Pulmonary sarcoidosis presenting with acute respiratory failure.

Abstract: This is a case report of pulmonary sarcoidosis presenting

with acute respiratory failure. A 33-year-old black man presented with 4 days of headache and fever. He had subsequent development of respiratory failure on the seventh hospital day. Workup showed high serum angiotensin-converting enzyme and increased pulmonary parenchymal uptake of gallium. Extensive workup for collagen vascular disease and infectious pathology were negative. Transbronchial biopsy specimens of the lung parenchyma showed noncaseating epithelioid granulomas consistent with sarcoidosis. The patient was treated with intravenous methylprednisolone succinate with dramatic clinical improvement.

Key Words: acute respiratory failure, noncaseating epithelioid granuloma, sarcoidosis

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Sarcoidosis is a systemic inflammatory disease of unknown cause. The clinical presentation of sarcoidosis can vary enormously. However, sarcoidosis initially presenting with acute respiratory failure is unusual.

Case Report

A 33-year-old black man, previously healthy, was hospitalized for acute onset of severe headache and fever that started 4 days before admission. His headache was in the frontal region and his temperature was 105[degrees]F on the night before admission. There were no known precipitating factors for his symptoms, and his review of systems was otherwise negative. He had been a student at a community college and worked part-time in the frozen meat department at a large store. He smoked cigarettes minimally and drank alcohol in moderation. At admission, he had a temperature of 105.4[degrees]F, blood pressure of 107/57 mm Hg, pulse of 86 beats/min, and respiratory rate of 24 breaths/min. Physical examination at admission was remarkable only for minimal inguinal lymphadenopathy. Complete blood count, basic chemistry panel, and liver function tests were within normal limits, except for low albumin of 2.8 g/dL (reference range, 3.4 to 4.7 g/dL). Chest radiography at admission was remarkable only for the presence of minimal blunting of both costophrenic angles. Computed tomography scan of the brain was normal. Cerebrospinal fluid analysis showed normal findings. Blood culture and cerebrospinal fluid culture were negative. The patient was started on ceftriaxone empirically, which was subsequently changed to levofloxacin and doxycycline. The patient continued to have high fever and severe headache. An extensive search for infectious causes, including urine serology for Legionella, histoplasma, and human immunodeficiency virus antibodies were all negative. Epstein-Barr virus and cytomegalovirus serologies were also negative. Serologic studies for collagen vascular disease showed normal complement levels and normal value of rheumatoid factor. Antinuclear antibody titer was found to be slightly elevated at 1:80 (speckled type). Serum angiotensin-converting enzyme was high at 76 U/L (reference range, 9 to 67 U/L). Magnetic resonance imaging with gadolinium showed right frontal venous angioma and punctate foci of white matter within bilateral cerebral hemisphere. Computed tomography scan of the chest with contrast showed minimal bilateral pleural effusions, and minimal mediastinal lymphadenopathy, particularly within the subcarinal region without any significant parenchymal abnormalities (Fig. 1). On the seventh hospital day, the patient had acute respiratory distress and hypoxemia. Room air arterial blood gas showed PaC[O.sub.2] of 35.4 mm Hg, Pa[O.sub.2] of 42.9 mm Hg, and Sa[O.sub.2] of 81.4%. Chest radiography obtained at that time revealed bilateral patchy pulmonary infiltrates (Fig. 2). Levofloxacin was discontinued, and trimethoprim/sulfamethoxazole was added empirically for presumed Pneumocystis carinii pneumonia. Gallium scan demonstrated significant increased uptake in both lungs. On the ninth hospital day, fiberoptic bronchoscopy was performed. Bronchoalveolar lavage (BAL), transbronchial biopsies of the lung, and Wang needle aspiration of the subcarinal lymph node were performed. BAL fluid analysis showed no eosinophils and a C[D.sub.4]/C[D.sub.8] ratio of 0.19. There was no evidence of acid-fast bacilli, fungi, or neoplasm. Wang needle aspiration of the subcarinal lymph node showed benign bronchial cells and an aggregate of lymphocytes. Transbronchial biopsy of the lung parenchyma revealed well-formed noncaseating epithelioid granulomas compatible with sarcoidosis (Fig. 3). At that time, the patient was requiring 100% FI[O.sub.2] delivered by high-flow face mask, but he did not require ventilatory support. Intravenous methylprednisolone succinate was started on the 10th hospital day. Trimethoprim/sulfamethoxazole and doxycycline were discontinued. Fever and hypoxemia improved within 24 hours of initiation of steroid. Within 3 days, dyspnea and hypoxemia were resolved. The patient was subsequently discharged home on 40 mg/d prednisone.

One week after hospital discharge, our patient reported complete resolution of symptoms. His chest radiograph showed improvement of pulmonary infiltrates and resolution of pleural effusions. His pulmonary function test was normal except for moderate reduction of diffusion capacity of carbon monoxide (61% of predicted value). The patient tolerated gradual withdrawal of steroids within 10 months without relapse. Diffusion capacity of carbon monoxide normalized to 93% of the predicted value within 5 months of treatment.

Discussion

Sarcoidosis has many unusual clinical presentations. Respiratory symptoms are common among symptomatic patients. (1) Generally, sarcoidosis has a chronic or subacute clinical course. Lofgren syndrome has been recognized as an acute presentation of sarcoidosis. (1) Acute respiratory failure, however, is a rare presentation of sarcoidosis.

Several diagnostic tests and imaging modalities, although nonspecific, may provide supportive evidence for the diagnosis of sarcoidosis. Elevation of angiotensin-converting enzyme level, BAL lymphocytosis (C[D.sub.4]/C[D.sub.8] ratio >3:5), panda, and lambda sign of gallium scan are highly consistent with sarcoidosis. (2) The finding of noncaseating epithelioid granulomas in biopsy specimens requires the presence of a correlating clinical syndrome consistent with sarcoidosis and the exclusion of alternative diseases to confidently establish the diagnosis. (3)

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We report a case of unusual presentation of pulmonary sarcoidosis. The diagnosis was confirmed by transbronchial lung biopsy, revealing well-formed noncaseating epithelioid granulomas in a background of otherwise normal lung parenchyma, which helps exclude other diagnoses such as acute respiratory distress syndrome, bacterial pneumonia, and pulmonary edema. Lack of eosinophils from BAL fluid analysis makes eosinophilic pneumonia unlikely. Hypersensitivity pneumonitis is associated with poorly formed granuloma and interstitial lymphocytic infiltrates, which was not seen in our patient. (4) The absence of prodromal viral infection-like symptoms and the presence of mediastinal lymphadenopathy make bronchiolitis obliterans organizing pneumonia less likely. Tuberculosis and fungal infection were excluded by negative acid-fast bacilli, fungal stains, and cultures. The C[D.sub.4]/C[D.sub.8] ratio, which is frequently increased in sarcoidosis, was found to be decreased in this case. However, two studies demonstrated that the C[D.sub.4]/C[D.sub.8] ratio can be highly variable in biopsy-proven sarcoidosis, with a C[D.sub.4]/C[D.sub.8] ratio less than 1 documented in 3.8 to 12% of patients. (5,6) To our knowledge, this is the first case report in English literature of isolated pulmonary sarcoidosis presenting with acute respiratory failure. There was one previous case report in English literature of acute respiratory failure secondary to acute respiratory distress syndrome associated with acute presentation of pulmonary sarcoidosis. (7) Essop et al (8) reported another case of atypical pulmonary sarcoidosis presenting as acute atypical pneumonia and respiratory failure. However, on presentation, their patient's chest radiograph showed evidence of pleural calcifications and parenchymal cavitation, which suggests the presence of underlying chronic lung disease. There was a single case report of sarcoidosis presenting with high fever and acute respiratory failure in Japanese literature. (9)

Conclusion

Our case is another example of the variable presentation of sarcoidosis. Diagnosis is established when clinicoradiologic findings are supported by histologic evidence of noncaseating epithelioid granulomas as well as the exclusion of other possible diseases.

Silence is argument carried out by other means.
--Ernesto Che Guevara

Accepted November 4, 2004.

Please see Muthiah Pugazenthi's editorial on page 265 of this issue.

References

1. Blackmon GM, Raghu G. Pulmonary sarcoidosis: a mimic of respiratory infection. Semin Respir Infect 1995;10:176-186.

2. Baughman RP, Lower EE, Bois RM. Sarcoidosis. Lancet 2003;361:1111-1118.

3. Thomas KW, Hunninghake GW. Sarcoidosis. JAMA 2003;289:3300-3303.

4. King DW. Idiopathic interstitial pneumonia and other diffuse parenchymal lung disease, in King DW, Sobin LS, Stocker JT, et al (eds): Atlas of Nontumor Pathology: Nonneoplastic Disorders of the Lower Respiratory Tract. Washington, DC, ARP and AFIP, 2002, pp 49-197.

5. Kantrow SP, Meyer KC, Kidd P, et al. The C[D.sub.4]/C[D.sub.8] ratio in BAL is highly variable in sarcoidosis. Eur Respir J 1997;10:2716-2721.

6. Agostini C, Trentin L, Zambello R, et al. C[D.sub.8] alveolitis in sarcoidosis: incidence, phenotypic characteristics, and clinical features. Am J Med 1993;95:466-472.

7. Sabbagh F, Gibbs C, Efferen LS. Pulmonary sarcoidosis and the acute respiratory distress syndrome (ARDS). Thorax 2002;57:655-656.

8. Essop AR, Moosa MR, Ally R. Atypical pulmonary sarcoidosis: a case report. S Afr Med J 1984;66:71-74.

9. Suyama T, Satoh H, Inoue T, et al. A case of sarcoidosis presenting with high fever and acute respiratory failure. Kekkaku 1990;65:811-819.

RELATED ARTICLE: Key Points

* Sarcoidosis is a multisystemic granulomatous disorder, most commonly involving the lungs.

* Initial presentation of pulmonary sarcoidosis can vary enormously, but sarcoidosis rarely presents with acute respiratory failure.

* Diagnosis of sarcoidosis requires correlating clinicoradiologic findings, histologic evidence of noncaseating epithelioid granulomas, and the exclusion of alternative diseases.

Naricha Chirakalwasan, MD, and Mohammed M. Dallal, MD, FCCP

From the Department of Internal Medicine, Miami Valley Hospital, Wright State University, Dayton, OH.

Reprint requests to Dr. Mohammed M. Dallal, 1520 South Main St., Suite 2, Dayton, OH 45458. Email: [e-mail]