Updates in SJS/TEN: collaboration, innovation, and community.

Stevens-Johnson Syndrome/Toxic Epidermal Necrolysis (SJS/TEN) is a predominantly drug-induced disease, with a mortality rate of 15-20%, that engages the expertise of multiple disciplines: dermatology, allergy, immunology, clinical pharmacology, burn surgery, ophthalmology, urogynecology, and psychiatry. SJS/TEN has an incidence of 1-5/million persons per year in the United States, with even higher rates globally. One of the challenges of SJS/TEN has been developing the research infrastructure and coordination to answer questions capable of transforming clinical care and leading to improved patient outcomes. SJS/TEN 2021, the third research meeting of its kind, was held as a virtual meeting on August 28-29, 2021. The meeting brought together 428 international scientists, in addition to a community of 140 SJS/TEN survivors and family members. The goal of the meeting was to brainstorm strategies to support the continued growth of an international SJS/TEN research network, bridging science and the community. The community workshop section of the meeting focused on eight primary themes: mental health, eye care, SJS/TEN in children, non-drug induced SJS/TEN, long-term health complications, new advances in mechanisms and basic science, managing long-term scarring, considerations for skin of color, and COVID-19 vaccines. The meeting featured several important updates and identified areas of unmet research and clinical need that will be highlighted in this white paper.

Development of a Skin-Directed Scoring System for Stevens-Johnson Syndrome and Epidermal Necrolysis: A Delphi Consensus Exercise.

Importance: Scoring systems for Stevens-Johnson syndrome and epidermal necrolysis (EN) only estimate patient prognosis and are weighted toward comorbidities and systemic features; morphologic terminology for EN lesions is inconsistent. Objectives: To establish consensus among expert dermatologists on EN terminology, morphologic progression, and most-affected sites, and to build a framework for developing a skin-directed scoring system for EN. Evidence Review: A Delphi consensus using the RAND/UCLA appropriateness criteria was initiated with a core group from the Society of Dermatology Hospitalists to establish agreement on the optimal design for an EN cutaneous scoring instrument, terminology, morphologic traits, and sites of involvement. Findings: In round 1, the 54 participating dermatology hospitalists reached consensus on all 49 statements (30 appropriate, 3 inappropriate, 16 uncertain). In round 2, they agreed on another 15 statements (8 appropriate, 7 uncertain). There was consistent agreement on the need for a skin-specific instrument; on the most-often affected skin sites (head and neck, chest, upper back, ocular mucosa, oral mucosa); and that blanching erythema, dusky erythema, targetoid erythema, vesicles/bullae, desquamation, and erosions comprise the morphologic traits of EN and can be consistently differentiated. Conclusions and Relevance: This consensus exercise confirmed the need for an EN skin-directed scoring system, nomenclature, and differentiation of specific morphologic traits, and identified the sites most affected. It also established a baseline consensus for a standardized EN instrument with consistent terminology.

Heterologous effect of influenza vaccination on molluscum contagiosum infection; a case report of siblings.

BACKGROUND: Molluscum contagiosum virus (MCV) is a benign, common cutaneous infection predominantly affecting the younger pediatric population. Traditional treatments may be time consuming with variable efficacy. Time to spontaneous resolution is variable and treatment is often sought to shorten duration of infection, prevent further autoinoculation, prevent infectious spread to others and treat cosmetic intolerability. CASE PRESENTATION: We present the case of two patients with complete, simultaneous clearance of their molluscum contagiosum infections after receiving a routine 2018 quadrivalent influenza vaccination. Neither patient has had recurrence of molluscum contagiosum or permanent scarring. We review trials of intralesional immunotherapy in treatment of cutaneous infections to theorize the mechanism of MCV infection clearance post influenza vaccination. CONCLUSION: We propose a delayed-type hypersensitivity reaction was induced as a heterologous effect of the influenza vaccination, similar to that seen in current immunotherapy treatments. This is the first reported case of MCV-directed immune reaction with infection clearance after influenza vaccination.

Society of Dermatology Hospitalists supportive care guidelines for the management of Stevens-Johnson syndrome/toxic epidermal necrolysis in adults.

Stevens-Johnson syndrome (SJS) and toxic epidermal necrolysis (TEN) are life-threatening conditions with high morbidity and mortality. Supportive care management of SJS/TEN is highly variable. A systematic review of the literature was performed by dermatologists, ophthalmologists, intensivists, and gynecologists with expertise in SJS/TEN to generate statements for supportive care guideline development. Members of the Society of Dermatology Hospitalists with expertise in SJS/TEN were invited to participate in a modified, online Delphi-consensus. Participants were administered 9-point Likert scale questionnaires regarding 135 statements. The RAND/UCLA Appropriateness Method was used to evaluate and select proposed statements for guideline inclusion; statements with median ratings of 6.5 to 9 and a disagreement index of ≤1 were included in the guideline. For the final round, the guidelines were appraised by all of the participants. Included are an evidence-based discussion and recommendations for hospital setting and care team, wound care, ocular care, oral care, urogenital care, pain management, infection surveillance, fluid and electrolyte management, nutrition and stress ulcer prophylaxis, airway management, and anticoagulation in adult patients with SJS/TEN.

SJS/TEN 2019: From science to translation.

Stevens-Johnson syndrome and toxic epidermal necrolysis (SJS/TEN) are potentially life-threatening, immune-mediated adverse reactions characterized by widespread erythema, epidermal necrosis, and detachment of skin and mucosa. Efforts to grow and develop functional international collaborations and a multidisciplinary interactive network focusing on SJS/TEN as an uncommon but high burden disease will be necessary to improve efforts in prevention, early diagnosis and improved acute and long-term management. SJS/TEN 2019: From Science to Translation was a 1.5-day scientific program held April 26-27, 2019, in Vancouver, Canada. The meeting successfully engaged clinicians, researchers, and patients and conducted many productive discussions on research and patient care needs.

Temporal shifts in the collective dermatologic microbiome of military trainees.

BACKGROUND:  New military members undergo a highly-regimented 7-week training course during which trainees live and work within the same group of approximately 50 subjects for nearly 24 hours a day. This creates an optimal environment for assessing the impact of communal living on the collective skin microbiome. PURPOSE: The objective of this pilot study was to investigate dynamic changes of the skin microbiome in basic military trainees (BMT), in light of the unique environmental influences faced by this population. PATIENTS AND METHODS:  We evaluated collective changes in the skin microbiome of normal healthy adult basic trainees in response to communal living and universal Group A Strep prophylaxis with penicillin over the course of their initial 7-week training course. Samples from 10 flights of trainees were collected by swabbing upon arrival at Lackland AFB for their training (week 0) which is prior to prophylaxis with penicillin, at the 4 week point, and at the conclusion of their 7-week course of basic military training. Three separate high-throughput sequencing platforms and three bioinformatic pipeline analysis tools were utilized to assess the data. RESULTS: At all three time points we found that the top three bacterial genus identified were Propionibacterium, Staphylococcus, and Corynebacterium. We detected a community membership difference between the initial week 0 samples and the week 4 and 7 samples. A strong inverse correlation between Propionibacterium and Staphylococcus was noted with Propionibacterium being high at week 0 and much lower at weeks 4 and 7; conversely, Staphylococcus was low at week 0 and higher at weeks 4 and 7, this relationship was noted in both the individual and collective specimens. CONCLUSION: The collective dermatologic microbiome in the military trainee population examined exhibited a relative increase in Staphylococcus and Corynebacterium abundance coupled with a relative decrease in Propionibacterium abundance in this observational pilot study. Additional studies are needed to further assess the causal impact of communal living and widespread penicillin chemoprophylaxis.

Immune-mediated adverse reactions to vaccines.

Vaccination continues to be the single most important and successful public health intervention, due to its prevention of morbidity and mortality from prevalent infectious diseases. Severe immunologically mediated reactions are rare and less common with the vaccine than the true infection. However, these events can cause public fearfulness and loss of confidence in the safety of vaccination. In this paper, we perform a systematic literature search and narrative review of immune-mediated vaccine adverse events and their known and proposed mechanisms, and outline directions for future research. Improving our knowledge base of severe immunologically mediated vaccine reactions and their management drives better vaccine safety and efficacy outcomes.

Efficacy of Laser Resurfacing and Facial Plastic Surgery Using Age, Glogau, and Fitzpatrick Rating.

BACKGROUND: To assess clinical outcomes based on established rating scales in patients who underwent treatment for rhytids using laser resurfacing with and without facial plastic surgery. METHODS: Retrospective case review of 48 patients treated by the senior author (J.E.B) between 2009 and 2016. Three reviewers assigned ratings to a total of 48 patients using estimated age and Fitzpatrick, Modified Fitzpatrick, and Glogau scales. Reviewers were blinded to patient demographics and before and after photographs. Patients elected to receive laser-only treatment or combination laser plus facial plastic surgery. Participants included forty-eight patients were selected on the basis that they had either laser treatment alone or laser plus facial plastic surgery and pre- and postoperative photographs. RESULTS: Patients with higher Fitzpatrick scores had a greater reduction in Glogau score (ß = 1.66; SE = 0.59; P < 0.01). With respect to modified Fitzpatrick scores after surgery, patients with higher Glogau scores of 3 or 4 before surgery (P < 0.01) had higher scores after surgery ((ß = 0.07; SE = 0.02; P < 0.01). For estimated age, the average change was -1.7 years after laser resurfacing (P = 0.038; 95% CI, 2.96-3.06 years) and -2.07 years when combined with surgery (P = 0.01; 95% CI, 2.89-3.19 years). CONCLUSIONS: Patients with Fitzpatrick scores of 3, 4, 5, younger patients, and those with less rhytids before surgery tended to have lower Glogau scores after surgery. These findings provide insight on an approach to treating ethnic skin and aging face concerns.

Preliminary Efficacy Testing of the Disinfectant MicrobeCare XLP for Potential Use in Military Operational Environments.

Introduction: A safe, easy-to-use, permanently bonded antiseptic that does not require post-exposure bioload reduction but maintains effectiveness over time would have far-reaching implications across multiple industries. Health care is one such arena, particularly in austere military settings where resources are at a premium. MicrobeCare XLP (MicrobeCare, Buffalo Grove, IL, USA) is a commercially available spray-on agent that is advertised to covalently bond to surfaces and provide a long-lasting antimicrobial coating inhospitable to >99.99% of surface microorganisms. A pilot study was devised to gather baseline data regarding product efficacy and laboratory parameters before consideration of extended investigations and military utilization. The product manufacturer recommends bioload reductions before product application, following product application, and after each pathogenic exposure. To investigate the product's efficacy in circumstances more closely simulating a military operational setting in which post-pathogenic exposure bioload reduction would not be possible, this step was deliberately excluded from the test sequences. Materials and Methods: Using autoclaved surgical forceps, growth of Staphylococcus aureus and Acinetobacter baumannii was evaluated in a controlled manner under multiple conditions. Test variations included duration of submersion in the MicrobeCare XLP solution and air-drying and a second autoclave sterilization. Control and treated forceps were exposed to a bacterial suspension and air-dried before being submerged in sterile saline and vortex mixed. The saline solution was serially diluted and plated on tryptic soy agar (TSA) II plates. Plates were incubated for 24 h and bacterial colony-forming units (CFU)/mL were counted. Results: Statistical significance was defined according to the American Society for Testing and Materials (ASTM) International passing criteria of 3 Log10 or 99.9% reduction of microorganisms. Additionally, p-values were calculated using two-tailed unpaired two-sample t-tests with unequal variance with a threshold of 0.05. In the S. aureus tests, none of the reduction calculations met the ASTM International passing criteria. In addition, the difference between the means of the colony counts in the MicrobeCare XLP-treated forceps and untreated control forceps was not statistically significant (p-value 0.109). Conversely, in the A. baumannii tests, each of the percent reduction calculations met the ASTM International passing criteria; the difference between the means of the colony counts in the treatment and control groups was statistically significant (p-value 0.008). Conclusion: In these independent tests, MicrobeCare XLP effectively prevented growth of A. baumannii but had unpredictable results suppressing S. aureus. These results may relate to inherent properties of the bacteria or autoclave exposure, although the manufacturer asserts that the coating withstands such degradation. Additional testing could be performed using a broader range of microorganisms and exposure to varying conditions including other sterilization methods.

Segmental distribution of nodules on trunk.

A 70-year-old Caucasian man presented with a longstanding history of numerous nontender, fleshy, skin-colored papules on his trunk, ranging from 3 to 8 mm in size. They were noted incidentally during an examination of unrelated nonhealing lesions on the patient's left cheek. He said the lesions on his trunk first appeared when he was 28 years old and had continued to grow in size and number. The patient said his son had at least one similar lesion on his upper back, but otherwise there was no family history of these lesions. A biopsy was performed on one of the nodules. WHAT IS YOUR DIAGNOSIS? HOW WOULD YOU TREAT THIS PATIENT?

CYP2C19*2 status in patients with Stevens-Johnson syndrome and toxic epidermal necrolysis.

PURPOSE: Genetic polymorphisms have been linked to an increased predisposition to developing certain diseases. For example, patients of Han-Chinese descent carrying the HLA-B*1502 allele are at an increased risk of developing Stevens-Johnson syndrome and toxic epidermal necrolysis (SJS/TEN) if given carbamazepine. Given the complexity of in vivo drug metabolism, it is plausible that the activity of enzyme systems unrelated to specific drug metabolism may be important. Although multiple biomarkers have been identified in unique ethnic groups, there has yet to be a study investigating the presence of the slow metabolizing allele of CYP2C19, denoted CYP2C19*2, in diverse groups and the risk of developing SJS/TEN. PATIENTS AND METHODS: This study looked into the carrier status of CYP2C19*2, a poor metabolizing variant of CYP2C19, in patients diagnosed with SJS/TEN. We looked at its status in our series as a whole and when patients were divided by ethnicity. Genomic DNA was extracted from formalin-fixed paraffin-embedded tissue of patients with biopsy-proven SJS/TEN and real-time polymerase chain reaction was used to assess for the presence of CYP2C19*2. RESULTS: CYP2C19*2 status was determined in 47 patients. Twenty-nine of these 47 patients had a single medication implicated as causing their disease, and eight of these patients were heterozygous or homozygous for CYP2C19*2. There was insufficient evidence to conclude that the presence of CYP2C19*2 is an independent predictor of risk for developing SJS/TEN in our series as a whole. This analysis also confirmed that the frequency of the CYP2C19*2 polymorphism within the different ethnicities in our series did not vary statistically from reported ethnic rates. CONCLUSION: Our study was unable to show a relationship between CYP2C19*2 status and predisposition toward SJS/TEN. We had a heterogeneous population, making it difficult to control for possible confounding factors.

Novel R634W c-kit mutation identified in familial mastocytosis.

Familial mastocytosis is a well-documented but rare entity, with fewer than 100 cases reported in the literature. The etiology has most commonly been linked to activating c-kit mutations, with several mutations reported to date. We present a novel familial mastocytosis-associated c-kit mutation (R634W) in three siblings with urticaria pigmentosa. This mutation has been previously described in mucosal melanoma, chronic myelomonocytic leukemia, and acute myeloid leukemia. Because this is a rare mutation, it is unclear whether screening for other disease states associated with the mutation would be of benefit.

Syphilis: a reemerging infection.

Rates of primary and secondary syphilis have increased in the past decade, warranting renewed attention to the diagnosis and treatment of this disease. Men who have sex with men are particularly affected; however, increases in infection rates have also been noted in women, as well as in all age groups and ethnicities. Physicians need to vigilantly screen high-risk patients. The concurrent rise in congenital syphilis also requires special attention and reemphasizes the need for continued early prenatal care and syphilis screening for all pregnant women. Syphilis infection in patients coinfected with human immunodeficiency virus has also become more common. New experimental diagnostic approaches, including using the B cell chemoattractant chemokine (CXC motif) ligand 13 as a cerebrospinal fluid marker, may help identify suspected neurosyphilis cases. Additionally, point-of-care immunochromatographic strip testing has been suggested for screening high-risk populations in developing countries. Nontreponemal screening tests followed by treponemal confirmatory tests continue to be standard diagnostics; however, interpreting false-negative and false-positive test results, and identifying serofast reactions, can be challenging. Although doxycycline, tetracycline, ceftriaxone, and azithromycin have been used to successfully treat syphilis, penicillin remains the drug of choice in all stages of infection and is the therapy recommended by the Centers for Disease Control and Prevention. Close follow-up is necessary to ensure treatment success.

Pruritic rash on trunk.

The patient had been treated with topical antifungals and steroids without relief, but a more detailed history suggested a serious infectious etiology.