The Impact of Lebrikizumab on Vaccine-Induced Immune Responses: Results from a Phase 3 Study in Adult Patients with Moderate-to-Severe Atopic Dermatitis.

INTRODUCTION: Lebrikizumab, a high-affinity IgG4 monoclonal antibody that selectively inhibits interleukin-13 with high binding affinity and slow dissociation rate, prevents the formation of the interleukin-4Rα/interleukin-13Rα1 heterodimer receptor signaling complex. Here we report the impact of lebrikizumab on responses to two non-live vaccines in adult patients with moderate-to-severe atopic dermatitis (AD). METHODS: ADopt-VA (NCT04626297) was a double-blind, placebo-controlled, parallel-group, 16-week, phase 3 randomized study to assess the impact of lebrikizumab treatment on non-live vaccine immune responses, and efficacy and safety of lebrikizumab compared with placebo. Eligible patients included adults from 18 to 55 years of age with moderate-to-severe chronic AD who were randomly assigned 1:1 to lebrikizumab 250 mg every 2 weeks or placebo and stratified according to disease severity. The primary endpoints were the development of a booster response to tetanus toxoid and a positive antibody response to meningococcal conjugate vaccine (MCV), 4 weeks after administration of the corresponding vaccine. RESULTS: At week 16, 73.6% of patients in the lebrikizumab group (n = 78/106) achieved Tdap booster response compared with 73.4% of patients in the placebo group (n = 58/79). MCV vaccine response was observed in 86.9% of patients in the lebrikizumab group (n = 86/99) and 75.0% of patients in the placebo group (n = 60/80). At week 16, IGA 0,1 with ≥ 2-point improvement from baseline was achieved by 40.6% (n = 51/125) of patients treated with lebrikizumab and 18.9% (n = 23/122) of patients who received placebo (p < 0.001). There was a higher proportion of patients achieving EASI 75 at week 16 in the lebrikizumab-treated patients (58.0%, n = 72/125) compared with placebo (32.7%, n = 40/122, p < 0.001). CONCLUSIONS: Treatment with lebrikizumab did not impact response to non-live vaccines Tdap and MCV in this study. Lebrikizumab treatment had a significant degree of efficacy compared to placebo across multiple endpoints. TRIAL REGISTRATION: ClinicalTrials.gov identifier NCT04626297.

A clinical impact study of dermatologists' use of diagnostic gene expression profile testing to guide patient management.

Aim: Cutaneous melanocytic neoplasms with diagnostic and/or clinical ambiguity pose patient management challenges. Methods: Six randomized case scenarios with diagnostic/clinical uncertainty were described with/without a benign or malignant diagnostic gene expression profile (GEP) result. Results: Clinical impact was assessed by reporting the mean increase/decrease of management changes normalized to baseline (n = 32 dermatologists). Benign GEP results prompted clinicians to decrease surgical margins (84.2%). Malignant GEP results escalated surgical excision recommendations (100%). A majority (72.2%) reduced and nearly all (98.9%) increased follow-up frequency for benign or malignant GEP results, respectively. There was an overall increase in management plan confidence with GEP results. Conclusion: Diagnostic GEP tests help guide clinical decision-making in a variety of diagnostically ambiguous or clinicopathologically discordant scenarios.

Dermatologists' use of diagnostic gene expression profiles for personalized patient care. When your doctor takes a piece of a mole, that mole is looked at under the microscope by a pathologist. The pathologist is responsible for figuring out if the mole is dangerous or not. Dangerous moles are removed with surgery to make sure all the dangerous tissue is gone. Moles without a health threat are left alone. Sometimes figuring out how dangerous a mole is is difficult. The pathologist may not provide the doctor with enough information for them to know how to treat your mole. There is a test that can provide information on whether your mole is unsafe. This test is called diagnostic gene expression profiling or GEP. In this study, GEP is used to help doctors figure out how to treat a mole and how often the patient should be seen in the office for skin checks. With GEP, important changes in patient treatment were identified. These include the need for an additional surgery, how much healthy tissue should be removed during surgery and how often the patient should be seen in the office. For suspicious moles where the pathology report is unclear, GEP can provide information that leads to more appropriate and personalized patient care.

Ancillary diagnostic gene expression profile testing for ambiguous cutaneous melanocytic lesions helps optimize dermatologist recommendations for excision margin and follow-up.

Efficacy and complication rates of full-thickness skin graft repair of lower extremity wounds after Mohs micrographic surgery.

BACKGROUND: Repair of below-the-knee lower extremity defects after Mohs micrographic surgery (MMS) that are not amenable to primary closure can be challenging given the high propensity for complications. No criterion standard exists for management of these wounds, but secondary-intention healing, partial- and full-thickness skin grafts (FTSGs), and various flaps are possible options to manage these wounds. Few data exist on the efficacy of FTSG repairs for lower extremity wounds. OBJECTIVES: Assess the efficacy and complications rates of FTSG repairs for lower extremity wounds after MMS. METHODS: This was a retrospective review of 80 FTSG repairs performed after MMS. Data were derived from 45 cases at Beth Israel Deaconess Medical Center and 35 cases at University of California, San Diego (UCSD) Medical Center. RESULTS: Seventy-two of 80 cases (90%) had full graft survival, six (7.5%) had partial failure, and two (2.5%) had complete failure. In the cases where grafts had failed, wounds healed by secondary intention without further complications. Other complications included infections in nine (11%) cases and hematoma formation in two (2.5%). CONCLUSION: FTSG is a consistent and safe reconstructive option for the management of lower extremity wounds after MMS.

Basal cell carcinoma on the ear is more likely to be of an aggressive phenotype in both men and women.

BACKGROUND: We observed that basal cell carcinoma (BCC) on the ear demonstrates a more aggressive phenotype compared with other body sites. OBJECTIVE: We sought to determine if it is statistically significant that BCC on the ear is more aggressive. METHODS: We queried our 2009 database for all BCCs biopsied from the ear. Multiple data points, including tumor subtype and risk level, were analyzed for 100 BCCs on the ear and 100 BCCs on the cheek. RESULTS: BCC on the ear was diagnosed 471 times. Of the first 100 occurrences of BCC on the ear, 57% were high risk compared with 38% on the cheek (odds ratio 2.16, 95% confidence interval 1.23-3.81, P = .01). Men were more likely to have BCC on the ear: 79% male on the ear and 53% male on the cheek (P < .001). However, BCC on the ear in women is also more likely to be aggressive (57%, 12 of 21). LIMITATIONS: The data were retrieved from a single year at our institution, and there could potentially be regional bias given that the population of data is from a single institution. Many of the specimens we evaluate are reviewed in consultation and may thus represent a selection bias. CONCLUSION: BCC on the ear presents as an aggressive phenotype in the majority of cases for both men and women, and it occurs much more frequently in men. Knowledge of this information can help guide physicians and ensure that these tumors are adequately biopsied and treated.

Expanded evidence that the 31-gene expression profile test provides clinical utility for melanoma management in a multicenter study.

OBJECTIVE: National Comprehensive Cancer Network (NCCN) guidelines for cutaneous melanoma (CM) recommend physicians consider increased surveillance for patients who typically have lower melanoma survival rates (stages IIB-IV as determined by the American Joint Committee on Cancer (AJCC), 8th edition). However, up to 15% of patients identified as having a low recurrence risk (stages I-IIA) experience disease recurrence, and some patients identified as having a high recurrence risk will not experience any recurrence. The 31-gene expression profile test (31-GEP) stratifies patient recurrence risk into low (Class 1) and high (Class 2) and has demonstrated risk-appropriate impact on disease management and clinical decisions. METHODS: Five-year plans for lab work, frequency of clinical visits, and imaging pre- and post-31-GEP test results were assessed for a cohort of 509 stage I-III patients following an interim subset analysis of 247 patients. RESULTS: After receiving 31-GEP results, 50.6% of patients had a change in management plans in at least one of the following categories-clinical visits, lab work, or surveillance imaging. The changes aligned with the risk predicted by the 31-GEP for 76.1% of patients with a Class 1 result and 78.7% of patients with a Class 2 result. A Class 1 31-GEP result was associated with changes toward low-intensity management recommendations, while a Class 2 result was associated with changes toward high-intensity management recommendations. CONCLUSION: The 31-GEP can stratify patient recurrence risk in patients with CM, and clinicians understand and apply the prognostic ability of the 31-GEP test to alter patient management in risk-appropriate directions.

When caught early, cancer of the skin can usually be removed, and patients have excellent chances of survival. However, some patients will have their cancer come back or spread to a new location in their body.The 31-gene expression profile (GEP) test measures the expression levels of 31 genes from an individual patient's tumor. A proprietary formula uses this information to identify the risk of recurrence or spread as low risk (Class 1) or high risk (Class 2). Cancers with low-risk 31-GEP scores have a lower chance of cancer recurrence or spread than patients with a high-risk score.In this study, we wanted to determine if doctors treated patients with low-risk scores differently from patients with high-risk scores. We found that doctors changed approximately half of patient treatment plans (doctor visits, lab work, or imaging to see if the cancer has come back) after learning the 31-GEP test results. Doctors usually planned less frequent follow-up visits for Class 1 results and more frequent follow up for Class 2 results.This study found doctors understand and make changes to their treatment plans based on the patient's 31-GEP test result.

Gnathostomiasis in a patient who frequently consumes sushi.

A 45-year-old woman presented for evaluation of a solitary pruritic nodule on the abdomen that suddenly appeared 3 weeks before. She was healthy without a significant medical history, travel history, exposures, medications, or pets. She reported that she consumed sushi at least weekly in the city of San Francisco. A punch biopsy revealed a superficial and deep perivascular and interstitial infiltrates consisting of lymphocytes, plasma cells, and many eosinophils. Most notably, there was a parasite centered in the reticular dermis with prominent lateral chords, a well-developed muscular esophagus, and an intestine that contained a brush border and multinucleate cells. Evaluation of these histological sections by the Centers for Disease Control and Prevention determined the parasite to be a nematode of the genus Gnathostoma. The patient underwent a systemic work-up for gnathostomiasis, including imaging, and no other abnormalities were found. She completed a 3-week course of albendazole and has remained asymptomatic since the biopsy of her abdominal lesion. Although gnathostomiasis is often a systemic illness, this patient did well with apparently only localized cutaneous disease. Gnathostomiasis should be considered in patients who present with nonspecific papules and nodules, especially when there is a history of frequent consumption of raw fish.

Infectious granulomatous dermatitis associated with Rothia mucilaginosa bacteremia: A case report.

Infections with rare pathogens are being recognized with increasing frequency in severely immunocompromised patients. As a result of these patients' underlying compromised defenses and susceptibility to atypical organisms, tissue biopsies from patients within this population may demonstrate nonclassical histopathological findings. Here, we describe an unusual granulomatous reaction to gram-positive cocci in the skin of a 52-year-old man undergoing salvage chemotherapy for acute myeloid leukemia. The patient presented with a papular eruption on the arms, trunk, and face and fever; concomitant blood cultures were positive for Rothia mucilaginosa and Streptococcus salivarius. Histologic evaluation revealed a granulomatous dermatitis associated with numerous small, round, predominantly intracellular bacteria. Classically, cutaneous infiltrates associated with coccoid bacterial infections are suppurative and not granulomatous. The intracellular organisms stained positive for Gram, periodic acid-Schiff, and Grocott methenamine silver stains, suggestive of R. mucilaginosa. Rothia mucilaginosa, a component of the oral flora, was first reported as a human pathogen in 1978. Although the majority of cases in the literature have described R. mucilaginosa bacteremia, other reported manifestations include meningitis, endocarditis, pneumonia, osteomyelitis, and peritonitis. To our knowledge, however, only 1 prior report has described a cutaneous manifestation of R. mucilaginosa septicemia, which occurred in a patient with neutropenia. This is the second reported case of an infectious granulomatous dermatitis associated with R. mucilaginosa bacteremia and raises awareness of this unusual histopathological presentation in the setting of a bacterial infection affecting the skin.

Lues maligna in early HIV infection case report and review of the literature.

BACKGROUND: Lues maligna (also known as malignant syphilis or ulceronodular syphilis) is a rare dermatologic manifestation of syphilis more commonly seen in patients with HIV infection. The classic lesion of lues maligna is an oval, papulopustular skin lesion with well demarcated borders sometimes covered with a lamellar crust, but myriad clinical presentations of this disease also exist. GOALS: To report a presentation of lues maligna in a patient with probable early HIV infection, emphasizing the diagnostic criteria and clinical manifestations of lues maligna. STUDY DESIGN: Case report of lues maligna in a patient with probable early HIV infection. CONCLUSIONS: As syphilis becomes more common in many developed regions, it is important to recognize even atypical presentations of this clinical entity, especially among individuals who have unrecognized or early HIV infection.

Uncombable hair syndrome.

A 4-year-old boy was noted to have unruly, spangled hair, which could not be combed flat. His mother reported that his hair had always had that texture and that it seemed to grow slowly. A hair pull test demonstrated that hairs could not be easily extracted, and light microscopic examination of the hair revealed pathognomonic characteristics of uncombable hair syndrome, including a triangular cross-sectional shape and canal-like longitudinal depressions.

Lupus erythematosus tumidus of the scalp masquerading as alopecia areata.

Lupus erythematosus tumidus (LET) is a unique subset of chronic cutaneous lupus erythematosus (CCLE) that generally presents as urticarialike papules and plaques with induration and erythema on the face, trunk, and upper extremities. Lesions rarely present on the scalp or below the waist. We report a unique case of LET on the scalp of a woman that presented clinically as alopecia areata. Resistance to the standard treatment for alopecia areata prompted a biopsy that proved the diagnosis.

PET/CT imaging of squamoid eccrine ductal carcinoma.

Squamoid eccrine ductal carcinoma is an extremely uncommon type of eccrine carcinoma (EC). An important distinguishing feature of EC is potential for metastasis. Eccrine carcinoma has been reported to metastasize in up to 50% of cases. Despite tumor aggressivity, no recommendations for staging exist. We present the case of a 91-year-old woman with a lesion involving the left index finger confirmed to be squamoid eccrine ductal carcinoma by dermatopathologic evaluation. 18F-FDG PET/CT images revealed widespread multifocal FDG-avid metastatic disease. Although rare, staging of EC with 18F-FDG PET/CT imaging of the entire body is indicated.

The RAS/mitogen activated protein (MAP) kinase pathway in melanoma biology and therapeutics.

An effective treatment for metastatic melanoma remains one of the most elusive goals in all of oncology. Several generations of therapeutic trials have yet to yield any agents that can significantly prolong survival for widespread disease. Despite this disheartening history, our understanding of the biology and molecular genetics of melanoma hold the promise of a new era of molecular targets. One pathway that appears to be universally activated in and critically needed for melanoma growth is the Ras/mitogen activated protein (MAP) kinase signaling cascade. Since the enzymatic functions of the signaling partners are well characterized, this pathway offers many potential "druggable" candidates including Braf, Mek and Ras itself. In this review, we describe this pathway in the context of melanoma tumorigenesis and discuss some of the current relevant pharmacologic treatments and clinical trials.