Prominent skin involvement is a defining characteristic of autoinflammatory disorders caused by abnormal IL-1 signaling. However, the pathways and cell types that drive cutaneous autoinflammatory features remain poorly understood. We sought to address this issue by investigating the pathogenesis of pustular psoriasis, a model of autoinflammatory disorders with predominant cutaneous manifestations. We specifically characterized the impact of mutations affecting AP1S3, a disease gene previously identified by our group and validated here in a newly ascertained patient resource. We first showed that AP1S3 expression is distinctively elevated in keratinocytes. Because AP1S3 encodes a protein implicated in autophagosome formation, we next investigated the effects of gene silencing on this pathway. We found that AP1S3 knockout disrupts keratinocyte autophagy, causing abnormal accumulation of p62, an adaptor protein mediating NF-κB activation. We showed that as a consequence, AP1S3-deficient cells up-regulate IL-1 signaling and overexpress IL-36α, a cytokine that is emerging as an important mediator of skin inflammation. These abnormal immune profiles were recapitulated by pharmacological inhibition of autophagy and verified in patient keratinocytes, where they were reversed by IL-36 blockade. These findings show that keratinocytes play a key role in skin autoinflammation and identify autophagy modulation of IL-36 signaling as a therapeutic target.

Cytokines classically are secreted "messenger" proteins that modulate cellular function of immune cells. Chemokines attract immune cells to the site where they exert various functions in inflammation, autoimmunity or cancer. Increasing evidence is emerging that cytokines or chemokines can act as "neuro-modulators" by activating high-affinity receptors on peripheral or central neurons, microglia cells or Schwann cells. Very recently, cytokines have been shown to act as pruritogens in rodents and humans, while a role of chemokines in itch has thus far been only demonstrated in mice. Upon stimulation, cytokines are released by skin or immune cells and form a "bridge of communication" between the immune and nervous system. For some cytokines such as IL-31 and TSLP, the evidence for this role is strong in rodents. For cytokines such as IL-4, there is some convincing evidence, while for cytokines such as oncostatin M, IL-2, IL-6, IL-8 and IL-13, direct evidence is currently limited. Current clinical trials support the idea that cytokines and chemokines and their receptors or signalling pathways are promising targets for the future therapy of certain subtypes of itch.

The majority of consultations conducted by the dermatology hospital consulting service were for the management of common skin diseases, such as cutaneous infections, dermatitis, and drug eruptions. Most consultations were requested by the departments of internal medicine, hematology and oncology, and surgical services.

This study reveals a high prevalence of FMS (57%) among subjects with chronic HCV infection, one third of whom reported some degree of functional impairment. Recognition and management of this condition in such patients will help improve their quality of life.

Data describing the management of pediatric patients admitted to a hospital under the care of a dermatologist and dermatology hospital consults for pediatric inpatients are limited. We aim to describe the role of an inpatient hospital service jointly run by dermatology and pediatrics and the activities of a pediatric dermatology hospital consult service. We retrospectively identified pediatric (age < 18 yrs) dermatology inpatients and hospital consult patients from January 1, 2009, through December 31, 2010. We examined patient demographics, indications for admission, length of stay, treatment provided, consult-requesting service, and consult diagnosis. One hundred eight admissions were by a dermatologist. The mean age was 5.8 years; the median length of stay was 3 days. Indications for admission included atopic dermatitis (86.1%), psoriasis (3.7%), and eczema herpeticum (2.8%). The main treatment provided was wet dressings (97.2%). Eighty-three dermatology hospital consults were requested. The mean age was 7.4 years. The main indications for dermatology consultation included drug rash (12.1%), cutaneous infections (12.1%), contact dermatitis (9.6%), psoriasis (8.4%), atopic dermatitis (6.0%), and hemangiomas (6.0%). This study describes the utility of the hospital pediatric dermatology inpatient and consult services in treating patients with severe skin disease.