Hyper IgM Syndrome: a Report from the USIDNET Registry.

PURPOSE: The United States Immunodeficiency Network (USIDNET) patient registry was used to characterize the presentation, genetics, phenotypes, and treatment of patients with Hyper IgM Syndrome (HIGM). METHODS: The USIDNET Registry was queried for HIGM patient data collected from October 1992 to July 2015. Data fields included demographics, criteria for diagnosis, pedigree analysis, mutations, clinical features, treatment and transplant records, laboratory findings, and mortality. RESULTS: Fifty-two physicians entered data from 145 patients of ages 2 months to 62 years (median 12 years); 131 were males. Using patients' age at last entry, data from 2072 patient years are included. Mutations were recorded for 85 subjects; 82 were in CD40LG. Eighteen subjects had non-X-linked HIGM. 40 % had a normal serum IgM and 15 %, normal IgA. Infections were reported for 91 %, with pulmonary, ear, and sinus infections being the most common. 42 % had Pneumocystis jirovecii pneumonia; 6 % had Cryptosporidium. 41 % had neutropenia. 78 % experienced non-infectious complications: chronic diarrhea (n = 22), aphthous ulcers (n = 28), and neoplasms (n = 8) including colon cancer, adrenal adenoma, liver adenocarcinoma, pancreatic carcinoid, acute myeloid leukemia, hepatoma, and, in a female with an autosomal dominant gain of function mutation in PIK3CD, an ovarian dysgerminoma. Thirteen patients had a hematopoietic marrow or stem cell transplant; three had solid organ transplants. Thirteen were known to have died (median age = 14 years). CONCLUSIONS: Analysis of the USIDNET Registry provides data on the common clinical features of this rare syndrome, and in contrast with previously published data, demonstrates longer survival times and reduced gastrointestinal manifestations.

Behavioral, immunologic, and virologic correlates of oral human papillomavirus infection in HIV-infected youth.

BACKGROUND: Little is known about the epidemiology or risk factors for oral human papillomavirus (HPV) in HIV-infected youth. The objectives of this study were to determine the prevalence and correlates of oral HPV infection and to explore the association between HPV vaccination and oral infection in HIV-infected youth. METHODS: Youth 12 to 24 years of age with behaviorally acquired HIV were recruited for this cross-sectional study. Procedures involved medical chart review, survey, and collection of an oral rinse sample. Univariable and multivariable logistic regression models were used to determine whether demographic, behavioral, immunologic, and virologic factors and history of vaccination were significantly associated with oral HPV infection. RESULTS: Mean age of the 272 participants was 21.5 years; 64% were non-Hispanic black and 20.2% were Hispanic; and 10.8% of men compared with 20.3% of women were fully vaccinated. Human papillomavirus prevalence was 19.7% in men and 18.6% in women (P = 1.0). Only men were positive for vaccine-type HPV: 5.6% were positive for HPV-6, HPV-11, HPV-16, and/or HPV-18, and 4.2% were positive for HPV-16 and/or HPV-18. Among men who were fully vaccinated, none were positive for HPV-6, HPV-11, HPV-16, and/or HPV-18, compared with 12 (6.3%) of men who were not fully vaccinated (P = 0.37). Two variables were marginally associated with oral HPV (P < 0.10): marijuana use in the previous 3 months and lower CD4+ T-cell count. CONCLUSIONS: Prevalence rates of oral HPV were relatively high in this population of HIV-infected youth and were similar in male and female youth. No fully vaccinated men were infected with vaccine-type HPV.

A syndrome of hypoplastic sinuses, hydrocephalus, bronchiectasis, and hypogammaglobulinemia with functional antibody deficiency in twin girls.

BACKGROUND: A variety of syndromes are known to be associated with immune deficiency, some as a major part of the syndrome and some as an occasional finding. OBJECTIVES: To report a newly defined syndrome of hydrocephalus, hypoplastic sinuses, cartilaginous webbing of the bronchi, bronchiectasis, and hypogammaglobulinemia with functional antibody deficiency in identical twin girls. METHODS: Spirometry, radiography, computed tomography (CT), bronchoscopy, and laboratory tests were performed for diagnosis. RESULTS: A girl (twin A) was evaluated at the age of 7 years for chronic cough and wheeze that worsened with exercise. Hydrocephalus had been diagnosed a year before evaluation. She was treated for cough variant asthma and was lost to follow-up until the age of 10 years. The cough had worsened progressively, and dyspnea was now apparent. Spirometry was consistent with reversible airway obstruction. A chest radiograph was suggestive of bronchiectasis. A chest CT scan showed bilateral upper lobe bronchiectasis. Hypogammaglobulinemia and functional antibody deficiency were noted. A CT scan of the sinuses revealed aplasia or severe hypoplasia of all the paranasal sinuses. Bronchoscopy revealed a grossly abnormal bronchial structure and atrophic-appearing bronchial mucosa. Twin B also had a history of hydrocephalus. Although she had no respiratory symptoms, chest CT revealed bronchiectasis, and she had obstruction on spirometry. Laboratory analysis revealed hypogammaglobulinemia and functional antibody deficiency. She became symptomatic 2 years after twin A. CONCLUSIONS: This is a newly reported syndrome of hydrocephalus, absent sinuses, abnormalities of the bronchi, and functional antibody deficiency, which initially presented as cough and wheeze.

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.