ABSTRACT
Adverse drug reactions are frequently reported in pediatric patients. In this review article, the authors discuss pediatric drug allergies with emphasis on the most common culprits, beta-lactam antibiotics and non-steroidal anti-inflammatory drugs. The authors also discuss reactions to non-beta-lactam antibiotics and chemotherapeutics. Skin testing has not yet been validated for many drugs, although notable exceptions include penicillin and carboplatin. The gold standard for diagnosis in most cases remains drug challenge, and the need for penicillin skin testing prior to oral provocation challenge has been questioned in recent studies. Successful desensitizations have also been reported with several drugs.
Subject(s)
Drug Hypersensitivity , Pharmaceutical Preparations , Anti-Bacterial Agents/adverse effects , Anti-Inflammatory Agents, Non-Steroidal/adverse effects , Child , Drug Hypersensitivity/diagnosis , Drug Hypersensitivity/epidemiology , Humans , Skin Tests , beta-Lactams/adverse effectsABSTRACT
The newborn screen for severe combined immunodeficiency (SCID) uses real-time quantitative polymerase chain reaction for T-cell receptor excision circles and is highly sensitive for SCID. However, T-cell lymphopenia from other primary and secondary causes, such as DiGeorge syndrome, prematurity, thymic involution from stress, and thymectomy during cardiac surgery, is also detected. We present a newborn girl with T-cell lymphopenia of unknown etiology detected via abnormal newborn screen.
Subject(s)
Immunologic Deficiency Syndromes/diagnosis , Infant, Premature , Lymphopenia/diagnosis , T-Lymphocytes/pathology , Anti-Inflammatory Agents/adverse effects , Betamethasone/adverse effects , Cells, Cultured , Female , Humans , Immunophenotyping , Immunosuppression Therapy , Infant , Infant, Newborn , Neonatal Screening , Receptors, Antigen, T-Cell/geneticsABSTRACT
Adverse drug reactions are frequently reported in pediatric patients. In this review article, the authors discuss pediatric drug allergies with emphasis on the most common culprits, beta-lactam antibiotics and non-steroidal anti-inflammatory drugs. The authors also discuss reactions to non-beta-lactam antibiotics and chemotherapeutics. Skin testing has not yet been validated for many drugs, although notable exceptions include penicillin and carboplatin. The gold standard for diagnosis in most cases remains drug challenge, and the need for penicillin skin testing prior to oral provocation challenge has been questioned in recent studies. Successful desensitizations have also been reported with several drugs.
Subject(s)
Anti-Inflammatory Agents, Non-Steroidal/adverse effects , Antineoplastic Agents/adverse effects , Drug Hypersensitivity/diagnosis , Drug Hypersensitivity/etiology , beta-Lactams/adverse effects , Child , Desensitization, Immunologic , HumansABSTRACT
CYLD has been recognized as a tumor suppressor due to its dominant genetic linkage to multiple types of epidermal tumors and a range of other cancers. The molecular mechanisms governing CYLD control of skin cancer are still unclear. Here, we showed that K14-driven epidermal expression of a patient-relevant and catalytically deficient CYLD truncated mutant (CYLD(m)) sensitized mice to skin tumor development in response to 7,12-dimethylbenz[α]anthracene (DMBA)/(12-O-tetradecanoylphorbol-13-acetate) TPA challenge. Tumors developed on transgenic mice were prone to malignant progression and lymph node metastasis and displayed increased activation of c-Jun-NH2-kinase (JNK) and the downstream c-Jun and c-Fos proteins. Most importantly, topical application of a pharmacologic JNK inhibitor significantly reduced tumor development and abolished metastasis in the transgenic mice. Further in line with these animal data, exogenous expression of CYLD(m) in A431, a human squamous cell carcinoma (SCC) cell line, markedly enhanced cell growth, migration, and subcutaneous tumor growth in an AP1-depdendent manner. In contrast, expression of the wild-type CYLD inhibited SCC tumorigenesis and AP1 function. Most importantly, CYLD(m) not only increased JNK activation but also induced an upregulation of K63 ubiquitination on both c-Jun and c-Fos, leading to sustained AP1 activation. Our findings uncovered c-Jun and c-Fos as novel CYLD targets and underscore that CYLD controls epidermal tumorigenesis through blocking the JNK/AP1 signaling pathway at multiple levels.
