Drug‐induced aseptic meningitis: a mini‐review

Abstract

Aseptic meningitis associates a typical clinical picture of meningitis with the absence of bacterial or fungal material in the cerebrospinal fluid. Drug-induced aseptic meningitis (DIAM) may be due to two mechanisms: (i) a direct meningeal irritation caused by the intrathecal administration of drugs and (ii) an immunologic hypersensitivity reaction to a systemic administration. If the direct meningeal irritation allows a rather easy recognition, the immunologic hypersensitivity reaction is a source of challenging diagnostics. DIAM linked to a systemic treatment exerts typically an early onset, usually within a week. This period can be shortened to a few hours in case of drug rechallenge. The fast and spontaneous regression of clinical symptoms is usual after stopping the suspected drug. Apart from these chronological aspects, no specific clinical or biological parameters are pathognomonic. CSF analysis usually shows pleiocytosis. The proteinorachia is increased while glycorachia remains normal. Underlying pathologies can stimulate the occurrence of DIAM. Thus, systemic lupus erythematosus appears to promote DIAM during NSAID therapy, especially ibuprofen-based one. Similarly, some patients with chronic migraine are prone to intravenous immunoglobulin-induced aseptic meningitis. DIAM will be mainly evoked on chronological criteria such as rapid occurrence after initiation, rapid regression after discontinuation, and recurrence after rechallenge of the suspected drug. When occurring, positive rechallenge may be very useful in the absence of initial diagnosis. Finally, DIAM remains a diagnosis of elimination. It should be suggested only after all infectious causes have been ruled out.

Drug‐induced aseptic meningitis: 329 cases from the French pharmacovigilance database analysis

“…Unfortunately, the mechanisms of DIAM are poorly understood and have precluded the identification of any biomarker. Two categories of mechanisms can be proposed: (i) hypersensitivity reactions; and (ii) direct inflammation of the meninges …”

“…Two categories of mechanisms can be proposed: (i) hypersensitivity reactions; and (ii) direct inflammation of the meninges. 13,25…”

Tranexamic acid‐induced fixed drug eruption confirmed by the drug lymphocyte transformation test

“…In this case, although LTT was performed 5 days after the discontinuation of prednisolone, it would have been better to perform LTT at least 4 weeks after treatment with prednisolone, when the positivity of LTT would have been higher. Drug‐induced aseptic meningitis may be attributable to type III and type IV hypersensitivity, which enhances lymphocyte and neutrophil activities . The patient was reluctant to undergo a biopsy and patch test, and the lack of these results could be a limitation of this case report, as LTT is not a completely validated technique.…”

Predictive factors of first dosage intravenous immunoglobulin-related adverse effects in children

“…At present, there is inadequate evidence for the efficacy of pretreatments for IVIG-AEs, and such treatments are controversial. Although pretreatments cannot prevent IVIG-AEs, some treatments, such as hydration, acetaminophen, nonsteroidal anti-inflammatory drugs, antihistamines, and corticosteroids, have been reported to reduce the incidence of IVIG-AEs [1,3,4,6,8,[13][14][15][16]33]. It is difficult to distinguish between IVIG-AEs and exacerbation of underlying diseases, especially for relatively inexperienced physicians.…”

“…In contrast, the symptoms of delayed AEs include severe symptoms, such as acute renal failure, thromboembolic events, neurological toxicity (i.e., aseptic meningitis), hematological toxicity, dermatological toxicity, pseudohyponatremia, arthritis, and pulmonary complications [1,3,5,13,14]. Several previous studies suggested that migraine may be a risk factor for aseptic meningitis associated with IVIG [4,15,16]. Other studies suggested that IVIG infusion rate, primary infusion of IVIG, history of IVIG-AEs, hydration before and after IVIG infusion, immunoglobulin preparation, underlying diseases (immunoglobulin A deficiency, hypertension, thrombopoiesis, etc.…”