Histoplasmosis

By

Anastassia Doutova R2

10/06/06

Background First described by a United States Army

physician in Panama in 1906 Histoplasma capsulatum is a dimorphic fungus

that remains in a mycelial form at ambient temperatures and grows as yeast at body temperature in mammals.

Endemic to the Ohio, Missouri, and Mississippi River valleys (US) and river valleys between latitudes 45° north and 30° south in North and Central America.

Birds cannot be infected by the fungus and do not transmit the disease but their excretions enrich the growth medium for the mycelium;

bats can become infected, and transmit the fungus through droppings.

Contaminated soil can be potentially infectious for years.

BackgroundCause

inhalation of aerosolized conidia and mycelial fragments from soil results in alveolar deposition

Reactivation can occure Reinfection is possible although controversial

BackgroundRoute

Epidemiology

Most prevalent endemic mycosis in US 250-500K individuals are infected annually 50 million people infected in US Clinical illness occurs in <5% in people with underlying lung disease

chronic pulmonary histoplasmosis occurs at a rate of 1 per 100,000 persons per year

Clinical symptoms are more frequent in males than in females ratio of 4:1. Except for Rheumatologic manifestations which occur predominantly in females.

T lymphocytes are essential in limiting the extent of infection.

Cytokines activate macrophages for fungistatic activity against intracellular yeasts.

Organisms are confined to macrophages Delayed-type hypersensitivity to histoplasmal

antigens occurs 3-6 wk after exposure 85-90% of immunocompetent individuals

produce a positive response to skin antigen test calcified fibrinous granulomas with areas of

caseous necrosis develope over weeks to months.

Host Response

Course

Can take form of acute or chronic pulmonary infection but may also hematogenously spread systemically

spread may occur through the lymphatics to regional lymph nodes or the liver and spleen.

Progressive disseminated histoplasmosis is rare in adult hosts who are immunocompetent.

PresentationAcute Most individuals are asymptomatic Those who develop clinical manifestation

- usually immunocompromised

- or exposed to a high quantity onset occurs 3-14 days after exposure

Common: Fever, headache, malaise, myalgia, abdominal pain, and chills, cough, hemoptysis, dyspnea, chest pain

Large innoculum: severe dyspnea Uncomon:

Joint pain=arthritis and skin lesions=erythema multiforme, and erythema nodosum (5-6%) mostly in females.

Enlarged hilar and mediastinal lymph nodes are present in 5-10% of patients.

SVC syndrome Pericarditis In 5% causing cardiac temponade in 40%

Acute PresentationSymptoms/findings

occurs mostly in patients with underlying pulmonary disease

Reccurent histoplasmosis

- latent in healed granulomas

PresentationChronic

cough, weight loss, fevers, and malaise. ~ 90% of patients develop cavities that may

enlarge and result in necrosis. cavitations may cause hemoptysis, sputum

production, and increasing dyspnea formation of bronchopleural fistulae Broncholiths mediastinal granuloma and fibrosing

mediastinitis

Chronic PresentationSymptoms/findings

Presentation Dessiminated Histoplasmosis Occures in 1 out of 2000 acute cases but in patients with

impaired cellular immunity it happens in 4-27% Can present as subacute, acute or Hyperacute

syndrome typically involves CNS

liver spleen rheumatologic ocular Lymphnodes Mucosal ulcers in 50-60%

Dessiminated HistoplasmosisSymptoms Subacute/chronic form: constitutional symptoms

and GI: diarrhea and abdominal pain, abdominal

mass or intestinal ulcers and lesions, Pancreatitis or cholecystitis

Cards: valvular disease, cardiac insufficiency, vegetations causing dyspnea, edema, angina, and fever.

CNS: headache, visual and gait disturbances, confusion, seizures, altered consciousness, and neck stiffness or pain (meningitis most common)

Other: Hypercalcemia, Mediastinal fibrosis

Acute form: generalized symptoms Severe respiratory distress, DIC, Sepsis organomegaly CNS involvement (encephalopathy and

meningitis) in 5-20% Cutaneous lesions in10%

Accute Dessiminated HistoplasmosisSymptoms

Ocular histoplasmosis syndrome Macula involvement may result in blindness 10% of patients have bilateral involvement histo spots are Atrophic scars containing foci

of lymphocytic cell infiltration

Dessiminated HistoplasmosisOTHER

Differential diagnosis

Penumonia

Aspergillosis

Blasto

Carcinoid

Lymphoma

Ulcerative colitis

PCP

Sarcoidosis

Mycoplasma

TB

Lung Cancer

Chlamedial Pneumonitis

Diagnositc studies Acute pulm

Sputum cult pos in 10-15% Fungal Stain (sens 10%) Complement-fixing Antibodies ( 1:8 exposure, 1:32 active

dz) in 5-15% after 3 wks, 95% after 8wks Anti-M antibody is detected in 50-80% Anti-H antibody is detected in only 10-20% becomes

undetectable in 6m Serum and urine antigen (sens 25-75%) Skin test becomes pos only after 1y CXR: normal, LA, Patchy infiltrates (lower lung fields),

reticular nodular or miliary pattern in severe cases

Chronic pulm Mild anemia Alk Phosph elevated Sputum cult pos (sens 50-85%) Fungal stain (sens 40%) Complement-fixing Antibodies pos in 70-90% Anti-M antibody in nearly 100% Serum and urine antigen (sens 15%) CXR: Histoplasmomas, Cavitations (upper lobes)

in 90%, fibrotic scarring in long-standing cases.

Diagnositc studies

Acute disseminated Pancytopenia in 70-90% Blood cult pos in 50-90% Alk Phosph elevated Anti-H antibody Anti-M antibody Serum and urine antigen (pos in 90%) CXR hilar lymphadenopathy with diffuse nodular infiltrates

in 50% of patients.

Subacute Disseminated Pancytopenia rarely Complement-fixing Antibodies pos CXR has no acute findings

OTHER: PFT’s, Serum angiotensin converting enzyme concentrations , CT (adrenal insufficiency), Bronchoscopy, biopsy

Diagnositc studies

Treatment for symptomatic disease No treatment for asymptomatic immunocompetent

individuals All chronic histo patients should be treated

Mild forms can be treated with Itraconazole or Ketoconazole PO for 3-6wks

Most cases may require 12-24m course PO meds effective 75-85%, high relapse rates Hospitalized Patients should be treated with

amphoteracinB IV effective 59-100% given for total of 35 mg/kg

Small cavitary lesions can be monitored, lesions that persist or develop thick walls>3mm should be treated medically /surgically

Disseminated histo not requiring hospitalization, immunocompetant host - Itraconazole alone 6-18m

Severe dissemintated illness or failure of PO meds can be treated with amphoteracinB IV

Steroids can be used in disseminated histo with respiratory compromise in immunocompetant host (prednisone 60 qd for 2wks)

Patients with AIDS must be on life long therapy weakly amphoteracinB IV effective 81-97% Itroconazole effective 90% Fluconazole effective 88% high relapse

Treatment for Disseminated disease

Outcome

Acute pulmonary has excellent prognosis, mediastinal LA resolves over months, rarely diffuse fibrosis occures

Chronic pulmonary Histo can cause cavities that may enlarge and result in necrosis.

Untreated cases may lead to progressive pulmonary fibrosis that results in respiratory and cardiac failure and recurrent infections.

Relapse chronic pulmonary 20% acute disseminated 50%, and decreases to 10-20%

with life-long antifungal maintenance

subacute disseminated death occurs within 2-24 months in untreated cases 90% of cases resolve with treatment Hospitalization frequently required May be a problem for years with frequent relapse

acute Disseminated death within weeks if untreated, 50% mortality despite

treatment Almost always requires hospitalization DIC and sepsis are common Approximately 5-10% of patients, treated or not, develop

adrenal insufficiency Approximately 10% of individuals develop hyperacute

syndrome, which results in death.

Outcome

Reinfection can occur

Outcome

Summary

Most prevalent endemic mycosis in US Majority of cases asymptomatic In immunocompromized host can become

disseminated Diagnostics include serologies, antigen,

cultures, radiological findings All chronic /disseminated cases should be

treated Treatment depends on severity Great mimicker

Reference EMedicine

Histoplasmosis Author: Ryan C. Chang M.D. Consulting Staff, Department of Internal Medicine, Divisions of Pulmonary and Critical Care, Kaiser Permanente

UpToDate Pathogenesis and clinical manifestations of disseminated

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