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.

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 antece...

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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.

The first therapeutic indication, and still currently the most applied of gamma globulin, is the one which uses its substitutive capacity in patients with antibodies deficiencies. Its immunomodulatory effectiveness with pro and anti-inflammatory activity holds a second place in their indications, in autoimmune and inflammatory illnesses. The first gamma globulin to be used in patients with agammaglobulinemia in the 50's, were of intramuscular administration, with significant limitations on the volume and the infusion's amount, as well as being painful . For over 20 years intravenous immunoglobulin (IVIG) has been widely used in human pathology. The first proteolytic enzyme-treated intravenous immunoglobulins allowed large doses infusions, thereby getting higher levels of IgC circulating in plasma, a subclass profile similar to the normal population, as well as a much higher average life expectancy. The pharmaceutical industry efforts brought about new more purified and viral safer immunoglobulins. The Cohn and cold ethanol methods were quickly supplemented with ulterior procedures that strengthened the viral safety of these products. The application of molecular techniques to the screening study of plasma donors, as well as incorporating new viral inactivation procedures during its manufacture, have made of IVIG a safe product whose consumption has exponentially increased in recent years. IVIG's high cost, the hypothetical plasma supply problems and risks associated to its administration made essential the writing of usage protocols for official agencies, which, besides, hospitals also adopted.