmed DADA2 were included in the study. The median duration of active disease activity prior to anti-TNF treatment was 73 months (inter-quartile range [IQR] 27.5-133.5 months). Twenty seven/31 patients received anti-TNF treatment for a median of 32 months (IQR 12.0-71.5 months). The median event rate of central nervous system (CNS) and non-CNS ischemic events before anti-TNF treatment was 2.37 per 100 patient-months (IQR 1.25-3.63); compared with 0.00 per 100 patient-months (IQR 0.0-0.0) post-treatment (p< 0.0001). Paediatric vasculitis activity score (PVAS) was also significantly reduced: median score of 20/63 (IQR 13.0-25.8/63) pre-treatment vs. 2/63 (IQR 0.0-3.8/63) following anti-TNF treatment (p< 0.0001), with mild livedoid rash being the main persisting feature. Anti-TNF treatment was not effective for severe immunodeficiency or bone marrow failure, which required haematopoietic stem cell transplantation (HSCT). CONCLUSION: Anti-TNF treatment significantly reduced the incidence of ischaemic events and other vasculitic manifestations of DADA2, but was not effective for immunodeficiency or bone marrow failure.

Contrast CT Scan Evaluation of Incidence and Pattern of Thyroid Gland Involvement in Locally Advanced Ca Larynx Modifying the Need of Routine Thyroidectomy with Total Laryngectomy.

In locally advanced cases of carcinoma larynx, which are being treated with total laryngectomy, routine excision of the thyroid gland (either total or hemi section) is carried out. This study was carried out to evaluate the requirement of routine thyroidectomise with total laryngectomy. An analysis of the final histology of 83 patients, who underwent the traditional treatment, together with the preoperative contrast enhanced CT scan was carried out. Among 58 cases of T3 carcinoma larynx 2 revealed thyroid involvement by metastasis (3.45%), 1 of them was suspected in preoperative CT and confirmed by FNAC. Among 25 cases of T4a carcinoma larynx 6 revealed thyroid involvement by direct extension (24%) with evidence of same in preoperative CT. Risk of thyroid involvement is low in T3 cases (3.45%) and is by metastasis. Risk of thyroid involvement is higher in T4a cases (24%) and is by direct extension. Preoperative CECT is a good tool to predict thyroid gland involvement either by metastasis or by direct spread. This study thus raises doubts about the requirement of routine thyroidectomise in association with total laryngectomies in advanced carcinoma larynx. We thus believe that further investigations, on a larger scale and multi-institutional, is warranted.

Changing trends in mortality in systemic lupus erythematosus? An analysis of SLE inpatient mortality at University Hospital Coventry and Warwickshire NHS Trust from 2007 to 2016.

The aim of this study was to determine the causes of mortality in patients with systemic lupus erythematosus (SLE) at the University Hospital Coventry and Warwickshire (UHCW) NHS Trust over a 10 year period. This was a retrospective study of patients who had died in UHCW NHS Trust between 2007 and 2016, where SLE or lupus was mentioned on the death certificate. Ethics approval was obtained from the Research and Development. We identified 22 patients out of 1979 admissions with SLE who had died during the period between 2007 and 2016, 7 of these patients were under 50 years of age. The leading cause of death was infection with pneumococcus being associated with two deaths. Active disease was associated with younger age at death. Median age at death was 58.5 years, with median duration of disease of 14.5 years. Constitutional and mucocutaneous features were the most common items scoring on disease activity, seen in 68.2% and 45.45%, respectively. We identified three patients with biopsy proven lupus nephritis and one patient with CNS lupus. Surprisingly, none of the patients died because of vascular problems. The study suggests a changing trend in SLE mortality with none of the deaths in this cohort being due to cardiovascular or cerebrovascular disease. Infection continues to be the biggest reason for mortality in this cohort and greater emphasis is needed on vaccination for preventable infections like pneumococcus.

Lymphoproliferative disorder due to sulphasalazine.

We present the case of a 57-year-old man who had been on sulphasalazine for 20 years for seropositive non-erosive rheumatoid arthritis and developed a lymphoproliferative disorder, which resolved completely on cessation of sulphasalazine. This is the first report of lymphoproliferative disorder secondary to sulphasalazine. Lymphoproliferative disorders are well recognised with methotrexate and cyclosporine, and recognition of this disorder is critical due to the fact that a number of patients' symptoms will resolve completely with discontinuation of the drug and will not need further treatment. This case report discusses the literature on lymphoproliferative disorders as well as differential diagnoses like drug rash with eosinophilia and systemic symptoms (DRESS) syndrome.

C-ANCA positive systemic vasculitis in a patient with rheumatoid arthritis treated with infliximab.

The advent of anti-tumour necrosis factor (TNF) agents to treat inflammatory arthritis has dramatically changed the management of patients in the last few years. Other possible indications for these agents are currently being explored in preliminary studies. However, whether this therapy can be safely and efficaciously applied to other inflammatory disorders requires further case-controlled studies. Since these agents are increasingly used in the last 7 years, there has been the expected emergence of reports on uncommon side effects. The literature on the side effects of anti-TNF agents has focused on infective complications and development of autoantibodies. Reports concerning vasculitis have been contradictory, with TNF blockade being implicated in both the development and treatment of vasculitis. We present the first published report of necrotising crescentic glomerulonephritis associated with positive antineutrophil cytoplasmic antibody in a man receiving treatment with infliximab for rheumatoid arthritis. We discuss the literature and potential causal mechanisms.