The Immunoglobulin M Response to Pneumococcal Polysaccharide Vaccine Is Sufficient for Conferring Immunity.

In mice, pneumococcal polysaccharide (PPS) vaccines generate antigen-specific immunoglobulin M (IgM) and immunoglobulins G1, G2, and G3. Antibody and complement-dependent opsonophagocytosis correlates with the protection induced by PPS vaccines in vivo. Since IgM is a very efficient immunoglobulin isotype in activating the complement system, we evaluated whether anti-PPS IgM alone is sufficient to confer protective immunity to Streptococcus pneumoniae. We found that immunization of wild-type and activation-induced cytidine deaminase-deficient mice capable of producing only IgM with Pneumovax 23 generated comparable anti-PPS IgM and resistance to lethal systemic challenge with S pneumoniae. These data suggest that an IgM response to PPS vaccines is sufficient for conferring immunity.

Phenotypic parameters predict time to normalization in infants with hypogammaglobulinemia.

PURPOSE: Infants with recurrent infection may be found to have hypogammaglobulinemia without impaired specific antibody responses. Many will be diagnosed with transient hypogammaglobulinemia of infancy. METHODS: This study used a parametric survival analysis of 100 infants with hypogammaglobulinemia to predict time to normalization. RESULTS: Aggregate initial immunoglobulins (IgG + IgA + IgM), as a percentage of age-adjusted normal, predicted time to resolution: median time to resolution for the infants in the lowest quartile of aggregate levels (≤81 % of age-adjusted lower limits) was greater than 5 years, with 34 % resolving in 3 years. For infants in the highest quartile (≥130 % of age-adjusted lower limits), the median was 9.9 months, with 77 % resolving in 3 years (P = 0.008). Initial IgG level, as a percentage of age-adjusted normal, also predicted resolution: the median time in the lowest quartile (≤78 % of age-adjusted lower limits) was greater than 5 years, with 36 % resolving in 3 years. In the highest quartile (≥128 %), the median time was 14.5 months, with 70 % resolving in 3 years (P = 0.010). Male sex was associated with more rapid resolution. The median time in males was 13 months, with 73 % resolution in 3 years. The median time in females was greater than 5 years, with 32 % resolution in 3 years. CONCLUSIONS: These results suggest that if a term infant presents with hypogammaglobulinemia, protective specific antibody titers, and an absence of other known immune deficiency, initial immunoglobulin levels and sex may predict time to normalization.

Infants with low immunoglobulin levels: Isolated low IgA level vs other immunoglobulin abnormalities.

BACKGROUND: The International Union of Immunological Societies defined transient hypogammaglobulinemia of infancy as decreased IgG and IgA levels. Some others, however, include decreased IgA level alone. We compared infants with decreased levels of IgG and IgA, all isotypes, and IgA alone. OBJECTIVE: To determine whether infants presenting with diminished IgA only differ clinically and in time of immunoglobulin recovery, from those with decreased levels of IgG and IgA, or of all major isotypes. METHODS: Eighty-seven term infants found to have immunoglobulin isotype(s) 2 or more SDs below mean, normal antibody response, intact cellular immunity, and absence of other immunodeficiency syndrome features were evaluated between January 1, 1977 and December 31, 2008. Infants had decreased IgA level (group 1, n = 43), decreased IgA and IgG levels (group 2, n = 39), or low IgA, IgG, and IgM levels (group 3, n = 5). RESULTS: Groups had similar histories. Immunoglobulins normalized in a similar percentage of all groups during infancy but earlier for group 1 (P = .005). CONCLUSION: Little reason exists to separate infants with isolated decreased IgA levels from those with decreased levels of IgA and IgG or all isotypes.

Radiologic outcomes in children with chronic rhinosinusitis and ostiomeatal complex obstruction after medical management.

BACKGROUND: The presence of ostiomeatal complex obstruction can be a key component in chronic rhinosinusitis, and the medical management of this condition has not been well studied, particularly in children. OBJECTIVE: To compare the effectiveness of antibiotics, intranasal topical corticosteroids, and oral systemic corticosteroids on radiologic outcomes in children with chronic rhinosinusitis and ostiomeatal complex obstruction. METHODS: We reviewed the reports of 1,741 computed tomography scans performed on children at Alfred I. duPont Hospital for Children, Wilmington, Delaware, from October 1, 2001, through February 28, 2007, identifying those patients who had 2 scans performed at least 2 weeks apart but no more than 6 months apart. Forty-five instances involving abnormal ostiomeatal complex anatomy documented on the initial study with obtainable treatment information were selected for further review. RESULTS: Of the 3 treatment modalities examined, only oral systemic corticosteroids (P = .03) and intranasal topical corticosteroids (P = .03) were found to provide significant independent contributions to predicting treatment outcome, with the former promoting a positive outcome and the latter predicting a negative outcome. The model that contained just these 2 factors also provided a significant fit to the outcome data (P = .01), producing a diminished rate of improvement expected from a combination of positive and negative influences. Neither antibiotics nor any other combination of modalities contributed to a significant improvement in model fit. CONCLUSION: The use of oral systemic corticosteroids was found to be the only beneficial intervention, with regard to radiologic improvement, in the treatment of ostiomeatal complex obstruction in children.

A 15-year-old girl with recurrent pneumonia.

Hodgkin's disease (HD) represents a group of lymphomas with distinct clinical and histopathological features that account for approximately 5% of cancers in patients who are <15 years old and approximately 15% in patients who are 15-19 years old. Although the cause of HD is unknown, serologically confirmed infectious mononucleosis has been associated with an increased risk of HD, in addition to its known association with Burkitt's lymphoma. The Reed-Sternberg (RS) cell, a large and multinucleated cell with unique morphology, is the hallmark cell of HD. RS cells are clonal tumor cells that recently have been shown to be derived from B cells originating from germinal centers. Of four histological subtypes of HD, three have a good to excellent prognosis when recognized and treated early. We report a case of HD in a 15-year-old adolescent with a 14-month history of recurrent pneumonia. Open lung biopsy ultimately led to the diagnosis of HD. Although uncommon in this age group, the need to consider the possibility of neoplasm in the setting of recurrent respiratory infection is illustrated in this case. Early diagnosis and intervention may determine the prognosis of such neoplasms.

Selective IgM deficiency and 22q11.2 deletion syndrome.

BACKGROUND: The 22q11.2 deletion syndrome is a common chromosomal disorder with highly variable phenotypic expression and immunologic defects. Humoral immunity is mostly unaffected, but selective IgA deficiency occurs in up to 13% of patients. Selective IgM deficiency associated with 22q11.2 deletion has been reported in 1 patient. OBJECTIVE: To describe another 2 patients with 22q11.2 deletion syndrome and IgM deficiency. METHODS: Patient 1 was a 6-year-old boy with recurrent otitis media, sinopulmonary infections, wheezing, and speech delay. His serum IgM level was 18 mg/dL, and his IgA and IgG levels were normal. Antibody titers to protein and carbohydrate antigens were protective. Workup for velopharyngeal insufficiency resulted in the diagnosis of 22q11.2 deletion syndrome 3 years later. Patient 2 was a 14-year-old girl diagnosed as having 22q11.2 deletion at 9 years of age after presenting with neonatal seizures, atrial and ventricular septal defects, recurrent otitis media, mental retardation, and asthma. Her serum IgM level was 11 mg/dL, with normal IgG and IgA levels. Antibody titers to protein and carbohydrate antigens were protective. Patient 3 was a previously described 15-year-old girl with persistently draining ears, 22q11.2 deletion, and an IgM level less than 6 mg/dL. Her clinical and laboratory features are summarized. RESULTS: Results of further testing on the patients, including lymphocyte enumeration, were normal. The literature is reviewed regarding decreased IgM levels in 22q11.2 deletion syndrome. CONCLUSIONS: Fluorescence in situ hybridization analysis for chromosome 22q11.2 deletion should be considered in patients with selective IgM deficiency, especially if concurrent chronic otitis media, developmental delay, velopharyngeal insufficiency, or dysmorphic features are present.

Patient, home residence, and neighborhood characteristics in pediatric emergency department visits for asthma.

OBJECTIVE: To identify patient, home residence, and neighborhood characteristics of children with asthma-related emergency department visits. METHODS: Medical records of children with one (group A) or more than one (group B) asthma-related pediatric emergency department visit were reviewed. RESULTS: A significantly higher percentage of group B had Medicaid insurance (p = 0.04), history of asthma-related hospitalizations (p = 0.04), and passive tobacco smoke exposure (p = 0.03). Neighborhood characteristics were similar between the two groups. CONCLUSIONS: Smoking cessation counseling and close monitoring of patients with a history of asthma-related hospitalizations and patients with Medicaid insurance may be helpful in decreasing emergency department visits.

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.

Lack of cross-reactivity between 5-aminosalicylic acid-based drugs: a case report and review of the literature.

BACKGROUND: 5-Aminosalicylic acid (5-ASA)-containing drugs are the mainstay of therapy in inflammatory bowel disease, but adverse reactions to these medications are relatively common. Because there may be a lack of cross-reactivity among the various 5-ASA formulations, treatment with alternative preparations is sometimes possible even after an apparent allergic reaction to a 5-ASA product. OBJECTIVE: To describe a patient with a possible allergy to 2 different 5-ASA drugs who tolerated a third. METHODS: A 27-year-old man with Crohn disease developed a rash while taking mesalamine (Pentasa and Asacol). Treatment with 5-ASA products was discontinued, and 6-mercaptopurine and prednisone were prescribed. He then experienced multiorgan failure secondary to herpes simplex infection, which required discontinuation of the immunosuppressive therapy. After recovery from the acute infection, he underwent successful graded challenge with balsalazide. RESULTS: The patient continued treatment with balsalazide for 9 months, with good control of his inflammatory bowel disease and no adverse effects. CONCLUSIONS: Adverse reactions to 1 or more 5-ASA medications do not necessarily preclude the use of others in the same class. A treatment algorithm for patients with adverse reactions to 5-ASA is outlined based on the case report and review of the literature.

A 5-month-old boy with recurrent respiratory infections, failure to thrive, and borderline elevated sweat chloride levels.

Both severe combined immunodeficiency (SCID) and cystic fibrosis (CF) may present in infancy with a history of respiratory infections and failure to thrive. Elevated sweat chloride levels on multiple sweat tests is diagnostic of CF; transient elevation of sweat chloride has been reported in patients with hypogammaglobulinemia and antibody deficiency without CF. This article presents a case report of a 5-month-old boy with recurrent respiratory infections, failure to thrive, and two borderline elevated sweat test levels. Laboratory evaluation including testing for CF as well as immune deficiency was performed in this patient. Two borderline abnormal sweat chloride tests together with isolation of Pseudomonas from the airway caused clinicians initially to suspect CF; however, mutation in gene coding for the gamma-chain of the IL-2 receptor and a negative CF genetic mutation analysis ultimately led to the final diagnosis of SCID. It is essential to make the diagnosis of SCID as early as possible because infants with SCID who do not undergo reconstitution of their immune system universally die in infancy because of infection. Early diagnosis and intervention can lead to an excellent prognosis in a previously fatal disease.

Developing resources to teach and assess the core competencies: a collaborative approach.

Graduate medical education programs face new challenges as they seek to comply with the mandate from the Accreditation Council on Graduate Medical Education to demonstrate that they are teaching and assessing residents on the six core competencies. The authors describe a project designed as a collaborative venture between the American Academy of Allergy, Asthma, and Immunology (AAAAI) and the Center for Educational Outcomes at Dartmouth College (CEdO) to provide residency programs in allergy/immunology with resources for teaching and assessing the core competencies. The goal was to create a set of learning and assessment resources that maximized the content knowledge expertise provided by the AAAAI and the learning expertise provided by CEdO. A highly interactive, iterative process was used to create a set of Web-based modules. Bilateral communication, buy-in, and active involvement in the process were seen as crucial to the development of resources and their successful implementation. Approximately 18 months after the modules were made available to training program directors, 80% of the directors surveyed were aware of and had accessed the modules. The joint creation process used in this project, designed to be generally applicable across specialties, reveals how the burden of meeting new requirements can be decreased when experts in content knowledge and experts in learning collaborate.

Immunocompetence and allergy.

Developed nations are experiencing a marked increase in prevalence of the familial allergic diseases including asthma, allergic rhinitis, atopic dermatitis, and allergic gastroenteropathy, which are often called atopic diseases. No satisfactory explanation for this epidemic is known, but it has been proposed that some facets of modern life tend to bias immune responses away from the Th1 cellular immune responses that protect against many infections and toward Th2 responses that favor atopy. There are 2 hypotheses to explain why this epidemic is occurring now. Hypothesis 1 suggests that nutritional patterns have changed or that we are exposed to environmental toxicants that were not previously present. Hypothesis 2 holds that some aspects of modern lifestyles in affluent nations have minimized exposure to infectious agents or to their by-products, such as endotoxin. This feature of contemporary lifestyle, it is suggested, has favored the development of Th2 immune responses to environmental allergens and the development of the attendant atopic diseases. This latter theory has been designated the "hygiene hypothesis." Although there is evidence both for and against both hypotheses, evidence for hypothesis 2 is stronger and more convincing.

Antibody response in common variable immunodeficiency.

BACKGROUND: Common variable immunodeficiency (CVID) describes a heterogeneous group of immunologic disorders of unknown etiology. It is characterized by low levels of serum immunoglobulin (Ig) and impaired antibody response. OBJECTIVE: To describe antibody response and the kinetics of IgG decline in patients identified with CVID. METHODS: Clinical and immunologic observations of four patients identified with CVID were obtained by chart review. RESULTS: Antibody response to polysaccharide antigens in patients identified with CVID is lost earlier than the antibody response to protein antigens, which may be preserved even in the face of profound hypogammaglobulinemia. In three patients who were followed prospectively, the Ig loss was progressive. CONCLUSIONS: Absence of antibody response to polysaccharide antigens may be a universal finding in patients with CVID, whereas preservation of T cell-dependent protein antibody response may be seen.

Lactic acidosis and status asthmaticus: how common in pediatrics?

BACKGROUND: Lactic acidosis is a well described phenomenon in adult patients with severe asthma. However, this entity is rarely reported in children with status asthmaticus. OBJECTIVE: To report our experience in a 13-year-old girl who developed lactic acidosis as a complication of status asthmaticus and to investigate the prevalence of this complication of severe asthma. We sought to determine the frequency of lactic acidosis in such patients and to review etiologies of lactic acidosis. METHODS: 1) Observations on the clinical and laboratory findings in an adolescent girl with status asthmaticus who developed lactic acidosis were recorded. 2) The medical records of 100 children and adolescents with status asthmaticus admitted to an intensive care unit were reviewed for laboratory evidence of lactic acidosis. 3) We also reviewed our own previous experience of status asthmaticus with respiratory failure. RESULTS: Among 100 patients admitted to a pediatric intensive care unit for status asthmaticus, a single case of isolated metabolic acidosis was identified. This proved to be attributable to lactic acidosis. When records of patients with severe respiratory failure were examined, no cases of metabolic acidosis were found. CONCLUSIONS: Although rare, lactic acidosis does occur in pediatric-aged patients during status asthmaticus. It is important that this complication be recognized and treated because acidosis may inhibit the effectiveness of bronchodilator therapy, produce electrolyte disturbances, and cause serious adverse effects on the patient's cardiovascular system.