[Severe small bowel involvement and chronic intestinal pseudo-obstruction in systemic sclerosis (scleroderma): Pathophysiological, diagnostic and therapeutic basis, including parenteral nutrition]. / Atteinte sévère de l'intestin grêle et pseudo-obstruction intestinale chronique au cours de la sclérodermie systémique : bases physiopathologiques, diagnostiques et thérapeutiques, dont la nutrition parentérale.

Gastrointestinal involvement in systemic sclerosis can be severe, reaching the critical point of chronic intestinal pseudo-obstruction, secondary to major disorders of small bowel motility. It is associated with some clinical and biological characteristics, in particular the positivity of anti-fibrillarin/U3RNP antibodies. Chronic intestinal pseudo-obstruction (CIPO) is complicated by a small intestinal bacterial overgrowth that requires cyclic antibiotic therapy. CIPO leads to a reduction of the food intake, due to painful symptoms, nausea and vomiting caused by meals, and ultimately to severe malnutrition. Meal splitting is often transiently effective and patients require exogenous nutritional support, mostly parenteral. Systemic sclerosis is not an obstacle to initiation and long-term continuation of parenteral nutrition and central venous catheter implantation is not associated with an increased risk of cutaneous or infectious complications. However, continuation of long-term parenteral nutrition requires monitoring in an expert nutrition center in order to adapt nutritional volumes and intakes and to limit potentially fatal cardiac and hepatobiliary complications. In addition to nutrition, prokinetic treatments, whose side effects must be known, can be associated. Invasive procedures, whose risk-benefit ratio must be carefully assessed, can also be used to treat symptoms exclusively.

[New diagnostic and therapeutic aspects of hyper-IgE syndrome. Report of 3 cases]. / Nuevos aspectos diagnósticos y terapéuticos del síndrome de hiper-IgE. A propósito de 3 casos.

Three female patients, 46, 34, and 19 years old, diagnosed of hyper-IgE syndrome are reported. The most relevant clinical findings are recurrent sinopulmonary tract infections, cold staphylococcal abscesses and chronic dermatitis. All patients presented elevated serum IgE levels (> 3,000 U/ml) and blood eosinophilia (> 0.6 x 10(9) cel/l). Two patients presented impaired antibody forming capacity to tetanus and pneumococcal antigens; one of these patients also had low serum IgG2 levels. After initiation of the intravenous gammaglobulin therapy, a marked improvement of infectious problems was observed. The controversial pathophysiology of this syndrome, the antibody deficiency present in some patients and the rationale for intravenous gammaglobulin therapy are discussed.

[Common variable immunodeficiency. Review]. / Inmunodeficiencia variable común. Revisión.

Common variable immunodeficiency (CVI) is a primary immunodeficiency characterized by deficient antibody production. The cause of this immunodeficiency is unknown; several in vitro studies have revealed a significant number of alterations that could explain the hypogammaglobulinemia present in this syndrome. Among those described are primary B cell alterations, numerical and functional T cell abnormalities, and defects in the interaction between accessory cells. The alteration typical of CVI is the failure of B lymphocytes to differentiate from antibody-producing cells, resulting in deficient immunoglobulin secretion. Among the T cell abnormalities described are a diminished proliferative response to mitogens and antigens, alterations in the level of production of several cytokines, especially reduction in the production of IL-2, diminished antigen-specific T cells and increase basal apoptosis after stimulation. Antigen presenting cells, monocytes and dendritic cells can also present alterations and contribute to deficient antigen response. The clinical manifestations of these patients is variable; most present recurrent bacterial infections due to encapsulated bacteria, especially sinusitis, otitis, bronchitis, and pneumonias. A few patients can present mycobacterial or fungal infection and occasionally Pneumocystis carinii. Viral infection is uncommon in these patients although some suffer recurrent herpes zoster infection. Clinical features of septicemia and central nervous system infections are less frequent. The incidence of digestive tract infections in these patients is high. The most common cause of diarrhea is Giardia lamblia; Salmonella, Shigella and Campylobacter are also common pathogens. Autoimmune disease is also more prevalent in these patients than in the general population. The most frequently associated diseases are hemolytic anemia, idiopathic thrombocytopenic purpura and autoimmune neutropenia. Cancer is also frequently associated with CVI, the most common forms being lymphoproliferative syndromes, especially non-Hodgkin's lymphoma. Granulomas are a unusual manifestation in some patients with CVI; their localization varies but the most commonly affected organs are the spleen and lungs. Some authors have compared these granulomas with those characterizing sarcoidosis, especially when appearing in the lung. Diagnosis of CVI is usually by exclusion of other diseases, such as cystic fibrosis, immotile cilia syndrome or allergic processes. CVI should be suspected in all patients with recurrent bacterial infections especially those localized in the respiratory tract. Other primary immunodeficiencies which present clinical findings similar to CVI and which should be ruled out are selective IgG subclass deficiency, IgA deficiency and selective deficiency in the response to polysaccharide antigens with normal immunoglobulin levels. The serum hypogammaglobulinemia present in all patients with CVI provides the diagnostic key. The age at which clinical manifestations appear, the absence of familial antecedents and the presence of circulating B lymphocytes form the basis of the differential diagnosis between X-linked agammaglobulinemia and autosomal recessive forms. The treatment of choice of patients with CVI is treatment with human gamma-globulin. Currently, the most common route of administration is intravenous; these molecules have a half-life of approximately 21 days and a high degree of safety concerning the possible transmission of viral infections. Adverse reactions are generally few and clinically unimportant. The most frequently used doses oscillate between 200 and 400 mg/kg body weight every 2-4 weeks. Both the dose and its frequency should be personalized for each patient. Early diagnosis of patients with CVI, application of treatment with appropriate antibiotics for infections and treatment with gamma-globulins prevent long-term complications of this disease and dramatically improve the quality of life and life expectancy of these patients.

[The Spanish Registry of Primary Immunodeficiencies (REDIP)]. / Registro español de inmunodeficiencias primarias (REDIP).

Two thousand and fifty cases (n = 2050) of primary immunodeficiencies (PID) were registered up to February 2001. The Spanish Register for Primary Immunodeficiencies (REDIP) began in 1993. PID nomenclature and diagnostic criteria were made according to the report of the World Health Organization Scientific Group (1999). The most frequent disorders were IgA deficiency (797 registers) and common variable immunodeficiency (CVI) (389), followed by severe combined immunodeficiency and predominantly T cell defects (268), complement deficiencies (207 registers), X-linked agammaglobulinemia (87), IgG subclass deficiency (71), chronic granulomatous disease (64). Gammaglobulin replacement was the therapy in 638 patients (76%) belonging to antibody deficient group. 61 bone marrow transplants were done, 46 severe combined immunodeficiencies, 6 phagocytic disorders and 1 unclassified. Important differences in the number of cases submitted from different country areas were found.

[An increase in gamma-delta T-lymphocytes in the peripheral blood of cystic fibrosis patients]. / Incremento de linfocitos T gamma-delta en sangre periférica de pacientes afectos de fibrosis quística.

The function of the T gamma-delta cells of the human immune system is not well known at present. Only 3-10% of the T cells express the heterodimer composed of the gamma-delta chains. Recent studies have demonstrated a role of the T gamma-delta cells in the immunopathogenesis of autoimmune and infectious diseases. The present study was designed to evaluate the quantity of T gamma-delta cells in patients with cystic fibrosis with P. aeruginosa infections. These results were compared to blood levels of T cells found in patients with acute pulmonary infections, chronic pulmonary infections and healthy control patients. The cellular phenotype was determined by flow cytometry. Monoclonal antibodies against the different cell types studied were employed. The means of each group were compared by a Student's T test of Mann Whitney. We found that the percentage of T gamma-delta cells (TCR 1+) was significantly increased in patients with cystic fibrosis when compared to the pathological controls and healthy children. We conclude that our results demonstrate that children with cystic fibrosis infected with Pseudomonas aeruginosa demonstrate and increase in the subclass of T cells with the gamma-delta receptor.

Primary immunodeficiency syndrome in Spain: first report of the National Registry in Children and Adults.

The Spanish Registry for Primary Immunodeficiency Diseases (REDIP) was organized in 1993. One thousand sixty-nine cases of primary immunodeficiency diseases (PID) were registered in patients diagnosed between January 1980 and December 1995. PID diagnosis was made according to the World Health Organization criteria. The most frequent disorders were IgA deficiency (n = 394) and common variable immunodeficiency (n = 213), followed by severe combined immunodeficiency (n = 61), C1 inhibitor deficiency (n = 52), X-linked agammaglobulinemia (n = 49), IgG subclass deficiency (n = 48), and chronic granulomatous disease (n = 32). A comparative study between REDIP and data recently obtained from the European registry (ESID Report, 1995) revealed important differences between phagocytic disorders and complement deficiencies reported in both registries, 4.9 vs 8.7 and 6.0 vs 3.6, while percentages of predominantly antibody deficiencies and T cell and combined deficiencies concurred with those reported in the European registry, 69.3 vs 64.7 and 14.7 vs 20.2, respectively. The heterogeneous nature of the geographical distribution of cases submitted may indicate underdiagnosis of PID in some country areas; surprisingly, the interval between the onset of clinical symptoms and diagnosis was significant, even in immunodeficiency diseases, such as IgA deficiency, which are easy to diagnose.

CD34+ cell dose and CD33- subsets: collection and engraftment kinetics in autologous peripheral blood stem cells transplantation.

BACKGROUND AND OBJECTIVE: We analyzed the factors that affected the number and quality of peripheral blood stem cells (PBSC) collected for transplant in order to establish a minimum threshold for rapid hematopoietic recovery. DESIGN AND METHODS: From January 1995 to November 1996, a consecutive series of 67 patients, with hematologic and solid tumors underwent autologous PBSC transplantation. Collection of PBSC was performed after mobilization with granulocyte-colony stimulating factor (G-CSF) or with chemotherapy (CT) plus G-CSF. We calculated the factors that influenced PBSC collection, the kinetics of granulocyte and platelet recovery and the threshold value of CD34+ cells for a rapid recovery. The data were analyzed by means of multivariate Cox regression model and the receiver operating characteristic (ROC) methodology. RESULTS: Our results showed that mobilization with chemotherapy plus G-CSF was associated with a higher yield of PBSC in comparison with mobilization with G-CSF alone. Disease status, fewer cycles of conventional prior chemotherapy and absence of prior radiation therapy also influenced the yield of PBSC. The number of CD34+ cells, CD34+CD33- cell subsets, the mobilization schedule, and the conditioning regimen correlated significantly with time to hematopoietic recovery. In the multivariate analysis only the CD34+CD33- cell content and the total number of CD34+ were related with rapid neutrophil and platelet recovery, respectively. Use of G-CSF after transplant significantly shortened the neutrophil recovery time only in patients transplanted with suboptimal dose of PBSC. INTERPRETATION AND CONCLUSIONS: These data suggest the utility of quantitation of CD34+ cells subsets to predict quick engraftment.