Objectives To provide an in-depth review of the classification and diagnostic evaluation of hypereosinophilia (HE), with a focus on eosinophilic neoplasms. Methods A review of published literature was performed, and exemplary HE cases were identified. Results Causes of HE are diverse and can be grouped under three categories: primary (neoplastic), secondary (reactive), and idiopathic. Advances in cytogenetics and molecular diagnostics have led to elucidation of the genetic basis for many neoplastic hypereosinophilic disorders. One common molecular feature is formation of a fusion gene, resulting in the expression of an aberrantly activated tyrosine kinase (TK). The World Health Organization endorsed a biologically oriented classification scheme and created a new major disease category, namely, “myeloid/lymphoid neoplasms with eosinophilia and rearrangement of PDGFRA, PDGFRB or FGFR1, or with PCM1-JAK2.” Rearrangement of other TK genes and activating somatic mutation(s) in TK genes have also been reported in eosinophilic neoplasms. Diagnostic evaluation of HE involves a combination of clinical, histopathologic, and immunophenotypic analyses, as well as molecular genetic testing, including next-generation sequencing-based mutation panels. The management of primary HE is largely guided by the underlying molecular genetic abnormalities. Conclusions A good knowledge of recent advances in HE is necessary to ensure prompt and accurate diagnosis, as well as to help optimize patient care.

Superantigens (SAgs) are a class of immunostimulatory exotoxins that activate large numbers of T cells, leading to overproduction of cytokines and subsequent inflammatory reactions and systemic toxicity. Staphylococcal enterotoxin C (SEC), a SAg secreted by Staphylococcus aureus, has been implicated in various illnesses including non-menstrual toxic shock syndrome (TSS) and necrotizing pneumonia. SEC has been shown to cause TSS illness in rabbits and the toxin contributes to lethality associated with methicillin-resistant S.aureus (MRSA) in a rabbit model of pneumonia. With the goal of reducing morbidity and mortality associated with SEC, a high-affinity variant of the extracellular variable domain of the T-cell receptor beta-chain for SEC (~14 kDa) was generated by directed evolution using yeast display. This protein was characterized biochemically and shown to cross-react with the homologous (65% identical) SAg staphylococcal enterotoxin B (SEB). The soluble, high-affinity T-cell receptor protein neutralized SEC and SEB in vitro and also significantly reduced the bacterial burden of an SEC-positive strain of MRSA (USA400 MW2) in an infective endocarditis model. The neutralizing agent also prevented lethality due to MW2 in a necrotizing pneumonia rabbit model. These studies characterize a soluble high-affinity neutralizing agent against SEC, which is cross-reactive with SEB, and that has potential to be used intravenously with antibiotics to manage staphylococcal diseases that involve these SAgs.

Staphylococcus aureus and Streptococcus pyogenes secrete exotoxins that act as superantigens, proteins that cause hyperimmune reactions by binding the variable domain of the T-cell receptor beta chain (V␤), leading to stimulation of a large fraction of the T-cell repertoire. To develop potential neutralizing agents, we engineered V␤ mutants with high affinity for the superantigens staphylococcal enterotoxin B (SEB), SEC3, and streptococcal pyrogenic exotoxin A (SpeA). Unexpectedly, the high-affinity V␤ mutants generated against SEB cross-reacted with SpeA to a greater extent than they did with SEC3, despite greater sequence similarity between SEB and SEC3. Likewise, the V␤ mutants generated against SpeA cross-reacted with SEB to a greater extent than with SEC3. The structural basis of the high affinity and cross-reactivity was examined by single-site mutational analyses. The cross-reactivity seems to involve only one or two toxin residues. Soluble forms of the cross-reactive V␤ regions neutralized both SEB and SpeA in vivo, suggesting structure-based strategies for generating high-affinity neutralizing agents that can cross-react with multiple exotoxins.

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bStaphylococcal contamination of food products and staphylococcal food-borne illnesses continue to be a problem worldwide. Screening of food for the presence of Staphylococcus aureus and/or enterotoxins using traditional methods is laborious. Reliable and rapid multiplex detection methods from a single food extract or culture supernatant would simplify testing. A fluorescence-based cytometric bead array was developed for the detection of staphylococcal enterotoxin B (SEB), using magnetic microspheres coupled with either an engineered, enterotoxin-specific V␤ domain of the T-cell receptor (V␤-TCR) or polyclonal antibodies. The binding affinity of the V␤-TCR for SEB has been shown to be in the picomolar range, comparable to the best monoclonal antibodies. The coupled beads were validated with purified enterotoxins and tested in a variety of food matrices spiked with enterotoxins. The V␤-TCR or antibody was shown to specifically bind SEB in four different food matrices, including milk, mashed potatoes, vanilla pudding, and cooked chicken. The use of traditional polyclonal antibodies and V␤-TCR provides a redundant system that ensures accurate identification of the enterotoxin, and the use of labeled microspheres permits simultaneous testing of multiple enterotoxins from a single sample. Staphylococcus aureus is among the top five common pathogens associated with food-borne illness nationwide. The Centers for Disease Control and Prevention (CDC) estimates that there are about 240,000 illnesses with 1,000 hospitalizations and 6 deaths associated with staphylococcal food poisoning (SFP) annually (1). SFP is directly linked to small (25-to 30-kDa) exotoxins, known as staphylococcal enterotoxins (SEs), that are heat resistant, tolerate low pH, and often persist long after the microbe has been rendered nonviable. SEs are superantigens that induce nonspecific T-cell activation, which can rapidly cascade to a massive release of inflammatory mediators and may lead to toxic shock (2, 3). SFP occurs when improperly handled food contaminated with as little as 100 ng of SE is consumed. SFP is marked by severe gastrointestinal symptoms such as emesis, diarrhea, and/or abdominal pain after a 4-h incubation period (4).Suspect food products are typically analyzed by using traditional culture techniques followed by identification of enterotoxigenic staphylococcal strains. Food extracts positive for bacteria may then be evaluated for the presence of preformed SEs (5). A recent outbreak in Japan from milk contaminated with staphylococcal enterotoxin A (SEA) illustrated the challenges of conventional methods, since viable bacteria were not detected (6, 7). PCR methods would be a useful screening tool for samples that are culture negative and enterotoxin positive (8). PCR methods are sensitive and can detect low levels of gene targets; however, this does not verify the presence of expressed proteins, and it is unacceptable as a definitive method for SE detection in the regulatory arena. Therefore, immunological techniques using either m...

Background: Pinterest is a social media internet service utilized by individuals, organizations, and businesses to collect and share ideas related to projects or interests. Objective:The literature related to dermatology-related content on Pinterest is scarce. This study aims to investigate the presence of dermatology related content available on Pinterest.Methods: Investigators searched five terms related to dermatology in the "pins" and "boards" search categories of pinterest. The first 20 results were evaluated for content and assigned to a content group of "advocacy," "informative," or "home remedies." Boards were also categorized as being posted by an MD or professional society versus others. The top ten dermatology journals were also searched for under the boards category.Results: Informative pins were the most common (49%) followed by advocacy (37%) and home remedies (14%). Informative boards were the most common (53%) followed by home remedies (31%) and advocacy (16%). We identified that only 24% of boards were created by either M.D.s or advocacy organizations. The top ten dermatology journals identified by prior studies had little presence, with only one board posted by JAMA Dermatology. Conclusions:Our study contributes to a growing body of data that dermatology organizations are relatively absent from new social media sites, and Pinterest represents a potential outlet for targeted intervention in high-risk groups for skin disease.

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A 71-year-old female with breast cancer presented with a generalized papular rash that began following the initiation of rebastinib. Examination revealed scattered pink to skin-colored verrucous papules on the forehead, extremities, and back. A biopsy showed hyperkeratosis, hypergranulosis, digitated epidermal hyperplasia, and dilated blood vessels at the tips of dermal papillae consistent with verruca vulgaris. The patient discontinued rebastinib due to muscle weakness and the lesions resolved. Rebastinib is an antineoplastic agent that targets several tyrosine kinases. Tyrosine kinase inhibitors (TKI) frequently cause cutaneous adverse events, but to date, there have been no reported cases of a verruca vulgaris eruption arising in the setting of TKI treatment. Recent studies indicate that TKIs can have immunosuppressive effects by decreasing T-cell levels. We postulate that rebastinib induced an immunosuppressive state in our patient which permitted human papillomavirus (HPV) proliferation. To our knowledge, this is the first report describing a verruca vulgaris eruption with TKI therapy.