INTRODUCTION

TOP ABSTRACT INTRODUCTION CASE REPORT DISCUSSION REFERENCES

Mycobacterium haemophilum has recently been recognized as a pathogen in immunocompromised patients (1). Disease manifestations have been predominantly cutaneous lesions, arthritis, and osteomyelitis but a few cases of pneumonia have been described (2). Disease caused by this organism has also occurred in a few healthy children, where manifestations are cervical, submandibular, and perihilar adenitis (2, 5). We report a well-documented case of a pulmonary nodular lesion with this mycobacterium in an immunocompetent woman. Our case expands the spectrum of disease previously recognized with this organism and raises the possibility that M. haemophilum is a cause of granulomatous pulmonary disease that may be underrecognized.

	CASE REPORT

TOP ABSTRACT INTRODUCTION CASE REPORT DISCUSSION REFERENCES

A 62-yr-old woman from the Philippines was found on a routine chest radiograph in September 1998 to have a small masslike infiltrate in the right lower lobe which was new compared with a prior radiograph in December 1997. She had a mild nonproductive cough without other symptoms. She was treated with a 1-wk course of clarithromycin with improvement. A chest radiograph a month later at Memorial Sloan Kettering Cancer Center (MSKCC) in New York City showed a 2 cm nodular lesion in the right lower lobe, which had minimally increased compared with the prior radiograph (Figure 1). Her only symptom was a mild nonproductive cough; there was no dyspnea, chest pain, fever, chills, sweats, or weight loss.

View larger version (128K): [in this window] [in a new window]   Figure 1.   Posterior anterior chest radiograph shows a nodular infiltrate in the right midlung field peripherally.

She had undergone a right lumpectomy and axillary lymph node dissection at MSKCC in August 1994 for a stage I breast cancer with negative hormone receptors. She received 6 mo of adjuvant chemotherapy with cyclophosphamide, methotrexate, and 5-fluorouracil as well as local radiation to the breast. Her history was also notable for hypertension, intermittent gastritis, and seasonal allergies. She smoked one pack per day of cigarettes for 20 yr stopping 10 yr before. Her father died of tuberculosis and she was known to have a positive skin test but had not received prophylactic treatment. She worked as a florist. She lived in an urban area close to Manila but had traveled extensively to rural areas. She had two dogs but no exposure to farm animals.

Physical examination was of note for a well appearing woman who was afebrile. Her examination was normal except for healed surgical scars. Routine laboratory values were within normal limits. A chest computerized tomography showed an indistinct lobulated 2 × 2 cm nodule in the right lower lobe with some adjacent indistinct infiltrative change (Figure 2). No cavitation or calcification was seen. There were two punctate nodules in the right middle lobe. There was no thoracic adenopathy or abdominal abnormalities. Because of concern for malignancy in a former smoker with a history of breast cancer, she underwent mediastinoscopy and open lung biopsy. At mediastinoscopy, a right level 10 node showed non-necrotizing granulomatous inflammation and wedge resection of the mass showed non-necrotizing granulomatous inflammation with multinucleated giant cells. No organisms were seen on the pathology specimen but rare acid-fast bacteria were seen with the auramine stain in the microbiology laboratory. In addition to conventional cultures, specimens were processed on Middlebrook 7H11 agar plates with X-factor strips (Becton-Dickson Microbiology Systems, Cockeysville, MD), incubated at 30° C in an atmosphere of 10% CO₂. Colonies were detected at 5 wk and the organism was identified as M. haemophilum by growth characteristics, DNA probe analysis, and conventional mycobacterial identification tests. Antimicrobial susceptibility studies using a disk elution method (9) showed the organism was sensitive to ciprofloxacin, clarithromycin, ethambutol, doxycycline, amikacin, and streptomycin.

View larger version (102K): [in this window] [in a new window]   Figure 2.   Computerized chest tomography shows a nodular 2 × 2 cm lesion with surrounding infiltrate in the right lower lobe.

The patient was initially treated with isoniazid, rifampin, pyrazinamide, and ethambutol for presumed tuberculosis, although the lack of necrosis on pathological specimens was recognized as unusual. After 2 mo of four-drug therapy, she continued on isoniazid (INH) and rifampin for 1 mo but all drugs were stopped after final identification of the organism. She remains clinically well at 5 mo after the biopsy. The chest radiograph postoperatively showed only scarring in the area of the biopsy. A chest radiograph several months after treatment was stopped showed no evidence of active pulmonary disease.

	DISCUSSION

TOP ABSTRACT INTRODUCTION CASE REPORT DISCUSSION REFERENCES

Mycobacterium haemophilum has only recently been recognized as a cause of disease in humans. In 1978, it was recovered from cutaneous lesions of an Israeli patient with Hodgkin's disease (10). Since then, approximately 80 cases have been described worldwide (2, 8). Most have been in patients who are immunocompromised, including patients with acquired immunodeficiency syndrome (AIDS), lymphoma, rheumatoid arthritis, Crohn's disease, or following bone marrow and solid organ transplants. The most common manifestations have been tender ulcerating skin lesions. Joint and bone disease as well as multisystem disease and bacteremia have also been reported (2, 3). Four cases of pneumonia (2) and three additional cases of recovery of the organism from respiratory secretions (1, 11, 12) have been described in immunocompromised patients and are listed in Table 1.

Two of the cases of pneumonia were in allogeneic bone marrow transplant recipients and presented as pneumonia without skin lesions (3, 4). One of these patients had a focal lower lobe infiltrate which progressed to bilateral infiltrates. Bronchoscopy had been negative on two occasions (although specimens were not inoculated on media for culture of M. haemophilum) and an open lung biopsy showed non-necrotizing granulomatous infection with multiple acid-fast organisms seen; cultures grew M. haemophilum. A second bone marrow transplant patient had a cavitary infiltrate with recovery of the organism from sputum and lung tissue. Both of these patients died from their pneumonias, despite treatment. Two patients with AIDS presented initially with skin lesions which responded to treatment but subsequently developed pulmonary disease (2, 3). Both died of other complications of AIDS. There were three cases where respiratory cultures grew M. haemophilum, without clear-cut evidence of pneumonia, although two had respiratory symptoms (1, 11, 12).

In immunocompetent patients the organism has caused lymphadenitis in children (2, 5) and there is one case of a cutaneous lesion in a woman after coronary artery bypass surgery (9). Our patient is the first reported case of a pulmonary lesion with this organism in an immunocompetent patient. Although the patient had a history of breast cancer, there was no evidence of active cancer and she had not received chemotherapy for several years.

The reservoir of infection and mode of transmission of M. haemophilum are unknown. Cases have been reported from North America, Europe, Australia, Israel, and Taiwan, suggesting a wide distribution (2). A large number of cases have been reported from New York City, but the reason for this is unknown (1, 13). Our patient had been in New York City 2 yr prior to diagnosis of this infection but her chest radiograph had been normal at that time and she had no respiratory symptoms. She became symptomatic in the Philippines with a new abnormality on her chest radiograph, and it is likely that her infection was obtained there. Her source of exposure was unknown.

In the immunocompromised host, prolonged antimicrobial therapy has usually been needed for treatment. The organism is most susceptible to ciprofloxacin, clarithromycin, rifabutin, and rifampin. Treatment is often given with ciprofloxacin, clarithromycin, and one of the rifamycins, with length of therapy guided by the underlying condition and clinical response (2). The immunocompetent children have done well with excision of the infected tissue in most cases and the role of antimicrobial therapy in this setting is unclear. Because our patient had already received 3 mo of antituberculosis treatment and the lesion had been resected, and because she was clinically well without radiographic evidence of disease, we elected to stop treatment and observe.

M. haemophilum is a fastidious and slow growing mycobacterium that requires lower temperatures for incubation than most mycobacteria. The optimal temperature for growth is 30 to 32° C and growth requires iron supplementation of the media (2). Because it is difficult to grow M. haemophilum under routine culture conditions, it is possible that this organism may not be cultured in specimens in which it is present. The organism was recovered from our patient because our laboratory routinely inoculates media containing an iron supplement 30° C for the following situations: all specimens that are smear- positive for acid-fast bacteria, and all cases of cutaneous ulcerations or septic arthritis in immunocompromised patients, undiagnosed pulmonary lesions in bone marrow transplant recipients, and adenitis in children.

We present this case to make clinicians aware that pulmonary lesions in a normal host may be caused by M. haemophilum. Only with further description of cases will we know the full spectrum of disease associated with the organism and begin to understand more about its method of acquisition. In appropriate clinical settings, particularly those with a smear positive for acid-fast bacteria but negative cultures or in cases of unusual or undiagnosed non-necrotizing granulomatous pneumonias, clinicians need to communicate with their laboratory that M. haemophilum may be a consideration. The laboratory should also communicate to clinicians the need for appropriate culture condition for this organism. The development of appropriate culturing routines for specific clinical settings, as are in place at our institution, may also be helpful.