Direct oral anticoagulant medications in calciphylaxis.

BACKGROUND: Recent studies suggest that calciphylaxis is a thrombotic condition in which arteriolar thrombosis leads to painful skin infarcts and consequent morbidity and mortality. Paradoxically, warfarin is implicated as a risk factor for calciphylaxis. Our objective is to report the use of oral direct thrombin and factor Xa inhibitors (termed direct oral anticoagulants [DOACs]) in patients with calciphylaxis. METHODS: We retrospectively reviewed records of 16 patients with calciphylaxis who received concomitant administration of novel anticoagulants. Patient data, including demographics, comorbidities, other treatments, and adverse events, were abstracted from the health records. RESULTS: Eleven patients (69%) had chronic kidney disease (stage ≥3A), and eight (50%) received dialysis. Apixaban was the most frequently used agent (n = 11 [69%]). Dabigatran (n = 4 [25%]) and rivaroxaban (n = 2 [13%]) were reserved for patients with mild renal impairment (stage ≤2). One clinically relevant but nonmajor bleeding event occurred. There were no major bleeding events. Nine patients (56%) were alive at last follow-up, and five (31%) had complete resolution of their calciphylaxis (mean follow-up, 523 days; range, 26-1884 days). CONCLUSION: DOACs were safe and well tolerated in patients with calciphylaxis, in this initial experience. Several patients had improvement or resolution of calciphylaxis in response to therapy that included DOACs. The degree of renal impairment should guide DOAC choice. Randomized trials are required to determine treatment efficacy.

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.

Retrospective analysis of tissue plasminogen activator as an adjuvant treatment for calciphylaxis.

OBJECTIVE: To report our experience with low-dose tissue plasminogen activator in the treatment of calciphylaxis, a rare, usually fatal thrombotic condition that results in ischemia, necrosis, and infarction of adipose and cutaneous tissue. DESIGN: Retrospective chart review. SETTING: Tertiary care academic medical center. PATIENTS: Fifteen patients (4 men and 11 women) with calciphylaxis, treated from January 1, 2002, through December 31, 2010. INTERVENTION: Treatment with tissue plasminogen activator, concomitant wound care, and management of calcium-phosphate status. MAIN OUTCOME MEASURES: Short-term ulcer healing, long-term survival. RESULTS: Patients received daily low-dose infusions of tissue plasminogen activator (mean treatment duration, 11 days). Six patients had no adverse reactions, 3 had minor bleeding, 6 required blood transfusions, and 3 had life-threatening bleeding. No patients died of treatment-related complications. Ten patients died (median time to death, 3.6 months; range, 23 days to 4.2 years). Of the remaining 5 patients, the median duration of follow-up was 36.8 months (range, 70 days to 4.3 years). Patients treated with tissue plasminogen activator had approximately 30% greater survival than controls, but the difference was not significant (P= .14). Our results were limited by the use of concomitant therapies, referral bias for advanced disease, and retrospective case-series design. CONCLUSIONS: Thrombolytic tissue plasminogen activator may be a useful adjunctive treatment in the management of patients with calciphylaxis. However, a multidisciplinary approach that includes aggressive wound care, débridement, thrombolytic therapy, restoration of tissue oxygenation, avoidance of infection, and control of calcium-phosphate homeostasis also is essential.

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.