Quality of life in common variable immunodeficiency requiring intravenous immunoglobulin therapy.

BACKGROUND: There are no studies of patients with primary immunodeficiency states receiving intravenous immunoglobulin (IVIG) therapy that assess health-related quality of life (HRQOL) using a well-standardized and reproducible method. OBJECTIVES: To determine the HRQOL of patients with common variable immunodeficiency (CVID) requiring IVIG therapy, to compare these patients with patients with diabetes mellitus (DM) and congestive heart failure (CHF), to determine the factors that affect HRQOL, and to develop normative data on the HRQOL of these CVID patients, which can be used to follow the effects of future therapies. METHODS: Fifty-eight adults with CVID receiving IVIG therapy completed the Medical Outcomes Study 36-Item Short-Form Health Survey to evaluate their HRQOL and were compared with DM and CHF patients. The impact of demographic, socioeconomic, and disease-related variables and comorbid conditions was examined in the CVID population. RESULTS: Patients with CVID had lower HRQOL scores in all dimensions compared with patients with DM and in 4 of 8 dimensions compared with patients with CHF. Increasing age and female sex were negatively associated with certain aspects of HRQOL. There were no significant effects from other socioeconomic or disease-related variables or comorbid conditions examined. CONCLUSIONS: Patients with CVID receiving IVIG therapy have a significantly worse HRQOL than patients with other chronic illnesses, indicating there is much room for improvement in future therapies for this primary immunodeficiency state. The effects of future therapies can be evaluated by comparison with the normative data developed in this study.     

Subcutaneous immunoglobulin therapy in an 11-year-old patient with common variable immunodeficiency and von Willebrand disease.

BACKGROUND: Subcutaneous immunoglobulin (SCIG) is an option for replacement therapy in patients with humoral immune deficiencies. OBJECTIVE: To describe a patient with common variable immunodeficiency (CVID) and von Willebrand disease who tolerated immunoglobulin replacement via the subcutaneous route. METHODS: An 11-year-old boy receiving monthly intravenous immunoglobulin (IVIG) since 5 years of age presented to an academic medical center after moving to the area. The patient also had a history of von Willebrand disease. He had started receiving IVIG because of recurrent infections and an absent IgG subclass 3. Further immunologic assessment revealed a normal B-cell count, decreased IgM level, and an abnormal response to bacteriophage phiX174. Given these findings and the lack of another cause, the patient was diagnosed as having CVID. Because of difficult intravenous access, a port was placed for IVIG administration in 1999. The initial port was removed because of infectious complications, and a second port was found to be distally displaced in the right atrium, requiring removal. RESULTS: Continued difficulties with intravenous access and the potential complications with maintaining a long-term indwelling catheter prompted consideration of alternative methods for immunoglobulin administration. After removal of the port, the patient was prescribed weekly SCIG infusions. He tolerated the infusions well without bleeding complications related to the von Willebrand disease and was able to transition to home infusions. CONCLUSIONS: SCIG was well tolerated by a pediatric patient with CVID and von Willebrand disease without any significant bleeding complications.     

Efficacy of intravenous immunoglobulin in the prevention of pneumonia in patients with common variable immunodeficiency

BACKGROUND: Common variable immunodeficiency (CVID) is a primary immune disorder characterized by antibody deficiency and a decrease in serum IgG and IgA, IgM, or both levels at least 2 SDs below the mean for age and not attributed to other known immunologic disorders. These patients often present with frequent and severe episodes of pneumonia before diagnosis. The standard treatment, intravenous immunoglobulin (IVIG), has been available for the past 20 years. No large-scale study has compared the incidence of pneumonia in these patients before and after IVIG treatment. OBJECTIVE: The aim of this study was to document the effectiveness of intravenous immunoglobulin treatment on the incidence of pneumonia in patients with CVID. METHODS: We performed chart reviews and interviews of patients with laboratory-confirmed CVID seen at our clinical center. The number of episodes of pneumonia was documented before and after treatment with immunoglobulin replacement therapy. RESULTS: The histories of 50 patients were reviewed (mean current age, 42 +/- 16.3 years; age range, 10-78 years; 20 male and 30 female patients). Forty-two (84%) of the 50 patients with CVID had pneumonia at least once before receiving immunoglobulin treatment, and 11 of 42 of these patients had multiple episodes. After treatment with gamma globulin over a mean period of 6.6 +/- 5.2 years (range, <1-20 years), the number of patients experiencing pneumonia significantly decreased to 11 (22%) of 50. In most cases these patients had pneumonia in the first year of immunoglobulin treatment. CONCLUSION: The treatment of CVID with IVIG significantly reduces the incidence of pneumonia.     

Effect of regular intravenous immunoglobulin therapy on prevention of pneumonia in patients with common variable immunodeficiency.

BACKGROUND AND PURPOSE: Common variable immunodeficiency (CVID) is a primary immunodeficiency disorder, which presents with hypogammaglobulinemia and recurrent bacterial infections. Patients with CVID have frequent and severe episodes of pneumonia. The standard intravenous immunoglobulins (IVIG) therapy has led to the reduction of pulmonary infections in these patients. The aim of this study was to evaluate the effectiveness of IVIG treatment in reducing the incidence of pneumonia in patients with CVID. METHODS: Twenty six Iranian patients with CVID whose diseases had been diagnosed at the Children Medical Center and had received regular IVIG for at least 9 months were selected. The numbers of episodes of pneumonia and hospital admissions were documented before and during treatment with IVIG. RESULTS: Of 26 patients with CVID, 80.5% had experienced pneumonia at least once before receiving immunoglobulin and 88.5% required hospital admission. After starting treatment with IVIG (mean treatment period, 41.5 +/- 35.4 months), the annual incidence of pneumonia significantly decreased from 80.5% to 34.6% (p=0.0017), and the rate of hospitalization from 88.5% to 46% (p=0.0025) .The incidence of pneumonia requiring treatment or hospitalization fell from 3.4 to 0.7 per year (p<0.0005). CONCLUSIONS: Regular IVIG therapy can significantly reduce the incidence of pneumonia and hospital admission due to infections in patients with CVID.     

Changes in serum immunoglobulin patterns in adults with common variable immunodeficiency

Striking variations of serum immunoglobulin class and IgG subclass levels were observed in five patients with common variable immunodeficiency. They occurred mainly in untreated patients or, in those patients who received substitutive therapy, could not be merely due to replacement. They result in major changes in the immunoglobulin deficiency patterns, such as a shift from profound hypoimmunoglobulinaemia to IgA/IgG2/IgG4 deficiency or to isolated IgG2 deficiency. These findings have practical implications for the diagnosis and management of patients with primary humoral immunodeficiency.     

Panhypopituitarism in a child with common variable immunodeficiency.

BACKGROUND: Common variable immunodeficiency (CVID) represents a group of heterogeneous, still undifferentiated, syndromes that are all characterized by defective antibody formation. It is often associated with autoimmune disease. METHODS: An African-American girl was diagnosed with CVID at age 3 years. She was seen during an adrenal crisis precipitated by pneumonia at the age of 8 years and 10 months. The diagnosis of panhypopituitarism was established soon after. RESULTS: Panhypopituitarism in this patient was believed to be the result of the autoimmune process known as lymphocytic hypophysitis. This hypothesis was suggested by the results of magnetic resonance imaging. CONCLUSIONS: Awareness of the possibility of this process in children or adults with CVID may lead to earlier diagnosis of panhypopituitarism. These patients also have failure to thrive, and earlier diagnosis may avoid a life-threatening event.     

Clinical and immunological features of 65 Iranian patients with common variable immunodeficiency

Common variable immunodeficiency (CVID) is a primary immunodeficiency disease characterized by hypogammaglobulinemia and recurrent bacterial infections. The records of 65 patients with CVID (37 males and 28 females) in the age range of 24 to 537 months were reviewed. By the year 2003, 11 patients had died and seven patients could not be located. The total follow-up period was 221 patient-years. The median diagnostic delay (time between onset and diagnosis) in our patient group was 60 months. At the time of diagnosis, the baseline serum immunoglobulin G (IgG), IgM, and IgA levels were below the level normal for the patients' age; the medians for this group were 120, 10, and 0 mg/dl, respectively. All of the patients presented with infectious diseases at the time of onset, the most common of which were otitis media, diarrhea, pneumonia, and sinusitis. Acute and recurrent infections were also found in almost all of the patients, particularly involving respiratory and gastrointestinal systems. The most common infections, before diagnosis and during follow-up, were pneumonia, acute diarrhea, acute sinusitis, and otitis media. CVID should be considered in any patient with a history of recurrent infections and decreased levels of all serum immunoglobulin isotypes.     

In vivo modulation of the expressions of Fas and CD25 by intravenous immunoglobulin in common variable immunodeficiency

Although the presence of physiologic anti-CD95 (Fas, APO-1) autoantibodies in intravenous immunoglobulin (IVIG) preparations is known, the effects of these antibodies in patients with common variable immunodeficiency are unclear (CVID). The aim of the study was to assess the effects of IVIG in Fas expression, activation markers and the subsets of T cells in patients with CVID. We studied 15 cases with CVID and 10 healthy controls with no signs of immunodeficiency. The Fas expression of T cells, activation markers (CD25, CD69 and HLA-DR) and T-cell subsets were analyzed by four-color flow cytometry. We found that the Fas expression of CD3⁺ T cells in patients was significantly higher than in controls. In addition, there was a significant increase in the Fas expression of CD3⁺ T cells and CD4⁺ T cells, and the CD25 expression of CD3⁺ and CD4⁺ T cells after IVIG supplementation (P < 0.05). The CD69 and HLA-DR expressions of T cells and CD8⁺ T cells were not affected by IVIG infusion. Our observation showed that IVIG replacement causes an increase in the Fas and CD25 expressions in patients with CVID. These data suggest that the Fas protein may have an important role in the effects of IVIG for the control of autoimmunity in patients with CVID, as well as in the generation of autoimmune disease.     

Hodgkin's disease in a patient with common variable immunodeficiency.

A 61 year old man with long standing common variable immunodeficiency presented with pyrexia, anaemia and leucopenia. A diagnoses of Hodgkin's disease of the bone marrow was made. The typical histopathological and immunophenotypic appearances were clearly distinct from those of T cell lymphoma with Reed-Sternberg-like cells which, in contrast to Hodgkin's disease, is a known complication of common variable immunodeficiency. Complete clinical and histological remission was achieved with combination chemotherapy. The latter was complicated by severe myelosuppression, unusually severe erosive mucositis and viral retinitis.     

Role of apoptosis in common variable immunodeficiency and selective immunoglobulin A deficiency

Common variable immunodeficiency (CVID) and selective IgA deficiency (SIgAD) are the most common primary immunodeficiencies in human. Both diseases share clinical manifestation and molecular defects. Increased apoptosis may be one of the mechanisms involved in the pathogenesis of CVID and SIgAD. Elevated apoptosis in this disorder leads to defective long-term survival of B-cells, reduced antibody production, decreased lymphocyte proliferation and defective cytokine secretion. For the first time, we reviewed the role of apoptosis in CVID and SIgAD.     

Chlamydia pneumoniae arthritis in a patient with common variable immunodeficiency.

BACKGROUND: Arthritis is an important and sometimes life-threatening complication in patients with common variable immunodeficiency (CVID). OBJECTIVE: To describe a patient with CVID and arthritis due to Chlamydia pneumoniae, which is usually regarded as a respiratory tract pathogen and has not previously been detected in the synovial fluid by cell culture technique. METHODS: Routine bacteriologic, virologic, mycologic, and tuberculosis cultures were performed. The patient's synovial fluid was examined for fastidious organisms that might be causative pathogens of arthritis, such as chlamydiae, and special cell culture methods were used. Serologic tests were performed to determine viral and bacteriologic etiology. RESULTS: The patient had a history of recurrent respiratory tract infections, and the latest exacerbation was followed by arthritis. Cytologic examination of the fluid yielded abundant lymphocytes. Chlamydia pneumoniae was detected in synovial fluid specimens by cell culture technique. Her nasopharyngeal swab and sputum culture specimens were also positive for this pathogen. She was diagnosed as having arthritis caused by C pneumoniae and was given antibiotherapy. CONCLUSION: Chlamydia pneumoniae should be kept in mind as a causative pathogen in patients with CVID and arthritis, especially when effusion fluid is full of lymphocytes rather than polymorphonuclear cells and no organism is grown on routine cultures.     

Diversity in DNA rearrangements and in RNA expressions of immunoglobulin gene on common variable immunodeficiency.

Six heterogeneous common variable immunodeficiency (CVID) patients were analysed for germ-line DNA, DNA rearrangements, and RNA expressions of immunoglobulin (Ig) gene by Southern or northern blotting using appropriate probes. We detected no polymorphism in neutrophil DNA hybridized to a C mu and a C gamma probe. In three patients, both serum Ig and Ig-bearing cells were scarcely detected, and by northern hybridization methods, neither mu mRNA, gamma mRNA, alpha mRNA nor kappa mRNA was detected. However, one Epstein-Barr virus-transformed B lymphoblastoid cell line (LCL) of these three patients was different from the germ line in the region of JH, C gamma, and C kappa, and expressed mu mRNA at a higher level. The B cell defects of these three patients lay on the B cell maturation stage similar to X-linked agammaglobulinaemia (XLA). In two others among the six CVID patients, serum IgM and IgM-bearing cells were detected to a certain degree, and by northern hybridization, mu mRNA was detected at a lower level, but neither mu mRNA, alpha mRNA, nor kappa mRNA was detected. One LCL of these two patients could express mu mRNA at the normal level. In the last patient, the serum IgM was normal, serum IgG and IgA were somewhat low, Ig-bearing cells were normal, mu mRNA and kappa mRNA were detected at the normal level, and gamma mRNA and alpha mRNA were detected at a lower level. The defect of this patient affected the class switch stage. These results showed that primary B cell defects in CVID occurred at several B cell differentiation stages which could be classified by expression of the Ig gene, and at the degree of clonal diversity in the B cell repertoire. Furthermore, this study provides support for the idea that the CVID defect is related to a more generalized cellular function, such as regulating the proliferation and/or clonal expansion of cells of the B lymphoid lineage.     

Lymphoepithelial cyst of the pancreas in a 65-year-old man.

A case of an extremely rare cystic lesion of the pancreas is presented. The multilocular cyst was found adjacent to the upper border of the pancreatic body, and the cyst contained bean curd lees-like substances. Histologically, the cyst wall consisted of mature keratinizing squamous epithelium and surrounding lymphoid tissue stroma, and the cyst was filled with keratinized materials. A histopathologic diagnosis of typical lymphoepithelial cyst of the pancreas, proposed by Truong et al (Am J Surg Pathol 11:899-903, 1987), was made. Its histogenesis is still unknown; however, we hypothesize that it might arise from a benign epithelial inclusion of a peripancreatic lymph node, followed by squamous metaplasia of the epithelial inclusion. We recently found a retropyloric lymph node with a squamous epithelial inclusion, which might support this hypothesis regarding the histogenesis of the cyst.