Symptomatic Pulmonary Histoplasmosis: This fungal lung infection is notably linked to inhalation of dust ridden with fungal spores from bird or bat droppings from excavation, construction, or cleaning of farm buildings. A limited number of individuals exposed to H. capsulatum develop symptoms. Often the symptoms present weeks following exposure and are mild in nature. However, this type of infection can occur if the patient is immunocompromised. The most common symptoms include fever, chills, headache, myalgias, anorexia, cough, and pleuritic chest pain. The physical examination is typically unremarkable with potential for fever, rales, and evidence of consolidation by percussion or tactile fremitus. On radiological exam, the lung fields will show focal infiltrates and mediastinal or hilar lymphadenopathy but may also be normal. Histoplasmosis should be considered as a differential diagnosis for CAP that does not respond to empirical antibacterial therapy.
Acute Diffuse Pulmonary Histoplasmosis: This type of H. capsulatum infection occurs following a heavy exposure to soil that is saturated with droppings from birds or bats. On x-ray, diffuse reticulonodular pulmonary infiltrates are present and the disease can progress quickly to a respiratory emergency. Treatment is recommended for this level of infection and following recovery, the patient may complain of symptoms of shortness of breath and exhaustion for months.
Chronic Pulmonary Histoplasmosis: The chronic nature of a H. capsulatum infection correlates with chronic lung disease. These patients often have a chronic productive cough, dyspnea, chest pain, fatigue, fevers, and sweats according to multiple sources. X-rays or CT scans reveal fibrotic apical infiltrates with cavitation and the findings are alike those seen in patients with reactivation tuberculosis. With this infection, the cavities continue to grow and gravitate towards new areas of the lung and can result in complications such as fistulas. Of clinical importance is the disproportionate level of inflammatory response in the lung fields. It is critical to evaluate for both tuberculosis and histoplasmosis for proper treatment. Potential complications complicate treatment and require evaluation and treatment. Due to the prevalence of tobacco abuse among these patients, lung cancer should be considered in all patients that have nodular lesions that are not responsive to treatment or that spontaneously develop during the course of treatment.
Broncholithiasis: Calcification of the lymph nodes and pulmonary nodules may occur within several years in adults. Occasionally, the calcification can cause damage to the bronchi leading to chronic cough, wheezing, hemoptysis, fever, chills, purulent sputum, or expectoration of gravel-like stones. The gritty sputum should warrant consideration of histoplasmosis as a differential diagnosis. Surgical removal may be necessary for patients with hemoptysis or other complications of the infection.
Mediastinal Granuloma: Although rare, clinicians should be aware of the potential complication of enlarged mediastinal lymph nodes (mediastinal granulomas). These granulomas are encapsulated and caseous in nature. The complexity related to this development of compression to the associated structures and is highlighted by complaints of chest pain, hemoptysis, and shortness of breath. Respiratory distress is possible and particularly of concern in those of younger age. CT imaging reveals the necrotic nature of the mediastinal lymph nodes; however, older lesions will be notably calcified. If the lesions are liquified, rupture is possible and may result in cystic lesions that are air-filled.
Fibrosing Mediastinitis: This condition is notable for extensive fibrosis and is common in individuals ages 20-40 that have an infection from the H. capsulatum microbe. Complications from the fibrotic nature of these cases include invasive disease progression to the related structures such as the esophagus, vascular structures, and the main airways.
Pericarditis: This is a rare manifestation with histoplasmosis but is thought to be associated with an immune response to the microbe. Due to the potential for undetected H. capsulatum infection with only mild respiratory symptoms, the clinician should be aware that pericarditis can occur as a result of the infection for several weeks to months post-infection. Often the presentation includes a patient with notable chest pain and fever. On exam, a pericardial friction rub and pleural effusions often accompanies this manifestation linked to histoplasmosis.
Rheumatic Complications: Histoplasmosis can cause polyarticular pain in a small number of individuals and is more predominant in women. This complication is believed to a systemic inflammatory response to the acute infection rather that dissemination of the microbe in the related structures. The affected joints can be small or large and upper or lower extremity involvement is possible. Symptoms often disappear spontaneously but may require a short course of NSAIDs or corticosteroids but should be used cautiously because it may cause a flair of a progressive infection due to the immunosuppressive side effects of the steroids.
Sarcoidosis: Clinical manifestations are similar to those associated with histoplasmosis. In fact, a small number of patients with sarcoidosis may present with elevated antibody titers to the H. capsulatum microbe. The association between this finding is still unclear. The primary precaution in this differential consideration lies with the treatment options for sarcoidosis and the use of corticosteroids which may prompt dissemination of the H. capsulatum infection. Recommendations include testing to rule out active histoplasmosis prior to treatment for suspected sarcoidosis.
The CDC notes that those at highest risk for the development of histoplasmosis infection include:
- Those that work in environments that disturb soil or are involved in construction or renovation of older buildings that may have heavy bird or bat droppings on site
- Immunocompromised patients
- Those taking long term corticosteroids or TNF-inhibitors
- Organ transplant recipients
- Older adults; age 55 and older
The CDC recommends antigen testing via urine or serum screening although other methods are available. Antigen detection can be done on urine or serum samples and provides rapid detection of the microbe which is particularly helpful in those patients with severe illness. Utilization of the EIA may result in cross-reactions, specifically those with blastomycosis. Antibody testing is available but the testing takes several weeks and may delay treatment. PCR testing has not been proven as a preferred method of diagnostic evaluation; however, recent studies do indicate that this method is showing clinical value. Cultures take weeks for results and are most useful for patients suspected of having chronic pulmonary histoplasmosis.
Primary focus for treatment should be aimed at the clinical presentation and symptoms. Often, treatment is not necessary in those with a mild infection. However, those with severe illness typically require treatment with antifungal agents like itraconazole, fluconazole, voriconazole, posaconazole, isavuconazole, and amphotericin B. Recommended treatment for mild to moderate histoplasmosis infections includes the use of itraconazole and utilization of amphotericin B should be initiated for those with moderately severe to severe infections. The CDC recommends referral to these guidelines for the most up to date information regarding treatment of histoplasmosis.
Amphotericin B: Potential nephrotoxicity; Warrants in-patient evaluation & monitoring
Itraconazole: Serum concentration should be evaluated after 2 weeks of therapy
Corticosteroids: Avoid use due to the potential for progressive disseminated histoplasmosis infection
Chronic histoplasmosis disease requires treatment because failure to treat may result in permanent lung disease or death in some cases. The preferred treatment in these cases is itraconazole. Therapy begins with a loading dose and then is followed with a maintenance dose for a minimum of one year. Therapy should be maintained until findings on imaging have stabilized. Relapse is possible and often occurs within two years of discontinuing treatment. The clinician should regularly evaluate the patient for five years and a chest x-ray should be evaluated bi-annually during the first year of treatment and then annually or upon recurrence of symptoms.
The patient with moderate to severe disease or those with other complications related to the H. capsulatum infection should be referred to a pulmonologist for evaluation and treatment. Patients with pericarditis associated with this infections should see a cardiologist. Rheumatic complications can be managed with the use of NSAIDs and corticosteroid use should be reserved for those patients that fail NSAID treatment. Antifungal treatment is required for those that present with disseminated disease and should be followed by infectious disease or other specialists with disease specific knowledge.
Precautions, Identification, & Prevention
Prevention of histoplasmosis infections can be difficult in some industries. The CDC provides a document for those workers that are most a risk and should be offered as part of a wellness check to individuals that have occupational risk factors. Click here for a copy of the document.
Centers for Disease Control and Prevention (CDC), (2018). Fungal disease: Histoplasmosis. Retrieved from https://www.cdc.gov/fungal/diseases/histoplasmosis/index.html
Kauffman, C. A. (2020). Diagnosis and treatment of pulmonary histoplasmosis. UpToDate. Retrieved 7/11/2020, from https://www.uptodate.com/contents/diagnosis-and-treatment-of-pulmonary-histoplasmosis?search=diagnosis%20and%20treatment%20of%20pulmonary%20histoplasmosis&source=search_result&selectedTitle=1~33&usage_type=default&display_rank=1
Kauffman, C. A. (2020). Pathogenesis and clinical features of pulmonary histoplasmosis. UpToDate. Retrieved 7/11/2020, from https://www.uptodate.com/contents/pathogenesis-and-clinical-features-of-pulmonary-histoplasmosis?search=diagnosis%20and%20treatment%20of%20pulmonary%20histoplasmosis&source=search_result&selectedTitle=2~33&usage_type=default&display_rank=2