Unusual case of pyopneumothorax in Tennessee.

Abstract: Rupture of a coccidioidal pulmonary cavity with subsequent pyopneumothorax is a rare clinical event, even in areas endemic for coccidioidomycosis. Our encounter with a patient diagnosed with this condition in northeast Tennessee serves notice to clinicians that coccidioidomycosis is indeed a traveling fungal disease, and practitioners must be alert to common and uncommon manifestations of infection associated with this fungus. A literature review pertaining to coccidioidal pyopneumothorax revealed that patients usually present with a recent onset of chest pain. Serologic testing and pleural fluid culture are highly useful, and management includes surgical intervention with or without antifungal therapy.

Key Words: Coccidioidomycosis, empyema, pulmonary cavity, pyopneumothorax

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Although coccidioidomycosis is considered endemic to the southwestern region of the United States, it has also been referred to as the traveling fungal disease, (1) as illness caused by Coccidioides spp has been recorded in nonendemic parts of the United States and other countries. Certain occupations such as long-distance truck driving, tourism, and military assignments allow individuals from various sections of the country or other parts of the world to come into contact with this soil-dwelling fungus, even during brief visits to endemic areas. (1) In this regard, various authors (1-5) have encouraged practicing clinicians to be alert to the characteristics of Coccidioides spp infection, including both the usual and unusual disease presentations. On rare occasions, coccidioidomycosis may present as empyema with hydropneumothorax and this can pose a diagnostic dilemma even for clinicians practicing in endemic areas. (6) Our interaction with a Tennessee resident who had pyopneumothorax caused by Coccidioides immitis encouraged us to review the literature pertaining to this unusual entity and report the case, as it represents an excellent example of this traveling fungal disease.

Case Report

A 70-year-old retired long-distance truck driver was admitted to a Johnson City, Tennessee, hospital complaining of the sudden onset of shortness of breath and sharp, right-sided chest pain. He reported no fever, sweats, anorexia, weight loss, or hemoptysis. His medical history was positive for coronary artery disease, hypertension, chronic obstructive pulmonary disease, rheumatoid arthritis that required prednisone therapy for several months, and a history of positive tuberculin skin test for which he had received appropriate treatment. Social history was positive for previous tobacco use. He was a retired long-distance truck driver, and his work brought him to the southwest region of the United States on several occasions. Chest radiography at the time of admission showed apical bullae and a small right pneumothorax. His chest pain and shortness of breath improved, and he was discharged after a few days without undergoing further studies or interventions. Within 1 week's time, however, the patient's right-sided chest discomfort recurred and he was readmitted to the hospital. Physical examination revealed dullness to percussion and diminished breath sounds over the right mid to lower lung field. Chest radiography now showed a right hydropneumothorax and apical cystic changes. Complete blood count revealed a hemoglobin of 13 g/dL, white blood cell count of 15,800/[mm.sup.3], and platelet count of 249,000/[mm.sup.3]; the chemistry panel was within normal range. Chest CT scan demonstrated the right hydropneumothorax, as well as other changes consistent with emphysema and cystic changes, particularly in the right apex. A right-side chest tube was placed, and pleural fluid showed a white blood cell count of 345/[mm.sup.3] (62% mononuclear cells and 38% polymorphonuclear neutrophils), glucose of 0 mg/dL, protein of 3.5 g/dL and lactate dehydrogenase of 3,772 U/mL. Routine bacterial culture revealed no growth, stains and cultures for acid-fast bacilli were negative, and fungal cultures grew white, fluffy colonies within a few days. Microscopic evaluation of the fungal culture showed chains of barrel-shaped arthroconidia suggestive of Coccidioides spp. The fungal isolate was forwarded to the Tennessee State Laboratory and to the Centers for Disease Control and Prevention and it was confirmed as C immitis. The patient's complement fixation serologic test for C immitis was negative, a Spherulin skin test was positive at 15 mm, and pleural biopsy showed necrotizing granuloma with foreign body giant cells and inflammatory exudates. The patient received a 4-week course of amphotericin B, followed by a lengthy course of itraconazole. He also underwent thoracotomy with decortication and eventually recovered.

Discussion

Human infection associated with Coccidioides spp (C immitis and Coccidioides posadasii) is endemic in the southwestern region of the United States, where this dimorphic fungus can be recovered from soil samples from states ranging from California to Texas. Most infections are the result of inhaling arthroconidia and, in the majority of cases, the infections are subclinical or very mild. (7) Patients with symptomatic pulmonary infection may demonstrate nonspecific unilateral lung infiltrates as well as hilar adenopathy and pleural effusion on chest radiography, and most of these infections resolve without complication. (2) When associated with primary pulmonary coccidioidomycosis, pleural effusions may occur with or without evidence of parenchymal involvement. They are often unilateral and usually clear rapidly and completely without complication. (8) On occasion, the pulmonary Coccidioides infection may evolve into a cavitary lesion, and these are usually solitary, thin-walled, and located in an upper lobe. (6) Although coccidioidal pulmonary cavitation may be asymptomatic, some patients will have chest pain, cough, or hemoptysis, and, in certain cases, a mycetoma will develop within the cavity. (6) A limited number of patients, approximately 2.6% of those with cavitary coccidioidomycosis, will have spontaneous hydropneumothorax as a consequence of rupture of a subpleural, thin-walled cavity with associated bronchopleural fistula. (6) In this regard, we had an opportunity to provide care for an elderly man who resided in rural northeast Tennessee and who presented with spontaneous hydropneumothorax (case report). Infection caused by Coccidioides spp was not listed among the possible causes for this event, and the positive result of the pleural fluid culture was received with surprise. On further questioning, the patient elaborated on his previous occupation as a truck driver and stated that his driving regularly brought him to various states in the southwest United States. He probably encountered the organism during one of his forays into endemic territory, and he had subsequent development of this unusual complication some years after the primary infection. Conceivably, his use of corticosteroid medication for arthritis could have contributed to the disease activity.

This unique case for our rural area in northeast Tennessee stimulated a literature review (Table) that uncovered only one other case of cavitary coccidioidomycosis with rupture that was diagnosed outside of the usual endemic area. (9) Of these 31 well-described reported cases, (1,2,6,9-13) 29 were diagnosed in western states, and most of these (23 cases) were reported by Cunningham and Einstein (10) from Bakersfield, California. The majority of patients are young men, and only 22.6% had a documented history of pulmonary coccidioidomycosis infection. Complement fixation serology can be very helpful (positive in 29 of 30 tested), Coccidioidin skin test results were variable, and pleural fluid or lung specimen cultures were usually positive. There were no deaths attributed to the pulmonary infection. Management often included surgical intervention, in which 26 patients underwent partial or complete lobectomy with or without decortication. Fourteen patients also received courses of amphotericin B and/or azole therapy. Since our patient was receiving corticosteroid therapy, he was given a course of amphotericin B followed by itraconazole.

In summary, important lessons were learned both from our personal experience and from our literature review concerning hydropneumothorax as a complication of pulmonary coccidioidomycosis infection. Perhaps most notably, we can offer firm support to the designation of coccidioidomycosis as the "traveling" fungal disease. (1) Clearly, various occupations, recreational activities, and so forth, will allow individuals from distant geographic areas to encounter Coccidioides during visits to endemic sites and to possibly manifest symptoms of illness on their return to nonendemic regions. Furthermore, the signs and symptoms associated with coccidioidomycosis hydropneumothorax are nonspecific, and chest radiography may initially only show pneumothorax, as in our case, followed by pleural fluid collection on subsequent studies. (10) Diagnosis usually hinges on the recovery of Coccidioides from pleural fluid, and management commonly involves surgical intervention (closed-chest drainage, resection and decortication). (10) With regard to the need for antifungal therapy, Cunningham and Einstein (10) have suggested that amphotericin B is not routinely indicated in patients with well-controlled disease who receive prompt surgical intervention. These authors recommended the use of amphotericin B therapy if there is a delay in surgical intervention, when the cavity ruptures during the acute phase of infection, when there is otherwise active residual disease, and when the patient has certain concomitant risk factors and medical problems such as diabetes or a bronchopleural fistula. However, with the availability of effective and less toxic azole antifungal agents such as fluconazole and itraconazole, we recognize that clinicians probably would choose to offer combined medical and surgical therapies for patients with this unusual complication of cavitary coccidioidomycosis.

References

1. Bayer AS, Yoshikawa TT, Galpin JE, et al. Unusual syndromes of coccidioidomycosis: diagnostic and therapeutic considerations. Medicine 1976;55:131-152.

2. Edelstein G, Levitt RG. Cavitary coccidioidomycosis presenting as spontaneous pneumothorax. Am J Roentgenol 1983;141:533-534.

3. Snyder LS, Galgiani JN. Coccidioidomycosis: the initial pulmonary infection and beyond. Semin Respir Crit Care Med 1997;18:235-247.

4. Desai SA, Minai OA, Gordon SM, et al. Coccidioidomycosis in nonendemic areas: a case series. Respir Med 2001;95:305-309.

5. Crum NF, Lederman ER, Stafford CM, et al. Coccidioidomycosis: a descriptive survey of a reemerging disease: clinical characteristics and current controversies. Medicine 2004;83:149-175.

6. Smith CE, Beard RR, Saito MT. Pathogenesis of coccidioidomycosis with special reference to pulmonary cavitation. Ann Intern Med 1948; 29:623-655.

7. Smith CE, Beard RR, Whiting EG, et al. Varieties of coccidioidal infection in relation to the epidemiology and control of the disease. Am J Public Health 1946;36:1394-1402.

8. Batra P. Pulmonary coccidioidomycosis. J Thorac Imaging 1992;7:29-38.

9. Scully RE, Mark EJ, McNeely WF, et al. Case records of the Massachusetts General Hospital: case 21-1994. N Engl J Med 1994;330:1516-1522.

10. Cunningham RT, Einstein H. Coccidioidal pulmonary cavities with rupture. J Thorac Cardiovasc Surg 1982;84:172-177.

11. Haber K, Freundlich IM. Spontaneous pneumothorax with unusual manifestations. Chest 1974;65:675-676.

12. Dolan MJ, Lattuada CP, Melcher GP, et al. Coccidioides immitis presenting as a mycelial pathogen with empyema and hydropneumothorax. J Med Veterinary Mycol 1992;30:249-255.

13. Hyde L, Holman DC. Coccidioidal spontaneous hydropneumothorax. Ann Intern Med 1957;47:1234-1242.

Souad S. Youssef, MD, Vijay Ramu, MD, and Felix A. Sarubbi, MD

From James H. Quillen Veterans Affairs Medical Center and James H. Quillen College of Medicine, Johnson City, TN.

Reprint requests to Dr. Felix A. Sarubbi, Department of Medicine, James H. Quillen College of Medicine, East Tennessee State University, Johnson City, TN 37614. Email: [e-mail]

Accepted July 14, 2005.

No financial support was obtained for this paper. The authors of this paper have no commercial or proprietary interest in any drug, device, or equipment mentioned in the article.

RELATED ARTICLE: Key Points

* Infection due to Coccidioides can be encountered outside the usual endemic areas and clinicians must be aware of the clinical spectrum.

* Rupture of a coccidioidal pulmonary cavity is a rare event and can result in pyopneumothorax.

* Treatment of pyopneumothorax due to Coccidioides requires surgical intervention with or without antifungal therapy.

Table. Coccidioidomycosis and spontaneous hydropneumothorax

Characteristics for 31 patients

Males: 24                     Females: 7
Age range (yr): 11-70         Mean age (yr): 27.2
Patient location
  at time of diagnosis
  (No. of cases)
California (25)               Arizona (2)          Texas (1)
Common symptoms: recent
  chest pain, shortness of
  breath
                              Positive             Negative
Coccidioidin skin test         6                   14
Complement fixation serology  29                    1
Coccidioides spp culture      29                    2
Surgical procedures (No.)
Lobectomy or wedge            Closed chest         Closed chest drainage
  resection, with or Closed     drainage (3)         and decortication
  without decortication (26)                         (1)
Amphotericin B and/or azole
  therapy: 14

Characteristics for 31 patients

Males: 24
Age range (yr): 11-70
Patient location
  at time of diagnosis
  (No. of cases)
California (25)               Washington     Massachusetts  Tennessee
                              State (1) (a)  (1) (b)        (1)
Common symptoms: recent
  chest pain, shortness of
  breath
                              Not done
Coccidioidin skin test        11
Complement fixation serology   1
Coccidioides spp culture      -
Surgical procedures (No.)
Lobectomy or wedge            Thoracentesis
  resection, with or          (1)
  without decortication (26)
Amphotericin B and/or azole
  therapy: 14

(a) The Washington State patient was originally from California.
(b) The Massachusetts patient was originally from Mexico.