Painful generalized erythematous patches: A very rare cutaneous adverse effect of pemetrexed

Castellanos-González, María; Ballesteros Bargues, Javier

doi:10.1016/j.medcle.2016.02.049

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In some cases, they can mimic other diseases, making its diagnose difficult and causing the patient to receive treatments that do not result in any improvement. In addition, sometimes, its onset requires the change or discontinuation of the treatment. Therefore, it is important to know these entities, so as to avoid misdiagnosis and improve patient treatment.One example is the occurrence of oedema associated with erythema in the lower limbs, simulating cellulitis or erysipelas in patients receiving pemetrexed, which has been recently described, having only a few cases published to date. The case presented corresponds to the first case published in Spanish.The patient is a 70-year-old male, with a history of stage IV non-small cell lung carcinoma (NSCLC), who had initially been treated with pemetrexed in combination with cisplatin, and that in the last five months was only receiving pemetrexed as maintenance therapy. 2 erythematous and oedematous plaques, with well-defined borders, appeared two days after receiving his fifth treatment cycle, distributed symmetrically in the ankles and the back of the foot. The patient reported severe pain and even had trouble walking.On physical examination, there were no signs of an increased local temperature or lesions in another location. The oral and genital mucosa were normal. No fever or other systemic symptoms were present. The patient had been treated with topical corticosteroids without clear improvement.The blood count showed 11.4g/dl haemoglobin and 448×109/l platelets, neutrophils were within the normal range. A skin ultrasound was carried out, which only found oedema in the subcutaneous cellular tissue without data indicative of deep vein thrombosis.The diagnosis was pemetrexed-induced cutaneous toxicity. Because of the clinical stability of the underlying disease, it was decided to delay the next cycle of treatment and recommend lifting the lower limbs and medium compression stockings, with a significant improvement for the patient.Pemetrexed is approved by the FDA as a first line treatment for malignant mesothelioma and as second-line for advanced and metastatic NSCLC, combined with cisplatin or alone.<a class="elsevierStyleCrossRef" href="#bib0030">1</a> It is generally well tolerated, and although its use may result in the appearance of different side effects, these are generally mild. Alterations at cutaneous level have been described in approximately 17–22% of the cases, appearing as rash, desquamative diffuse hyperpigmentation, urticarial vasculitis, acute generalized exanthematous pustulosis and, less often, toxic epidermal necrolysis.<a class="elsevierStyleCrossRef" href="#bib0035">2</a> Frouin et al. described 3 patients with symptoms of asteatotic eczema, with a biopsy compatible with interface dermatitis, after 5–7 days with pemetrexed.<a class="elsevierStyleCrossRef" href="#bib0040">3</a>A search was carried out in PubMed using different combinations that included “pemetrexed”, “cutaneous”, “skin”, “erythema” and “adverse effect”, finding articles on these subjects from 2007 to 2014. Some publications describing the presentation of an erythematous oedema in the lower limbs in patients receiving this medication have started to appear in recent years, which was previously unknown, and often initially misdiagnosed as cellulite and/or as erysipelas.Vitiello et al. were the first to describe, in 2011, 2 patients receiving pemetrexed and presenting a similar picture to that of our patient. Diagnosed as bilateral cellulite to start with, they were initially prescribed with vancomycin, followed by piperacillin/tazobactam and cefazolin, without any improvement. The fact that it was bilateral and did not respond well to broad-spectrum antibiotics led them to rethink the diagnosis and to establish a new manifestation of pemetrexed-induced cutaneous toxicity, previously unknown.<a class="elsevierStyleCrossRef" href="#bib0045">4</a> Katsenos et al., in their paper, discussed the case of a patient with similar symptoms while receiving this medication and proposed the discontinuation of therapy for its control and the use of topical corticosteroids to improve it.<a class="elsevierStyleCrossRef" href="#bib0050">5</a>The mechanism by which skin toxicity occurs is poorly understood. Some studies show that it may be related to the patient's nutrition status and the incidence could be reduced with the intake of folic acid and prophylactic administration of systemic corticoid therapy.<a class="elsevierStyleCrossRef" href="#bib0035">2</a> However, our patient was receiving both medications when the clinical features appeared." 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Gaudy-Marqueste" 5 => "M.A. Richard" ] ] ] ] ] "host" => array:1 [ 0 => array:1 [ "Revista" => array:6 [ "tituloSerie" => "Rev Mal Respir" "fecha" => "2007" "volumen" => "24" "paginaInicial" => "635" "paginaFinal" => "638" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/17519817" "web" => "Medline" ] ] ] ] ] ] ] ] 1 => array:3 [ "identificador" => "bib0035" "etiqueta" => "2" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Dermatologic toxicity of chemotherapeutic agents" "autores" => array:1 [ 0 => array:2 [ "etal" => false "autores" => array:3 [ 0 => "A.S. Payne" 1 => "W.D. James" 2 => "R.B. Weiss" ] ] ] ] ] "host" => array:1 [ 0 => array:2 [ "doi" => "10.1053/j.seminoncol.2005.11.004" "Revista" => array:6 [ "tituloSerie" => "Semin Oncol" "fecha" => "2006" "volumen" => "33" "paginaInicial" => "86" "paginaFinal" => "97" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/16473647" "web" => "Medline" ] ] ] ] ] ] ] ] 2 => array:3 [ "identificador" => "bib0040" "etiqueta" => "3" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Asteatotic eczema (‘eczema craquelé’) with histopathological interface dermatitis: a new cutaneous reaction following pemetrexed" "autores" => array:1 [ 0 => array:2 [ "etal" => true "autores" => array:6 [ 0 => "E. Frouin" 1 => "G. Sebille" 2 => "S. Freudenberger" 3 => "B. Menecier" 4 => "E. Quoix" 5 => "B. Cribier" ] ] ] ] ] "host" => array:1 [ 0 => array:2 [ "doi" => "10.1111/j.1365-2133.2011.10777.x" "Revista" => array:6 [ "tituloSerie" => "Br J Dermatol" "fecha" => "2012" "volumen" => "166" "paginaInicial" => "1359" "paginaFinal" => "1360" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/22182200" "web" => "Medline" ] ] ] ] ] ] ] ] 3 => array:3 [ "identificador" => "bib0045" "etiqueta" => "4" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Painful generalized erythematous patches: a severe and unusual cutaneous reaction to pemetrexed" "autores" => array:1 [ 0 => array:2 [ "etal" => false "autores" => array:3 [ 0 => "M. Vitiello" 1 => "P. Romanelli" 2 => "F.A. Kerdel" ] ] ] ] ] "host" => array:1 [ 0 => array:2 [ "doi" => "10.1016/j.jaad.2010.01.003" "Revista" => array:6 [ "tituloSerie" => "J Am Acad Dermatol" "fecha" => "2011" "volumen" => "65" "paginaInicial" => "243" "paginaFinal" => "244" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/21679840" "web" => "Medline" ] ] ] ] ] ] ] ] 4 => array:3 [ "identificador" => "bib0050" "etiqueta" => "5" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Pemetrexed-induced cellulitis: a rare toxicity in non-small cell lung cancer treatment" "autores" => array:1 [ 0 => array:2 [ "etal" => false "autores" => array:3 [ 0 => "S. Katsenos" 1 => "A. Psara" 2 => "C. Panagou" ] ] ] ] ] "host" => array:1 [ 0 => array:2 [ "doi" => "10.1177/1078155212438453" "Revista" => array:6 [ "tituloSerie" => "J Oncol Pharm Pract" "fecha" => "2013" "volumen" => "19" "paginaInicial" => "93" "paginaFinal" => "94" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/22357637" "web" => "Medline" ] ] ] ] ] ] ] ] ] ] ] ] ] "idiomaDefecto" => "en" "url" => "/23870206/0000014500000008/v1_201604030058/S2387020616001145/v1_201604030058/en/main.assets" "Apartado" => array:4 [ "identificador" => "43309" "tipo" => "SECCION" "en" => array:2 [ "titulo" => "Letters to the Editor" "idiomaDefecto" => true ] "idiomaDefecto" => "en" ] "PDF" => "https://static.elsevier.es/multimedia/23870206/0000014500000008/v1_201604030058/S2387020616001145/v1_201604030058/en/main.pdf?idApp=UINPBA00004N&text.app=https://www.elsevier.es/" "EPUB" => "https://multimedia.elsevier.es/PublicationsMultimediaV1/item/epub/S2387020616001145?idApp=UINPBA00004N"]

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Vol. 145. Issue 8.

Pages 372-373 (October 2015)

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