Clinical Case Report

A Case Report Of Systemic Blastomycosis In An Adult Male

Krista Anders, M.D., Helena Karnani, M.D. & Annette Laubscher, M.D.
Krista Anders, M.D., Helena Karnani, M.D. and Annette Laubscher, M.D.
are with the Family Practice Residency Program at St. Vincent's Medical Center.

Case Report

A 37-year-old African-American Male with no significant past medical history and social history significant for smoking and intermittent incarceration was initially admitted with left lower lobe pneumonia in January 2000. The patient denied any history of IV drug abuse or other risk factors for HIV. He was treated with intravenous Ceftriaxone and Erythromycin. Blood and sputum cultures failed to grow any pathologic organisms. A skin test demonstrated anergy to tuberculosis, mumps and candida. HIV antibody test was non-reactive. The patient clinically improved and was discharged on oral Azithromycin after 5 days of intravenous therapy. He was seen 3 days later in follow up as an outpatient and since he did not fill the previous prescription, he was given 10 days worth of Clarithromycin samples.

Approximately one month later, the patient presented back to the Emergency Department with persistent fever, malaise and a painful right arm mass, which had been present for two weeks. He denied trauma to the arm, but did admit to poor compliance with the Clarithromycin. The patient denied any recent travel out of the state of Florida and his social history was unchanged. He was afebrile and appeared nontoxic. His lung examination was normal and the only significant finding on examination was a firm mass, 3x5cm in diameter, palpable adjacent to the biceps muscle of the right arm. The mass was tender, but not warm, erythematous or fluctuant. No skin lesions were noted. Complete blood count was significant for a leucocytosis of 27,000 with predominant neutrophilia and a thrombocytosis of 529,000. Arterial blood gases and serum chemistries were normal. Chest x-ray revealed a left lung infiltrate, increased in size since his previous hospitalization (Figure 1.) Right arm x-ray revealed no bony abnormalities.

Figure 1. Admitting chest x-ray, February 2000.

The patient was admitted and placed on Ceftriaxone and Erythromycin. Sputum cultures and gram stains were negative for acid-fast bacilli and other pathological organisms. A repeat HIV antibody screen was non-reactive. CT examination of the chest indicated a left lower lobe and lingula infiltrate and a small nodule in the right middle lobe. Imaging studies of right upper extremity revealed a 6x2cm area of soft tissue swelling with an apparent necrotic center. Bronchoscopy was performed and transbronchial biopsies obtained revealed granulomatous inflammation with a single yeast-like structure identified. AFB stains, PCP stains and stains for viral inclusions were negative. An incision and drainage was performed of the right arm mass and cultures and biopsies were obtained from adjacent muscle tissue.

Serum cryptococcal antigen and Blastomycoses antibody tests were negative as well as Bartonella Henselae and Toxoplasma Titers. Subsequently, the cultures from the right arm grew out a similar fungal form to that identified from the bronchoscopy specimens. A tentative diagnosis of Blastomyces Dermatitides was confirmed by a reference laboratory per the Gen-Probe technique.

The patient was placed on Amphotericin B and his fevers and leucocytosis subsequently subsided. His medication was changed to Itraconazole and he was discharged on a dose of 200mg daily for a recommended duration of 6 months.

On retrospective questioning, the patient recalled a trip to Oklahoma during the past year, which included an overnight stay along the road at a small motel, the location of which he could not remember. He admitted taking an early morning run in a fairly wooded area at this location.

Discussion

Blastomycosis is a granulomatous fungal infection caused by the organism Blastomyces dermatididis. It is endemic in the midwestern and south central United States but not commonly seen in Florida. It most commonly infects normal healthy people with a predominance in males.

Spores reside in the soil and enter the body by inhalation. The spores may either be cleared by alveolar macrophages or undergo transition to a yeast phase. The yeast phase is not transmissible from person to person but can disseminate via the bloodstream to other organs in the body. Infection initially produces a suppurative response with polymorphonuclear leukocytes followed by an influx of macrophages forming a distinctive granulomatous reaction. The granulomas typically do not caseate, as is the case in tuberculosis.

Patients with blastomycosis can present with symptoms of acute pneumonia, chronic pneumonia or no pulmonary symptoms at all. The symptoms, therefore, can range from fever, chills and cough productive of purulent sputum and frequently, hemoptysis, to constitutional symptoms, such as weight loss, night sweats, fever, malaise, and other nonspecific complaints. There are a few reports of pulmonary blastomycosis progressing to severe ARDS, and death occurs in about 5% of all reported cases. In some patients the pulmonary phase can resolve spontaneously without progression to extrapulmonary disease.

In most cases, the chest radiographs commonly show an alveolar or mass-like infiltrate, leading to a suspicion of carcinoma or tuberculosis. Many other findings have also been reported, such as miliary or reticulonodular patterns and, more rarely, cavities or pleural effusions.

Cutaneous lesions are the most common extrapulmonary manifestation of blastomycosis and tend to occur on exposed parts of the body. They may be verrucous with erythema and crusting or sometimes ulcerative. The lesions are usually painless. Blastomycosis has also been associated with erythema nodosum.

After the skin, the musculoskeletal and genitourinary systems are the most commonly affected organ systems, but lesions of blastomycosis can occur in virtually any organ. Abscesses can form in the subcutaneous tissue, but can also be found in the brain, skeletal system, prostate, heart, sinuses, and pituitary or adrenal glands.

Genitourinary infections are commonly asymptomatic but may present with dysuria, pyuria or hematuria and prostatitis and epidydimoorchitis in men. The central nervous system may also be infected and presents as meningitis or more commonly as an epidural or cranial abscess.

Specific endocrine abnormalities may appear in patients with blastomycosis. Adrenal insufficiency from gland destruction, thyroid infection and hypercalcemia have been reported.

Diagnosis

The "gold standard" for the diagnosis of blastomycosis is the visualization of the fungus in tissue or exudate, followed by cultures from sputum, tissues or other infected biological material. When identified, the presence of large single-budding yeast-forms is demonstrated on potassium hydroxide smears. Culture identification of Blastomyces dermatitides can be time-consuming, since the organism may take up to 30 days to grow on culture. For early identification of culture isolates, a specific DNA-probe has been developed and is a reliable confirmation of the diagnosis.

Serological tests are available, such as complement fixation, immunodiffusion tests and enzyme immunoassays, but are not very sensitive and therefore, cannot rule out the infection if negative. Skin testing with blastomycin is unfortunately no better as a diagnostic procedure.

In the pulmonary form of the disease, sputum cultures are often negative. The infection often becomes well localized in the lung, making the organism difficult to recover from sputum secretions. Occasionally, to obtain adequate specimens for culture or smears, bronchoscopy for bronchial washings, or even open lung biopsy must be performed. Since the history of the disease often suggest a carcinoma, the organism is sometimes identified with cytology smears. Skin lesions are more likely to yield a definitive diagnosis of blastomycosis than sputum secretions in a patient who presents with pulmonary and cutaneous symptoms.

Treatment

Amphotericin B is the drug of choice for severely immunocompromised patients and for patients with life threatening disease, central nervous system disease, or patients whose disease progresses while taking an oral azole. If the patient has an initial good response to amphotericin B they can be switched to a 6-month course of an oral agent, usually itraconazole at 200mg per day. Amphotericin B remains the drug of choice in children. Patients with mild to moderate pneumonia or skin lesions can be initiated on oral medications - usually itraconazole. This is preferred to ketoconazole as it has less GI side effects and is better absorbed.

Conclusion

Blastomycosis can present with a wide spectrum of clinical symptoms and signs, ranging from pneumonia, or mild cutaneous lesions to fulminant multi-organ involvement. The diagnosis of blastomycosis should be suspected in patients who fail to respond to customary treatment for community acquired pneumonia, when travel to an endemic area in the preceding months has been reported. To make a definitive diagnosis, occasionally invasive procedures such as bronchoscopy or open lung biopsy are required. The organism can be identified on smears or culture, but a DNA- probe is available for early confirmation of the diagnosis when suspected. Amphotericin B is the treatment of choice for seriously ill patients, but the oral agent itraconazole is used for treatment of patients with less fulminant involvement.

July, 2000/ Jacksonville Medicine

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