Histoplasmosis is the most prevalent of the systemic mycoses; cases are reported on every continent except Antarctica. Temperate zones between latitudes 40°N and 30°S provide the 35 to 50 inches of rainfall, 67% to 87% humidity, and temperature range of 22°C to 29°C needed for the mycelial phase of the fungus to grow. Temperature and humidity may affect infection rate and severity of clinical manifestations. The fungus prefers acidic soil conditions with high nitrogen content. This is thought to account for the association of histoplasmosis with avian and bat guano. Infections of a broad array of mammals have been reported, but the avian species appear to escape disease because of their higher body temperatures (1,2,3).

Infection with Histoplasma capsulatum begins with inhalation of microconidia. The vast majority of those infected will have no immediate symptoms. Symptoms of the acute pulmonary phase include fever of 42°C, headache, arthralgia, myalgias, a nonpleuric substernal chest pain from mediastinal and hilar lymph node enlargement, erythema nodosum or

Table 28.1. Systemic fungi.


Microscopic description of yeast (infectious) form

Histoplasma capsulatum

Polar budding with thin neck between mother and daughter

cells (3-4 microns) |m

Blastomyces dermatitidis

Thick refractile wall; multinucleated with single, broad -

based bud (8-15 microns)

Coccidioides immitis

Spherule with many endospores

Coccidioides posadaii

Sporothrix schenckii

Oval or cigar-shaped yeast with budding

Source: Data from Kaplan (1) and MacKinnon (2).

Source: Data from Kaplan (1) and MacKinnon (2).

erythema multiformi, pericarditis, and a patchy pneumonitis on chest x-ray. They begin 7 to 21 days after exposure. Symptoms usually resolve within 10 days. Evidence of past infection includes pulmonary calcifications with a Ghon-like complex on chest x-ray and liver or splenic calcifications (3).

Approximately 5% of immunocompetent patients with histoplasmosis will develop progressive disseminated histoplasmosis (PDH). The incidence in immunocompromised patients such as HIV, transplant recipients, or the elderly is higher. PDH can develop after reactivation of dormant disease or reinfection with a large inoculum. PDH produces a wide range of disease that is categorized by clinical presentation into acute, subacute, or chronic (2,3).

Acute PDH is mostly seen in infants or immunocompromised patients. Patients develop abrupt onset of fever and malaise, weight loss, diarrhea, cough, hepatomegaly, lymphadenopathy and pancytopenia. Fatality is nearly universal without treatment. Subacute PDH has a more prolonged presentation with less fever and less striking laboratory abnormalities. The prolonged course of subacute PDH produces more distinctive clinical features such as ulcers in the large and small bowel with diarrhea, cramping, or perforation, endocarditis, intracranial masses, or chronic meningitis. Involvement of the adrenal gland occurs in 80% of subacute PDH patients, but symptoms of adrenal insufficiency are uncommon. Chronic PDH has a more prolonged presentation with milder symptoms. Malaise and lethargy are the most common complaints with oropharyngeal ulcers being the most common physical finding. There is notable absence of major organ involvement as seen in sub-acute PDH (1,2,3).

In addition to PDH, histoplasmosis has several clinical entities associated with chronic inflammation. Involvement of the lymph nodes can produce a mediastinal fibrosis that encroaches on vital structures. A fibrous mass called a histoplasmoma may develop from chronic inflammation, usually in the lung. Anterior uveitis or panophthalmitis may develop. More commonly seen is the ocular histoplasmosis syndrome that is characterized as a posterior uveitis/chorioditis that may result in neovascularization, scarring, and macular hemorrhage. Cavitary pulmonary histoplasmosis is characterized by fever, productive cough, dyspnea, weight loss, night sweats, hemoptysis, and upper lobe cavitations on the chest x-ray (1,2,3).

In addition to Histoplasma capsulatum, African soil also supports Histo-plasma duboisii. The clinical presentation of this species is usually restricted to skin and bone, although progressive disseminated disease has been reported. Skin lesions are usually ulcers, nodules, or plaques resembling psoriasis or subcutaneous nodules without inflammation (cold abscess). The skull, ribs, or other bones develop oteolytic lesions with associated sinus tract or cystic bone formation (3).

The definitive diagnosis of histoplasmosis comes from culturing the organism from the patient or by visualization on a tissue specimen with silver stain (Figure 28.1). Antigen testing for histoplasmosis is most useful for rapid diagnosis and may be used to monitor therapy and relapse. Anti-histoplasma antibodies develop 2 to 6 weeks after infection. Interpretation of this antibody testing has limitations that must be considered, such as cross reactivity with blastomycosis and coccidioidomycosis. Development of commercial PCR testing will allow rapid and specific diagnosis. Skin testing is useful for epidemiologic studies but has little diagnostic value (3).

Patients with acute pulmonary and cavitary histoplasmosis may resolve without treatment. Patients with severe symptoms, mediastinal fibrosis, sub-acute or chronic PDH should be treated with itraconazole, ketoconazole or amphotericin B. Patients with acute PDH, meningitis, or endocarditis can be treated with amphotericin B. The fibrous histoplasmoma do not require treatment unless there is anatomical encroachment at which time they should be surgically removed (3).

Figure 28.1. Intracellular histoplasmosis capsulatum: macrophage on peripheral blood smear. Photo courtesy of Dr. Alan Scott Ragland.
0 0

Post a comment