Kinetics of hypogammaglobulinemia in patients with common variable immunodeficiency

We investigated the production of immunoglobulin (Ig) in six patients with common variable immunodeficiency and analyzed the courses of their levels of serum Ig for a period of 8–13 years. In all patients, levels of serum IgM, IgG and IgA were markedly low at the first examination, except for the IgM level in one patient. Improvement of serum Ig levels was observed in the patients in whom Ig production of non-T cells at the first examination and Cμ gene expression had been detected to a slight degree, but serum Ig levels remained low in the patients in whom Ig production of non-T cells and Cμ gene expression had not been detected. Our results suggest that some hypogammaglobulinemia in common variable immunodeficiency develops or improves with age.     

Coexistence of common variable immunodeficiency and autoimmune polyglandular syndrome type 2

A six year-old boy with common variable immunodeficiency developed insulin dependent diabetes mellitus, autoimmune thyroiditis, and total alopecia leading to the diagnosis of autoimmune polyglandular syndrome type 2. Previously unreported co-occurence of these two entities may be explained by strong autoimmunity and HLA association of both conditions.     

Hodgkin lymphoma in two siblings with common variable immunodeficiency

Common variable immunodeficiency (CVID) is a heterogeneous group of disorders, characterized by decreased serum immunoglobulin levels, and increased susceptibility to recurrent bacterial infections, malignancies, and autoimmune disorders. In this report, 2 siblings with CVID who developed Hodgkin lymphoma are presented: a 16-year-old girl at stage IIB and her 12-year-old brother at stage IIIB of Hodgkin lymphoma. Their father and 1 uncle were also affected by the same cancer with no immunodeficiency state. The presence of lymphoma should be considered in the patients with CVID, especially in those with family history of malignancies.     

Development of hypogammaglobulinaemia in a patient with common variable immunodeficiency

A 3-year-old boy who developed common variable immunodeficiency was investigated for the development of hypogammaglobulinaemia. During a period of 4 years, the combined deficiency of IgA, IgG2 and IgG4 proceeded to include IgG1 and finally IgG3 and IgM. This order of isotypes of IgG subclass deficiencies corresponded to the gene order for the heavy chain constant region for immunoglobulins on chromosome 14.     

Multifocal adenocarcinoma of the stomach in a child with common variable immunodeficiency

The clinical course of a child who developed an adenocarcinoma of the stomach at 11 years of age is described. At 6 years of age, the child was evaluated for abdominal pain, weight loss, and vomiting. She was found to have hemorrhagic, atrophic gastritis, achlorhydria, and panhypogammaglobulinemia. The gastritis improved with corticosteroid therapy, but relapsed each time that the steroid dosage was tapered. The clinical course was marked by severe growth failure, recurrent infections, and intermittent abdominal pain. Radiographic studies done when the patient was 11 years of age demonstrated a large fungating mass on the lesser curvature of the stomach. Endoscopy and biopsies done 1 year previously had not revealed any sign of malignancy. A radical gastrectomy was performed. Microscopic studies revealed multifocal adenocarcinoma of the stomach with no evidence of invasion of the submucosa or local lymph nodes. The patient died of Candida septicemia and pneumonia 6 months after the gastrectomy. There was no evidence of recurrence of the tumor on autopsy. The relationship between common variable immunodeficiency and gastrointestinal disease is described.     

Detection of pulmonary complications in common variable immunodeficiency

Touw CML, van de Ven AA, de Jong PA, Terheggen‐Lagro S, Beek E, Sanders EAM, van Montfrans JM. Detection of pulmonary complications in common variable immunodeficiency.
Pediatr Allergy Immunol 2010: 21: 793–805.
© 2009 John Wiley & Sons A/S Pulmonary complications are frequently observed in common variable immunodeficiency (CVID). We reviewed the literature related to radiologic imaging techniques and pulmonary function tests (PFT) for diagnosing pulmonary complications in CVID. Scientific publications related to CVID (or primary hypogammaglobulinemia), pulmonary complications, PFT, chest X‐ray (CXR), and high‐resolution computed tomography scan (HRCT) were detected in PubMed, Embase and in reference lists of selected articles. Twenty‐six articles including 1047 patients (587 patients with CVID) were reviewed. Up to 73% of CVID patients develop chronic structural pulmonary complications, of which bronchiectasis and bronchial wall thickening are most frequently detected. HRCT is the most sensitive method for identification of structural abnormalities, detecting pulmonary complications that were missed on CXR and PFT in 2–59% of patients. On PFT, obstructive flow‐volume curves were most commonly found, eventually occurring in 50–94% of patients. HRCT is an important diagnostic tool for pulmonary complications in CVID at the time of diagnosis and at regular time‐points during follow‐up, with the proper follow‐up interval yet to be determined.     

Primary lymphoma of the central nervous system in children with acquired immunodeficiency syndrome

Three children with acquired immunodeficiency syndrome and primary lymphoma of the CNS are described. All three children had clinical signs of focal mass lesions and progressive neurologic deficits. In one child the deterioration was extremely rapid. New lesions appeared on serial CT scans every few days, simulating an infectious process and leading to death within 3 weeks. Results of neuroradiologic studies in these patients demonstrated multicentric lesions that were often periventricular. On CT scans, the lesions were hyperdense before contrast and were enhanced with contrast medium. Double-dose delayed contrast CT scans and magnetic resonance imaging studies were more sensitive in indicating additional lesions. Histologically, all three tumors were B cell neoplasms; two lymphomas were large cell type, whereas one was small cell, noncleaved (Burkitt-like). Primary CNS lymphoma occurred with an incidence of 1/26 (4%) in our autopsy series and 3/100 (3%) of all pediatric cases of human immunodeficiency virus-type 1 infection, living and dead, that have been seen at the Children's Hospital of New Jersey. By comparison, opportunistic and reactivated latent CNS infections were less common in this same population and never appeared clinically as mass lesions. Therefore, in our experience, primary lymphoma is the most common cause of focal or multifocal mass lesions in the brains of children with acquired immunodeficiency syndrome. This tumor may be radiosensitive. In most cases, early biopsy is probably necessary to establish the diagnosis.     

Development of common variable immunodeficiency in a patient with Evans syndrome treated by autologous stem cell transplantation

We describe a case report of a patient who developed common variable immunodeficiency (CVID) after autologous haematopoietic stem cell transplantation (SCT) for recurrent Evans syndrome. The disease manifested as attacks of haemolytic anaemia, thrombocytopenia and neutropenia from the age of 12 years. Presence of autoantibodies to blood elements was confirmed together with C4 deficiency. The patient also suffered from dermatitis herpetiformis Duhring without signs of coeliac disease. Autologous T cell-depleted peripheral blood stem cell (PBSC) transplant following conditioning regimen was performed at the age of 20 years. Immunological reconstitution was incomplete and 2 years after SCT he fulfilled laboratory criteria for common variable immunodeficiency (CVID). The patient was found to be a carrier of a risk haplotype for development of CVID DRB1*03/DQB1*0201. We conclude that T cell-depleted SCT here performed for autoimmune manifestations can hasten development of CVID in genetically predisposed patients.     

A case of common variable immunodeficiency associated with cyclic thrombocytopenia

A 12 year old boy was found to be deficient in immunoglobulins (Ig) A, G₂ and G₄, and common variable immunodeficiency was diagnosed. He also had cyclic thrombocytopenia at intervals of approximately 28–30 days. His bone marrow revealed normocellular with slightly decreased megakaryocytes. In vitro colony assays showed markedly imparied megakaryocytopoiesis, erythropoiesis and granulopoiesis. Platelet-associated IgG was elevated at his thrombocytopenic phase. Direct Coombs' test was repeatedly positive. Although not defined at present, we suggest the autoimmune nature of the disease.     

Rapidly progressive hepatitis C in a patient with common variable immunodeficiency

A 15-year-old girl with common variable immunodeficiency contracted hepatitis C, which progressed to liver cirrhosis and finally to hepatic failure 5 years later. Since she was agammaglobulinaemic, hepatitis C virus (HCV) infection was diagnosed on the basis of HCV-RNA detection. Quantification of her sera showed high levels of HCV-RNA (more than 10⁷ copies of RNA/mL), which implied active viral replication. There were no other hepatotoxic factors except HCV infection. The initial liver biopsy at 16 years of age and the autopsy confirmed a rapid progression in liver histopathological change over 4 years.     

Liver transplantation for severe hepatitis in patients with common variable immunodeficiency

CVID is a heterogeneous group of primary immunodeficiency diseases characterized by hypogammaglobulinemia, recurrent bacterial infections, and frequent autoimmune manifestations. The post-transplant course of liver transplant recipients with CVID is rarely described. We report two patients with CVID complicated by severe enteropathy who underwent living donor liver transplantation for liver failure because of severe hepatitis. The post-transplant course was complicated by recurrent acute rejection, leading to ductopenic rejection in one and recurrent hepatitis in the other. We reviewed the tissue samples histologically and immunohistochemically. Native livers showed submassive hepatocyte necrosis in one and cirrhotic liver with active hepatitis in the other, both with infiltration of CD8+ T cells accompanied by endothelialitis and bile duct damage; the intestine contained increased numbers of intraepithelial CD8+ T cells with apoptosis of epithelial cells. The liver allograft exhibited acute rejection, with prominent CD8+ T cells infiltrating the bile duct or endothelium. In the allograft following the diagnosis of post-transplant recurrent hepatitis, CD8+ T cells comprised the majority of infiltrating cells in portal areas spilling over into hepatic parenchyma. Our cases suggest that T cells contribute to the pathogenesis of CVID in native organs as well as allografts and may constitute evidence of T-cell deregulation in the pathogenesis of CVID.     

Chronic inflammatory bowel disease in a patient with common variable immunodeficiency

Common variable immunodeficiency (CVID) is a primary defect of the immune system involving an increased risk of respiratory and digestive tract infections and autoimmune diseases. Recently, it has been reported that chronic inflammatory bowel disease (CIBD) might occur with increased frequency (20%) in patients with CVID. A nine-year-old boy with CVID developed CIBD during follow-up and periodic intravenous immunoglobulin administration. Serum tumor necrosis factor-a concentration, which is suggested to show disease activity in CBD, was very high. The patient's radiological evaluation, both in active and remission periods, had characteristic features of CBD. We herewith present and discuss this case with both diseases, CVID and CIBD.     

Diagnosis of common variable immunodeficiency in a patient with primary ciliary dyskinesia

In this case report we describe the first account in the literature of a patient with primary ciliary dyskinesia and common variable immunodeficiency. A 17-year-old boy with previously diagnosed Kartagener syndrome and stable lung disease developed a deteriorating clinical course that prompted the search for a secondary diagnosis. Although both of these rare conditions can result in similar lung pathology, they require different management strategies, which illustrates the need to consider associated diagnoses in complicated clinical situations.     

Tuberculosis in children with acquired immunodeficiency syndrome

With AIDS related tuberculosis in the pediatric population on the rise, we review our experience with 14 such children. A brief review of the pertinent literature is also presented. Received: 20 March 1996 Accepted: 25 June 1996     

Nephrotic syndrome associated with acquired immunodeficiency syndrome in children

We report here the cases of 15 children in whom nephrotic syndrome developed, from among 164 children (55% male, 90% black) followed in our acquired immunodeficiency syndrome clinic from 1984 through 1990. Mean age at onset of nephrotic syndrome was 4.9 +/- 2.6 years. Fourteen patients were black and one was Hispanic. Seventy-three percent of our patients with nephrotic syndrome were girls. The mean duration of clinical acquired immunodeficiency syndrome before development of nephrotic syndrome was 1.7 +/- 1.1 years. In eight patients, nephrotic syndrome appeared between 3 and 11 months after intravenous infusions of immune globulin or albumin were administered as part of a research protocol; this incidence (8/47) was higher than the incidence of nephrotic syndrome among those who did not receive intravenous infusions (7/117, p less than 0.05). Tissue for histologic examination was available for 80% of the patients, and histologic examination demonstrated mesangial hypercellularity (5 patients), focal segmental glomerulosclerosis (4 patients), minimal change disease (2 patients), and IgM nephropathy (1 patient). Deposition of one or more immunoglobulins was noted in all but one patient studied with immunofluorescence. Corresponding electron-dense deposits were seen by electron microscopy in 78% of specimens. Prednisone did not induce a remission of nephrotic syndrome in the 13 patients treated, whereas cyclosporine did so in the 3 patients to whom it was administered. Five patients were in the end stage of renal disease within 8 months. Successful maintenance peritoneal dialysis was performed in three patients, but 80% of patients have died of human immunodeficiency virus-related complications; one patient was lost to follow-up. We conclude that immune-complex deposition is consistently seen in children with human immunodeficiency virus-associated nephrotic syndrome. This nephrotic syndrome is resistant to steroid therapy, but we observed a remission of the proteinuria with cyclosporine therapy in three patients. For patients with end-stage renal disease, maintenance peritoneal dialysis may improve the quality of life.