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ID Rounds: A Fungus Among Us

Isaacs, Lawrence MD

doi: 10.1097/01.EEM.0000389823.56232.d4
ID Rounds
The fungus

The fungus

Sporotrichosis, histoplasmosis, and aspergillosis are not as common as an infection like athlete's foot, but all can cause serious disease in immunocompetent and immunosuppressed individuals. All are found around the world, with histoplasmosis and aspergillosis contracted by inhalation and sporotrichosis most often by skin contact.

Sporotrichosis is caused by the fungus Sporothrix schenckii, a mold found worldwide but that grows primarily in warmer climates. S. schenckii lives on decaying organic material like moss, hay, pine needles, and soil. The disease begins when the fungus in mold form is inoculated into the skin, converting to the yeast phase and then spreading through the lymphatics. Patients with certain underlying conditions like diabetes, alcoholism, COPD, and HIV are at risk for dissemination of the organism to the lungs, meninges, or the osteoarticular structures.

One patient being treated with a TNF antagonist developed sporotrichosis. (Clin Infect Dis 2003;37[6]:838.) The most common form, lymphocutaneous, generally affects immunocompetent individuals under 35. The largest and most well documented outbreak occurred in South Africa from 1941 to 1944. More than 3000 gold miners acquired the disease through contact with mine timbers. (Infect Dis Clin North Am 2003; 17[1]:59.) The pulmonary form is thought to be contracted by inhalation, similar to other fungal pulmonary infections.

After inoculation, a papule develops at the site within days to weeks, which ulcerates with nodules appearing proximal to the original lesion, following the lymphatic distribution. These nodules also ulcerate. The primary lesion will remain until treated. The osteoarticular manifestation is usually a large joint effusion, monoarticular in immunocompetent hosts and polyarticular in immunocompromised ones. Patients rarely have a fever, and the joint fluid is diagnostic by culture only. The pulmonary form of the disease is the least common, presenting with productive cough, dyspnea, night sweats, and occasionally hemoptysis. Chest x-ray commonly reveals cavitary lesions.

The gold standard is a culture of aspirated material from the lesion; no serological or antigen-based testing exists. The treatment of the lymphocutaneous, pulmonary, and osteoarticular disease is itraconazole, commonly for three to six months for cutaneous and one to two years for osteoarticular. Fluconazole and SSKI (saturated solution of potassium iodide) are other treatment options. The treatment of disseminated disease is amphotericin B, and if immunocompromised (i.e., HIV), lifelong suppressive therapy with itraconazole is required. (Infect Dis Clin North Am 2006;20[3]:645.)

Histoplasmosis is caused by the fungus Histoplasma capsulatum, which is endemic to the Mississippi and Ohio River valleys, Central America, Southeast Asia, and the Mediterranean. The mold phase is found in nitrogen-rich soil, often bird and bat roosting areas. Unlike S. schenckii, the infection begins with inhalation. The usual initial symptoms are fever, chills, dyspnea, and nonproductive cough, and chest pain. The chest x-ray will show patchy lobar or multilobar infiltrates with hilar adenopathy. Immunocompromised patients can have a severe, life-threatening pneumonia, leading to ARDS. Most patients, however, have a self-limited illness or good response to therapy. (Infect Dis Clin North Am 2006; 20[3]:645.)

Although most patients have an uncomplicated course, several rare complications occur, all related to mediastinal involvement. Pericarditis, thought to be an inflammatory reaction to the mediastinal involvement, presents with typical symptoms; the fluid is usually sterile, and the condition is benign and self-limited. Two types of mediastinitis — granulomatous and fibrosing — are associated with histoplasmosis; both are rare, with fibrosing being the more serious. Disseminated infection, like disseminated S. schenckii, is a disease of the immunosuppressed. The patient will be febrile and pancytopenic, with hepatosplenomegly. Overwhelming infection presents like sepsis, with DIC and ARDS common. Even more uncommon are infections of the CNS, prostate, and epididymis.

The diagnosis can be made via blood and sputum cultures or, unlike S. schenckii, by a urine-based antigen test or serology detecting the presence of antibodies. The serology is not useful in severely immunosuppressed patients. Most patients with histoplasmosis do not require treatment because it is a self-limiting disease. Patients with severe disease or with symptoms for more than a month can be treated with itraconazole or amphotericin B. (Centers for Disease Control and Prevention Yellow Book.

Aspergillosis, the disease caused by the mold species Aspergillus, is caused by inhalation of the organism. Approximately 180 species of Aspergillus exist, but only 34 have been reported to cause disease in humans. The most common is A. fumigatus, with A. flavus, A. niger, A. versicolor, and A. terreus accounting for most human cases. Like S. schenckii and H. capsulatum, Aspergillus grows on organic matter; we inhale the mold almost daily, but only an unlucky few develop illness. Most individuals' lung macrophages destroy the mold, and no disease develops. In some, even with intact immune systems, the mold spores bud, an inflammatory response ensues, and disease develops.

In some patients, their immune system reacts inappropriately, and a disease develops, ranging from asthma and allergic sinusitis to invasive pulmonary disease. Evidence suggests that molds, including Aspergillus, are a cause of severe asthma. (Eur Respir J 2006; 27[3]:615.) The sinusitis caused by fungi is a noninvasive inflammatory sinusitis usually affecting younger, atopic patients. Allergic bronchopulmonary aspergillosis is a manifestation of a robust response to Aspergillus inhalation. It presents like asthma plus fever and hemoptysis. If untreated or inadequately treated, permanent lung injury with fibrosis will result. The diagnosis is made by chest x-ray (infiltrates that resolve with steroid treatment and central bronchiectasis) and detection of a serum IgE specific for Aspergillus. The treatment is oral steroids and itraconazole during the acute illness. (Infect Dis Clin North Am 2006;20[3]:545.) Aspergillus also can cause noninvasive pulmonary fungal balls; these usually occur in patients with underlying structural pulmonary disease. The fungus invades dead pulmonary spaces; the treatment is surgical removal of the fungus ball.

The invasive and disseminated forms of the disease are the most serious, with mortality reaching 100 percent in immunocompromised patients. The patients at highest risk for invasive and disseminated disease are stem-cell transplant recipients and long-term neutropenic patients. Also at risk, although lower than the stem cell transplant patients, are patients with HIV, diabetes, multiple myeloma, cystic fibrosis, and on chronic steroids. The clinical picture is fever, cough, pleuritic pain, and hemoptysis. Diagnosis is made by CT, looking for a “halo sign” (Radiology 1985;157[3]:611), culture, and an ELISA assay.

The treatment of invasive Aspergillus historically was amphotericin B and itraconazole, but recently voriconazole has been shown superior to amphotericin B with fewer side effects. (N Engl J Med 2002;347[6]:408.)

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Dr. Isaacs

Dr. Isaacs

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