Coccidioidin (Monograph)

Drug class: Fungi
- Skin Test Antigen
- Cell-mediated Immunity Function
- Immunity Function, Cell-mediated
VA class: DX300
CAS number: 12622-73-0

Medically reviewed by Drugs.com on Dec 23, 2024. Written by ASHP.

Introduction

Coccidioidin is a skin test antigen derived from by-products of Coccidiodes imitis.

Uses for Coccidioidin

Coccidioidomycosis

Coccidioidin is a skin test antigen. It is used as an aid in the diagnosis of coccidioidomycosis and in the differentiation of suspected coccidioidomycosis from other mycotic or bacterial infections such as blastomycosis, histoplasmosis, or tuberculosis, or from sarcoidosis.

Absolute diagnosis of coccidioidomycosis can be established only by isolation of the organism although the diagnosis can be suggested by a positive reaction to an intradermal skin test with coccidioidin or demonstration of a high titer of complement-fixing antibodies. Precipitins and complement-fixing antibodies are regularly present early in the progressive form of coccidioidomycosis and in the more severe primary form of the disease, but in the latter they disappear on recovery. Intradermal administration of coccidioidin does not adversely affect results of serologic tests for coccidioidomycosis (e.g., tube precipitin, complement-fixation, immunodiffusion) and these tests may be done simultaneously.

A positive reaction to an intradermal skin test with coccidioidin generally indicates either a present or past infection with C. immitis; however, other fungi with related immunologic properties (e.g., Histoplasma capsulatum, Blastomyces) may cause cross-reactions with coccidioidin. Negative reactions to coccidioidin, which are usually the result of waning sensitivity or anergy, occur frequently in patients with disseminated coccidioidomycosis or in patients with thin-walled coccidioidal pulmonary cavities. Repeated negative reactions to coccidioidin during chronic pulmonary infections suggest that an organism other than C. immitis is responsible; tests with tuberculin and histoplasmin should then be used in conjunction with coccidioidin.

Cell-mediated Immunity

Coccidioidin is used in conjunction with other antigens (e.g., candida, histoplasmin, mumps skin test antigen, trichophyton, tuberculin) to assess the status of cell-mediated immunity, especially in malnourished patients, surgical patients, or patients with cancer. Because the cell-mediated response to these antigens depends on previous exposure to or infection with them, only those antigens to which the patient has probably been exposed in the past should be used. These skin test antigens are used as screening tests and can only indicate the presence or absence of cell-mediated immunity. In vitro tests (e.g., lymphocyte stimulation, assays for T and B cells) are necessary to diagnose specific immunologic disorders.

Coccidioidin Dosage and Administration

Coccidioidin is administered only by intradermal injection into the flexor surface of the forearm.

Coccidioidin is injected intradermally using a tuberculin syringe with a (3/8)–½ inch 26- or 27-gauge needle. With the bevel of the needle pointing outward, the needle is inserted into the most superficial layers of the skin and the solution slowly injected. If the injection is correctly made, a small bleb or wheal should form at the injection site. A scrupulously clean syringe and needle must be used in the preparation and administration of coccidioidin. The syringe used for coccidioidin should not be used for tuberculin or other material.

Coccidioidomycosis

The usual dose of coccidioidin used as an aid in the diagnosis of coccidioidomycosis is 0.1 mL of the 1:100 dilution. Since patients with disseminated coccidioidomycosis or thin-walled coccidioidal pulmonary cavities frequently have negative reactions to the 1:100 dilution, 0.1 mL of the 1:10 dilution may be used for skin testing in these patients.

The coccidioidin test site should be examined after 24 hours; an additional reading at 48 hours has been recommended to avoid false-negative results. A positive reaction to coccidioidin consists of an area of induration measuring 5 mm or greater in diameter. Erythema without induration is a negative reaction.

Since patients with coccidioidal erythema nodosum are likely to be hypersensitive to coccidioidin, an initial dilution of 1:10,000 should be used in these patients and whenever a high degree of sensitivity to the antigen is suspected. If the test using a 1:10,000 dilution is negative, a 1:1000 dilution may be used; the 1:100 dilution should be used only if a negative reaction is obtained with the 1:1000 dilution. Dilutions of coccidioidin may be made using 0.9% sodium chloride injection.

Cell-mediated Immunity

When coccidioidin is used in conjunction with other antigens to assess the status of cell-mediated immunity, a battery of at least 4 different antigens to which the patient has probably been exposed in the past is used. The antigens are administered intradermally 5–10 cm apart on the forearm. The usual dose of coccidioidin used to assess cell-mediated immunity is 0.1 mL of the 1:100 dilution.

The reaction sites should be examined in 24–48 hours. An induration reaction at the coccidioidin test site measuring 5 mm or more in diameter (with or without erythema) is considered a positive reaction. A positive reaction to one or more antigens may indicate the presence of cell-mediated immunity. If there is no response to 4 or more antigens, the individual is generally considered to be anergic.

Cautions for Coccidioidin

Accurate dilution, dosage, and administration are essential with the use of coccidioidin. Excessive dosage may produce severe erythema and induration followed by necrosis and ulceration. Systemic reactions may occur if too high a concentration of coccidioidin is used for skin testing and, in recently acquired infections, erythema nodosum may be precipitated.

Patients with coccidioidal erythema nodosum may have severe reactions to coccidioidin and a dilution of 1:10,000 should be used for the initial skin test in these patients and whenever a high degree of sensitivity to the antigen is suspected.

Following administration of coccidioidin, the patient should be observed for 15 minutes in case an immediate systemic allergic reaction occurs. Occasionally, an immediate hypersensitivity reaction consisting of a wheal or flare occurs at the injection site.

Commercially available coccidioidin contains thimerosal as a preservative and is contraindicated in individuals who are sensitive to mercury.

Pharmacology

Natural infection with C. immitis usually initiates a cell-mediated immune response and results in T-lymphocytes sensitized to the organism. Once an individual has become sensitized to C. immitis, intradermal administration of coccidioidin evokes a delayed hypersensitivity response at the site of administration if the immune system is intact. In patients with primary pulmonary coccidioidomycosis, sensitization to coccidioidin generally develops 3 days to 3 weeks after the onset of symptoms of the infection.

Chemistry and Stability

Chemistry

Coccidioidin is a sterile solution containing antigens obtained from the by-products of mycelial growth or from spherules of Coccidioides immitis. Coccidioidin occurs as a clear, practically colorless or amber-colored liquid. Commercially available coccidioidin meets standards established by the Center for Biologics Evaluation and Research of the US Food and Drug Administration. Potency of the commercially available 1:100 dilution of coccidioidin is equivalent to US Reference Coccidioidin 1:100. Commercially available coccidioidin injection contains thimerosal as a preservative.

Stability

Commercially available 1:10 and 1:100 dilutions of coccidioidin should be stored at 2–8°C; further dilutions of the antigen should be stored at 2–8°C and used within 24 hours.

Preparations

Excipients in commercially available drug preparations may have clinically important effects in some individuals; consult specific product labeling for details.

Please refer to the ASHP Drug Shortages Resource Center for information on shortages of one or more of these preparations.

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