Myasthenia gravis and large granular lymphocytic leukemia

Muñoz Muñoz, Cándido; Homedes Pedret, Christian; López Vivancos, Josefa

doi:10.1016/j.medcle.2018.05.052

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It is a chronic low-grade lymphoproliferative syndrome characterised by the presence of cytopenias, lymphocytosis, splenomegaly and increased susceptibility to infections, and may be associated with autoimmune pathology.<a class="elsevierStyleCrossRefs" href="#bib0030">1–3</a>We present the case of a patient affected by myasthenia gravis associated with T-cell large granular lymphocyte leukaemia. We reviewed the existing literature on similar cases (PubMed) without a date filter using the search terms, “Myasthenia gravis” and “large granular lymphocytic leukemia”, “autoimmune diseases” and “large granular lymphocytic leukemia” and we did not find a published case with this association.We present the case of an 81-year-old male patient with a history of claudication of the lower limbs attributed to stenosis of the medullary canal and macrocytic anaemia of one-year evolution, who was admitted due to weakness of the lower limbs and progressive dyspnoea of two weeks’ evolution. Physical examination revealed mucocutaneous pallor and II/VI pansystolic murmur, predominantly in the apex. Results of note from the analytical tests included: haemoglobin: 5.7g/dl and MCV: 120; the rest of the blood count, coagulation, kidney function, LDH, CK, liver enzymes, ionogram, ferritin, transferrin saturation, folic acid and vitamin B12, were normal. Normal electrocardiogram Chest X-ray with vascular redistribution and clamping of both costophrenic sinuses. He was diagnosed as acute chronic anaemia with secondary heart failure; treatment was initiated with intravenous furosemide and two packed red cells, and a bone marrow biopsy was scheduled. The next day, the patient presented a more severe dyspnoea and a tendency to drowsiness, with a recovered loss of consciousness. He was admitted to the Intensive Care Unit, where he underwent orotracheal intubation and mechanical ventilation due to hypercapnic respiratory failure with acidosis. A thoracic ultrasound showed bilateral diaphragmatic paralysis, and we suspected neuromuscular pathology. Relatives were re-interrogated, who reported that the patient had dropped head syndrome symptoms and long-standing fatigue of shoulder girdle, with episodes of diplopia and dextroversion. An autoimmunity study was performed, which was normal, and one into acetylcholine antireceptor antibodies, which were positive (1/2560). The thoracic CT ruled out the presence of mediastinal lesions suggestive of thymoma or thymic hyperplasia. With a diagnosis of myasthenia gravis, treatment with prednisone and pyridostigmine was initiated. Ten days after the start of this treatment, a sensory and motor neurography was performed in the patient's upper and lower limbs, ruling out neuropathy, and an electromyographic study showed no evidence of polyradiculopathy, motor neuron involvement or myopathy. The repetitive stimulation study at 3Hz showed amplitude falls without actually reaching pathological values (>10%). In view of the persistence of the symptoms, infusion of immunoglobulins was indicated, after which the patient presented an improvement in his neurological symptoms. A bone marrow biopsy was subsequently performed, which showed the presence of a CD8+T-lymphoid population of atypical phenotype compatible with T-cell granular lymphocyte leukaemia; we started treatment with cyclophosphamide, with both clinical and analytical improvement, which is maintained during follow-up.We know that there is an association between autoimmune processes and T-cell large granular lymphocyte leukaemia.<a class="elsevierStyleCrossRefs" href="#bib0030">1,2</a> Chronic activation of T-cells by a viral or autoreactive antigen and a polyclonal autoimmune response could explain the association of T-cell large granular lymphocyte leukaemia with autoimmune diseases.<a class="elsevierStyleCrossRef" href="#bib0035">2</a> In an analysis of a cohort of 201 patients with this oncohematological pathology, 74 of them (37%) had an associated autoimmune disease.<a class="elsevierStyleCrossRef" href="#bib0040">3</a> This condition has been associated with numerous autoimmune diseases,<a class="elsevierStyleCrossRefs" href="#bib0035">2,3</a> such as inflammatory bowel disease, Sjögren's syndrome, rheumatoid arthritis, thyroiditis, multiple sclerosis, and other autoimmune diseases of haematological origin,<a class="elsevierStyleCrossRef" href="#bib0045">4</a> such as autoimmune haemolytic anaemia, or idiopathic thrombocytopenic purpura. In certain studies, the percentage of patients affected by T-cell large granular lymphocyte with associated autoimmune pathology reaches 90%.<a class="elsevierStyleCrossRef" href="#bib0050">5</a> We present a new case of association between T-cell large granular lymphocyte and an autoimmune disease, with the peculiarity of being the first case related to myasthenia gravis. When treating a patient with anaemia, with no related aetiology and associated autoimmune disease, the diagnostic possibility of a T-cell large granular lymphocyte leukaemia should be considered, and in turn, any patient affected by T-cell large granular lymphocyte leukaemia should be studied to rule out any associated autoimmune disease." "pdfFichero" => "main.pdf" "tienePdf" => true "NotaPie" => array:1 [ 0 => array:2 [ "etiqueta" => "☆" "nota" => "Please cite this article as: Muñoz Muñoz C, Homedes Pedret C, López Vivancos J. Miastenia gravis y leucemia de linfocitos T grandes granulares. Med Clin (Barc). 2019;152:163–164." ] ] "bibliografia" => array:2 [ "titulo" => "References" "seccion" => array:1 [ 0 => array:2 [ "identificador" => "bibs0015" "bibliografiaReferencia" => array:5 [ 0 => array:3 [ "identificador" => "bib0030" "etiqueta" => "1" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Large granular lymphocytic leukemia. Current diagnostic and therapeutic approaches and novel treatment options" "autores" => array:1 [ 0 => array:2 [ "etal" => false "autores" => array:1 [ 0 => "E. Matutes" ] ] ] ] ] "host" => array:1 [ 0 => array:2 [ "doi" => "10.1080/17474086.2017.1284585" "Revista" => array:6 [ "tituloSerie" => "Expert Rev Hematol" "fecha" => "2017" "volumen" => "10" "paginaInicial" => "251" "paginaFinal" => "258" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/28128670" "web" => "Medline" ] ] ] ] ] ] ] ] 1 => array:3 [ "identificador" => "bib0035" "etiqueta" => "2" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Autoimmune manifestations in large granular lymphocyte leukemia. Clinical lymphoma" "autores" => array:1 [ 0 => array:2 [ "etal" => false "autores" => array:2 [ 0 => "B. Bockorny" 1 => "C.A. Dasanu" ] ] ] ] ] "host" => array:1 [ 0 => array:2 [ "doi" => "10.1016/j.clml.2012.06.006" "Revista" => array:6 [ "tituloSerie" => "Clin Lymphoma Myeloma Leuk" "fecha" => "2012" "volumen" => "12" "paginaInicial" => "400" "paginaFinal" => "405" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/22999943" "web" => "Medline" ] ] ] ] ] ] ] ] 2 => array:3 [ "identificador" => "bib0040" "etiqueta" => "3" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Analysis of a French cohort of patients with large granular lymphocyte leukemia: a report on 229" "autores" => array:1 [ 0 => array:2 [ "etal" => true "autores" => array:6 [ 0 => "B. Bareau" 1 => "J. Rey" 2 => "M. Hamidou" 3 => "J. Donadieu" 4 => "J. Morcet" 5 => "O. Reman" ] ] ] ] ] "host" => array:1 [ 0 => array:2 [ "doi" => "10.3324/haematol.2009.018481" "Revista" => array:6 [ "tituloSerie" => "Haematologica" "fecha" => "2010" "volumen" => "95" "paginaInicial" => "1534" "paginaFinal" => "1541" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/20378561" "web" => "Medline" ] ] ] ] ] ] ] ] 3 => array:3 [ "identificador" => "bib0045" "etiqueta" => "4" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "T-Cell large granular leukemia and related proliferations" "autores" => array:1 [ 0 => array:2 [ "etal" => false "autores" => array:1 [ 0 => "D.P. O’Malley" ] ] ] ] ] "host" => array:1 [ 0 => array:2 [ "doi" => "10.1309/A8FHDA0VVRJ05GJP" "Revista" => array:6 [ "tituloSerie" => "Am J Clin Pathol" "fecha" => "2007" "volumen" => "127" "paginaInicial" => "850" "paginaFinal" => "859" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/17509982" "web" => "Medline" ] ] ] ] ] ] ] ] 4 => array:3 [ "identificador" => "bib0050" "etiqueta" => "5" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Prevalence of autoimmune hematologic and non-hematologic conditions in large granular lymphocytic leukemia: exploratory analysis of a series of consecutive patients" "autores" => array:1 [ 0 => array:2 [ "etal" => false "autores" => array:3 [ 0 => "B. Bockorny" 1 => "I. Codreanu" 2 => "C.A. Dasanu" ] ] ] ] ] "host" => array:1 [ 0 => array:2 [ "doi" => "10.3109/10428194.2013.831090" "Revista" => array:6 [ "tituloSerie" => "Leuk Lymphoma" "fecha" => "2014" "volumen" => "55" "paginaInicial" => "1399" "paginaFinal" => "1401" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/23927392" "web" => "Medline" ] ] ] ] ] ] ] ] ] ] ] ] ] "idiomaDefecto" => "en" "url" => "/23870206/0000015200000004/v1_201902100719/S2387020618305849/v1_201902100719/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/23870206/0000015200000004/v1_201902100719/S2387020618305849/v1_201902100719/en/main.pdf?idApp=UINPBA00004N&text.app=https://www.elsevier.es/" "EPUB" => "https://multimedia.elsevier.es/PublicationsMultimediaV1/item/epub/S2387020618305849?idApp=UINPBA00004N"]

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Vol. 152. Issue 4.

Pages 163-164 (February 2019)

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