US Pharm. 2015;40(4):HS-14-HS-16.

The severest form of this fungal infection, which originates in the soil, is sometimes fatal as the disease spreads from the lungs to the patient’s bloodstream.

Valley fever (coccidioidomycosis) is a fungal infection caused by two species of the soil-borne fungus Coccidioides. In this disease, wind-borne spores are inhaled into the lungs, where the infection starts. It can cause fever, tiredness, chest pain, wheezing, and coughing.1

For many people, valley fever symptoms are very similar to those of the flu or the common cold. Serious forms of valley fever infection produce pneumonia-like symptoms requiring medication, bed rest, and hospitalization.

When soils containing the fungus are disturbed and dust is raised by activities such as farming, construction, car racing, and military maneuvers, or by strong winds, spores may be inhaled. Once inside the lungs, the spores transform into larger, multicellular structures called spherules, which release endospores that develop into new spherules.

Of all the people infected with valley fever, 1 or more out of 200 will develop the disseminated and most severe form of the disease, which is devastating and can be fatal. These are cases in which the disease spreads beyond the lungs and through the bloodstream—typically to the skin, bones, and membranes surrounding the brain, causing meningitis.2

Valley fever derives its name from its discovery in the San Joaquin Valley of California, where it was also referred to as San Joaquin valley fever. Valley fever is prevalent in the San Joaquin and Central valleys of California and in the hot, desert regions of southern Arizona, Nevada, Utah, New Mexico, western Texas, and Mexico. In addition, the species of Coccidioides immitis is found in certain soils in Central and South America.1,2

SIGNS AND SYMPTOMS

Mild cases of valley fever usually resolve on their own, and most people infected with the fungi  have minimal to no symptoms. In more severe cases, physicians prescribe antifungal medications to treat the underlying infection.

Mild Valley Fever

The initial form of coccidioidomycosis is often mild, with few symptoms. Signs and symptoms do appear 1 to 3 weeks after exposure and resolve over a matter of the few weeks. Symptoms include fever and chills, cough, headache, fatigue, inflammation of joints and muscle pain, and occasionally a red rash over the body.2

Sometimes, valley fever is accompanied by a rash that mainly appears on the lower legs, but sometimes on the chest, arms, and back. The red rash can also lead to blisters or eruptions that look like pimples.2

Individuals who do not become ill from valley fever may later show a positive skin or blood test, or even exhibit small areas of residual infection in the lungs that can be detected by a chest x-ray.3

It can take months to fully recover from valley fever. Joint and muscle aches can last for several months. The severity of the disease depends on the overall health of the infected individual and the number of fungus spores the individual inhaled.3

Moderate Valley Fever

If the initial valley fever infection does not completely resolve, it may progress to a chronic form of the disease—bronchitis and pneumonia. This complication is most common in people with weakened immune systems. Patients with the chronic form of the disease are likely to have periods with harsh symptoms alternating with periods of recovery. Other signs and symptoms of moderate valley fever involve severe lung disease and inflammation of tissues lining the brain, soft tissues, joints, and bones.2,3

Severe and Disseminated Valley Fever

The most serious form of the disease is when the infection spreads beyond the lungs to other parts of the body. Most often these parts include the skin, bones, liver, brain, heart, and meninges.

The signs and symptoms of the severe and disseminated disease depend on which parts of the body are affected and may include painful lesions in the skull, spine, or other bones; swollen joints, especially in the knees or ankles; and meningitis—the most deadly complication of valley fever.2,4

RISK FACTORS

In older adults and high-risk individuals, recovery can be slow, and the risk of developing a severe form of the disease is high. People who live in or have recently traveled to an area where this disease is common are also at high risk. Valley fever has been reported in individuals who spend just a few days camping or hiking in Arizona.2

Some experts estimate that up to half the people living in areas where valley fever is common have been infected. Many people with jobs that expose them to dust are most at risk—construction workers, road and agricultural workers, ranchers, archeologists, and military personnel serving near these areas.3

Pregnant women are vulnerable to more serious infections during the third trimester, and new mothers are vulnerable right after giving birth.

Anyone with a weakened immune system is at increased risk of serious complications. The disseminated form of coccidioidomycosis can disturb the body, causing skin ulcers, abscesses, bone lesions, and swollen joints with severe pain. Patients being treated with steroids, chemotherapy, or antirejection drugs after transplant surgery are at higher risk.3

COMPLICATIONS FROM VALLEY FEVER

Many people recover from coccidioidomycosis-related pneumonia without complications. Some may become very ill. Serious complications may occur in patients with weakened immune systems, including severe pneumonia and lung infections in which the infection spreads throughout the body. A small percentage of people develop thin-walled nodules in their lungs, causing chest pain, difficulty breathing, and damage to airways that might require surgery. In its most severe form, valley fever can be a potentially fatal infection of the membranes and fluid covering the brain and spinal cord.4

DIAGNOSIS

Valley fever diagnosis relies on the combination of an infected person’s signs and symptoms. Sometimes, the disease is difficult to diagnose on the basis of signs and symptoms only, which are usually nonspecific, or from a chest x-ray, which cannot distinguish valley fever from other lung diseases. CT scans are a more reliable imaging technique in these cases.

A definitive diagnosis depends on finding evidence of coccidioides organisms in tissue, blood, or other body secretions. For this reason, clinicians are likely to recommend sputum smear or culture tests. These diagnostic tools check a sample of sputum for the presence of coccidioides organisms. In addition, through a blood test, clinicians can check for antibodies against the fungi that cause valley fever.5

TREATMENTS FOR VALLEY FEVER

Significant disease develops in less than 5% of those infected and typically occurs in those with a weakened immune system. The best therapy for otherwise healthy adults is often bed rest and fluids—the same approach used for colds and the flu. Still, clinicians carefully monitor people with valley fever.6

If symptoms do not improve or become worse, clinicians may prescribe an antifungal medication such as fluconazole. Antifungal medications are also used for people with severe or disseminated disease. In general, the antifungal drugs fluconazole or itraconazole are used for all but the most serious forms of coccidioidomycosis disease.

More serious infection may be treated initially with an IV antifungal medication such as amphotericin B. For patients who experience immediate infusion-related reactions, premedication with the following drugs 30 to 60 minutes prior to administration is necessary: diphenhydramine, acetaminophen, hydrocortisone, or in severe cases, meperidine. A test dose is necessary with this last drug, and an infusion of 1 mg of amphotericin B infused over 20 to 30 minutes will reveal whether the patient can tolerate it. The amphotericin B dose will be 0.3 to 1.5 mg/kg/day every other day.

All antifungals can have serious side effects. However, these side effects usually go away once the medication is stopped. The most common side effects of fluconazole and itraconazole are nausea, vomiting, abdominal pain, and diarrhea.

These medications control the fungus, but sometimes they do not destroy it, and relapses may occur. For many people, a single episode of valley fever results in lifelong immunity, but the disease can be reactivated. A person can also be reinfected if his or her immune system is significantly weakened.6

Those who live or visit areas where valley fever is common should take common-sense precautions, especially during the summer months when the chance of infection is highest. They should consider wearing a mask, staying inside during dust storms, wetting soil before digging, and keeping doors and windows tightly closed.7

REFERENCES

1. Galgiani JN. Coccidioidomycosis. In: Goldman L, Schafer AI, eds. Goldman’s Cecil Medicine. 24th ed. Philadelphia, PA: Saunders Elsevier; 2011:chap 341.
2. Mayo Clinic Website. Valley fever. www.mayoclinic.org/diseases-conditions/valley-fever/basics/definition/con-20027390.
3. Huang JY, Coccidioidomycosis-associated deaths, United States, 1990–2008. Emerg Infect Dis. 2012;18(11):1723-1728.
4. American Public Health Association. Coccidioidomycosis. In: DL Heymann, ed. Control of Communicable Diseases Manual. 19th ed. Washington, DC: American Public Health Association; 2008:139-141.
5. Davies SF, Knox KS, Sarasi GA, et al. Fungal infections. In: Mason RJ, Broaddus VC, Martin TR, et al, eds. Murray and Nadel’s Textbook of Respiratory Medicine. 5th ed. Philadelphia, PA: Saunders Elsevier; 2010;1:811-849.
6. Tsang CA, Anderson SM, Imholte SB, et al. Enhanced surveillance of coccidioidomycosis, Arizona, USA, 2007–2008. Emerg Infect Dis. 2010;16(11):1738-1744.
7. Galgiani JN. Coccidioides species. In: Mandell GL, Bennett JE, Dolin R, eds. Principles and Practice of Infectious Diseases. 7th ed. Philadelphia, PA: Elsevier Churchill Livingstone; 2009:chap 266.

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