Jonathan Cotliar

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.

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.

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.

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.

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.

Association of Dermatology Consultation With Accuracy of Cutaneous Disorder Diagnoses in Hospitalized Patients: A Multicenter Analysis

topical lidocaine cream, 4%, is typically used to produce anesthesia 60 minutes after application.4,6 Our results suggest that the use of microneedle pretreatment can reduce the incubation time to 30 minutes—perhaps even to 10 minutes in more pain-sensitive individuals—to achieve sufficient anesthesia for needle insertion. Our study has several limitations. First, the pain stimulus was needle based and it is not known how laseror scalpelbased pain would have been altered. Second, our study was limited to men; future studies should include women. Finally, this study evaluated pain on the volar forearms, but pain sensitivity can vary by anatomical site. Because the participants served as their own controls and the anatomical site at each pain assessment had a symmetrically placed control, the role of the site was minimized. The study should be repeated using other anatomical sites. Randomized clinical trials should be conducted with laseror scalpel-based stimuli to simulate other dermatologic procedures. In particular, studies in a pediatric population can help clarify the role of microneedle pretreatment in topical anesthesia before invasive procedures. Regardless, the findings of this studyarepromising,showingthatmicroneedlesofferaminimally painful method of enhancing the effects of topical anesthesia.

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.

Purpura Fulminans From Meningococcemia Mimicking Stevens-Johnson Syndrome in an Adult Patient Taking Etanercept

Comment. Vemurafenib, a BRAF inhibitor, was approved recently for treatment of BRAF V600E mutation– positive metastatic melanoma. It has been associated with KP-like eruptions and epidermal cysts and atypical melanocytic proliferations. Eruptive melanocytic nevi (EMN) have been described in patients treated with sorafenib, a serine/threonine and tyrosine-kinase inhibitor with nonselective activity against wild-type and V600E mutant BRAF. Our case is novel for the severity of the patient’s scalp involvement and association with hidradenitis and EMN. Paradoxical activation of the MAPK pathway by vemurafenib is a potential mechanism for this reaction, affecting both wild-type keratinocyte differentiation and melanocyte proliferation. Although our patient received multiple chemotherapy agents and steroids prior to his skin eruption, and EMN are known to occur in the setting of systemic immunosuppression and after chemotherapy, the time course is most consistent with vemurafenib initiation: the last chemotherapy dose was administered 7 months prior to the KP-like eruption and hidradenitis, and 10 months prior to the EMN. Histologic findings were notable for the absence of solar elastosis, sclerosis, atypical fibroblasts, and degenerative changes, suggesting photoinduced or radiation-induced Favre-Racouchot syndrome. The axillary lesions were not biopsied but were clinically consistent with hidradenitis due to draining nodules and multiheaded open comedones. The patient’s hidradenitis improved moderately with doxycycline and benzoyl peroxide treatment, and the scalp with application of tretinoin, 0.025%, cream. Discontinuation of vemurafenib therapy owing to progression of his metastatic melanoma resulted in almost complete resolution of his KP-like eruption, cysts, and hidradenitis after 6 weeks (Figure 1C). The nevi have persisted.

Acute generalized exanthematous pustulosis in a patient receiving high-dose recombinant interleukin-2

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Lichen Sclerosus in a Patient With a History of Hereditary Nonpolyposis Colorectal Cancer

Lynch syndrome, also known as hereditary nonpolyposis colorectal cancer, is an autosomal dominant genetic syndrome caused by germline mutations in 1 or more of the mismatch repair genes, including MLH1, MSH2, MSH6 or PMS2 or all these (Table). The DNA mismatch repair plays an essential role in the maintenance of genome stability as a postreplicative system that repairs normal or damaged single-base mismatches, as well as insertions and deletions in the DNA. A heterozygous germline genetic mutation at 1 of these sites leads to microsatellite instability (MSI), a phenomenon of genetic hypermutability that predisposes one to develop errors in the DNA replication process. Regular dermatologic follow-up is recommended as these patients may develop a number of cutaneous malignancies, establishing patients with Lynch syndrome with an additional diagnosis of Muir-Torre syndrome (MTS). A phenotypic variant of Lynch syndrome, MTS is diagnosed when a patient has 1 of any number of typical hereditary nonpolyposis colorectal cancer tumors including colon, endometrial, urologic, small bowel, ovarian, hepatobiliary and brain, in addition to a sebaceous gland tumor (adenoma, epithelioma or carcinoma). Sebaceous adenomas are the most frequent skin lesions found in patients with MTS, and they present as yellow papules or nodules most commonly localized on the face. A 65-year-old White male with Lynch syndrome presented to a dermatology clinic for an annual total body skin examination. He had a history of multiple colonic polyps resected during the previous 15 years, with 1