Elsevier

Clinics in Chest Medicine

Volume 19, Issue 4, 1 December 1998, Pages 667-685
Clinics in Chest Medicine

PULMONARY MANIFESTATIONS OF RHEUMATOID ARTHRITIS

https://doi.org/10.1016/S0272-5231(05)70109-XGet rights and content

Rheumatoid arthritis (RA) is the most common of the classic connective tissue diseases. Its clinical hallmark is the presence of symmetric inflammatory arthritis. Although disease may occur at any age, peak onset is seen in the fourth and fifth decades of life. As is the case with many other systemic diseases, the diagnosis of RA may be established only after the accumulation of signs and symptoms, sometimes over a lengthy span of time. The American Rheumatism Association criteria for the diagnosis of RA are6:

The diagnosis of rheumatoid arthritis can be made if four or more criteria are present.6 The course of disease is variable, with some patients having only self-limited episodes of arthritis, whereas others present with chronic and relentless progression to severe physical deformity and debilitation or with systemic manifestations that may cause significant end-organ disease. The cause of the abnormal connective tissue metabolism of this disease is unknown. Observed phenomena including the prevalence of IgM rheumatoid factor, the association of RA with certain Class II major histocompatibility complex antigens, the characteristic joint infiltration by immune and inflammatory cells, and the recognized disease response to therapies directed at immune suppression, however, support the hypothesis that RA is an autoimmune disease.

As is the case in most other connective tissue diseases, RA affects women disproportionately with a 2:1 female to male ratio. Extra-articular disease is seen frequently. Identifying systemic disease may be important as a higher mortality has been reported in RA patients with extra-articular manifestations, particularly in patients 50 years of age or less.54 Interestingly, the pleuropulmonary manifestations of RA are seen more commonly in men than women. As is the case with systemic lupus erythematosus (SLE), the pleuropulmonary manifestations of RA are varied, the most common of which are pleural abnormalities and interstitial lung disease.75, 81, 85, 110, 118, 137 The spectrum of RA-associated lung disease is extremely broad (Table 1). Furthermore, therapy-related pulmonary complications and pulmonary infection in patients with RA merit consideration in the overall evaluation and management of these patients. (See also the article by Libby and White.)

Table 1. PLEUROPULMONARY MANIFESTATIONS OF RHEUMATOID ARTHRITIS

Pleural disease
 Pleuritis
 Pleural effusion
 Pneumothorax
 Bronchopleural fistula
 Empyema
Rheumatoid nodules
 Necrobiotic nodules
 Caplan's syndrome
 Rheumatoid nodulosis
Interstitial lung disease
Airway involvement
 Airway obstruction
 Upper airway disease
  Cricoarytenoid arthritis
 Bronchiectasis
 Bronchiolitis obliterans with organizing pneumonia
 Bronchiolitis obliterans
Pulmonary vascular disease
 Vasculitis
 Primary or secondary pulmonary hypertension
Drug-related lung disease
Miscellaneous
 Infection
 Fibrobullous disease
 Amyloidosis

Section snippets

PLEURAL DISEASE

Pleural disease is common in patients with RA. In autopsy series the prevalence of histologic pleural disease is reported between 38% and 73%.75 Involvement of the pleura may be clinically silent or may result in pleurisy or the accumulation of pleural fluid. Pathologic findings in the pleura can vary. Pleural nodules are often seen; biopsy of a pleural nodule may reveal granulation tissue surrounding mononuclear cells palisading around central areas of fibronoid necrosis.81 Nonspecific

RHEUMATOID NODULES

Necrobiotic nodules are a common finding in RA. Subcutaneous nodules occur in 20% of patients seropositive for rheumatoid factor but are rarely seen in patients with seronegative RA.85 These may regress spontaneously or in response to therapy directed at joint or systemic disease. Pathologically, rheumatoid nodules are composed of a central area of fibrinoid necrosis surrounded by palisading mononuclear cells with an outer zone consisting of chronic inflammatory cells and granulation tissue

INTERSTITIAL LUNG DISEASE

Interstitial lung disease (ILD) is the most common pulmonary manifestation of RA. In many cases, disease is clinically silent and is identified by radiographic or physiologic abnormalities or by changes in bronchoalveolar lavage cell profile. Depending on the diagnostic modality used to detect disease, prevalence rates of ILD in RA are reported with wide variance. In general, ILD is seen more frequently in men than women, in the presence of a high rheumatoid factor titer, and in the setting of

Airway Obstruction

Chronic airway obstruction is a common finding in RA.50, 58, 90, 102, 108, 135 In a study by Geddes et al of 100 patients with RA and normal chest radiographs and 84 control subjects matched for age, sex, and smoking habits, indices of air flow obstruction (FEV1, FEV1/FVC, and MMEFR) were significantly lower in the group with RA.50 Overall, the prevalence of air flow obstruction in the RA group was 38%. This study, like other earlier studies, was confounded by the inclusion of large numbers of

Vasculitis

Systemic vasculitis associated with RA usually presents with skin ulcers, mononeuritis multiplex, and digital ischemia. In general, systemic vasculitis in patients with RA is rare. It, however, has been postulated that rheumatoid nodules, a common finding in RA, result from a vasculitic process.42

Primary pulmonary vasculitis is rarely seen in RA. Alveolar hemorrhage and hemoptysis have been described in the setting of a pulmonary renal syndrome.93 Alveolar hemorrhage has also been seen in RA in

DRUG-INDUCED LUNG DISEASE

Several of the medications commonly used to treat RA can be associated with lung injury. A comprehensive review of pulmonary complications of drugs used to treat RA and other connective tissue diseases is presented in the article by Libby and White. A brief overview is provided here.

Infection

Respiratory tract infection is an important source of morbidity in patients with RA. The exact prevalence of pulmonary infection in this population is reported variably. In one study an incidence of bacterial pulmonary infection of 25% was reported.68, 87 The presence of bronchiectasis, airway abnormalities, and parenchymal lung disease may increase the likelihood of infection and the morbidity with which these infections are associated.123 Patients with severe interstitial lung disease, for

CONCLUSION

It should be clear that RA can present in the chest in many different ways. Given the prevalence of RA and the fact that pulmonary complications are frequent, it is likely that practicing clinicians will encounter patients with pulmonary manifestations of RA. In the setting of respiratory symptoms or chest radiographic abnormalities in such patients, an understanding of the types of pleuropulmonary diseases that can be associated with RA should guide diagnostic evaluation and treatment. As some

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