Scientific Letter
Thiamazole-Induced Agranulocytosis Leading to Abscessus Pneumonia-Rare, But Challenging
Agranulocitosis inducida por tiamazol que lleva a absceso pumonar. Un reto infrecuente
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Un reto infrecuente" ] ] "contieneTextoCompleto" => array:1 [ "en" => true ] "contienePdf" => array:1 [ "en" => true ] "resumenGrafico" => array:2 [ "original" => 0 "multimedia" => array:7 [ "identificador" => "fig0005" "etiqueta" => "Fig. 1" "tipo" => "MULTIMEDIAFIGURA" "mostrarFloat" => true "mostrarDisplay" => false "figura" => array:1 [ 0 => array:4 [ "imagen" => "gr1.jpeg" "Alto" => 987 "Ancho" => 2083 "Tamanyo" => 262962 ] ] "descripcion" => array:1 [ "en" => "<p id="spar0005" class="elsevierStyleSimplePara elsevierViewall">Chest X ray showing abscessus pneumonia (A); HRCT demonstrated extensive pulmonary abscessus over both the lungs (B).</p>" ] ] ] "autores" => array:1 [ 0 => array:2 [ "autoresLista" => "Biljana Lazovic, Vuk Andrejevic, Aleksandar Ivanovic, Vladimir Zugic" "autores" => array:4 [ 0 => array:2 [ "nombre" => "Biljana" "apellidos" => "Lazovic" ] 1 => array:2 [ "nombre" => "Vuk" "apellidos" => "Andrejevic" ] 2 => array:2 [ "nombre" => "Aleksandar" "apellidos" => "Ivanovic" ] 3 => array:2 [ "nombre" => "Vladimir" "apellidos" => "Zugic" ] ] ] ] ] "idiomaDefecto" => "en" "Traduccion" => array:1 [ "en" => array:9 [ "pii" => "S0300289617303940" "doi" => "10.1016/j.arbres.2017.10.005" "estado" => "S300" "subdocumento" => "" "abierto" => array:3 [ "ES" => true "ES2" => true "LATM" => true ] "gratuito" => true "lecturas" => array:1 [ "total" => 0 ] "idiomaDefecto" => "en" "EPUB" => "https://multimedia.elsevier.es/PublicationsMultimediaV1/item/epub/S0300289617303940?idApp=UINPBA00003Z" ] ] "EPUB" => "https://multimedia.elsevier.es/PublicationsMultimediaV1/item/epub/S1579212918301423?idApp=UINPBA00003Z" "url" => "/15792129/0000005400000005/v1_201804290447/S1579212918301423/v1_201804290447/en/main.assets" ] ] "itemSiguiente" => array:19 [ "pii" => "S0300289617303976" "issn" => "03002896" "doi" => "10.1016/j.arbres.2017.10.008" "estado" => "S300" "fechaPublicacion" => "2018-05-01" "aid" => "1751" "copyright" => "SEPAR" "documento" => "simple-article" "crossmark" => 1 "subdocumento" => "crp" "cita" => "Arch Bronconeumol. 2018;54:290-2" "abierto" => array:3 [ "ES" => true "ES2" => true "LATM" => true ] "gratuito" => true "lecturas" => array:2 [ "total" => 8385 "formatos" => array:3 [ "EPUB" => 154 "HTML" => 7451 "PDF" => 780 ] ] "es" => array:11 [ "idiomaDefecto" => true "cabecera" => "<span class="elsevierStyleTextfn">Carta científica</span>" "titulo" => "Expresión de PD-L1 en muestras de cáncer pulmonar no microcítico obtenidas por EBUS-TBNA" "tienePdf" => "es" "tieneTextoCompleto" => "es" "paginas" => array:1 [ 0 => array:2 [ "paginaInicial" => "290" "paginaFinal" => "292" ] ] "titulosAlternativos" => array:1 [ "en" => array:1 [ "titulo" => "PD-L1 Expression in a Non-Small Cell Lung Cancer Specimen Obtained by EBUS-TBNA" ] ] "contieneTextoCompleto" => array:1 [ "es" => true ] "contienePdf" => array:1 [ "es" => true ] "resumenGrafico" => array:2 [ "original" => 0 "multimedia" => array:7 [ "identificador" => "fig0005" "etiqueta" => "Figura 1" "tipo" => "MULTIMEDIAFIGURA" "mostrarFloat" => true "mostrarDisplay" => false "figura" => array:1 [ 0 => array:4 [ "imagen" => "gr1.jpeg" "Alto" => 1873 "Ancho" => 2500 "Tamanyo" => 729087 ] ] "descripcion" => array:1 [ "es" => "<p id="spar0005" class="elsevierStyleSimplePara elsevierViewall">Imágenes microscópicas del tumor en muestras obtenidas por EBUS-TBNA y de las respectivas tinciones inmunohistoquímicas con anticuerpo anti-PD-L1 E1L3N. 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"apellidos" => "Lazovic" "email" => array:1 [ 0 => "lazovic.biljana@gmail.com" ] "referencia" => array:3 [ 0 => array:2 [ "etiqueta" => "<span class="elsevierStyleSup">a</span>" "identificador" => "aff0005" ] 1 => array:2 [ "etiqueta" => "<span class="elsevierStyleSup">c</span>" "identificador" => "aff0015" ] 2 => array:2 [ "etiqueta" => "<span class="elsevierStyleSup">*</span>" "identificador" => "cor0005" ] ] ] 1 => array:3 [ "nombre" => "Vuk" "apellidos" => "Andrejevic" "referencia" => array:1 [ 0 => array:2 [ "etiqueta" => "<span class="elsevierStyleSup">a</span>" "identificador" => "aff0005" ] ] ] 2 => array:3 [ "nombre" => "Aleksandar" "apellidos" => "Ivanovic" "referencia" => array:1 [ 0 => array:2 [ "etiqueta" => "<span class="elsevierStyleSup">a</span>" "identificador" => "aff0005" ] ] ] 3 => array:3 [ "nombre" => "Vladimir" "apellidos" => "Zugic" "referencia" => array:2 [ 0 => array:2 [ "etiqueta" => "<span class="elsevierStyleSup">b</span>" "identificador" => "aff0010" ] 1 => array:2 [ "etiqueta" => "<span class="elsevierStyleSup">c</span>" "identificador" => "aff0015" ] ] ] ] "afiliaciones" => array:3 [ 0 => array:3 [ "entidad" => "University Clinical Center “Zemun”, Belgrade, Serbia" "etiqueta" => "a" "identificador" => "aff0005" ] 1 => array:3 [ "entidad" => "Clinic for Lung Diseases, Clinical Center of SERBIA, Belgrade, Serbia" "etiqueta" => "b" "identificador" => "aff0010" ] 2 => array:3 [ "entidad" => "School of Medicine, University of Belgrade, Serbia" "etiqueta" => "c" "identificador" => "aff0015" ] ] "correspondencia" => array:1 [ 0 => array:3 [ "identificador" => "cor0005" "etiqueta" => "⁎" "correspondencia" => "Corresponding author." ] ] ] ] "titulosAlternativos" => array:1 [ "es" => array:1 [ "titulo" => "Agranulocitosis inducida por tiamazol que lleva a absceso pumonar. Un reto infrecuente" ] ] "resumenGrafico" => array:2 [ "original" => 0 "multimedia" => array:7 [ "identificador" => "fig0005" "etiqueta" => "Fig. 1" "tipo" => "MULTIMEDIAFIGURA" "mostrarFloat" => true "mostrarDisplay" => false "figura" => array:1 [ 0 => array:4 [ "imagen" => "gr1.jpeg" "Alto" => 987 "Ancho" => 2083 "Tamanyo" => 262962 ] ] "descripcion" => array:1 [ "en" => "<p id="spar0005" class="elsevierStyleSimplePara elsevierViewall">Chest X ray showing abscessus pneumonia (A); HRCT demonstrated extensive pulmonary abscessus over both the lungs (B).</p>" ] ] ] "textoCompleto" => "<span class="elsevierStyleSections"><p id="par0005" class="elsevierStylePara elsevierViewall">The antithyroid agents (carbimazole, methimazole, thiamazole, propylthiouracil and benzylthiouracile) are the drug class that is associated with a high risk of agranulocytosis. Isolated severe neutropenia or agranulocytosis, defined as an absolute neutrophil count of less than 0.5<span class="elsevierStyleHsp" style=""></span>×<span class="elsevierStyleHsp" style=""></span>10<span class="elsevierStyleSup">9</span>/L occurring in a subject treated with antithyroid agents should be considered as a drug-induced agranulocytosis, until proven otherwise. Agranulocytosis is rare and may develop in 0.2–0.5% patients using antithyroid drug therapy.<a class="elsevierStyleCrossRef" href="#bib0040"><span class="elsevierStyleSup">1</span></a> The clinical evidence of infectious complications associated with antithyroid-drug-induced (ATD) agranulocytosis is usually symptomatology in fever (92%) and sore throat (85%), pharyngitis (46%), acute tonsillitis (38%), pneumonia (15%) and urinary tract infection (8%).<a class="elsevierStyleCrossRef" href="#bib0045"><span class="elsevierStyleSup">2</span></a></p><p id="par0010" class="elsevierStylePara elsevierViewall">A 61-year-old, Caucasian female was admitted to the emergency department with complaints with fever up to 39<span class="elsevierStyleHsp" style=""></span>°C, chills and cough and general weaknesses which started a day after discharge from other hospital (hematology department) where she was treated for gastric pain and neutropenia (leukocyte was 1.2<span class="elsevierStyleHsp" style=""></span>×<span class="elsevierStyleHsp" style=""></span>10<span class="elsevierStyleSup">9</span>/L, neutrophils 0.03<span class="elsevierStyleHsp" style=""></span>×<span class="elsevierStyleHsp" style=""></span>10<span class="elsevierStyleSup">9</span>/L) induced by thiamazole. She was afebrile. Chest X ray was normal. She recovered successfully after 10th days with granulocyte colony-stimulating factor and discharged from hospital. Previously, she has been with hyperthyroidism for 21 years, six month ago before hospital admission her therapy was changed to thiamazole.</p><p id="par0015" class="elsevierStylePara elsevierViewall">On admission to our hospital, her vital signs were within normal limits, except for a temperature of 38.8<span class="elsevierStyleHsp" style=""></span>°C and respiratory rate 22/min. Physical examination revealed atonic bilateral equal air entry with no added rhonchi or wheezing. Cardiovascular and neurological examinations revealed no abnormalities. The abdomen was soft and non-tender, without palpable visceromegaly. Her initial chest X-ray showed a multifocal abscessing pneumonia (<a class="elsevierStyleCrossRef" href="#fig0005">Fig. 1</a>A). CT was immediately performed which confirmed multifocal abscessus in lungs (<a class="elsevierStyleCrossRef" href="#fig0005">Fig. 1</a>B). Admission labs revealed hemoglobin 12.5 gm/dL, white count 8.8<span class="elsevierStyleHsp" style=""></span>×<span class="elsevierStyleHsp" style=""></span>10<span class="elsevierStyleSup">9</span>/L, neutrophil 5.59<span class="elsevierStyleHsp" style=""></span>×<span class="elsevierStyleHsp" style=""></span>10<span class="elsevierStyleSup">9</span>, platelets count 197<span class="elsevierStyleHsp" style=""></span>×<span class="elsevierStyleHsp" style=""></span>10<span class="elsevierStyleSup">9</span>/L. Her serum sodium levels were 138<span class="elsevierStyleHsp" style=""></span>mEq/dL, and the blood urea nitrogen (BUN) and creatinine values were 20<span class="elsevierStyleHsp" style=""></span>mg/dL and 0.9<span class="elsevierStyleHsp" style=""></span>mg/dL respectively. C reactive protein (CRP) was 252<span class="elsevierStyleHsp" style=""></span>ng/ml, while procalcitonin was 78.7<span class="elsevierStyleHsp" style=""></span>μg/L. Arterial blood gas showed a pH of 7.30 and PaO<span class="elsevierStyleInf">2</span> of 60<span class="elsevierStyleHsp" style=""></span>mmHg, PCO<span class="elsevierStyleInf">2</span> 46<span class="elsevierStyleHsp" style=""></span>mmHg, SaO<span class="elsevierStyleInf">2</span> 90%.</p><elsevierMultimedia ident="fig0005"></elsevierMultimedia><p id="par0020" class="elsevierStylePara elsevierViewall">Initially, the patient was started empirically with broad-spectrum antibiotics: Vancomycin 1<span class="elsevierStyleHsp" style=""></span>g/12<span class="elsevierStyleHsp" style=""></span>h, Amikacin 1<span class="elsevierStyleHsp" style=""></span>g/12<span class="elsevierStyleHsp" style=""></span>g and Orvagyl 500<span class="elsevierStyleHsp" style=""></span>mg/8<span class="elsevierStyleHsp" style=""></span>h. Blood culture, throat culture, blood fungal culture, acid-fast bacillus blood culture, and urine culture were all negative. Despite antibiotics therapy, patient was febrile up to 38<span class="elsevierStyleHsp" style=""></span>°C, and in the absence of adequate laboratory as well as radiologically answer, therapy was changed into Meropenem 1<span class="elsevierStyleHsp" style=""></span>g/12<span class="elsevierStyleHsp" style=""></span>h and Orvagyl 500<span class="elsevierStyleHsp" style=""></span>mg/8<span class="elsevierStyleHsp" style=""></span>h. On third day, patient was afebrile and feeling better. Her CRP was 9.7<span class="elsevierStyleHsp" style=""></span>ng/ml, white count 11.2<span class="elsevierStyleHsp" style=""></span>×<span class="elsevierStyleHsp" style=""></span>10<span class="elsevierStyleSup">9</span>/L, platelets 210<span class="elsevierStyleHsp" style=""></span>×<span class="elsevierStyleHsp" style=""></span>10<span class="elsevierStyleSup">9</span>/L. During the following days, the patient's condition, and laboratory parameters improved in parallel with the neutrophil count. She received above mentioned therapy for fourteen days after she was discharged in good condition and radiological finding. She was released from the hospital with recommended Propylthiouracil 50<span class="elsevierStyleHsp" style=""></span>mg twice daily. She was regularly checked up by endocrinologist and pulmonologist with no relapse of disease.</p><p id="par0025" class="elsevierStylePara elsevierViewall">Antithyroid drugs, especially thioamides—including propylthiouracil, methimazole and carbimazole—have adverse hematological effects, ranging from mild leukopenia to agranulocytosis and aplastic anemia. Agranulocytosis, defined as a marked decrease in the number of granulocytes, frequently <500/μL, is a rare complication. Fever and sore throat are common symptoms of antithyroid drug induced agranulocytosis.<a class="elsevierStyleCrossRef" href="#bib0050"><span class="elsevierStyleSup">3</span></a> Patients with an absolute neutrophil count <100/μL tend to have a greater risk of infectious and fatal complications than do patients with a neutrophil count >100/μL. The mortality rate is greater in patients aged ≥65 years than in those aged <65 years.<a class="elsevierStyleCrossRef" href="#bib0055"><span class="elsevierStyleSup">4</span></a></p><p id="par0030" class="elsevierStylePara elsevierViewall">The lungs are the most common organ to be infected in febrile neutropenic patients. The chest radiograph is the standard initial investigation to look for pulmonary changes, but its sensitivity has been shown to be very low. High resolution computed tomography (HRCT) chest can detect the abnormality with a high degree of accuracy, as well as differentiate between different types of infections.<a class="elsevierStyleCrossRef" href="#bib0060"><span class="elsevierStyleSup">5</span></a> It is extremely useful in early detection or exclusion of a focus of infection and characterization of the focus. Exact etiological diagnosis is not possible in most of the cases, but identification of broad category of infective causes itself is very important for the appropriate therapy. Previous studies have proven that the most common cause of febrile condition is Pseudomonas aeruginosa.<a class="elsevierStyleCrossRef" href="#bib0060"><span class="elsevierStyleSup">5</span></a> Our case was different from previous described in literature, in its beginning, but similar in good prognosis after granulocyte colony-stimulating factor and empirical antibiotic therapy. However, the recovery time in our cases was slightly longer than in previous cases (14 vs. 6.8 days).<a class="elsevierStyleCrossRef" href="#bib0065"><span class="elsevierStyleSup">6</span></a> Nowadays, more people are undergoing surgical treatment as a permanent solution.<a class="elsevierStyleCrossRef" href="#bib0070"><span class="elsevierStyleSup">7</span></a></p><p id="par0035" class="elsevierStylePara elsevierViewall">In conclusion, ATD-induced agranulocytosis is rare, but the severity of this possibly life-threatening condition means its management is essential to a good prognosis. Our case suggests that patients with antithyroid drug-induced agranulocytosis who present with severe infections should be treated empirically with broad-spectrum antibiotics with antipseudomonal activity.</p><p id="par0040" class="elsevierStylePara elsevierViewall">Alternative way in patients with hyperthyroidisms is surgery or radioactive iodine which seem to be effective options to restore an euthyroid state. In fact, radioactive iodine was demonstrated as a successful option, with 88.8% of patients experiencing euthyroidism after treatment.</p></span>" "pdfFichero" => "main.pdf" "tienePdf" => true "multimedia" => array:1 [ 0 => array:7 [ "identificador" => "fig0005" "etiqueta" => "Fig. 1" "tipo" => "MULTIMEDIAFIGURA" "mostrarFloat" => true "mostrarDisplay" => false "figura" => array:1 [ 0 => array:4 [ "imagen" => "gr1.jpeg" "Alto" => 987 "Ancho" => 2083 "Tamanyo" => 262962 ] ] "descripcion" => array:1 [ "en" => "<p id="spar0005" class="elsevierStyleSimplePara elsevierViewall">Chest X ray showing abscessus pneumonia (A); HRCT demonstrated extensive pulmonary abscessus over both the lungs (B).</p>" ] ] ] "bibliografia" => array:2 [ "titulo" => "References" "seccion" => array:1 [ 0 => array:2 [ "identificador" => "bibs0015" "bibliografiaReferencia" => array:7 [ 0 => array:3 [ "identificador" => "bib0040" "etiqueta" => "1" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Antithyroid drug-induced agranulocytosis: state of the art on diagnosis and management" "autores" => array:1 [ 0 => array:2 [ "etal" => false "autores" => array:4 [ 0 => "N. 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| Year/Month | Html | Total | |
|---|---|---|---|
| 2024 November | 5 | 4 | 9 |
| 2024 October | 82 | 23 | 105 |
| 2024 September | 69 | 15 | 84 |
| 2024 August | 99 | 36 | 135 |
| 2024 July | 62 | 21 | 83 |
| 2024 June | 83 | 35 | 118 |
| 2024 May | 83 | 33 | 116 |
| 2024 April | 58 | 27 | 85 |
| 2024 March | 46 | 26 | 72 |
| 2024 February | 44 | 23 | 67 |
| 2023 March | 22 | 6 | 28 |
| 2023 February | 92 | 28 | 120 |
| 2023 January | 67 | 30 | 97 |
| 2022 December | 80 | 47 | 127 |
| 2022 November | 127 | 30 | 157 |
| 2022 October | 109 | 51 | 160 |
| 2022 September | 74 | 40 | 114 |
| 2022 August | 75 | 53 | 128 |
| 2022 July | 67 | 51 | 118 |
| 2022 June | 66 | 51 | 117 |
| 2022 May | 95 | 48 | 143 |
| 2022 April | 89 | 51 | 140 |
| 2022 March | 90 | 51 | 141 |
| 2022 February | 98 | 36 | 134 |
| 2022 January | 94 | 51 | 145 |
| 2021 December | 77 | 39 | 116 |
| 2021 November | 60 | 56 | 116 |
| 2021 October | 80 | 58 | 138 |
| 2021 September | 54 | 48 | 102 |
| 2021 August | 54 | 52 | 106 |
| 2021 July | 54 | 43 | 97 |
| 2021 June | 89 | 79 | 168 |
| 2021 May | 101 | 50 | 151 |
| 2021 April | 178 | 116 | 294 |
| 2021 March | 95 | 31 | 126 |
| 2021 February | 93 | 38 | 131 |
| 2021 January | 71 | 38 | 109 |
| 2020 December | 65 | 40 | 105 |
| 2020 November | 49 | 35 | 84 |
| 2020 October | 56 | 34 | 90 |
| 2020 September | 41 | 16 | 57 |
| 2020 August | 34 | 26 | 60 |
| 2020 July | 43 | 33 | 76 |
| 2020 June | 38 | 21 | 59 |
| 2020 May | 58 | 24 | 82 |
| 2020 April | 4 | 0 | 4 |
| 2020 March | 21 | 13 | 34 |
| 2020 February | 50 | 33 | 83 |
| 2020 January | 55 | 25 | 80 |
| 2019 December | 36 | 11 | 47 |
| 2019 November | 37 | 25 | 62 |
| 2019 October | 32 | 12 | 44 |
| 2019 September | 34 | 21 | 55 |
| 2019 August | 42 | 30 | 72 |
| 2019 July | 50 | 32 | 82 |
| 2019 June | 35 | 27 | 62 |
| 2019 May | 41 | 13 | 54 |
| 2019 April | 27 | 43 | 70 |
| 2019 March | 58 | 31 | 89 |
| 2019 February | 44 | 31 | 75 |
| 2019 January | 51 | 30 | 81 |
| 2018 December | 70 | 39 | 109 |
| 2018 November | 96 | 41 | 137 |
| 2018 October | 21 | 6 | 27 |
| 2018 September | 3 | 0 | 3 |
| 2018 May | 4 | 2 | 6 |
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