What is the cause of a worsening rash after administration of dexamethasone (corticosteroid)?

From the Guidelines

If your rash is worsening after receiving dexamethasone, you should contact your healthcare provider immediately as this could indicate an allergic reaction to the medication itself. Dexamethasone is a corticosteroid that typically reduces inflammation and allergic responses, so a worsening rash suggests either an adverse reaction to the medication or that your underlying condition requires different treatment. The most recent and highest quality study on the management of dermatological toxicities related to anticancer agents, published in 2021 in the Annals of Oncology 1, provides guidance on the prevention and treatment of skin reactions, but does not specifically address the worsening of a rash after dexamethasone administration. However, the study suggests that topical high-potency steroids and oral dexamethasone may be used to treat skin reactions, which implies that dexamethasone can be effective in reducing inflammation, but may not be suitable for everyone. Other studies, such as the 2011 German expert opinion on the interdisciplinary management of EGFR-inhibitor-induced skin reactions, published in the Annals of Oncology 1, provide guidance on the treatment of skin reactions, including the use of topical antibiotics, moisturizers, and oral antihistamines, but do not specifically address the use of dexamethasone. Given the potential for an allergic reaction, it is essential to seek medical attention promptly, and your doctor may need to switch you to an alternative medication, such as prednisone or methylprednisolone, if you need continued steroid therapy. They might also prescribe antihistamines, like diphenhydramine (25-50mg every 4-6 hours) or cetirizine (10mg daily), to help manage the allergic reaction. While waiting to see your doctor, you can apply cool compresses to the affected area and avoid scratching to prevent further irritation. Allergic reactions to corticosteroids are uncommon but can occur due to the active ingredient or preservatives in the formulation, and prompt medical evaluation is essential to determine the appropriate next steps in your treatment. Some key considerations for managing skin reactions include:

• Avoiding irritants and mechanical stress
• Using topical moisturizers and steroids
• Considering oral antibiotics and antihistamines
• Seeking medical attention promptly if symptoms worsen or do not improve.

From the FDA Drug Label

Anaphylactoid and hypersensitivity reactions have been reported for dexamethasone sodium phosphate injection. The cause of a worsening rash after administration of dexamethasone may be due to anaphylactoid or hypersensitivity reactions 2.

From the Research

Possible Causes of Worsening Rash after Dexamethasone Administration

• Allergic reactions to dexamethasone, as it is a corticosteroid that may cause allergic contact dermatitis or systemic allergic reactions, although rare 3
• Rebound inflammation after cessation of dexamethasone therapy, as seen in a case of severe COVID-19 pneumonia where the patient's condition deteriorated after discontinuing corticosteroids 4
• Hypersensitivity reactions, including severe rash, as experienced by some patients who received dexamethasone pre-medication for docetaxel infusion 5
• Orally elicited allergic contact dermatitis, as reported in a patient with multiple topical corticosteroid allergic contact dermatitis who also exhibited polysensitivity to oral corticosteroids, including dexamethasone 6

Factors to Consider

• Cross-reactivity to other corticosteroids, as patients allergic to one corticosteroid often exhibit cross-reactivity to other corticoids 3, 6
• Individual patient response to dexamethasone, as the timing and length of dexamethasone medication should be tailored to the individual patient 4
• Potential for side effects, such as persistent urticaria activity, associated with oral corticosteroid therapy 7