AUTHOR INFORMATION

Section 1 of 11

Authored by James de la Torre, MD, Staff Physician, Resident Emergency Medicine, Department of Emergency Medicine, University of Southern California/Los Angeles County Medical Center

Coauthored by Allison J Richard, MD, Instructor of Clinical Emergency Medicine, Keck School of Medicine, University of Southern California, Consulting Staff, Department of Emergency Medicine, Los Angeles County-University of Southern California Hospital; Joseph Kim, MD, Chairman, Department of Emergency Medicine, Western Medical Center; Clinical Instructor Univ of Calif at Irvine

Edited by David FM Brown, MD, Assistant Professor, Department of Medicine, Division of Emergency Medicine, Harvard Medical School; Vice-Chair, Department of Emergency Medicine, Massachusetts General Hospital; Francisco Talavera, PharmD, PhD, Senior Pharmacy Editor, eMedicine; Barry J Sheridan, DO, Chief, Department of Emergency Medical Services, Brooke Army Medical Center; John Halamka, MD, Chief Information Officer, CareGroup Healthcare System, Assistant Professor of Medicine, Department of Emergency Medicine, Beth Israel Deaconess Medical Center; Assistant Professor of Medicine, Harvard Medical School; and Barry Brenner, MD, PhD, FACEP, Professor of Emergency Medicine, Professor of Internal Medicine, and Professor of Anatomy and Neurobiology, Research Director, Department of Emergency Medicine, University of Arkansas for Medical Sciences

Author's Email:	James de la Torre, MD
Editor's Email:	David FM Brown, MD

eMedicine Journal, September 28 2006, VOLUME 7, Number 9

INTRODUCTION

Section 2 of 11

Background: Coccidioides immitis (CI), the etiologic agent responsible for coccidioidomycosis and the more well-known San Joaquin Valley Fever, is a dimorphic fungus, existing in both mold and a yeast form, endemic to the Southwestern United States and other lower Sonoran climates of Central America and South America. It was first described in the late 1800s; however, most cases at this time were consistent with more severe cases of C immitis infection, and many of the more benign cases were not recognized until 1929 with an unintentional exposure of a medical student at Stanford University. The medical student subsequently developed a respiratory tract infection and lived, thus sparking interest and the eventual connection between C immitis and Valley Fever.

Pathophysiology: C immitis infections occur when inhaled arthroconidia (spores) are deposited in the lower airways and subsequently change morphology to a spherule. These spherules enlarge, divide, and rupture to release hundreds of 2-5 micron spherule particles, which reproduce similarly. During primary infection, a mononuclear infiltrate may develop followed by subsequent conversion to PMN predominance.

Important in the development of effective immunity is the role of Th1-helper cells. Observational data and experimental models show that lack of Th1 or predominance of Th2 cells results in higher rates of disseminated disease (ie, in HIV/AIDS, certain lymphomas, transplant patients, chronically steroid dependent patients). C immitis infection can also occur by direct inoculation such as in contaminated penetrating objects. Other rare case reports have been documented such an infected lung transplant and sexually transmitted cases. It has also been theorized that some of the phagocytized arthroconidia are transported back to draining lymph nodes by macrophages and can cause a lymphangitis. It is generally accepted that the inoculating dose responsible for infection is small and may be 10 or less arthroconidia.

Frequency:

• In the US: C immitis infection rates are typically quoted in the 100,000 per year range within the United States. Peak incidence occurs during the summer to early fall months and is related to the variations in weather and spore formation. In particular, outbreaks have been documented during earthquakes and wind storms, which agitate arthroconidia causing them to become airborne.

  Historically, people at greatest risk for contact are farmers, construction workers, and archaeologists. In fact, in recent time, the Northridge earthquake and outbreaks among archaeologists highlight these events. Thus, otherwise healthy persons exposed to high spore burdens have a higher likelihood of more severe disease. C immitis cases are by no means confined to the southwestern United States, and, in fact, cases have been reported in travelers visiting endemic areas. This illustrates the need for careful history taking and possible exposure in endemic areas.

• Internationally: Affected areas are in the lower Sonoran areas, which are characterized by semiarid climates with hot summers and alkaline soil. These areas include northern Mexico, Central America, and South America.

Mortality/Morbidity: C immitis infection is rarely fatal except in those who may be extremely immunocompromised. Five to 10 percent of patients will harbor residual pulmonary disease, and only about 1% of patients progress to have disseminated CI disease.

Any person with impaired cellular immunity has a greater risk for disseminated CI disease. HIV/AIDS patients are particularly susceptible to more severe CI disease, especially at CD4 counts less than 250. Also there is an increased risk of dissemination during pregnancy, with each trimester at slightly higher risk. Patients with lymphoma, those with solid organ transplantation, and patients on long-term corticosteroid treatment are also at higher risk of dissemination. Recent advances in immunosuppressive therapy with TNF-alpha inhibitors have also been proposed as a risk factor for advanced or disseminated disease.

Race: Filipinos, blacks, and Hispanics have an increased risk of disseminated disease as compared with Caucasians. Studies have shown that genotypic variations in HLA either confer increased or reduced risk of dissemination. Hispanics with A or B type blood groups are also at slightly higher risk for advanced and/or disseminated disease when compared with the population as a whole.

• Low income has been associated with a predisposition for severe pulmonary infection and disseminated disease. Although it is unclear what role health care access has in this observation.

Sex: Incidence is equal in males and females.

Age: All age groups can be affected.

• Congenital infection is rarely a factor in childhood coccidioidomycosis. In disseminated disease, the mortality rates in neonates and infants are much higher than those in children, adolescents, and adults.

CLINICAL

Section 3 of 11

History: The natural history of C immitis infection is usually one of a self-limited respiratory tract infection, which occurs 1-3 weeks after exposure. Most cases (60%) are subclinical, never reaching the attention of a physician.

Common complaints of those cases making it to clinical attention are nonspecific and consist of fever, cough, chest pain, fatigue, dyspnea, headache, arthralgias, and/or myalgias. Skin manifestations are also seen in a small percentage of cases. In addition to the above clinical scenarios, CI can progress to a variety of presentations. The triad of fever, erythema nodosum, and arthralgias is commonly referred to as San Joaquin Valley Fever or desert rheumatism.

Primary pulmonary infection may progress to overt pneumonia, chronic lung infections, hematogenous spread, disseminated disease, and meningitis. Important in the diagnosis of CI is clinical suspicion and eliciting a history of possible exposure or travel to an endemic area.

Physical:

• Pulmonary

• In addition to the asymptomatic infection and benign/unrecognized respiratory infections, CI can also go on to a progressive disease forming pneumonias of varying degree. Infiltrates can range from segmental or lobar pneumonias to diffuse reticulonodular infiltrates, but it can also progress to complete respiratory failure.

• A small percentage of patients may present with asymptomatic pulmonary nodules, which may be confused with malignancy. Nodules, although asymptomatic, may persist over time and can degenerate into thin-walled cavitations, which may erode into adjacent small airways resulting in hemoptysis or pneumothorax.

• Chronic pulmonary patterns may also develop including chronic fibrocavitary lesions.

• Physical examination findings are generally nonspecific but can include rales, pleural rubs, wheezing, and decreased breath sounds from effusions.

• Dermatologic

• A variety of dermatologic sequelae can result from CI infection. The best known of these is erythema nodosum, which presents as tender, erythematous nodules on the anterior lower extremities. These nodules are immune complexes consistent with immune complex phenomena.

• Disseminated infection can also result in ulceration and fistulas from underlying infection. Lesions can also present as ulcerations or verrucous lesions with a predilection for the nasolabial area.

• CNS

• As in other organ systems, CI can present in a variety of ways and CNS is no exception. The most serious form of disseminated CI is meningitis. As with other etiologies of meningitis, symptoms typically include fever, headache, meningismus, nausea, vomiting, and altered mental status.

• Basilar meninges are often affected, and inflammation may result in a noncommunicating hydrocephalus, increased ICP, and subsequent death if left untreated. Cranial nerve palsies, abscesses, and vasculitides are also described complications of CNS infection.

• Cardiovascular

• Cardiovascular complications of CI are rare and account for an extremely small percentage of clinical presentations. However, when they do occur they can be devastating.

• Pericardial effusions are a rare but recognized occurrence in CI, and they can produce cardiovascular compromise and tamponade in extreme cases.

• Musculoskeletal

• The most common manifestations of CI with respect to the musculoskeletal system are osteomyelitis, septic arthritis, and synovitis. The latter two often need to be differentiated clinically.

• Arthritis is usually monoarticular, but it can be migratory in nature. Typically, the weightbearing joints, such as the knee, are affected. Arthrocentesis samples typically show an exudative effusion. Presence of organisms varies, and literature shows that typically direct visualization of organisms is rare but can occur in up to half of cases.

• Although osteomyelitis can occur from direct inoculation of bone from contaminated penetrating objects, it is more commonly a result of hematogenous spread and disproportionately affects the vertebra, and paraspinal abscesses are a possible complication. Other common sites of involvement include the tibia, femur, skull, and bones of the hands and feet. Lesions in the larger bones typically appear as radiopaque lesions, whereas smaller bones tend to have an appearance more typical of osteomyelitis.

• Disseminated CI

• CI can virtually present in any organ system. In addition to the above, patients with disseminated CI may present in septic shock.

Causes: Coccidioides immitis, a soil fungus particularly adapted to arid conditions, causes coccidioidomycosis.

DIFFERENTIALS

Section 4 of 11

Babesiosis
Erythema Multiforme
Granuloma, Annulare and Pyogenic
Meningitis
Neoplasms, Lung
Pleural Effusion
Pneumonia, Aspiration
Pneumonia, Bacterial
Pneumonia, Empyema and Abscess
Pneumonia, Immunocompromised
Pneumonia, Mycoplasma
Pneumonia, Viral
Sarcoidosis
Tuberculosis

Other Problems to be Considered:

Histoplasmosis
Blastomycosis
Paracoccidioidomycosis
Other fungi
Lung abscess
Lymphoma
Other causes of cough, fever, and fatigue
Old granuloma

WORKUP

Section 5 of 11

Lab Studies:

• Guide diagnostic evaluation by index of suspicion and patient's clinical presentation. A variety of testing may aid or confirm the diagnosis.

• CBC may reveal a leukocytosis with a eosinophilia, lymphocytosis, or monocytosis.

• Direct observation: Observe for direct evidence of spherules of C immitis from various aspirates/body fluids or biopsies. Various fungal stains may increase sensitivity.

• Skin testing: Delayed-type hypersensitivity reactions may become positive as early as 1-3 weeks. Although reactivity may endure for a lifetime, it may wane in some individuals particularly those who may be anergic.

• Serology tube precipitin assays for IgM may detect acute infection. IgM reactivity usually does not persist for more than 6 months. Complement fixation is useful in detecting IgG immunity and is particularly useful in evaluating the extent and response to meningeal disease.

• Culture may be performed, but results are usually delayed given a 5- to 7-day incubation.

• Immunoprecipitant assays

• Immunodiffusion

Imaging Studies:

• Chest x-ray should be done routinely to check for signs of pulmonary infection.

• May be normal

• Infiltrates

• Nodules

• Cavity

• Mediastinal or hilar adenopathy

• Pleural effusion

• Radiographs of affected areas of the body are done to check for osteomyelitis.

Procedures:

• If unable to obtain a diagnosis by skin testing or serology, consider performing the following:

• Bronchoscopy

• Fine-needle biopsy

• Open-lung biopsy

• Pleural biopsy

• Bone/skin/node biopsy

TREATMENT

Section 6 of 11

Emergency Department Care: Rarely is therapy started in ED, but infectious disease consultants often expedite therapy in endemic areas. Therapies include amphotericin B and the azoles, including ketoconazole and fluconazole.

Consultations: Report cases to infectious disease and local health departments.

• Consult pulmonology.

MEDICATION

Section 7 of 11

In general, severity and tempo of disease usually dictates tempo of treatment. In patients with suspected or documented uncomplicated primary CI, treatment opinion varies from careful observation to treatment with long-term azole therapy.

Some authors have suggested that empiric treatment may decrease the rate of disseminated infection, but this has not been proven in any controlled studies and no conclusive guidelines exist on which uncomplicated infections need treatment. However, at risk groups for dissemination such as blacks, Filipinos, HIV/AIDS patients, DM, and third trimester pregnancies warrant more aggressive treatment. Typically, this may be accomplished with fluconazole except in pregnant women, as azole antifungals are teratogenic. Pregnant women with suspected CI infection may be treated with amphotericin B. To date, few RCTs have looked specifically at the efficacy of the different azoles for treatment of CI. Of note, Galgiani et al compared fluconazole and itraconazole in a RCT for treatment of CI. Although no statistically significant difference was noted, there was a trend in the better outcomes in musculoskeletal CI with itraconazole.

Patients with more advanced disease require more aggressive treatment. In particular, patients exhibiting signs of meningitis need either IV antibiotic therapy with amphotericin unless otherwise contraindicated or high-dose azole therapy with or without intrathecal amphotericin. Some recent case reports have suggested that voriconazole or posaconazole may be therapeutic options in these patients, although these are only anecdotal to date, and no comparative studies have been performed. The role of caspofungin in combination with fluconazole has recently been cited as beneficial in a case report of a Korean gentleman with CI pneumonia. Steroids may be of some benefit in patients with vasculitis.

Drug Category: Antifungal agents -- Their mechanism of action may involve an alteration of RNA and DNA metabolism or an intracellular accumulation of peroxide that is toxic to the fungal cell.

Drug Name	Amphotericin B (AmBisome, Fungizone) -- Depending on concentration attained in body fluids and on fungal susceptibility, agent can be fungistatic or fungicidal. This polyene antibiotic produced by strain of Streptomyces nodosus changes membrane permeability by binding to sterols in fungal cell membrane; fungal cell death results.
Adult Dose	0.5-1 mg/kg/d IV; not to exceed 2-4 g/dose
Pediatric Dose	2.5 mg/kg/d IV
Contraindications	Documented hypersensitivity
Interactions	Antineoplastic agents may enhance potential of amphotericin B for renal toxicity, bronchospasm, and hypotension; corticosteroids, digitalis, and thiazides may potentiate hypokalemia; risk of renal toxicity increased with cyclosporine
Pregnancy	B - Usually safe but benefits must outweigh the risks.
Precautions	Monitor renal function, serum electrolytes such as magnesium and potassium, liver function, CBC, and hemoglobin concentrations; resume therapy at lowest dose (eg, 0.25 mg/kg) when interrupted for > 7 d; hypoxemia, acute dyspnea, and interstitial infiltrates may occur in neutropenic patients receiving leukocyte transfusions (separate time of amphotericin infusion from time of leukocyte transfusion)

Drug Name	Fluconazole (Diflucan) -- Synthetic bistriazole antifungal agent; highly selective inhibitor of fungal cytochrome P-450 and sterol C-14 alpha-demethylation with broad-spectrum activity.
Adult Dose	200-400 mg PO qd
Pediatric Dose	3-6 mg/kg PO qd for 14-28 d depending on severity of infection
Contraindications	Documented hypersensitivity
Interactions	Levels may increase with hydrochlorothiazides; levels may decrease with long-term coadministration of rifampin; may decrease phenytoin concentrations; may increase concentrations of theophylline, tolbutamide, glyburide, and glipizide; may increase effects of anticoagulants; may increase cyclosporine concentration
Pregnancy	C - Safety for use during pregnancy has not been established.
Precautions	Not recommended for breastfeeding mothers Monitor closely if rashes develop and discontinue drug if lesions progress; may cause clinical hepatitis, cholestasis and fulminant hepatic failure (including death) with underlying medical conditions such as AIDS or a malignancy and while taking multiple concomitant medications

Drug Name	Ketoconazole (Nizoral) -- Imidazole broad-spectrum antifungal agent. Impairs synthesis of ergosterol, allowing increased permeability and leakage of cellular components.
Adult Dose	200-400 mg PO qd
Pediatric Dose	Not established
Contraindications	Documented hypersensitivity; fungal meningitis
Interactions	Isoniazid may decrease bioavailability; coadministration with rifampin decreases effects of either drug; may increase effect of anticoagulants; may increase toxicity of corticosteroids and cyclosporine (cyclosporine dosage can be adjusted); may decrease theophylline levels
Pregnancy	C - Safety for use during pregnancy has not been established.
Precautions	Hepatotoxicity may occur; may reversibly decrease corticosteroid serum levels (adverse effects avoided with dose of 200-400 mg/d) Testosterone levels are reduced by doses of 800 mg/d and abolished by doses of 1600 mg/d (once therapy discontinued, levels return to baseline values); decreases ACTH-induced corticosteroid serum levels at high doses (to avoid these effects, closely follow recommended dose of 200-400 mg/d) Requires acidity for dissolution and absorption (if antacids, anticholinergics, or H2-blockers are needed, give > 2 h after ketoconazole)

Drug Name	Itraconazole (Sporanox) -- Triazole analogue of ketoconazole
Adult Dose	400-600 mg PO qd
Pediatric Dose	Specific dosing in children with CI not studied; in other antifungal regimen recommend dose is 5 mg/kg/d PO divided qd/bid; max dose 10 mg/kg/d
Contraindications	Documented or suspected drug allergies or hypersensitivity; CHF or liver dysfunction
Interactions	Antacids may reduce absorption; edema may occur with coadministration of calcium channel blockers (eg, amlodipine, nifedipine); hypoglycemia may occur with sulfonylureas; high doses may increase tacrolimus and cyclosporine plasma concentrations; rhabdomyolysis may occur with coadministration of HMG-CoA reductase inhibitors (lovastatin or simvastatin); coadministration with cisapride can cause cardiac rhythm abnormalities and death; may increase digoxin levels; coadministration may increase plasma levels of midazolam or triazolam; phenytoin and rifampin may reduce levels (phenytoin metabolism may be altered)
Pregnancy	C - Safety for use during pregnancy has not been established.
Precautions	Use cautiously in patients with hepatic insufficiency

Drug Name	Voriconazole (Vfend) -- Triazole antifungal agent that inhibits fungal cytochrome P450-mediated 14 alpha-lanosterol demethylation, which is essential in fungal ergosterol biosynthesis.
Adult Dose	200 mg PO bid or 3-6 mg/kg IV q12h
Pediatric Dose	Not established
Contraindications	Documented hypersensitivity; CrCl <50 mL/min (decreased excretion of IV vehicle) if administering IV; coadministration with rifampin, rifabutin, carbamazepine, barbiturates, sirolimus, pimozide, quinidine, cisapride, ergot alkaloids
Interactions	CYP450 2C19 (highest affinity), 2C9, and 3A4 (minor) substrate and inhibitor; CYP450 inducers (eg, rifampin) have shown to decrease steady state peak plasma levels by up to 93%; may increase serum levels of drugs metabolized by CYP450 2C19 or 2C9, of which some are contraindicated (eg, sirolimus, pimozide, quinidine, cisapride, ergot alkaloids), others may need more frequent monitoring (eg, cyclosporine, tacrolimus, warfarin, HMG-CoA inhibitors, benzodiazepines, calcium channel blockers)
Pregnancy	D - Unsafe in pregnancy
Precautions	Decrease maintenance dose in hepatic dysfunction; common adverse effects include visual disturbances, fever, rash, vomiting, nausea, diarrhea, headache, sepsis, peripheral edema, abdominal pain, rash (including Stevens-Johnson syndrome and phototoxicity), and respiratory disorder; rare cases of severe hepatotoxicity reported; administer PO dosage form 1 h ac or pc

Drug Name	Posaconazole (Noxafil) -- Triazole antifungal agent that possesses structural similarities to itraconazole. Blocks ergosterol synthesis by inhibiting the enzyme lanosterol 14-alpha-demethylase and sterol precursor accumulation. This action results in cell membrane disruption. Available as oral susp (200 mg/5 mL). Indicated for prophylaxis of invasive Aspergillus and Candida infections in patients at high risk because of severe immunosuppression.
Adult Dose	200 mg (5 mL) PO tid with food or liquid nutritional supplement to enhance absorption
Pediatric Dose	<13 years: Not established >13 years: Administer as in adults
Contraindications	Documented hypersensitivity; coadministration with ergot alkaloids; coadministration with CYP3A4 substrates likely to result in serious toxicities (eg, terfenadine, astemizole, cisapride, pimozide, halofantrine, quinidine)
Interactions	Metabolized via UDP glucuronidation; P-gp efflux substrate; CYP3A4 inhibitor UDP-G inducers (eg, rifabutin, phenytoin) and drugs that increase gastric pH (eg, cimetidine) decrease serum levels (avoid concomitant use unless benefit outweighs risk) Inhibits CYP3A4 and may elevate serum levels of cyclosporine, tacrolimus, sirolimus, rifabutin, midazolam, phenytoin, calcium channel blockers (eg, nifedipine, bepridil), HMG-CoA reductase inhibitors (eg, lovastatin, pravastatin), ergot alkaloids, terfenadine, astemizole, cisapride, pimozide, halofantrine, quinidine, or vinca alkaloids (eg, vincristine, vinblastine)
Pregnancy	C - Safety for use during pregnancy has not been established.
Precautions	Common adverse effects include nausea, vomiting, diarrhea, rash, hypokalemia, thrombocytopenia, and elevated liver enzyme levels; closely monitor patients with severe diarrhea or vomiting for breakthrough fungal infections; rare adverse events include arrhythmias caused by QTc prolongation, bilirubinemia, or liver function impairment; caution with preexisting cardiac risk factors (eg, history of arrhythmia, hypokalemia, hypomagnesemia); food improves absorption and provides optimal serum concentration; shake well before use; administer with measuring spoon provided in package; avoid if breastfeeding

Drug Name	Caspofungin (Cancidas) -- First of a new class of antifungal drugs (glucan synthesis inhibitors). Inhibits synthesis of beta-(1,3)-D-glucan, an essential component of fungal cell wall.
Adult Dose	Not established; typical antifungal regimens suggest starting at 70 mg IV on day 1 followed by 50 mg IV qd
Pediatric Dose	Not established
Contraindications	Documented or suspected drug allergies or hypersensitivity
Interactions	Coadministration with cyclosporine may increase risk of hepatotoxicity; carbamazepine, nelfinavir, efavirenz, or dexamethasone may decrease levels of caspofungin; caspofungin may decrease levels of tacrolimus; rifampin decreases caspofungin levels by 30% (ie, adjust dose to 70 mg/d)
Pregnancy	C - Safety for use during pregnancy has not been established.
Precautions	Caution in moderate hepatic dysfunction (ie, decrease dose to 35 mg/d); may exacerbate preexisting renal dysfunction or myelosuppression

FOLLOW-UP

Section 8 of 11

Further Inpatient Care:

• Indications for admission

• Immunocompromised conditions

• Dissemination

• Any need for symptomatic support or intravenous therapy

Complications:

• Severe cases are fatal, particularly if associated with meningitis.

• Obstruction of pulmonary tissue due to scarring or cavities may occur.

Prognosis:

• Most cases are self-limited and resolve within a few months.

• Prognosis is poor if the patient has a weak cell-mediated immunity or high IgG.

• Relapse of extrapulmonary or disseminated disease is common.

Patient Education:

• Educate populations at high risk (eg, immunocompromised, pregnant women, African Americans, Filipinos, those with diabetes) on avoidance of high-risk activities (eg, construction, archeological digs).

MISCELLANEOUS

Section 9 of 11

Medical/Legal Pitfalls:

• Failure to consider this or other fungal infections in patients in whom other therapies have failed and in those who appear to have a chronic illness or are resident of (or traveler to) endemic regions

• In recent times, CI has regained interest due to its potential as a bioterrorism weapon. CI is listed in some texts as a potential agent for biological warfare. Although the exact outcome of a CI attack cannot be known, CI possesses some properties that could make it attractive as a weapon. In particular, CI spores can be disseminated and aerosolized rather easily. However, the infectivity in this capacity is unknown and effects probably are limited.

TEST QUESTIONS

Section 10 of 11

CME Question 1: Which of the following patients would have the highest likelihood of coccidioidomycosis dissemination?

A: A 58-year-old African American male smoker
B: A 24-year-old Hispanic male archaeologist
C: A 23-year-old white female intravenous drug user
D: A 15-year-old Hispanic male farm laborer visiting from Mexico
E: A 21-year-old pregnant Filipino female

The correct answer is E: Filipinos have the highest rate of dissemination. Pregnancy confers an additional risk of dissemination, 40-100 times greater than that of the general population.

CME Question 2: Which of the following is associated with disseminated coccidioidomycotic disease?

A: Hilar adenopathy
B: Pneumonia
C: Bronchopleural fistulas
D: None of the above
E: All of the above

The correct answer is D: Disseminated coccidioidomycosis refers to extrapulmonary disease and may involve hematopoietic tissues, skin, kidneys, bones, CNS, and myocardium. Resulting meningitis takes the form of granulomatous inflammation and may present as either noncommunicating hydrocephalus or communicating hydrocephalus.

Pearl Question 1 (T/F): A positive skin test for cocci confers a bad prognosis for coccidioidomycosis.

The correct answer is False: A positive skin test indicates immunocompetence and exposure to the cocci agent. A negative skin test in the presence of a positive serologic study confers a slightly worse prognosis.

Pearl Question 2 (T/F): Coccidioidomycosis meningitis takes the form of granulomatous inflammation and may present as either noncommunicating or communicating hydrocephalus.

The correct answer is True: Pathophysiology involves granulomatous changes of the ependymal cell layer and resulting obstruction in the ventricles.

Pearl Question 3 (T/F): A rising cocci serologic titer indicates progression toward dissemination or relapse.

The correct answer is True: Over 40% of patients with disseminated disease have titers of 1:64 or greater. A rising titer indicates progression of disease.

Pearl Question 4 (T/F): A patient with coccidioidomycosis undergoing amphotericin B therapy presents with hypotension and prolonged QT interval on the cardiac monitor strip. A stat expanded chemistry panel is an important diagnostic consideration.

The correct answer is True: A stat expanded chemistry panel (which includes potassium, BUN, and creatinine) may indicate hyperkalemia with marked renal insufficiency, the result of amphotericin B nephrotoxicity.

BIBLIOGRAPHY

Section 11 of 11

• Ampel NM: Combating opportunistic infections: coccidioidomycosis. Expert Opin Pharmacother 2004 Feb; 5(2): 255-61[Medline].
• Anstead GM, Corcoran G, Lewis J: Refractory coccidioidomycosis treated with posaconazole. Clin Infect Dis 2005 Jun 15; 40(12): 1770-6[Medline].
• Bergstrom L, Yocum DE, Ampel NM: Increased risk of coccidioidomycosis in patients treated with tumor necrosis factor alpha antagonists. Arthritis Rheum 2004 Jun; 50(6): 1959-66[Medline].
• Blair JE, Smilack JD, Caples SM: Coccidioidomycosis in patients with hematologic malignancies. Arch Intern Med 2005 Jan 10; 165(1): 113-7[Medline].
• Catanzaro A: Coccidioidomycosis. In: Manual of Clinical Problems in Pulmonary Medicine. 5th ed. Lippincott Williams & Wilkins; 2000.
• CDC: Increase in coccidioidomycosis--Arizona, 1998-2001. MMWR Morb Mortal Wkly Rep 2003 Feb 14; 52(6): 109-12[Medline].
• CDC: From the Centers for Disease Control and Prevention. Coccidioidomycosis following the Northridge earthquake--California, 1994. JAMA 1994 Jun 8; 271(22): 1735[Medline].
• Comrie AC: Climate factors influencing coccidioidomycosis seasonality and outbreaks. Environ Health Perspect 2005 Jun; 113(6): 688-92[Medline].
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• Deresinski SC, Mirels LF, Kemper CA: Coccidioides immitis. In: Infectious Diseases. Philadelphia: Lippincott Williams & Wilkins; 2004:2227-46.
• Galgiani J: Coccidioides immitis. In: Principles and Practice of Infectious Diseases. New York: Churchill Livingstone; 2000:2746-57.
• Galgiani JN, Catanzaro A, Cloud GA: Comparison of oral fluconazole and itraconazole for progressive, nonmeningeal coccidioidomycosis. A randomized, double-blind trial. Mycoses Study Group. Ann Intern Med 2000 Nov 7; 133(9): 676-86[Medline].
• Jones JL, Fleming PL, Ciesielski CA: Coccidioidomycosis among persons with AIDS in the United States. J Infect Dis 1995 Apr; 171(4): 961-6[Medline].
• Louie L, Ng S, Hajjeh R: Influence of host genetics on the severity of coccidioidomycosis. Emerg Infect Dis 1999 Sep-Oct; 5(5): 672-80[Medline].
• Park DW, Sohn JW, Cheong HJ: Combination therapy of disseminated coccidioidomycosis with caspofungin and fluconazole. BMC Infect Dis 2006; 6: 26[Medline].
• Prabhu RM, Bonnell M, Currier BL: Successful treatment of disseminated nonmeningeal coccidioidomycosis with voriconazole. Clin Infect Dis 2004 Oct 1; 39(7): e74-7[Medline].
• Rosenstein NE, Emery KW, Werner SB: Risk factors for severe pulmonary and disseminated coccidioidomycosis: Kern County, California, 1995-1996. Clin Infect Dis 2001 Mar 1; 32(5): 708-15[Medline].
• Schneider E, Hajjeh RA, Spiegel RA: A coccidioidomycosis outbreak following the Northridge, Calif, earthquake. JAMA 1997 Mar 19; 277(11): 904-8[Medline].

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