New World cutaneous leishmaniasis: current challenges in diagnosis and parenteral treatment.

Many physicians in the United States and other nonendemic countries lack familiarity with New World cutaneous leishmaniasis (CL) and fail to include it in their differential diagnosis when seeing patients with suggestive lesions and recent high-risk travel. Moreover, even when the diagnosis of New World CL is considered and confirmed, physicians in the United States still face obstacles in obtaining appropriate treatment. In this report, we present 3 cases of New World CL that were either initially misdiagnosed or faced significant delays in therapy. We also discuss the optimal approach by which to confirm New World CL and to collaborate with professional colleagues at the Centers for Disease Control and Prevention in treating individual patients. In particular, when pentavalent antimonial treatment is needed for treatment, physicians must obtain appropriate diagnostic studies, communicate with experts at the Centers for Disease Control and Prevention, complete necessary paperwork, and obtain approval from their local institutional review board to administer it.

A role for interleukin-5 in promoting increased immunoglobulin M at the site of disease in leprosy.

Leprosy is an infectious disease in which the clinical manifestations correlate with the type of immune response mounted to the pathogen, Mycobacterium leprae. To investigate which biological pathways or gene sets are over-represented in lepromatous (L-Lep) versus tuberculoid (T-Lep) patients that might be relevant in disease pathogenesis, we compared the gene expression profiles of L-lep versus T-lep skin lesions using knowledge-guided bioinformatic analysis, incorporating data on likely biological functions, including gene ontology information and regulatory data. Analysis of probe sets comparatively increased in expression in L-lep versus T-lep revealed multiple pathways and functional groups involving B-cell genes (P values all < 0.005) relevant to the dataset. Further pathways analysis of B-cell genes comparatively increased in expression in L-lep versus T-lep lesions revealed a potential network linking the expression of immunoglobulin M (IgM) and interleukin-5 (IL-5). Analysis of the leprosy lesions by immunohistology indicated that there was approximately 8% more IgM-positive cells in L-lep lesions than in T-lep lesions. Furthermore, IL-5 synergized in vitro with M. leprae to enhance total IgM secretion from peripheral blood mononuclear cells. This pathways analysis of leprosy in combination with our in vitro studies implicates a role for IL-5 in the increased IgM at the site of disease in leprosy.

The local lymph node assay compared with the human maximization test as an indicator of allergic potency in humans using patch test clinic populations.

The human maximization test (HMT) is a method to evaluate potency in humans, while the local lymph node assay (LLNA) is a test method that allows for the measuring of the allergic potency of a substance in a rodent. It has been proposed that an EC3 value (the value obtained by the LLNA test, ie, the concentration of an allergen leading to a 3-fold increase of baseline proliferation rate) would be a reliable indicator for a compound's allergic potency in humans. This paper compares the correlation between the EC3 value of a compound and its allergic occurrence in the general population with the correlation between the HMT of the compound and its allergic occurrence in the general population, to determine the relationship to potency. The correlation values when outliers were removed from the sample were -0.56 and -0.71 for LLNA and HMT, respectively, suggesting that there is a possible 20% error margin in LLNA's ability to predict potency. The data also suggest that other factors (such as exposure) could play up to a 30% role in the determination of allergic occurrence in the general population. The potency assays might be made more clinically relevant for predicting allergic frequencies by including a frequency factor and other factors in its dermatotoxicological interpretation.

Quantitative relationships between patch test reactivity and use test reactivity: an overview.

Use tests such as the provocative use test (PUT) or repeated open application test (ROAT) have been created to better understand the clinical significance of patch test results. It has been suggested that since these tests typically utilize only one substance at a time and avoid occlusion, they minimize the occurrence of irritation and false positives and, thus, are more reflective of real-life exposure to an allergen. In this analysis, we compare and analyze different studies comparing patch test and use test reactivity. With regard to colophony, cinnamic aldehyde, methyldibromo glutaronitrile, 5-chloro-2-methyl-4-isothiazolin-3-one and 2-methyl-4-isothiazolin-3-one, and isoeugenol, increased patch test sensitivity resulted in increased use test sensitivity. However, this was not true for formaldehyde or chromium. The reason for the latter allergens' divergence from the trend is not yet understood. Additionally, we note the presence of an increasing slope in the relationship between use test reactivity and minimum eliciting concentration on patch testing for methyldibromo glutaronitrile. Expansion of databases relating serial dilution patch test reactivity and use test data should aid dermatologic management, public health policy, and an understanding of the complexity of allergic contact dermatitis in humans.

Survey of safety and efficacy information in drug inserts for topical prescription medications.

BACKGROUND AND OBJECTIVE: Drug inserts are an important source of information for patients and physicians regarding the safety and proper administration of a drug. However, recent studies have found that inserts are still missing key information regarding a drug's safety and efficacy. The aim of this study was to ascertain whether inserts in US-sold topical prescription drugs are deficient with respect to key safety and efficacy information required by the US FDA. METHOD: We evaluated the inserts of 15 topical prescription medications sold in the US against a set of 14 safety criteria based on FDA requirements. RESULTS: Inserts were deficient in several key safety categories for patients, including information regarding pregnancy, nursing women, and pediatric and geriatric patients. Additionally, in a majority of inserts, information was not provided on how to deal with an administrative error made when attempting to apply a drug. CONCLUSION: To improve drug inserts the industry must address these deficiencies as well as implement a safety index for nursing, pediatric, and geriatric patients detailing how dangerous the drug can be to these populations depending on available animal or human studies. Companies should also provide contact information for a dermatologist on staff who can provide answers to safety questions when these are not clearly detailed in the insert.