Letter to the Editor
Rheumatoid arthritis and T cell large granular lymphocyte leukaemia: A case report
Artritis reumatoide y leucemia de linfocitos grandes granulares T. A propósito de un caso
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Jarilla-Fernández, Francisco Jiménez-Burgos, Elisa Sánchez-Rodriguez" "autores" => array:4 [ 0 => array:4 [ "nombre" => "María del Mar" "apellidos" => "Herráez-Albendea" "email" => array:1 [ 0 => "marherraez@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" => "María del Castillo" "apellidos" => "Jarilla-Fernández" "referencia" => array:1 [ 0 => array:2 [ "etiqueta" => "<span class="elsevierStyleSup">a</span>" "identificador" => "aff0005" ] ] ] 2 => array:3 [ "nombre" => "Francisco" "apellidos" => "Jiménez-Burgos" "referencia" => array:1 [ 0 => array:2 [ "etiqueta" => "<span class="elsevierStyleSup">b</span>" "identificador" => "aff0010" ] ] ] 3 => array:3 [ "nombre" => "Elisa" "apellidos" => "Sánchez-Rodriguez" "referencia" => array:1 [ 0 => array:2 [ "etiqueta" => "<span class="elsevierStyleSup">c</span>" "identificador" => "aff0015" ] ] ] ] "afiliaciones" => array:3 [ 0 => array:3 [ "entidad" => "Servicio Hematología, Hospital de Santa Bárbara, Puertollano, Ciudad Real, Spain" "etiqueta" => "a" "identificador" => "aff0005" ] 1 => array:3 [ "entidad" => "Servicio de Anatomía Patológica, Hospital de Santa Bárbara, Puertollano, Ciudad Real, Spain" "etiqueta" => "b" "identificador" => "aff0010" ] 2 => array:3 [ "entidad" => "Servicio Reumatología, Hospital de Santa Bárbara, Puertollano, Ciudad Real, Spain" "etiqueta" => "c" "identificador" => "aff0015" ] ] "correspondencia" => array:1 [ 0 => array:3 [ "identificador" => "cor0005" "etiqueta" => "⁎" "correspondencia" => "Corresponding author." ] ] ] ] "titulosAlternativos" => array:1 [ "es" => array:1 [ "titulo" => "Artritis reumatoide y leucemia de linfocitos grandes granulares T. A propósito de un caso" ] ] "textoCompleto" => "<span class="elsevierStyleSections"><p id="par0005" class="elsevierStylePara elsevierViewall">Large granular lymphocytic (LGL) leukaemia was described by Loughran et al. in 1985. It is characterized as an unusual heterogeneous disorder with clonal expansion of mature T lymphocytes. Although the cause is unknown, antigenic stimuli responsible for inducing the activation of large granular CD8+ effector lymphocytes via different signaling pathways have been implicated. It has been associated with a wide spectrum of signs and symptoms that can be the first or only manifestation of the disease, including asymptomatic periods, splenomegaly, cytopenias, recurrent bacterial infections, B symptoms, hepatomegaly, lymph node involvement, neuropathy and pulmonary hypertension.<a class="elsevierStyleCrossRef" href="#bib0035"><span class="elsevierStyleSup">1</span></a> In addition, an association has been established between LGL leukaemia and autoimmune diseases, forming part of an entity known as pseudo-Felty's syndrome.<a class="elsevierStyleCrossRef" href="#bib0040"><span class="elsevierStyleSup">2</span></a> We report the case of a 62-year-old woman who developed LGL leukaemia 30 years after being diagnosed with seronegative rheumatoid arthritis (RA).</p><p id="par0010" class="elsevierStylePara elsevierViewall">When she presented to our hospital, the patient was being treated with 5<span class="elsevierStyleHsp" style=""></span>mg prednisone and 150<span class="elsevierStyleHsp" style=""></span>mg ranitidine. On physical examination, she had pale skin and mucous membranes, deformed metacarpophalangeal and interphalangeal joints, and splenomegaly. Her laboratory tests were normal, with the exception of a leukocyte count of 1.82<span class="elsevierStyleHsp" style=""></span>×<span class="elsevierStyleHsp" style=""></span>10<span class="elsevierStyleSup">9</span>/L; neutrophils, 0.877<span class="elsevierStyleHsp" style=""></span>×<span class="elsevierStyleHsp" style=""></span>10<span class="elsevierStyleSup">9</span>/L; iron deficiency anemia; platelets, 139<span class="elsevierStyleHsp" style=""></span>×<span class="elsevierStyleHsp" style=""></span>10<span class="elsevierStyleSup">9</span>/L; complement C3, 70.9<span class="elsevierStyleHsp" style=""></span>mg/dL; complement C4, 5.1<span class="elsevierStyleHsp" style=""></span>mg/dL; and positive antinuclear antibodies with a homogeneous pattern. Oral iron therapy and weekly methotrexate were started and her prednisone dose was raised. In view of the clinical course (especially RA and neutropenia), as well as the presence of splenomegaly, we considered a diagnosis of Felty's syndrome (FS). Computed tomography confirmed the splenomegaly and a bone marrow study revealed the presence of an interstitial and nodular infiltrate of T lymphocytes expressing CD3, CD8, T-cell receptor (TCR) βF1, and CD57, suggestive of infiltration by LGL leukaemia. Four months after the initiation of treatment with methotrexate, the patient developed an abdominal wall abscess requiring antibiotic therapy and surgical drainage.</p><p id="par0015" class="elsevierStylePara elsevierViewall">Large granular lymphocytic leukaemia is an uncommon clinical condition, characterized by an indolent, nonprogressive clinical course. The symptoms present during the sixth decade of life, and it affects both sexes equally. It constitutes 2–5% of all T/natural killer (NK) cell neoplasms. To date, 400 cases have been reported in the literature.<a class="elsevierStyleCrossRef" href="#bib0035"><span class="elsevierStyleSup">1</span></a> Given the criteria established for LGL leukaemia, which require the presence of clonal expansion of LGL in peripheral blood >0.5<span class="elsevierStyleHsp" style=""></span>×<span class="elsevierStyleHsp" style=""></span>10<span class="elsevierStyleSup">9</span>/L and/or bone marrow and a study showing the characteristic immunophenotype (CD3+/CD8+/CD57+ and/or CD16+), as well as clonal TCR gene rearrangement,<a class="elsevierStyleCrossRef" href="#bib0045"><span class="elsevierStyleSup">3</span></a> we considered a possible diagnosis of this disease, as our findings were consistent with the reported features. In view of the patient's medical history, we ruled out other conditions like FS, a systemic complication of RA characterized by the triad of RA, persistent neutropenia and splenomegaly, which is closely associated with the HLA-DR4 haplotype (nearly 95% of the patients), although some authors have suggested that FS and LGL leukaemia associated with RA are expressions of a single entity characterized by LGL proliferation.<a class="elsevierStyleCrossRefs" href="#bib0040"><span class="elsevierStyleSup">2,4</span></a> It must also be distinguished from infections, hematologic neoplasms, solid tumors and autoimmune diseases. We consider it of interest to highlight the association between LGL leukaemia and certain autoimmune diseases, including RA, Sjögren's syndrome, polymyositis, rheumatic polymyalgia, vasculitis,<a class="elsevierStyleCrossRef" href="#bib0055"><span class="elsevierStyleSup">5</span></a> endocrine disorders, celiac disease and autoimmune polyendocrinopathy-mucocutaneous candidiasis-ectodermal dystrophy syndrome, among others, resulting in a condition known as pseudo-Felty's syndrome.<a class="elsevierStyleCrossRef" href="#bib0040"><span class="elsevierStyleSup">2</span></a></p><p id="par0020" class="elsevierStylePara elsevierViewall">In conclusion, the diagnosis of LGL leukaemia associated with RA requires a high index of suspicion, based on the connections between patient history and analytical and radiological criteria, as well as the confirmation of a characteristic immunophenotype in peripheral blood and/or bone marrow.<a class="elsevierStyleCrossRef" href="#bib0060"><span class="elsevierStyleSup">6</span></a> Detailed descriptions of new cases could contribute to the achievement of a better understanding of this condition and to the awareness of the importance of early diagnosis and therapeutic intervention.</p></span>" "pdfFichero" => "main.pdf" "tienePdf" => true "NotaPie" => array:1 [ 0 => array:2 [ "etiqueta" => "☆" "nota" => "<p class="elsevierStyleNotepara" id="npar0005">Please cite this article as: Herráez-Albendea MM, Jarilla-Fernández MC, Jiménez-Burgos F, Sánchez-Rodriguez E. Artritis reumatoide y leucemia de linfocitos grandes granulares T. A propósito de un caso. Reumatol Clin. 2016;12:239–240.</p>" ] ] "bibliografia" => array:2 [ "titulo" => "References" "seccion" => array:1 [ 0 => array:2 [ "identificador" => "bibs0005" "bibliografiaReferencia" => array:6 [ 0 => array:3 [ "identificador" => "bib0035" "etiqueta" => "1" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Clinical features of large granular lymphocyte leukemia" "autores" => array:1 [ 0 => array:2 [ "etal" => false "autores" => array:2 [ 0 => "T. Lamy" 1 => "T.P. 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Loughran Jr." ] ] ] ] ] "host" => array:1 [ 0 => array:1 [ "Revista" => array:5 [ "tituloSerie" => "Hematol Am Soc Hematol Educ Program" "fecha" => "2012" "volumen" => "2012" "paginaInicial" => "652" "paginaFinal" => "659" ] ] ] ] ] ] ] ] ] ] ] "idiomaDefecto" => "en" "url" => "/21735743/0000001200000004/v3_201704050048/S2173574316300107/v3_201704050048/en/main.assets" "Apartado" => array:4 [ "identificador" => "8400" "tipo" => "SECCION" "en" => array:2 [ "titulo" => "Letters to the Editor" "idiomaDefecto" => true ] "idiomaDefecto" => "en" ] "PDF" => "https://static.elsevier.es/multimedia/21735743/0000001200000004/v3_201704050048/S2173574316300107/v3_201704050048/en/main.pdf?idApp=UINPBA00004M&text.app=https://reumatologiaclinica.org/" "EPUB" => "https://multimedia.elsevier.es/PublicationsMultimediaV1/item/epub/S2173574316300107?idApp=UINPBA00004M" ]
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