Meningeal cryptococcosis in a patient with angioimmunoblastic lymphoma treated with alemtuzumab

Cruz, David; Costa, Paula; Sagüés, Miguel

doi:10.1016/j.medcle.2018.05.054

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Distribution is worldwide. This genus includes about 50 species, Cryptococcus neoformans and Cryptococcus gattii being the most frequent human pathogens. Depending on its capsular composition, 5 serotypes have been reported: A (C. neoformans var. grubii), D (C. neoformans var. neoformans) and AD (C. neoformans hybrid) and serotypes B and C (C. gattii). The main reservoir is soil contaminated with excrement, mostly from birds, bats and organic matter.<a class="elsevierStyleCrossRefs" href="#bib0030">1,2</a> It is acquired mainly by the respiratory route (inhaled), and rarely by the gastrointestinal tract and skin.<a class="elsevierStyleCrossRef" href="#bib0035">2</a>The estimated incidence in our country is 0.5/1,000,000 inhabitants.<a class="elsevierStyleCrossRef" href="#bib0040">3</a>The main risk factor is cellular immunodeficiency.<a class="elsevierStyleCrossRef" href="#bib0035">2</a> The main risk groups include patients with HIV infection, oncohematological patients and transplant recipients.<a class="elsevierStyleCrossRef" href="#bib0040">3</a>C. gattii has traditionally been associated with the disease in immunocompetent individuals in tropical and subtropical regions.<a class="elsevierStyleCrossRefs" href="#bib0030">1,2</a>The most common symptomatology includes headache in up to 75% cases, usually lasting about 2–4 weeks. Frequently it occurs with fever, nausea, vomiting and seizures, but neck stiffness and typical signs of meningism have been reported in fewer than 25% cases.<a class="elsevierStyleCrossRef" href="#bib0045">4</a>The diagnosis is based on the identification of the yeasts in biological fluids, by observing the capsule in the India ink stain, the isolation in cultures or the detection of capsular antigens.<a class="elsevierStyleCrossRef" href="#bib0045">4</a>Treatment includes an induction phase with intravenous liposomal amphotericin B and oral flucytosine. After the normalization of cerebrospinal fluid (CSF) results, oral fluconazole is used for maintenance therapy.<a class="elsevierStyleCrossRef" href="#bib0045">4</a>Alemtuzumab is a recombinant monoclonal antibody that binds to CD52, present on B and T lymphocytes, monocytes, NK cells and some granulocytes. Lysis of CD52 positive cells occurs by complement activation, antibody-dependent cytotoxicity and apoptosis. It is indicated in the treatment of chronic lymphatic leukemia and other T-cell lymphoproliferative neoplasms. It causes dose-independent lymphopenia and increases the risk of developing opportunistic infections.<a class="elsevierStyleCrossRef" href="#bib0050">5</a>We present a case report of meningeal cryptococcosis in a patient with angioimmunoblastic T-cell lymphoma and treated with alemtuzumab, in January 2016.A 57-year-old woman diagnosed with angioimmunoblastic T-cell lymphoma in June 2014. She received first-line chemotherapy in accordance with the R-CHOP regimen (rituximab, cyclophosphamide, adriamycin, vincristine and prednisone) for 6 cycles without obtaining a response; subsequently alemtuzumab was administered, which had to be withdrawn due to cytomegalovirus (CMV) infection. She underwent a third-line treatment with ciclosporin until progression and a fourth-line treatment with lenalidomide, without response. Eventually, she restarted treatment with alemtuzumab.The patient went to the emergency department due to a 4-day occipital headache, that awakened her at night, and disorientation, with no fever and no further symptoms.She was hemodynamically stable. Physical examination revealed a disorientation in time, space and person. She had neck stiffness and positive Kernig and Brudzinski signs. The complete blood count showed: hemoglobin 113g/L, platelets 195×109/L, leukocytes 6.59×109/L (normal formula). Plasma coagulation and basic biochemistry were normal. The patient underwent a cranial computed tomography that showed no relevant pathological changes. The CSF study showed: glucose 36mg/dL [50–80] and proteins 81.7mg/dL [15–45]. Gram staining was negative for bacteria and pneumococcal antigen. The polymerase chain reaction tests for CMV, JC virus, Epstein-Barr virus, herpes simplex virus 1 and 2, varicella-zoster virus and Listeria monocytogenes were all negative. Given the suspicion of opportunistic infection, we used India ink stain which showed capsule yeasts.C. neoformans var. grubii was isolated in the CSF culture.The patient underwent treatment with liposomal amphotericin B and flucytosine for 24 days, and she was discharged with maintenance oral fluconazole therapy, completing a 7-month treatment." "pdfFichero" => "main.pdf" "tienePdf" => true "NotaPie" => array:1 [ 0 => array:2 [ "etiqueta" => "☆" "nota" => "Please cite this article as: Cruz D, Costa P, Sagüés M. Criptococosis meníngea en una paciente con diagnóstico de linfoma T angioinmunoblástico y tratamiento con alemtuzumab. Med Clin (Barc). 2019;152:e19–e20." ] ] "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" => "Cryptococcal meningitis: epidemiology and therapeutic options" "autores" => array:1 [ 0 => array:2 [ "etal" => false "autores" => array:2 [ 0 => "D.J. Sloan" 1 => "V. Parris" ] ] ] ] ] "host" => array:1 [ 0 => array:2 [ "doi" => "10.2147/CLEP.S38850" "Revista" => array:6 [ "tituloSerie" => "Clin Epidemiol" "fecha" => "2014" "volumen" => "6" "paginaInicial" => "169" "paginaFinal" => "182" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/24872723" "web" => "Medline" ] ] ] ] ] ] ] ] 1 => array:3 [ "identificador" => "bib0035" "etiqueta" => "2" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Systemic fungal infections in patients with human inmunodeficiency virus" "autores" => array:1 [ 0 => array:2 [ "etal" => false "autores" => array:6 [ 0 => "C. Rodríguez-Cerdeira" 1 => "R. Arenas" 2 => "G. Moreno-Coutiño" 3 => "E. Vásquez" 4 => "R. Fernández" 5 => "P. Chang" ] ] ] ] ] "host" => array:1 [ 0 => array:2 [ "doi" => "10.1016/j.ad.2012.06.017" "Revista" => array:6 [ "tituloSerie" => "Actas Dermosifiliogr" "fecha" => "2014" "volumen" => "105" "paginaInicial" => "5" "paginaFinal" => "17" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/23107866" "web" => "Medline" ] ] ] ] ] ] ] ] 2 => array:3 [ "identificador" => "bib0040" "etiqueta" => "3" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Estudio epidemiológico de la criptococosis en España: primeros resultados" "autores" => array:1 [ 0 => array:2 [ "etal" => true "autores" => array:6 [ 0 => "M.F. Colom" 1 => "S. Frasés" 2 => "C. Ferrer" 3 => "E. Martín-Mazuelos" 4 => "M. Hermoso-de-Mendoza" 5 => "J.M. Torres-Rodríguez" ] ] ] ] ] "host" => array:1 [ 0 => array:1 [ "Revista" => array:6 [ "tituloSerie" => "Rev Iberoam Micol" "fecha" => "2001" "volumen" => "18" "paginaInicial" => "99" "paginaFinal" => "104" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/15487916" "web" => "Medline" ] ] ] ] ] ] ] ] 3 => array:3 [ "identificador" => "bib0045" "etiqueta" => "4" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Treatment of acute cryptococcal meningitis in HIV infected adults, with an emphasis on resource-limited settings" "autores" => array:1 [ 0 => array:2 [ "etal" => false "autores" => array:4 [ 0 => "D. Sloan" 1 => "S. Dlamini" 2 => "N. Paul" 3 => "M. Dedicoat" ] ] ] ] ] "host" => array:1 [ 0 => array:1 [ "Revista" => array:3 [ "tituloSerie" => "Cochrane Database Syst Rev" "fecha" => "2008" "paginaInicial" => "CD005647" ] ] ] ] ] ] 4 => array:3 [ "identificador" => "bib0050" "etiqueta" => "5" "referencia" => array:1 [ 0 => array:1 [ "referenciaCompleta" => "BC Cancer. Monográfico alemtuzumab. Available from: <a id="intr0010" class="elsevierStyleInterRef" href="http://www.bccancer.bc.ca/drug-database-site/Drug%20Index/Alemtuzumab_Monograph_1May2015.pdf">http://www.bccancer.bc.ca/drug-database-site/Drug%20Index/Alemtuzumab_Monograph_1May2015.pdf</a> [accessed 24 Feb 2017]." ] ] ] ] ] ] ] ] "idiomaDefecto" => "en" "url" => "/23870206/0000015200000004/v1_201902100719/S2387020618305862/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/S2387020618305862/v1_201902100719/en/main.pdf?idApp=UINPBA00004N&text.app=https://www.elsevier.es/" "EPUB" => "https://multimedia.elsevier.es/PublicationsMultimediaV1/item/epub/S2387020618305862?idApp=UINPBA00004N"]

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Vol. 152. Issue 4.

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