ABSTRACT
Atopic dermatitis (AD) is a common immune-medicated skin disease. Previous studies have explored the relationship between Human Leukocyte Antigen (HLA) allelic variation and AD with conflicting results. The aim was to examine HLA Class I genetic variation, specifically peptide binding groove variation, and associations with AD. A case-control study was designed to evaluate HLA class I allelic variation and binding pocket polymorphisms, using next generation sequencing on 464 subjects with AD and 388 without AD. Logistic regression was used to evaluate associations with AD by estimating odds ratios (95% confidence intervals). Significant associations were noted with susceptibility to AD (B*53:01) and protection from AD (A*01:01, A*02:01, B*07:02 and C*07:02). Evaluation of polymorphic residues in Class I binding pockets revealed six amino acid residues conferring protection against AD: A9F (HLA-A, position 9, phenylalanine) [pocket B/C], A97I [pocket C/E], A152V [pocket E], A156R [pocket D/E], B163E [pocket A] and C116S [pocket F]. These findings demonstrate that specific HLA class I components are associated with susceptibility or protection from AD. Individual amino acid residues are relevant to protection from AD and set the foundation for evaluating potential HLA Class I molecules in complex with peptides/antigens that may initiate or interfere with T-cell responses.
Subject(s)
Dermatitis, Atopic/genetics , Genetic Predisposition to Disease , Genetic Variation , Histocompatibility Antigens Class I/genetics , Alleles , Case-Control Studies , Dermatitis, Atopic/diagnosis , Gene Frequency , Genetic Association Studies , Genotype , Histocompatibility Antigens Class I/chemistry , Humans , Models, Molecular , Odds Ratio , Polymorphism, Single Nucleotide , Protein Conformation , Sequence Analysis, DNA , Structure-Activity RelationshipABSTRACT
BACKGROUND: Human herpesvirus (HHV)6 positivity in the context of drug hypersensitivity syndrome (DHS) may influence disease severity. Systemic corticosteroid treatment of those with DHS testing positive for HHV6 has been speculated to prolong the duration of disease. OBJECTIVES: To evaluate whether paediatric HHV6-positive patients with DHS develop a more severe illness than those without presumed reactivation, and to evaluate the response to systemic corticosteroid treatment. METHODS: A retrospective case series of 29 paediatric inpatients treated for DHS and tested for HHV6 was undertaken. HHV6-positive and -negative patients were identified and stratified into groups treated or not treated with systemic corticosteroids to examine their disease severity on the basis of hospital length of stay (LOS), total number of febrile days (Tfeb) and days until cessation of progression (CTP). RESULTS: Human herpesvirus6-positive patients had similar demographic characteristics to those of HHV6-negative patients, but had significantly longer hospital LOS (11·5 days vs. 5 days, P = 0·039), Tfeb (12·5 days vs. 3 days, P = 0·032) and CTP (4 days vs. 2 days, P = 0·014). All HHV6-positive patients and most (80%) of the HHV6-negative patients received systemic corticosteroids. Among the HHV6-negative patients, those who received corticosteroids showed significantly shorter CTP than those who did not (3 days vs. 2 days, P = 0·043). Additionally, there was a trend towards shorter hospital LOS and Tfeb among HHV6-negative patients who received corticosteroids vs. those who did not, although these differences were not statistically significant. The most common inciting drugs included trimethoprim-sulfamethoxazole (34%), phenytoin (10%) and amoxicillin (10%). CONCLUSIONS: Human herpesvirus6 positivity with DHS is associated with a more severe disease course. Treatment with systemic corticosteroids was associated with a trend towards reduced hospital LOS and Tfeb, and a significantly reduced number of days until cessation of progression.
Subject(s)
Adrenal Cortex Hormones/therapeutic use , Antiviral Agents/therapeutic use , Drug Hypersensitivity Syndrome/virology , Herpesvirus 6, Human , Roseolovirus Infections/drug therapy , Adolescent , Child , Child, Preschool , Female , Humans , Infant , Length of Stay , Male , Retrospective Studies , Roseolovirus Infections/complications , Time Factors , Treatment OutcomeABSTRACT
Aquagenic palmoplantar keratoderma is an acquired condition characterized by burning and edema limited to the hands after brief immersion in water. The 3 patients described possess a striking similarity to those with transient reactive papulotranslucent acrokeratoderma. All 3 patients manifested the "hand-in-the-bucket" sign, having presented to a physician with a hand immersed in a bucket of water to more promptly demonstrate the physical findings. Aluminum chloride hexahydrate represents a potentially valuable therapeutic option for this unusual condition.
Subject(s)
Keratoderma, Palmoplantar/etiology , Water/adverse effects , Adolescent , Adult , Aluminum Chloride , Aluminum Compounds/therapeutic use , Astringents/therapeutic use , Child , Chlorides/therapeutic use , Female , HumansABSTRACT
Bupivacaine is a commonly used local anesthetic in dental, ophthalmologic, and simple surgical procedures. Its current popularity derives from its potency and relatively long half-life. Widespread use of bupivacaine has resulted in sometimes severe adverse reactions when significant systemic absorption has occurred. This report documents a life-threatening event following use of bupivacaine, briefly reviews its neurotoxic and cardiotoxic effects, and raises questions about current management strategies when toxicity occurs.
