Response to imatinib in patient with corticosteroid-unresponsive idiopatic hypereosinophilic syndrome
I.. Yilmaza,
, L.. Kaynarb, N.. Tutarc, C.. Palab, O.. Canozd, H.. Buyukoglanc, I.. Gulmezc
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a Erciyes University School of Medicine, Department of Chest Diseases, Division of Immunology and Allergy, Kayseri, Turkey
b Erciyes University School of Medicine, Department of Internal Medicine, Division of Hematology, Turkey
c Erciyes University School of Medicine, Department of Chest Diseases, Turkey
d Erciyes University School of Medicine, Department of Pathology, Turkey
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Axial CT image at lung window setting showing centrilobular ground-glass nodules (circles)." ] ] ] "textoCompleto" => "<p class="elsevierStylePara">Dear Editor,</p><p class="elsevierStylePara">Hypereosinophilia (HE) is defined as peripheral blood eosinophils >1.5 eosinophils × 10<span class="elsevierStyleSup">9</span>/L blood on 2 examinations and/or tissue HE defined by the following: (1) the percentage of eosinophils in the bone marrow section exceeds 20% of all nucleated cells and/or (2) the pathologist is of the opinion that tissue infiltration by eosinophils is extensive and/or (3) marked deposition of eosinophil granule proteins is found (in the absence or presence of major tissue infiltration by eosinophils). Hypereosinophilic syndrome (HES) is defined by the following: (1) criteria for peripheral blood hypereosiniphilia (HE) fulfilled and (2) organ damage and/or dysfunction attributable to tissue HE and (3) exclusion of other disorders or conditions as major reason for organ damage. HES subtypes have been defined; these include (1) idiopathic HES, (2) primary (neoplastic) HES, (3) secondary (reactive) HES.<a href="#bib8" class="elsevierStyleCrossRefs"><span class="elsevierStyleSup">1</span></a> We here report a case of idiopathic hypereosinophilic syndrome successfully treated with imatinib.</p><p class="elsevierStylePara">A forty-six-year-old male patient was admitted to our clinic with complaints of itching, cough, shortness of breath, and stomach pain. The symptoms had increased over the last six months. He had a history of chronic smoking (30 pack-years). There was no history of any drug use. Admission blood pressure: 110/80 mmHg; respiratory rate 20/min; pulse 95/min; saturation in room air was found to be 95%. Breath sounds were bilaterally decreased. Widely excoriated itchy lesions were present. There was tenderness in the epigastric region. Blood eosinophil rate was 55.4% (9880/mm<span class="elsevierStyleSup">3</span>). Parasite stool examination and serologic tests were negative. A mild obstructive pattern was present in the pulmonary function test. However, the patient did not benefit from treatment with high doses of inhaled corticosteroids/β2 agonists. Laboratory tests showed no significant alterations except increased vitamin B12: 1081 pg/ml (reference range: 111–663 pg/ml) and total IgE: 194 IU/ml (reference range: <100 IU/ml) autoimmunity work-up was negative. Troponin T and echocardiography were normal.</p><p class="elsevierStylePara">Centrilobular ground-glass nodules were found to be more prominent in the upper lobes of the lungs in thorax computed tomography (CT) (<a href="#f0005" class="elsevierStyleCrossRefs">Figure 1a</a>). Abdominal CT and ultrasonography were found to be normal. Endoscopic biopsy for stomach pain was reported as eosinophilic gastritis. Eosinophilic infiltration was observed on transbronchial lung biopsy. Numerous eosinophilic granulocytes (40%) were observed in bone marrow biopsy without increased blast cells. A prominent mast cell population was not observed. There was no malignant infiltration. FIPLI-PDGFRα mutation, JAK-2 mutation and Philadelphia chromosome were also found to be negative.</p><a name="f0005" class="elsevierStyleCrossRefs"></a><p class="elsevierStylePara"><img src="320v22n01-90447952fig1a.jpg" alt="Axial CT image at lung window setting showing centrilobular ground-glass nodules (circles)."></img></p><p class="elsevierStylePara">Figure 1a. Axial CT image at lung window setting showing centrilobular ground-glass nodules (circles).</p><p class="elsevierStylePara">In our case, differential diagnosis was performed for primary (hematopoietic neoplasms with HE) and secondary HES, (helminth infections, allergic reactions, atopic diseases, drug reactions (allergic or toxic), Hodgkin disease, B- or T-cell lymphoma/leukemia, Langerhans cell histiocytosis, indolent systemic mastocytosis, solid tumors/malignancy, allergic bronchopulmonary aspergillosis, chronic inflammatory disorders, autoimmune diseases and lymphoid variant of HES), organ-restricted conditions accompanied by HE (eosinophilic gastrointestinal disorders, eosinophilic pneumonia, dermatologic diseases, etc.) and specific syndromes accompanied by HE (Gleich syndrome, Churg-Strauss syndrome, eosinophilia myalgia syndrome, Hyper-IgE syndrome).<a href="#bib8" class="elsevierStyleCrossRefs"><span class="elsevierStyleSup">1</span></a><span class="elsevierStyleSup">, </span><a href="#bib9" class="elsevierStyleCrossRefs"><span class="elsevierStyleSup">2</span></a><span class="elsevierStyleSup">, </span><a href="#bib10" class="elsevierStyleCrossRefs"><span class="elsevierStyleSup">3</span></a><span class="elsevierStyleSup">, </span><a href="#bib11" class="elsevierStyleCrossRefs"><span class="elsevierStyleSup">4</span></a><span class="elsevierStyleSup">, </span><a href="#bib12" class="elsevierStyleCrossRefs"><span class="elsevierStyleSup">5</span></a><span class="elsevierStyleSup">, </span><a href="#bib13" class="elsevierStyleCrossRefs"><span class="elsevierStyleSup">6</span></a> The patient was diagnosed with idiopatic HES after exclusion of all primary and secondary causes and exclusion of other conditions and syndromes. The patient was started on imatinib mesylate therapy with 400 mg/day because he did not respond to corticosteroids (CS) and hydroxyurea therapy. The treatment was reduced to a 100 mg in the third month of treatment due to normalization of eosinophil levels and disappearance of all complaints. The ground-glass nodules disappeared after 1 year of imatinib treatment (<a href="#f0010" class="elsevierStyleCrossRefs">Figure 1b</a>).</p><a name="f0010" class="elsevierStyleCrossRefs"></a><p class="elsevierStylePara"><img src="320v22n01-90447952fig1b.jpg" alt="Axial CT image at the same level as in <cross-ref>Fig. 1a</cross-ref> showing disappearance of ground-glass nodules."></img></p><p class="elsevierStylePara">Figure 1b. Axial CT image at the same level as in Fig. 1a showing disappearance of ground-glass nodules.</p><p class="elsevierStylePara">CS have been used for decades in the treatment of HES, with the exception of PDGFR-α associated HES. A number of cytotoxic therapies have been used for the management of corticosteroid-refractory HES. Of these, hydroxyurea has been the most extensively studied. However, the utility of hydroxyurea monotherapy is limited in the treatment of HES. Imatinib mesylate is a tyrosine kinase inhibitor with activity against several receptor tyrosine kinases, including the fusion kinase FIP1L1/PDGFR-α, which is responsible for PDGFR-α-associated HES. The utility of imatinib therapy in hypereosinophilic patients without a demonstrable FIP1L1/PDGFR-α mutation remains controversial, although some patients have demonstrated a response. In such cases, imatinib could be prescribed as second-line treatment, after demonstration of complete resistance to CS.<a href="#bib10" class="elsevierStyleCrossRefs"><span class="elsevierStyleSup">3</span></a><span class="elsevierStyleSup">, </span><a href="#bib12" class="elsevierStyleCrossRefs"><span class="elsevierStyleSup">5</span></a><span class="elsevierStyleSup">, </span><a href="#bib13" class="elsevierStyleCrossRefs"><span class="elsevierStyleSup">6</span></a><span class="elsevierStyleSup">, </span><a href="#bib14" class="elsevierStyleCrossRefs"><span class="elsevierStyleSup">7</span></a></p><p class="elsevierStylePara">In conclusion, idiopatic HES is an exclusion diagnosis. Therefore, a wide differential diagnosis is required. Imatinib should be reserved for corticosteroid nonresponders cases with idiopatic HES.</p><a name="sec0025" class="elsevierStyleCrossRefs"></a><span class="elsevierStyleSectionTitle">Conflicts of interest</span><p class="elsevierStylePara">The authors have no conflicts of interest to declare.</p><p class="elsevierStylePara">Corresponding author. insu2004@yahoo.com</p>" "pdfFichero" => "320v22n01a90447952pdf001.pdf" "tienePdf" => true "multimedia" => array:4 [ 0 => array:8 [ "identificador" => "fig1" "etiqueta" => "Figure 1" "tipo" => "MULTIMEDIAFIGURA" "mostrarFloat" => true "mostrarDisplay" => false "copyright" => "Elsevier España" "figura" => array:1 [ 0 => array:4 [ "imagen" => "320v22n01-90447952fig1a.jpg" "Alto" => 693 "Ancho" => 995 "Tamanyo" => 268599 ] ] "descripcion" => array:1 [ "en" => "a. 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Axial CT image at the same level as in Fig. 1a showing disappearance of ground-glass nodules." ] ] 2 => array:6 [ "identificador" => "fig3" "tipo" => "MULTIMEDIAFIGURA" "mostrarFloat" => true "mostrarDisplay" => false "copyright" => "Elsevier España" "descripcion" => array:1 [ "en" => "Axial CT image at lung window setting showing centrilobular ground-glass nodules (circles)." ] ] 3 => array:5 [ "identificador" => "fig4" "tipo" => "MULTIMEDIAFIGURA" "mostrarFloat" => true "mostrarDisplay" => false "copyright" => "Elsevier España" ] ] "bibliografia" => array:2 [ "titulo" => "Bibliography" "seccion" => array:1 [ 0 => array:1 [ "bibliografiaReferencia" => array:7 [ 0 => array:3 [ "identificador" => "bib8" "etiqueta" => "1" "referencia" => array:1 [ 0 => array:3 [ "referenciaCompleta" => "Contemporary consensus proposal on criteria and classification of eosinophilic disorders and related syndromes. J Allergy Clin Immunol. 2012; 130:607-12." 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| Year/Month | Html | Total | |
|---|---|---|---|
| 2024 November | 9 | 3 | 12 |
| 2024 October | 36 | 23 | 59 |
| 2024 September | 45 | 31 | 76 |
| 2024 August | 52 | 58 | 110 |
| 2024 July | 33 | 26 | 59 |
| 2024 June | 50 | 40 | 90 |
| 2024 May | 35 | 22 | 57 |
| 2024 April | 26 | 22 | 48 |
| 2024 March | 26 | 17 | 43 |
| 2024 February | 33 | 19 | 52 |
| 2024 January | 28 | 30 | 58 |
| 2023 December | 18 | 24 | 42 |
| 2023 November | 32 | 33 | 65 |
| 2023 October | 28 | 31 | 59 |
| 2023 September | 31 | 31 | 62 |
| 2023 August | 31 | 9 | 40 |
| 2023 July | 15 | 18 | 33 |
| 2023 June | 15 | 25 | 40 |
| 2023 May | 20 | 20 | 40 |
| 2018 July | 2 | 0 | 2 |
| 2018 April | 2 | 0 | 2 |
| 2018 February | 3 | 0 | 3 |
| 2018 January | 2 | 0 | 2 |
| 2017 December | 4 | 0 | 4 |
| 2017 November | 4 | 0 | 4 |
| 2017 October | 2 | 0 | 2 |
| 2017 September | 3 | 0 | 3 |
| 2017 August | 2 | 0 | 2 |
| 2017 July | 2 | 0 | 2 |
| 2017 June | 4 | 0 | 4 |
| 2017 May | 2 | 0 | 2 |
| 2017 April | 2 | 0 | 2 |
| 2017 March | 4 | 0 | 4 |
| 2017 February | 4 | 1 | 5 |
| 2017 January | 3 | 0 | 3 |
| 2016 December | 5 | 0 | 5 |
| 2016 November | 3 | 1 | 4 |
| 2016 October | 7 | 0 | 7 |
| 2016 September | 8 | 3 | 11 |
| 2016 August | 4 | 2 | 6 |
| 2016 July | 3 | 4 | 7 |
| 2016 April | 31 | 9 | 40 |
| 2016 March | 64 | 42 | 106 |
| 2016 February | 106 | 82 | 188 |
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