Idiopathic Intracranial Hypertension Induced by Topical Application of Vitamin A

A 21-year-old nonobese woman developed headaches and papilledema while excessively using 3 topical preparations of vitamin A. Neuroimaging studies were unremarkable and opening pressure on lumbar puncture was 300 mm H2O with normal cerebrospinal fluid composition. After discontinuation of the topical vitamin A preparations, the symptoms and signs of increased intracranial pressure resolved. The association of intracranial hypertension and topical vitamin A application has only been reported once previously.

Clinical Observation Idiopathic Intracranial Hypertension Induced by Topical Application of Vitamin A Yousef M. Mohammad, MD, MSc, Ismail R. Raslan, MD, Fawaz A. Al-Hussain, MD, MPH Abstract: A 21-year-old nonobese woman developed headaches and papilledema while excessively using 3 topical preparations of vitamin A. Neuroimaging studies were unremarkable and opening pressure on lumbar puncture was 300 mm H2O with normal cerebrospinal fluid composition. After discontinuation of the topical vitamin A preparations, the symptoms and signs of increased intracranial pressure resolved. The association of intracranial hypertension and topical vitamin A application has only been reported once previously. Journal of Neuro-Ophthalmology 2016;36:412-413 doi: 10.1097/WNO.0000000000000374 © 2016 by North American Neuro-Ophthalmology Society A variety of risk factors have been associated with intracranial hypertension, including obesity, female gender, use of tetracycline, and withdrawal from systemic steroids. Oral vitamin A, which is regularly prescribed for the treatment of acne, also has been an established risk factor. In lieu of the prescribed oral form of vitamin A, many individuals used over-the-counter, topical formulas. Only 1 previous case report has linked intracranial hypertension to the use of topical form of vitamin A (1). We describe a second such case. CASE REPORT A 21-year-old woman was admitted to the hospital for the evaluation of headache described as diffuse, pressure-like, moderately intense, and constant, which worsened during physical activity. She also reported a recent sudden loss in Department of Internal Medicine, King Saud University, Riyadh, Saudi Arabia. Supported by College of Medicine Research Center; deanship of scientific research, King Saud University, Riyadh, Saudi Arabia. The authors report no conflicts of interest. Address correspondence to Yousef M. Mohammad, MD, MSc, Department of Internal Medicine, King Saud University, PO Box 7805, 11472 Riyadh, Saudi Arabia; E-mail: [e-mail] 412 her vision that lasted for only few seconds, but prompted her to seek medical attention. She did not suffer from any past medical illness and she denied any recent change in her weight. For facial acne, the patient had been using multiple over-the-counter topical preparations of vitamin A, including 1) Avotin (0.05% cream); 2) Retin-A gel (0.01% topical gel; 3) Isotrexin gel (isotretinoin 0.05%, erythromycin 2.0%). All were applied twice daily. Her general physical examination was normal and the patient had a body mass index (BMI) of 22 kg/m2. Neurologic and ophthalmic examinations were unremarkable with the exception of bilateral optic disc edema (Fig. 1). Magnetic resonance imaging and angiography were normal. Opening pressure on lumbar puncture was 300 mm H2O with a normal cerebrospinal composition. The patient was prescribed acetazolamide and instructed to discontinue all the topical vitamin A preparation. At a 2-month follow-up, she reported significant reduction in headaches. Funduscopic examination showed improvement in the bilateral papilledema. She has been compliant in avoiding all the vitamin A preparations but admitted discontinuing acetazolamide after only 1 week because of associated paresthesia. Her BMI has remained constant at 22 kg/m2. DISCUSSION Oral intake of vitamin A is a well established risk for the development of intracranial hypertension (2,3). Although the exact mechanism of how vitamin A induces intracranial hypertension remains to be established, most evidence suggests an interference with cerebrospinal fluid homeostasis (4). The association of intracranial hypertension and application of topical vitamin A was first reported by Givre and Fleischman (1). A 23-year-old woman had been using adapalene (0.1% gel) for 7-8 weeks before developing intracranial hypertension. However, her BMI was 25.8 kg/m2 and she had recently gained 10-20 pounds. Her Mohammad et al: J Neuro-Ophthalmol 2016; 36: 412-413 Copyright © North American Neuro-Ophthalmology Society. Unauthorized reproduction of this article is prohibited. Clinical Observation FIG. 1. There is bilateral optic disc edema. intracranial hypertension resolved when she stopped using topical vitamin A. A small proportion of topically applied medications can be absorbed systemically and the bioavailability through this route is in the range of 5%-10% (5,6). It is likely that our patient had considerable vitamin A percutaneous penetration and absorption because of her excessive and frequent use of the topical agents. These preparations are readily available over-the-counter and are extensively used, often without recommendation by a physician, for the purpose of treating acne. It is crucial for clinicians to be vigilant in inquiring about the use of topical preparations of vitamin A in patients suspected of having intracranial hypertension. Additionally, it is imperative for the pharmacists to be aware of this association and to warn individuals against the excessive use of vitamin A topical formulas. STATEMENT OF AUTHORSHIP Category 1: a. Conception and design: Y. M. Mohammad, I. R. Raslan, and F. A. Al-Hussain; b. Acquisition of data: Y. M. Mohammad, and I. R. Raslan; c. Analysis and interpretation of data: Y. M. Mohammad, I. R. Raslan, and F. A. Al-Hussain. Category 2: a. Drafting the manuscript: Y. M. Mohammad, I. R. Raslan, and F. A. Al-Hussain; b. Revising it for intellectual content: Y. M. Mohammad, I. R. Raslan, and F. A. Mohammad et al: J Neuro-Ophthalmol 2016; 36: 412-413 Al-Hussain. Category 3: a. Final approval of the completed manuscript: Y. M. Mohammad, I. R. Raslan, and F. A. Al-Hussain. REFERENCES 1. Givre SJ, Fleischman D. Intracranial hypertension in a patient using topical adapalene. J Neuroophthalmol. 2008;29:156- 158. 2. Warner JE, Bernstein PS, Yemelyanov A, Alder SC, Farnsworth ST, Digre KB. Vitamin A in the cerebrospinal fluid of patients with and without idiopathic intracranial hypertension. Ann Neurol. 2002;52:647-650. 3. Bruce BB, Biousse V, Newman NJ. Update on idiopathic intracranial hypertension. Am J Ophthalmol. 2001;152:163- 169. 4. Warner JE, Larson AJ, Bhosale P, Digre KD, Henley C, Alder SC, Katz BJ, Vernstein PS. Retinol-binding protein and retinaol analysis in cerebrospinal fluid and serum of patients with and without idiopathic intracranial hypertension. J Neuroophthalmol. 2007;27:258-262. 5. Surber C, Davis AF. Bioavailability and bioequivalence of dermatological formulations. In: Walters KA, ed. Dermatological and Transdermal Formulations: Drugs and the Pharmaceutical Sciences. Boca Raton, FL: CRC Press; 2002:401-498. 6. Van Hoogdalem EJ. Transdermal absorption of topical anti-acne agents in man; review of clinical pharmacokinetic data. J Eur Acad Dermatol Venereol. 1998;11(suppl 1):S13-S19; discussion S28-S29. 413 Copyright © North American Neuro-Ophthalmology Society. Unauthorized reproduction of this article is prohibited.