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Quinine-Induced Thrombocytopenia in a 64-Year-Old Man Who Consumed Tonic Water to Relieve Nocturnal Leg Cramps

      To the Editor: The addition of quinine to seltzer water to create tonic water probably dates from the days of the British Raj in India. The bitter flavor of quinine is appealing to some,
      • Brasic JR
      Should people with nocturnal leg cramps drink tonic water and bitter lemon?.
      and quinine is consumed in tonic water, bitter lemon, and other beverages, either alone or mixed with an alcoholic drink. The medicinal properties of quinine have been touted to prevent a number of ailments ranging from fevers and malaria to atrial fibrillation. One presumed beneficial use of quinine is the treatment of nocturnal leg muscle cramps.
      • Abreu–Gerke L
      • Goerz G
      • Miller A
      • Ruzicka T
      Acral necrosis after quinine sulfate therapy for nocturnal leg cramps [in German].
      • Crum NF
      • Gable P
      Quinine–induced hemolytic–uremic syndrome.
      • Kedia RK
      • Wright AJ
      Quinine–mediated disseminated intravascular coagulation.
      • Khan N
      • Burchett S
      • Adelman HM
      A woman with leg cramps and rash.
      • Kojouri K
      • Perdue JJ
      • Medina PJ
      • George JN
      Occult quinine–induced thrombocytopenia.
      • Pinn G
      Quinine for cramps.
      This therapeutic effect is a possible result of hyperpolarization of myofibrils by activation of Ca++-dependent K+ channels.
      • Kiss E
      • Balázs C
      • Bene L
      • Damjanovich S
      • Matkó J
      Effect of TSH and anti–TSH receptor antibodies on the plasma membrane potential of polymorphonuclear granulocytes.
      Among the serious adverse effects of quinine is thrombocytopenia induced by the formation of antibodies for platelet membrane glycoproteins.
      • Aster RH
      Drug–induced immune thrombocytopenia: an overview of pathogenesis.
      • Bednar B
      • Cook JJ
      • Holahan MA
      • et al.
      Fibrinogen receptor antagonist–induced thrombocytopenia in chimpanzee and rhesus monkey associated with preexisting drug–dependent antibodies to platelet glycoprotein IIb/IIIa.
      • Bougie DW
      • Wilker PR
      • Aster RH
      Patients with quinine–induced thrombocytopenia have two antibodies: one specific for drug alone and the other reactive with platelets in the presence of soluble drug [abstract].
      • Burgess JK
      • Lopez JA
      • Gaudry LE
      • Chong BH
      Rifampicin–dependent antibodies bind a similar or identical epitope to glycoprotein IX–specific quinine–dependent antibodies.
      The following case of quinine-induced thrombocytopenia presented as bright red blood per rectum.
      Report of a Case.—A 64-year-old man went to the emergency department with a 2-day history of rectal bleeding of bright red blood. He complained of loose stools with bright red blood approximately twice daily for 2 days. He had a history of drinking 1.9 L of tonic water daily for leg cramps for 2 to 3 weeks before admission. On some days, he drank up to 5 L of tonic water. He reported easy bruising and gingival bleeding for 2 weeks. Three weeks before admission he had pneumonia treated with clarithromycin. He denied abdominal pain, nausea, vomiting, and hematemesis.
      On examination he was a slightly pale obese man in no acute respiratory distress. Vital signs were normal except for a heart rate of 107 beats/min. Ecchymoses were present on his arms. Gingival mucosa was friable but not hemorrhagic. Rectal examination revealed dark brown-black stool, which was positive for occult blood.
      The initial laboratory findings included hemoglobin level, 12.4 g/dL; hematocrit reading, 36.7%; leukocyte count, 6.9 × 109/L; platelet count, 3 × 109/L; prothrombin time, 11.6 seconds; international normalized ratio, 0.9; and partial thromboplastin time, 21.2 seconds.
      On the second hospital day, evaluation for quinine-induced platelet antibody determined that he was negative for drug-dependent antibody (IgG and IgM) and positive for non-drug-dependent antibody (IgG and IgM).
      He was initially treated with intravenous methylprednisolone sodium succinate and platelet transfusions. Due to lack of initial response, he also received intravenous immunoglobulin for 2 days. He was transfused with 2 U of packed red blood cells when his hemoglobin level reached 7.7 g/dL. Lower gastrointestinal tract endoscopy revealed a mass at 20 cm from the anal ring and identified by histology as a villous adenoma. On his ninth hospital day, he underwent lower anterior sigmoid resection. When the patient was discharged 13 days after admission, his platelet count was 169 × 109/L, and his hemoglobin level was 9 g/dL. A regimen of prednisone, 30 mg by mouth daily, and ferrous sulfate, 325 mg by mouth twice daily, was prescribed when he was discharged.
      Comment.—This case of quinine-induced thrombocytopenia presenting as bright red blood per rectum in a 64-year-old man with villous adenoma was precipitated by the voluminous consumption of tonic water for leg cramps for 2 or 3 weeks before admission. The presence of non-drug-dependent quinine-induced platelet antibodies without drug-dependent quinine-induced platelet antibodies is likely explained by the sensitization of the patient to metabolites of quinine.
      • Aster RH
      Drug–induced immune thrombocytopenia: an overview of pathogenesis.
      The onset of symptoms led to coincidental diagnosis and successful removal of the colonic tumor. This case illustrates the need to consider quinine-induced thrombocytopenia in the differential diagnosis of bright red blood per rectum.
      This occurrence of rectal bleeding associated with ingestion of tonic water by a man with villous adenoma of the rectum suggests also that health warnings may be needed on bottles of tonic water, bitter lemon, and other quinine-containing beverages to prevent the morbidity and mortality sustained by susceptible individuals who consume them, unaware of the medical risks.
      • Rabetoy G
      • Hansen M
      • Brosnahan G
      • Hartung L
      The lady who had muscle cramps and developed thrombotic microangiopathy.
      Residents of the United States currently may not purchase quinine in the form of over-the-counter preparations dispensed without prescription. Due to the uncertain efficacy of quinine for muscle cramps,
      • Villani P
      • Mugnier B
      • Bouvenot G
      Muscle cramps: reevaluation of the efficacy of quinine salts [in French].
      in 1995 the Food and Drug Administration restricted nonprescription availability of quinine to protect the public from the risks of exposure, including rash, pruritus, generalized anaphylaxis, urticaria, erythema multiforme, photosensitivity,
      • Abreu–Gerke L
      • Goerz G
      • Miller A
      • Ruzicka T
      Acral necrosis after quinine sulfate therapy for nocturnal leg cramps [in German].
      hepatitis,
      • Hou M
      • Horney E
      • Stockelberg D
      • Jacobsson S
      • Kutti J
      • Wadenvik H
      Multiple quinine–dependent antibodies in a patient with episodic thrombocytopenia, neutropenia, lymphocytopenia, and granulomatous hepatitis.
      thrombocytopenia,
      • Crum NF
      • Gable P
      Quinine–induced hemolytic–uremic syndrome.
      • Kojouri K
      • Perdue JJ
      • Medina PJ
      • George JN
      Occult quinine–induced thrombocytopenia.
      hemolytic-uremic syndrome,
      • Crum NF
      • Gable P
      Quinine–induced hemolytic–uremic syndrome.
      • Schattner A
      Quinine hypersensitivity simulating sepsis.
      neutropenia,
      • Chuah TL
      • Denaro C
      A case of quinine–induced thrombocytopenia and neutropenia [letter].
      disseminated intravascular coagulation,
      • Crum NF
      • Gable P
      Quinine–induced hemolytic–uremic syndrome.
      • Kedia RK
      • Wright AJ
      Quinine–mediated disseminated intravascular coagulation.
      and coma.
      • Gelchsheimer M
      • Seiler O
      • Wenker O
      Interactive case report: coma and thrombocytopenia in Kenya.
      Nevertheless, anyone may freely purchase quinine in the form of tonic water, bitter lemon, and other beverages and in other preparations, including herbal and alternative treatments,
      • Kojouri K
      • Perdue JJ
      • Medina PJ
      • George JN
      Occult quinine–induced thrombocytopenia.
      commonly available in health food stores, supermarkets, and on the Internet.
      • Kojouri K
      • Perdue JJ
      • Medina PJ
      • George JN
      Occult quinine–induced thrombocytopenia.
      The estimate of 26 cases of acute thrombocytopenic purpura due to quinine or quinidine per million users is likely low because of underreporting.
      • Aster RH
      Drug–induced immune thrombocytopenia: an overview of pathogenesis.
      The proliferation of reports from many locations to confirm the occurrence of thrombocytopenia secondary to ingestion of quinine in tonic water suggests that the incidence of the condition is increasing.
      • Pinn G
      Quinine for cramps.
      Dr Braić is a 2000 Young National Alliance for Research on Schizophrenia and Depression Essel Investigator. He has served as an expert witness in litigation matters involving quinine-containing beverages.

      REFERENCES

        • Brasic JR
        Should people with nocturnal leg cramps drink tonic water and bitter lemon?.
        Psychol Rep. 1999; 84: 355-367
        • Abreu–Gerke L
        • Goerz G
        • Miller A
        • Ruzicka T
        Acral necrosis after quinine sulfate therapy for nocturnal leg cramps [in German].
        Hautarzt. 2000; 51: 332-335
        • Crum NF
        • Gable P
        Quinine–induced hemolytic–uremic syndrome.
        South Med J. 2000; 93: 726-728
        • Kedia RK
        • Wright AJ
        Quinine–mediated disseminated intravascular coagulation.
        Postgrad Med J. 1999; 75: 429-430
        • Khan N
        • Burchett S
        • Adelman HM
        A woman with leg cramps and rash.
        Hosp Pract (Off Ed). June 2000; 35 (17): 21-22
        • Kojouri K
        • Perdue JJ
        • Medina PJ
        • George JN
        Occult quinine–induced thrombocytopenia.
        J Okla State Med Assoc. 2000; 93: 519-521
        • Pinn G
        Quinine for cramps.
        Aust Fam Physician. 1998; 27: 922-923
        • Kiss E
        • Balázs C
        • Bene L
        • Damjanovich S
        • Matkó J
        Effect of TSH and anti–TSH receptor antibodies on the plasma membrane potential of polymorphonuclear granulocytes.
        Immunol Lett. 1997; 55: 173-177
        • Aster RH
        Drug–induced immune thrombocytopenia: an overview of pathogenesis.
        Semin Hematol. 1999; 36: 2-–6
        • Bednar B
        • Cook JJ
        • Holahan MA
        • et al.
        Fibrinogen receptor antagonist–induced thrombocytopenia in chimpanzee and rhesus monkey associated with preexisting drug–dependent antibodies to platelet glycoprotein IIb/IIIa.
        Blood. 1999; 94: 587-599
        • Bougie DW
        • Wilker PR
        • Aster RH
        Patients with quinine–induced thrombocytopenia have two antibodies: one specific for drug alone and the other reactive with platelets in the presence of soluble drug [abstract].
        Blood. 1999; 94 (Abstract 61.): 17a
        • Burgess JK
        • Lopez JA
        • Gaudry LE
        • Chong BH
        Rifampicin–dependent antibodies bind a similar or identical epitope to glycoprotein IX–specific quinine–dependent antibodies.
        Blood. 2000; 95: 1988-1992
        • Rabetoy G
        • Hansen M
        • Brosnahan G
        • Hartung L
        The lady who had muscle cramps and developed thrombotic microangiopathy.
        Nephrol Dial Transplant. 2000; 15: 1464-1467
        • Villani P
        • Mugnier B
        • Bouvenot G
        Muscle cramps: reevaluation of the efficacy of quinine salts [in French].
        Presse Med. 1999; 28: 1309-1312
        • Hou M
        • Horney E
        • Stockelberg D
        • Jacobsson S
        • Kutti J
        • Wadenvik H
        Multiple quinine–dependent antibodies in a patient with episodic thrombocytopenia, neutropenia, lymphocytopenia, and granulomatous hepatitis.
        Blood. 1997; 90: 4806-4811
        • Schattner A
        Quinine hypersensitivity simulating sepsis.
        Am J Med. 1998; 104: 488-490
        • Chuah TL
        • Denaro C
        A case of quinine–induced thrombocytopenia and neutropenia [letter].
        Aust N Z J Med. 2000; 30: 96
        • Gelchsheimer M
        • Seiler O
        • Wenker O
        Interactive case report: coma and thrombocytopenia in Kenya.
        Internet J Rescue Disaster Med. 1999; 1 (Accessibility verified June 13, 2001.)