BASICS
DESCRIPTION
- A pulmonary fungal infection endemic to the southwestern deserts of the United States:
- Rarely progresses to involve extrapulmonary sites (<1%): bone, CNS, endocrine/metabolic, musculoskeletal, nervous, pulmonary, skin, and exocrine systems
- Incubation period is 1 to 4 weeks after exposure.
- Most common clinical presentation is a self-limited community-acquired pneumonia (1).
- Synonym(s): desert rheumatism; cocci; valley fever
EPIDEMIOLOGY
Affects patients of all ages, with no gender predilection
Incidence
- In the United States: 150,000 cases estimated per year (0.5% extrapulmonary). Overall incidence is rising. 73% increase in African Americans, who also have a higher rate of invasive disease than Caucasians (2).
- Endemic in
- Southern Arizona
- Southern and Central California
- Southwestern New Mexico, West Texas
- Parts of Mexico, Central and South America
Prevalence
Can account for up to 20% or more of all community-acquired pneumonias in endemic areas
ETIOLOGY AND PATHOPHYSIOLOGY
- Coccidioides immitis is a soil-dwelling fungus well-adapted to arid conditions. The organism can remain dormant in the soil for years.
- Liberated spores (arthroconidia) are inhaled when soil is disturbed. Upon inhalation, spores convert to spherules in the lung to cause clinical disease.
- Less commonly, spores are introduced through a wound.
RISK FACTORS
- Certain groups are more prone to dissemination:
- Immunosuppressed patients: chemotherapy and/or immunosuppressive drugs for cancer or transplant patients, diabetes mellitus, HIV/AIDS, long-term steroid use, transplant patients, pregnancy
- Blacks and Filipinos
- Previously infected patients can experience relapse years later through cell-mediated immune deficiency.
- CNS involvement is more common in young white men.
GENERAL PREVENTION
- No person-to-person spread
- Lab cultures are highly contagious (inhalation); use caution when handling specimens.
- High-risk patients should avoid archaeologic digs, spelunking, or exposure to dust in endemic areas (latter can be difficult to accomplish due to construction, dust storms, etc.).
DIAGNOSIS
HISTORY
- Travel history is essential when investigating pulmonary conditions not responding to normal measures.
- Most humans infected with coccidioidomycosis are asymptomatic or have minimal symptoms (3).
- ~95% of those who develop symptoms have self-limited disease that resolve within several weeks (3).
- Cough, fever, chest pain, and fatigue are the most common presenting symptoms:
- Severity can range from very mild to debilitating.
- A variety of other symptoms may be present in any combination and can last for months.
- Fever, chills, sweats, weight loss
- Cyanosis, tachycardia
- Anorexia, arthralgias
- Chest pain, pleurisy, cough (dry or productive), dyspnea
- Rash, erythema nodosum, toxic erythema
- Fatigue, malaise, headache, sore throat
- Disseminated cases may involve CNS symptoms, bone pain, skin lesions, and so forth.
PHYSICAL EXAM
- May be normal even with active disease
- Pertinent positives:
- Fever
- Dyspnea, tachycardia
- Pulmonary findings: wheeze, rales, rhonchi, decreased breath sounds, dullness, egophony
- Erythema nodosum, other rashes or lesions
DIFFERENTIAL DIAGNOSIS
- Community-acquired pneumonia
- Lung carcinoma
- Sarcoidosis
- Histoplasmosis, other fungi
- Lung abscess
- Tuberculosis
- Lymphoma
- Old cocci granulomas can be mistaken for tumors.
DIAGNOSTIC TESTS & INTERPRETATION
Initial Tests (lab, imaging)
- Serology: Immunodiffusion or enzyme immunoassay (EIA) measures IgM and IgG antibodies. IgM rises within 2 weeks and falls after 2 months; IgG rises at 1 to 3 months. Patients with mild symptoms may never be detected serologically.
- Negative serology may represent window between falling IgM and rising IgG levels. If suspicious for coccidioidomycosis, repeat serology in 1 to 2 weeks. Antibody production may lag behind illness by weeks or, in immunocompromised patients, by months (2).
- If IgG EIA is positive, send to a specialized reference lab for confirmation and quantification usually via the IgG immunodiffusion complement fixation quantification testing or traditional complement fixation testing (3). High titers suggest dissemination (3).
- May have elevated ESR and peripheral eosinophilia (4)[C]
- Fungal culture of sputum, wound, and joint aspirate may yield diagnosis; fungus is unlikely to grow in urine, blood, or pleural fluid.
- Urinary antigen (Ag) test for coccidioidomycosis may be useful for immunocompromised patients with suspected coccidioidomycosis or patients with suspected extrathoracic disease (5)[B].
- Chest x-ray (CXR) findings range from normal to infiltrate(s) and nodule(s)-particularly in upper lung fields, cavity, adenopathy (mediastinal or hilar), and pleural effusion. Severe cases may show diffuse lung disease.
- Chest CT may help clarify CXR findings.
Follow-Up Tests & Special Considerations
Follow abnormal CXRs generally to resolution or calcification of a nodule with documented stability over time (months).
Diagnostic Procedures/Other
- Biopsy of affected tissue (lung nodule, skin lesion)
- If unable to establish diagnosis from serology and/or biopsy: bronchoscopy, fine needle biopsy, open lung biopsy, pleural biopsy, bone/skin/node biopsy, CSF stain, serology, or culture
- A diagnosis of coccidioidomycosis can be established on bronchoalveolar lavage specimens in 30-64% of cases (3).
Test Interpretation
Fungal elements, spherules
TREATMENT
GENERAL MEASURES
- Cool mist humidifier for dry cough or sore throat, antitussives
- Supportive therapy
- Most cases resolve without antifungal treatment.
MEDICATION
First Line
- In mild cases, treatment is symptomatic:
- Treat pleuritic pain with analgesics.
- In general, avoid steroids.
- Antitussives for cough
- Optimal duration of treatment for mild to moderate pulmonary coccidioidomycosis is undefined (6)[B].
- Complications are seen when patients undergoing treatment discontinue medications prematurely (7)[B].
- Persistent or severe cases should receive antifungal treatment and generally should be referred to a pulmonary or infectious disease specialist.
- The Infectious Diseases Society of America acknowledges that expert opinions vary regarding in the need to treat primary coccidioidomycosis (6)[B]. The following patients with moderate to severe symptoms might benefit from antifungal therapy:
- Symptoms >2 months
- Night sweats >3 weeks
- Weight loss >10%
- Inability to work
- Serologic complement titer >1:16
- Bilateral infiltration or involvement of at least 1/2 of lung
- Hilar lymphadenopathy (6)[B]
- Immunosuppressed patients (HIV/AIDS, receiving chemotherapy, transplant recipients) require treatment (3).
- Consensus guidelines (American Thoracic Society) suggest (2)
- Ketoconazole: 400 mg/day
- Fluconazole: 400 mg/day. Fluconazole is also the treatment of choice for coccidioidomeningitis with a usual dose of 800 mg/day (consultation needed).
- Itraconazole: 200 mg BID
- Itraconazole superior to fluconazole for treating skeletal coccidioidomycosis (5)[C]
- Contraindications: Avoid steroid therapy if possible.
- Significant possible interactions:
- Ketoconazole given with H2 blockers shows decreased absorption (requires acidic pH for absorption).
- Azole antifungals: prolongation of QT segment and ventricular arrhythmias
- Seek expert consultation because drug choice and therapy duration (generally 3 to 6 months for nondisseminated disease) remain controversial.
Second Line
- Severe and rapidly progressive disease, including late pregnancy, may require amphotericin B.
- Precautions: Amphotericin is highly nephrotoxic.
ISSUES FOR REFERRAL
Unless the treating physician has experience and familiarity with coccidioidomycosis, consultation with a pulmonary or infectious disease expert is recommended if antifungal therapy is required.
SURGERY/OTHER PROCEDURES
Surgery is sometimes needed for resection of cavitary lesions with hemoptysis or severely diseased sections of lung tissue.
INPATIENT CONSIDERATIONS
Admission Criteria/Initial Stabilization
- For patients who have unstable pulmonary symptoms, such as hypoxemia, or for dehydration
- Respiratory isolation not indicated.
- Outpatient except in severe cases; admit for respiratory instability
IV Fluids
As needed
Discharge Criteria
Pulmonary stability
ONGOING CARE
FOLLOW-UP RECOMMENDATIONS
Patient Monitoring
- If serology is negative but index of suspicion is high, repeat every 2 weeks.
- With positive serology, follow titers every 2 weeks until are dropping or negative and the patient improves clinically.
- Observe and repeat abnormal CXRs until findings are resolved or scarring process is complete and stable.
DIET
No special considerations
PATIENT EDUCATION
American Lung Association, 1740 Broadway, New York, NY 10019; 212-315-8700; http://www.lungusa.org
PROGNOSIS
- Most cases are self-limited and resolve within a few months. Progressive and disseminated disease can be difficult to eradicate.
- Prognosis is poor if weak cell-mediated immunity response or high IgG is present.
- Relapse of extrapulmonary or disseminated disease is common.
COMPLICATIONS
Severe cases (e.g. meningitis) are often fatal. Coccidioidomycosis can cause destruction of pulmonary tissue owing to scarring, cavities, and other factors.
REFERENCES
11 Galgiani JN, Ampel NM, Blair JE, et al. Coccidioidomycosis. Clin Infect Dis. 2005;41(9):1217-1223.22 Ruddy BE, Mayer AP, Ko MG, et al. Coccidioidomyocosis in African Americans. Mayo Clin Proc. 2011;86(1);63-69. doi: 4065/mcp.2010.0423.33 Malo J, Luraschi-Monjagatta C, Wolk DM, et al. Update on the diagnosis of pulmonary coccidioidomycosis. Ann Am Thorac Soc. 2014;11(2):243-253.44 Simons CM, Stratton CW, Kim AS. Peripheral blood eosinophilia as a clue to the diagnosis of an occult Coccidioides infection. Hum Pathol. 2011;42(3):449-453.55 Ampel NM. New perspectives on coccidioidomyocosis. Proc Am Thorac Soc. 2010;7(3):181-185.66 Blair JE, Chang YH, Cheng MR, et al. Characteristics of patients with mild to moderate primary pulmonary coccidioidomycosis. Emerg Infect Dis. 2014;20(6):983-990. http://wwwnc.cdc.gov/eid/. Accessed 2014.77 Ampel NM. Coccidioidomycosis: a review of recent advances. Clin Chest Med. 2009;30(2):241-251.
ADDITIONAL READING
- Cadena J, Hartzler A, Hsue G, et al. Coccidioidomycoiss and tuberculosis coinfection at a tuberculosis hospital: clinical features and literature review. Medicine (Baltimore). 2009;88(1):66-76.
- Ramos-e-Silva M, Lima CM, Schechtman RC, et al. Systemic mycoses in immunodepressed patients (AIDS). Clin Dermatol. 2012;30(6):616-627.
- Szeyko LA, Taljanovic MS, Dzioba RB, et al. Vertebral coccidioidomycosis: presentation and multidisciplinary management. Am J Med. 2012;125(3):304-314.
- Trible R, Edgerton N, Hayek S, et al. Antiretroviral therapy-associated coccidioidal meningitis. Emerg Infect Dis. 2013;19(1):163-165.
CODES
ICD10
- B38.9 Coccidioidomycosis, unspecified
- B38.2 Pulmonary coccidioidomycosis, unspecified
- B38.0 Acute pulmonary coccidioidomycosis
- B38.1 Chronic pulmonary coccidioidomycosis
- B38.89 Other forms of coccidioidomycosis
- B38.3 Cutaneous coccidioidomycosis
- B38.4 Coccidioidomycosis meningitis
- B38.81 Prostatic coccidioidomycosis
- B38.7 Disseminated coccidioidomycosis
ICD9
- 114.9 Coccidioidomycosis, unspecified
- 114.5 Pulmonary coccidioidomycosis, unspecified
- 114.0 Primary coccidioidomycosis (pulmonary)
- 114.4 Chronic pulmonary coccidioidomycosis
- 114.1 Primary extrapulmonary coccidioidomycosis
- 114.2 Coccidioidal meningitis
- 114.3 Other forms of progressive coccidioidomycosis
SNOMED
- Coccidioidomycosis (disorder)
- Pulmonary coccidioidomycosis (disorder)
- Primary pulmonary coccidioidomycosis (disorder)
- acute pulmonary coccidioidomycosis (disorder)
- Cutaneous coccidioidomycosis (disorder)
- Chronic pulmonary coccidioidomycosis
CLINICAL PEARLS
- Consider coccidioidomycosis in patients with travel to endemic areas and persistent pulmonary symptoms that do not respond to routine treatment.
- Minimal exposure in an endemic area can result in infection.
- Most cases are mild or subclinical.
- An infected person is not contagious.
- Consult with infectious disease or pulmonary specialist for patients requiring antifungal therapy.
- Consider coinfection with coccidioidomycosis in tuberculosis patients who fail to improve clinically or radiologically despite appropriate culture-directed therapy (6).