Letter to the Editor
Painful polyneuropathy secondary to prolonged treatment with linezolid: Presentation of a case
Polineuropatía dolorosa secundaria a tratamiento prolongado con linezolid: a propósito de un caso
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Gil Villar, C. García Arguedas, S. Santos Lasaosa, P. Cía Blasco" "autores" => array:4 [ 0 => array:4 [ "nombre" => "M.P." "apellidos" => "Gil Villar" "email" => array:1 [ 0 => "mapi.gil.villar@gmail.com" ] "referencia" => array:2 [ 0 => array:2 [ "etiqueta" => "<span class="elsevierStyleSup">a</span>" "identificador" => "aff0005" ] 1 => array:2 [ "etiqueta" => "<span class="elsevierStyleSup">¿</span>" "identificador" => "cor0005" ] ] ] 1 => array:3 [ "nombre" => "C." "apellidos" => "García Arguedas" "referencia" => array:1 [ 0 => array:2 [ "etiqueta" => "<span class="elsevierStyleSup">a</span>" "identificador" => "aff0005" ] ] ] 2 => array:3 [ "nombre" => "S." "apellidos" => "Santos Lasaosa" "referencia" => array:1 [ 0 => array:2 [ "etiqueta" => "<span class="elsevierStyleSup">a</span>" "identificador" => "aff0005" ] ] ] 3 => array:3 [ "nombre" => "P." "apellidos" => "Cía Blasco" "referencia" => array:1 [ 0 => array:2 [ "etiqueta" => "<span class="elsevierStyleSup">b</span>" "identificador" => "aff0010" ] ] ] ] "afiliaciones" => array:2 [ 0 => array:3 [ "entidad" => "Servicio de Neurología, Hospital Clínico Universitario Lozano Blesa, Zaragoza, Spain" "etiqueta" => "<span class="elsevierStyleSup">a</span>" "identificador" => "aff0005" ] 1 => array:3 [ "entidad" => "Unidad de Dolor, Hospital Clínico Universitario Lozano Blesa, Zaragoza, Spain" "etiqueta" => "<span class="elsevierStyleSup">b</span>" "identificador" => "aff0010" ] ] "correspondencia" => array:1 [ 0 => array:3 [ "identificador" => "cor0005" "etiqueta" => "⁎" "correspondencia" => "Corresponding author." ] ] ] ] "titulosAlternativos" => array:1 [ "es" => array:1 [ "titulo" => "Polineuropatía dolorosa secundaria a tratamiento prolongado con linezolid: a propósito de un caso" ] ] "textoCompleto" => "<span class="elsevierStyleSections"><p id="par0005" class="elsevierStylePara elsevierViewall">Polyneuropathy is a common disease that requires an exhaustive aetiological study. Even so, the cause goes undiscovered on some occasions. Toxic neuropathies represent a small percentage of this group's diseases; some cases may be reversible, which makes identifying them all the more important.<a class="elsevierStyleCrossRef" href="#bib0005"><span class="elsevierStyleSup">1</span></a> At present, the appearance of new drugs such as linezolid means that we have to be especially alert in order to detect potential neurotoxic side effects that had not been described before those drugs were marketed.</p><p id="par0010" class="elsevierStylePara elsevierViewall">Our patient was a 24-year-old female smoker (20 cigarettes per day) with no other history of drug use. She was being treated with paroxetine for depressive disorder and used a vaginal ring; there was no other relevant medical or surgical history. She was referred to the hospital by her primary care doctor, who had observed positive Mantoux and bacilloscopy in a contact tracing study; her partner had recently been diagnosed with pleuropulmonary TB. Upon admission, the patient was completely asymptomatic and reported no fever, wasting syndrome, or respiratory problems. We began treatment with isoniazid, rifampicin, and pyrazinamide. After checking for good tolerance to the treatment (the patient only showed a slight increase in uric acid caused by the pyrazinamide) and a negative bacilloscopy, the patient was discharged. Since the sputum culture was positive for <span class="elsevierStyleItalic">Mycobacterium chelonae</span>, tuberculostatic treatment was replaced with clarithromycin, ethambutol, and linezolid dosed at 1200<span class="elsevierStyleHsp" style=""></span>mg daily. Three months after the treatment modification, she was readmitted for symptoms of dyspepsia, diarrhoea, and major asthenia. Analytical tests revealed normocytic anaemia (haemoglobin 6.8<span class="elsevierStyleHsp" style=""></span>mg/dl and 20.1% haematocrit). The patient also reported a painful dysaesthetic sensation in both feet. Examination revealed superficial tactile hypoaesthesia of the feet with Achilles tendon areflexia, patellar tendon hyporeflexia, mildly ataxic wide-based gait, and very slight heel-knee dysmetry. Results from the nerve conduction study were compatible with predominantly sensory and axonal neuropathy of the lower extremities. Analyses for vitamin B<span class="elsevierStyleInf">12</span>, folic acid, cryoglobulins, immunoelectrophoresis, serology studies (for Borrelia, Brucella, syphilis, hepatitis B and C, cytomegalovirus, HIV, herpes simplex, and varicella zoster) and TSH were all normal. We also performed a visual evoked potential test and brain and cervical MRI scans; there were no pathological findings. Anaemia and digestive symptoms were studied with the aid of coprocultures, fibrogastroscopy, marked leukocyte scintigraphy, and bone marrow biopsy, all of which returned normal results. In principle, all symptoms are compatible with the side effects of linezolid treatment. The digestive problems and the anaemia both abated after suspension of the drug. The painful polyneuropathy of the lower limbs required invasive treatment in the pain unit. An epidural catheter with an infusion of levobupivacaine remained in place for approximately 1 month. A year later, the patient required treatment with oxcarbazepine, duloxetine and delayed-release tramadol. Although ethambutol was also administered in this case and may also cause peripheral neuropathy, the clinical manifestations with anaemia and gastrointestinal problems have already been described as side effects of linezolid. This leads us to believe that the polyneuropathy was secondary to linezolid, although we cannot rule out the possibility of a synergistic effect exerted by both drugs.</p><p id="par0015" class="elsevierStylePara elsevierViewall">Linezolid is the first antibiotic in the oxazolidinone group to be effective against Gram-positive micro-organisms that are resistant to meticillin and vancomycin. The drug's action profile and good level of tolerance among patients meant that its first main use was the treatment of chronic osteomyelitis and infections in prostheses. A treatment duration of less than 28 days was initially recommended, but prolonged use caused reversible myelosuppression in addition to other then unknown side effects, such as neuritis optica<a class="elsevierStyleCrossRef" href="#bib0010"><span class="elsevierStyleSup">2</span></a> and polyneuropathy.<a class="elsevierStyleCrossRef" href="#bib0015"><span class="elsevierStyleSup">3</span></a> A number of case studies have also shown linezolid to be effective in treating strains of <span class="elsevierStyleItalic">Mycobacterium tuberculosis</span> resistant to other first-line drugs.<a class="elsevierStyleCrossRefs" href="#bib0020"><span class="elsevierStyleSup">4–8</span></a> This is why continuing linezolid use more than 28 days is increasingly common, and the literature confirms a link between prolonged use and toxic neuropathy.<a class="elsevierStyleCrossRefs" href="#bib0045"><span class="elsevierStyleSup">9,10</span></a> Associating treatment with vitamin B<span class="elsevierStyleInf">6</span> is proven to decrease the risk of blood toxicity. Although an article by Spellberg et al. claims that the drug does not seem to affect neuropathy, that article only refers to a series of 2 cases.<a class="elsevierStyleCrossRef" href="#bib0055"><span class="elsevierStyleSup">11</span></a> A recently published study<a class="elsevierStyleCrossRef" href="#bib0060"><span class="elsevierStyleSup">12</span></a> on treating multi-drug-resistant tuberculosis with linezolid includes 30 cases, of which 5 developed polyneuropathy. Of those 5 cases, 4 had been treated over 15–25 months, and increasing the vitamin B<span class="elsevierStyleInf">6</span> dose improved neurological symptoms in a single case. In the last case, intractable polyneuropathy led doctors to suspend treatment in the fifth month. The same patient had poorly controlled diabetes mellitus, as did case 2 in the article by Rho et al.<a class="elsevierStyleCrossRef" href="#bib0010"><span class="elsevierStyleSup">2</span></a> In both diabetic patients, painful neuropathy proved difficult to treat. Diabetes, even with no prior history of neuropathy, may be a concomitant factor that should be taken into account. The series of 85 patients published by Migliori et al.<a class="elsevierStyleCrossRef" href="#bib0040"><span class="elsevierStyleSup">8</span></a> reports 3 cases of polyneuropathy. Doses of 1200<span class="elsevierStyleHsp" style=""></span>mg daily were administered in 2 of the cases; the remaining case received a daily dose of 600<span class="elsevierStyleHsp" style=""></span>mg. Furthermore, this article concludes that while drug effectiveness is the same for both doses, the rate of side effects is significantly higher for the higher dose (4 of the 28 patients on 600<span class="elsevierStyleHsp" style=""></span>mg/day had side effects vs 31 of the 57 patients on 1200<span class="elsevierStyleHsp" style=""></span>mg/day).</p><p id="par0020" class="elsevierStylePara elsevierViewall">Lastly, we must point out that in all articles in the literature describing the characteristics of this type of neuropathy, the neuropathy was painful. We have even found a case<a class="elsevierStyleCrossRef" href="#bib0065"><span class="elsevierStyleSup">13</span></a> description in which the nerve conduction study was normal, but cutaneous biopsy showed fine fibre neuropathy. Therefore, knowing that a patient experiencing neuropathic pain has been treated with linezolid is extremely relevant to the diagnosis of the neuropathy. Furthermore, this condition may become more widespread if linezolid use becomes more widespread and prolonged.</p></span>" "pdfFichero" => "main.pdf" "tienePdf" => true "NotaPie" => array:1 [ 0 => array:2 [ "etiqueta" => "☆" "nota" => "<p class="elsevierStyleNotepara">Please cite this article as: Gil Villar MP, et al. Polineuropatía dolorosa secundaria a tratamiento prolongado con linezolid: a propósito de un caso. Neurología. 2012;27:443–5.</p>" ] ] "bibliografia" => array:2 [ "titulo" => "References" "seccion" => array:1 [ 0 => array:2 [ "identificador" => "bibs0005" "bibliografiaReferencia" => array:13 [ 0 => array:3 [ "identificador" => "bib0005" "etiqueta" => "1" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Update on medication-induced peripheral neuropathy" "autores" => array:1 [ 0 => array:2 [ "etal" => false "autores" => array:2 [ 0 => "L.H. Weimer" 1 => "N. 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| Year/Month | Html | Total | |
|---|---|---|---|
| 2024 November | 3 | 1 | 4 |
| 2024 October | 32 | 8 | 40 |
| 2024 September | 49 | 16 | 65 |
| 2024 August | 42 | 16 | 58 |
| 2024 July | 48 | 9 | 57 |
| 2024 June | 75 | 8 | 83 |
| 2024 May | 86 | 6 | 92 |
| 2024 April | 42 | 6 | 48 |
| 2024 March | 60 | 11 | 71 |
| 2024 February | 81 | 7 | 88 |
| 2024 January | 68 | 9 | 77 |
| 2023 December | 57 | 9 | 66 |
| 2023 November | 103 | 14 | 117 |
| 2023 October | 109 | 16 | 125 |
| 2023 September | 60 | 11 | 71 |
| 2023 August | 67 | 6 | 73 |
| 2023 July | 100 | 20 | 120 |
| 2023 June | 51 | 9 | 60 |
| 2023 May | 103 | 16 | 119 |
| 2023 April | 95 | 13 | 108 |
| 2023 March | 63 | 9 | 72 |
| 2023 February | 66 | 20 | 86 |
| 2023 January | 89 | 16 | 105 |
| 2022 December | 81 | 7 | 88 |
| 2022 November | 107 | 12 | 119 |
| 2022 October | 67 | 16 | 83 |
| 2022 September | 78 | 37 | 115 |
| 2022 August | 67 | 41 | 108 |
| 2022 July | 59 | 11 | 70 |
| 2022 June | 58 | 16 | 74 |
| 2022 May | 47 | 15 | 62 |
| 2022 April | 62 | 17 | 79 |
| 2022 March | 70 | 15 | 85 |
| 2022 February | 81 | 13 | 94 |
| 2022 January | 76 | 21 | 97 |
| 2021 December | 74 | 27 | 101 |
| 2021 November | 62 | 11 | 73 |
| 2021 October | 83 | 8 | 91 |
| 2021 September | 74 | 17 | 91 |
| 2021 August | 87 | 14 | 101 |
| 2021 July | 48 | 9 | 57 |
| 2021 June | 50 | 12 | 62 |
| 2021 May | 54 | 7 | 61 |
| 2021 April | 106 | 17 | 123 |
| 2021 March | 62 | 13 | 75 |
| 2021 February | 49 | 15 | 64 |
| 2021 January | 50 | 13 | 63 |
| 2020 December | 48 | 20 | 68 |
| 2020 November | 39 | 17 | 56 |
| 2020 October | 52 | 13 | 65 |
| 2020 September | 34 | 11 | 45 |
| 2020 August | 42 | 14 | 56 |
| 2020 July | 39 | 15 | 54 |
| 2020 June | 27 | 7 | 34 |
| 2020 May | 40 | 20 | 60 |
| 2020 April | 29 | 6 | 35 |
| 2020 March | 41 | 9 | 50 |
| 2020 February | 30 | 8 | 38 |
| 2020 January | 27 | 6 | 33 |
| 2019 December | 125 | 16 | 141 |
| 2019 November | 388 | 6 | 394 |
| 2019 October | 387 | 3 | 390 |
| 2019 September | 173 | 12 | 185 |
| 2019 August | 9 | 3 | 12 |
| 2019 July | 20 | 19 | 39 |
| 2019 June | 22 | 35 | 57 |
| 2019 May | 95 | 97 | 192 |
| 2019 April | 26 | 46 | 72 |
| 2019 March | 7 | 10 | 17 |
| 2019 February | 11 | 21 | 32 |
| 2019 January | 12 | 11 | 23 |
| 2018 December | 16 | 14 | 30 |
| 2018 November | 11 | 10 | 21 |
| 2018 October | 14 | 25 | 39 |
| 2018 September | 5 | 6 | 11 |
| 2018 August | 4 | 22 | 26 |
| 2018 July | 1 | 12 | 13 |
| 2018 June | 2 | 15 | 17 |
| 2018 May | 3 | 16 | 19 |
| 2018 April | 3 | 8 | 11 |
| 2018 March | 2 | 6 | 8 |
| 2018 February | 2 | 6 | 8 |
| 2018 January | 8 | 10 | 18 |
| 2017 December | 5 | 11 | 16 |
| 2017 November | 12 | 5 | 17 |
| 2017 October | 15 | 7 | 22 |
| 2017 September | 38 | 7 | 45 |
| 2017 August | 32 | 5 | 37 |
| 2017 July | 22 | 12 | 34 |
| 2017 June | 29 | 18 | 47 |
| 2017 May | 38 | 27 | 65 |
| 2017 April | 32 | 12 | 44 |
| 2017 March | 24 | 28 | 52 |
| 2017 February | 22 | 9 | 31 |
| 2017 January | 11 | 3 | 14 |
| 2016 December | 15 | 12 | 27 |
| 2016 November | 8 | 4 | 12 |
| 2016 October | 20 | 11 | 31 |
| 2016 September | 18 | 9 | 27 |
| 2016 August | 19 | 4 | 23 |
| 2016 July | 9 | 3 | 12 |
| 2016 June | 10 | 10 | 20 |
| 2016 May | 15 | 21 | 36 |
| 2016 April | 10 | 9 | 19 |
| 2016 March | 21 | 21 | 42 |
| 2016 February | 14 | 13 | 27 |
| 2016 January | 9 | 11 | 20 |
| 2015 December | 9 | 9 | 18 |
| 2015 November | 13 | 13 | 26 |
| 2015 October | 23 | 21 | 44 |
| 2015 September | 17 | 8 | 25 |
| 2015 August | 9 | 6 | 15 |
| 2015 July | 8 | 6 | 14 |
| 2015 June | 5 | 2 | 7 |
| 2015 May | 10 | 8 | 18 |
| 2015 April | 19 | 13 | 32 |
| 2015 March | 13 | 12 | 25 |
| 2015 February | 11 | 4 | 15 |
| 2015 January | 17 | 4 | 21 |
| 2014 December | 30 | 11 | 41 |
| 2014 November | 18 | 1 | 19 |
| 2014 October | 16 | 3 | 19 |
| 2014 September | 22 | 2 | 24 |
| 2014 August | 26 | 6 | 32 |
| 2014 July | 37 | 7 | 44 |
| 2014 June | 18 | 5 | 23 |
| 2014 May | 14 | 4 | 18 |
| 2014 April | 15 | 5 | 20 |
| 2014 March | 11 | 8 | 19 |
| 2014 February | 21 | 0 | 21 |
| 2014 January | 9 | 4 | 13 |
| 2013 December | 21 | 3 | 24 |
| 2013 November | 19 | 8 | 27 |
| 2013 October | 24 | 11 | 35 |
| 2013 September | 37 | 6 | 43 |
| 2013 August | 29 | 9 | 38 |
| 2013 July | 17 | 3 | 20 |
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