Visual diagnosis: 4-month-old girl with diffuse, varied dermatitis and bullae.

Pediatric autoimmune blistering disorders are exceedingly rare. Of these, childhood bullous pemphigoid (CBP) is the most common IgG-mediated subepidermal bullous disease in the pediatric population. Tense acral blisters, especially on the soles and palms, are characteristic of the infantile presentation. Patients with CBP present with varied dermatoses, making clinical diagnosis alone difficult. Definitive diagnosis is made with direct immunofluorescence revealing linear deposition of IgG and/or C3 at the basement membrane zone (BMZ) or indirect immunofluorescence revealing IgG antibodies reacting with the BMZ. First-line treatment is oral prednisolone dosed at 1 to 2 mg/kg and then tapered slowly to avoid rebound disease. The length of treatment depends on the rate of remission.

Twenty-four-hour hospitalization for patients initiating systemic propranolol therapy for infantile hemangiomas--is it indicated?

In recent years, oral propranolol has risen from serendipitous discovery to first-line, albeit off-label, therapy for infantile hemangiomas (IHs). This retrospective study explored the utility of a 24-hour hospitalization for the initiation of propranolol therapy in children with problematic IHs by evaluating the effects of systemic propranolol on hemodynamics and blood sugar levels. Thirty-one children were admitted to the hospital to begin oral propranolol at a dose of 2 mg/kg/per day. Heart rate (HR), blood pressure (BP), and blood glucose (BG) measurements were obtained at baseline and 1 to 3 hours before and after each dose of propranolol. No caregivers reported any adverse effects during the hospitalization. On average, HR decreased by 5 beats per minute (bpm) (p < 0.01) and systolic BP decreased by 4 mmHg (p < 0.01) after propranolol administration. There was no statistically significant change in diastolic BP or BG with propranolol therapy. Over the first three doses of propranolol we saw statistically significant attenuation of the effects of propranolol on HR, with HR approaching baseline values during the hospitalization (p = 0.04). We did not see statistically significant changes in BP over the course of three doses of propranolol. This study suggests that 24-hour hospitalization with hemodynamic monitoring may not be necessary for safe initiation of propranolol therapy in otherwise healthy infants. Parental education on frequent feedings to decrease the chance of hypoglycemia may be as effective as 24-hour hospitalization.

Adiponectin induces vascular smooth muscle cell differentiation via repression of mammalian target of rapamycin complex 1 and FoxO4.

OBJECTIVE: The adipocyte-secreted hormone adiponectin exerts important cardioprotective and antidiabetic effects. Little is known about its effect on vascular smooth muscle cells (VSMC), key cells in restenosis, hypertension, and atherosclerosis. METHODS AND RESULTS: Using human coronary artery VSMC, we found that recombinant adiponectin in the high-molecular-weight or trimeric forms but not the globular form induced VSMC differentiation through a mechanism similar to the classic feedback signaling used by rapamycin, a drug known to effectively inhibit restenosis on drug-eluting stents. Using a combination of pharmacological agents, small interfering RNA, and overexpression approaches, we demonstrated that adiponectin activated 5'-AMP-activated protein kinase α2 isoform, leading to inhibition of mammalian target of rapamycin complex 1 and S6K1. This in turn stabilized insulin receptor substrate-1, driving Akt2-mediated inhibition of FoxO4 and subsequent contractile protein induction. Although adiponectin and rapamycin have similarly beneficial effects on VSMC phenotype in both cell and organ culture, a direct comparison of the effects of rapamycin versus adiponectin on endothelial cells revealed distinct differences: rapamycin inhibited Akt phosphorylation, whereas adiponectin maintained it. Importantly, Akt activity preserves endothelial function. CONCLUSION: Adiponectin promotes VSMC differentiation and preserves endothelial cell Akt signaling, suggesting that targeting the adiponectin pathway may have advantages over rapamycin in developing new drug-eluting stent therapeutics.

Molecularly targeted therapies for nonmelanoma skin cancers.

Over the past two decades, advances in the fields of cancer genetics and molecular biology have elucidated molecular pathways that cause numerous cutaneous malignancies. This in turn has spurred the rational design of molecularly targeted therapies. In this review, we discuss the molecular pathways critical to the development of nonmelanoma skin cancers and the novel pharmacologic agents that target them. Included is a review of vismodegib for basal cell carcinoma, cetuximab for squamous cell carcinomas, imatinib for dermatofibrosarcoma protuberans, and sirolimus for Kaposi's sarcoma.

Molecularly targeted therapies for melanoma.

Systemic and topical targeted therapies are emerging as a rational approach to the management of skin cancers. In this article, we review the molecular pathways critical to the development of melanoma and the novel pharmacologic agents that have been rationally designed to target it. Included is a review of vemurafenib, imatinib, and ipilimumab for metastatic or unresectable melanoma.