Differentials
Community-acquired pneumonia
SIGNS / SYMPTOMS
Cough, fever, and pleuritic chest pain are usually of a shorter duration than in histoplasmosis pneumonia.
INVESTIGATIONS
Chest x-ray with lobar consolidation for typical pneumonia or bilateral interstitial infiltrates for atypical pneumonia.
Hilar lymphadenopathy is not seen.
Sputum Gram stain and culture with many neutrophils and bacteria other than normal oral flora.
Good response to appropriate antibiotic therapy.
Pneumocystis jirovecii pneumonia (PCP)
SIGNS / SYMPTOMS
Patients with advanced HIV/AIDS with Pneumocystis jirovecii pneumonia present with fevers and night sweats that may be indistinguishable from features of pulmonary histoplasmosis.
INVESTIGATIONS
Sputum staining with methenamine silver ('silver stain') demonstrating round or crescent-shaped cysts typical of P jiroveci. Elevated serum bronchoalveolar lavage (LDH) >3.64 microkat/L (>220 units/L). Although elevated levels of LDH are a non-specific finding, rising levels despite adequate therapy are a marker for poor prognosis in patients with PCP. Chest x-ray shows diffuse bilateral interstitial pulmonary infiltrates.
Pulmonary tuberculosis
SIGNS / SYMPTOMS
Presents with symptoms that can be difficult to differentiate clinically from acute and chronic histoplasmosis pneumonia.
INVESTIGATIONS
Sputum smears demonstrating the presence of acid-fast bacilli. Sputum cultures growing Mycobacterium tuberculosis. Purified protein derivative skin test with ≥15 mm induration.
Sarcoidosis
SIGNS / SYMPTOMS
Autoimmune disorder characterised by non-caseating granulomas of various organs and multi-system involvement including erythema nodosum, polyarthritis, uveitis, cranial neuropathy, and other features.
INVESTIGATIONS
Chest x-ray shows hilar and/or paratracheal adenopathy with upper lobe predominant, bilateral infiltrates, pleural effusions (rare), and egg shell calcifications (very rare).
Elevated serum ACE level >40 micrograms/L.
Non-small-cell lung cancer
SIGNS / SYMPTOMS
Symptoms include cough, haemoptysis, chest pain, and/or dyspnoea.
INVESTIGATIONS
Sputum cytology showing malignant cells. Chest CT scan will show pulmonary nodules or hilar lymphadenopathy, or secondary pulmonary metastases from other cancers.
Pathological confirmation of malignancy is the only widely accepted method of diagnosing lung cancer. Tissue is sampled from bronchoscopy where possible, and malignant cells identified by pathology. Transthoracic needle aspiration biopsy, typically using CT guidance, is used to biopsy suspicious peripheral pulmonary lesions that are not accessible with bronchoscopy. Alternatively, lymph node biopsy or biopsy during mediastinoscopy, video-assisted thoracoscopic surgery, or an open surgical procedure are used.
Cryptococcosis
SIGNS / SYMPTOMS
Primary pulmonary infection with Cryptococcus is often clinically silent and is usually associated with exposure to soil contaminated with pigeon droppings.[46]
Pulmonary manifestations of cryptococcal pneumonia are clinically indistinguishable from those of histoplasmosis pneumonia.
INVESTIGATIONS
Sputum culture growing Cryptococcus.
Serum antigen test demonstrating the presence of cryptococcal antigens.
Coccidioidomycosis
SIGNS / SYMPTOMS
Infection is sub-clinical in the majority of patients, although symptomatic infection may be clinically very similar to histoplasmosis pneumonia.
Regions endemic for Coccidioides in the US are distinct from those for Histoplasma capsulatum and include southern California, Arizona, New Mexico, and western Texas.[47]
Patients with coccidioidal infection may also develop a constellation of fever, rash, and transient arthritis/arthralgia.
INVESTIGATIONS
Enzyme immunoassay demonstrating the presence of IgM antibodies.
Complement fixation assay with IgG titres of ≥1:32.
Blastomycosis
SIGNS / SYMPTOMS
Presents as acute pneumonia in patients with a history of travel to endemic areas including south-eastern and central US states bordering the Mississippi and Ohio River basins, mid-western states, and Canadian provinces bordering the Great Lakes and areas along the St. Lawrence River.[48]
Pulmonary manifestations are clinically indistinguishable from those of histoplasmosis pneumonia.
INVESTIGATIONS
Direct examination of sputum showing yeast-like forms of Blastomyces.
Sputum culture growing Blastomyces.
Enzyme immunoassay and complement fixation assays demonstrating the presence of antibodies to Blastomyces.
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