Development and Validation of a Risk Prediction Model for In-Hospital Mortality Among Patients With Stevens-Johnson Syndrome/Toxic Epidermal Necrolysis-ABCD-10.

Importance: Stevens-Johnson syndrome/toxic epidermal necrolysis (SJS/TEN) is a spectrum of severe mucocutaneous drug reaction associated with significant morbidity and mortality. A previously developed SJS/TEN-specific severity-of-illness model (Score of Toxic Epidermal Necrolysis [SCORTEN]) has been reported to overestimate and underestimate SJS/TEN-related in-hospital mortality in various populations. Objective: To derive a risk prediction model for in-hospital mortality among patients with SJS/TEN and to compare prognostic accuracy with the SCORTEN model in a multi-institutional cohort of patients in the United States. Design, Setting, and Participants: Data from a multicenter cohort of patients 18 years and older treated for SJS/TEN between January 1, 2000, and June 1, 2015, were obtained from inpatient consult databases and electronic medical record systems at 18 medical centers in the United States as part of the Society for Dermatology Hospitalists. A risk model was derived based on data from 370 of these patients. Model discrimination (calculated as area under the receiver operating characteristic curve [AUC]) and calibration (calculated as predicted vs observed mortality, and examined using the Hosmer-Lemeshow goodness-of-fit statistic) were assessed, and the predictive accuracy was compared with that of SCORTEN. All analysis took place between December 2016 and April 2018. Main Outcomes and Measures: In-hospital mortality. Results: Among 370 patients (mean [SD] age 49.0 [19.1] years; 195 [52.7%] women), 54 (15.14%) did not survive to hospital discharge. Five covariates, measured at the time of admission, were independent predictors of in-hospital mortality: age in years (odds ratio [OR], 1.05; 95% CI, 1.02-1.07), body surface area (BSA) in percentage of epidermal detachment (OR, 1.02; 95% CI, 1.01-1.04), serum bicarbonate level below 20 mmol/L (OR, 2.90; 95% CI, 1.43-5.88), active cancer (OR, 4.40; 95% CI, 1.82-10.61), and dialysis prior to admission (OR, 15.94; 95% CI, 3.38-66.30). A severity-of-illness score was calculated by taking the sum of 1 point each for age 50 years or older, epidermal detachment greater than 10% of BSA, and serum bicarbonate level below 20 mmol/L; 2 points for the presence of active cancer; and 3 points for dialysis prior to admission. The score was named ABCD-10 (age, bicarbonate, cancer, dialysis, 10% BSA). The ABCD-10 model showed good discrimination (AUC, 0.816; 95% CI, 0.759-0.872) and calibration (Hosmer-Lemeshow goodness of fit test, P = .30). For SCORTEN, on admission, the AUC was 0.827 (95% CI, 0.774-0.879) and was not significantly different from that of the ABCD-10 model (P = .72). Conclusions and Relevance: In this cohort of patients with SJS/TEN, ABCD-10 accurately predicted in-hospital mortality, with discrimination that was not significantly different from SCORTEN. Additional research is needed to validate ABCD-10 in other populations. Future use of a new mortality prediction model may provide improved prognostic information for contemporary patients, including those enrolled in observational studies and therapeutic trials.

Ruxolitinib as Salvage Therapy for Chronic Graft-versus-Host Disease.

Chronic graft-versus-host disease (cGVHD) continues to be a major complication after allogeneic hematopoietic cell transplantation, significantly affecting patients' quality of life. A regimen of systemic corticosteroids is considered first-line therapy but is often associated with inadequate responses and multiple side effects. In patients with refractory disease, an evidenced-based consensus is lacking as to the single best approach to managing symptoms. Ruxolitinib, a selective JAK1/2 inhibitor, has recently gained favor as a second-line approach in patients with steroid-refractory cGVHD. In this retrospective study, we evaluated the outcomes of 46 patients who received ruxolitinib for cGVHD between March 2016 and December 2017 at our institution, and evaluated ruxolitinib's impact at 6 and 12 months, based on the National Institutes of Health Severity Scale, including organ-specific responses, and mean prednisone dose. Furthermore, we present the first reported probability of ruxolitinib's treatment failure-free survival (FFS) in patients with cGVHD. After 12 months of ruxolitinib therapy, complete response, partial response, and stable disease was observed in 13% (n = 6), 30.4% (n = 14), and 10.9% (n = 5) of patients, respectively. The 1-year probability of FFS was 54.2% (95% confidence interval, .388 to .673), and ruxolitinib use was associated with a reduction in prednisone dose. In conclusion, our data, which represent the largest cohort of patients with cGVHD reported to date, support the use of ruxolitinib for cGVHD refractory to steroids and currently available salvage therapies, discontinued due to lack of response and high cost.

Cutaneous Involvement in a Case of Intravascular T-Cell Lymphoma With a γδ Phenotype.

Intravascular lymphomas (IVL) are uncommon variants of extranodal non-Hodgkin which are usually difficult to diagnose because of their lack of clinical uniformity. Most cases are of B-cell differentiation followed by natural killer/T-cell differentiation and underlying CD30 lymphoproliferative conditions. Epstein-Barr virus is pathogenically related in most of the natural killer/T-cell variants, and the skin is a common site of presentation noted in approximately 40% of cases. Recently, cases with uncommon phenotypes have been described, expanding our understanding of the pathogenesis of this condition. In this report, we describe a 67-year-old man with a 3-month history of constitutional symptoms associated with linear purpuric macules on the trunk, pancytopenia, and high levels of serum lactate dehydrogenase. He had been followed for longstanding adenopathy and hepatosplenomegaly. Skin biopsy demonstrated a intravascular lymphocytic proliferation with positivity for CD3, CD2, CD5, and γδ T-cell receptor marker; in situ hybridization Epstein-Barr virus RNA was negative. The patient was subsequently treated with chemotherapy and allogenic stem cell transplant. He remains in complete remission 6 months posttransplant. Although the presence of hepatosplenomegaly led to consideration of a hepatosplenic T-cell lymphoma, it was pre-existing for several years making the diagnosis doubtful. To our knowledge, this is the first case report of an IVL γδ T-cell lymphoma.

Prospective randomized pilot study of Y90+/-sorafenib as bridge to transplantation in hepatocellular carcinoma.

BACKGROUND & AIMS: To investigate the safety and adverse event profile of sorafenib plus radioembolization (Y90) compared to Y90 alone in patients awaiting liver transplantation. METHODS: 20 patients with HCC were randomized to Y90 alone (Group A) or Y90+sorafenib (Group B). Adverse events, dose reductions, and peri-transplant complications were assessed. RESULTS: All patients in the sorafenib group necessitated dose reductions. Seventeen of 20 patients underwent liver transplantation; median time-to-transplant was 7.8 months (range: 4.2-20.3) and similar between groups (p = 0.35). In the sorafenib group, there were 4/8 peri-transplant (<30 days) biliary complications (p = 0.029) and 3/8 acute rejections (p = 0.082); there were none in the Y90-only group. Survival rates were 70% (Group A) and 72% (Group B) at 3 years (p = 0.57). CONCLUSIONS: The addition of sorafenib to Y90 necessitated dose reductions in all patients awaiting transplantation. Preliminary data suggest that the combination was associated with more peri-transplant biliary complications and potentially trended towards more acute rejections. Caution should be exercised when considering sorafenib in the transplant setting. Further investigation is warranted.

Demodex folliculitis mimicking acute graft-vs-host disease.

IMPORTANCE: Acute graft-vs-host disease (GVHD) typically requires high-dose systemic steroids as first-line treatment. Like drug eruptions, viral exanthema, and toxic erythema of chemotherapy, Demodex folliculitis is a clinical mimicker of acute GVHD and requires nonimmunosuppressive therapy. This case of Demodex folliculitis mimicking acute GVHD highlights the need for skin biopsy in patients who have undergone a stem cell transplant with eruptions on the head and neck. OBSERVATIONS: A 46-year-old white woman with a history of Fms-like tyrosine kinase 3 acute myeloid leukemia presented to the dermatology clinic with a 5-day history of a nonpruritic eruption on her face and neck 28 days after undergoing a double umbilical cord blood hematopoietic stem cell transplant (HSCT). Findings from the skin biopsy demonstrated a deep dermal lymphocytic infiltrate adjacent to follicular units along with an abundance of Demodex mites noted within the hair follicles consistent with Demodex folliculitis. Oral ivermectin, 12 mg, was given, and the eruption cleared within 24 hours. CONCLUSIONS AND RELEVANCE: To our knowledge, this is only the fifth reported case of Demodex folliculitis following HSCT, but the first ever reported to be successfully treated with oral ivermectin. Demodex folliculitis should be added to the differential diagnosis of skin eruptions that arise after HSCT.

Grading dermatologic adverse events of cancer treatments: the Common Terminology Criteria for Adverse Events Version 4.0.

Dermatologic adverse events to cancer therapies have become more prevalent and may to lead to dose modifications or discontinuation of life-saving or prolonging treatments. This has resulted in a new collaboration between oncologists and dermatologists, which requires accurate cataloging and grading of side effects. The Common Terminology Criteria for Adverse Events Version 4.0 is a descriptive terminology and grading system that can be used for uniform reporting of adverse events. A proper understanding of this standardized classification system is essential for dermatologists to properly communicate with all physicians caring for patients with cancer.

Capecitabine-induced hand-foot syndrome complicated by pseudomonal superinfection resulting in bacterial sepsis and death: case report and review of the literature.

BACKGROUND: Hand-foot syndrome (HFS) is a relatively common dermatologic toxic reaction to certain anticancer therapies. Although not life-threatening, this complication can reduce patient quality of life. Dose modification of the inciting agent serves as the most effective management of HFS, although a variety of anecdotal reports suggest that other agents may also be efficacious. We present the first reported case of fatal HFS (to our knowledge) and provide a comprehensive review of this condition. OBSERVATIONS: A 61-year-old woman with metastatic breast cancer who was undergoing treatment with capecitabine developed erythema, fissuring, and erosions over both hands and feet, consistent with HFS. Pseudomonal superinfection leading to bacterial sepsis and death rapidly ensued. CONCLUSIONS: Although HFS is widely regarded as a non-life-threatening toxic reaction to cancer treatment, our case demonstrates that infectious complications of this condition can prove fatal. Prevention, early recognition, and implementation of various management strategies for HFS and its infectious complications are important in optimizing patient quality of life and minimizing unfavorable outcomes.

Acute graft-versus-host disease following hematopoietic stem-cell transplantation.

Hematopoietic stem-cell transplantation has become the standard of care for numerous malignant and nonmalignant conditions. As the number of stem-cell transplants performed worldwide rises, it is imperative that dermatologists taking care of these patients are able to understand the methods of transplantation, as well as to recognize and treat the cutaneous complications that commonly follow transplant, particularly acute graft-versus-host disease.

Stevens-Johnson syndrome and toxic epidermal necrolysis: a review of treatment options.

Stevens-Johnson syndrome (SJS) and toxic epidermal necrolysis (TEN) are severe cutaneous reactions that are medication-induced in most instances. While the clinical manifestations of SJS and TEN are well-defined, the optimal treatment for these disorders is not. Case reports have shown benefit with the use of a variety of agents including tumor necrosis factor-alpha inhibitors and cyclophosphamide, whereas thalidomide was associated with an increased mortality. Plasmapheresis and cyclosporine have also demonstrated efficacy anecdotally, albeit with an even smaller number of cases in the literature. Most of the reporting has focused on the use of systemic corticosteroids and intravenous immunoglobulin (IVIG) for these severe reactions. The majority of studies analyzing the use of IVIG in the treatment of SJS/TEN show a benefit, though more recent series cast doubt upon this conclusion. The results of these studies are summarized in this present review study.

Dermatologic toxicities of targeted anticancer therapies.

The discovery of the intricate intracellular signaling networks that regulate normal cellular proliferation and survival but can also drive the oncogenic process when aberrantly activated has led to the emergence of targeted agents in oncology. The introduction of such agents has resulted in improved survival and more tolerable treatments, reducing systemic toxicities such as myelosuppression. Nevertheless, it has become evident that these agents are associated with a wide spectrum of dermatologic toxicities that often manifest in cosmetically sensitive areas and may affect the majority of patients. Associated pain and pruritus can negatively impact quality of life, resulting in dose modification or treatment interruptions that interfere with potentially life-prolonging therapy. Extensive efforts throughout the past decade have concentrated on describing the clinicohistopathologic characteristics, elucidating the underlying mechanisms, and investigating potential management strategies. Currently, however, proposed treatment guidelines arise from expert opinions, anecdotal evidence, and few data from clinical trials. This article reviews the spectrum of dermatologic toxicities associated with a variety of targeted agents used alone or in combination with other modalities, delineating their clinical presentation, underlying mechanisms, and management options.

Acute graft-versus-host disease after pediatric solid organ transplant.

Acute graft-versus-host disease (GVHD) is a rare and life threatening complication after solid organ transplantation. The diagnosis can be made with clinical and laboratory evidence of skin, liver, or intestinal involvement. The role of skin biopsy in confirming acute GVHD is debatable. However, it is proposed that the skin biopsy is a valuable tool in confirming the diagnosis in low prior probability settings. An atypical case of acute GVHD following orthotopic liver and small bowel transplantation in a 2-year-old male is presented. Seven weeks posttransplantation, the patient developed a bullous eruption limited to the buttocks and upper thighs. A skin biopsy was performed which showed interface dermatitis and epidermal necrosis consistent with acute GVHD. Prompt treatment with daclizumab and intravenous corticosteroids was given and the patient survived without evidence of systemic GVHD. This case highlights the importance of skin biopsy in establishing the prompt diagnosis of GVHD in low prior probability settings.