RESUMEN
The transcriptional programs that guide lymphocyte differentiation depend on the precise expression and timing of transcription factors (TFs). The TF BACH2 is essential for T and B lymphocytes and is associated with an archetypal super-enhancer (SE). Single-nucleotide variants in the BACH2 locus are associated with several autoimmune diseases, but BACH2 mutations that cause Mendelian monogenic primary immunodeficiency have not previously been identified. Here we describe a syndrome of BACH2-related immunodeficiency and autoimmunity (BRIDA) that results from BACH2 haploinsufficiency. Affected subjects had lymphocyte-maturation defects that caused immunoglobulin deficiency and intestinal inflammation. The mutations disrupted protein stability by interfering with homodimerization or by causing aggregation. We observed analogous lymphocyte defects in Bach2-heterozygous mice. More generally, we observed that genes that cause monogenic haploinsufficient diseases were substantially enriched for TFs and SE architecture. These findings reveal a previously unrecognized feature of SE architecture in Mendelian diseases of immunity: heterozygous mutations in SE-regulated genes identified by whole-exome/genome sequencing may have greater significance than previously recognized.
Asunto(s)
Enfermedades Autoinmunes/genética , Factores de Transcripción con Cremalleras de Leucina de Carácter Básico/genética , Síndromes de Inmunodeficiencia/genética , Corticoesteroides/uso terapéutico , Adulto , Enfermedades Autoinmunes/complicaciones , Colitis/complicaciones , Colitis/genética , Colitis/patología , Femenino , Fiebre/complicaciones , Fiebre/tratamiento farmacológico , Fiebre/genética , Haploinsuficiencia , Heterocigoto , Humanos , Síndromes de Inmunodeficiencia/complicaciones , Linfopenia/complicaciones , Linfopenia/genética , Masculino , Persona de Mediana Edad , Mutación , Pancitopenia/complicaciones , Pancitopenia/tratamiento farmacológico , Pancitopenia/genética , Linaje , Polimorfismo de Nucleótido Simple , Recurrencia , Infecciones del Sistema Respiratorio/complicaciones , Infecciones del Sistema Respiratorio/diagnóstico por imagen , Infecciones del Sistema Respiratorio/genética , Esplenomegalia/complicaciones , Esplenomegalia/genética , Síndrome , Tomografía Computarizada por Rayos X , Adulto JovenRESUMEN
Pancytopenia with hypocellular bone marrow is the hallmark of aplastic anaemia (AA) and the diagnosis is confirmed after careful evaluation, following exclusion of alternate diagnosis including hypoplastic myelodysplastic syndromes. Emerging use of molecular cyto-genomics is helpful in delineating immune mediated AA from inherited bone marrow failures (IBMF). Camitta criteria is used to assess disease severity, which along with age and availability of human leucocyte antigen compatible donor are determinants for therapeutic decisions. Supportive care with blood and platelet transfusion support, along with anti-microbial prophylaxis and prompt management of opportunistic infections remain key throughout the disease course. The standard first-line treatment for newly diagnosed acquired severe/very severe AA patients is horse anti-thymocyte globulin and ciclosporin-based immunosuppressive therapy (IST) with eltrombopag or allogeneic haemopoietic stem cell transplant (HSCT) from a matched sibling donor. Unrelated donor HSCT in adults should be considered after lack of response to IST, and up front for young adults with severe infections and a readily available matched unrelated donor. Management of IBMF, AA in pregnancy and in elderly require special attention. In view of the rarity of AA and complexity of management, appropriate discussion in multidisciplinary meetings and involvement of expert centres is strongly recommended to improve patient outcomes.
Asunto(s)
Anemia Aplásica , Hematología , Trasplante de Células Madre Hematopoyéticas , Pancitopenia , Adulto Joven , Humanos , Anciano , Anemia Aplásica/terapia , Inmunosupresores/uso terapéutico , Ciclosporina/uso terapéutico , Trastornos de Fallo de la Médula Ósea/tratamiento farmacológico , Donante no Emparentado , Pancitopenia/tratamiento farmacológicoRESUMEN
BACKGROUND: Aplastic anemia (AA) is a rare but fatal disorder characterized by pancytopenia due to bone marrow hypoplasia. Anti-glomerular basement membrane disease (anti-GBM disease) is an immune complex small-vessel vasculitis that presents as rapidly progressive glomerulonephritis and/or pulmonary hemorrhage. Although both involve autoreactive T cells that are partially triggered by human leukocyte antigen (HLA)-DR15, there have been no reports of their co-existence and the treatment strategy is not well understood. CASE PRESENTATION: A 67-year-old woman presented with fever, malaise, and acute kidney injury with proteinuria and hematuria requiring hemodialysis. She was diagnosed with anti-GBM antibody disease based on high serum anti-GBM antibody titer and crescentic glomerulonephritis on a renal biopsy. Pulse administration of methylprednisolone (MP), oral prednisolone (PSL), and plasmapheresis were performed. Only 2 weeks after the diagnosis of anti-GBM disease, the patient developed pancytopenia requiring frequent blood transfusions. The blood cell count did not recover even 1 month after discontinuing the drugs that could cause pancytopenia. Bone marrow examination showed hypocellularity without abnormal infiltrates or fibrosis, which led to the diagnosis of severe acquired AA. Further HLA phenotyping revealed that she had HLA-DR15. Increased dose of PSL with the secondary MP pulse and the addition of cyclosporine improved pancytopenia. Although she remained dialysis-dependent, anti-GBM disease and pancytopenia did not recur for more than 2 years. CONCLUSIONS: We report the first case of acquired AA complicated with anti-GBM disease in an elderly woman with HLA-DR15, which was successfully treated with immunosuppressive therapy (IST). This report is valuable not only because it shows they may co-occur, but also because it provides a therapeutic option for this complex condition. It was also suggested that pancytopenia in patients with anti-GBM disease recalls serious hematologic diseases including AA that require immediate treatment based on bone marrow examination.
Asunto(s)
Anemia Aplásica , Enfermedad por Anticuerpos Antimembrana Basal Glomerular , Glomerulonefritis , Pancitopenia , Anciano , Anemia Aplásica/complicaciones , Anemia Aplásica/tratamiento farmacológico , Enfermedad por Anticuerpos Antimembrana Basal Glomerular/complicaciones , Enfermedad por Anticuerpos Antimembrana Basal Glomerular/diagnóstico , Enfermedad por Anticuerpos Antimembrana Basal Glomerular/tratamiento farmacológico , Autoanticuerpos , Femenino , Glomerulonefritis/diagnóstico , Humanos , Terapia de Inmunosupresión , Inmunosupresores/uso terapéutico , Metilprednisolona/uso terapéutico , Pancitopenia/complicaciones , Pancitopenia/tratamiento farmacológicoRESUMEN
INTRODUCTION: Multiple myeloma (MM) is the second most common hematological malignancy, accounting for 1% of all cancers, with median age of diagnosis between 66-70 years. MM remains incurable despite advances in treatment over time. Lenalidomide is an important medication used in induction therapy for MM and is also used for maintenance therapy for standard risk patients. With its increasing use, data is emerging about its use being associated with increased risk of secondary primary malignancies (SPM), especially when used as maintenance therapy. CASE SERIES: In this case series, we describe three patients with refractory MM treated with lenalidomide maintenance who later developed sALL. All had a common presentation of pancytopenia. They developed cytopenias while being on lenalidomide which was refractory to lenalidomide cessation, prompting bone marrow biopsy. MANAGEMENT AND OUTCOME: Lenalidomide was subsequently stopped, and patients were treated for secondary B-ALL. However, all passed away either due to relapse of disease or complications arising from treatment. DISCUSSION: The mechanism of lenalidomide associated SPMs is not well understood however its incidence is well documented. At least 13 cases of ALL (predominantly B-cell ALL) following Immunomodulator imide drugs (IMiDs) have been reported in literature. An analysis of a larger cohort of patients is required to determine causality of lenalidomide with sALL. However, benefits of maintenance lenalidomide in patients with MM outweighs the risk of developing SPMs. Albeit persistent pancytopenia on lenalidomide therapy should be evaluated with bone marrow biopsy since it could be caused by secondary B -cell ALL.
Asunto(s)
Mieloma Múltiple , Pancitopenia , Humanos , Anciano , Mieloma Múltiple/terapia , Lenalidomida/efectos adversos , Talidomida/efectos adversos , Pancitopenia/tratamiento farmacológico , Recurrencia Local de Neoplasia/tratamiento farmacológicoRESUMEN
BACKGROUND: We aimed to report the clinical characteristics, immunological features, and treatment of one patient with a de novo STAT3 gain-of-function mutation identified by next generation sequencing. We investigated the efficacy of tocilizumab therapy in immune dysregulation diseases caused by STAT3 mutation. RESULTS: The patient was a 16-year-old girl. She presented with recurrent respiratory infections and chronic diarrhea after birth. She had life-threatening autoimmune pancytopenia at 14 years old. After receiving glucocorticoid therapy, she developed diabetes. However, her pancytopenia relapsed when the glucocorticoid was tapered. Next-generation sequencing showed a de novo heterozygous mutation in the STAT3 gene, c.1261G > A (p. G421R), which was previously described as a gain-of-function mutation. After tocilizumab therapy, her pancytopenia fully resolved, and insulin and glucocorticoid therapies were gradually discontinued within 12 months. She had lymphopenia and an inverted CD4/CD8 ratio before therapy. Lymphocyte subpopulation analysis indicated an expansion of effector memory CD4+, effector memory CD8+ and central memory CD4+ T cells. The proportions of memory B cells and naive CD4+ T cells were decreased, and the proportion of naïve B cells was increased. None of the abnormal lymphocytic changes improved significantly. STAT3 GOF mutations were identified by next gene sequencing in those with early-onset multi-organ autoimmunity. Including our patient, 13 patients with STAT3 GOF mutations received targeted treatment. Twelve of them were treated with tocilizumab alone or combination tocilizumab with JAK inhibitor, and ten patients improved. CONCLUSIONS: Gene sequencing should be performed for patients with early-onset refractory or multiorgan immune dysregulation diseases. Targeted drugs can effectively improve the clinical problems associated with STAT3 gain-of-function mutations, while nontargeted immunosuppressive therapy is usually insufficient.
Asunto(s)
Anticuerpos Monoclonales Humanizados/uso terapéutico , Pancitopenia/tratamiento farmacológico , Pancitopenia/genética , Factor de Transcripción STAT3/genética , Adolescente , Linfocitos B/efectos de los fármacos , Femenino , Mutación con Ganancia de Función , Humanos , Interleucina-6/sangre , Subgrupos Linfocitarios/efectos de los fármacos , Pancitopenia/inmunología , Linfocitos T/efectos de los fármacos , Resultado del TratamientoRESUMEN
Progressive cytopenia is a serious complication among paediatric patients with inherited bone marrow failure syndromes (IBMFS). Androgens have been used to improve blood counts in different bone marrow failure conditions. Little is known about efficacy and toxicity with new androgens (i.e., danazol) in different types of IBMFS. We identified 29 patients from the Canadian Inherited Marrow Failure Registry, who received oxymetholone or danazol. Sixteen (55%) had haematological response including patients with unclassified IBMFS (45%). Danazol showed a better toxicity profile and similar efficacy compared to oxymetholone. Androgens are an effective and safe option to ameliorate bone marrow failure in IBMFS.
Asunto(s)
Andrógenos/uso terapéutico , Trastornos de Fallo de la Médula Ósea/tratamiento farmacológico , Adolescente , Adulto , Andrógenos/efectos adversos , Trastornos de Fallo de la Médula Ósea/sangre , Trastornos de Fallo de la Médula Ósea/genética , Trastornos de Fallo de la Médula Ósea/terapia , Canadá/epidemiología , Linaje de la Célula , Niño , Preescolar , Terapia Combinada , Danazol/efectos adversos , Danazol/uso terapéutico , Progresión de la Enfermedad , Sustitución de Medicamentos , Femenino , Trasplante de Células Madre Hematopoyéticas , Humanos , Lactante , Masculino , Persona de Mediana Edad , Oximetolona/efectos adversos , Oximetolona/uso terapéutico , Pancitopenia/tratamiento farmacológico , Pancitopenia/etiología , Sistema de Registros , Trombocitopenia/tratamiento farmacológico , Trombocitopenia/etiología , Resultado del Tratamiento , Virilismo/inducido químicamenteRESUMEN
INTRODUCTION: Prognosis of metastatic castrate-resistant prostate cancer is poor with a median survival of 12 to 36 months. Bone metastasis is common, and bone marrow metastasis occurs later in the disease course. The median survival in these patients after bone marrow involvement is less than six months. We report a case of castrate-resistant prostate cancer patient presented with severe pancytopenia due to bone marrow involvement of prostate cancer, treated successfully with docetaxel chemotherapy. Post chemotherapy, the patient became transfusion independent and prostate-specific antigen improved to 0.1 ng/ml from 1051 ng/ml. CASE REPORT: A 70-year-old gentleman with a history of metastatic prostate cancer on androgen deprivation therapy and polycythemia vera presented to emergency room with dizziness and melena. Workup revealed severe pancytopenia with platelet count of 12k and hemoglobin of 4.5 gm/dl. Bone marrow biopsy confirmed diffuse involvement of bone marrow with prostate cancer. Prostate-specific antigen was 1051 gm/dl. Management and outcome: The patient received 14 units of packed red blood cell, 10 units of platelet transfusion within one week. Docetaxel chemotherapy was started along with thrombopoietin agonist romiplostim and pegylated filgrastim. He received five cycles of docetaxel treatment. Post chemotherapy, the patient became transfusion independent and prostate-specific antigen improved to 1.17 ng/ml from 1051 ng/ml. The patient is still alive one year after the presentation with good quality of life and the prostate-specific antigen further improved to 0.1 ng/dl. CONCLUSION: This case suggests that selected patients with severe pancytopenia, due to bone marrow infiltration of prostate cancer, can be treated with docetaxel chemotherapy and romiplostim support with significant response. Docetaxel treatment may be beneficial to unpack the marrow and for quicker response in patients with good performance status.
Asunto(s)
Antineoplásicos/uso terapéutico , Docetaxel/uso terapéutico , Pancitopenia/tratamiento farmacológico , Neoplasias de la Próstata Resistentes a la Castración/tratamiento farmacológico , Índice de Severidad de la Enfermedad , Anciano , Humanos , Masculino , Pancitopenia/diagnóstico por imagen , Antígeno Prostático Específico/sangre , Neoplasias de la Próstata Resistentes a la Castración/sangre , Neoplasias de la Próstata Resistentes a la Castración/diagnóstico por imagen , Resultado del TratamientoRESUMEN
BACKGROUND & OBJECTIVES: Brucellosis can lead to haematological abnormalities including cytopenia confusing with haematological malignancies. The aim of this study was to compare the main characteristics of brucellosis patients without cytopenia (Group 1) and with cytopenia (Group 2). METHODS: This five-year period study which was performed in two referral hospitals in Turkey, included all adult brucellosis patients. Abnormally, low counts of leucocyte or haemoglobin or platelets in a patient were considered as cytopenia. The demographics, clinical, laboratory, treatment and outcome data were analyzed. RESULTS: A total of 484 brucellosis patients were enrolled. Among the cases, 162 (33.5%) of them had cytopenia. One hundred and four (21.5%) had anaemia, 88 (18.8%) had thrombocytopenia, 71 (14.6%) had leucopenia and 28 (5.8%) had pancytopenia. The mean age of group 2 was 35.01±16.05 yr and it was 33.31±14.39 yr in group 1. While there was no difference between the groups in terms of duration of treatment, the median length of hospital stay (LOS) was significantly longer in group 2 (9 vs 10 days; P<0.001). The most frequently applied combination therapy consisted of doxycycline plus rifampicin and doxycycline plus streptomycin regimens. No significant difference was observed in terms of duration of treatment, LOS and restoration time of cytopenia between the patients who received either of these combinations. INTERPRETATION & CONCLUSIONS: Our findings suggested that the patients with cytopenia should be investigated for brucellosis, especially if living in, or with a history of travel to, endemic areas, in view of the increase in world travel.
Asunto(s)
Brucelosis/tratamiento farmacológico , Neoplasias Hematológicas/tratamiento farmacológico , Pancitopenia/tratamiento farmacológico , Trombocitopenia/tratamiento farmacológico , Adulto , Anemia/complicaciones , Anemia/tratamiento farmacológico , Anemia/epidemiología , Brucelosis/complicaciones , Brucelosis/epidemiología , Doxiciclina/administración & dosificación , Femenino , Neoplasias Hematológicas/complicaciones , Neoplasias Hematológicas/epidemiología , Humanos , Masculino , Persona de Mediana Edad , Pancitopenia/complicaciones , Pancitopenia/epidemiología , Rifampin/administración & dosificación , Estreptomicina/administración & dosificación , Trombocitopenia/complicaciones , Trombocitopenia/epidemiología , TurquíaRESUMEN
Autoimmune lymphoproliferative syndrome (ALPS) is a disorder of lymphocyte apoptosis. Children present with chronic nonmalignant lymphadenopathy, hepatosplenomegaly, and autoimmune cytopenias. Recent advances show efficacy of treatment with immunosuppressive drugs. Sirolimus, an mammalian target of rapamycin inhibitor, improves autoimmune cytopenias and lymphoproliferation, with a safe profile. We present 2 patients, a 5-year-old girl and 15-year-old boy, diagnosed with ALPS with initial partial response to steroid treatment. Autoimmune cytopenias and lymphoproliferation then became refractory to treatment, with recurrence of symptoms. In both cases, treatment with sirolimus was started, with a rapid response, complete remission of cytopenias, and resolution of lymphoproliferation, with no significant adverse effects. CONCLUSION: sirolimus is an effective and safe drug for controlling children with cytopenias and lymphoproliferation linked to ALPS.
Asunto(s)
Síndrome Linfoproliferativo Autoinmune/tratamiento farmacológico , Pancitopenia/tratamiento farmacológico , Sirolimus/administración & dosificación , Adolescente , Preescolar , Femenino , Humanos , Trastornos Linfoproliferativos/tratamiento farmacológico , Masculino , Sirolimus/uso terapéutico , Resultado del TratamientoRESUMEN
An 8-year-old spayed Portuguese water dog was presented with dysuria, lethargy, and anorexia. A profound neutropenia and pancytopenia were identified. Bone marrow aspirates revealed neutrophilic hyperplasia, a significant left shift, and toxic changes, suggesting immune-mediated destruction as a likely underlying mechanism. Immunosuppressive therapy was instituted and clinical signs improved.
Neutropénie à médiation immunitaire suspectée et pancytopénie répondant aux corticostéroïdes chez un Chien d'eau portugais. Un Chien d'eau portugais femelle stérilisée âgée de 8 ans a été présentée avec de la dysurie, de la léthargie et de l'anorexie. Une neutropénie profonde et de la pancytopénie ont été identifiées. Des aspirations de la moelle osseuse ont révélé une hyperplasie neutrophilique, un virage important vers la gauche et des changements toxiques suggérant une destruction à médiation immunitaire comme mécanisme sous-jacent probable. Une thérapie immunosuppressive a été instituée et les signes cliniques se sont améliorés.(Traduit par Isabelle Vallières).
Asunto(s)
Dexametasona/uso terapéutico , Enfermedades de los Perros/inmunología , Neutropenia/veterinaria , Pancitopenia/veterinaria , Prednisona/uso terapéutico , Animales , Enfermedades de los Perros/tratamiento farmacológico , Perros , Femenino , Glucocorticoides/uso terapéutico , Neutropenia/tratamiento farmacológico , Pancitopenia/tratamiento farmacológicoRESUMEN
Hematological abnormalities, such as anemia, leucopenia, and thrombocytopenia, secondary to peripheral destruction, are common in systemic lupus erythematosus (SLE). However, cytopenias from autoimmune myelofibrosis (AIMF) are extremely uncommon in SLE, with less than 40 reported cases in the literature. We report the case of a 33-year-old female who presented with bullous skin lesions and pancytopenia as the presenting manifestation of what was ultimately diagnosed as SLE with AIMF. She responded well to glucocorticoids and mycophenolate mofetil.
Asunto(s)
Enfermedades Autoinmunes/tratamiento farmacológico , Glucocorticoides/uso terapéutico , Inmunosupresores/uso terapéutico , Lupus Eritematoso Sistémico/tratamiento farmacológico , Pancitopenia/tratamiento farmacológico , Prednisona/uso terapéutico , Mielofibrosis Primaria/tratamiento farmacológico , Adulto , Enfermedades Autoinmunes/complicaciones , Enfermedades Autoinmunes/diagnóstico , Biopsia , Femenino , Humanos , Lupus Eritematoso Sistémico/complicaciones , Lupus Eritematoso Sistémico/diagnóstico , Ácido Micofenólico/uso terapéutico , Pancitopenia/diagnóstico , Pancitopenia/etiología , Mielofibrosis Primaria/complicaciones , Mielofibrosis Primaria/diagnóstico , Resultado del TratamientoAsunto(s)
Dolor Abdominal/etiología , Lupus Eritematoso Sistémico/diagnóstico por imagen , Paniculitis Peritoneal/diagnóstico por imagen , Tomografía Computarizada por Rayos X/métodos , Dolor Abdominal/tratamiento farmacológico , Anciano , Fatiga/tratamiento farmacológico , Fatiga/etiología , Femenino , Humanos , Lupus Eritematoso Sistémico/complicaciones , Pancitopenia/tratamiento farmacológico , Paniculitis de Lupus Eritematoso/diagnóstico por imagen , Prednisolona/uso terapéutico , Tacrolimus/uso terapéuticoRESUMEN
Filgrastim is a granulocyte colony-stimulating factor commonly used in the prophylaxis and treatment of neutropenia associated with chemotherapy in cancer patients. It is a well-tolerated and safe drug but some unusual serious adverse effects may occur. We expose a case of a 37-year-old woman who was hospitalized with severe pancitopenia after the first cycle of chemotherapy with a cisplatin doublet and bevacizumab. Filgrastim was administered for 3 days with the aim of increasing neutrophils and not delay the next chemotherapy cycle. Due to acute respiratory failure she was transferred to the Intensive Care Unit for symptomatic control where required oxygen therapy. Fungal and bacterial culture were made and so blood serologies, all of them were negative. It was diagnosed as pneumonitis secondary to a probable side effect of filgrastim. Although the case was resolved properly it is important monitor the administration of filgrastim because of the severity of these events.
Asunto(s)
Filgrastim/efectos adversos , Fármacos Hematológicos/efectos adversos , Pancitopenia/tratamiento farmacológico , Neumonía/inducido químicamente , Insuficiencia Respiratoria/inducido químicamente , Adulto , Protocolos de Quimioterapia Combinada Antineoplásica/efectos adversos , Bevacizumab/administración & dosificación , Carcinoma de Células Escamosas/tratamiento farmacológico , Cisplatino/administración & dosificación , Enfermedad Crítica , Femenino , Humanos , Terapia por Inhalación de Oxígeno , Pancitopenia/inducido químicamente , Neumonía/diagnóstico por imagen , Neumonía/terapia , Radiografía Torácica , Insuficiencia Respiratoria/diagnóstico por imagen , Insuficiencia Respiratoria/terapia , Neoplasias del Cuello Uterino/tratamiento farmacológicoRESUMEN
Pharmacogenetics is a study of how genetic variation of an individual affects the drug response. We report a case of recurrent pancytopenia resulting from maintenance chemotherapy in a patient with acute promyelocytic leukemia and two pharmacogenetic mutations, namely, methylene tetrahydrofolate reductase C677T homozygous mutation and thiopurine methyltransferase mutation.
Asunto(s)
Leucemia Promielocítica Aguda/genética , Quimioterapia de Mantención/métodos , Metilenotetrahidrofolato Reductasa (NADPH2)/genética , Metiltransferasas/genética , Mutación/genética , Pancitopenia/genética , Humanos , Leucemia Promielocítica Aguda/tratamiento farmacológico , Masculino , Persona de Mediana Edad , Pancitopenia/tratamiento farmacológico , RecurrenciaRESUMEN
A 73-year-old woman was admitted to our hospital because of pancytopenia. Bone marrow aspiration showed increased cellularity with no dysplastic change. Laboratory tests revealed increased reticulated erythrocytes and reticulated platelets, positive direct Coombs test, and hemolysis. These findings led to the diagnosis of Evans syndrome. Relatively decreased mature neutrophils in the bone marrow aspirate raised the possibility of autoimmune neutropenia. Antineutrophil antibody was detected by the 6 cell-lineage immunofluorescence test, consistent with the diagnosis of autoimmune neutropenia. The patient had no underlying diseases, and was therefore considered to have idiopathic autoimmune pancytopenia. Due to rapid progression of the disease, prednisolone was administered at an initial dose of 0.5 mg/kg per day and the pancytopenia improved promptly.
Asunto(s)
Anemia Hemolítica Autoinmune/diagnóstico , Anemia Hemolítica Autoinmune/tratamiento farmacológico , Glucocorticoides/uso terapéutico , Pancitopenia/tratamiento farmacológico , Prednisolona/uso terapéutico , Trombocitopenia/diagnóstico , Trombocitopenia/tratamiento farmacológico , Anciano , Anemia Hemolítica Autoinmune/complicaciones , Anemia Hemolítica Autoinmune/patología , Biopsia , Linaje de la Célula , Progresión de la Enfermedad , Femenino , Humanos , Pancitopenia/etiología , Pancitopenia/patología , Trombocitopenia/complicaciones , Trombocitopenia/patologíaAsunto(s)
Proteínas Adaptadoras Transductoras de Señales/genética , Enfermedades Autoinmunes/tratamiento farmacológico , Enfermedades Autoinmunes/etiología , Inmunosupresores/uso terapéutico , Mutación , Pancitopenia/tratamiento farmacológico , Pancitopenia/etiología , Sirolimus/uso terapéutico , Enfermedades Autoinmunes/diagnóstico , Manejo de la Enfermedad , Susceptibilidad a Enfermedades , Predisposición Genética a la Enfermedad , Humanos , Inmunosupresores/administración & dosificación , Masculino , Pancitopenia/diagnóstico , Sirolimus/administración & dosificaciónAsunto(s)
Pancitopenia/etiología , Púrpura Trombocitopénica Idiopática/complicaciones , Anciano , Benzoatos/uso terapéutico , Médula Ósea/efectos de los fármacos , Médula Ósea/patología , Enfermedad Crónica , Ciclosporina/uso terapéutico , Humanos , Hidrazinas/uso terapéutico , Factores Inmunológicos/uso terapéutico , Inmunosupresores/uso terapéutico , Masculino , Pancitopenia/tratamiento farmacológico , Pancitopenia/patología , Púrpura Trombocitopénica Idiopática/tratamiento farmacológico , Púrpura Trombocitopénica Idiopática/patología , Pirazoles/uso terapéutico , Receptores de Trombopoyetina/agonistas , Rituximab/uso terapéuticoRESUMEN
In rare cases, pancytopenia results from hormonal deficiencies that arise in the setting of panhypopituitarism. Here we describe the unusual case of a 60-year-old man who presented with progressive fatigue and polyuria, and whose laboratory workup revealed a deficiency of the five hormones associated with the action of the anterior pituitary (thyroid hormone, testosterone, cortisol, prolactin, and insulin-like growth factor-1). Imaging of the pituitary demonstrated a cystic mass consistent with a pituitary adenoma replacing much of the normal pituitary tissue. His symptoms and hematologic abnormalities rapidly resolved with prednisone and levothyroxine supplementation. While the majority of reported cases of panhypopituitarism with bone marrow suppression are the result of peripartum sepsis or hemorrhage leading to pituitary gland necrosis (Sheehan's syndrome), it is also important to consider the diagnosis of hypopituitarism in patients with hypothyroidism, low cortisol levels, and pancytopenia. The causal relationship between pancytopenia and panhypopituitarism is not well understood, though it does reinforce the important influence of these endocrine hormones on the health of the bone marrow.
Asunto(s)
Adenoma/diagnóstico , Hipopituitarismo/diagnóstico , Pancitopenia/diagnóstico , Neoplasias Hipofisarias/diagnóstico , Prednisona/uso terapéutico , Tiroxina/uso terapéutico , Adenoma/complicaciones , Adenoma/tratamiento farmacológico , Médula Ósea/patología , Quimioterapia Combinada , Pruebas Hematológicas , Humanos , Hipopituitarismo/complicaciones , Hipopituitarismo/tratamiento farmacológico , Pruebas de Función Renal , Imagen por Resonancia Magnética/métodos , Masculino , Persona de Mediana Edad , Pancitopenia/complicaciones , Pancitopenia/tratamiento farmacológico , Neoplasias Hipofisarias/complicaciones , Neoplasias Hipofisarias/tratamiento farmacológico , Enfermedades Raras , Resultado del TratamientoRESUMEN
Pancytopenia is a very rare complication of thymoma and has been sporadically reported in only a few cases. We report a case of a 68-year-old woman who presented with pancytopenia associated with thymoma. After failing high-dose corticosteroids, she responded to cyclosporine treatment and underwent successful thymectomy. We also reviewed all other similar cases published in the English language literature. Surgical resection by itself was generally ineffective for treatment of pancytopenia, and immunosuppressive therapy was required for bone marrow recovery. Resolution of pancytopenia was most frequently associated with cyclosporine-based therapy with a response rate (RR) of 66.6 %. In conclusion, pancytopenia associated with thymoma requires medical treatment, and the evidence presented here suggests that a cyclosporine-based regimen should be considered for initial therapy.