Enfermedad linfoproliferativa asociada a artritis reumatoide: reporte de tres casos / Lymphoproliferative disease associated with rheumatoid arthritis: report of three cases

Las investigaciones en la última década han demostrado que el riesgo de desarrollar linfoma en pacientes con artritis reumatoide es el doble que el riesgo de la población general. Sin embargo, no se cuenta con datos de la magnitud de este problema en Cuba. Se presentan los casos de tres pacientes con diagnóstico de artritis reumatoide seropositiva tratadas con metotrexate, que durante su evolución desarrollaron linfoma no Hodgkin. Las pacientes recibieron quimioterapia de primera línea y alcanzaron remisión total con supervivencia de tres años hasta el momento. El diagnóstico de las enfermedades linfoproliferativas en pacientes con artritis reumatoide es un desafío; por lo que es necesario un elevado índice de sospecha que, en ausencia de marcadores fiables de linfomagénesis, permita el manejo oportuno de estos pacientes(AU)

Research in the last decade has shown that the risk of developing lymphoma in patients with rheumatoid arthritis is twice the risk of the general population. However, there is not data on the magnitude of this problem in Cuba.We present the cases of three patients with a diagnosis of seropositive rheumatoid arthritis treated with methotrexate who during their evolution developed non-Hodgkin's lymphoma.The patients received first-line chemotherapy and they achieved total remission with three-year survival so far.The diagnosis of lymphoproliferative diseases in patients with rheumatoid arthritis is a challenge; therefore, a high index of suspicion is necessary that, in the absence of reliable markers of lymphomagenesis, allows the timely management of these patients(AU)

Doença de Still como causa de febre de origem indeterminada: relato de caso / Still's disease as a cause of fever of undetermined origin: case report

POS, 22 anos, sexo feminino, foi admitida na enfermaria de Clínica Médica para investigação diagnóstica de quadro consumptivo. Queixava-se perda ponderal (45 kg no total), febre vespertina, artralgias e hiporexia.Relatava internações recorrentes devido a fraqueza. Na história pregressa constava aborto espontâneo, tendo sido aventada a hipótese de infecção pelo zika vírus, porém não foram realizados exames sorológicos confirmatórios.Tinha contato com irmão portador de paracoccidioidomicose e tio com tuberculose. Apresentava-se emagrecida,com flacidez notável, sarcopenia, palidez cutânea mucosa grave, linfadenomegalia generalizada e hepatoesplenomegalia. Diante do quadro clínico, suspeitou-se inicialmente de doença linfoproliferativa. Apresentou anemia microcítica e hipocrômica, sorologias negativas para HIV, sífilis, leishmaniose e hepatites virais, FAN positivo, padrão nuclear pontilhado, PCR e VSH elevados, leucocitose e ferritina maior que 2000 em dois exames. O PPD era não reator. Os anatomopatológicos apresentavam pesquisa negativa para fungos e parasitas e sugeriam doença linfoproliferativa,entretanto as imunohistoquímicas revelaram padrão de linfonodos reacionais. Devido à suspeita inicial de doença linfoproliferativa foi iniciado profilaxia para lise tumoral com hidratação e alopurinol.Além disso devido as diversas linfonodomegalias foi iniciado tratamento empírico com Prednisona 80 mg/dia, com melhora do quadro clínico, remissão da febre e artralgia. Como os anatomopatológicos e imunohistoquímicas descartaram doenças proliferativas, foi iniciado desmame do corticoide, com ressurgimento da febre, dessa vez acompanhada de rash cutâneo evanescente em membros e artrite em joelho direito. Após afastar doenças infecciosas, neoplásicas e outras etiologias, considerou-se o diagnóstico de doença de Still, uma vez que a paciente apresentava quadro clínico compatível e preenchia os critérios de Yamaguchi. Iniciada terapia com metotrexate, com melhora do quadro clínico e alta hospitalar. (AU)

POS, 22 years old, female, was admitted for a diagnostic investigation of the consumptive condition. Weight loss (45 in total), afternoon fever, arthralgia and hyporexia were noted. Reported recurrent hospitalizations due to weakness. Previous history consisted of spontaneous abortion, having been hypothesized to be infected by zika virus, but no confirmatory serological tests were performed. He had contact with a brother with paracoccidioidomycosis and uncle with tuberculosis. He was emaciated, with remarkable flaccidity, sarcopenia, severe mucosal skin paleness, generalized lymphadenomegaly and hepatosplenomegaly. In the clinical picture, lymphoproliferative disease was initially suspected. It presented microcytic and hypochromic anemia, HIV negative serology, syphilis, leishmaniasis and viral hepatitis, (PPS) was not a reactor. The anatomopathologicals presented negative research for fungi and parasites and suggested lymphoproliferative disease. However, immunohistochemistry revealed a pattern of reactional lymph nodes. Due to the initial suspicion of lymphoproliferative disease, prophylaxis was started for tumoral lysis with hydration and allopurinol. In addition, due to the various lymph node metastasis, empiric treatment with Prednisone 80 mg / day was initiated, with improvement of the clinical picture, remission of fever and arthralgia. and immunohistochemistry discarded proliferative diseases, weaning of the corticosteroid was started, with a resurgence of fever, this time accompanied by evanescent cutaneous rash in limbs and right knee arthritis. After eliminating infectious, neoplastic and other etiologies diseases, it was considered the diagnosis of Still, once the patient presented a compatible clinical picture and fulfilled Yamaguchi criteria. Initiated therapy with methotrexate, with improvement of the clinical picture and hospital discharge. (AU)

Glomerulonefritis rápidamente progresiva asociada a nefritis lúpica en una paciente de mediana edad / Quickly progressive glomerulonephritis associated with lupus nephritis in a middle age patient

Se describe el caso clínico de una paciente de 47 años de edad con antecedentes de síndrome linfoproliferativo, que fue ingresada en la sala de Hematología del Hospital General Docente Dr Juan Bruno Zayas Alfonso de Santiago de Cuba, y luego se le trasladó al Servicio de Nefrología por presentar dolor poliarticular, fiebre, edemas, disminución de la diuresis y aumento progresivo de la creatinina plasmática. El cuadro clínico y los exámenes complementarios permitieron diagnosticar una glomerulonefritis rápidamente progresiva como consecuencia de una nefritis lúpica de clase IV. La paciente fue tratada con prednisona y ciclofosfamida, y mostró una evolución satisfactoria sin necesidad de recurrir a tratamiento hemodialítico

The case report of a 47 years patient is described with a history of lymphoproliferative syndrome who was admitted at the Hematology room of Dr Juan Bruno Zayas Alfonso Teaching General Hospital in Santiago de Cuba, and then she was transferred to the Nephrology Service due to a polyarticular pain, fever, edemas, decrease of diuresis and progressive increase of the plasmatic creatinine. The clinical pattern and the lab tests allowed to diagnose a quickly progressive glomerulonephritis as consequence of a lupus nephritis class IV. The patient was treated with prednisone and cyclophosphamide, and she showed a satisfactory clinical course without the necessity of using hemodyalisis treatment

Síndrome linfoproliferativo postrasplante con compromiso cerebral: reporte de un caso / Post-transplantation lymphoproliferative disorder with brain involvement: a case report

Abstract. Post-transplantation lymphoproliferative disorder is a low incidence complication of transplant recipient patients. However, mortality is high if the diagnosis and management are not appropriate. For this reason the radiologist should be aware when dealing with images of these patients, particularly in the first year following the transplantation. In this article the case is presented of a woman who was recipient of a kidney, and developed post-transplantation lymphoproliferative disorder, affecting the central nervous system.

Resumen. El síndrome linfoproliferativo postrasplante es una complicación que se presenta con una baja incidencia en los pacientes que han sido trasplantados. Sin embargo, si el diagnóstico y manejo no son oportunos su mortalidad es alta. Por esta razón el radiólogo debe estar atento al diagnóstico al interpretar estudios de este tipo de pacientes, especialmente en el año siguiente al trasplante. Presentamos el caso de una paciente con antecedente de trasplante renal y síndrome linfoproliferativo postrasplante con afección del sistema nervioso central.

A case of autoimmune lymphoproliferactive syndrome and literature review / 中华儿科杂志

<p><b>OBJECTIVE</b>To summarize the clinical characteristics, diagnosis and treatment of a case with autoimmune lymphoproliferative syndrome (ALPS) .</p><p><b>METHOD</b>The patient was diagnosed as autoimmune lymphoproliferactive syndrome (ALPS) after being admitted to the Department of Rheumatism and Immunology of Tianjin Children's Hospital in February 20, 2014. The clinical characteristics, physical examination, laboratory tests, gene tests, and treatment process were analyzed and related literature was reviewed.</p><p><b>RESULT</b>The patient was a 16-month- old boy.Since the first month of life, he started to have repeatedly fever, diarrhea, shortness of breath, lymphadenopathy, hepatosplenomegaly, anemia (HGBmin 50 g/L) and thrombocytopenia (min 35 × 10⁹/L) . But multiple exams showed a normal peripheral blood leukocyte count, hypergammaglobulinemia (IgG 19 800 mg/L, IgA 1 710 mg/L, IgM 2 590 mg/L) and significantly increased serum vitamin B12. Flow cytometric measures showed that CD3⁺ CD4⁻ CD8⁻ T lymphocytes significantly increased ( > 10%) at four times. The count of CD3⁺ TCRαβ⁺ CD4⁻ CD8⁻T lymphocytes (double negative T cells; DNTs) >3% twice. The genetic test showed that 309th FAS gene area showed heterozygous mutations, the boy was diagnosed as ALPS. Added examinations of lymphocytes apoptosis induced by FAS was positive. He was treated with prednisone 15 mg once daily and immunomodulator 150 mg three times a day, while in maintaining period with normal levels of hemoglobin and platelet, the dose of prednisone was reduced gradually. Till now, the patient has been treated and observed for 8 months. We retrieved the reports of ALPS in the databases at home and abroad published in recent 10 years, more than 400 cases reported from foreign countries, but there were only 5 domestic cases. Among those, 4 had onset in infancy and 1 at 6-years of age. All the cases presented servere lymphadenopathy and hepatosplenomegaly with anemia (4 of them with hemolytic anemia) and thrombocytopenia. Three cases had a history of frequent infection, one of them had glomerulonephritis. All patient with significant high level of serum immunoglobulin ( > 1.5 times upper limit of normal range), in 3 of them serum vitamin B12 was > 1.5 pg/L (the other 2 cases missed the exam). In 5 cases CD3⁺ CD4⁻ CD8⁻T cells > 10%, and in 2 case DNTs were 8.9% and 15.7% respectively (the other 3 cases missed the exam). Three cases were clearly detected with FAS mutations. All patients were treated with corticosteroid, 2 of them were added with mycophenolate mofetil. The therapy presented effective result in early 1-3 months, but no long-term follow-up reports were available.</p><p><b>CONCLUSION</b>ALPS is a disorder of disrupted lymphocyte homeostasis caused by defective Fas-mediated apoptosis, and it is one of the primary immunodeficiency diseases. The onset of the disease occurs during infancy mainly. Clinical lymphoid hyperplasia and autoimmune phenomena are outstanding signs, which can be associated with frequent infections and allergies. The level of serum vitamin B12 > 1.5 pg/L and the count of CD3⁺ CD4⁻ CD8⁻ T cell show important significance. Exact diagnosis should depend on detecting DNTs and FAS gene.</p>

Experiencia en el desarrollo y la aplicación de la inmunología en los últimos 10 años / Experience in development and application of Immunology in the past 10 years

Se presentan los resultados alcanzados en las investigaciones inmunológicas realizadas en el Instituto de Hematología e Inmunología en los últimos 10 años. Se describen las investigaciones básicas fundamentales relacionadas con el estudio de las moléculas de adhesión en condiciones fisiológicas y patológicas, como el síndrome coronario agudo y la anemia drepanocítica (AD). Se refieren los trabajos relacionados con el diagnóstico inmunológico de los síndromes linfoproliferativos que aportaron datos a la inmunoepidemiología de las hemopatías malignas, especialmente en sus características fenotípicas; los aspectos de mayor interés en el estudio de la AD, como la disminución de los niveles de los anticuerpos naturales anti-banda 3 en los enfermos con crisis vasooclusivas y su posible participación en el fenómeno de vasooclusión, así como la importancia de las moléculas de adhesión en su etiopatogenia. Se describen los resultados del estudio de detección de anticuerpos contra la proteína de fusión PML/RARa en la leucemia promielocítica y su posible utilidad como marcador de diferenciación celular a partir de la presencia o ausencia de la proteína de fusión en la célula leucémica. Los resultados obtenidos han contribuido notablemente al desarrollo de la Inmunología en Cuba y servirán de pauta para el desarrollo futuro de la especialidad

Authors showed the results achieved in immunological researches in the Institute of Hematology and Immunology during past 10 years. The main basic researches are described in relation to the study of adhesion molecules under physiological and pathological conditions like in the case of the acute coronary syndrome and the drepanocythemia (D). The papers related to the immunological diagnosis of lymphoproliferative syndromes are refered which provide data to the immunoepidemiology of malignant hemopathies, specially in its phenotypic characteristics; the features of more interest in the study of the D, e.g. the decrease of levels of anti-band 3 natural antibodies in patients with vaso-occlusive crisis and its possible participation in the phenomenon of vaso-occlusion, as well as the significance of adhesion molecules in its etiopathogenesis. The results from the study of antibodies detection to PML/RARa fusion protein in the promyelocyte leukemia and its possible usefulness as marker of cellular differentiation from the presence or absence of fusion protein in the leukemic cell are described. The results achieved have contributing very much to development of Immunology in Cuba and will become standard for the future development of the specialty