Survival, Risk Factors, and Effect of Treatment in 101 Patients With Calciphylaxis.

OBJECTIVE: To report on the survival and the associations of treatments upon survival of patients with calciphylaxis seen at a single center. PATIENTS AND METHODS: Using the International Classification of Diseases, Ninth Revision diagnosis code of 275.49 and the keyword "calciphylaxis" in the dismissal narrative, we retrospectively identified 101 patients with calciphylaxis seen at our institution between January 1, 1999, through September 20, 2014, using a predefined, consensus-developed classification scheme. RESULTS: The average age of patients was 60 years: 81 (80.2%) were women; 68 (68.0%) were obese; 19 (18.8%) had stage 0 to 2 chronic kidney disease (CKD), 19 (18.9%) had stage 3 or 4 CKD; 63 (62.4%) had stage 5 or 5D (dialysis) CKD. Seventy-five patients died during follow-up. Six-month survival was 57%. Lack of surgical debridement was associated with insignificantly lower 6-month survival (hazard ratio [HR]=1.99; 95% CI, 0.96-4.15; P=.07) and significantly poorer survival for the entire duration of follow-up (HR=1.98; 95% CI, 1.15-3.41; P=.01), which was most pronounced in stage 5 or 5D CKD (HR=1.91; 95% CI, 1.03-3.56; P=.04). Among patients with stage 5/5D CKD, subtotal parathyroidectomy (performed only in patients with hyperparathyroidism) was associated with better 6-month (HR=0.12; 95% CI, 0.02-0.90; P=.04) and overall survival (HR= 0.37; 95% CI, 0.15-0.87; P=.02). CONCLUSION: Calciphylaxis is associated with a high mortality rate. Significantly effective treatments included surgical debridement and subtotal parathyroidectomy in patients with stage 5/5D CKD with hyperparathyroidism. Treatments with tissue-plasminogen activator, sodium thiosulfate, and hyperbaric oxygen therapy were not associated with higher mortality.

Isotretinoin Exposure and Risk of Celiac Disease.

BACKGROUND: Isotretinoin (13-cis retinoic acid) is a metabolite of vitamin A and has anti-inflammatory and immunoregulatory effects; however, a recent publication by DePaolo et al. demonstrated that in the presence of IL-15, retinoic acid can act as an adjuvant and promote inflammation against dietary proteins. OBJECTIVE: To evaluate the risk of overt and latent celiac disease (CD) among users of isotretinoin. MATERIAL AND METHODS: Medical records of patients from 1995 to 2011 who had a mention of isotretinoin in their records (N = 8393) were searched for CD diagnosis using ICD-09CM codes. Isotretinoin exposure was compared across overt CD patients and their age- and gender-matched controls from the same pool. To evaluate the risk of latent CD with isotretinoin exposure, patients were overlapped with a community-based list of patients with waste serum samples that were tested for CD serology, excluding those with overt CD (2006-2011). Isotretinoin exposure was defined as the use of isotretinoin prior to CD diagnosis or serology. RESULTS: Of 8393 patients, 25 had a confirmed CD diagnosis. Compared to matched controls (N = 75), isotretinoin exposure was not significantly different between overt CD patients versus controls (36% versus 39%, respectively; P = 0.712). Likewise, latent CD defined as positive serology was not statistically different between isotretinoin exposed (N = 506) versus non-exposed (N = 571) groups (1.8% versus 1.4%, respectively; P = 0.474). CONCLUSIONS: There was no association between isotretinoin use and risk of either overt or latent CD.

Wet dressing therapy in conjunction with topical corticosteroids is effective for rapid control of severe pediatric atopic dermatitis: experience with 218 patients over 30 years at Mayo Clinic.

BACKGROUND: At our institution, hospitalization for intensive treatment (combining wet dressings and topical corticosteroids) is a primary intervention for severe pediatric atopic dermatitis. Prior reports of this treatment are limited. OBJECTIVE: We sought to review the efficacy of wet dressings for pediatric atopic dermatitis. METHODS: We reviewed records of pediatric patients hospitalized from January 1, 1980, through April 20, 2010, who received intensive topical treatments for atopic dermatitis. RESULTS: In total, 218 pediatric patients had widespread atopic dermatitis severe enough to warrant hospitalization, despite prior outpatient topical treatments and other interventions such as immunomodulating agents, phototherapy, dietary manipulation, or contact allergen avoidance. Mean (SD) age was 5.97 (4.91) years (range, 2 months-17 years); 141 patients (65%) were female. There were 266 hospitalizations: 192 patients (72%) had one admission, 15 (6%) had two admissions, and 11 (4%) had 3 or more admissions. Mean (SD) duration of hospitalization was 3.61 (2.23) days (range, 1-16 days). Upon discharge, all patients showed improvement. In 239 of 266 hospitalizations, patient records showed quantification of improvement (global assessment): 121 (45%) had 75% to 100% improvement, 102 (38%) had 50% to 75% improvement, and 16 (6%) had 25% to 50% improvement. LIMITATIONS: This was a retrospective study. CONCLUSION: Intensive inpatient treatment (with wet dressings and topical corticosteroids) was highly effective in controlling severe and recalcitrant atopic dermatitis. Intensive topical treatment, although underused, is an effective first-line approach for patients with severe atopic dermatitis.

Calmodulin-like protein upregulates myosin-10 in human keratinocytes and is regulated during epidermal wound healing in vivo.

Epidermal wound healing is required for normal skin barrier function. Cell motility is a key factor in the ability of keratinocytes to heal epithelial damage. Calmodulin-like protein (CLP) is an epithelial-specific Ca(2+)-binding protein that is regulated during terminal keratinocyte differentiation. CLP is a specific light chain of unconventional myosin-10 (Myo10) and its expression increases filopodial length, filopodial number, and Myo10-dependent cell motility in vitro. However, the effects of CLP expression on keratinocyte motility are unknown. Here we used cultured human keratinocytes to study the role of CLP in regulating Myo10 and the effects of Myo10 and CLP on cell migration. CLP and Myo10 expression were correlated in vitro and required for keratinocyte motility in wound-healing assays. We examined the localization of CLP in wounded skin by immunohistochemistry and found an upregulation and peripheral localization of CLP in the basal and suprabasal cells adjacent to and immediately over the wound bed in vivo. The results suggest that increased CLP expression and CLP-mediated Myo10 function are important for skin differentiation and wound reepithelialization.

Chelation of gadolinium with deferoxamine in a patient with nephrogenic systemic fibrosis.

A 65-year-old female with biopsy-confirmed nephrogenic systemic fibrosis (NSF) received a kidney transplantation. Despite good kidney function, her symptoms continued to progress. Deferoxamine was administered intramuscularly at 500 mg/day and later 1000 mg/day after 1 week with no adverse effects. Urine excretion of gadolinium increased from 6.0 µg/day to 11.6 µg/day and subsequently to 13.0 µg/day with 500 mg/day and 1000 mg/day of deferoxamine, respectively. Serum levels, however, remain unchanged from 1.7 ng/ml to 1.4 ng/ml. Although chelation therapy may have a role in the treatment of NSF, deferoxamine is too weak and a stronger chelator is needed.