Case and Research Letter
Optic Neuritis Probably Induced by Isotretinoin
Neuritis óptica probablemente inducida por isotretinoína
L. Pérez-Pérez
, J. García-Gavín, F. Allegue, A. Zulaica
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Servicio de Dermatología, Complejo Hospitalario Universitario de Vigo, Vigo, Spain
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Pérez-Pérez, J. García-Gavín, F. Allegue, A. Zulaica" "autores" => array:4 [ 0 => array:4 [ "nombre" => "L." "apellidos" => "Pérez-Pérez" "email" => array:1 [ 0 => "lidiacomba@yahoo.es" ] "referencia" => array:1 [ 0 => array:2 [ "etiqueta" => "<span class="elsevierStyleSup">¿</span>" "identificador" => "cor0005" ] ] ] 1 => array:2 [ "nombre" => "J." "apellidos" => "García-Gavín" ] 2 => array:2 [ "nombre" => "F." "apellidos" => "Allegue" ] 3 => array:2 [ "nombre" => "A." "apellidos" => "Zulaica" ] ] "afiliaciones" => array:1 [ 0 => array:1 [ "entidad" => "Servicio de Dermatología, Complejo Hospitalario Universitario de Vigo, Vigo, Spain" ] ] "correspondencia" => array:1 [ 0 => array:3 [ "identificador" => "cor0005" "etiqueta" => "⁎" "correspondencia" => "Corresponding author." ] ] ] ] "titulosAlternativos" => array:1 [ "es" => array:1 [ "titulo" => "Neuritis óptica probablemente inducida por isotretinoína" ] ] "textoCompleto" => "<span class="elsevierStyleSections"><p id="par0005" class="elsevierStylePara elsevierViewall">Isotretinoin is a drug indicated in dermatology for the treatment of acne and used off-label for other skin and mucosal disorders.<a class="elsevierStyleCrossRefs" href="#bib0005"><span class="elsevierStyleSup">1–4</span></a></p><p id="par0010" class="elsevierStylePara elsevierViewall">Most patients treated with isotretinoin develop mild adverse effects that do not affect the course of treatment. However, it can have less common unpredictable effects that are more serious and must be known by those who habitually use this drug in clinical practice.<a class="elsevierStyleCrossRefs" href="#bib0020"><span class="elsevierStyleSup">4,5</span></a></p><p id="par0015" class="elsevierStylePara elsevierViewall">A 16-year-old girl weighing 63<span class="elsevierStyleHsp" style=""></span>kg with no relevant past medical history or treatment for chronic disease was evaluated in our department for moderate, predominantly facial juvenile acne that had not been controlled with topical treatment (adapalene and benzoyl peroxide in combination) or oral antibiotics (oral doxycycline 50<span class="elsevierStyleHsp" style=""></span>mg for 2 months, interrupted 2 months before she started treatment with oral retinoids). Three months after starting treatment with oral isotretinoin (30<span class="elsevierStyleHsp" style=""></span>mg daily, 0.47<span class="elsevierStyleHsp" style=""></span>mg/kg/d), the patient began to notice vision loss and blurred vision in her right eye. She did not report pain with eye movements, impaired color vision, photophobia, or headache.</p><p id="par0020" class="elsevierStylePara elsevierViewall">The patient was evaluated by an ophthalmologist, who detected a peripheral visual field deficit in the right eye and established the clinical diagnosis of retrobulbar optic neuritis. Slit lamp examination and funduscopy showed normal findings in both eyes. The intraocular pressure was within the normal range in both eyes. On suspicion of an adverse reaction to isotretinoin, the patient was referred urgently to our clinic; when she attended she had reduced the daily dose from 30 to 20<span class="elsevierStyleHsp" style=""></span>mg and her vision had improved considerably. At that time it was decided to stop treatment. Nuclear magnetic resonance imaging was requested to rule out demyelinating disease and the patient was referred to the neurology department. The general neurological examination was normal. A lumbar puncture revealed no pathological findings. The visual evoked potential responses revealed P100 waves with prolonged latency, decreased amplitude, and altered morphology and confirmed the presence of bilateral optic neuropathy. The other additional tests revealed no pathological findings.</p><p id="par0025" class="elsevierStylePara elsevierViewall">Six months after withdrawal of the drug, the patient had recovered vision completely and no ophthalmologic sequelae were observed in later examinations. The patient is studying abroad, so at the time of writing it has not been possible to confirm the return to normal values by repeating the ophthalmologic studies and visual evoked potentials.</p><p id="par0030" class="elsevierStylePara elsevierViewall">A recent review of the adverse effects of isotretinoin in a series of 1743 patients showed that ocular manifestations may occur in up to 3.4% of cases.<a class="elsevierStyleCrossRef" href="#bib0020"><span class="elsevierStyleSup">4</span></a></p><p id="par0035" class="elsevierStylePara elsevierViewall">The most common manifestations are mild cases of blurred vision, keratitis, and keratoconjunctivitis (<a class="elsevierStyleCrossRef" href="#tbl0005">Table 1</a>). However, there have been isolated reports of potentially serious ophthalmic adverse events.</p><elsevierMultimedia ident="tbl0005"></elsevierMultimedia><p id="par0040" class="elsevierStylePara elsevierViewall">Optic neuritis is an inflammatory disease of the optic nerve that is generally associated with acute or subacute loss of vision.<a class="elsevierStyleCrossRef" href="#bib0030"><span class="elsevierStyleSup">6</span></a> This condition is included in the list of possible adverse effects of isotretinoin in the drug's summary of product characteristics in some countries<a class="elsevierStyleCrossRefs" href="#bib0035"><span class="elsevierStyleSup">7,8</span></a> and in several review articles.<a class="elsevierStyleCrossRefs" href="#bib0045"><span class="elsevierStyleSup">9–11</span></a> Fraunfelder et al.<a class="elsevierStyleCrossRef" href="#bib0050"><span class="elsevierStyleSup">10</span></a> reviewed a total of 2379 possible ocular adverse effects related to the administration of isotretinoin and identified 33 cases of optic neuritis, of which 22 occurred in women with a mean age of 25.6 years. Fraunfelder et al. classified optic neuritis as a “possible” ocular adverse effect of isotretinoin according to the World Health Organization classification system.<a class="elsevierStyleCrossRef" href="#bib0050"><span class="elsevierStyleSup">10</span></a> In our case, the timing, the improvement in symptoms after the initial dose reduction and subsequent interruption of the treatment, and the absence of other objective causes support the diagnosis of adverse drug reaction.</p><p id="par0045" class="elsevierStylePara elsevierViewall">It has recently been suggested that isotretinoin can cause alterations in synaptic activity and in the propagation of action potentials, leading to conduction defects within the optic nerve.<a class="elsevierStyleCrossRef" href="#bib0060"><span class="elsevierStyleSup">12</span></a> Visual evoked potentials may be useful for detecting and monitoring subclinical visual changes.<a class="elsevierStyleCrossRef" href="#bib0060"><span class="elsevierStyleSup">12</span></a></p><p id="par0050" class="elsevierStylePara elsevierViewall">Although most ocular adverse effects in patients treated with isotretinoin are mild and dose-dependent and do not interfere with the completion of the course of treatment, potentially serious ophthalmologic changes have been described. Providing patients with complete information and appropriate clinical monitoring can facilitate early detection of these effects and prevent long-term complications.</p></span>" "pdfFichero" => "main.pdf" "tienePdf" => true "NotaPie" => array:1 [ 0 => array:2 [ "etiqueta" => "☆" "nota" => "<p class="elsevierStyleNotepara">Pérez-Pérez L, et al. Neuritis óptica probablemente inducida por isotretinoína. Actas Dermosifiliogr. 2012;103:846-7.</p>" ] ] "multimedia" => array:1 [ 0 => array:7 [ "identificador" => "tbl0005" "etiqueta" => "Table 1" "tipo" => "MULTIMEDIATABLA" "mostrarFloat" => true "mostrarDisplay" => false "tabla" => array:2 [ "tablatextoimagen" => array:1 [ 0 => array:2 [ "tabla" => array:1 [ 0 => """ <table border="0" frame="\n \t\t\t\t\tvoid\n \t\t\t\t" class=""><thead title="thead"><tr title="table-row"><td class="td" title="\n \t\t\t\t\ttable-head\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t" style="border-bottom: 2px solid black">Adverse Effect \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-head\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t" style="border-bottom: 2px solid black">Frequency, %<a class="elsevierStyleCrossRef" href="#tblfn0005"><span class="elsevierStyleSup">a</span></a> \t\t\t\t\t\t\n \t\t\t\t</td></tr></thead><tbody title="tbody"><tr title="table-row"><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Blurred vision \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">19.9 \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Keratitis \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">16.6 \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Blepharoconjunctivitis \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">10.9 \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Dry eye \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">10.2 \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Decreased dark adaptation \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">5.9 \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Corneal opacities \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">5 \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Intracranial hypertension \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">4.6 \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Photophobia \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">3.7 \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Refractive disorders \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">3.5 \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Cataracts \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">2.1 \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Altered accommodation, decreased tolerance to contact lenses, subconjunctival hemorrhage, optic neuritis, diplopia, iritis, mydriasis, palpebral angioedema, glaucoma, scleritis, decreased color vision, epiphora \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t"><<span class="elsevierStyleHsp" style=""></span>2 \t\t\t\t\t\t\n \t\t\t\t</td></tr></tbody></table> """ ] "imagenFichero" => array:1 [ 0 => "xTab182591.png" ] ] ] "notaPie" => array:1 [ 0 => array:3 [ "identificador" => "tblfn0005" "etiqueta" => "a" "nota" => "<p class="elsevierStyleNotepara">Percentages of 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| año/Mes | Html | Total | |
|---|---|---|---|
| 2024 Noviembre | 21 | 15 | 36 |
| 2024 Octubre | 183 | 64 | 247 |
| 2024 Septiembre | 222 | 74 | 296 |
| 2024 Agosto | 256 | 120 | 376 |
| 2024 Julio | 226 | 74 | 300 |
| 2024 Junio | 229 | 83 | 312 |
| 2024 Mayo | 205 | 72 | 277 |
| 2024 Abril | 166 | 62 | 228 |
| 2024 Marzo | 202 | 103 | 305 |
| 2024 Febrero | 156 | 136 | 292 |
| 2024 Enero | 142 | 140 | 282 |
| 2023 Diciembre | 145 | 87 | 232 |
| 2023 Noviembre | 96 | 94 | 190 |
| 2023 Octubre | 104 | 94 | 198 |
| 2023 Septiembre | 110 | 68 | 178 |
| 2023 Agosto | 74 | 74 | 148 |
| 2023 Julio | 97 | 139 | 236 |
| 2023 Junio | 113 | 84 | 197 |
| 2023 Mayo | 193 | 92 | 285 |
| 2023 Abril | 124 | 78 | 202 |
| 2023 Marzo | 154 | 73 | 227 |
| 2023 Febrero | 103 | 77 | 180 |
| 2023 Enero | 86 | 81 | 167 |
| 2022 Diciembre | 90 | 121 | 211 |
| 2022 Noviembre | 34 | 166 | 200 |
| 2022 Octubre | 47 | 180 | 227 |
| 2022 Septiembre | 39 | 142 | 181 |
| 2022 Agosto | 26 | 120 | 146 |
| 2022 Julio | 26 | 115 | 141 |
| 2022 Junio | 37 | 90 | 127 |
| 2022 Mayo | 199 | 129 | 328 |
| 2022 Abril | 220 | 114 | 334 |
| 2022 Marzo | 156 | 136 | 292 |
| 2022 Febrero | 132 | 142 | 274 |
| 2022 Enero | 112 | 141 | 253 |
| 2021 Diciembre | 127 | 112 | 239 |
| 2021 Noviembre | 112 | 134 | 246 |
| 2021 Octubre | 74 | 148 | 222 |
| 2021 Septiembre | 55 | 103 | 158 |
| 2021 Agosto | 47 | 101 | 148 |
| 2021 Julio | 57 | 108 | 165 |
| 2021 Junio | 50 | 121 | 171 |
| 2021 Mayo | 51 | 212 | 263 |
| 2021 Abril | 117 | 279 | 396 |
| 2021 Marzo | 45 | 130 | 175 |
| 2021 Febrero | 56 | 93 | 149 |
| 2021 Enero | 58 | 93 | 151 |
| 2020 Diciembre | 51 | 91 | 142 |
| 2020 Noviembre | 37 | 47 | 84 |
| 2020 Octubre | 30 | 58 | 88 |
| 2020 Septiembre | 43 | 30 | 73 |
| 2020 Agosto | 36 | 67 | 103 |
| 2020 Julio | 25 | 49 | 74 |
| 2020 Junio | 41 | 70 | 111 |
| 2020 Mayo | 20 | 56 | 76 |
| 2020 Abril | 32 | 45 | 77 |
| 2020 Marzo | 30 | 47 | 77 |
| 2020 Febrero | 8 | 39 | 47 |
| 2020 Enero | 4 | 45 | 49 |
| 2019 Diciembre | 8 | 39 | 47 |
| 2019 Noviembre | 2 | 26 | 28 |
| 2019 Octubre | 0 | 59 | 59 |
| 2019 Septiembre | 8 | 28 | 36 |
| 2019 Agosto | 4 | 34 | 38 |
| 2019 Julio | 4 | 52 | 56 |
| 2019 Junio | 6 | 38 | 44 |
| 2019 Mayo | 4 | 113 | 117 |
| 2019 Abril | 2 | 78 | 80 |
| 2019 Marzo | 2 | 20 | 22 |
| 2019 Febrero | 2 | 12 | 14 |
| 2019 Enero | 2 | 1 | 3 |
| 2018 Diciembre | 5 | 7 | 12 |
| 2018 Noviembre | 2 | 0 | 2 |
| 2018 Octubre | 2 | 0 | 2 |
| 2018 Septiembre | 4 | 19 | 23 |
| 2018 Agosto | 0 | 20 | 20 |
| 2018 Julio | 0 | 17 | 17 |
| 2018 Junio | 0 | 9 | 9 |
| 2018 Mayo | 0 | 3 | 3 |
| 2018 Abril | 0 | 7 | 7 |
| 2018 Marzo | 17 | 7 | 24 |
| 2018 Febrero | 72 | 19 | 91 |
| 2018 Enero | 72 | 11 | 83 |
| 2017 Diciembre | 87 | 16 | 103 |
| 2017 Noviembre | 74 | 19 | 93 |
| 2017 Octubre | 76 | 14 | 90 |
| 2017 Septiembre | 84 | 17 | 101 |
| 2017 Agosto | 101 | 18 | 119 |
| 2017 Julio | 97 | 42 | 139 |
| 2017 Junio | 92 | 39 | 131 |
| 2017 Mayo | 76 | 26 | 102 |
| 2017 Abril | 89 | 27 | 116 |
| 2017 Marzo | 85 | 36 | 121 |
| 2017 Febrero | 75 | 26 | 101 |
| 2017 Enero | 113 | 21 | 134 |
| 2016 Diciembre | 105 | 16 | 121 |
| 2016 Noviembre | 160 | 20 | 180 |
| 2016 Octubre | 120 | 12 | 132 |
| 2016 Septiembre | 148 | 28 | 176 |
| 2016 Agosto | 121 | 27 | 148 |
| 2016 Julio | 82 | 31 | 113 |
| 2016 Junio | 12 | 20 | 32 |
| 2016 Mayo | 5 | 16 | 21 |
| 2016 Abril | 4 | 1 | 5 |
| 2016 Marzo | 8 | 16 | 24 |
| 2016 Febrero | 9 | 1 | 10 |
| 2016 Enero | 13 | 1 | 14 |
| 2015 Diciembre | 19 | 1 | 20 |
| 2015 Noviembre | 20 | 6 | 26 |
| 2015 Octubre | 17 | 5 | 22 |
| 2015 Septiembre | 13 | 1 | 14 |
| 2015 Agosto | 14 | 8 | 22 |
| 2015 Julio | 65 | 7 | 72 |
| 2015 Junio | 65 | 7 | 72 |
| 2015 Mayo | 126 | 9 | 135 |
| 2015 Abril | 88 | 16 | 104 |
| 2015 Marzo | 87 | 8 | 95 |
| 2015 Febrero | 69 | 7 | 76 |
| 2015 Enero | 65 | 11 | 76 |
| 2014 Diciembre | 54 | 12 | 66 |
| 2014 Noviembre | 60 | 11 | 71 |
| 2014 Octubre | 38 | 8 | 46 |
| 2014 Septiembre | 23 | 5 | 28 |
| 2014 Agosto | 23 | 3 | 26 |
| 2014 Julio | 23 | 9 | 32 |
| 2014 Junio | 23 | 7 | 30 |
| 2014 Mayo | 31 | 8 | 39 |
| 2014 Abril | 21 | 4 | 25 |
| 2014 Marzo | 27 | 8 | 35 |
| 2014 Febrero | 26 | 17 | 43 |
| 2014 Enero | 30 | 13 | 43 |
| 2013 Diciembre | 36 | 16 | 52 |
| 2013 Noviembre | 17 | 12 | 29 |
| 2013 Octubre | 8 | 15 | 23 |
| 2013 Septiembre | 12 | 13 | 25 |
| 2013 Agosto | 9 | 20 | 29 |
| 2013 Julio | 13 | 24 | 37 |
| 2013 Junio | 8 | 18 | 26 |
| 2013 Mayo | 10 | 22 | 32 |
| 2013 Abril | 10 | 29 | 39 |
| 2013 Marzo | 20 | 13 | 33 |
| 2013 Febrero | 35 | 9 | 44 |
| 2013 Enero | 20 | 9 | 29 |
| 2012 Diciembre | 15 | 8 | 23 |
| 2012 Noviembre | 1 | 0 | 1 |
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