Toxic epidermal necrolysis in adult patients: Experience from the West Australian Collaboration.

Toxic epidermal necrolysis (TEN) is a rare and life-threatening mucocutaneous disease triggered by a reaction to a drug. Despite reported mortality of 30%, management differs between healthcare settings. Our hospital was established in February 2015 becoming the new state burns centre in Western Australia (WA). Following this, we collaborated on comprehensive multidisciplinary guidelines for the management of TEN. These guidelines are updated annually to reflect the weight of emerging evidence in managing TEN. Our aim was to review the management and outcomes of TEN patients presenting to our hospital between February 2015 and May 2021 (inclusive). We collected data for 10 patients on year, age, ethnicity, gender, medical history, culprit drug and exposure, SCORTEN, length of stay, maximum percentage of skin detachment, mucosal surface involvement, ophthalmic amniotic membrane transplant, burns unit input/admission, intensive care unit admission, weight, systemic treatment(s), complications and outcome. We excluded 7 out of 17 flagged patients who did not strictly meet the definition of TEN as greater than 30% epidermal detachment, with epidermal detachment defined as bullae, erosions, and/or positive Nikolsky. We found that the mortality rate in WA from TEN is improving compared with two previous WA studies, with a mortality rate in our study of 20% (2 deaths). Though limited by small sample size and retrospective design, our study suggests a shift towards at least one systemic therapy per patient (most commonly cyclosporine), the growing use of etanercept and the ophthalmic use of amniotic membrane transplants. It demonstrates the importance of burns unit input and the utility of comprehensive multidisciplinary guidelines. While the management and outcomes of TEN patients in WA are continuing to improve, we support calls for large registry data to facilitate evidence growth and collaboration for this rare life-threatening condition.

Subcutaneous panniculitis-like T-cell lymphoma in a 14-year-old female homozygous for HAVCR2 mutation.

Subcutaneous panniculitis-like T-cell lymphoma (SPTCL) is a rare cytotoxic T-cell lymphoma preferentially involving subcutis. A link between patients with SPTCL and HAVCR2 mutations has recently been discovered. We present a 14-year-old girl of Chinese heritage who was diagnosed with SPTCL in the context of homozygous HAVCR2 status for c.245A>G p. (Tyr82Cys) and achieved complete remission after treatment with cyclosporin and steroids. Dermatologists should be aware of the diagnostic, management and familial genetic counselling utility of HAVCR2 for investigating and managing patients with SPTCL.

Systematic review of sirolimus in dermatological conditions.

Sirolimus is a mammalian target of rapamycin inhibitor (mTORI) with anti-proliferative, antiangiogenic and immunosuppressive properties. While approved in Australia as an anti-rejection medication for renal transplant patients, there is mounting evidence regarding the utility of oral and topical sirolimus in treating a plethora of dermatological conditions or conditions with cutaneous manifestations. Our aim was to present an overview of the evidence for current usage and breadth of the application of sirolimus in dermatology. We carried out a systematic review of all the literature published up to 31 August 2019 on oral and topical sirolimus with respect to dermatological conditions or conditions otherwise relevant to dermatology. While 3368 papers were initially produced in our search, 238 papers met our inclusion criteria and were examined in our review. The conditions examined were categorised into genodermatoses (9 conditions), infection (1 condition), inflammatory/autoimmune (10 conditions), neoplasm (3 conditions) and vascular (17 conditions). We extracted data on first author, publication year, journal, characteristics of the study and study patients, condition, drug modalities, drug efficacy, side effects, blood level of mTORI, co-interventions and follow-up. While there is level 1 evidence for the efficacy of sirolimus in conditions such as tuberous sclerosis complex (TSC) and GVHD prophylaxis, for many other conditions, the evidence is limited to level 4 evidence. Regarding oral systemic therapy, dosing regimens varied with the most common for children 0.8mg/m2 twice daily and for adults 1 mg twice daily. Doses were often adjusted to reach a typical trough level of between 5 and 15 ng/mL, though targets often varied. In the overall majority of cases, side effects were minimal or tolerable, including mucositis, cytopenias, lipid abnormalities and nausea/vomiting, and only a few cases had to stop due to adverse effects. Regarding topical therapy, concentration of formulations varied from 0.1% to 1% and were compounded into creams, ointments or gels and administered typically once or twice per day. The most common side effect was skin irritation. There were a number of limitations to our study. In particular, many of the published studies were case reports or case series with no comparator arm, leading to susceptibility of bias in conclusions drawn, in particular a high likelihood of publication bias. Given the heterogeneity amongst studies, comparisons or aggregation of results was difficult. There continues to be growing use of oral and topical sirolimus in dermatological conditions. It provides new therapeutic options to patients where previous therapies have either failed or are limited due to toxicity. However, further studies are warranted.

Complete remission of stage IV erythrodermic mycosis fungoides with large cell transformation through combination of pralatrexate and romidepsin followed by allogeneic hematopoietic stem cell transplantation.

We report the case of a 59-year-old woman with stage IV erythrodermic mycosis fungoides (MF) and large cell transformation who, despite failing multiple previous treatments, achieved complete remission through a combination of pralatrexate and romidepsin followed by allogeneic hematopoietic stem cell transplantation (alloSCT). Further studies are needed in focussing on this combined regimen in treating cutaneous T-cell lymphoma (CTCL) and its efficacy as a bridging regimen in facilitating successful alloSCT.

Pruritus as an early sign of abnormal scarring in the re-epithelialising phase of Toxic Epidermal Necrolysis.

We present a 28-year-old remote-living male who presented to our dermatology clinic with increasing pruritus over his torso and limbs in the context of a recent admission for Toxic Epidermal Necrolysis (TEN) secondary to paliperidone depot. Our case demonstrates that pruritus in the re-epithelialising phase of TEN may be a sign of abnormal scarring. Early assessment and measurement for compression garments is recommended.