par Nutrimuscle-Conseils » 22 Déc 2022 00:57
High-Dose Vitamin D for the Management of Toxic Erythema of Chemotherapy in Hospitalized Patients
Cuong V. Nguyen, JAMA Dermatol. Published online December 21, 2022.
Toxic erythema of chemotherapy (TEC) is a unifying term for the broad spectrum of cutaneous dose-dependent cytotoxic reactions that may occur with receipt of chemotherapeutic agents.1 In acute cases of TEC, patients can develop severe erythema, pain, swelling, and/or blistering, which may require inpatient management. However, therapeutic options for TEC are limited. Chemotherapy cessation, delay, or dose modification are the only reliable methods of resolving TEC. Supportive agents, such as high-potency topical corticosteroids, topical keratolytics, wound care, and pain control, have a variable response. These agents are associated with relatively slow improvement, involving 2 to 4 weeks of recovery after chemotherapy interuption.1
In this case series, we described 6 patients seen on the inpatient dermatology consultative service for evaluation and management of TEC. Patients received high-dose vitamin D with rapid improvement in cutaneous symptoms.
Methods
Patients who were evaluated for TEC by the consultative dermatology service at an academic medical center and received high-dose vitamin D from January 2019 to July 2022 were reviewed. Oncologic history and clinical characteristics were abstracted from electronic health records. The Northwestern University Institutional Review Board approved this retrospective case series and waived the informed consent requirement because deidentified data were used. We followed the AJO reporting guideline.
Results
Six inpatients (mean [range] age, 54.5 [36-68] years) with TEC received high-dose vitamin D (clinical features summarized in Table). Five patients had a hematologic condition (4 with acute myeloid leukemia; 1 with aplastic anemia) that required induction chemotherapy before hematopoietic stem cell transplant. One patient developed TEC secondary to regorafenib for treatment of glioblastoma multiforme. Diagnosis of TEC was established by clinical presentation, with 5 of 6 patients undergoing a biopsy. Biopsy findings in 3 patients were consistent with a TEC diagnosis, whereas findings in 2 patients showed nonspecific perivascular dermatitis. Onset of TEC occurred after a mean (range) of 8.5 (5-16) days after culprit drug administration. Vitamin D, 50 000 IU (for 1 patient) to 100 000 IU (for 5 patients), was administered once with repeat administration in 7 days (mean [range] time to first administration from rash onset, 4.3 [1-7] days). Topical corticosteroids with triamcinolone, 0.1%, or clobetasol, 0.05%, ointments were also prescribed.
All patients experienced symptomatic improvement in pain, pruritus, or swelling by the next day and improvement in redness within 1 to 4 days. The Figure provides representative clinical images before and after high-dose vitamin D treatment.
Discussion
High-dose vitamin D has been used off-label to treat acute skin injury due to sun-related UV radiation.2 Administered in single doses of 50 000 to 200 000 IU, vitamin D has a dose-dependent anti-inflammatory response, reducing redness and swelling within 24 to 48 hours of intake without substantial increase in serum vitamin D or calcium levels.2 Improvement in epidermal regeneration and inflammatory suppression is likely secondary to upregulation in M2 macrophage autophagy.3
Administration of high-dose vitamin D at single doses of 200 000 to 600 000 IU in patients with critical illness appears to be safe, without adverse consequences for 90-day mortality and length of hospital stay or increased risk of serious adverse events.4,5 Similarly, use of high-dose vitamin D in patients with advanced or metastatic cancer does not increase risk of cancer progression or decrease cancer treatment response.6
This study found a reduction in the time to TEC improvement from 2 to 4 weeks to 1 to 4 days. These findings suggest that high-dose vitamin D provides a novel inpatient treatment strategy to alleviating TEC-associated acute epidermal injury. Study limitations include the small cohort size, retrospective design, lack of long-term follow-up, and single-center data source. Further investigation is needed to identify optimal high-dose vitamin D dosing, delineate safety concerns and potential role in cancer treatment, and establish whether a durable response in patients with continuous chemotherapy, such as in the outpatient setting, is possible.
