Differentials
Tuberculosis
SIGNS / SYMPTOMS
Symptoms and signs of tuberculosis and coccidioidomycosis may be similar. For patients with suspected tuberculosis, residence in, or travel to an endemic area for coccidioidomycosis is not needed for diagnosis.
Tuberculosis has an indolent onset and symptoms are unremitting until proper treatment is begun.
INVESTIGATIONS
Mycobacterial culture of sputum or other sites of clinical involvement will yield positive results for Mycobacterium tuberculosis.
Chest x-ray may show chronic infiltrate, fibrosis, cavities, and retraction, often upper lobe.
Non-tuberculous pulmonary mycobacterial infections
SIGNS / SYMPTOMS
Residence in or travel to an endemic area for coccidioidomycosis is not needed for diagnosis.
Onset of symptoms may be acute, but often indolent.
INVESTIGATIONS
Mycobacterial culture of sputum or other sites of clinical involvement will yield positive results.
Community-acquired pneumonia
SIGNS / SYMPTOMS
Signs of lobar or atypical pneumonia, including crackles and dyspnoea.
Generally, shorter duration of symptoms compared with tuberculosis or coccidioidomycosis.
If diagnosis is in doubt, presumptive treatment for bacterial pneumonia is recommended (without using fluoroquinolones, or other antibiotics with significant antituberculous activity), and assessment for response.
INVESTIGATIONS
Sputum examination with presence of bacteria other than normal flora.
Histoplasmosis
SIGNS / SYMPTOMS
Residence in or travel to an area endemic for histoplasmosis (Mississippi and Ohio river valleys).
Around 50% to 90% of patients have self-limited or asymptomatic pulmonary infection not requiring treatment.[44] Symptoms include dry cough, chest pain, sweating, fever, and weight loss.
INVESTIGATIONS
Fungal culture will grow Histoplasma capsulatum.
Biopsy shows characteristic organism with fungal stains.
Histoplasma urine and serum antigen positivity.
Histoplasma antibody assays may be positive.[44]
Blastomycosis
SIGNS / SYMPTOMS
Residence in or travel to an area endemic for blastomycosis (southeastern and south-central states, especially bordering on the Mississippi or Ohio rivers).[45]
Symptoms include cough, fever, night sweats, weight loss, chest pain, and dyspnoea.
INVESTIGATIONS
Culture of sputum or bronchoalveolar lavage fluid.
Histopathology of biopsied specimens.[45]
Cryptococcosis
SIGNS / SYMPTOMS
History of immune deficiency. Headache, pyrexia, cranial neuropathies, and alteration of consciousness indicate central nervous system involvement.
Cutaneous involvement presents with molluscum contagiosum-like and acneiform lesions.
INVESTIGATIONS
Cryptococcal polysaccharide antigen is positive in serum, cerebrospinal fluid, and pleural fluid.
Cultures positive with growth of Cryptococcus species.
Actinomycosis
SIGNS / SYMPTOMS
Typically presents as a chronic, slowly progressive, indurated mass. History of previous injury to mucosal surface or aspiration enhances the risk of pulmonary disease.
Cough may be productive of blood-streaked sputum.
INVESTIGATIONS
Culture of pus or affected tissue positive for actinomycetes.
Histology of affected tissue demonstrates acute or chronic inflammation and granulation tissue; sulphur granules may also be seen.
Sporotrichosis
SIGNS / SYMPTOMS
Clinical presentation of pulmonary sporotrichosis is similar to that of pulmonary tuberculosis with fever, chills, night sweats, weight loss, malaise, cough, shortness of breath, and, occasionally, haemoptysis.
INVESTIGATIONS
Repeated cultures from sputum, bronchoalveolar lavage, or bronchial biopsy may be positive.
Bronchial biopsy may demonstrate cigar- or oval-shaped Sporothrix yeast forms.
Aspergillosis
SIGNS / SYMPTOMS
History of immune deficiency. Mostly asymptomatic but commonly presents as self-limiting mild haemoptysis. Other symptoms include cough and pleuritic chest pain.
Fever is rare.
May have concomitant skin involvement and/or invasive sinus disease.
INVESTIGATIONS
High-resolution chest CT scan demonstrates nodules with or without halo sign or air-crescent sign.
Small cell lung cancer
SIGNS / SYMPTOMS
Strong risk factors include cigarette smoking and exposure to second-hand tobacco smoke, radon gas, and asbestos; more common in patients aged 65 to 70 years and in men; presents most commonly with cough, dyspnoea, haemoptysis, chest pain, weight loss; other presenting features related to metastases to brain, bone, and lymph nodes.
INVESTIGATIONS
Chest x-ray: central mass, hilar lymphadenopathy, pleural effusion.
CT chest, liver, and adrenal glands: massive lymphadenopathy and direct mediastinal invasion are common features of small cell lung cancer; determines extent of disease.
Sputum cytology: malignant cells in sputum.
Bronchoscopy: endobronchial lesions.
Biopsy: malignant cells, high nuclear to cytoplasmic ratio, nuclear fragmentation often present.
Thoracentesis: malignant cells within the pleural fluid.
Thoracoscopy: pleural involvement.
Further tests depend on the presence of metastasis.
Non-small cell lung cancer
SIGNS / SYMPTOMS
Most signs and symptoms are similar to small cell lung cancer. Typical features include cough, haemoptysis, chest pain, dyspnoea, and hoarseness (if recurrent laryngeal nerve paralysis). Patients frequently appear ill and short of breath, with signs of recent weight loss.
Finger clubbing and hypertrophic osteoarthropathy may be present and are more common in non-small cell lung cancer.
INVESTIGATIONS
Chest x-ray variable; may detect a solitary pulmonary nodule, mass, pleural effusion, lung collapse, or mediastinal or hilar fullness.
CT chest shows size, location, and extent of primary tumour; evaluates for hilar and/or mediastinal lymphadenopathy and distant metastases.
Sputum cytology shows characteristic malignant cells. Specificity >95%, sensitivity variable between 20% and 70%. More likely to be positive with central lesions compared with peripheral lesions.
Flexible bronchoscopy plus biopsy provides pathological confirmation of diagnosis. Endobronchial masses can be biopsied with forceps. Endobronchial brushings, washings, and alveolar lavage increase the diagnostic yield. Transbronchial needle aspiration biopsy of accessible parenchymal lesions and mediastinal lymph nodes is now possible. Detection of small peripheral lesions (<2 cm) is improved by use of endobronchial ultrasound.
Pneumocystis jirovecii pneumonia
SIGNS / SYMPTOMS
Can occur within or outside the Coccidioides-endemic area in persons with severe cellular immunodeficiency. May be similar in presentation to miliary coccidioidomycosis with dyspnoea, cough, fever, and diffuse infiltrates.
INVESTIGATIONS
Induced sputum and (more often) flexible bronchoscopy with bronchoalveolar lavage, with cytology and special stains or polymerase chain reaction for Pneumocystis. Serum lactate dehydrogenase may be elevated.
Eosinophilic pneumonia (eosinophilic granulomatosis with polyangiitis)
SIGNS / SYMPTOMS
Can occur within or outside the Coccidioides-endemic area. May be similar with eosinophilia and focal nodular infiltrates, cough, and chest pain.
INVESTIGATIONS
Flexible bronchoscopy and biopsy with histopathology; serum anti-neutrophil cytoplasmic antibodies (ANCA) may be positive. Peripheral eosinophilia >10% of total WBC count. Asthma, sinus disease, and neuropathy may be present, as well as kidney disease.
Coronavirus disease 2019 (COVID-19)
SIGNS / SYMPTOMS
Residence in/travel to a country/area or territory with local transmission, or close contact with a confirmed or probable case of COVID-19, in the 14 days prior to symptom onset.
See our COVID-19 topic for further information.
INVESTIGATIONS
Real-time reverse transcription polymerase chain reaction (RT-PCR): positive for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) RNA.
Distinguishing covid and coccidioidomycosis is often possible radiographically.
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