**Part 3**

**Clinical Manifestations and Diagnosis of Rheumatic Diseases** 

62 Challenges in Rheumatology

Webb, P., Nguyen, P., Valentine, C, Lopez, G.N., Kwok, G.R., McInerney, E.,

Wilson, M.G., Michet, C.J. Jr., Ilstrup, D.M. & Melton, L.J. (1990). Idiopathic symptomatic

Wluka, A.E., Davis, S.R., Bailey, M., Stuckey, S.L. & Cicuttini, F.M. (2001). Users of oestrogen

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Vol. 60, No. 4, (Apr 2001), pp. (332-336)

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Katzenellenbogen, B.S., Enmark, E., Gustafsson, J.A., Nilsson, S. & Kushner, P.J. (1999). The estrogen receptor enhances AP-1 activity by two distinct mechanisms with different requirements for receptor *trans*activation functions. *Mol. Endocrinol.,*

osteoarthritis of the hip and knee: A population-based incidence study. *Mayo Clin* 

replacement therapy have more knee cartilage than non-users. *Ann. Rheum. Dis.,*

**5** 

*Canada* 

**Rheumatoid Arthritis Interstitial Lung Disease** 

Rheumatoid arthritis (RA) is a systemic, autoimmune, inflammatory disorder affecting 0.5- 1% of the North American population (Gabriel, 2001). It has a predilection for young women with an incidence rate of up to 130 per 100,000 compared with 70 per 100,000 in men [Minaur et al, 2004]. It is associated with a median survival decrease of up to 11 years compared to the general population (Minaur et al., 2004). The disease course may be complicated by extra-articular manifestations that confer an added burden of morbidity and mortality. RA-associated cardiovascular and infectious complications are commonly highlighted as major causes of morbidity and mortality in these patients (Maradit-Kremers et al., 2005). However, pulmonary involvement, the third leading extra-articular manifestation of RA, is now also recognized as a major cause of morbidity and mortality in RA patients. This was demonstrated in an autopsy study of 81 RA patients where the cause of death was determined to be infectious in 23.5%, cardiovascular in 17.3% and respiratory in 9.9% of patients (Suzuki et al., 1994). Pulmonary complications are the presenting manifestation of RA in up to 20% of patients (Brown, 2007). These complications include airway disease, pleural effusion, pulmonary nodules, and interstitial lung disease (ILD). This chapter will discuss the epidemiology, clinical features, management of RA-associated ILD (RA-ILD) and highlight the links between pulmonary involvement and autoimmunity.

Reports of the prevalence of RA-ILD are widely variable and likely comprise significant underestimates owing to inconsistency of clinical criteria used to define the condition, methods used for disease detection, and heterogeneity of study populations. Identification of ILD is further confounded by the fact that many of the medications used for the treatment of RA have potential deleterious effects on the lungs. A recent population-based study from the Rochester Epidemiology Project suggested that as many as 1 in 10 patients with RA will

RA patients with extra-articular manifestations, in particular those with respiratory disease, are at increased mortality risk, with a standardized mortality ratio ranging from 2.5 to 5.0 (Brown, 2007). RA-ILD remains a major cause of death in RA; the median and 5-year survival is 3.5 years and between 37-39%, respectively (Hakala, 1988). The mortality risk was found to be most significant in the first 5 years after an initial hospitalization. In a more recent incident-based study from the Rochester cohort of 582 patients with RA, the risk of

be diagnosed with ILD over the course of the disease (Bongartz et al., 2010).

**1. Introduction** 

**2. RA-ILD** 

**2.1 Scope and epidemiology** 

Ophir Vinik, Theodore Marras, Shane Shapera and Shikha Mittoo

*University of Toronto, Department of Medicine* 
