Case Report of Calciphylaxis Secondary to Calcium and Vitamin D3 Supplementation.

BACKGROUND: Calciphylaxis is a rare disorder that is very unusual outside the setting of end-stage kidney disease. CASE SUMMARY: A 64-year-old woman with normal renal function presented with painful leg ulcers. She had previously received 300 000 IU of vitamin D3 followed by daily calcium and vitamin D3 supplementation. A skin biopsy was consistent with calciphylaxis, and she was treated with sodium thiosulphate infusions and wound debridement. CONCLUSION: Calcium and vitamin D3 supplements are widely prescribed. We report a case of calciphylaxis triggered by calcium and vitamin D3 supplementation in a patient with none of the typical risk factors. Our patient had an excellent response to treatment with sodium thiosulphate.

Role of cytokines and chemokines in itch.

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.

Pediatric hospital dermatology: experience with inpatient and consult services at the Mayo Clinic.

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.

AP1S3 Mutations Cause Skin Autoinflammation by Disrupting Keratinocyte Autophagy and Up-Regulating IL-36 Production.

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.

Experience of a year of adult hospital dermatology consultations.

BACKGROUND: Dermatology consultations are frequently requested by inpatient hospital services. As inpatient dermatology services in the USA decline, dermatology hospital consultations are becoming increasingly important. OBJECTIVES: We aim to describe the spectrum of skin diseases encountered and the health care subspecialties requesting dermatology hospital consultations. METHODS: We performed a retrospective chart review of adult patient (age: ≥18 years) dermatology hospital consultations from January 1 to December 31, 2010. We examined patient demographic characteristics, consultation requesting services, and consultation diagnoses. RESULTS: Among dermatology services, 614 patients had 674 separate inpatient dermatology consultations during 2010. Of these patients, 55.9% were male (mean age: 59 years). In total, 205 consultations (30.4%) were requested by the internal medicine subspecialty, 137 (20.3%) by the hematology and oncology subspecialty, and 93 (13.8%) by the surgical subspecialty. The most common conditions seen by the hospital dermatology consulting service were skin infections (n = 125, 18.5%), dermatitis (n = 120, 17.8%), drug eruptions (n = 87, 12.9%), chronic wounds and ulcers (n = 55, 8.1%), cutaneous neoplasms (n = 39, 5.8%), graft-versus-host disease (n = 37, 5.5%), ecchymosis, purpura simplex or petechia (n = 26, 3.8%), intertrigo (n = 21, 3.1%), and urticaria (n = 20, 3.0%). CONCLUSIONS: 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.

Filling a critical practice gap: experience with a dermatology day treatment center at Mayo Clinic.

BACKGROUND: Intensive treatment options are lacking for patients with severe skin disease recalcitrant to outpatient therapy. The availability of inpatient dermatology care has almost disappeared in many parts of the United States. One possible solution for this is a day treatment center for patients with severe dermatologic disease recalcitrant to outpatient therapy. METHODS: Descriptive study based on retrospective medical record review of all patients attending the day hospital for treatment in 2010. We collected data on patient demographics, distribution of admission diagnosis, treatments used, and length of stay. RESULTS: A total of 211 patients had 235 admissions. Mean age was 57.7 years (range 3.8-92.1 years). The most common indications for admission were dermatitis (139 admissions [59.2%]), psoriasis (58 [24.7%]), and mycosis fungoides (eight [3.4%]). The main treatment interventions were wet dressings (195 admissions [83.0%]) and Goeckerman treatment (38 [16.2%]). The median number of days of treatment was three (interquartile range, 2-5 days) for wet dressings and 22 days (interquartile range, 21-24 days) for Goeckerman therapy. CONCLUSIONS: The dermatology day treatment center provided intensive skin-directed therapy and filled a critical practice gap in the management of our patients with severe widespread skin diseases recalcitrant to outpatient therapy. We propose that the dermatology day treatment center is a valuable model that could be considered by both private practitioners and academic centers in the United States as an important adjunct to fill the gap in availability of intensive topical treatments for patients with severe skin disease.

Sustained virologic response following HCV eradication in two brothers with X-linked agammaglobulinaemia.

X-linked agammaglobulinaemia (XLA) is a humoral immunodeficiency syndrome characterized from childhood by the absence of circulating B lymphocytes, absent or reduced levels of serum immunoglobulin and recurrent bacterial infections. For many affected patients, regular treatment with immunoglobulin is life saving. Hepatitis C viral (HCV) infection acquired through contaminated blood products is widely described in this patient cohort. The natural history of HCV infection in patients with XLA tends to follow a more rapid and aggressive course compared to immunocompetent individuals. Furthermore, standard anti-viral therapy appears to be less efficacious in this patient cohort. Here we report the cases of two brothers with XLA who contracted HCV through contaminated blood products. They were treated with a six month course of Interferon alpha-2b and Ribavirin. We report a sustained virologic response five years after completing treatment.