Sarcoidosis presenting as acute respiratory failure.

Sarcoidosis is a multisystem disease of unknown cause with a myriad of potential clinical manifestations. A vast majority of patients with sarcoidosis present with lymph node and lung involvement. In the acute stage, sarcoidosis can present clinically as one of the well-defined classic syndromes (Lofgren or Heerfordt syndrome); however, sarcoidosis presenting as acute respiratory failure requiring mechanical ventilation is rare. There have been very few reported cases of sarcoidosis initially presenting as acute respiratory failure, although patients with known sarcoidosis may sometimes progress to respiratory failure over time.

Corticosteroids continue to be the mainstay of treatment in patients with sarcoidosis. Most patients respond favorably to systemic corticosteroid therapy, which provides the necessary immunosuppression/immunomodulation needed to decrease inflammation in acute presentations or acute exacerbations of sarcoidosis.

The pathogenesis of sarcoidosis still lingers around the excess production of various cytokines, including tumor necrosis factor (TNF)-[alpha] in the chronic phase, (1) although there are conflicting results from various studies. This is the biological basis of the usefulness of infliximab, (2) which is a TNF-[alpha] antagonist, in the treatment of corticosteroid-refractory sarcoidosis. Other agents that have been shown to reduce TNF-[alpha] production include thalidomide and pentoxifylline, both of which have been shown to decrease the clinical manifestations of sarcoidosis in small case series. (3,4)

Sarcoidosis is a diagnosis of exclusion, which makes tissue biopsy demonstrating well-formed, noncaseating granulomas essential for diagnosis. It is also necessary to exclude mycobacterial and fungal disease, which can be associated with granulomatous inflammation, to make a diagnosis of sarcoidosis.

Unlike other interstitial lung diseases, transbronchial biopsy renders a diagnosis of sarcoidosis in more than 80% of patients with the disease. This is especially true when endobronchial biopsies are performed concurrently with transbronchial biopsies. (5) Finding a predominantly lymphocytic bronchoalveolar lavage fluid with a CD4:CD8 ratio exceeding 4 also increases the likelihood of a diagnosis of sarcoidosis. (6)

In this issue of the Journal, Chirakalwasan and Mohammed (7) report the case of a 33-year-old black man who presented with systemic inflammatory response syndrome, a fever of 105.4[degrees]F, and a respiratory rate of 24 breaths per minute, who was treated initially for community-acquired pneumonia. Despite lack of significant pulmonary parenchymal abnormalities by chest computed tomography, he had severe hypoxemia, with a widened A-a gradient. Gallium scan demonstrated significant uptake in both lungs; transbronchial biopsy later revealed noncaseating granulomas compatible with the diagnosis of sarcoidosis. Tuberculosis and granulomatous fungal infections were excluded by negative acid-fast bacillus and fungal stains and culture. Within 24 hours of initiating systemic corticosteroid therapy, the patient's dyspnea and hypoxemia completely resolved, once again demonstrating the responsiveness of sarcoidosis to these agents.

Acute respiratory failure is another manifestation of acute sarcoidosis. Other acute lung diseases that respond dramatically to corticosteroids include acute eosinophilic pneumonia and cryptogenic organizing pneumonia (previously called BOOP, or bronchiolitis obliterans organizing pneumonia), both of which are not associated with granuloma formation.

In patients with the appropriate demographic/risk factors (ie, young to middle-aged and black, especially females, with a family history of sarcoidosis), the possibility of sarcoidosis should be considered in the differential diagnosis of otherwise unexplained acute respiratory failure. If recognized early, appropriate treatment can result in successful outcomes, as this case report so dramatically documents.

Accepted November 22, 2004.

Please see "Pulmonary Sarcoidosis Presenting with Acute Respiratory Failure" on page 382 of this issue.

References

1. Baughman RP, Strohofer SA, Buchsbaum J, et al. Release of tumour necrosis factor by alveolar macrophages of patients with sarcoidosis. J Lab Clin Med 1990;115:36-42.

2. Baughman RP, Lower EE. Infliximab for refractory sarcoidosis. Sarcoidosis Vasc Diffuse Lung Dis 2001;18:70-74.

3. Baughman RP, Judson MA, Teirstein AS, et al. Thalidomide for chronic sarcoidosis. Chest 2002;122:227-232.

4. Zabel P, Entzian P, Dalhoff K, et al. Pentoxifylline in treatment of sarcoidosis. Am J Respir Crit Care Med 1997;155:1665-1669.

5. Shorr AF, Torrington KG, Hnatiuk OW. Endobronchial biopsy for sarcoidosis: a prospective study. Chest 2001;120:109-114.

6. Winterbauer RH, Lammert J, Selland M, et al. Bronchoalveolar lavage cell populations in the diagnosis of sarcoidosis. Chest 1993;104:352-361.

7. Chirakalwasan N, Dallal MM. Pulmonary sarcoidosis presenting with acute respiratory failure. South Med J 2005;98:382-384.

Muthiah Pugazhenthi, MD

From the Pulmonary and Critical Care Division, University of Tennessee, Memphis, TN.

Reprint requests to Dr. Muthiah Pugazhenthi, 956 Court Ave., Room H314, Memphis, TN 38163. Email: [e-mail]