Pulmonary eosinophilia associated with valproic acid

San Miguel López de Uralde, Sonia María; Prieto Peraita, Marta; Blanco Bengoechea, Emilio Javier

doi:10.1016/j.medcle.2014.07.007

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We present the case of a female patient who developed eosinophilic pleural effusion, with bilateral pulmonary infiltrates.The patient is a 39-year old female, who had smoked one pack of cigarettes/day (for the last 4 weeks). Previously, she had been a former smoker from 20 years of age, with a cumulative index of 4 packs of cigarettes/year.She was admitted to the Psychiatric Hospital for stabilisation after several serious suicide attempts. She was diagnosed with an adjustment disorder and symptoms of anxiety and depression and treated with lactulose, clonazepam (5mg/day), valproic acid (500mg/12h) and lormetazepam (rescue therapy). The month before, during her previous admission to the Acute Psychiatric Unit, treatment with valproic acid as an impulse modulator had been started, since the patient also had a family history of bipolar disorder.Over the course of 48h, the patient developed the appearance of symptoms of slowly progressive dyspnoea with acute respiratory failure and few previous signs of infection. Consequently, she was referred to the aforementioned hospital.On admission to Pneumology, the patient had bilateral pulmonary infiltrates with bilateral pleural effusion, and progressive respiratory failure which, added to the appearance of high fever during the first 24h, supported the broad-spectrum antibiotic treatment that was administered from the beginning. Analytical tests showed an increase in C-reactive protein, left shift leukocytosis, a negative urinary antigen test for pneumococcus and Legionella, and negative serologies for Mycoplasma, Legionella, Coxiella and Chlamydophila.Due to the presence of bilateral pleural effusion, two diagnostic thoracocentesis were performed, in which liquid with eosinophilic exudate characteristics (11% and 16% of eosinophils, respectively) was evacuated. In both thoracocentesis, we also performed an ADA (11 and 40, respectively), cultures for aerobic and anaerobic organisms, and microbacteria (all negative), plus cytologies, which also proved an eosinophilic inflammatory infiltrate without malignant characteristics. In the same way, sputum cultures, pleural liquid and blood cultures came back negative. Bronchoalveolar lavage was performed, which also informed about 36% of the eosinophils (cultures and cytologies were also negative).On the basis of these findings, autoimmune disease was discarded (negative RF, ANA and ANCA) and a serous precipitin study was requested, which was also negative.Antibiotic treatment was continued, valproic acid was suspended and high doses of corticotherapy were added. The patient experienced a rapid clinical and radiological improvement, allowing the withdrawal of oxygen therapy and her discharge from the hospital.Today, the patient, still on corticotherapy, remains asymptomatic and the previously described radiological alterations have been completely resolved.Having discarded other causes of eosinophilic pleural effusion, and in view of clinical progress, we conclude that valproic acid was responsible for the effusion and pulmonary infiltrates, which were definitively resolved. This adverse reaction reaches a score of 6 in Naranjo's algorithm, which allows us to define it as possible. All the above is reinforced by a systematic search of PubMed to seek out titles published between 2000 and 2014 that matched the terms “valproic acid” with “adverse drug reactions” or “eosinophilic pneumonia” or “drug eosinophilic reaction.” Our suspicion of adverse reaction was communicated to the Basque Pharmacovigilance Centre by the yellow card scheme.Several cases have been described in which pleural effusion<a class="elsevierStyleCrossRefs" href="#bib0030">1–3</a> with eosinophilic prevalence has been associated with valproic acid treatment. Most of them had no associated pulmonary involvement, as distinct to our case. In all the cases in which pulmonary infiltrates are described, these arise from a pulmonary haemorrhage<a class="elsevierStyleCrossRef" href="#bib0045">4</a> or a pneumonitis<a class="elsevierStyleCrossRef" href="#bib0050">5</a> in the context of a DRESS syndrome with organic involvement.Eosinophilic pleural effusion associated with valproic acid can be present with peripheral eosinophilia,<a class="elsevierStyleCrossRef" href="#bib0030">1</a> which also disappears after the withdrawal of the drug. The presence of fever and leukocytosis with peripheral deviations does not discount valproic acid as responsible for the symptoms, even though it initially leans towards an infectious origin. The mechanism<a class="elsevierStyleCrossRef" href="#bib0035">2</a> by which valproic acid can cause the appearance of eosinophilic pleural effusion is unknown, but it can happen at any time during treatment, not necessarily at the onset or with a modification of the dose, and with any level of dose, not necessarily a high dosage." "pdfFichero" => "main.pdf" "tienePdf" => true "NotaPie" => array:1 [ 0 => array:2 [ "etiqueta" => "☆" "nota" => "Please cite this article as: San Miguel López de Uralde SM, Prieto Peraita M, Blanco Bengoechea EJ. Eosinofilia pulmonar asociada a ácido valproico. Med Clin (Barc). 2015;144:527–528." ] ] "bibliografia" => array:2 [ "titulo" => "References" "seccion" => array:1 [ 0 => array:2 [ "identificador" => "bibs0005" "bibliografiaReferencia" => array:5 [ 0 => array:3 [ "identificador" => "bib0030" "etiqueta" => "1" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Sodium valproate as a cause of recurrent transudative pleural effusion: a case report" "autores" => array:1 [ 0 => array:2 [ "etal" => false "autores" => array:6 [ 0 => "S. Tryfon" 1 => "M. Saroglou" 2 => "K. Kazanas" 3 => "C. Mermigkis" 4 => "K. Psathakis" 5 => "N. Galanis" ] ] ] ] ] "host" => array:1 [ 0 => array:2 [ "doi" => "10.1186/1752-1947-3-51" "Revista" => array:5 [ "tituloSerie" => "J Med Case Rep" "fecha" => "2009" "volumen" => "3" "paginaInicial" => "51" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/19203367" "web" => "Medline" ] ] ] ] ] ] ] ] 1 => array:3 [ "identificador" => "bib0035" "etiqueta" => "2" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Valproic acid-induced eosinophilic pleural effusion: a case report and review of the literature" "autores" => array:1 [ 0 => array:2 [ "etal" => false "autores" => array:3 [ 0 => "W. Bullington" 1 => "S.A. Sahn" 2 => "M.A. Judson" ] ] ] ] ] "host" => array:1 [ 0 => array:2 [ "doi" => "10.1097/MAJ.0b013e31805339ae" "Revista" => array:6 [ "tituloSerie" => "Am J Med Sci" "fecha" => "2007" "volumen" => "333" "paginaInicial" => "290" "paginaFinal" => "292" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/17505171" "web" => "Medline" ] ] ] ] ] ] ] ] 2 => array:3 [ "identificador" => "bib0040" "etiqueta" => "3" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Valproic acid-induced eosinophilic pleural effusion: a case report and review of the literature" "autores" => array:1 [ 0 => array:2 [ "etal" => false "autores" => array:5 [ 0 => "Z. Kamenetsky" 1 => "N. Da’as" 2 => "Y. Esayag" 3 => "Y. Kleinman" 4 => "N. Samuels" ] ] ] ] ] "host" => array:1 [ 0 => array:2 [ "doi" => "10.1097/NRL.0b013e31823d7a6d" "Revista" => array:6 [ "tituloSerie" => "Neurologist" "fecha" => "2012" "volumen" => "18" "paginaInicial" => "39" "paginaFinal" => "40" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/22217614" "web" => "Medline" ] ] ] ] ] ] ] ] 3 => array:3 [ "identificador" => "bib0045" "etiqueta" => "4" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Adverse drug reactions induced by valproic acid" "autores" => array:1 [ 0 => array:2 [ "etal" => false "autores" => array:2 [ 0 => "R.M. Nanau" 1 => "M.G. Neuman" ] ] ] ] ] "host" => array:1 [ 0 => array:2 [ "doi" => "10.1016/j.clinbiochem.2013.06.012" "Revista" => array:6 [ "tituloSerie" => "Clin Biochem" "fecha" => "2013" "volumen" => "46" "paginaInicial" => "1323" "paginaFinal" => "1338" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/23792104" "web" => "Medline" ] ] ] ] ] ] ] ] 4 => array:3 [ "identificador" => "bib0050" "etiqueta" => "5" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Successful treatment of antiepileptic drug-induced DRESS syndrome with pulse methylprednisolone" "autores" => array:1 [ 0 => array:2 [ "etal" => false "autores" => array:5 [ 0 => "C. Kocaoglu" 1 => "C. Cilasun" 2 => "E.S. Solak" 3 => "G.S. Kurtipek" 4 => "S. Arslan" ] ] ] ] ] "host" => array:1 [ 0 => array:2 [ "doi" => "10.1155/2013/928910" "Revista" => array:5 [ "tituloSerie" => "Case Rep Pediatr" "fecha" => "2013" "volumen" => "2013" "paginaInicial" => "928910" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/23691411" "web" => "Medline" ] ] ] ] ] ] ] ] ] ] ] ] ] "idiomaDefecto" => "en" "url" => "/23870206/0000014400000011/v1_201602060036/S2387020615002600/v1_201602060036/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/23870206/0000014400000011/v1_201602060036/S2387020615002600/v1_201602060036/en/main.pdf?idApp=UINPBA00004N&text.app=https://www.elsevier.es/" "EPUB" => "https://multimedia.elsevier.es/PublicationsMultimediaV1/item/epub/S2387020615002600?idApp=UINPBA00004N"]

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Vol. 144. Issue 11.

Pages 527-528 (June 2015)

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