Julie Dawson

Rheumatoid arthritis-related interstitial lung disease: associations, prognostic factors and physiological and radiological characteristics—a large multicentre UK study

OBJECTIVES The prevalence of interstitial lung disease (ILD) in RA is ∼5%. Previous work identified increasing age, active articular disease and articular damage as risk factors for RA-associated ILD (RA-ILD). The roles of high-resolution CT (HRCT) and lung function testing in defining the nature and extent of pulmonary involvement have recently been explored. This study is the first to examine predictive and prognostic factors for the development of RA-ILD and to report on the physiological and radiological characteristics of the condition from a large multicentre UK network. METHODS We collected data from centres across the UK on patients with both RA and ILD (proved on HRCT) diagnosed over a 25-year period from 1987 to 2012 using a standard pro forma. Potential predictors of RA-ILD were analysed. Baseline lung function data were recorded and related to HRCT findings. We analysed HRCT for subtype and extent of lung involved and examined the relationship between these and both all-cause and pulmonary mortality. We compared our results with case controls matched for age and gender using computer-generated selection from the RA population from one contributing centre. RESULTS A total of 230 patients were identified from across the UK with proven RA-ILD diagnosed over 25 years. Median age at diagnosis was 64 years and the male:female ratio was 1:1.09. Univariate analysis showed anti-CCP antibody titres to be the single most strongly associated predictor of RA-ILD. Male gender, age at onset, smoking and RF were all independently associated with RA-ILD on multivariate analysis. Vital capacity (VC) was preserved in limited disease but reduced in extensive disease, while gas transfer was reduced in both. Usual interstitial pneumonia (UIP) was the most common subtype on HRCT and both this and extensive disease were associated with increased all-cause mortality. CONCLUSION This is the largest study of RA-ILD in the UK. Anti-CCP antibodies were strongly associated with RA-ILD in both sexes. Smoking was strongly associated with ILD in males, which may explain the higher frequency of RA-ILD in men. The predominant HRCT pattern was UIP and most patients had limited disease at presentation. The presence of UIP and extensive disease are associated with increased mortality. Baseline gas transfer is a useful screening tool for ILD, while the preservation of VC at baseline might predict limited disease on HRCT.

Methotrexate Induced Pneumonitis: A Review Article

Abstract: Low dose methotrexate (MTX) is used frequently in a wide variety of conditions. This includes rheumatologi-cal conditions such as rheumatoid arthritis (RA) and non-rheumatological conditions such as inflammatory bowel disease. One of the most serious although infrequent side effects of low dose MTX is MTX induced pneumonitis (MTX-P). The latest literature on epidemiology, risk factors, pathophysiology and clinical features of MTX-P will be critically reviewed and highlighted. This review will pay special attention to diagnostic criteria, high resolution computerised tomography (HRCT) scan findings, and when to consider bronchoalveolar lavage (BAL) and lung biopsy. We propose the 2008 diag-nostic criteria adapted from existing criteria. We will also discuss the new issue of interstitial lung disease (ILD) in pa-tients receiving both methotrexate and anti-TNF therapy. Keywords: Methotrexate, interstitial lung disease, pneumonitis, chest high resolution computed tomography (HRCT), diagnos-tic criteria, tumour necrosis factor (TNF).

Methotrexate-induced pancytopenia associated with co-prescription of penicillin and trimethoprim

Dear Editor, We read Singh et al.’s [1] brief report on methotrexate induced pancytopenia with great interest. They summarized other studies where renal dysfunction, hypoalbuminemia, folate deficiency, advanced age, concomitant infection, lack of folate supplementation, and concomitant use of more than five drugs were predisposing factors for developing pancytopenia. Their own study revealed hypoalbuminemia, raised transaminase levels, recent increase in methotrexate dose, and poor primary care physician and patient knowledge of methotrexate usage as predisposing factors. No mention was made of the risks associated with co-prescription of penicillins and trimethoprim with methotrexate. Penicillin has been shown to compete with the renal tubular secretion of methotrexate and, hence, its clearance. This was shown by Williams et al. [2] in vivo and in vitro in rhesus and cynomolgus monkeys. It works by inhibiting the cellular uptake of methotrexate, hence, stimulating its efflux. The findings were backed up in Bloom et al.’s [3] work in four patients who received high-dose methotrexate. Reduced renal excretion of methotrexate was demonstrated when penicillins were co-prescribed. A total of five cases of methotrexate-induced neutropenia in association with penicillin co-prescription have been reported in the literature [4, 5]. Trimethoprim has been shown by Kahn et al. [6] and Jenkins et al. [7] to affect hemoglobin, neutrophil and platelet counts, and folic acid levels in vivo. Sive et al. [8] showed in vitro studies on bone marrow that trimethoprim was an inhibitor of dihydrofolate reductase. Pancytopenia can occur with trimethoprim monotherapy [9, 10], as well as in combination with methotrexate. We found ten cases of pancytopenia in patients on methotrexate who were coprescribed trimethoprim [11–19]. Case series by Al-Awaadi et al. [20] and Kitsuwa et al. [21] identified trimethoprim as a risk factor for developing pancytopenia in patients who are taking methotrexate. Of the patient’s in Singh et al.’s [1] study, there was no mention of which antibiotics were used preadmission or during their treatment when they became pancytopenic. Education on the interactions between penicillin, trimethoprim, and methotrexate should be provided to medical practitioners and patients.