Depression is one of the most frequent comorbidities in rheumatoid arthritis (RA); it takes an important toll on the quality of life of these patients and also leads to a decrease in life expectancy. The current article is a narrative review on depression in RA, with the objective to emphasize and raise awareness on the high prevalence, pathogenic mechanisms, and effects that depression has on RA patients. In RA, the prevalence of depression has been shown to be 2 to 3 times higher than in the general population, with a meta-analysis reporting that 16.8% of RA patients have a major depressive disorder. Future studies are needed to determine the most accurate self-reported depression questionnaires and their ideal threshold for defining depression as compared to diagnostic interview as gold-standard for patients with RA to allow better comparisons across studies. The pathogenesis of depression remains to be fully understood, but recent specialty literature suggests that immune-mediated processes are involved and that there are similarities between the neural networks recruited in inflammation and those implicated in the pathophysiology of depression. Depression in patients with RA is associated with poor long-term outcomes. Multiple studies have shown that depression in RA is associated with increased pain, fatigue, and physical disability. It alters treatment compliance, causes more comorbidities, and leads to higher mortality, partly through increased suicide risk. Depression in RA also increases health service utilization and healthcare costs directly through hospitalization, but also indirectly through loss of work productivity. Assessing depression could be a significant psychomarker of rheumatological outcome in RA.
The current study aimed to evaluate rheumatoid arthritis (RA) patients with interstitial lung disease (ILD) in clinical practice and whether disease characteristics are associated with X-ray and high-resolution computed tomography (HR-CT) findings. Medical history of RA patients from a tertiary rheumatology clinic was retrieved from its electronic database starting from 1 January 2019 until the study date (8 August 2022) using International Classification of Disease version 10 codes for RA, ILD and exclusion criteria. The study included 78 RA patients (75.6% women, 15.4% active smokers), with average time from RA to ILD of 5.6 years. Regarding chest X-ray findings, men had a higher prevalence of nodules, combined fibrosis and nodules and combined bronchiectasis and nodules, rheumatoid factor (RF)-positive patients had a higher prevalence of fibrosis and anti-cyclic citrullinated peptide antibodies (ACPA)-positive patients had a higher prevalence of bronchiectasis. Regarding HR-CT findings, patients actively treated with methotrexate had a higher prevalence of nodules; a combination of fibrosis and nodules; combination of emphysema and nodules; and combination of fibrosis, emphysema and nodules. ILD develops within approximately 5 years from RA diagnosis, and ILD-associated imaging findings on chest X-rays and HR-CT are more prevalent among men with RA, among patients with positive RA serology (RF and/or ACPA) and RA patients on methotrexate.
Interstitial lung diseases (ILD), of which the most well-known is idiopathic pulmonary fibrosis (IPF), are a heterogeneous group of diseases, with similar, inflammatory and/or fibrosing mechanisms, which lead to the rapid decline of lung function and implicitly to a high degree of morbidity and mortality. Besides IPF, other interstitial lung diseases, such as those associated with connective tissue diseases, the most common being rheumatoid arthritis and systemic sclerosis, can develop a progressive fibrosing phenotype. Thus, because they have similar pathogenic mechanisms and clinical manifestations, all these diseases are described under the term of progressive fibrosing interstitial lung disease (PF-ILD). It is recommended that the diagnosis, clinical and paraclinical evaluation of ILD be made through a standardized management, within a multidisciplinary team that must include a pulmonologist, radiologist and rheumatologist, evaluation after which the subsequent treatment will be decided. Early diagnosis leads to an effective therapeutic intervention and decreased mortality. The progressive character has been defined if the progression occurs despite the current optimal management and treatment, which includes glucocorticoids and immunosuppressive therapy, at which point the indication of the antifibrotic treatment appears. The complete evaluation of ILD involves a rigorous anamnesis and clinical examination to identify environmental and professional risk factors, the patient’s chronic medication, family and personal history, the onset of the disease, as well as the identification by auscultation of bilateral basal crackles. From the paraclinical examination, the most important is the imaging studies (standard chest X-rays and mandatory HR-CT) which provide information about the anatomy, pattern, evolution in time or clues related to the underlying disease. The progressive character has been defined if the progression occurs despite the current optimal management and treatment, which includes glucocorticoids and immunosuppressive therapy, at which point the indication of the antifibrotic treatment appears. Evaluation of lung function is very important to complete the patient picture with PF-ILD, and the gold standard is the combination of spirometry, body plethysmography with diffusing capacity for carbon monoxide (DLCO), gasometry and an exercise test. Using this information, the optimal treatment will be led by the same multidisciplinary team that established the diagnosis, taking into account many aspects related to the characteristics of the disease, the cause, the safety profile and it will be monitored according to the existing protocols.
BackgroundPsychiatric comorbidities are frequent extra-articular manifestations in rheumatoid arthritis (RA) and depression is the most common [1]. A 2013 study estimated that 16.8 % of RA patients suffer from major depressive disorder, being more prevalent than diabetes, Parkinson’s disease or cancer [2-3]. Patients with RA have constitutional symptoms, frequently encountered in depression, like fatigue, weight loss, insomnia and lack of appetite. The overlap of depression in inflammatory immune mediated diseases is recognized for some time [4]. Studies show that immune mediated inflammation affects and modulates neurogenesis, neurotransmission, neuroendocrine activity and neuroplasticity [5]. Depression has important effects on RA patients: worse prognosis, pain, fatigue, functional deficit, more comorbidities, higher rate of mortality, increased healthcare resource utilization and lowered quality of life [6].ObjectivesThe scope of this article is to highlight the importance of managing depression in RA. The primary objective was to estimate the prevalence of depression in a cohort of RA patients. The secondary objective was to describe the phenotypic characteristics of RA patients with depression.MethodsRA patients from the Center of Rheumatic Diseases in Bucharest were included in the study if they were at least 18 years-old and if they had two or three follow-ups, after 2019. The protocol included collection of demographical, clinical and biological data. Prevalence of depression is derived from patients’ medical history, known depression. Demographical characteristics and RA phenotype were compared between the two groups. Disease activity was estimated with DAS28 and its components, tender joint count, swollen joint count, CRP and were followed over time to compare disease activity between patients with known depression and patients without depression.ResultsWe collected data from 203 patients with RA, among whom 37 were known with depression, generating a prevalence of 18.2%. A meta-analysis from 2013 reported that 16.8 % patients with RA suffer from a major depression disorder [1]. Most of the patients with depression were women (87.2%). Female sex is a potential risk factor for depression [7]. The prevalence of active smoking among the depression subgroup was higher (8.1%, 1.8%, p = 0.041). Depression is a known risk factor for negative behaviors like smoking [8]. Patients had a longer disease duration (in median, 13 years compared to 10 years, p = 0.059) and also the seropositivity prevalence was lower. In 2022 a correlation between depression and seronegative RA was found [9]. DAS28 and the components of DAS28 were higher in the depression RA subgroup; DAS28 was higher at all time points (p < 0.001). Higher tender joint count was expected (p < 0.001), but swollen joint count was also higher among depressive RA patients (p < 0.001), as well as CRP (p = 0.009, Figure 1).Figure 1.Median CRP levels as three time points among depressive and non-depressive RA patients (ANCOVA)ConclusionDepression is prevalent among RA patients and it has an important impact on the quality of life; so depressive symptoms should be addressed in clinical practice. The correlation between the prognosis of rheumatic disease and depression is strong, regardless of the direction of causality. The assessment of depression could be a psychomarker for assessing RA prognosis. DAS28 is used to make therapeutic decisions, so given that depression scores increase DAS28, it follows that they also influence therapeutic decisions.References[1] Morf H et al.Clin Rheumatol2021, 40(5):1779-1787.[2] Overman CL et al.Arthritis Care Res (Hoboken) 2014, 66(5):671-678.[3] Jamshidi T et al.Open Access Rheumatol2019, 11:53-59.[4] Nerurkar L et al.Lancet Psychiatry2019, 6(2):164-173.[5] Muller N et al.Mol Psychiatry2007, 12(11):988-1000.[6] Yilmaz V et al.Eur J Rheumatol2017, 4(2):127-132.[7] Kim SY et al.Rheumatology (Oxford) 2020 Aug 1;59(8):1889-1897.[8] Englbrecht M et al.PLoS One2019, 14(5):e0217412.[9] Kwiatkowska B et al.Reumatologia2018, 56(4):219-227.Acknowledgements:NIL.Disclosure of InterestsNone Declared.
Lung disease is the second most frequent extra articular manifestation in rheumatoid arthritis (RA) patients. It can be present in up to 80% RA cases and represents a major cause of morbidity and mortality. One of the most common types of lung involvement in RA patients is the interstitial lung disease (ILD). Computed tomography studies show evidence of ILD in a large proportion of patients with RA (over 50% in some studies) and it can be clinically symptomatic in 5% of cases. The CT aspect classifies four forms of ILD, listed in order of frequency: usual interstitial pneumonia (UIP) - the most common form, non-specific interstitial pneumonia (NSIP), organizing pneumonia (OP) and diffuse alveolar damage (DAD) which is the least common form. We present a long-standing case of rheumatoid arthritis overlapping systemic sclerosis with interstitial lung disease.
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