A case of Mycobacterium avium complex pulmonary disease in an immunocompetent host.

Abstract: Mycobacterium avium complex is the most common of nontuberculous mycobacterium capable of causing disease in humans. The manifestations can vary from asymptomatic exposure to hypersensitivity pneumonitis to advanced fibrocavitary disease. We describe the case of a 37-year-old male with advanced cavitary disease from Mycobacterium avium complex. The patient had no previous history of pulmonary disease, but did have a history of snorting crushed Lortab (hydrocodone/acetaminophen) tablets and we postulate that possible injury to the lung from talc or other chemicals in the tablets may have predisposed him to develop Mycobacterium avium pulmonary disease.

Key Words: Mycobacterium avium complex, Mycobacterium avium complex pulmonary disease, bronchiectasis, fibrocavitary lung disease

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Mycobacterium avium complex is the most common of nontuberculous mycobacterium capable of causing disease in humans. The manifestations can vary from asymptomatic exposure to hypersensitivity pneumonitis to advanced fibrocavitary disease. We describe the case of a 37-year-old male with advanced cavitary disease from M avium complex. The patient had no previous history of pulmonary disease but did have a history of snorting crushed Lortab (hydrocodone/acetaminophen) tablets, and we postulate that possible injury to the lung from talc or other chemicals in the tablets may have predisposed him to develop M avium pulmonary disease.

Case Report

A 37-year-old white male with no prior medical history was admitted through the emergency room with increasing shortness of breath which gradually worsened over the course of one year. His shortness of breath had progressed to the point that mobilization from room to room was difficult. He complained of cough accompanied by whitish phlegm, a feverish feeling, chills with some night sweats, nausea, and decreased appetite. In addition, the patient had lost approximately 30 pounds over the previous year. He had no other medical problems and was not on any medications. He had a 5-pack-a-year smoking history, but had quit 3 months before admission. Social history was positive for occasional alcohol consumption, but he had not consumed alcohol for the previous 3 months, due to an inability to "hold it down." He snorted crushed Lortab (hydrocodone/acetaminophen) pills regularly, but had no history of IV drug abuse. There was no family history of breathing problems, and no one else in the household complained of similar symptoms. On physical examination his temperature was 98.4[degrees] with pulse of 97, respirations 22, blood pressure of 98/60 and pulse oximetry of 90% on room air. He looked emaciated and lung examination revealed crackles at both bases and scattered wheezes. His laboratory data showed a white blood cell count of 8.7 with 76% neutrophils and 13% bands. Serum electrolytes and liver function tests were normal. HIV test was negative. His [alpha]-1 antitrypsin level and cystic fibrosis screen were normal. Sputum acid-fast bacillus stain was positive. Silver staining of sputum was negative for Pneumocystis carinii. X-ray (Fig. 1) and CT scans of thechest (Fig. 2) were performed. A heavy growth of M avium complex was isolated from the sputum. He was started on treatment for MAC and subsequently was discharged home. He was lost to follow up and was admitted again six months later with associated Pseudomonas pneumonia and died during admission from complications of sepsis.

Discussion

M avium complex (MAC) is the most common of the nontuberculous mycobacteria that causes disease in humans. This group contains M avium and Mycobacterium intracellulare. (1) It is a ubiquitous environmental organism that can be recovered from fresh and seawater, soil, dust, and numerous animal species including chickens, pigs, dogs, cats, and insects. Stain analysis suggests that animal to human transmission is not an important source of infection. (2) Generally, transmission is thought to be due to inhalation of environmentally derived airborne organisms rather than person to person. (3) Oral ingestion may also be a route of infection but is generally considered more likely in the immunocompromised host. In immunocompetent patients, two patterns of pulmonary MAC disease (MAC-PD) are described: a "primary" form in healthy nonsmokers and a "secondary" form in patients with underlying lung disease, including chronic obstructive lung disease, old tuberculosis, bronchiectasis, cystic fibrosis, etc.

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The primary form usually affects nonsmoking women over age 50 who have interstitial patterns on chest radiography. A syndrome of right middle lobe or lingular infiltrates, sometimes called the Lady Windermere syndrome, has been noted in elderly women without predisposing lung disease, volume loss, adenopathy, or cavitations. The secondary form usually affects middle aged to older white men (4) who usually present with worsening cough, hemoptysis, and constitutional symptoms (night sweats, weight loss, and anorexia). The classical radiographic picture mimics reactivation tuberculosis with cavitations and is characterized by progressive fibronodular opacities (< 5 mm nodules) with cavities. (6) Distribution typically involves the upper lung fields.

Symptoms are variable and nonspecific. Cough is the most common symptom; hemoptysis and constitutional symptoms are less frequent (5) as compared with tuberculosis. The radiographic picture most frequently shows multiple, small, ill-defined nodules with associated bronchiectasis with a predominant middle lobe and/or lingular abnormalities with or without overinflation. (7) Serial CT scans in untreated disease show worsening of bronchiectasis, suggesting that bronchiectasis not only may predispose the patient to MAC infection, but can also be caused by it.

No specific immune defect has been associated with predisposition to MAC infection. Tumor necrosis factor (TNF) [alpha] and interferon (IFN) [gamma] are important in the defense against mycobacterial disease, and abnormalities of these cytokines have been linked to increased susceptibility to MAC infection. (2) Abnormalities of the lung defense mechanisms, including injury to respiratory mucosa due to snorting talc or other chemicals in the crushed Lortab pills may have predisposed our patient to the infection with MAC.

The diagnosis of pulmonary disease due to nontuberculous mycobacteria is based on a combination of clinical, microbiologic, and radiological criteria published by the American Thoracic Society. (8) These require clinical criteria plus one radiographic criterion and one bacteriologic criterion (Table 1). The sensitivity of sputum cultures has recently been questioned and bronchoscopy has been suggested to exclude disease if there is a strong clinical suspicion with negative sputum cultures. (5)

It is recommended that every MAC isolate should be carefully evaluated within the context of the patient's overall clinical status. In general, almost any patient with two or three positive respiratory cultures for MAC has MAC-PD, and treatment is recommended to prevent the development or progression of lung disease. (8) If a decision is made to observe a patient (due to minimal symptoms, a belief that the treatment seems worse than the disease, or major medical problems), lifelong monitoring of sputum specimens for acid-fast bacillus analysis as well as follow-up chest x-rays and/or CT scans are recommended, as MAC disease will likely progress at some point. (8) Pulmonary disease is more likely to progress in patients with certain characteristics, including older age, decreased body mass index, increased erythrocyte sedimentation rate, and increased number of neutrophils in bronchoalveolar lavage fluid. (9)

Recommended treatment for patients with MAC-PD without AIDS includes daily ethambutol (25 mg/kg a day for 2 months then 15 mg/kg a day) and rifampicin (600 mg) or rifabutin (300 mg/d) plus a macrolide (either clarithromycin 500 mg twice daily or azithromycin 250 mg once daily). Concomitant streptomycin (500-1000 mg twice or thrice weekly) is recommended for patients with extensive cavitary disease for the first 8 weeks. Duration of treatment should be at least 12 months after cultures revert to negative. (8,10) Surgical options including lung resection can be considered in patients with failed medical therapy and adequate pulmonary reserve. However, to the best of our knowledge, no controlled surgical trials for MAC disease have been published.

Conclusion

This report describes a case of severe M avium complex pulmonary disease in a patient without any pre-existing lung disease. The patient's habit of snorting Lortab tablets may have predisposed him to this infection.

References

1. Murray and Nadall. Textbook of Pulmonary Medicine, 3rd edition, pp 1090-1094.

2. Field SK, Fisher D, Cowie RL. Mycobacterium avium complex pulmonary disease in patients without HIV infection. Chest 2004;126:556-581.

3. Aksamit TR. Mycobacterium avium complex pulmonary disease in patients with preexisting pulmonary disease. Clinics in Chest Medicine 2002;23:643-53.

4. Reich J, Johnson R. Mycobacterium avium complex lung disease in women. Chest 1995;107:293-294.

5. Huang JH, Kao PN, Adi V, et al. Mycobacterium avium-intracellulare pulmonary infection in hiv-negative patients without preexisting lung disease. Chest 1999;115:1033-1040.

6. Levin DL. Radiology of Pulmonary Mycobacterium avium-intracellulare complex. Clinics in Chest Medicine 2002;23:603-612.

7. C Wittram, G L Weisbrod. Mycobacterium Avium Lung Disease in immunocompetent patients: radiography-CT correlation. Br J Radiol 2002;75:340-344.

8. American Thoracic Society. Diagnosis and treatment of disease caused by nontuberculous mycobacteria. Am J Respir Crit Care Med 1997;156:S1-25.

9. Yamazaki Y, Kubo K, TakamizawaA, et al. Markers indicating deterioration of pulmonary mycobacterium avium-intracellulare infection. Am J Respir Crit Care Med 1999;160:1851-1855.

10. Iseman MD. Medical management of pulmonary disease caused by mycobacterium avium complex. Clinics in Chest Medicine 2002;23:633-41.

Zaka U. Khan, MD, Juan Guardiola, MD, and Gary Salzman, MD

From the University of Missouri at Kansas City School of Medicine, Kansas City, MO and the University of Louisville, KY.

Reprint requests to: Gary Salzman, MD, UMKC School of Medicine, 2411 Holmes St, Kansas City, Missouri 64108. Email: [e-mail]

Accepted June 24, 2005.

RELATED ARTICLE: Key Points

* Mycobacterium avium complex (MAC) is the most common of nontuberculous mycobacteria that is capable of causing disease in humans.

* In immunocompetent patients, two patterns of pulmonary MAC disease (MAC-PD) are described as "primary" and "secondary."

* The symptoms are variable and not specific.

* The diagnosis of pulmonary disease due to nontuberculous mycobacteria is based on a combination of clinical, microbiologic and radiological criteria published by the American Thoracic Society

* Snorting crushed Lortab pills may have predisposed our patient to the development of M avium complex pulmonary disease.

Table. Criteria for the diagnosis of pulmonary disease due to
nontuberculous mycobacteria (a,b)

Category       Requirement

Clinical       Compatible symptoms (eg fever and cough), and
                 deterioration in clinical status (if underlying lung
                 disease present), and reasonable exclusion of other
                 disease.
Radiologic     Chest radiograph: infiltrates with or without nodules,
                 either persistent ([greater than or equal to] 2 months)
                 or progressive; or cavitations; or multiple nodules
                 alone.
               High resolution CT: Multiple small nodules; or multifocal
                 bronchiectasis with or without small nodules.
Bacteriologic  Sputum/bronchial wash: At least three positive cultures
                 in 1 year.
               Bronchial wash only: At least one positive culture with
                 moderate growth or positive AFB smear.
               Lung Biopsy: Positive culture.

Diagnosis requires clinical criteria plus one radiologic criterion and
one bacteriologic criterion.
(a) AFB, acid-fast bacillus.
(b) Source: Adapted from RJ Wallace, et al. Am Rev Respir Crit Care Med
1997;156:S1.