Diversity and severity of adverse reactions to quinine: A systematic review

Abstract

Quinine is a common cause of drug-induced thrombocytopenia and the most common cause of druginduced thrombotic microangiopathy. Other quinine-induced systemic disorders have been described. To understand the complete clinical spectrum of adverse reactions to quinine we searched 11 databases for articles that provided sufficient data to allow evaluation of levels of evidence supporting a causal association with quinine. Three reviewers independently determined the levels of evidence, including both immune-mediated and toxic adverse reactions. The principal focus of this review was on acute, immunemediated reactions. The source of quinine exposure, the involved organ systems, the severity of the adverse reactions, and patient outcomes were documented. One hundred-fourteen articles described 142 patients with definite or probable evidence for a causal association of quinine with acute, immune-mediated reactions. These reactions included chills, fever, hypotension, painful acral cyanosis, disseminated intravascular coagulation, hemolytic anemia, thrombocytopenia, neutropenia, acute kidney injury, rhabdomyolysis, liver toxicity, cardiac ischemia, respiratory failure, hypoglycemia, blindness, and toxic epidermal necrolysis. One hundred-two (72%) reactions were caused by quinine pills; 28 (20%) by quinine-containing beverages; 12 (8%) by five other types of exposures. Excluding 41 patients who had only dermatologic reactions, 92 (91%) of 101 patients had required hospitalization for severe illness; 30 required renal replacement therapy; three died. Quinine, even with only minute exposure from common beverages, can cause severe adverse reactions involving multiple organ systems. In patients with acute, multi-system disorders of unknown origin, an adverse reaction to quinine should be considered.

None of the above: thrombotic microangiopathy beyond TTP and HUS

“…[28][29][30] The first and most common drug associated with an immune-mediated reaction is quinine. 31 The second mechanism is through a direct, toxic effect. Although the mechanism is not fully understood, decreased expression of VEGF seems to play a role.…”

Quinine induced thrombotic microangiopathy and thrombocytopenia: A teaching hospital's perspective

“…[3,8] These patients experience a diverse reaction to the drug and many have been shown to have a picture appearing of systemic inflammatory response. [7] What was interesting is that in our case the patient was adamant on not being exposed to any quinine during her lifetime including tonic water, yet after ingestion of one tablet of quinine, she developed signs of rhabdomyolysis, acute liver failure, severe hypothyroidism, progressive renal failure, and thrombocytopenia. The only possible substance noted in the detailed history obtained by multiple members of her inpatient care team was previous abuse of crack-cocaine, which as previously mentioned, may be unsuspectingly "laced" with quinine products.…”

“…[2] Most documented cases of quinine induced reactions occur with prior exposure and due to a sensitization reaction. [6,7] Although ingestion of the medication for approximately one week is typically required to develop sensitization, drug-dependent antibodies may develop after only a single previous exposure. [3,8] These patients experience a diverse reaction to the drug and many have been shown to have a picture appearing of systemic inflammatory response.…”

“…It has been shown that patients who require renal replace-ment therapy have higher risk of progression to long term CKD (chronic kidney disease), can lead to renal failure [9] and doubles the risk of long term death. [7] When the diagnostic confidence of DITMA is high based on history and laboratory values, the mainstay intervention involves supportive care and it is not recommended to initiate plasma exchange or anti-compliment therapy, as these therapeutic modalities have been shown to be ineffective or harmful in patients with quinine-induced TMA. For patients diagnosed with immune-mediated DITMA, it is imperative that the implicated agent be completely avoided for life, as even miniscule subsequent levels of exposure may result in death.…”

Stimulation of Erythrocyte Cell Membrane Scrambling by Quinine

“…Moreover, quinine is used against muscle cramps [23][24][25][26][27][28] and has antiepileptic effects in animals but apparently not in humans [29]. Side effects of quinine include chills, fever, hypotension, painful acral cyanosis, disseminated intravascular coagulation, hemolytic anemia, thrombocytopenia, neutropenia, bronchiolitis obliterans organizing pneumonia, respiratory failure, hemolytic uremic syndrome, acute kidney injury, rhabdomyolysis, liver toxicity, vomiting, cardiotoxicity, hypoglycemia, ototoxicity, ocular toxicity, and toxic epidermal necrolysis [12,20,[30][31][32][33][34][35][36][37][38][39][40].…”