Download Final Diagnosis - Clinical Correlations

Final Diagnosis
Reactivated Pulmonary Histoplasmosis
in the setting of TNF alpha antagonist therapy
Histoplasma capsulatum
• Dimorphic fungus
– Mold in environment
– Yeast phase in vivo
• Found primarily in North and Central America
– Mississippi and Ohio River Valleys
• Most common endemic mycosis in the United States
• Reservoir is soil that contains bird or bat guano
H. capsulatum Transmission
• Microconidia are inhaled from disrupted soil
• Deposition in bronchioles and alveoli
• Convert into yeast form
• Uptake by macrophages
• May remain latent in granulomas
Histoplasmosis
Categories of Disease
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Acute Pulmonary Histoplasmosis
Chronic Cavitary Pulmonary Histoplasmosis
Disseminated Histoplasmosis
Histoplasmosis Associated with Anti-Tumor
Necrosis Factor Alpha Therapy
Acute Pulmonary Histoplasmosis
• Self-limited illness
• Generally asymptomatic infection
• Chest radiograph: patchy infiltrate, hilar and mediastinal
lymphadenopathy, often calcified nodules later noted
Acute Severe Pulmonary Histoplasmosis
• Symptoms: fever, malaise, headache, weakness, chest
discomfort and dry cough
• May be associated with myalgias and arthralgias
• Physical exam: diffuse rales
• Chest radiograph: diffuse reticulonodular infiltrates
Chronic Cavitary Pulmonary Histoplasmosis
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Older patients with underlying lung disease
Interstitial inflammation adjacent to bullae
Large apical cavities
Calcified mediastinal nodes
Systemic symptoms: fatigue, fever, weight loss
Pulmonary symptoms: productive cough,
dyspnea, mild hemoptysis
Disseminated Histoplasmosis
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Immunocompromised host
Parasitized macrophages
Symptoms: fever, anorexia, malaise
Severe disease: sepsis, disseminated intravascular
coagulation, renal failure, adult respiratory distress
syndrome
• Physical Exam: hepatosplenomegaly,
lymphadenopathy, mucous membrane ulceration,
pallor/petechiae
• Other organs: gastrointestinal tract, genitourinary
system, adrenals, bone, central nervous system,
endocarditis
Histoplasmosis Associated with Anti-Tumor
Necrosis Factor Alpha Therapy
• Patients with various inflammatory disorders being
treated with either infliximab, adalimumab or etanercept
• Acute infection or reactivation of latent disease
• Symptoms: fever, malaise, headache, cough, dyspnea
• Chest radiograph: diffuse interstitial infiltrates
Diagnosis
• Culture
– Several weeks for growth
– DNA probe
– Exoantigen test
• Histopathology
– Budding yeast within macrophages or free in tissue
• Antigen Tests
– Urine or blood
• Antibody Tests
– Complement fixation
– Immunodiffusion
Treatment
• Acute Pulmonary Histoplasmosis
– Treatment not usually required
– Itraconazole therapy for 6-12 weeks for severe cases
– If severe: amphotericin B then itraconazole for 12 weeks
• Chronic Cavitary Pulmonary Histoplasmosis
– Itraconazole therapy for 1-2 years
• Disseminated Histoplasmosis
– Amphotericin B (if severe)
– Itraconazole for 6-18 months
• Histoplasmosis Associated with Anti-Tumor Necrosis
Factor Alpha Therapy
– As above
– Cessation of anti-tumor necrosis alpha inhibitor
Special Considerations
• AIDS patients with history of histoplasmosis should remain on
itraconazole until CD4 count is above 200 cells/ml
• Prophylaxis is recommended for AIDS patients in endemic
areas with CD4 counts less than 150 cells/ml
• No formal recommendations about prophylaxis for patients
with other forms of immunosuppression
Ankylosing Spondylitis
Tobacco use
Thoracic Spine Involvement
Obstructive Lung Disease
Restrictive Lung Disease
Obstructive Sleep Apnea
Chronic Hypoxemia
and Hypercapnia
Etanercept
Reactivation of
Histoplasmosis
Worsening Hypoxia
Breathlessness
Remote Exposure
to Histoplasmosis
Fever
Chills
Patient Follow-up
• Hospital day #18: Based on preliminary bronchoalveolar lavage
results, the patient was started on amphotericin B. Etanercept
therapy was discontinued.
• Hospital day #20: Patient was switched to liposomal formulation of
amphotericin because of concerns about nephrotoxicity.
• Hospital day #28: Patient’s respiratory status began to improve. He
was then converted to PO itraconazole.
• Hospital day #31: Oxygen requirements continued to decreased
• Hospital day #36: Pt was discharged to a nursing home
• Pt has returned home and is functioning at baseline. The current
plan is for nine months of itraconazole therapy. He remains off
tumor necrosis factor antagonist therapy.
References
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