What is Histoplasmosis?

Histoplasmosis (Histo) is a fungal infection caused by the germ Histoplasma capsulatum. This fungus is common in certain parts of the United States and Latin America, including the Ohio, Mississippi and St. Lawrence River valleys, particularly Indiana, Ohio, Kentucky, Tennessee, Illinois, and Missouri.  However, histo can be acquired in areas outside the endemic region. Histo is found in the soil, particularly soil which has been enriched with bird or bat droppings. Histo may also be found in chicken houses, barns, belfries of churches or attics where bats have lived, lofts, caves harboring bats, and in woods where birds have roosted. Exposure to histo occurs when humans or animals come into contact with sites such as those listed above. Of note, not all sites contain the organism.

How Do People Get Histo?

People get histo by breathing air which contains small spore forms of the organism.  Commonly such individuals have been exposed to environmental sites such as excavation projects in areas where birds had previously roosted, have hobbies which expose them to bird roosts or bat habitats, have remodeled old buildings which had been inhabited by birds or bats, or have cut timber in a woods which had been a roosting site for blackbirds.   However, in most cases patients do not recall a specific exposure. Because the organism is so tiny, it cannot be seen in the air. Histo may be spread by the winds to miles away from the contaminated environmental site, and patients may not be aware of their exposure. Illness may first appear years after leaving the area where histo was acquired. This type of infection is called reactivation histo and occurs in patients with serious underlying disorders, such as organ transplantation or acquired immunodeficiency syndrome (AIDS). After breathing in air containing the organism, it causes infection in the lungs and may spread by the blood stream to involve other parts of the body.

Are Some People More at Risk than Others?

While histo is capable of infecting healthy individuals, it causes more severe disease in patients with diseases which impair their body's ability to fight infection. In healthy individuals histo usually causes no symptoms or mild flu-like symptoms with fever, cough, chest pain and fatigue. If such symptoms occur, they typically last only a few weeks and cause no long-term ill effects. But in individuals with impaired defense against infection, histo causes more severe illness with long-term consequences. For example, in patients who have emphysema caused by heavy tobacco use histo causes a chronic lung infection which usually requires treatment. Also, in patients with diseases which impair their immunity, including AIDS, organ transplantation, and use of corticosteroids, histo may spread from the lungs to involve other parts of the body. In such cases the infection is progressive and usually fatal if left untreated.

What Are the Symptoms of Histoplasmosis?

Histo causes a spectrum of illness, and the symptoms vary depending on the type of infection, the underlying health of the patient and the extent of the exposure. For example histo would be more severe in a worker who inhaled thousands of spores while cleaning a contaminated barn than in a jogger who inhaled a few while running down a nearby country road. Similarly, illness would be less severe in a healthy individual than in his/her friend with cancer or AIDS who was exposed at the same time. Histo usually causes mild illness which resolves on its own (self-limited) but may cause severe, even fatal disease, which progresses if not treated.

Acute self-limited histo.

In the healthy individual histo may cause no symptoms or may cause a flu-like illness with fever, cough, chest pain and fatigue. Typically histo causes pneumonia and enlargement of the lymph glands within the lungs, producing masses on the chest X-ray. The X-ray may give the appearance of a cancer or lymphoma. Biopsy of the lymph glands, however, shows histo or granulomas rather than cancer or lymphoma.

In some healthy individuals histo may cause joint pain, muscle pain and painful red lumps on the arms or legs (erythema nodosum). This type of histo often is mis-diagnosed as sarcoidosis, a non-specific inflammatory condition involving the lungs, nearby lymph glands, joints, and skin.

Histo also can cause inflammation of the lining around the heart, termed "pericarditis." In contrast to the usual flu-type illness which is caused by a virus, which typically improves within one week, symptoms of histoplasmosis usually persist several weeks before they disappear. These types of histo generally resolve on their own, although patients may remain ill for several weeks. Medicines which reduce inflammation may hasten the recovery particularly in a patient with pericarditis or inflammation of the joints.

Chronic pulmonary histo.

In patients with underlying emphysema histo causes chronic lung infection, and patients experience cough productive of yellow or green sputum (phlegm), chest pain, weight loss, night sweats and fatigue. These symptoms last several months and typically are progressive, leading to worsening of lung function. These findings are similar to those seen with tuberculosis explaining why some patients with histo are misdiagnosed to have TB. Treatment is reasonably effective but some patients may require second courses of treatment or chronic treatment to prevent relapse.

Disseminated histo.

In patients with impaired immunity histo causes severe disease spreading outside the lungs to involve other parts of the body, so called disseminated histo. The areas commonly involved are the bone marrow, causing anemia, lowering of the white blood cells or platelets, liver, spleen, lymph nodes, mouth, intestines, adrenal glands, and occasionally the brain. These patients usually have chronic fever and weight loss and usually die if not diagnosed and treated. This type of histo responds well to treatment.

Fibrosing mediastinitis.

Fibrosing mediastinitis is a less common but serious complication of histoplasmosis. Scarring extends from the lymph glands located in the chest to important nearby structures such as the large blood vessels entering the heart or lungs, the large breathing tubes (trachea and bronchi), the esophagus and even the heart. It is felt to represent a scarring response to a prior episode of histoplasmosis rather than an active infection and often is progressive in nature, causing a variety of serious complications. Treatment is not felt to be effective for this type of histo but often is tried at least once.

Presumed ocular histoplasmosis

. Histo may be a cause for spots on the back of the eye, "so-called" histo spots. These spots may be asymptomatic or may cause visual loss including blindness. Although "histo spots" have been attributed to histoplasmosis, there is no scientific basis establishing H. capsulatum as its cause. The association has been based on high rates of skin test reactivity rather than demonstration of the fungus in the tissues, and skin test results are insufficient to establish the role of histoplasmosis as a cause for eye disease. Occurrence of identical clinical findings in patients from areas where histoplasmosis is rare is evidence against histoplasmosis as a cause for this syndrome. The eye may be involved in patients with disseminated histoplasmosis, however. Therapy for histo is not effective and should not be tried in patients with presumed ocular histo. Laser treatment, corticosteroids and surgery often are helpful in patients with presumed ocular histo. Such treatments are supervised by ophthalmologists experienced with diseases of the retina rather than by internal medicine or infectious disease specialists

How Can Histoplasmosis be Diagnosed?

Several tests are useful for diagnosing histoplasmosis. Since histo is acquired by breathing the germ into the lungs, it usually causes abnormalities on chest X-ray. Although a chest X-ray does not provide an exact diagnosis of histo, it is often useful for suggesting the possibility of histo to your doctor. In more severe forms of histo, the diagnosis may be established by examination of specimens of sputum (phlegm), blood or biopsies from various tissues. Also, tests of (antibody) or blood and urine (antigen) measuring your response to histo or measuring substances which are produced by the fungus may be helpful.

Can Histo be Treated?

No treatment is required in most normal individuals with histo because the infection does not cause long-term ill effects and because the infection clears without treatment with no long-term complications. However, in individuals with underlying diseases which predispose them to the more severe forms of infection, treatment is available and is generally recommended. Amphotericin B is a medication which is given by daily or intermittent administration into your veins. Amphotericin B must be administered for prolonged periods, usually 4-12 weeks, to eradicate histo. In patients with severe underlying disorders, such as AIDS, life-long treatment is required to prevent the infection from recurring.
Itraconazole is used for most patients who require treatment, and is given by mouth for variable lengths of time depending on the type and severity of histo, and other conditions which affect the patient's overall health. Itraconazole is well tolerated but cannot be taken with several other medications and may lead to side effects of several other medications... Amphotericin B is used in patients with more severe manifestations or in those who cannot take itraconazole. It is highly effective but inconvenient to take because of the requirement for prolonged intravenous administration, and amphotericin B causes unpleasant side effects, including nausea, vomiting, and loss of appetite, chills, fever, muscle aches and fatigue. It also causes kidney damage and anemia which are reversible after the treatment is completed. Ketoconazole is another oral treatment for histo, but it has largely been replaced by itraconazole because itraconazole is more effective and better tolerated. Fluconazole can be used but is not as effective as itraconazole and should be reserved for patients who cannot take itraconazole.

Are There Any New Drugs Available for Treating Histo?

A study evaluating an intravenous form of itraconazole or a new liposomal form of amphotericin B (AmBisome) for treatment of histo is available at many medical centers throughout the United States