Hemofilia adquirida como manifestación inicial de recidiva de adenocarcinoma colorrectal / Acquired hemophilia as the initial manifestation of colorectal cancer's recurrence

Resumen Presentamos el caso de un varón de 86 años con un hematoma espontáneo en el músculo ilíaco izquierdo y diagnóstico previo de cáncer de colon en 1998 (estadio pT3N0M0), tratado quirúrgicamente mediante colectomía transversal, considerado en remisión completa. Tras realización de estudios complementarios se demostró la presencia de autoanticuerpos inhibidores del Factor VIII que confirmaron el diagnóstico de hemofilia adquirida. Durante el ingreso el paciente presentó un sangrado digestivo bajo que conllevó al descubrimiento de recidiva del adenocarcinoma colorrectal tratado previamente. Respondió de forma favorable a la terapia inicial con corticoides sistémicos y el complejo coagulante anti inhibidor que incluye el Factor VII activado [FEIBA].

Abstract We report the case of an 86-year-old man presenting with a spontaneous hematoma in the left iliac muscle and previous diagnosis of colon cancer in 1998 (stage pT3N0M0) treated with transverse colectomy and considered in complete remission. After a complete study, it was possible to identify the presence of Factor VIII inhibitors antibodies that confirmed the presence of acquired hemophilia. During hospitalization the patient presented a lower gastrointestinal bleeding leading to the diagnosis of recurrence of a previously treated colorectal adenocarcinoma. He responded to initial therapy with systemic corticoids and anti-inhibitory coagulant complex which includes activated VII Factor [FEIBA].

[Acquired hemophilia as the initial manifestation of colorectal cancer's recurrence]. / Hemofilia adquirida como manifestación inicial de recidiva de adenocarcinoma colorrectal.

We report the case of an 86-year-old man presenting with a spontaneous hematoma in the left iliac muscle and previous diagnosis of colon cancer in 1998 (stage pT3N0M0) treated with transverse colectomy and considered in complete remission. After a complete study, it was possible to identify the presence of Factor VIII inhibitors antibodies that confirmed the presence of acquired hemophilia. During hospitalization the patient presented a lower gastrointestinal bleeding leading to the diagnosis of recurrence of a previously treated colorectal adenocarcinoma. He responded to initial therapy with systemic corticoids and anti-inhibitory coagulant complex which includes activated VII Factor [FEIBA].

Presentamos el caso de un varón de 86 años con un hematoma espontáneo en el músculo ilíaco izquierdo y diagnóstico previo de cáncer de colon en 1998 (estadio pT3N0M0), tratado quirúrgicamente mediante colectomía transversal, considerado en remisión completa. Tras realización de estudios complementarios se demostró la presencia de autoanticuerpos inhibidores del Factor VIII que confirmaron el diagnóstico de hemofilia adquirida. Durante el ingreso el paciente presentó un sangrado digestivo bajo que conllevó al descubrimiento de recidiva del adenocarcinoma colorrectal tratado previamente. Respondió de forma favorable a la terapia inicial con corticoides sistémicos y el complejo coagulante anti inhibidor que incluye el Factor VII activado [FEIBA].

Idiosyncratic Drug-Induced Neutropenia and Agranulocytosis in Elderly Patients.

Agranulocytosis is a rare, but serious and life-threatening hematologic disorder in elderly patients. Idiosyncratic drug-induced agranulocytosis (IDIA) has been classically defined by a neutrophil count below 0.5 × 109/L. The annual incidence of IDIA in Europe is about 1.6-9.2 cases per million inhabitants. Increasing age and female sex have been considered as risk factors for the development of this condition. Besides, it is well known that older people take on average more drugs than younger people. This condition is most often associated with the intake of antibacterial agents, antiplatelets, antithyroids, antipsychotics, antiepileptics and nonsteroidal anti-inflammatory drugs (NSAIDs). Initially, agranulocytosis may present without symptoms, but may quickly progress to a severe infection and sepsis. The causative drug should be immediately stopped. In febrile patients, blood cultures and where indicated, site-specific cultures should be obtained and early treatment with empirical broad-spectrum antibiotics started. Even with adequate treatment, the mortality rate is higher in elderly patients reaching up to 20%. Hematopoietic growth factors have proven to be useful as they shorten the duration of neutropenia. However, data on neutropenia and agranulocytosis in the elderly meeting the criteria of evidence-based medicine are still poor in the literature. This review analyzes the results of our experience as well as other published studies of the universal literature.

Severe Neutropenia and Agranulocytosis Related to Antithyroid Drugs: A Study of 30 Cases Managed in A Single Reference Center.

BACKGROUND: The most important series devoted to antithyroid drug-induced severe neutropenia and agranulocytosis are Japanese studies, almost specifically in relation to the intake of methimazole. The clinical data of 30 Caucasian patients followed up for antithyroid drug-induced neutropenia at a third-level hospital are reported. Methods: The data of 30 patients with idiosyncratic antithyroid drug-induced neutropenia and agranulocytosis from a cohort study on drug-induced neutropenia and agranulocytosis conducted at the University Hospital of Strasbourg (France) were retrospectively reviewed. Results: The mean patient age was 61.7 years old (range: 20-87), and the gender ratio (F/M) was 4. Several comorbidities were reported in 23 patients (76.7%), with the mean Charlson comorbidity index of 1. The causative drugs were carbimazole and benzylthiouracil, in 28 (93.3%) and 2 cases, respectively, prescribed primarily for multi-hetero-nodular goiter or thyroid nodule to 18 patients (60%). Sore throat and acute tonsillitis (40%), isolated fever (20%), septicemia (13.3%), documented pneumonia (6.7%), and septic shock (6.7%) were the main clinical features upon admission. The mean neutrophil count at nadir was 0.02 and 0 × 109/L (range: 0-0.3). Regarding the patients' hospital course: 13 cases (43.3%) worsened during hospitalization, severe sepsis was found in 26.7%, systemic inflammatory response syndrome-in 13.3%, and septic shock-in 3.3% of the cases, respectively. Broad-spectrum antibiotics were indicated for all the patients, and 21 (73.3%) of them received hematopoietic growth factors. Hematological recovery (neutrophil count ≥ 1.5 × 109/L) was seen at 8.3 days (range: 2-24), but faster in those receiving hematopoietic growth factors (4.9 days, p = 0.046). Two patients died during hospitalization, and the rest had a favorable clinical outcome. Conclusions: Antithyroid drug-induced neutropenia represents a serious complication resulting from the rates of severe infections especially in those cases severe neutropenia. In this setting, an established procedure for the management of patients seems useful or even indispensable in view of potential mortality.

[Frailty syndrome: evaluation of its knowledge and screening tools by general medicine interns]. / Syndrome de fragilité : évaluation des connaissances et de ses outils de dépistage concernant les internes de médecine générale.

Screening and management of frail elderly patients is essential in general practice. OBJECTIVE: This study aims to describe and evaluate the knowledge about frailty, its screening tests and management in a population of general practice interns. METHOD: A prospective, descriptive and mono-centric study using an online survey was conducted. The 2018's promotion of general practice interns in Rouen's University participated. Evaluation of the general knowledge (e.g diagnostic criteria) and specific knowledge (e.g ranking different conditions such as: undernourishment leading to asthenia) and management algorithm (e.g to address the patient for geriatric evaluation) Results: 90 questionnaires were analyzed. Ten interns (11%) stated to know at least one screening test or to know a set of 4 major frailty criteria. Thirty four interns knew at least 4 frailty criteria (major or minor) and 46 interns had partial knowledge. Fried's phenotype was the most known. Seventy-five interns (83%) stated to know the frailty syndrome. However, 88% of the interns had little knowledge about its pathophysiology. Concerning frailty management, 78% (70 interns) stated to know how to screen frailty and prescribe first line treatments. Thirty-one among them knew how to reassess initial treatment if failure. In 59 interns (65%), identifying frailty would have led to a geriatric consultation. Seventy-nine interns (87%) were favorable to go through further training on frailty. CONCLUSION: These general practice interns were able to identify frailty criterion but, in contrast, global understanding of the syndrome was missing. Further training about this topic seems to be necessary.

[Hypervitaminosis B12. Our experience and a review]. / Hipervitaminosis B12. Nuestra experiencia y una revisión.

High serum levels of vitamin B12 or cobalamin, also called hypervitaminemia B12, is a frequently underestimated biological abnormality. According to the literature, some of the entities related to this finding are solid neoplasia (primary or metastatic) and acute or chronic hematological diseases. Other causes include liver disorders, monoclonal gammapathy of undetermined significance, renal failure and, less frequently, excess of vitamin B12 intake, inflammatory or autoimmune diseases, and transient hematological disorders (neutrophilia and secondary eosinophilia). This article reports on causes of hypervitaminosis B12, our experience and a review of the literature.

Los altos niveles de vitamina B12 o cobalamina, también denominado hipervitaminosis B12 es una anormalidad analítica frecuentemente subestimada. De acuerdo con la literatura algunas de las entidades relacionadas con este hallazgo son las neoplasias sólidas (primarias o metastásicas) y las enfermedades hematológicas agudas o crónicas. Otras causas incluyen la afección hepática, la gammapatía monoclonal de significación indeterminada, la insuficiencia renal y, con menor frecuencia, un exceso de consumo de vitamina B12, enfermedades inflamatorias o autoinmunes y los trastornos hematológicos transitorios (neutrofilia y eosinofilia secundaria). Este artículo informa sobre causas de hipervitaminosis B12, nuestra experiencia y hace una revisión de la literatura.

Hipervitaminosis B12: Nuestra experiencia y una revisión / Hypervitaminosis B12. Our experience and a review

Los altos niveles de vitamina B12 o cobalamina, también denominado hipervitaminosis B12 es una anormalidad analítica frecuentemente subestimada. De acuerdo con la literatura algunas de las entidades relacionadas con este hallazgo son las neoplasias sólidas (primarias o metastásicas) y las enfermedades hematológicas agudas o crónicas. Otras causas incluyen la afección hepática, la gammapatía monoclonal de significación indeterminada, la insuficiencia renal y, con menor frecuencia, un exceso de consumo de vitamina B12, enfermedades inflamatorias o autoinmunes y los trastornos hematológicos transitorios (neutrofilia y eosinofilia secundaria). Este artículo informa sobre causas de hipervitaminosis B12, nuestra experiencia y hace una revisión de la literatura.

High serum levels of vitamin B12 or cobalamin, also called hypervitaminemia B12, is a frequently underestimated biological abnormality. According to the literature, some of the entities related to this finding are solid neoplasia (primary or metastatic) and acute or chronic hematological diseases. Other causes include liver disorders, monoclonal gammapathy of undetermined significance, renal failure and, less frequently, excess of vitamin B12 intake, inflammatory or autoimmune diseases, and transient hematological disorders (neutrophilia and secondary eosinophilia). This article reports on causes of hypervitaminosis B12, our experience and a review of the literature.

State of Art of Idiosyncratic Drug-Induced Neutropenia or Agranulocytosis, with a Focus on Biotherapies.

INTRODUCTION: Idiosyncratic drug-induced neutropenia and agranulocytosis is seldom discussed in the literature, especially for new drugs such as biotherapies outside the context of oncology. In the present paper, we report and discuss the clinical data and management of this relatively rare disorder, with a focus on biotherapies used in autoimmune and auto-inflammatory diseases. MATERIALS AND METHODS: A review of the literature was carried out using the PubMed database of the US National Library of Medicine. We searched for articles published between January 2010 and May 2019 using the following key words or associations: "drug-induced neutropenia", "drug-induced agranulocytosis", and "idiosyncratic agranulocytosis". We included specific searches on several biotherapies used outside the context of oncology, including: tumor necrosis factor (TNF)-alpha inhibitors, anti-CD20 agents, anti-C52 agents, interleukin (IL) 6 inhibitors, IL 1 inhibitors, and B-cell activating factor inhibitor. RESULTS: Idiosyncratic neutropenia remains a potentially serious adverse event due to the frequency of severe sepsis with severe deep tissue infections (e.g., pneumonia), septicemia, and septic shock in approximately two-thirds of all hospitalized patients with grade 3 or 4 neutropenia (neutrophil count (NC) ≤ 0.5 × 109/L and ≤ 0.1 × 109/L, respectively). Over the last 20 years, several drugs have been strongly associated with the occurrence of idiosyncratic neutropenia, including antithyroid drugs, ticlopidine, clozapine, sulfasalazine, antibiotics such as trimethoprim-sulfamethoxazole, and deferiprone. Transient grade 1-2 neutropenia (absolute blood NC between 1.5 and 0.5 × 109/L) related to biotherapy is relatively common with these drugs. An approximate 10% prevalence of such neutropenia has been reported with several of these biotherapies (e.g., TNF-alpha inhibitors, IL6 inhibitors, and anti-CD52 agents). Grade 3-4 neutropenia or agranulocytosis and clinical manifestations related to sepsis are less common, with only a few case reports to date for most biotherapies. Special mention should be made of late onset and potentially severe neutropenia, especially following anti-CD52 agent therapy. During drug therapy, several prognostic factors have been identified that may be helpful when identifying 'susceptible' patients. Older age (>65 years), septicemia or shock, renal failure, and a neutrophil count ≤0.1 × 109/L have been identified as poor prognostic factors. Idiosyncratic neutropenia should be managed depending on clinical severity, with permanent/transient discontinuation or a lower dose of the drug, switching from one drug to another of the same or another class, broad-spectrum antibiotics in cases of sepsis, and hematopoietic growth factors (particularly G-CSF). CONCLUSION: Significant progress has been made in recent years in the field of idiosyncratic drug-induced neutropenia, leading to an improvement in their prognosis (currently, mortality rate between 5 and 10%). Clinicians must continue their efforts to improve their knowledge of these adverse events with new drugs as biotherapies.

[Codex and MMSE: what to choose?] / Codex et MMSE : que choisir ?

The objective of this study was to compare in general practice, patients aged 65 years and over: the MMSE, screening tools for cognitive disorder recommended by the HAS and the Codex. METHOD: 53 patients were included between June and October 2017 at La Charmille general practice in Limpiville in rural areas during an observational study. Patients over 65 years of age were included following a consultation with their general practitioner. The MMSE and the Codex were compared on their results, intrinsic variables, the time of handover. Geriatric comorbidity factors are compared between groups of patients "with" and "without" cognitive disorders detected. RESULTS: Of the 53 patients, 94% CI 95% [4.10; 20.25] had cognitive impairment, at an average age of 74.15 years. The predominance is female with 30 patients (57%). The passage time of the Codex is on average 1min 43s, significantly faster (p = 4,29*10-26) than the time of passing the MMSE 4min 51s on average. There is a better satisfaction of the Codex compared to the MMSE (p = 1.675*10-6) with an average digital scale score of 7.3 against 6.3 respectively. There is no significant difference between population with cognitive and non-cognitive impairment and geriatric comorbidity factor due to selection bias. CONCLUSION: Codex appears to be a rapid, reliable, reproducible cognitive impairment screening tool adapted to the general practice consultation format. An important axis to work, awareness, education of doctors at the university and continuing education on the screening and management of dementia syndromes and fragility.

Hypervitaminemia B12 and malignant diseases: report of a cross-sectional study in an acute geriatric unit.

Hypervitaminemia B12 has been associated or linked with a range of conditions, the majority of which are serious. Between March 26th, 2014 and June 30th, 2014, all patients aged ≥65 years, hospitalized in an acute geriatric unit in the university hospital center of Reims (France) were included in an observational study. 190 patients were included. 48 patients presented a hypervitaminemia B12 (25.3%). The gender ratio (M/F) of the population with elevated vitamin B12 levels was 0.5. 41 patients were aged ≥75 years (85.4%). The mean vitamin B12 level was 1,085 pg/mL (±428). 30 patients (62.5%) presented with moderate hypervitaminemia (<1,085 pg/mL), while 18 patients (37.5%) presented with elevated levels >1,085 pg/mL. Using the Chi2 or Fisher tests and the Student test, the factors with a significant link to hypervitaminemia B12 in univariate analysis were: acute renal failure (p=0.0002); liver diseases (p <0.0001) and solid neoplasia (p=0.0030). Using binary logistic regression for multivariate analysis, variables independently related to hypervitaminemia B12 were: acute renal failure: (odds ratio [OR]=6.3; 95%CI=2.7-8.1; p <0.0001); liver diseases (OR=5.4; 95%CI=3.1-6.9; p <0.0001); hematological disorders (OR=5.7; p=0.001); and age ≥75 years (OR=3.7; 95%CI=1.9-4.8; p=0.04). Moreover, there is an apparent correlation between rates of hypervitaminemia B12 and the number of etiologies identified (r=0.8; p=0.04). Our study confirm the significance of the link between hypervitaminemia B12 and hematological disorders in elderly patients, with a 5.7 fold higher risk.

[What to do before a hypervitaminia B12 in the elderly]. / Conduite à tenir devant une hypervitaminémie B12 chez le sujet âgé.

Hypervitanimia B12 is an early marker of serious pathologies. These include solid neoplasms, malignant blood diseases and acute/chronic hepatopathies. Hypervitaminemia B12 in geriatrics is thereby an indicator in the diagnosis and prognosis of these conditions.

[Iron deficiency and pernicious anemia: a rare association?]. / Carence martiale et maladie de Biermer : une association rare ?

The aim of this study was to determine the prevalence of iron deficiency among patients with pernicious anemia. We realized a retrospective study from 2000 to 2010 including 55 patients suffering from pernicious anemia who were followed in Reims and Strasbourg university hospitals. Inclusion criteria were histological diagnosis of immune atrophic fundic gastritis and criteria of gastric autoimmuninty, and for which ferritin was measured. Iron deficiency is defined as serum ferritin level <20 µg/L in women and <30 µg/L in men. 45 (81.8%) patients were female. The mean age was 61 ± 17 years (range: 25/98).There was anemia in 32 patients (58.2%). Macrocytosis was noted, with or without anemia, in 30 patients (54.5%); microcytosis, with or without anemia, was noted in 8 (14.5%) patients. 17 patients (30.9%) had normal mean corpuscular volume. Vitamin B12 deficiency was objectived in 42 patients (76.4%) in our series. 16 patients (29%) had iron deficiency. 14 patients were female. They were significantly younger than female subjects without iron deficiency (p =0.004). In conclusion, iron deficiency is not rare in patients with pernicious anemia. It could be a complication of achlorhydria. We suggest a dosage of serum ferritin for all patients with pernicious anemia.