If you don't remember your password, you can reset it by entering your email address and clicking the Reset Password button. You will then receive an email that contains a secure link for resetting your password
If the address matches a valid account an email will be sent to __email__ with instructions for resetting your password
Requests for reprints should be addressed to Daniel J. Pearson, MD, Department of Pulmonary Medicine, 3551 Roger Brooke Drive, Fort Sam Houston, San Antonio, TX 78234.
The illness responsible for a patient's left-sided chest pain was a fairly infrequent herald of autoimmune disease. A 31-year-old woman reported that her musculoskeletal pain began while hiking and evolved over 4 months into a progressive, dull, ache. Additional symptoms included weight loss, fatigue, anorexia, shortness of breath, fevers, and night sweats. She had no arthralgias, cough, sputum production, or any known exposure to tuberculosis. Her twin sister had breast cancer, but she had no family history of rheumatologic disease.
The patient's medical history was unremarkable; her only medication was a multivitamin. She denied use of tobacco or illicit drugs and consumed minimal alcohol. A flautist in a US Army band, she had no new occupational exposures. She had traveled extensively, living throughout Europe and the US. One year prior to her evaluation, she moved to rural Arizona, where she was an avid runner and exercised extensively in the desert. However, her symptoms were preventing her from running or playing the flute.
Assessment
On physical examination, the patient had a temperature of 37.9°C (100.3°F), a pulse rate of 117 beats per minute, a blood pressure of 110/70 mm Hg, a respiratory rate of 16 breaths per minute, and an oxygen saturation of 100% on room air. Although she appeared chronically ill, she was in no acute distress. No tenderness was elicited by palpation of the chest wall, and her lungs were clear to auscultation. She had no skin lesions or synovitis. Laboratory results revealed a hemoglobin level of 10.2 g/dL, a mean corpuscular volume of 70.2 fL, and a platelet count of 704,000 platelets/μL; results from her white blood cell count and blood differential test were unremarkable. Serologies for antibodies to Histoplasma capsulatum, Coccidioides species, and Blastomyces dermatitidis were negative, as was a tuberculin skin test.
Autoimmune and inflammatory markers showed the following: erythrocyte sedimentation rate, 103 mm/h; C-reactive protein level, 19.20 mg/dL; positive rheumatoid factor test, 1:4 titer; and cyclic citrullinated peptide antibody (anti-CCP) test, positive at >250 U/mL (normal, 0-19 U/mL). A myositis panel, an antineutrophil cytoplasmic antibody panel, an anti-double-stranded DNA test, an antinuclear antibody test, and a human immune deficiency virus test produced negative results. Pulmonary function tests showed a forced expiratory volume in 1 second (FEV1) of 2.12 L (71% predicted), a forced vital capacity (FVC) of 2.47 L (70% predicted), and an FEV1/FVC ratio of 0.86.
A chest radiograph revealed a central-appearing left upper lobe infiltrate and an elevated left hemidiaphragm (Figure 1). Computed tomography of the chest demonstrated a mass-like consolidation in the left upper lobe, with scattered peripheral opacities and pleural studding throughout the left upper lobe, oblique fissure, and left lower lobe. The right lung was unaffected (Figure 2, A-F).
Figure 1A chest radiograph disclosed infiltrate in the central portion of the left upper lobe. An elevated left hemidiaphragm indicated volume loss in the left hemithorax.
Figure 2Computed tomography (CT) images, A-F, demonstrated a left upper lobe mass-like lesion with peripheral nodularity that extended to the oblique fissure and left lower lobe. The right lung was unaffected.
Transbronchial biopsies were performed on the left upper lobe lesion. Generally, transthoracic or open lung biopsies are preferred for the diagnosis of interstitial lung disease because they are more likely to yield sufficient tissue for a definitive diagnosis. Yet, they also have higher complication rates.
Histopathology disclosed alveolated lung parenchyma marked by septal thickening and a cellular infiltrate of lymphocytes, plasma cells, neutrophils, and eosinophils. Multifocal airspace consolidation, granulation tissue embedded in a background myxoid matrix, and bronchiolar fibroblastic plugs or Masson's bodies were also noted. The Masson's bodies are a classic sign of organizing pneumonia and thus provided a diagnosis (Figure 3, A and B). Organizing pneumonia secondary to infection was unlikely, as special stains for acid-fast and fungal organisms were negative. Instead, the findings were consistent with organizing pneumonia associated with a high titer of anti-CCP antibodies in the absence of known connective tissue disease.
Figure 3(A) A transbronchial biopsy revealed focal air space consolidation composed of intra-alveolar fibroblastic foci or Masson's bodies (arrows) (hematoxylin and eosin, 10×). (B) Background lung tissue showed alveolar septal thickening with a mixed inflammatory infiltrate that included neutrophils, plasma cells, lymphocytes, and eosinophils. Reactive type II pneumocytes lined the alveoli.
Organizing pneumonia is characterized by the presence of intra-alveolar granulation tissue; the term cryptogenic organizing pneumonia is used when no underlying disorder is identified.
It is often secondary to infection, drugs, aspiration, radiation therapy, or autoimmune/inflammatory conditions. The epidemiology is uncertain, but one study estimated the incidence of secondary organizing pneumonia at 0.87/100,000/year and cryptogenic organizing pneumonia at 1.10/100,000/year.
Interstitial lung disease occurs in 7.7%-12% of patients with clinical rheumatoid arthritis. In fact, in 4%-14% of patients whose interstitial lung disease is ultimately tied to rheumatoid arthritis, the diagnosis of organizing pneumonia precedes the diagnosis of clinical rheumatoid arthritis; yet, lung disease associated with raised anti-CCP titers is increasingly recognized among patients without clinical rheumatoid arthritis.
One review of patients with high-titer anti-CCP-positive lung disease showed that over an average of 449 days, only 3 of 33 patients developed articular manifestations.
Anti-CCP antibodies are a more specific indication of rheumatoid arthritis than is rheumatoid factor, but they can be found in patients with other rheumatologic conditions.
The most common pulmonary manifestation, documented in 40%-62% of patients with rheumatoid arthritis and coinciding interstitial lung disease, is usual interstitial pneumonia. For 11% of these patients, organizing pneumonia is the pulmonary diagnosis.
Other forms of interstitial lung disease that are typically seen in this group are nonspecific interstitial pneumonia and acute interstitial pneumonia. Characteristic radiographic findings for organizing pneumonia, which is ordinarily bilateral and frequently migrates spontaneously, are bilateral patchy subpleural or peribronchovascular consolidations. In one study of patients with organizing pneumonia, 79% had consolidations, with immunocompetent patients having more than immunocompromised patients.
Glucocorticoids, the preferred treatment for organizing pneumonia, usually produce rapid symptomatic and radiographic improvement. While no guidelines exist for the treatment of patients who have interstitial pulmonary disease and an elevated anti-CCP antibody titer without articular symptoms, several authors suggest regular examinations to assess for subsequent development of articular evidence of rheumatoid arthritis.
Although cryptogenic organizing pneumonia is normally responsive to corticosteroids, up to 73% of patients have residual radiographic disease that tends to resemble a fibrotic nonspecific interstitial pneumonia.
Before a diagnosis of cryptogenic organizing pneumonia is rendered, a comprehensive evaluation for primary causes of organizing pneumonia should be conducted. Testing for anti-CCP antibodies and rheumatoid factor should be included even in the absence of synovitis or arthralgia.
Our patient's symptoms quickly improved after she started a regimen of 1 mg/kg/day of prednisone. After 4 weeks, she was asymptomatic and had nearly complete resolution of radiographic disease (Figure 4, A-D). The corticosteroids were tapered over 4 months. However, once the medication was withdrawn, she developed hand and foot arthralgias. At that point, her signs and symptoms fit the classic description of rheumatoid arthritis, and traditional therapy was initiated.
Figure 4Follow-up computed tomography was conducted 4 weeks after initiation of corticosteroids. (A, B) The mass-like infiltrate resolved, but there was residual scarring in the left upper lobe. (C) Nodules were evident along the fissure, pleura, and base of the left lung. (D) Nonetheless, the nodules were significantly reduced in size.
30349-2&id=gr1.jpg){kind=link}
30349-2&id=gr2.jpg){kind=link}
30349-2&id=gr3.jpg){kind=link}
30349-2&id=gr4.jpg){kind=link}