Pulmonology Histoplasmosis is a fungal infection which is caused by endemic fungas histoplasma capsulatum. May present with acute or chronic pulmonary histoplasmosis and disseminated histoplasmosis.
2. Histoplasmosis is a primary systemic mycosis
caused by the dimorphic endemic fungus
Histoplasma capsulatum affect both immune
competent and compromised individual.
3. Reservoir
• The primary reservoir of H. capsulatum is soil enriched by
bird and bat droppings, in which the fungus remains viable
for many years.
• Natural infections are found in bats, which represent a
secondary reservoir of infection.
• Histoplasmosis is a specific hazard for explorers of caves
and people who clear out bird (including chicken) roosts.
• Infection is by inhalation of infected dust.
4. Endemic areas
• It is endemic to east-central USA (especially the
Mississippi and Ohio river valleys), parts of Canada,
Latin America, Caribbean, East and South-east Asia, and
Africa.
• It occurs sporadically in Australia and India, and is very
rare in Europe.
5. Pathology
• The organism is inhaled in the form of conidia or hyphal
fragments and transforms to the yeast phase during
infection.
• Conidia or yeasts are phagocytosed by alveolar
macrophages and neutrophils, and this may be followed by
haematogenous dissemination to any organ.
• Subsequent development of a T-lymphocyte response brings
the infection under control, resulting in a latent state in most
exposed individuals.
6. Risk Factor
• Occupational risk factor
• Farmers
• Pest control workers
• Poultry keepers
• Construction workers
• Roofers
• Landscapers and gardeners
• Cave explorers
• Demolition workers
• Immunocompromised
• HIV/AIDS
• Organ transplant
• Corticosteroids or TNF-
inhibitors
• Infants
• Adults aged 55 and older
• Quantity of spores inhaled
7. Transmissibility
• Inhalation of infected dust containing spore from
environment causing Histoplasmosis.
• No human to human transmission.
• However, transmission has been reported in the setting of
organ transplant with reactivation of H. capsulatum in the
implanted organ.
• The risk of reactivation of endogenous infection during
immunosuppression is very low (<0.5%), even in high-risk
groups such as renal or bone marrow transplant patients.
8. Transmissibility
• The mycelial phase of H. capsulatum is extremely hazardous
to laboratory workers and the ability to disperse large
numbers of spores makes this organism a potential biological
weapon.
• Biosafety level 3 precautions are indicated when processing
H. capsulatum mold cultures, soil, or other material
potentially contaminated with conidia.
• Biosafety level 2 precautions are appropriate for the yeast
like form.
9. Clinical features
• Clinical feature and disease severity depends on the quantity
of spores inhaled and the immune status of the host.
• In most cases, infection is asymptomatic.
• Pattern of presentation_
• Acute pulmonary histoplasmosis
• Chronic pulmonary histoplasmosis
• Acute disseminated histoplasmosis
• Chronic disseminated histoplasmosis
10. Acute pulmonary histoplasmosis
• Acute disease manifests 1 to 3 weeks after exposure.
• Typically presents as flu-like illness with the rapid onset of
fever, chills, headache, myalgia, non-productive cough,
and chest pain.
• Approximately 10% of patients have rheumatologic
symptoms, such as arthritis or severe arthralgia
accompanied by erythema nodosum.
• Pericarditis can develop in approximately 10% of patients
with acute disease.
• Chest radiography may reveal a pneumonitis with hilar or
mediastinal lymphadenopathy.
11. Chronic Pulmonary Histoplasmosis
• Patients with pre-existing lung disease, such as COPD or
emphysema, may develop chronic pulmonary
histoplasmosis.
• Predominant features are fever, cough, dyspnoea, weight
loss and night sweats.
• Radiological findings include fibrosis, nodules, cavitation
and hilar/mediastinal lymphadenopathy. Bullae are most
frequently located in the apices.
• Disease manifestation is clinically and radiologically similar
to that of cavitary tuberculosis.
• Without therapy, progression of disease develops in
approximately 50% of affected individuals.
12. Disseminated Histoplasmosis
• Rapidly spread throughout an infected host as the fungus is transported
intracellularly by phagocytes from the lungs via the hilar lymphatics into
the systemic circulation.
• Although the majority of infected patients control this process, systemic
histoplasmosis develops in approximately 0.05% of individuals after
exposure.
• Disease most commonly disseminates in individuals with pre-existing
immunosuppression, largely due to malignancy, corticosteroid use,
or HIV.
• Clinical manifestations of disseminated histoplasmosis can vary from
indolent to fulminant disease.
• Patients typically present with fever, weight loss, and respiratory
symptoms with hepatomegaly and/or splenomegaly.
13. Disseminated Histoplasmosis
• Cutaneous and mucous membrane lesions are not uncommon and
patients should be considered to have disseminated disease if
Histoplasma is isolated from these sites.
• Patients with acute disease often have anemia, thrombocytopenia,
leukopenia, and abnormal liver function tests as well as
coagulopathies.
• The majority of patients have diffuse pulmonary opacities, but chest
radiographs can be unrevealing in approximately 30% of patients.
• The central nervous system can be involved in 10–20% of cases.
• Adrenal dysfunction, including bilateral adrenal masses, may develop in
approximately 50% of patients with disseminated histoplasmosis,
although adrenal insufficiency is uncommon.
• Acute progressive disease is lethal without treatment.
16. Investigation
• Microscopy: for detection of budding yeast in tissue or body
fluids, low sensitivity, but can provide a quick proven
diagnosis if positive.
• Culture: can be performed on tissue, blood, and other body
fluids, but may take up to 6 weeks to become positive; most
useful in the diagnosis of the severe forms of histoplasmosis.
• Histopathology: Small yeasts (2-4 µm) with narrow-based
budding grouped in clusters inside macrophages.
17. Antigen detection
• Enzyme immunoassay (EIA) is typically performed on
urine and/or serum, but can also be used on cerebrospinal
fluid or bronchoalveolar lavage fluid.
• These are useful in individuals who are
immunocompromised when antibody production may be
impaired.
18. Antibody detection
• Development of antibodies to Histoplasma can take two to
six weeks, antibody tests are not as useful as antigen
detection tests in diagnosing acute histoplasmosis or in
immunosuppressed persons, who may not mount a strong
immune response.
• Immunodiffusion (ID): Tests for the presence of H
(indicates chronic or severe acute infection) and M (develops
within weeks of acute infection and can persist for months to
years after the infection has resolved) precipitin bands;
~80% sensitivity.
• Complement Fixation (CF): Complement-fixing antibodies
may take up to 6 weeks to appear after infection. CF is more
sensitive but less specific than immunodiffusion.
19. Investigation
• CBC:
• Mild anemia may be present in chronic pulmonary
histoplasmosis.
• In acute progressive disseminated histoplasmosis,
pancytopenia occurs in 70-90% of patients, with a platelet
count less than 70,000.
• Pancytopenia may occur at a lower rate in chronic progressive
disseminated histoplasmosis.
• Alkaline phosphatase: levels are elevated in acute
progressive disseminated histoplasmosis and chronic
pulmonary histoplasmosis.
• Lactate dehydrogenase: Marked elevations in levels may
be seen in AIDS patients with disseminated histoplasmosis.
21. Mild to Moderate Acute Pulmonary Histoplasmosis
• If a patient has been symptomatic for more than 3 weeks or if a patient
has moderate disease, itraconazole is appropriate.
• Dosage: Loading dose of 200 mg three times daily for 3 days,
Followed by 200 mg twice daily for 6 to 12 weeks.
• Voriconazole and Posaconazole can be considered for use in patients not
responding to itraconazole.
• Ketoconazole should not be used as a systemic antifungal and
Fluconazole is less effective than itraconazole.
• Echinocandins should not be used to treat Histoplasma because of
intrinsic resistance of Histoplasma to this class of drugs.
22. Moderately Severe to Severe
Acute Pulmonary Histoplasmosis
• Liposomal amphotericin is more effective than itraconazole in
clearance of Histoplasma in experimental histoplasmosis.
• Liposomal amphotericin is favoured over the conventional deoxycholate
formulations because of less toxic.
• Dosage: Liposomal amphotericin 3 to 5 mg/kg daily for 1 to 2 weeks,
Followed by itraconazole 200 mg three times daily for 3 days
and then 200 mg twice daily for 12 weeks.
• If liposomal amphotericin is not available or if the patient is at low risk
for nephrotoxicity, 0.7 to 1 mg/kg deoxycholate amphotericin should be
used.
23. Moderately Severe to Severe
Acute Pulmonary Histoplasmosis
• In patients with hypoxemia or significant respiratory
distress, corticosteroids should be considered, particularly
in HIV-infected individuals receiving antiretroviral therapy
at risk for immune reconstitution syndromes.
• Methylprednisolone: 0.5 to 1 mg/kg intravenously
administered for the first 1 to 2 weeks adjunctively with
antifungals.
• Alternatively: oral prednisone 40 to 60 mg/day can be
used.
24. Chronic Cavitary Histoplasmosis
• Itraconazole should be given as a loading dose of 200 mg
three times daily for 3 days, followed by 200 mg twice
daily for a minimum of 1 year.
• Extending treatment to 18 to 24 months may reduce the
likelihood of relapse, which otherwise can be expected in
approximately 15% of patients.
• Critically ill patients may benefit from initial treatment with
amphotericin.
25. Disseminated Histoplasmosis
• Treatment should be initiated with liposomal amphotericin,
if available, for 1 to 2 weeks, followed by itraconazole.
• Treatment should be continued for a minimum of 1 year.
• Occasionally, disseminated disease can be diagnosed in
patients who have only mild to moderate symptoms. In
immunocompetent individuals, itraconazole can be
considered for initial therapy.
26. Immunocompromised Patients
• Therapy with itraconazole 200 mg once or twice daily
should be continued indefinitely in immunocompromised
patients whose immunosuppression cannot be discontinued.
• In patients with HIV, therapy should be continued lifelong
unless CD4 counts can be restored to levels greater than
200/μL.
• Patients on maintenance itraconazole should have
Histoplasma antigen testing performed each year.
27. Fibrosing mediastinitis
• Fibrosing mediastinitis, a rare but serious post infectious
complication, is a fibrosing process in the mediastinum that
may compress and occlude vital mediastinal structures,
including airways and vessels.
• Thought to be due to an abnormal inflammatory response to
residual Histoplasma proinflammatory components.
• Steroids or antifungal agents are not useful in combating
fibrosing mediastinitis, and surgery has not proven to be
effective, although endovascular stenting has been reported
to alleviate vascular complications
