Case and Research Letters
Levofloxacin-Induced Hyperpigmentation
Hiperpigmentación inducida por levofloxacino
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Áreas de dermis más profundas con abundantes siderófagos. Citoplasma con contenido pardo-dorado granular, débilmente refringente. b) Tinción de Perls (hierro): positiva, observándose un citoplasma azulado, granular en el interior de los macrófagos.</p>" ] ] ] "autores" => array:1 [ 0 => array:2 [ "autoresLista" => "M. Castellanos-González, M.L. González Morales, J. González-Granda Villalobos" "autores" => array:3 [ 0 => array:2 [ "nombre" => "M." "apellidos" => "Castellanos-González" ] 1 => array:2 [ "nombre" => "M.L." "apellidos" => "González Morales" ] 2 => array:2 [ "nombre" => "J." 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Castellanos-González, M.L. González Morales, J. González-Granda Villalobos" "autores" => array:3 [ 0 => array:4 [ "nombre" => "M." "apellidos" => "Castellanos-González" "email" => array:1 [ 0 => "maria.castellanos.gonzalez@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" => "M.L." "apellidos" => "González Morales" "referencia" => array:1 [ 0 => array:2 [ "etiqueta" => "<span class="elsevierStyleSup">b</span>" "identificador" => "aff0010" ] ] ] 2 => array:3 [ "nombre" => "J." "apellidos" => "González-Granda Villalobos" "referencia" => array:1 [ 0 => array:2 [ "etiqueta" => "<span class="elsevierStyleSup">c</span>" "identificador" => "aff0015" ] ] ] ] "afiliaciones" => array:3 [ 0 => array:3 [ "entidad" => "Departamento de Dermatología, Hospital del Sureste, Arganda del Rey, Madrid, España" "etiqueta" => "a" "identificador" => "aff0005" ] 1 => array:3 [ "entidad" => "Departamento de Anatomía Patológica, Hospital Clínico San Carlos, Madrid, España" "etiqueta" => "b" "identificador" => "aff0010" ] 2 => array:3 [ "entidad" => "Traumatología, Hospital del Sureste, Arganda del Rey Madrid, España" "etiqueta" => "c" "identificador" => "aff0015" ] ] "correspondencia" => array:1 [ 0 => array:3 [ "identificador" => "cor0005" "etiqueta" => "⁎" "correspondencia" => "Corresponding author." ] ] ] ] "titulosAlternativos" => array:1 [ "es" => array:1 [ "titulo" => "Hiperpigmentación inducida por levofloxacino" ] ] "resumenGrafico" => array:2 [ "original" => 0 "multimedia" => array:7 [ "identificador" => "fig0010" "etiqueta" => "Figure 2" "tipo" => "MULTIMEDIAFIGURA" "mostrarFloat" => true "mostrarDisplay" => false "figura" => array:1 [ 0 => array:4 [ "imagen" => "gr2.jpeg" "Alto" => 463 "Ancho" => 1255 "Tamanyo" => 298543 ] ] "descripcion" => array:1 [ "en" => "<p id="spar0010" class="elsevierStyleSimplePara elsevierViewall">A, Abundant siderophages in the deepest areas of the dermis (hematoxylin-eosin, original magnification ×20). Cytoplasm containing slightly refringent golden-brown granules. B, Positive Perls staining (iron), revealing bluish, granular cytoplasm inside the macrophages.</p>" ] ] ] "textoCompleto" => "<span class="elsevierStyleSections"><p id="par0005" class="elsevierStylePara elsevierViewall">Among the cutaneous adverse effects associated with drugs used in clinical practice, those caused by antibiotics are particularly frequent. Examples include minocycline-induced pigmentary changes of the skin or mucous membranes. However, these alterations are rarely associated with the use of other antibiotics. We report the uncommon case of a patient who developed blackish lesions on the lower limbs after beginning levofloxacin treatment.</p><span id="sec0005" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0005">Case Description</span><p id="par0010" class="elsevierStylePara elsevierViewall">A 72-year-old man with a previous biopsy-confirmed diagnosis of pigmented purpuric dermatosis (PPD) of the legs was seen for darkening of the skin of the lower limbs that had begun 10 months earlier. Two years earlier, the patient had undergone surgery for implantation of a prosthesis in the right shoulder. He had been receiving levofloxacin treatment for several months to treat an infection of the prosthesis. He reported that the skin discoloration appeared a few weeks after beginning levofloxacin treatment. Physical examination revealed very striking diffuse, blackish-gray pigmentation distributed bilaterally and symmetrically on the anterolateral aspects of the legs, from the knees to the toes, sparing the soles (<a class="elsevierStyleCrossRef" href="#fig0005">Fig. 1</a>). The mucous membranes were unaffected. The distal pulse was preserved and there were no other signs of ischemia.</p><elsevierMultimedia ident="fig0005"></elsevierMultimedia><p id="par0015" class="elsevierStylePara elsevierViewall">A biopsy showed extensive deposition in the superficial and middle dermis of macrophages containing brown granular refractive cytoplasm, and a focal lymphocytic inflammatory infiltrate containing extravasated red blood cells. Perls staining was strongly positive inside the macrophages (<a class="elsevierStyleCrossRef" href="#fig0010">Fig. 2</a>A, B). Von Kossa and Fontana Masson staining were negative.</p><elsevierMultimedia ident="fig0010"></elsevierMultimedia><p id="par0020" class="elsevierStylePara elsevierViewall">Levofloxacin treatment was suspended, resulting in a striking improvement in the skin pigmentation. Within 4 months, the patient's skin color had returned to normal (<a class="elsevierStyleCrossRef" href="#fig0015">Fig. 3</a>).</p><elsevierMultimedia ident="fig0015"></elsevierMultimedia></span><span id="sec0010" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0010">Discussion</span><p id="par0025" class="elsevierStylePara elsevierViewall">Quinolone treatment has been associated with certain cutaneous adverse effects. Specifically, levofloxacin can cause phototoxicity, toxic epidermal necrolysis,<a class="elsevierStyleCrossRef" href="#bib0055"><span class="elsevierStyleSup">1</span></a> drug reaction with eosinophilia and systemic symptoms (DRESS) syndrome,<a class="elsevierStyleCrossRef" href="#bib0060"><span class="elsevierStyleSup">2</span></a> fixed drug eruption,<a class="elsevierStyleCrossRef" href="#bib0065"><span class="elsevierStyleSup">3</span></a> and leukocytoclastic vasculitis,<a class="elsevierStyleCrossRef" href="#bib0070"><span class="elsevierStyleSup">4</span></a> among other conditions. However, no association between pigmentary disorders and levofloxacin use has been previously reported.</p><p id="par0030" class="elsevierStylePara elsevierViewall">To date, lesions similar to those of our patient have been attributed in almost all cases to minocycline, which causes pigmentation disorders in up to 50% of patients undergoing prolonged treatment.<a class="elsevierStyleCrossRefs" href="#bib0075"><span class="elsevierStyleSup">5,6</span></a> We have found only 2 descriptions of patients with blackish-blue lesions similar to those of our patient caused by levofloxacin. In one of those patients, the backs of the hands as well as the legs were affected. In both cases, the histological findings corresponded to those of our patient, and the lesions improved after discontinuation of levofloxacin therapy.<a class="elsevierStyleCrossRefs" href="#bib0085"><span class="elsevierStyleSup">7,8</span></a> A third report describes a case almost identical to ours that was caused by pefloxacin treatment and in which subsequent exposure to norfloxacin resulted in lesion recurrence.<a class="elsevierStyleCrossRef" href="#bib0095"><span class="elsevierStyleSup">9</span></a></p><p id="par0035" class="elsevierStylePara elsevierViewall">Our patient had been previously diagnosed with PPD, which worsened after beginning levofloxacin treatment. We have found no descriptions in the literature of PPD secondary to treatment with levofloxacin or other quinolones that could explain this disimprovement. Furthermore, Perls staining of the biopsy sample revealed positive staining exclusively inside macrophages, and not in the stroma, as would be expected in PPD. Therefore, we propose that the patient's condition was independent of the underlying PPD and mainly due to levofloxacin treatment.</p><p id="par0040" class="elsevierStylePara elsevierViewall">We believe that this case is of particular interest because it resembles, but is distinct from, pigmentation that typically occurs following minocycline treatment. The mechanism by which these cutaneous pigmentary alterations occur is unclear. In the case of minocycline-associated pigmentation the nature of the pigmented particles within the macrophages is unknown. Depending on the type of pigmentation, of which 3 distinct forms are described, histology shows dermal granules that are either free or located inside macrophages and contain iron and melanin, as revealed by Perls and Masson Fontana staining, respectively. Positive von Kossa staining, indicating the presence of calcium compounds, has been described in some cases.<a class="elsevierStyleCrossRef" href="#bib0100"><span class="elsevierStyleSup">10</span></a> Proposed explanations to account for the presence of these pigmented particles include the deposition of different types of drug metabolites, the presence of iron chelators within melanophages, and increases in the production of intracellular melanin.<a class="elsevierStyleCrossRef" href="#bib0085"><span class="elsevierStyleSup">7</span></a> In the case of levofloxacin-induced pigmentation it is difficult to draw conclusions owing to the paucity of cases described. Perls staining was positive in our patient and in the 2 previously described cases. Masson Fontana staining was also positive in the case described by Garval and coworkers,<a class="elsevierStyleCrossRef" href="#bib0085"><span class="elsevierStyleSup">7</span></a> but was negative in our patient, as was von Kossa staining, which was not described in either of the 2 published case reports. The study of additional similar cases would help to further our understanding of this unusual entity.</p></span><span id="sec0015" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0015">Conclusion</span><p id="par0045" class="elsevierStylePara elsevierViewall">We report a rare case of striking cutaneous pigmentation caused by levofloxacin treatment. This case underscores the importance of taking changes in the patient's usual medication into account when examining possible skin lesions.</p></span><span id="sec0020" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0020">Conflicts of Interest</span><p id="par0050" class="elsevierStylePara elsevierViewall">The authors declare that they have no conflicts of interest.</p></span></span>" "textoCompletoSecciones" => array:1 [ "secciones" => array:6 [ 0 => array:2 [ "identificador" => "sec0005" "titulo" => "Case Description" ] 1 => array:2 [ "identificador" => "sec0010" "titulo" => "Discussion" ] 2 => array:2 [ "identificador" => "sec0015" "titulo" => "Conclusion" ] 3 => array:2 [ "identificador" => "sec0020" "titulo" => "Conflicts of Interest" ] 4 => array:2 [ "identificador" => "xack429036" "titulo" => "Acknowledgments" ] 5 => array:1 [ "titulo" => "References" ] ] ] "pdfFichero" => "main.pdf" "tienePdf" => true "fechaRecibido" => "2017-12-14" "fechaAceptado" => "2018-04-08" "NotaPie" => array:1 [ 0 => array:2 [ "etiqueta" => "☆" "nota" => "<p class="elsevierStyleNotepara" id="npar0005">Please cite this article as: Castellanos-González M, González Morales ML, González-Granda Villalobos J. Levofloxacin-Induced Hyperpigmentation. Actas Dermosifiliogr. 2019;110:700–701.</p>" ] ] "multimedia" => array:3 [ 0 => array:7 [ "identificador" => "fig0005" "etiqueta" => "Figure 1" "tipo" => "MULTIMEDIAFIGURA" "mostrarFloat" => true "mostrarDisplay" => false "figura" => array:1 [ 0 => array:4 [ "imagen" => "gr1.jpeg" "Alto" => 718 "Ancho" => 955 "Tamanyo" => 178050 ] ] "descripcion" => array:1 [ "en" => "<p id="spar0005" class="elsevierStyleSimplePara elsevierViewall">Bilateral, symmetric, blackish pigmentation with irregular borders on the anterolateral aspects of both legs.</p>" ] ] 1 => array:7 [ "identificador" => "fig0010" "etiqueta" => "Figure 2" "tipo" => "MULTIMEDIAFIGURA" "mostrarFloat" => true "mostrarDisplay" => false "figura" => array:1 [ 0 => array:4 [ "imagen" => "gr2.jpeg" "Alto" => 463 "Ancho" => 1255 "Tamanyo" => 298543 ] ] "descripcion" => array:1 [ "en" => "<p id="spar0010" class="elsevierStyleSimplePara elsevierViewall">A, Abundant siderophages in the deepest areas of the dermis (hematoxylin-eosin, original magnification ×20). Cytoplasm containing slightly refringent golden-brown granules. B, Positive Perls staining (iron), revealing bluish, granular cytoplasm inside the macrophages.</p>" ] ] 2 => array:7 [ "identificador" => "fig0015" "etiqueta" => "Figure 3" "tipo" => "MULTIMEDIAFIGURA" "mostrarFloat" => true "mostrarDisplay" => false "figura" => array:1 [ 0 => array:4 [ "imagen" => "gr3.jpeg" "Alto" => 640 "Ancho" => 955 "Tamanyo" => 91398 ] ] "descripcion" => array:1 [ "en" => "<p id="spar0015" class="elsevierStyleSimplePara elsevierViewall">Significant lesion improvement and decreased pigment intensity after suspension of levofloxacin treatment.</p>" ] ] ] "bibliografia" => array:2 [ "titulo" => "References" "seccion" => array:1 [ 0 => array:2 [ "identificador" => "bibs0015" "bibliografiaReferencia" => array:10 [ 0 => array:3 [ "identificador" => "bib0055" "etiqueta" => "1" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Levofloxacin induced toxic epidermal necrolysis: successful therapy with omalizumab (Anti-IgE) and pulse prednisolone" "autores" => array:1 [ 0 => array:2 [ "etal" => false "autores" => array:5 [ 0 => "R. 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| Year/Month | Html | Total | |
|---|---|---|---|
| 2024 November | 15 | 15 | 30 |
| 2024 October | 143 | 66 | 209 |
| 2024 September | 116 | 35 | 151 |
| 2024 August | 158 | 58 | 216 |
| 2024 July | 130 | 41 | 171 |
| 2024 June | 106 | 29 | 135 |
| 2024 May | 100 | 32 | 132 |
| 2024 April | 103 | 31 | 134 |
| 2024 March | 113 | 40 | 153 |
| 2024 February | 100 | 45 | 145 |
| 2024 January | 130 | 34 | 164 |
| 2023 December | 112 | 23 | 135 |
| 2023 November | 191 | 32 | 223 |
| 2023 October | 161 | 35 | 196 |
| 2023 September | 174 | 38 | 212 |
| 2023 August | 148 | 24 | 172 |
| 2023 July | 163 | 39 | 202 |
| 2023 June | 112 | 31 | 143 |
| 2023 May | 174 | 32 | 206 |
| 2023 April | 129 | 27 | 156 |
| 2023 March | 188 | 37 | 225 |
| 2023 February | 172 | 40 | 212 |
| 2023 January | 128 | 38 | 166 |
| 2022 December | 150 | 36 | 186 |
| 2022 November | 134 | 37 | 171 |
| 2022 October | 133 | 34 | 167 |
| 2022 September | 118 | 50 | 168 |
| 2022 August | 74 | 36 | 110 |
| 2022 July | 136 | 44 | 180 |
| 2022 June | 62 | 25 | 87 |
| 2022 May | 151 | 35 | 186 |
| 2022 April | 195 | 38 | 233 |
| 2022 March | 221 | 53 | 274 |
| 2022 February | 183 | 31 | 214 |
| 2022 January | 246 | 42 | 288 |
| 2021 December | 158 | 42 | 200 |
| 2021 November | 159 | 44 | 203 |
| 2021 October | 146 | 48 | 194 |
| 2021 September | 133 | 41 | 174 |
| 2021 August | 142 | 37 | 179 |
| 2021 July | 146 | 20 | 166 |
| 2021 June | 115 | 27 | 142 |
| 2021 May | 171 | 34 | 205 |
| 2021 April | 224 | 95 | 319 |
| 2021 March | 124 | 40 | 164 |
| 2021 February | 73 | 28 | 101 |
| 2021 January | 58 | 16 | 74 |
| 2020 December | 58 | 17 | 75 |
| 2020 November | 64 | 18 | 82 |
| 2020 October | 64 | 10 | 74 |
| 2020 September | 44 | 11 | 55 |
| 2020 August | 43 | 19 | 62 |
| 2020 July | 31 | 16 | 47 |
| 2020 June | 33 | 18 | 51 |
| 2020 May | 62 | 21 | 83 |
| 2020 April | 59 | 16 | 75 |
| 2020 March | 25 | 14 | 39 |
| 2020 February | 10 | 12 | 22 |
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