Too many dangerous allergies

Mastocytosis is a rare clonal disease characterized by an abnormal proliferation of mast cells, which accumulate in one or several organ systems such as skin, bone marrow, liver, spleen, lymph nodes and gastrointestinal tract. The heterogeneity of the clinical presentation is typically related to different disease burdens in various tissues and symptoms due to the release of mast cell mediators. The diagnosis is often difficult and delayed. Here we describe the case of a 70-year old patient with a past history of drug-induced anaphylactic shock whose clinical presentation was dramatic and required intensive support: the diagnosis of systemic mastocytosis was reached after the exclusion of diseases more commonly encountered in routine clinical practice (e.g. stroke, pulmonary embolism)

Neonatal pyknocytosis in a preterm dizygotic twin

Infantile pyknocytosis (IP) is a rare, self-limited neonatal haemolytic anaemia that may require multiple blood transfusions. Only a little more than 50 cases have been reported in the medical literature, and the great majority of them concerns term infants. The etiology of IP is not well understood; most likely it results from a transient extra-corpuscular factor, whose nature is unknown, transmitted from mother to child or, alternatively, from a deficiency of an anti-oxidative agent. We report the case of two preterm twins, one of which suffered from IP and developed severe anaemia at age 2 wk, while the other was unaffected. Although no specific agent was identified as the cause of anaemia and IP, we speculate that the transmission of an agent from mother to child was unlikely, as only twin one suffered from IP. Smelly greenish diarrhoea occurred just before the presentation of IP, suggesting that the same agent led to both the diarrhoea and the oxidative injury. Because IP may remain underdiagnosed, it should be considered in cases of early unexplained severe hemolytic anemia

Incidence and outcome of Myelodysplastic Syndromes in province of Modena

Background As in the past Myelodisplastic Syndromes (MDS) were considered preneoplastic conditions, rarely data on these diseases were collected by cancer registries. Thus, there are few well documented population-based studies on the incidence and outcome of MDS. The aim of this study was to collect epidemiological data and clinical characteristics of MDS by studying all cases identified by the Modena Cancer Registry (MCR). Materials and methods We examined all cases of MDS diagnosed in the Province of Modena (population 633.993 at 2001 Census). MDS from 1997 to 2005 were identified using the MCR database and the archival files of the centralized hemolymphopathological laboratory at Modena Cancer Centre according to ICD-O-3 codes 9980,9982-87,9989. Death certificate, cytology and histology report, both local and national reports of Hospital admission, ICD-9 code reported in medical records were used as sources for identifying new MDS cases and their outcome. After collection, all cases were checked and validated by a hematologist (A.B.) and a pathologist (G.B.) by a review of the original pathology report. The large majority of bone marrow aspirate and biopsy were examined by the same pathologist (G.B.) making diagnostic criteria uniform. Clinical and follow-up data were retrieved by active search of discharge letters, review of hospital records, and interview of general practitioners. Information on vital status was achieved from official population registries. Age standardized rates (ASR) were calculated according to the World Standard population (Doll et al, 1966). The dates of diagnosis and death or the closing date of study (December 2006) were used to estimate survival. Observed survival and relative survival were calculated according to Kaplan-Meier method and the Hakulinen approach, respectively. Results A total of 205 cases of MDS were identified. The ASR of MDS was 1.2/100,000 varying slightly (from 0.9 to 1.5/100,000; p > 0.05) during the study period, and the crude incidence rate was 3.6/100,000. Median age at diagnosis was 75 years for men and 78 for women. Overall, 58% of patients aged more than 75 years, while only 1% were less than 45 years old. According to French, American and British (FAB) classification there were 35 cases (17% of all MDS) of Refractory Anemia (RA), 51 (25%) of RA with ringed sideroblasts, 73 cases (36%) of RA with excess of blasts (RAEB), 11 (5%) of RAEB in transformation, 31 (15%) of MDS not otherwise specified and 4 (2%) of other MDS. Overall the prognosis of MDS was poor, although we found statistically significant differences by clinical subtypes. In our MDS population the relative survival was 68%, 36% and 26% at 1, 3 and 5 years, respectively. Conclusions To our knowledge, this study is the first in Italy providing information on the incidence and outcome of MDS using population-based data. Our results confirm that the risk of developing MDS increases with age for both men and women. The incidence of MDS was substantially stable during the study period. Overall survival was poor reflecting the aggressiveness of these diseases and the advanced age of patients at time of diagnosis. As expected, we observed important differences in overall survival by FAB subtypes. In the last few years, innovative treatments for MDS are emerging and we believe that the availability of precise epidemiological data could help clinicians in choosing the most appropriate treatment

Human Herpesvirus 6 Latently Infects Early Bone Marrow Progenitors In Vivo

We have studied the in vivo tropism of human herpesvirus 6 (HHV-6) for hemopoietic cells in patients with latent HHV-6 infection. Having used a variety of cell purification, molecular, cytogenetic, and immunocytochemical procedures, we report the first evidence that HHV-6 latently infects early bone marrow progenitor cells and that HHV-6 may be transmitted longitudinally to cells which differentiate along the committed pathways

Physical contact with endothelial cells through β1- and β2- integrins rescues chronic lymphocytic leukemia cells from spontaneous and drug-induced apoptosis and induces a peculiar gene expression profile in leukemic cells

Background: Chronic lymphocytic leukemia B-cells display prolonged survival in vivo, but when cultured in vitro rapidly undergo spontaneous apoptosis. We hypothesize that interaction with endothelial cells in infiltrated tissues and during recirculation may have a pathogenetic role in chronic lymphocytic leukemia.Design and Methods: We evaluated apoptosis of leukemic cells after co-culture on HUVEC monolayer with addition of Fludarabine and blocking adhesion antibodies. Then, we compared microarray-based expression profiles between leukemic cells at baseline and after co-culture.\uf9Results: We found that endothelial layer protected leukemic cells from apoptosis inducing a 2-fold mean decrement in apoptotic cells after 2 days co-culture. Moreover, endothelial layer decreased sensitivity of chronic lymphocytic leukemia B-cells to Fludarabine-induced apoptosis. Physical contact with endothelium mediated by both \u3b21- and \u3b22- integrins is essential for survival advantage. In particular, blocking CD106 on endothelial cells or CD18 on leukemic B-cells determined the almost complete abrogation of survival advantage (>70% inhibition of viability). Conversely, a reduction of apoptosis was also measured in leukemic cells cultured in conditioned medium collected after 2 days of co-culture, implying that survival is partially mediated by soluble factors. Overall, the contact with endothelial cells modulated 1,944 genes on chronic lymphocytic leukemia B-cells, establishing a peculiar gene expression profile: up-regulation of angiogenesis-related genes, increase of genes involved in TGF\u3b2 and Wnt signalling pathways, secretion of cytokines recruiting stromal cells and macrophages and increase in anti-apoptotic molecules such as Bcl2 and Survivin. Conclusion: Our study supports the notion that endothelial cells are major players in chronic lymphocytic leukemia microenvironment. Adhesion to endothelium strongly sustains survival, protects from drug-induced apoptosis and widely modifies gene expression profile of leukemic cells

Chronic and recurrent benign lymphadenopathy without constitutional symptoms associated with human herpesvirus-6B reactivation

Chronic/recurrent behaviour may be encountered in some distinct atypical or malignant lymphoproliferations, while recurrences are not generally observed in reactive/benign lymphadenopathies. We retrospectively anal- ysed a consecutive series of 486 human immunodeficiency virus-negative adults, who underwent lymphadenectomy. Neoplastic and benign/reactive histopathological pictures were documented in 299 (61 5%) and 187 (38 5%) cases, respectively. Of note, seven of the 111 (6 3%) patients with benign lymphadenopathy without well-defined aetiology, showed chronic/ recurrent behaviour, without constitutional symptoms. Enlarged lymph nodes were round in shape and hypoechoic, mimicking lymphoma. Reac- tive follicular hyperplasia and paracortical expansion were observed. Human herpesvirus (HHV)-6B positive staining in follicular dendritic cells (FDCs) was documented in all seven patients. Serological, molecular and immunological examinations suggested HHV-6B reactivation. Among the remaining 104 cases with reactive lymphoid hyperplasia in the absence of well-known aetiology and without recurrences, positivity for HHV-6B on FDCs was found in three cases, whereas in seven further patients, a scanty positivity was documented in rare, scattered cells in inter-follicular regions. Immunohistochemistry for HHV-6A and HHV-6B was invariably negative on 134 lymph nodes, with either benign pictures with known aetiology or malignant lymphoproliferative disorders, tested as further controls. Future studies are warranted to investigate a potential association between HHV- 6B reactivation and chronic/recurrent benign lymphadenopathy