Dermatology hospital fellowships: present and future.

The question of what makes a successful dermatology hospitalist has risen to the forefront due to the rapidly increasing number of these providers. Inpatient dermatology fellowships have formed as a direct consequence. Though mostly in their infancy, these programs have primary or secondary goals to train providers in the dermatologic care of the hospitalized patient. This article presents a brief synopsis of the history of traditional hospitalist fellowships and extrapolates these findings to existing hospitalist dermatology fellowships. As more of these programs arise, these fellowships are poised to revolutionize dermatologic inpatient care from a systems perspective.

Updates in adult-onset Still disease: Atypical cutaneous manifestations and associations with delayed malignancy.

Adult-onset Still disease (AOSD) is a systemic inflammatory disorder that is clinically characterized by a heterogeneous constellation of symptoms and signs. Though an evanescent eruption is the classic cutaneous finding, recent literature has highlighted atypical rashes associated with Still disease. A second emerging concept in presentations of AOSD is its association with malignancy. This review focuses on these concepts: the clinical spectrum of atypical skin manifestations and AOSD as a paraneoplastic phenomenon. PubMed-MEDLINE was screened for peer-reviewed articles describing atypical presentations of AOSD and cases associated with malignancy. Erythematous, brown or violaceous, persistent papules and plaques were the most common cutaneous finding (28/30 [93%]). Linear configurations were also rarely described. Of these patients, 81% concurrently had the typical evanescent skin eruption. There were 31 patients with associated malignancies, most commonly breast cancer and lymphoma. The diagnosis of malignancy did not precede or immediately follow a clinical presentation otherwise consistent with AOSD in a considerable subset of patients (42%). Understanding the cutaneous spectrum of AOSD and heightened awareness for its delayed association with malignancy may lead to improved recognition of cutaneous variants and reinforce the need for diagnostic evaluation and long-term follow-up for malignancy in patients with this clinical presentation.

S-nitrosothiol transport via PEPT2 mediates biological effects of nitric oxide gas exposure in macrophages.

The pharmacological effects of nitric oxide (NO) administered as a gas are dependent on the conversion to S-nitrosocysteine, and as such are largely mediated by the L-type amino-acid transporters (LATs) in several cell types. The dipeptide transporter PEPT2 has been proposed as a second route for S-nitrosothiol (SNO) transport, but this has never been demonstrated. Because NO governs important immune functions in alveolar macrophages, we exposed rat alveolar macrophages (primary and NR8383 cells) to NO gas at the air-liquid interface ± LPS stimulation in the presence of PEPT2 substrate Cys-Gly (or the LAT substrate L-Cys) ± transporter competitors. We found that SNO uptake and NO-dependent actions, such as the activation of soluble guanylyl cyclase (sGC), the augmentation of sGC-dependent filamentous actin (F-actin) polymerization, phagocytosis, and the inhibition of NF-κB activation, were significantly augmented by the addition of Cys-Gly in a manner dependent on PEPT2 transport. We found parallel (and greater) effects that were dependent on LAT transport. The contribution of cystine/cysteine shuttling via system x cystine transporter (xCT) to SNO uptake was relatively minor. The observed effects were unaffected by NO synthase inhibition. The NO gas treatment of alveolar macrophages increased SNO uptake, the activation of sGC, F-actin polymerization, and phagocytosis, and inhibited NF-κB activation, in a manner dependent on SNO transport via PEPT2, as well as via LAT.

Non-response to Interleukin-1 Antagonist Canakinumab in Two Patients with Refractory Pyoderma Gangrenosum and Hidradenitis Suppurativa.

Pyoderma gangrenosum and hidradenitis suppurativa are skin conditions characterized by an intense neutrophil-mediated inflammatory response that is often difficult to effectively treat. Successful use of interleukin (IL)-1ß inhibition using canakinumab and anakinra has been reported in patients with concomitant pyoderma gangrenosum and hidradenitis suppurativa. We report two cases where targeted therapy with canakinumab failed to lead to improvement for patients with pyoderma gangrenosum and hidradenitis suppurativa. The reason behind the non-response to IL-1ß blockade seen in these patients is unclear. Our report suggests that further controlled studies are warranted to help clinicians predict treatment responses to anti-IL-1 therapies in these challenging patients.