Coccidiomycosis and histoplasmosis are endemic mycoses in the United States.
C & H are dimorphic mycoses that grow in mold in the environment and assume different structures when causing infections in a host.
Histoplasma is in many diverse areas worldwide, but in the Western Hemisphere, it is most commonly distributed in the central in the mid eastern US and Central America, where it thrives in soil with high nitrogen content.
Coccidioides is most prominent in arid regions, especially Arizona, and California.
Climate change is predicted to expand its prominence across much of the western US.
There are genetically and geographically two discrete clades of Coccidioides.
Coccidioides immitis primarily endemic in California and C. posadasii endemic elsewhere throughout the western hemisphere.
There of four species of histoplasmosis based on genetic differences.
There has been no clinical differences in the behavior of the varying Coccidioides and histoplasmosis species.
Coccidioidomycosis and histoplasmosis infections are required by inhalation of airborne spores (conidia) from the environment.
For most individuals this does not result in clinical illness.
Symptomatic disease occurs in a small portion of persons infected with Histoplasma.
Clinical disease, however, apparently develops in 1/3 of person is exposed to Coccidioides.
Ambient exposure accounts for most cases of infection with both fungi and is likely to be the result of an infection by very small numbers of conidia.
The likelihood of symptomatic infection and pulmonary infection that can be more severe occurs with exposure to higher inoculum of either fungus.
This type exposure occurs in the context of an outbreak related to a specific point source.
After exposure to coccidioides the illness develops after 1 to 3 week incubation, and the initial syndrome is not easily distinguished from community acquired pneumonia.
Chest x-rays show lobar disease, and may show peripneumonic effusions, and mediastinum adenopathy.
Systemic symptoms include fatigue, arthritis, myalgia, erythema nodosum and acute generalized exanthem.
Coccidioides infection is often debilitating with respiratory and other symptoms that persist for weeks to months.
Infection with Coccidioides is associated protracted symptoms due to a slow immunologic response to the infection.
Despite the significance of an uncomplicated coccicoidal infection, symptoms generally resolve without residual damage to the lungs or other organs.
A small number of patients become ill from exposure to histoplasma, with symptoms, developing 2 to 3 weeks later.
Most infections with histoplasmosis are related to inhalation of a small number of conidia during every day activities, and symptoms suggest community acquired pneumonia.
Arthralgias and erythema nodosum occur with histoplasmosis, but less often than noted with coccidiomycosis.
With histoplasmosis, an airspace disease, chest, x-rays frequently show hilar or mediastinal lymphadenopathy, which generally resolves in several weeks.
Some patients, those with more extensive pneumonia, have a prolonged course of asthenia after acute histoplasmosis.
The acute clinical illness of coccidioidomycosis or histoplasma, are largely self limiting so their underreporting is likely to be extensive.
Histoplasmosis is a reportable disease in only 13 states, and coccidioidomycosis is reportable, but many states did not conduct surveillance for this infection.
The initial infection in these diseases, in almost all persons who have specific T cell mediated immunity that activates macrophage to inhibit or kill the fungus.
With a coccidioidal infection, immunity is lifelong, and reinfection does not occur.
With a histoplasma infection, there is no guarantee for lifelong immunity, and reinfection can occur, especially with extensive exposure.
Both of these fungi can remain dormant for years after resolution of the initial infection, and no clinical significance occurs unless the patient becomes immunocompromised when T cell mediated immunity can no longer contain the organism and infection is reactivated.
The risk for reactivated infection is most common with HIV infection, and for those treated with tumor necrosis factor antagonist for rheumatologic, gastrointestinal or other diseases.
The highest risk for reactivated infection is with patients who have had solid organ transplants.
Following an uncomplicated coccicoidal infection, x-rays of the chest may have residual nodules up to several centimeters in diameter, that can appear solitary: CT scans may identify smaller satellite nodules.
These pulmonary nodules can persist for many years, usually do not calcify, and make them difficult to distinguish from malignant nodules.
Histoplasmosis infection may leave nodules in the lung that are small, numerous and calcified.
Calcifications in hilar and mediastinal lymph nodes are commonly observed in histoplasmosis, in contrast to coccidiomycosis.
Broncholithiasis rarely occurs with histoplasmosis, where calcified material intrudes into the bronchus, and is subsequently expectorated.
Mediastinal complications in histoplasmosis, not seen in coccidiomycosis, includes mediastinal lymphatitis, mediastinalmgranuloma, and mediastinal fibrosis.
Histopathology of coccidioidal pneumonia is characterized by acute inflammation with neutrophils and eosinophils with tissue necrosis, and in some cases liquefaction and cavitation.
Patients with histoplasmosis have lowly resolving initial pulmonary lesions, with small nodularities.
Chronic cavitary pulmonary histoplasmosis occurs, almost exclusively in patients with COPD.
Radiographically chronic histoplasmosis of the lungs shows multiple thick wall cavities, and progressive interstitial changes.
The natural history of this form of histoplasmosis is a progressive downhill process.
Histoplasmosis infection is spread hematogenously to organs of the reticuloendothelial system and occurs before an effective cell mediated immune response has occurred.
In immunocompetent individuals, the process is self limited, with multiple small splenic calcifications on radiographic studies, as the only residual evidence of infection.
Disseminated coccidiomycosis is characterized by destructive skeletal skin, and meninges lesions, which develop more frequently than does disseminated histoplasmosis in apparently in immunologically normal people.
Disseminated coccidiodomycosis risk factors include male gender, African or filipino ancestry or age beyond puberty.
Disseminated histoplasmosis in immunocompetent person occurs mostly in old men.
Skin and skeletal lesions are common in disseminated coccidioidal infection, but are infrequent in disseminated histoplasmosis.
Chronic forms of histoplasmosis include fevers, night sweats, weight loss, and fatigue.
Specific mutations in genes, controlling immune responses, including receptors for interferon gamma, and interleukin12 explain the development of disseminated coccidiomycosis or histoplasmosis, in some patients, but not appear to account for most cases of disseminated infection.
Disseminated coccidioidal infection among persons of color is several times higher than the overall risk of one percent or less in the general population.
Diagnosis of histoplasmosis and coccidioidomycosis is made by culture and histopathologic testing.
Other testing, including antigen detection allows for a rapid diagnosis of probable histoplasmosis and detection of specific anti-coccidioidal antibodies for the diagnosis of coccidioidomycosis.
Antigen testing in urine and serum specimens is a major tool for the rapid diagnosis of histoplasmosis, in disseminated disease, those with severe pulmonary infection, and some patients with acute pulmonary histoplasmosis.
Management: previously amphotericin B was the only treatment for most forms of coccidioidomycosis, and histoplasmosis.
The treatment of these diseases have been revolutionized by the treatment of triazole therapy.
In coccidioidomycosis symptomatic patients benefit from oral triazole treatment.
Triazole treatment is often required for years.
Patieents with coccidioidomycosis meningitis should be treated for life.
Most patients who require treatment of coccidioidomycosis, the triazole of choice is fluconazole.
Itraconazole is also effective, but has more variable absorption and adverse effects.
For patients with severe disease therapy with amphotericin B lipid form should be provided initially with step down to triazole once clinical improvement is established.
Severe pulmonary or disseminated histoplasmosis is initially treated with the lipid formulation of amphotericin B: histoplasmosis infection is sensitive to this agent and step down therapy for less severe disease with itraconazole is the treatment of choice.