The Australasian Registry for Severe Cutaneous Adverse Reactions (AUS-SCAR) - Providing a roadmap for closing the diagnostic, patient, and healthcare gaps for a group of rare drug eruptions.

Background: Severe cutaneous adverse reactions (SCAR) are a group of delayed presumed T-cell mediated hypersensitivities associated with significant morbidity and mortality. Despite their shared global healthcare burden and impact, the clinical phenotypes, genomic predisposition, drug causality, and treatment outcomes may vary. We describe the establishment and results from the first Australasian registry for SCAR (AUS-SCAR), that via a collaborative network advances strategies for the prevention, diagnosis and treatment of SCAR. Methods: Prospective multi-center registry of SCAR in Australian adult and adolescents, with planned regional expansion. The registry collects externally verified phenotypic data drug causality, therapeutics and long-term patient outcomes. In addition, biorepository specimens and DNA are collected at participating sites. Results: we report on the first 100 patients enrolled in the AUS-SCAR database. DRESS (50%) is the most predominant phenotype followed by SJS/TEN (39%) and AGEP (10%), with median age of 52 years old (IQR 37.5, 66) with 1:1 male-to-female ratio. The median latency for all implicated drugs is highly variable but similar for DRESS (median 15 days IQR 5,25) and SJS/TEN (median 21 days, IQR 7,27), while lowest for AGEP (median 2.5 days, IQR 1,8). Antibiotics (54.5%) are more commonly listed as primary implicated drug compare with non-antibiotics agent (45.5%). Mortality rate at 90 days was highest in SJS/TEN at 23.1%, followed by DRESS (4%) and AGEP (0%). Conclusion: In the first prospective national phenotypic and biorepository of SCAR in the southern hemisphere we demonstrate notable differences to other reported registries; including DRESS-predominant phenotype, varied antibiotic causality and low overall mortality rate. This study also highlights the lack of standardised preventative pharmacogenomic measures and in vitro/in vivo diagnostic strategies to ascertain drug causality. Trial registration: ANZCTR ACTRN12619000241134. Registered 19 February 2019.

Adult multisystem Langerhans cell histiocytosis with cutaneous involvement manifesting as extensive flexural erosions.

Langerhans cell histiocytosis is a great imitator of other diseases with an often-delayed diagnosis leading to a concerning delay in commencing treatment. We present the case of a male who was previously diagnosed with Hailey-Hailey disease, in whom several treatment options had failed, was referred to the dermatology team for evaluation of a 3-month atypical, extensive, painful and pruritic cutaneous flexural eruption. On systems review, he reported a 2-year history of polyuria and polydipsia. Repeat skin biopsy revealed a prominent histiocytic infiltrate on histopathology with corresponding positive expression of Langerin (CD207), S100, CyclinD1 and p-ERK on immunohistochemistry staining. An MRI of the brain demonstrated posterior pituitary enhancement. The clinical presentation, biopsy and investigations confirmed a diagnosis of a multisystem Langerhans cell histiocytosis, which resulted in longstanding patient morbidity. With considerable multidisciplinary teamwork, a gradual and sustained resolution of his lesions, pain, polyuria and polydipsia was achieved.

Cutaneous manifestations and treatment of arsenic toxicity: A systematic review.

Cutaneous and systemic signs of acute and chronic arsenic poisoning may be vague. Thus, an awareness of these signs is crucial to prevent late or missed diagnoses. This is especially true in non-endemic countries where individuals may present decades after exposure, or may still be ingesting arsenic via a non-classical exposure. Existing literature emphasizes several well-known cutaneous presentations of arsenic toxicity while ignoring the complete clinical spectrum, including several rare tumours of relevance to the dermatologist. This study aims to review the existing literature on dermatological presentations of arsenic toxicity and their management in adults.

New onset MDA-5 positive dermatomyositis and massive perivillous fibrin deposition in third trimester of pregnancy: A case report.

We report a case of a 42-year-old woman (Gravida 1, Para 1) who presented in her third trimester of pregnancy with a photo distributed eruption and arthralgias and was subsequently diagnosed with dermatomyositis. She had an emergency Caesarean section at 34 weeks plus 6 days gestation due to decreased fetal movements and non-reassuring fetal heart rate. Her placenta was sent for histopathology and showed features of massive perivillous fibrin deposition. To our knowledge, this is the first case of MDA-5 positive dermatomyositis in pregnancy with a live delivery.

Fixed drug eruptions - the common and novel culprits since 2000.

A fixed drug eruption (FDE) is a common cutaneous adverse drug reaction which occurs following administration of an offending drug. The aim of this review is to provide an update on the list of drugs causing FDE, with a focus on emerging drug culprits reported since the start of the century. Across published literature, triggers for FDE are widely varied. The most frequently implicated drugs include analgesics (nonsteroidal anti-inflammatory drugs [NSAIDs] and paracetamol) and antibiotics. Co-trimoxazole is perhaps the most well described single agent. Since the start of the century there have been over 200 drugs named in case reports on FDE. Newer, novel agents of note include cyclooxygenase-2 specific inhibitors, fluconazole, and phosphodiesterase 5 inhibitors. Other implicated drugs include vaccines, such as various SARS-CoV-2 vaccines. Drugs incriminated in FDE vary based on the geographical region studied and prescribing patterns at a given time. Newer drugs continue to enter the market and are playing an increasing role in the field of FDE. Awareness of rarer culprits and emerging novel agents can help identify a trigger, allowing for prompt withdrawal of the causative agent, preventing recurrence.

Discoid (nummular) eczema in the paediatric setting - An Australian/New Zealand narrative.

Discoid (nummular) eczema is a common and distinctive eczema variant, which has not been studied in depth. Although the principles of management are similar to that of classic atopic dermatitis, distinctions are made due to its unique presentation and persistent clinical course in children. Australian and New Zealand dermatologists with an interest in paediatric eczema developed a consensus narrative to assist clinicians in diagnosing and treating this subtype of eczema. Identifying triggers, potent topical corticosteroids under occlusion, skin barrier support and management of pruritus are first-line therapies, however, many eventually require systemic immunomodulatory agents.

Rivaroxaban in the treatment of TEK-related venous malformation.

Low-flow vascular malformations are rare congenital anomalies due to errors in vascular development and may be associated with known pathogenic genetic variants. Slow flow through the blood vessels can lead to localized intralesional thromboses, which can cause debilitating pain and impair quality of life. We present a case of venous malformation due to a variant in the TEK gene in a 38-year-old woman in whom treatment with low dose rivaroxaban was successful in controlling symptoms of chronic localized intravascular coagulation.

Successful secukinumab treatment of active bullous pemphigoid and chronic severe psoriasis: a case report.

Since the concurrence of bullous pemphigoid (BP) and psoriasis was first reported in 1929, an increasing number of studies has been published to analyse their relationship in recent years. However, the pathogenesis of the concurrence is not yet well understood, and the coexistence of the two conditions imposes a difficult therapeutic challenge. This case report demonstrates the first case of secukinumab achieving a dramatic clinical improvement of both chronic psoriasis and active BP.

De-escalation of anti-CD20 monoclonal antibody (Rituximab) protocols in Pemphigus Vulgaris - a systematic review.

Introduction: This review assesses current evidence supporting dose de-escalated rituximab therapy in pemphigus vulgaris, compared to standard protocols. Primary outcome measures were remission and relapse rates. Adverse effects, cumulative steroid dosages, and serological markers of disease activity were also reported.Areas covered: A literature search was performed to look for reports describing the use of de-escalated rituximab therapy in pemphigus vulgaris. Results from heterogenous studies showed a large variation in remission and relapse rates. Complete remission rates from de-escalated treatment ranged from 41.7 to 100.0%, while rates in the control groups ranged from 60.0 to 90.9%. Relapse rates varied from 8.0 to 81.3% in the de-escalated group and from 0.0 to 72.4% in the control group. Of the 165 patients included in this report, only two major adverse effects were reported.Expert Opinion: Overall, dose de-escalated rituximab protocols reported to date appear effective and safe. However, it is unclear if treatment effect parallels that of standard regimens in regard to disease control in the long term. A lower limit of effective dosing for rituximab in pemphigus vulgaris has not yet been reached or defined. The role for and timing of repeated cycles of low-dose rituximab therapy require further exploration.

Comparison of the EUROIMMUN Dermatology Profile ELISA to the novel BIOCHIP Mosaic 7 for the diagnosis of immunobullous skin disease.

BACKGROUND: The BIOCHIP is an indirect immunofluorescence diagnostic investigation which identifies multiple autoantibodies with a mosaic panel of target antigen-specific substrates in a single incubation field. The EUROIMMUN Dermatology Profile ELISA allows simultaneous investigation of the six most important autoantibodies in bullous autoimmune dermatoses. Evaluation of the BIOCHIP Mosaic 7, compared to that of the EUROIMMUN Dermatology Profile ELISA, when used as a diagnostic investigation in pemphigus and pemphigoid, was undertaken in an Australian cohort. METHODS: The serum of 27 patients was analysed including patients with pemphigus vulgaris (n = 10), pemphigus foliaceous (n = 4), bullous pemphigoid (n = 8), mucous membrane pemphigoid (n = 3) and negative controls (n = 2). Results of the BIOCHIP were compared with the EUROIMMUN Dermatology Profile ELISA, as well as with histology, direct immunofluorescence and indirect immunofluorescence. RESULTS: In pemphigus vulgaris, sensitivity & specificity for the BIOCHIP Mosaic 7 were 100% and 94.1%, comparable to that of the EUROIMMUN Dermatology Profile ELISA with 80% sensitivity and 100% specificity. In bullous pemphigoid, sensitivity of the BIOCHIP was 87.5% and sensitivity of the EUROIMMUN Dermatology ELISA profile was 75%, whilst specificities for both diagnostic methods were 100% in our limited cohort. There was substantial or almost perfect concordance between the BIOCHIP Mosaic 7 and EUROIMMUN Dermatology Profile ELISA for pemphigus vulgaris and bullous pemphigoid. CONCLUSION: The BIOCHIP Mosaic 7 is a rapid, reliable diagnostic investigation in pemphigus and bullous pemphigoid. Results indicate it is comparable to the EUROIMMUN Dermatology Profile ELISA, whilst also providing additional testing with salt split skin, on one field.