Journal of Clinical and Aesthetic Dermatology

OCT 2017

An evidence-based, peer-reviewed journal for practicing clinicians in the field of dermatology

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46 JCAD JOURNAL OF CLINICAL AND AESTHETIC DERMATOLOGY October 2017 • Volume 10 • Number 10 C A S E R E P O R T presented with erythematous papules, vesicles and edema. 4–6 One man ate the outer fruit and discarded the edible seed. Three days later, he initially presented with burning, tingling, and soreness of the mouth; a sensation of thickness of his tongue; perioral erythema and swelling; and erythema of his buccal mucosa, tongue, and tonisillar pillars. The next day, he had developed tenesmus, perirectal burning, and pruritus. 7 Skin and mucosal reactions to oral Ginkgo biloba leaf extract include a diffuse morbilliform eruption 8 and possibly Stevens-Johnson syndrome that evolves into toxic epidermal necrolysis. 9 A 66-year-old woman had ingested two 60mg doses of Trader Joe's Ginkgo biloba supplement about a week before developing a progressive erythematous eruption of macules and papules that began on her abdomen and progressed to cover most of her skin, including her face, neck, trunk, and extremities. 8 Yuste et al 9 suggested that Stevens-Johnson syndrome occurring in a 75-year-old man with arterial hypertension, hypercholesterolemia, and glaucoma was "probably because of the ingestion of Ginkgo biloba extract"; however, the authors also mentioned that the patient had been on doxazosin for years and that they did not know when the patient actually began taking the Ginkgo biloba extract (to improve blood supply) with regard to the onset of his skin condition. Vinpocetine is a synthetic ethyl ester of apovicamine. Vinpocetine has been used for the treatment of acute stroke, cerebrovascular disorders, cognitive decline, and dementia. Vinpocetine has also been used for preventing motion sickness and for treating chronic fatigue syndrome, menopause symptoms, and seizure disorders. The daily dose of vinpocetine varies between 15mg and 60mg; most patients receive between 30mg to 60mg each day for periods ranging from 12 to 16 weeks to up to one year. 12–15 Vinpocetine is considered to be safe for most people. In a study of patients with Alzheimer's disease receiving 60mg of vinpocetine daily and a placebo group, no significant difference regarding adverse effects was observed after one year of treatment. 12–13 Described side effects in some patients who have taken the agent include dizziness, headache, nausea, nervousness, sleep disturbances, and stomach pain. With the exception of facial flushing, cutaneous adverse events in patients taking vinpocetine have not been described. Similar to Ginkgo biloba, vinpocetine may slow clotting; therefore, it should not be used in patients with clotting disorders, should not taken with other anticoagulants, and should be discontinued before surgery. 16 The most frequent causative agents associated with fixed drug eruptions are analgesics (naproxen), antibiotics (such as tetracycline and trimethoprim- sulfamethoxazole), anticonvulsants, muscle relaxants, phenolphthalein (in stool softeners), and sedatives. Fixed drug eruptions are classified as delayed Type IV immune reactions in which intraepidermal effector-memory CD8+ T cells at the lesional site of the fixed drug eruption play a role in the subsequent development of localized tissue damage. To date, a fixed drug eruption has not been described in patients receiving either Ginkgo biloba or vinpocetine. 17-21 The reported patient not only developed pruritus and an annular erythematous patch on his distal penile shaft following initial daily ingestion of the Ginkgo biloba/vinpocetine product, but also systemic symptoms (tachycardia and gastrointestinal pain) within four days. Subsequent repeat daily challenge with the same agent produced the same cutaneous symptom (pruritus) and skin lesion (macular erythema) at the identical location, in addition to tachycardia and gastrointestinal pain, within two days. Additional oral challenge or patch testing to the Ginkgo biloba/ vinpocetine product or the individual agents was not recommended because of the systemic symptoms that he had experienced. CONCLUSION Ginkgo biloba and vinpocetine are natural products that have been used for several purposes, including to enhance memory in patients with dementia and/or age-related memory impairment conditions such as Alzheimer's disease. Both Ginkgo biloba and vinpocetine can inhibit clotting; however, systemic side effects from these agents are uncommon. Cutaneous adverse effects from these agents are infrequent. Topical exposure to Ginkgo biloba fruit can result in contact dermatitis, and oral exposure to the fruit, in one individual, resulted in mucosal symptoms of the mouth and anus. In addition, individual case reports describe either an erythematous maculopapular generalized eruption, or possibly Steven-Johnson syndrome after oral ingestion of the Ginkgo biloba leaf extract. Facial erythema has been associated with vinpocetine ingestion. A man with pruritus and annular erythema localized to the distal penile shaft who experienced the identical symptoms and lesion after repeat challenge with a Ginkgo biloba/ vinpocetine product is described here. Ginkgo biloba and vinpocetine should be added to the FIGURE 3. The Ginkgo biloba tree FIGURES 4A–B. Distant (A) and closer (B) views of the leaf of the Ginkgo biloba tree

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