Case Report: Secondary Hemophagocytic Lymphohistiocytosis With Disseminated Infection in Chronic Granulomatous Disease-A Serious Cause of Mortality.

Chronic granulomatous disease (CGD) is a primary immune deficiency due to defects in phagocyte respiratory burst leading to severe and life-threatening infections. Patients with CGD also suffer from disorders of inflammation and immune dysregulation including colitis and granulomatous lung disease, among others. Additionally, patients with CGD may be at increased risk of systemic inflammatory disorders such as hemophagocytic lymphohistiocytosis (HLH). The presentation of HLH often overlaps with symptoms of systemic inflammatory response syndrome (SIRS) or sepsis and therefore can be difficult to identify, especially in patients with a primary immune deficiency in which incidence of infection is increased. Thorough evaluation and empiric treatment for bacterial and fungal infections is necessary as HLH in CGD is almost always secondary to infection. Simultaneous treatment of infection with anti-microbials and inflammation with immunosuppression may be needed to blunt the hyperinflammatory response in secondary HLH. Herein, we present a series of X-linked CGD patients who developed HLH secondary to or with concurrent disseminated CGD-related infection. In two patients, CGD was a known diagnosis prior to development of HLH and in the other two CGD was diagnosed as part of the evaluation for HLH. Concurrent infection and HLH were fatal in three; one case was successfully treated, ultimately receiving hematopoietic stem cell transplantation. The current literature on presentation, diagnosis, and treatment of HLH in CGD is reviewed.

Advances in drug allergy, urticaria, angioedema, and anaphylaxis in 2018.

Many notable advances in drug allergy, urticaria, angioedema, and anaphylaxis were reported in 2018. Broad-spectrum antibiotic use and, consequently, antibiotic resistance are widespread, and algorithms to clarify ß-lactam allergy and optimize antibiotic use were described. Meaningful data emerged on the pathogenesis of delayed drug hypersensitivity reactions. Progress not only in defining biomarkers but also in understanding the effect on quality of life and developing better treatments has been made for patients with chronic idiopathic urticaria. Patients with hereditary angioedema (HAE) have gained additional access to highly efficacious therapies, with associated improvements in quality of life, and some progress was made in our understanding of recurrent angioedema in patients with normal laboratory results. Guidelines have defined clear goals to help providers optimize therapies in patients with HAE. The epidemiology and triggers of anaphylaxis and the mechanisms underlying anaphylaxis were elucidated further. In summary, these disorders (and labels) cause substantial burdens for individual persons and even society. Fortunately, publications in 2018 have informed on advancements in diagnosis and management and have provided better understanding of mechanisms that potentially could yield new therapies. This progress should lead to better health outcomes and paths forward in patients with drug allergy, urticaria, HAE, and anaphylaxis.

Reliability of allergy skin testing.

BACKGROUND: Percutaneous allergen skin testing remains an established benchmark for diagnosing atopic disease. The reliability of skin testing depends greatly on the performance of allergen extracts used, methods used, and the presence of antihistamine medications. OBJECTIVE: To determine the differential effect of cetirizine on 2 different concentrations of histamine control solution and 5 common allergens used for percutaneous skin testing. METHODS: Twelve individuals underwent skin testing with histamine (1 and 6 mg/mL), control diluent, and 5 common aeroallergens. Wheal and flare measurements were measured in a masked fashion by a single operator. Cetirizine was administered for 4 consecutive days to determine the effect on both histamine and allergen wheal and flare responses. RESULTS: A total of 384 skin tests were performed on 12 volunteers. Cetirizine began to suppress wheal and flare responses at 1 hour (P < .05), with maximum suppression at day 5 (P < .05). Wheal and flare responses returned to greater than 90% baseline within 4 days of not taking cetirizine. Suppression was more apparent with 1 vs 6 mg/mL of histamine (62% vs 33%). Four of the 12 individuals taking cetirizine had a positive skin test result using 6 mg/mL of histamine control when the 1-mg/mL histamine test result was negative. Importantly, twice as many individuals had false-negative allergen responses using 6 mg/mL of histamine vs the 1 mg/mL as a positive control, although this finding did not reach statistical significance. CONCLUSION: The use of a 6-mg/mL histamine control for some percutaneous skin test devices may result in more false-negative allergen responses because of the inability to detect the presence of antihistamines.

Diagnosing environmental allergies: Comparison of skin-prick, intradermal, and serum specific immunoglobulin E testing.

BACKGROUND: Allergists commonly perform intradermal skin testing (IDST) after negative skin-prick testing (SPT) to comprehensively diagnose environmental allergic sensitization. However, with the availability of modern methods to detect serum-specific immunoglobulin E (ssIgE), it is unclear if ssIgE testing could substitute for IDST. OBJECTIVE: To determine the efficacy of ssIgE testing and IDST when added to SPT in diagnosing environmental allergic sensitizations. METHODS: SPT, IDST, and ssIgE testing to nine common environmental allergens were analyzed in 75 patients with oculonasal symptoms who presented to our allergy clinics in the Bronx, New York, between January 2014 and May 2015. RESULTS: A total of 651 SPT and 499 ssIgE tests were independently performed and revealed 162 (25%) and 127 (25%) sensitizations, respectively. When SPT results were negative, IDST results revealed 108 of 452 additional sensitizations (24%). In contrast, when SPT results were negative, ssIgE test results only revealed 9% additional sensitizations. When both SPT and IDST results were negative, ssIgE testing only detected 3% of additional sensitizations, and ssIgE levels were typically low in these cases (median, 1.25 kU/L; range, 0.357-4.47 kU/L). When both SPT and ssIgE test results were negative, IDST results detected 15% additional sensitizations. CONCLUSION: IDST detected more additional environmental sensitizations compared with ssIgE testing. IDST, therefore, may be useful when the SPT and/or ssIgE testing results were negative, but the exposure history indicated relevant allergic sensitization. Serology added only a little more information if both SPT and IDST results were negative but may be useful in combination with SPT if IDST cannot be performed.

The effectiveness of the Spot Vision Screener in detecting amblyopia risk factors.

PURPOSE: To evaluate the updated Spot Vision Screener (PediaVision, Welch Allyn, Skaneateles Falls, NY) in detecting amblyopia risk factors using 2013 guidelines of American Association for Pediatric Ophthalmology and Strabismus (AAPOS). METHODS: In this prospective study, patients seen from June 2012 to November 2013 were tested with the Spot prior to examination by a pediatric ophthalmologist who was masked to test results. The following data were analyzed: age, subject testability, examination findings, and systemic and ocular pathology. Children were divided into three age groups to determine gold standard results according to the AAPOS guidelines. RESULTS: A total of 444 children (average age, 72 months) were included. Compared to the ophthalmologist's examination, the Spot sensitivity was 87.7% and the specificity was 75.9% in detecting amblyopia risk factors. Sensitivity did not differ significantly between age groups, although the positive predictive value improved in the older age groups. CONCLUSIONS: In our study cohort, the Spot provided good specificity and sensitivity in detecting amblyopia risk factors according 2013 AAPOS criteria, with minor improvements with updated versions.

Pancreatic duct ligation after almost complete ß-cell loss: exocrine regeneration but no evidence of ß-cell regeneration.

There has been great interest in the extent of ß-cell regeneration after pancreatic duct ligation (PDL) and whether α- to ß-cell conversion might account for ß-cell regeneration after near-complete ß-cell loss. To assess these questions, we established a PDL-model in adult male rats after almost complete beta-cell depletion achieved by giving a single high dose of streptozocin (STZ) in the fasted state. Because of the resultant severe diabetes, rats were given islet cell transplants to allow long-term follow-up. Although animals were followed up to 10 months, there was no meaningful ß-cell regeneration, be it through replication, neogenesis, or α- to ß-cell conversion. In contrast, the acinar cell compartment underwent massive changes with first severe acinar degeneration upon PDL injury followed by the appearance of pancreatic adipocytes, and finally near-complete reappearance of acini. We conclude that ß-cells and acinar cells, although originating from the same precursors during development, have very distinct regenerative potentials in our PDL model in adult rats.