Oral glycopyrrolate as second-line treatment for primary pediatric hyperhidrosis.

BACKGROUND: Primary focal hyperhidrosis not uncommonly begins during the first two decades of life, and can have a profound effect on quality of life. Few treatment options have been studied in children. OBJECTIVE: We sought to evaluate the response to oral glycopyrrolate in pediatric patients. METHODS: Records of pediatric patients with hyperhidrosis seen at a pediatric hospital in a 10-year period were reviewed retrospectively and, if possible, parents and patients were also interviewed. The efficacy and adverse effects of oral glycopyrrolate were assessed. RESULTS: In all, 31 children took at least one dose of oral glycopyrrolate. All had daily hyperhidrosis that affected their quality of life and were resistant or intolerant of aluminum salts. The mean age of hyperhidrosis onset was 10.3 years, and mean age of initiation of glycopyrrolate was 14.8 years. At a mean dosage of 2 mg daily, 90% of patients experienced improvement, which was major in 71% of responders. Improvement occurred within hours of administration and disappeared within a day of discontinuation. Duration of treatment averaged 2.1 years (range to 10 years). Side effects were noted by 29% of children, most commonly dry mouth (26%) and eyes (10%), and were dose-related. One patient developed blurred vision, which resolved with dosing below 5 mg/d; one patient experienced palpitations and discontinued the medication. LIMITATIONS: This was a retrospective analysis of a limited number of pediatric patients. CONCLUSION: Oral glycopyrrolate is a cost-effective, painless second-line therapy for children and adolescents with primary focal hyperhidrosis that impacts their quality of life.

Management of the difficult sentinel lymph node in patients with primary cutaneous melanoma.

Sentinel lymph nodes (SLN) are examined for occult melanoma metastases for accurate staging to dictate optimal therapy. The aim of this case series is to discuss clinical challenges in SLN biopsy. Ten challenging cases were identified from over 700 melanoma patients with SLN biopsy for primary cutaneous melanoma at the Yale Cancer Center Melanoma Unit. These cases were complicated by issues of (1) visualization of SLN, (2) concurrent and topographically close melanomas, (3) aberrant lymphatic drainage outside standard basins, (4) altered lymphatic drainage secondary to surgery, and (5) access to SLN. This case series identifies complex clinical scenarios encountered with SLN biopsy that should be familiar to a surgeon involved in the surgical care of melanoma patients.

Induction of indoleamine 2,3-dioxygenase in vascular smooth muscle cells by interferon-gamma contributes to medial immunoprivilege.

Atherosclerosis and graft arteriosclerosis are characterized by leukocytic infiltration of the vessel wall that spares the media. The mechanism(s) for medial immunoprivilege is unknown. In a chimeric humanized mouse model of allograft rejection, medial immunoprivilege was associated with expression of IDO by vascular smooth muscle cells (VSMCs) of rejecting human coronary artery grafts. Inhibition of IDO by 1-methyl-tryptophan (1-MT) increased medial infiltration by allogeneic T cells and increased VSMC loss. IFN-gamma-induced IDO expression and activity in cultured human VSMCs was considerably greater than in endothelial cells (ECs) or T cells. IFN-gamma-treated VSMCs, but not untreated VSMCs nor ECs with or without IFN-gamma pretreatment, inhibited memory Th cell alloresponses across a semipermeable membrane in vitro. This effect was reversed by 1-MT treatment or tryptophan supplementation and replicated by the absence of tryptophan, but not by addition of tryptophan metabolites. However, IFN-gamma-treated VSMCs did not activate allogeneic memory Th cells, even after addition of 1-MT or tryptophan. Our work extends the concept of medial immunoprivilege to include immune regulation, establishes the compartmentalization of immune responses within the vessel wall due to distinct microenvironments, and demonstrates a duality of stimulatory EC signals versus inhibitory VSMC signals to artery-infiltrating T cells that may contribute to the chronicity of arteriosclerotic diseases.

Chemokine-like receptor 1 expression and chemerin-directed chemotaxis distinguish plasmacytoid from myeloid dendritic cells in human blood.

Plasmacytoid dendritic cells (pDCs) are versatile cells of the immune response, secreting type I IFNs and differentiating into potent immunogenic or tolerogenic APCs. pDCs can express adhesion and chemokine receptors for lymphoid tissues, but are also recruited by unknown mechanisms during tissue inflammation. We use a novel mAb specific for serpentine chemokine-like receptor 1 (CMKLR1) to evaluate its expression by circulating leukocytes in humans. We show that CMKLR1 is expressed by circulating pDCs in human blood, whereas myeloid DCs (mDCs) as well as lymphocytes, monocytes, neutrophils, and eosinophils are negative. We identify a major serum agonist activity for CMKLR1 as chemerin, a proteolytically activated attractant and the sole known ligand for CMKLR1, and we show that chemerin is activated during blood coagulation and attracts pDC but not mDC in ex vivo chemotaxis assays. We conclude that CMKLR1 expression and chemerin-mediated chemotaxis distinguish circulating pDCs from mDCs, providing a potential mechanism for their differential contribution to or regulation of immune responses at sites of bleeding or inflammatory protease activity.