INTRODUCTION: Giant cell interstitial pneumonia (GIP) is a distinct and uncommon form of chronic interstitial pneumonia most frequently found in workers exposed to hard metals such as tungsten and cobalt. Nitrofurantoin-induced lung disease demonstrates a wide spectrum of histopathologic findings and, of these patterns, GIP is an exceedingly rare manifestation. To our knowledge, we report the second case of GIP associated with nitrofurantoin (1).
CASE PRESENTATION: A 77 year-old female presented with a six month history of progressive dyspnea and exercise intolerance. She had received daily nitrofurantoin therapy for the previous nine months for recurrent urinary infections. The patient had no other cardiopulmonary or constitutional symptoms. On physical exam, basilar "velcro" crackles were auscultated, and her room air oxygen saturation fell from 95% to 89% with minimal exertion. Hematologic, biochemical, and rheumatologic serologies were normal. The patient was taking no other medications and there was no evidence of active infection. She was a retired school librarian and had no history of heavy metal or other environmental exposures. Pulmonary function tests demonstrated pat- terns of mild obstruction and restriction with a severely decreased DLCO. CT of the chest showed nodular ground glass opacities within areas of peripheral intralobular septal thickening in both lungs with no lobar predominance (Figure 1). Flexible bronchoscopy was performed. The airway exam was normal and cultures were negative. Bronchoalveolar lavage fluid (BALF) showed a predominance of lymphocytes (71%), a mild eosinophilia (10%), and a CD4/CD8 ratio decreased at 0.25. BALF cytology demonstrated bizarre appearing multinucleated giant cells (MGC), and transbronchial biopsies demonstrated cellular interstitial infiltrates and scattered MGC consistent with GIP (Figure 2). Nitrofurantoin was discontinued; therapy with prednisone 1 mg/ kg/day was initiated and tapered over six months. Performance status and pulmonary function tests were dramatically improved after two months of therapy.
DISCUSSIONS: Although GIP has become nearly synonymous with hard metal pneumoconiosis, we report the second case of GIP associated with chronic nitrofurantoin therapy (1). The majority of cases of nitrofurantoin-induced pulmonary toxicity represent acute lung injury which resolves rapidly following cessation of nitrofurantoin. Chronic toxicity is more insidious and carries a worse prognosis. Both reported cases of GIP associated with nitrofurantoin occurred with chronic therapy and presented with a subtle onset of symptoms. Unlike some other forms of chronic nitrofurantoin toxicity and other forms of interstitial lung disease, rapid and appropriate diagnosis of GIP has been associated with a favorable outcome. Careful analysis of the BALF can support the diagnosis of GIP. While the presence of multinucleated giant cells in the BALF can be seen in many lung diseases, the finding of bizarre or cannibalistic MCG in the BALF may be more suggestive of GIP (2-4). After the observation of bizarre MCG, the diagnosis of GIP can be further supported by increased numbers of T-lymphocytes with an inverted T-cell helper/suppressor ratio in the BALF as seen in other cases of GIP as well as our patient (3,4). Ultimately, we feel that the diagnosis of GIP requires histopathologic confirmation.
CONCLUSION: It is important to recognize GIP as a rare manifestation of chronic nitrofurantoin toxicity as appropriate therapy can he associated with a favorable outcome.
REFERENCES:
(1) Magee F, Wright JL, Chan N, et al. Two unusual pathological reactions to nitrofurantoin: case reports. Histopathology 1986; 10: 701-706
(2) Kern I, Kecelj P, Kosnik M, et al. Multinucleated giant cells in bronchoalveolar lavage. Acta Cytol 2003; 47:426-430
(3) Kinoshita M, Sueyasu Y, Watanabe H, et al. Giant cell interstitial pneumonia in two hard metal workers: the role of bronchoalveolar lavage in diagnosis. Respirology 1999; 4:263-266
(4) Forni A. Bronchoalveolar lavage in the diagnosis of hard metal disease. Sci Total Environ 1994; 150:69-76
DISCLOSURE: Charles Hargett, None.
Charles W. Hargett MD * Thomas A. Sporn MD Victor Roggli MD John W. Hollingsworth MD Duke University Medical Center, Durham, NC
COPYRIGHT 2005 American College of Chest Physicians
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