Do NSAIDs (Non-Steroidal Anti-Inflammatory Drugs) cause eosinophilia?

From the Guidelines

NSAIDs typically do not cause eosinophilia, and any observed eosinophilia is more likely related to other conditions such as allergies, parasitic infections, or autoimmune disorders rather than NSAID use. In rare cases, some NSAIDs may cause drug-induced eosinophilia as part of a hypersensitivity reaction, such as in NSAID-exacerbated respiratory disease (N-ERD), a chronic eosinophilic inflammatory disorder of the respiratory tract occurring in patients with asthma and/or chronic rhinosinusitis with nasal polyps (CRSwNP) 1. However, this is extremely uncommon and not considered a typical effect of NSAIDs.

Key Points to Consider

• NSAIDs work by inhibiting cyclooxygenase enzymes, which are involved in prostaglandin synthesis, and this mechanism does not directly affect eosinophil production or activation 1.
• If a patient develops eosinophilia while taking NSAIDs, it's essential to consider other potential causes and not automatically attribute it to NSAID use unless other more common causes have been ruled out.
• The management options for N-ERD are essentially based on strict avoidance of the culprit drug and cross-reactive drugs 1.
• Allergic reactions to aspirin or NSAIDs can rarely manifest as pneumonitis, eosinophilic pneumonias, or meningitis, but these are not typical effects of NSAIDs 1.

Recommendation

In clinical practice, if eosinophilia is observed in a patient taking NSAIDs, it is advisable to investigate other potential causes and not automatically attribute it to NSAID use unless other more common causes have been ruled out. This approach prioritizes the patient's morbidity, mortality, and quality of life by ensuring that the underlying cause of eosinophilia is accurately diagnosed and treated.

From the FDA Drug Label

Drug Reaction with Eosinophilia and Systemic Symptoms (DRESS) has been reported in patients taking NSAIDs such as ibuprofen tablets. Some of these events have been fatal or life-threatening. DRESS typically, although not exclusively, presents with fever, rash, lymphadenopathy, and/or facial swelling Other clinical manifestations may include hepatitis, nephritis, hematological abnormalities, myocarditis, or myositis. Sometimes symptoms of DRESS may resemble an acute viral infection. Eosinophilia is often present.

Drug Reaction with Eosinophilia and Systemic Symptoms (DRESS) has been reported in patients taking NSAIDs such as diclofenac potassium tablets. Some of these events have been fatal or life-threatening. DRESS typically, although not exclusively, presents with fever, rash, lymphadenopathy, and/or facial swelling Other clinical manifestations may include hepatitis, nephritis, hematological abnormalities, myocarditis, or myositis. Sometimes symptoms of DRESS may resemble an acute viral infection. Eosinophilia is often present.

NSAIDs can cause eosinophilia as part of a condition known as Drug Reaction with Eosinophilia and Systemic Symptoms (DRESS), which has been reported in patients taking ibuprofen and diclofenac, among other NSAIDs 2, 3.

• Eosinophilia is often present in DRESS, which can be fatal or life-threatening.
• Clinical manifestations of DRESS may include fever, rash, lymphadenopathy, and/or facial swelling, as well as other symptoms such as hepatitis, nephritis, hematological abnormalities, myocarditis, or myositis.

From the Research

NSAIDs and Eosinophilia

• NSAIDs have been associated with eosinophilia in various studies, including cases of eosinophilic pneumonia 4 and drug reaction with eosinophilia and systemic symptoms (DRESS) syndrome 5.
• Eosinophilic pneumonia is a rare but serious adverse drug reaction induced by NSAIDs, with symptoms including weakness, dyspnea, and fever 4.
• DRESS syndrome is a severe, drug-induced hypersensitivity reaction characterized by widespread skin rash, multi-system involvement, and often eosinophilia, with NSAIDs such as celecoxib being rare triggers 5.
• Other studies have reported cases of eosinophilic arthritis, which is a type of arthritis characterized by hypereosinophilia and polyarthritis, with NSAIDs being used as a treatment option 6.

Mechanism and Treatment

• The mechanism of NSAID-induced eosinophilia is not fully understood, but it is thought to be related to an allergic or hypersensitivity reaction 4, 5.
• Treatment of NSAID-induced eosinophilia typically involves withdrawal of the offending drug and supportive care, with corticosteroids being used in more severe cases 4, 5, 7.
• In cases of DRESS syndrome, pulsed intravenous methylprednisolone followed by a short reducing course of oral prednisolone has been shown to be effective in reducing symptoms and eosinophil count 7.

Diagnosis and Classification

• Eosinophilia can be classified into different subtypes, including primary and secondary eosinophilia, with the World Health Organization establishing a semi-molecular classification scheme 8.
• Diagnosis of eosinophilia involves a combination of morphologic review of the blood and marrow, standard cytogenetics, fluorescent in situ-hybridization, flow immunocytometry, and T-cell clonality assessment 8.
• Identification of the subtype of eosinophilia is critical for determining prognosis and guiding treatment, with corticosteroids being first-line therapy for patients with lymphocyte-variant hypereosinophilia and idiopathic hypereosinophilic syndrome (HES) 8.