Pulmonary histoplasmosis.pptx

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.

1. Pulmonary Histoplasmosis Dr. Md. Shafiqul Islam Dewan Resident (Pulmonology) Dhaka Medical College

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. T ypically presents as flu-like illness with the rapid onset of fever, chills, headache, myalgia, non-productive cough, and chest pain. A pproximately 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 . P redominant 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. D isease 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 R apidly 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.

14. Investigation

15. Investigation Microscopy Culture Histopathology Antigen detection Antibody detection Chest x-ray, CT CBC Alkaline phosphatase Lactate dehydrogenase

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 D evelopment 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. I nvestigation 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.

20. Treatment

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: L oading 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 F luconazole 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. T hought 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