Histoplasmin (Monograph)

Drug class: Fungi
VA class: DX300

Medically reviewed by Drugs.com on Apr 10, 2025. Written by ASHP.

Introduction

Histoplasmin is a skin test antigen derived from by-products of Histoplasma capsulatum.

Uses for Histoplasmin

Histoplasmosis

Histoplasmin is a skin test antigen. Histoplasmin used as an aid in the diagnosis of histoplasmosis and in the differentiation of suspected histoplasmosis from other mycotic or bacterial infections such as blastomycosis, coccidioidomycosis, or tuberculosis, or from sarcoidosis. Histoplasmin may also be used as an aid in the interpretation of radiographs showing pulmonary infiltration and calcification.

Absolute diagnosis of histoplasmosis 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 histoplasmin or demonstration of a high titer of complement-fixing antibodies. Intradermal administration of histoplasmin may result in elevation of serum antibody titers to histoplasmin. Therefore, if serologic tests for histoplasmosis are indicated, the blood sample should preferably be drawn prior to administration of the histoplasmin skin test. If the blood sample is not drawn prior to skin testing, the sample should be obtained within 48–96 hours for accurate results.

A positive reaction to histoplasmin may indicate a past infection or a present mild, subacute or chronic infection with H. capsulatum; however, other fungi with related immunologic properties (e.g., Coccidioides immitis, Blastomyces) may cause cross-reactions with histoplasmin. Histoplasmin is of little value in diagnosing acute fulminating H. capsulatum infections since a negative reaction often occurs in such cases. Repeated negative reactions to histoplasmin during chronic pulmonary infections suggest that an organism other than H. capsulatum is responsible; tests with coccidioidin and tuberculin should then be used in conjunction with histoplasmin.

Cell-mediated Immunity

Histoplasmin is used in conjunction with other antigens (e.g., candida, coccidioidin, 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.

Histoplasmin Dosage and Administration

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

Histoplasmin 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 should be 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. To prevent transmission of hepatitis B infection and/or other infectious agents from one individual to another, a different sterile syringe and needle must be used for each individual who is administered histoplasmin. The syringe used for histoplasmin should not be used for tuberculin or other material.

Histoplasmosis

The usual dose of histoplasmin used as an aid in the diagnosis of histoplasmosis is 0.1 mL of the commercially available injection. A control test is not necessary.

The histoplasmin test site should be examined under adequate light after 48–72 hours. A positive reaction to histoplasmin consists of an area of induration measuring 5 mm or greater in diameter. A smaller area of induration, or erythema without induration, is considered a doubtful reaction. The total absence of induration or erythema less than 5 mm in diameter indicates a negative reaction.

Cell-mediated Immunity

When histoplasmin 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 histoplasmin used to assess cell-mediated immunity is 0.1 mL.

The reaction sites should be examined in 24–48 hours. An induration reaction at the histoplasmin 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 Histoplasmin

Accurate dosage and administration are essential with the use of histoplasmin. Excessive dosage may produce severe erythema and induration followed by necrosis and ulceration which may last for several weeks.

Intradermal administration of histoplasmin may cause vesiculation, ulceration, or necrosis at the test site in histoplasmin-sensitive individuals. Severe local reactions may result in scarring. It has been suggested that cold packs or topical corticosteroids be used for the symptomatic relief of local discomfort, pain, or pruritus if these effects occur.

Hypersensitivity reactions (e.g., urticaria, shortness of breath, excessive perspiration) may also occur following intradermal administration of histoplasmin. The manufacturer states that epinephrine should be available for immediate treatment of an anaphylactic reaction if it occurs.

Drug Interactions

Reactivity to the histoplasmin skin test may be suppressed in patients who have recently been immunized with any live virus vaccine or are receiving corticosteroids or other immunosuppressive agents. It has been recommended that histoplasmin skin tests not be performed within 3 weeks after administration of live virus vaccines.

Pharmacology

Natural infection with Histoplasma capsulatum usually initiates a cell-mediated immune response and results in T lymphocytes sensitized to the organism. Once an individual has become sensitized to H. capsulatum, intradermal administration of histoplasmin evokes a delayed hypersensitivity response at the site of administration if the immune system is intact. In patients with H. capsulatum infections, sensitization to histoplasmin generally develops within 2 weeks or more after exposure to the organism.

Chemistry and Stability

Chemistry

Histoplasmin is a sterile, standardized liquid concentrate of the soluble growth products of Histoplasma capsulatum. The culture used in the commercial preparation is grown in the mycelial phase on a synthetic medium. Histoplasmin occurs as a clear, red liquid and is miscible with water.

Commercially available histoplasmin injection meets standards established by the Center for Biologics Evaluation and Research of the US Food and Drug Administration. The injection has a potency equivalent to the US Reference Histoplasmin Standard diluted 1:100. Commercially available histoplasmin is stabilized with polysorbate (Tween) 80, buffered with potassium and sodium phosphates, and contains 0.5% phenol as a preservative.

Stability

Histoplasmin injection should be stored at 2–8°C.

Additional Information

The American Society of Health-System Pharmacists, Inc. represents that the information provided in the accompanying monograph was formulated with a reasonable standard of care, and in conformity with professional standards in the field. Readers are advised that decisions regarding use of drugs are complex medical decisions requiring the independent, informed decision of an appropriate health care professional, and that the information contained in the monograph is provided for informational purposes only. The manufacturer’s labeling should be consulted for more detailed information. The American Society of Health-System Pharmacists, Inc. does not endorse or recommend the use of any drug. The information contained in the monograph is not a substitute for medical care.

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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