Fulminant Pseudotumor Cerebri Syndrome Secondary to Over-the-Counter Topical Retinoids

Pseudotumor cerebri syndrome (PTCS) is a constellation of symptoms and signs related to increased intracranial pressure. Although most cases present with gradual development of symptoms, fulminant presentations occur, with occurrence of visual loss within 1 month of headache onset(1). Excessive oral intake of vitamin A is considered an important risk factor for the development of PTCS.Increased cerebrospinal fluid (CSF) outflow resistance, vita-min A metabolism dysregulation, venous sinus thrombosis,or venous hypertension have been suggested as possible pathogenic mechanisms (2). Topical retinoids are used in the treatment for a number of skin conditions such as psoriasis,warts, and facial acne. PTCS has only been associated with topical retinoids twice before (3,4), but this is the first report of a fulminant presentation after topical exposure.

Clinical Correspondence Fulminant Pseudotumor Cerebri Syndrome Secondary to Over-the-Counter Topical Retinoids Konstantinos A. A. Douglas, MD, DVM, MBA, Vivian P. Douglas, MD, DVM, MBA, Bart K. Chwalisz, MD P seudotumor cerebri syndrome (PTCS) is a constellation of symptoms and signs related to increased intracranial pressure. Although most cases present with gradual development of symptoms, fulminant presentations occur, with occurrence of visual loss within 1 month of headache onset (1). Excessive oral intake of vitamin A is considered an important risk factor for the development of PTCS. Increased cerebrospinal fluid (CSF) outflow resistance, vitamin A metabolism dysregulation, venous sinus thrombosis, or venous hypertension have been suggested as possible pathogenic mechanisms (2). Topical retinoids are used in the treatment for a number of skin conditions such as psoriasis, warts, and facial acne. PTCS has only been associated with topical retinoids twice before (3,4), but this is the first report of a fulminant presentation after topical exposure. A 33-year-old nonobese Caucasian woman was referred for headaches, visual field defects, and bilateral optic disc swelling. The patient has a BMI of 28.9, and her weight has been stable since the birth of her child in 2010. A week before presentation, the patient started experiencing mild pressure-like bilateral fronto-temporal headaches worse when lying down, bending over, and on waking up. Severity gradually increased to the point of no longer responding to ibuprofen. She also reported paracentral cloudiness that progressed to a superotemporal scotomata in both eyes. On closer questioning, the patient recalled that for the past 6 weeks, she had started using a topical over-thecounter vitamin A-derived skin cream (adapalene) for the treatment of facial acne. Adapalene is a third-generation retinoid with anticomedogenic, anti-inflammatory, and immunoregulatory properties that can be used as an over-thecounter gel for the treatment and prevention of facial acne (5). On examination, visual acuity was 20/20-2 bilaterally. The visual field on the right eye showed severe constriction while on the left eye, there was enlarged blind spot (Fig. 1A, B). Circumferential bilateral disc edema with hemorrhages and tortuous vessels was observed (Fig. 1C, D). Brain MRI with venogram showed a partially empty sella turcica but no cortical venous sinus thrombosis. Lumbar puncture yielded an elevated opening pressure of 36 cm H20, with normal CSF protein, glucose, and cell count. Adapalene was stopped. The patient was treated with acetazolamide, with gradual improvement in her papilledema. Her visual fields stabilized but did not fully normalize (Fig. 2A, B). Subsequent optical coherence tomography showed thinning of the peripapillary retinal nerve fiber layer and macular ganglion cell complex, confirming that optic atrophy had occurred (Fig. 2C, D). To the best of our knowledge, this is only the third report that use of topical retinoids can lead to intracranial hypertension and the first report of a fulminant PTCS presentation. These reports suggest that third-generation retinoids can lead to intracranial hypertension even when applied topically. Moreover, this case demonstrates that severe papilledema can develop rapidly in these cases and can progress to permanent vision loss. It is hoped that Neuro-Ophthalmology Service, Department of Ophthalmology, Massachusetts Eye and Ear Infirmary, Harvard Medical School, Boston, Massachusetts. The authors report no conflicts of interest. K. A. A. Douglas and V. P. Douglas contributed equally to the article. Address correspondence to Bart K. Chwalisz, MD, NeuroOphthalmology Service, 243 Charles Street, Boston, MA 02114; E-mail: [e-mail] 248 FIG. 1. At presentation: Visual fields with spot (A, left eye) and severe constriction (C, D) fundus photographs demonstrating bilateral disc edema with hemorrhages vessels. enlarged blind (B, right eye); circumferential and tortuous Douglas et al: J Neuro-Ophthalmol 2020; 40: 248-249 Copyright © North American Neuro-Ophthalmology Society. Unauthorized reproduction of this article is prohibited. Clinical Correspondence FIG. 2. After adapalene discontinuation and acetazolamide administration: (A, B) Visual fields with significant improvement; (C, D) optic atrophy with thinning of the peripapillary retinal nerve fiber layer and macular ganglion cell complex on optical coherence tomography. GCL, ganglion cell layer; IPL, inner plexiform layer; OD, right eye; OS, left eye. greater awareness of this rare complication of topical retinoids will lead to improved counseling and monitoring of at-risk patients. STATEMENT OF AUTHORSHIP Category 1: a. Conception and design: B. K. Chwalisz, K. A. A. Douglas, and V. P. Douglas; b. Acquisition of data: B. K. Chwalisz; c. Analysis and interpretation of data: B. K. Chwalisz. Category 2: a. Drafting the manuscript: B. K. Chwalisz, K. A. A. Douglas, and V. P. Douglas; b. Revising it for intellectual content: B. K. Chwalisz, K. A. A. Douglas, and V. P. Douglas; Category 3: a. Final approval of the completed manuscript: B. K Chwalisz. Douglas et al: J Neuro-Ophthalmol 2020; 40: 248-249 REFERENCES 1. Thambisetty M, Lavin PJ, Newman NJ, Biousse V. Fulminant idiopathic intracranial hypertension. Neurology. 2007;68:229- 232. 2. Wakerley BR, Tan MH, Ting EY. Idiopathic intracranial hypertension. Cephalalgia. 2014;35:248-261. 3. Givre SJ, Fleischman D. Intracranial hypertension in a patient using topical adapalene. J Neuroophthalmol. 2008;28:156- 158. 4. Mohammad YM, Raslan IR, Al-Hussain FA. Idiopathic intracranial hypertension induced by topical application of vitamin A. J Neuroophthalmol. 2016;36:412-413. 5. Leyden J. Recent advances in the use of adapalene 0.1%/ benzoyl peroxide 2.5% to treat patients with moderate to severe acne. J Dermatolog Treat. 2016;27(suppl 1):S4-S13. 249 Copyright © North American Neuro-Ophthalmology Society. Unauthorized reproduction of this article is prohibited.