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Stevens-Johnson Syndromewith Ginkgo Biloba
Liya Davydov, PharmDAlexandra L. Stirling, PharmD
ABSTRACT. Gingko biloba is a popular herbal remedy for improvingmemory. Its side effects include headaches, stomach upset, bleedingcomplications and dermatitis. We report another adverse reaction, acase of Stevens-Johnson syndrome (SJS), which appears to be associat-ed with use of gingko biloba. Ingestion by our patient of two doses of aginkgo-containing preparation resulted in exfoliative rash, blisteringand other symptoms consistent with SJS. Upon aggressive treatmentwith corticosteroids, her rash improved, however, she still had residualsymptoms five months after treatment. It is important for clinicians tobe aware of this possible side effect related to use of ginkgo prepara-tions. [Article copies available for a fee from The Haworth Document Deliv-ery Service: 1-800-342-9678. E-mail address: <[email protected]>Website: <http://www.HaworthPress.com> E 2001 by The Haworth Press, Inc.All rights reserved.]
KEYWORDS. Ginkgo, Stevens-Johnson syndrome (SJS), dermatitis,rash, corticosteroids
Ginkgo biloba is an herbal medicinal that has gained increasedpopularity as a ‘‘memory enhancer.’’ It reduces intermittent claudica-
At the time of writing Liya Davydov was PharmD candidate, College of Pharma-cy and Allied Health Professions, St. John’s University. Currently, she is PharmacyPractice Resident, Mount Sinai Medical Center, New York, NY.
Alexandra L. Stirling is Assistant Clinical Professor, College of Pharmacy andAllied Health Professions, St. John’s University, and Clinical Preceptor, InternalMedicine, North Shore University Hospital, Manhasset, NY.
Address correspondence to: Alexandra L. Stirling, St. John’s University, Depart-ment of Clinical Pharmacy Practice, 8000 Utopia Parkway, Jamaica, NY 11439(E-mail: [email protected]).
Journal of Herbal Pharmacotherapy, Vol. 1(3) 2001E 2001 by The Haworth Press, Inc. All rights reserved. 65
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tion and cerebrovascular insufficiency by increasing peripheral bloodflow and dilating peripheral capillary vessels as suggested by severaltrials deemed to be of ‘‘acceptable’’ quality.1 In addition, there isevidence that ginkgo improves cognitive performance in dementedpatients.2 The leaves and seeds of the ginkgo plant are used in com-mercial preparations in various forms (e.g., extract, tablets, teas).3
Side effects related to the use of gingko biloba include headaches,gastrointestinal upset, dizziness, palpitations, hemorrhagic complica-tions and possibly seizures and impaired fertility.3-6 Also, restlessness,lack of muscle tone and weakness, have been associated with the useof large doses.4 Hypersensitivity reactions have been reported andseem to be associated primarily, although not exclusively, with use ofthe seeds. Dermatitis has been described when there is contact with thefruit pulp.4 We describe herein a case of Stevens-Johnson syndrome(SJS) in a woman taking ginkgo biloba.Report of a case: A 40-year-old African-American female was
admitted to our hospital with a diagnosis of SJS. She had not receivedany antibiotics recently and did not take any medications prior to thisevent. The patient had no contributing family or past medical historyand no known drug allergies. The patient reported initiating two tab-lets of ginkgo biloba (unknown brand and lot number) approximatelyone year prior to this admission. Two weeks prior to admission shestarted taking ‘‘One-A-Day Memory and Concentration’’ vitamins(Bayer Pharmaceuticals). One day after her first dose she developed‘‘flu-like’’ symptoms, including fever and body aches. She skipped adose on that day, but restarted the following day. When her symptomsworsened she called her private doctor who advised her to stop takingthe ‘‘One-A-Day’’ preparation. Four days after her first dose she de-veloped a rash and tongue swelling. She then reported to the emergen-cy room, where she was originally given diphenhydramine for therash, with no improvement. She then was seen by a dermatologist,who subsequently diagnosed her with SJS and prescribed prednisone70 mg daily. Her rash was described as non-pruritic, erythematous,which began in her axilla, and spread to her upper chest, hands, part ofher face and tongue. At the time of admission (a week after her visit tothe dermatologist), she had a temperature of 37.7_C, a white bloodcell count of 12.3 103/mm (normal: 4.5-11.0 103/mm) with87.2% neutrophils (normal: 40-70%), hemoglobin of 11.8 g/dL (nor-mal: 11.5-16.0 g/dL), and an elevated erythrocyte sedimentation rate
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at 28 mm/h (normal: 0-20 mm/h). The rest of her blood count waswithin normal limits, including eosinophils. Ulceration and swellingof the upper tongue, rash on both arms (described as burning andtingling), exfoliation of hands and thighs, minimal blistering on righthand, difficulty swallowing, and joint pain were also noted. She wasprescribed methylprednisolone 125 mg intravenously in the emergen-cy room, then 80 mg daily, intravenous fluids, clotrimazole trochethree times daily and fluconazole 100 mg daily for oral thrush, andintravenous famotidine 20 mg twice daily. Upon discharge five dayslater, she had decreased swelling of the tongue and was instructed totake clotrimazole troche three times daily for five days, ranitidine 150mg twice daily, fluconazole 100 mg daily for five days, and predni-sone 60 mg daily for two days followed by 10 mg a day for two moredays. The patient agreed to avoid ingesting gingko biloba in the future.Five months later she still reported discolored skin, tenderness in thesoles of feet, and peeling of the nails.Discussion: The symptomatology present in this patient, including
the rather short lag time before rash manifestation, is consistent with adiagnosis of SJS.7 Although prior exposure is not needed for thedevelopment of SJS, the lag time before onset is shortened with re-peated exposure.7 The typical onset of SJS is thought to occur at amean of 14 days after exposure to the causative agent and about half ofthe patients exhibit a prodromal phase characterized by fever, malaise,headache, myalgia and arthralgia.7
The fact that our patient only had a 4-day lag time before onset ofsymptoms may be attributed to the fact, that she has had a priorexposure. We believe that her past use of ginkgo biloba could havesensitized the patient for this reaction.We are not able to verify the patient’s initial diagnosis or elaborate
more on her initial rash presentation because the diagnosis was madeon an outpatient basis by a private dermatologist prior to her admis-sion to our hospital and we did not have access to any of the outpatientrecords. We do know that the patient did not have any eye involve-ment, that she was not taking any drugs prior to onset of SJS, had nosignificant past medical history, no contributing family history, and noknown drug allergies.This patient’s length of hospitalization was rather short given the
potential seriousness of her diagnosis. We speculate that the earlyintervention with diphenhydramine and high-dose corticosteroids, and
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quick discontinuation of the suspected causative agent may have pre-vented the progression of her condition to more serious complications.While she was not rechallenged with ginkgo biloba, the temporal
sequence supports a causal relationship. Each tablet of ‘‘One-A-DayMemory and Concentration’’ is labeled as containing 60 mg of leafextract of ginkgo biloba, 1 mg of B6 vitamin, 3 mcg of B12 vitamin,and 60 mg of choline bitartate. Unfortunately, we were unable toquantitatively verify the contents of the ginkgo preparation and thepossibility exists that the product did not in fact contain the labeledingredients. However the gingko brand involved in this case has beenidentified by an independent testing agency as meeting standards ofquality and purity.8 There are reports in the literature describing hy-persensitivity reactions with ingestion of mega-doses of vitamins B6and B12,9 contact dermatitis with vitamin B6,10 as well as with cho-line chloride.11 However, these cannot be applied to our patient, as shedid not ingest mega-doses of the vitamins or report skin contact withcholine or vitamin B6. A literature search revealed no reports of SJSwith B-vitamins or choline. While there are reports in the literaturedescribing dermatological reactions with any part of ginkgo bilobaplant, no part of the plant has been previously implicated as a cause ofSJS.12,13
To our knowledge, this is the first case-report of ginkgo bilobainduced SJS. Clinicians should be aware that there is a potential forthis herb to cause this severe reaction.
REFERENCES
1. Zink T, Chaffin J. Herbal ‘Health’ products: What family physicians need toknow. Am Fam Physician 1998;58(5):1133-1140.
2. LeBars PL, Katz MM, Berman N, et al. A placebo-controlled, double-blind,randomized trial of an extract of ginkgo biloba for dementia. JAMA 1997;278:1327-1332.
3. Royal Pharmaceutical Society’s Herbal Medicines. Gingko monograph. En-glewood, CO: Micromedex 2000.
4. Jellin JM, Batz F, Hitchens K. Pharmacist’s Letter/Prescriber’s Letter NaturalMedicines Comprehensive Database. Stockton, CA: Therapeutic Research Faculty1999:418-422.
5. Vale S. Subarachnoid haemmorrhage associated with Ginkgo biloba. Lancet1998; 3352:36. [Letter]
6. Rowin J, Lewis SL. Spontaneous bilateral subdural hematomas associatedwith chronic Ginkgo biloba ingestion. Neurology 1996;46:1775-1776. [Letter]
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7. Fritsch PO, Ruiz-Maldonado R. Stevens-Johnson syndrome--toxic epidermalnecrolysis. In: Freedberg IM, Eisen AZ, Austen KF, Goldsmith LA, Katz SI, Fitzpa-trick TB, eds. Fitzpatrick’s dermatology in general medicine 5th ed. New York:McGraw-Hill; 1999;644-654.
8. ConsumerLab.com, LLC. www.consumerlab.com. Accessed 10/18/00.9.Sherertz EF. Acneiform eruption due to ‘‘megadose’’ vitamins B6 and B12.
Cutis 1991;48:119-120. [Letter]10. Rodriguez A, Echechipía S, Alvarez M, Muro MD. Occupational contact der-
matitis from vitamin B12. Contact Dermatitis 1994;31:271. [Letter]11. Fischer T. Contact allergy to choline chloride. Contact Dermatitis 1984;10(5):
316-317. [Letter]12. Tomb RR, Foussereau J, Sell Y. Mini-epidemic of contact dermatitis from
ginkgo tree fruit (Ginkgo biloba L.). Contact Dermatitis 1988;19:281-283. [Letter]13. Ellenhorn MJ. Ellenhorn’s Medical Toxicology. Baltimore, MD: Williams &
Wilkins;1997.
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