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.

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.

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.

Progressive overgrowth of the cerebriform connective tissue nevus in patients with Proteus syndrome.

BACKGROUND: Proteus syndrome is a rare overgrowth disorder that almost always affects the skin. OBJECTIVE: Our purpose was to evaluate progression of skin lesions in patients with Proteus syndrome. METHODS: Skin findings were documented in 36 patients with Proteus syndrome. Progression of skin lesions in 16 of these patients was assessed by comparing photographs obtained on repeated visits for an average total duration of 53 months. RESULTS: The skin lesion most characteristic of Proteus syndrome, the cerebriform connective tissue nevus, showed progression in 13 children but not in 3 adults. The cerebriform connective tissue nevus progressed by expansion into previously uninvolved skin, increased thickness, and development of new lesions. Lipomas increased in size, number, or both in 8 of 10 children with lipomas. In contrast, epidermal nevi and vascular malformations generally did not spread or increase in number. LIMITATIONS: Only 3 adults with Proteus syndrome were evaluated longitudinally. CONCLUSION: The cerebriform connective tissue nevus in Proteus syndrome grows throughout childhood but tends to remain stable in adulthood.

Adverse events following smallpox vaccination with ACAM2000 in a military population.

BACKGROUND: Generalized vaccinia and benign exanthems are 2 adverse events that have been associated with the smallpox vaccination. Accurate incidence and prevalence rates of each are not readily available, but these events are thought to be uncommon. To our knowledge, this is the first case series to provide clinical as well as pathologic descriptions of multiple papulovesicular eruptions occurring after receiving the second-generation smallpox vaccine, ACAM2000 (Acambis, Canton, Massachusetts), among a vaccinia-naïve military population. In addition, we report the first confirmed case, to our knowledge, of generalized vaccinia following administration of the ACAM2000 vaccine. OBSERVATIONS: All patients received primary smallpox immunization as well as 1 to 3 concurrent or near-concurrent (within the preceding 21 days) immunizations for typhoid, anthrax, hepatitis B, and/or seasonal influenza. One patient presented with a flulike prodrome and diffuse vesiclopustules covering the face, neck, chest, back, and upper and lower extremities. Vaccinia polymerase chain reaction confirmed generalized vaccinia. The remaining 7 patients presented with unusual, painful, and pruritic papulovesicular eruptions occurring on the extensor surfaces of their upper and lower extremities without systemic symptoms. Histologic findings revealed 2 general patterns, including a dermal hypersensitivity reaction with lymphocytic vasculitis and a vesicular spongiotic dermatitis with eosinophils. CONCLUSIONS: We present the first confirmed case of generalized vaccinia following immunization with the second-generation smallpox vaccine ACAM2000. In addition, we describe 7 cases of benign, acral, papulovesicular eruptions thought to be associated with ACAM2000 administration. Further research is needed to discern the pathogenesis of these benign eruptions as well as their incidence and prevalence and that of generalized vaccinia with ACAM2000.

Primary cutaneous nodular amyloidosis: case report and review of the literature.

Primary cutaneous nodular amyloidosis (PCNA) is a rare form of primary cutaneous amyloidosis. It presents as waxy yellow-red nodules that are located preferentially on the lower extremities, face, scalp, and genitals. Recognition of this condition is of particular importance, as primary systemic amyloidosis can have a similar cutaneous presentation. We report a case of PCNA in a 52-year-old woman with systemic lupus erythematosus (SLE) and Sjögren syndrome (SS). We discuss the need to evaluate for systemic disease and provide a concise review of the literature focusing on clinical presentation, disease associations, and management.

Pulmonary cutaneous metastasis: a case report and review of common cutaneous metastases.

The literature on cutaneous metastatic disease can be difficult to interpret because of inconsistent study design and analysis among authors. Furthermore, one should be careful when reviewing the statistics in the literature, as reported patient populations tend to vary and are not representative of the whole population. However, certain trends are notable and should be reported. Diagnosis of cutaneous metastatic disease carries a grave prognosis. We describe a patient with pulmonary cutaneous metastasis and provide a review of the literature on nonmelanomatous solid tumor malignancies that most commonly have cutaneous metastases. The review will focus on epidemiology, clinical presentation, histology and immunohistochemical staining, and prognosis and management. The most common cutaneous metastasizing carcinomas--breast, lung, and colorectal cancer--also are discussed.