Definition

A systemic mycosis caused by the inhalation of infective arthroconidia of the soil-borne fungus Coccidioides immitis.

Pathophysiology

• Grows in soil in the mycelial state.
• Inhalation of infective arthroconidia is the primary route of infection; at body temperature, all but one nucleus is shed and an immature spherule is produced within 2–3 days.
• Spherule matures and ruptures releasing 200–300 endospores which can produce new spherules.
• Neutrophils cannot penetrate the spherule wall but can phagocytize the endospores.
• Fewer than 10 inhaled arthrospores are sufficient to cause disease in susceptible animals.
• Respiratory signs are often noted 1–3 weeks after exposure; signs of dissemination may not be evident for several months.
• Most infections are mild or subclinical although dogs appear more susceptible to the development of disseminated disease.
• Fever, lethargy, inappetence, coughing, and joint pain or stiffness may be noticed. Dissemination may occur within 10 days, resulting in signs related to the organ system involved; skin lesions are usually associated with dissemination, but penetrating wounds have rarely been associated with skin lesions.

Systems Affected

• Respiratory-the site of initial infection.
• Extrapulmonary spread may occur to long bones and joints, eyes, pericardium and myocardium, skin, CNS, testes, and visceral organs.

Incidence/Prevalence

Not an uncommon disease in endemic areas, rare in non-endemic areas. It occurs more commonly in dogs and rarely in cats.

Geographic Distribution

• C. immitis is found in the southwestern United States in the geographic Lower Sonoran life zone.
• More common in Southern California, Arizona, and southwest Texas and is less prevalent in New Mexico, Nevada, and Utah.

Signalment

Signs

Causes

C. immitis grows several inches deep in the soil, where it survives high ambient temperatures and low moisture. After a period of rainfall, the organism returns to the soil surface where it sporulates, releasing many arthroconidia that are disseminated by wind and dust storms.

Risk Factors

• Aggressive nosing in contaminated soil and underbrush may expose susceptible animals to large numbers of arthroconidia.
• Dust storms after the rainy season; increased incidence noted after earthquakes.
• Land development with earth disruption may lead to increased exposure.

Differential Diagnosis

• Pulmonary lesions may resemble those of other systemic mycoses (e.g., histoplasmosis, blastomycosis).
• Lymphadenomegaly may be seen in lymphoma, other systemic mycoses, and localized bacterial infections.
• Bone lesions may resemble those caused by primary or metastatic bone tumors or bacterial osteomyelitis.
• Skin lesions must be differentiated from routine abscesses or other infective processes.
• For seizures and ataxia, consider inflammatory and oncologic etiologies.

CBC/Biochemistry/Urinalysis

• Hemogram-mild nonregenerative anemia, neutrophilic leukocytosis, monocytosis.
• Serum chemistry profile-hyperglobulinemia, hypoalbuminemia, other changes may be consistent with organ of involvement.
• Urinalysis-proteinuria with inflammatory glomerulonephritis.

Other Laboratory Tests

Serologic tests (generally by AGID or ELISA) for antibody to C. immitis may provide a presumptive diagnosis; may aid in monitoring response to therapy.

Imaging

• Radiography of lung (interstitial infiltrates) and bone lesions (osteolysis) may aid in diagnosis.
• MRI may help in diagnosing granulomas in the CNS.

Diagnostic Procedures

• Serologic testing; repeat serology titers in 4–6 weeks when low titers are accompanied by clinical signs.
• Microscopic identification of the large spherule form of C. immitis in lesion or biopsy material is the definitive method of diagnosis (large 10–80 µm round, double-walled structure containing endospores).
• Lymph node aspirates and impression smears of skin lesions or draining exudate may yield organisms.
• Cultures should be performed by trained laboratory personnel using protective hoods.
• Biopsy of infected tissue often is preferred to avoid false-negative results. Tissues involved, however, may not be readily accessible and finding the organism can be challenging; therefore, serologic testing can be a more logical approach.

Pathologic Findings

• Granulomatous, suppurative, or pyogranulomatous inflammation present in many tissues.
• Presence of the characteristic spherule forms in affected tissues.

Appropriate Health Care

• Generally treated as outpatient.
• Concurrent clinical symptoms (e.g., seizures, pain, coughing) should be treated appropriately.

Activity

Restrict activity until clinical signs begin to subside.

Diet

Feed a high-quality palatable diet to maintain body weight.

Client Education

• Treatment is potentially long (>6 months) and expensive.
• Relapse (especially with disseminated disease) is common.
• Reassure client that the infection is not zoonotic.

Surgical Considerations

In cases of focal granulomatous organ involvement (e.g., consolidated pulmonary lung lobe, eye, kidney), surgical removal of the affected organ may be indicated.

Drug(s) Of Choice

Coccidioidomycosis is considered one of the most severe and life threatening of the systemic mycoses. Treatment of disseminated disease often requires at least 1 year of aggressive antifungal therapy.

Contraindications

• Drugs metabolized primarily by the liver should be used with caution alongside any azole drugs.
• Drugs metabolized primarily by the kidneys should be used with caution along with AMB.

Precautions

• Side effects of azoles include inappetence, vomiting, and hepatotoxicity (typically ALT > ALP); liver values should be monitored; drugs may be stopped until signs abate and restarted at a lower dose, which may be slowly increased to the recommended dose if the animal is able to tolerate the drug; newer azoles (ITZ and FCZ) have fewer side effects.
• Side effects of AMB therapy can be severe, especially renal dysfunction, fever; use with caution if patient is azotemic but not an absolute contraindication if the infection is life-threatening.

Patient Monitoring

• Serologic titers should be monitored every 3–4 months; animals should be treated until their titers fall to less than 1:4; consider itraconazole levels (2–4 hour post-pill) in patients showing a poor response to itraconazole therapy, especially if using a generic or compounded formulation.
• Creatinine and urinalysis should be monitored in all animals treated with AMB; treatment should be temporarily discontinued if the creatinine rises above the reference range or greater than 20% above baseline or if granular casts are noted in the urine.

Prevention/Avoidance

• No vaccine is available for dogs or cats.
• Contaminated soil in endemic areas should be avoided, particularly during dust storms after the rainy season.

Possible Complications

Pulmonary disease resulting in severe coughing may temporarily worsen after therapy is begun owing to inflammation in the lungs. Low-dose short-term oral prednisone and cough suppressants may be required to alleviate the respiratory signs.

Expected Course and Prognosis

• The prognosis for localized respiratory disease is good.
• The prognosis for disseminated disease is more guarded; many dogs will improve following oral therapy with resolution of signs reported in up to 90% cases; however, relapses may be common, especially if therapy is shortened; overall recovery rate has been estimated at 60%.
• The prognosis with CNS involvement may be guarded to poor.
• The prognosis for cats is not well documented, but long-term therapy should be anticipated and relapses are common.
• Serologic testing every 3–4 months after completion of therapy is recommended to monitor the possibility of relapse.
• Spontaneous recovery from disseminated coccidioidomycosis without treatment is extremely rare.

Zoonotic Potential

• The spherule form of the fungus, as found in animal tissues, is not directly transmissible to humans or to other animals.
• Under certain rare circumstances, however, there could be reversion to growth of the infective mold form of the fungus on or within bandages placed over a draining lesion or in contaminated bedding; draining lesions can lead to contamination of the environment with arthrospores; care should be exercised whenever handling an infected draining lesion.
• Special precautions should be recommended to households in which the owners may be immunosuppressed.

Pregnancy/Fertility/Breeding

Azole drugs can be teratogenic and should be used in pregnant animals only if the potential benefit justifies the potential risk to offspring.

Synonyms

• Desert rheumatism (in humans)
• San Joaquin Valley fever
• Valley fever

Abbreviations

• AGID = agar gel immunodiffusion
• AMB = amphotericin B
• CNS = central nervous system
• ELISA = enzyme-linked immunosorbent assay
• FCZ = fluconazole
• ITZ = itraconazole
• KTZ = ketoconazole
• MRI = magnetic resonance imaging

Client Education Handout Available Online