Immune pathomechanism of drug hypersensitivity reactions

Drug hypersensitivity research has progressed enormously in recent years, and a greater understanding of mechanisms has contributed to improved drug safety. Progress has been made in genetics, enabling personalized medicine for certain drugs, and in understanding drug interactions with the immune system. In a recent meeting in Rome, the clinical, chemical, pharmacologic, immunologic, and genetic aspects of drug hypersensitivity were discussed, and certain aspects are briefly summarized here. Small chemicals, including drugs, can induce immune reactions by binding as a hapten to a carrier protein. Park (Liverpool, England) demonstrated (1) that drug haptens bind to protein in patients in a highly restricted manner and (2) that irreversibly modified carrier proteins are able to stimulate CD4(+) and CD8(+) T cells from hypersensitive patients. Drug haptens might also stimulate cells of the innate immune system, in particular dendritic cells, and thus give rise to a complex and complete immune reaction. Many drugs do not have hapten-like characteristics but might gain them on metabolism (so-called prohaptens). The group of Naisbitt found that the stimulation of dendritic cells and T cells can occur as a consequence of the transformation of a prohapten to a hapten in antigen-presenting cells and as such explain the immune-stimulatory capacity of prohaptens. The striking association between HLA-B alleles and the development of certain drug reactions was discussed in detail. Mallal (Perth, Australia) elegantly described a highly restricted HLA-B∗5701-specific T-cell response in abacavir-hypersensitive patients and healthy volunteers expressing HLA-B∗5701 but not closely related alleles. Expression of HLA-B∗1502 is a marker known to be necessary but not sufficient to predict carbamazepine-induced Stevens-Johnson syndrome/toxic epidermal necrolysis in Han Chinese. The group of Chen and Hong (Taiwan) described the possible "missing link" because they showed that the presence of certain T-cell receptor (TCR) clonotypes was necessary to elicit T-cell responses to carbamazepine. The role of TCRs in drug binding was also emphasized by Pichler (Bern, Switzerland). Following up on their "pharmacological interactions of drugs with immune receptors" concept (p-i concept), namely that drugs can bind directly to TCRs, MHC molecules, or both and thereby stimulate T cells, they looked for drug-binding sites for the drug sulfamethoxazole in drug-specific TCRs: modeling revealed up to 7 binding sites on the CDR3 and CDR2 regions of TCR Vα and Vβ. Among many other presentations, the important role of regulatory T cells in drug hypersensitivity was addressed.

Enhanced antigenicity leads to altered immunogenicity in sulfamethoxazole-hypersensitive patients with cystic fibrosis

Exposure of patients with cystic fibrosis to sulfonamides is associated with a high incidence of hypersensitivity reactions.

Severe complication of a bonded mandibular lingual retainer

Bonding a flexible spiral wire retainer to the lingual surfaces of all 6 anterior mandibular teeth is a commonly used type of retention. Complications are rare but can be serious enough to produce biologic damage. This article presents a serious complication of a lingual flexible spiral wire retainer. Four years after the orthodontic treatment, a 20-year-old man sought treatment for a broken flexible spiral wire retainer. The clinical examination showed about 35° of buccal root torque of that tooth. A cone-beam computed tomography image showed that the root and the apex of the tooth were almost completely out of the bone on its buccal side. Surprisingly, the tooth's vitality was preserved. The tooth was moved back, nearly to its original position; clinically, only a gingival recession remained. Orthodontists and dentists should be aware of possible complications of bonded retainers. Patients should be clearly informed how to detect problems at an early stage.

Reporting quality of abstracts of randomized controlled trials published in leading orthodontic journals from 2006 to 2011

Optimal reporting of randomized trials and abstracts enhances transparency and facilitates assessment and identification of trials. The purpose of this study was to investigate the quality of reporting of abstracts of randomized controlled trials published in orthodontic journals.

Mislabeling controlled clinical trials (CCTs) as "randomized clinical trials (RCTs)" in dental specialty journals

This study aimed to investigate whether studies published in dental journals with the highest impact factor, representing the 5 major dental specialties and titled as randomized clinical trials (RCTs) are truly RCTs. A second objective was to explore the association of journal type and other publication characteristics on correct classification.

Self-etch primers and conventional acid-etch technique for orthodontic bonding: a systematic review and meta-analysis

The use of self-etch primers has increased steadily because of their time savings and greater simplicity; however, overall benefits and potential disadvantages and harms have not been assessed systematically. In this study, we reviewed randomized controlled trials to assess the risk of attachment failure, bonding time, and demineralization adjacent to attachments between 1-stage (self-etch) and 2-stage (acid etch) bonding in orthodontic patients over a minimum follow-up period of 12 months.

What's in a title? An assessment of whether randomized controlled trial in a title means that it is one

In this study, we aimed to investigate whether studies published in orthodontic journals and titled as randomized clinical trials are truly randomized clinical trials. A second objective was to explore the association of journal type and other publication characteristics on correct classification.