Abstract
Fever (t>38°C) developed in association with drug usage is rare but sometimes severe side effect (SE). It could manifest as single symptom or as a part of such life-threatening syndromes like malignant hyperthermia (MH), serotonin syndrome (SS), neuroleptic malignant syndrome (NMS). Fever could be caused by different therapeutic groups of drugs but the leading positions are occupied by antibiotics (mainly beta-lactams), substances acting on central nervous system (CNS) and chemotherapeutic agents. Main mechanisms are allergic and receptive. Curative measures include discontinuation of the suspected drug, introduction of agents blocking the action of the trigger factor - dantrolene (МН), bromocriptine (NMS), cyproheptadine (SS). Purpose of this review: to present the global and Russian data concerning fever as a drug-induced side effect. To distinguish the groups of patients and drugs of the highest risk. To evaluate aid measures. Results: fever as monosymptom of drug allergy is a difficult condition to be diagnosed and there are only few things that could help to recognize it such as temporal association with the suspected drug use and manifestation of fever along with the following resolution after suspected drug discontinuation and recurrence fever after suspected drug re-challenge. Among four syndromes described in this review such as serum sickness-like reaction (SSLR), NMS, SS and MH just fever at MH is not only a sign like in case of three others but it is significant and life-threatening manifestation and therefore requires additional curative methods (in addition to pharmacological support with dantrolene) – rapid cooling measures: ice-water nasogastric and rectal lavage, infusion of crystalloid solutions cooled up to 4°C, ice packs placing on main blood vessels and liver area, ventilatory measurements.
Highlights
Normal temperature of human body is usually balanced around 37°C and its stability is supported by two main mechanisms: central system – anterior hypothalamus where “thermostat” is placed and peripheral part – skin blood circulation, muscular tonus and sweating.In general understanding fever is an adaptive physiological reaction that is resulted from synchronized response of vegetative and neuroendocrinal systems for disease or other injury
The common mechanism of fever development predominantly through increasing muscle tonus is typical for three other syndromes: neuroleptic malignant syndrome NMS), serotonin syndrome (SS) and malignant hyperthermia (MH)
Upon that SS, NMS and MH are distinguished among others by their consequences
Summary
Normal temperature of human body is usually balanced around 37°C and its stability (temperature homeostasis) is supported by two main mechanisms: central system – anterior hypothalamus where “thermostat” is placed and peripheral part – skin blood circulation, muscular tonus and sweating. In general understanding fever is an adaptive physiological reaction that is resulted from synchronized response of vegetative and neuroendocrinal systems for disease or other injury. Drug-induced fever (DF) is abnormal pathological phenomenon that coincides in time with the use of drug in the absence of other reasons for its manifestation. In accordance with data from Vigibase (2018) druginduced fever (t>38°C) was observed in 3,1% of children with variables in frequency in different age groups, countries [1,2,3], out-patient or in-patient practice where the intensity and volume of drugs administration is higher. Pharmacovigilance service of our hospital in 2006-2007 registered 22 cases of drug-induced fever (12,35% of all adverse side effects) and 18 cases from those were registered. American Journal of Pediatrics 2020; 6(4): 495-503 as a result of beta-lactam use (“beta-lactam fever”): ceftriaxone, ceftazidime, meropenem, cefepime
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