Hyper-IgE and Carcinoma in CADINS Disease.

Background: Atopic dermatitis (AD) affects up to 25% of children and 10% of adults in Western countries. When severe or recurrent infections and exceedingly elevated serum IgE levels occur in AD patients, an inborn error of immunity (IEI) may be suspected. The International Union of Immunological Societies classification lists variants in different genes responsible for so-called Hyper-IgE syndromes. Diagnosing an underlying IEI may influence treatment strategies. Methods: Clinical and diagnostic workup of family members are presented including a detailed immunological description and histology of the carcinoma. Functional testing of the novel variant in CARD11 underlying 'CARD11-associated atopy with dominant interference of NF-kB signaling' (CADINS) was performed. Results: We report on an 18-year-old patient with a long-standing history of infections, accompanied by hypogammaglobulinemia, intermittent agranulocytosis, atopy, eosinophilia and colitis. The working diagnosis of common variable immunodeficiency was revised when a novel heterozygous CARD11 variant [c.223C>T; p.(Arg75Trp)] was identified. Functional studies confirmed this variant to have a dominant negative (DN) effect, as previously described in patients with CADINS. Five other family members were affected by severe atopy associated with the above variant, but not hypogammaglobulinemia. Malignancies occurred in two generations: an HPV-positive squamous cell carcinoma and a cutaneous T-cell lymphoma. So far, one patient is under treatment with dupilumab, which has shown marked benefit in controlling severe eczema. Conclusion: The phenotypic spectrum associated with heterozygous CARD11 DN mutations is broad. Partial T-cell deficiency, diminished IFN-γ cytokine and increased IL-4 production, were identified as disease-causing mechanisms. Malignant disease associated with germline CARD11 DN variants has only been reported sporadically. HPV vaccination in teenage years, and cytology screening analogous with routine cervical swabs may be recommended. Treatment with dupilumab, a monoclonal antibody blocking interleukin-4- and interleukin-13 signaling, may be of benefit in controlling severe and extended AD for some patients as reported for STAT3 loss-of-function.

Comparison between F-18 fluorodeoxyglucose and Ga-68 DOTATOC in metastasized melanoma.

PURPOSE: Somatostatin binding to somatostatin receptors (SSTRs) is known to have an antiproliferative effect in neuroendocrine tumours. Melanoma cells are derived from the neural crest and thus express SSTR. Treatment options in metastasized melanomas are limited. Therefore, we aimed to investigate whether there is a relevant uptake of the SSTR analogue DOTATOC in metastasized melanoma patients, which could be used for therapy with radiolabelled SSTR analogues. MATERIALS AND METHODS: We investigated 18 patients (nine men and nine women; mean age 61 years) with metastasized melanoma using PET/CT, first with F-18 fluorodeoxyglucose ((18)F-FDG) and then with Ga-68 DOTATOC. The number of (18)F-FDG-positive or DOTATOC-positive lesions and the maximum standardized uptake value (SUV(max)) for an index lesion were determined for each patient. RESULTS: DOTATOC could reveal metastatic lesions in 11 of 18 patients (61%). However, on a lesion-by-lesion basis only 59 of 263 (22%) (18)F-FDG-avid metastases were seen with DOTATOC. Further, DOTATOC uptake was only faint. The mean SUV(max) was 3.1 (range, 1.2-4.2) for DOTATOC, in contrast to 28.2 (range, 2.3-115) for (18)F-FDG. CONCLUSION: Radiolabelled DOTATOC does not seem to be a promising agent for treatment of metastasized melanoma.

Severe allergic reactions to para-phenylenediamine in children and adolescents: should the patch test concentration of PPD be changed?

BACKGROUND: Semipermanent henna tattoos containing para-phenylenediamine (PPD) are a well-known cause of severe contact dermatitis, mainly in children. Another relevant exposure source to PPD are hair dyes, which are increasingly used by children and have also been reported to cause intense facial and scalp dermatitis. German patch test guidelines for children recommend that PPD should only be tested in patients who have had a henna tattoo, and then at a reduced concentration of PPD 0.5 % for 24 hours. PATIENTS AND METHODS: We report on patch test results in four patients, three children and one adolescent, with a history of contact dermatitis to henna tattoos or hair dye. We used the recommended or even lower patch test concentrations of PPD with 24-hours exposure in all patients. RESULTS AND CONCLUSION: All patients showed very strong patch test reactions to PPD and cross-reactions to related compounds even after dilution of PPD to as low as 0.05 %. Therefore, we suggest that in children with a history of allergic reactions to this compound, a titration test should be performed beginning at a concentration of maximal 0.05 %. This procedure has also been proposed previously based on a larger cases series in adults.