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Background Ibrutinib is an oral inhibitor of Bruton’s tyrosine kinase (BTK) that is FDA-approved for several lymphoproliferative disorders and chronic GVHD. Objective To characterize cutaneous eruptions arising from ibrutinib and highlight overlap with epidermal growth factor receptor inhibitor (EGFRi)-induced dermatologic adverse events (dAEs). Methods Single-center retrospective cohort of patients referred to the Skin Toxicities Program for management of cutaneous eruptions while taking ibrutinib. Results Among 19 patients, cutaneous eruptions manifested as facial-predominant papulopustular eruptions, petechiae or ecchymoses, photosensitivity, panniculitis, xerosis, and clinical staphylococcal overgrowth. The majority of patients were able to continue ibrutinib therapy with focused management of their cutaneous toxicities. Limitations This study represents cases at a single tertiary care center and is limited to patients referred for toxicity. Conclusions With the exception of petechiae, the cutaneous toxicities of ibrutinib overlap with those associated with selective EGFR inhibitors. We observed that these reactions can be successfully managed using approaches for EGFR inhibitor-induced cutaneous adverse events.

TABLE OF CONTENTS GENERAL INFORMATION TITLE AUTHORS AND BEST CONTACT LICENSES USEFUL LINKS DATE OF DATA COLLECTION FILE ORGANIZATION FUNDING ---- Release Notes:This is a pre-publication placeholder for primary data release for the publication listed below. In common with GEO, PRIDE, and other data repositories, this will be populated with final data following peer review. ---- GENERAL INFORMATION Publication Title:Immune Profiling of Dermatologic Adverse Events from Checkpoint Blockade using Tissue Cyclic Immunofluorescence Authors:Zoltan Maliga, Daniel Y. Kim, Ai-Tram N. Bui, Jia-Ren Lin, Anna K. Dewan, George G. Murphy, Ajit J. Nirmal, Christine G. Lian, Peter K. Sorger, Nicole R. LeBoeuf Contact Information Nicole LeBoeuf, MD, MPH Vice Chair of Dermatology,Dana-FarberCancer Institute,; Chief, Division of Oncodermatology, Brigham and Women's Hospital; Clinical Director, Center for Cutaneous Oncology, Dana-Farber/Brigham Cancer Center, HarvardMedical School nleboeuf@partners.org Publications that cite or use the data:** Maliga, M, Kim, DY, Tram, B, Lin, JR, Dewan, AK, Jadeja, S, Murphy, G, Nirmal, AJ, Lian, C, Sorger, PK, LeBoeuf, NR. Immune Profiling of Dermatologic Adverse Events from Checkpoint Blockade using Tissue Cyclic Immunofluorescence.https://doi.org/10.1101/2023.04.03.535435 Licenses/restrictions placed on the data:CC BYhttps://creativecommons.org/licenses/by/4.0/ ---- FILE ORGANIZATION FILE TYPES/SUMMARY:Each folder corresponds to a patient sample (N). The following files are available for each patient and are located on [Synapse/AWS/Etc]. File Type Description Location N.ome.tif Stitched multiplex CyCIF image pyramid in ome.tif format AWS N_IHC.ome.tiff Immunohistochemistry stained image of serial FFPE tissue section in .ome.tiff format AWS N_HE.ome.tiff Hematoxylin and eosin stained image of FFPE tissue section in .ome.tiff format AWS markers.csv List of all markers in ome.tif image Synapse N_Quantification.csv Single-cell feature table, including intensity data for all channels Synapse segmentation/ Folder of segmentation maps for tissue image in .tif format AWS Synapse Library:Edit this to link directly to your public Synapse Library Free account registration is required to download files from Synapse. Images and metadata are available in the bucket at the following AWS location:[ADD BUCKET DETAILS] To browse and download the data use either a graphical file transfer application that supports S3 such asCyberDuck, or theAWS CLI tools. A graphical tool may be more convenient but the CLI tools will likely offer higher download speeds. FILE LIST N.ome.tif LSP Slide ID File Name File Size LSP10925 LSP10925_CyCIF_Image.ome.tif 9.3 GB LSP10929 LSP10929_CyCIF_Image.ome.tif 6.0 GB LSP10931 LSP10931_CyCIF_Image.ome.tif 8.7 GB LSP10933 LSP10933_CyCIF_Image.ome.tif 6.7 GB LSP10951 LSP10951_CyCIF_Image.ome.tif 11 GB LSP10980 LSP10980_CyCIF_Image.ome.tif 9.3 GB 51 GB markers.csv File name File Size Synapse ID markers.csv 0.7 KB N_Quantification.csv LSP Slide ID File Name File Size Synapse ID LSP10925 LSP10925_CyCIF_Quantification.csv 20 MB LSP10929 LSP10929_CyCIF_Quantification.csv 12 MB LSP10931 LSP10931_CyCIF_Quantification.csv 5.9 MB LSP10933 LSP10933_CyCIF_Quantification.csv 7.5 MB LSP10951 LSP10951_CyCIF_Quantification.csv 8.3 MB LSP10980 LSP10980_CyCIF_Quantification.csv 12 MB segmentation/ LSP Slide ID File Name File Size LSP10925 LSP10925_cellRingMask.tif 20 MB LSP10929 LSP10929_cellRingMask.tif 12 MB LSP10931 LSP10931_cellRingMask.tif 5.9 MB LSP10933 LSP10933_cellRingMask.tif 7.5 MB LSP10951 LSP10951_cellRingMask.tif 8.3 MB LSP10980 LSP10980_cellRingMask.tif 12 MB 66 MB N_IHC.ome.tiff LSP Slide ID Description File name File Size LSP16237 CD103 Image LSP16237_IHC_CD103.ome.tiff 2.8 GB LSP16240 PD1 Image LSP16240_IHC_PD1.ome.tiff 3.1 GB LSP16241 MART1 Image LSP16241_IHC_MART1.ome.tiff 2.9 GB LSP16242 FOXP3 Image LSP16242_IHC_FOXP3.ome.tiff 3.5 GB LSP16243 CD3 Image LSP16243_IHC_CD3.ome.tiff 2.9 GB LSP16244 CD4 Image LSP16244_IHC_CD4.ome.tiff 3.2 GB LSP16245 CD8 Image LSP16245_IHC_CD8.ome.tiff 3.2 GB LSP16246 CD20 Image LSP16246_IHC_CD20.ome.tiff 3.2 GB LSP16247 CD19 Image LSP16247_IHC_CD19.ome.tiff 3.7 GB LSP16248 CD163 Image LSP16248_IHC_CD163.ome.tiff 4.0 GB LSP16249 PDL1 Image LSP16249_IHC_PDL1.ome.tiff 3.7 GB LSP16250 CD69 Image LSP16250_IHC_CD69.ome.tiff 3.2 GB 39 GB N_HE.ome.tiff LSP Slide ID Description File name File Size LSP16237 H&E Image LSP16234_HE.ome.tiff 14 GB 14 GB ---- FUNDING R50-CA252138, U2C-CA233262 and Ludwig Cancer Research

Importance Immune checkpoint inhibitors (ICIs) have emerged as active therapies for a variety of cancers. Cutaneous toxicities are common immune-related adverse events and patients will often be referred to dermatologists for evaluation. Observations Cutaneous adverse events to ICIs can have a variety of clinical presentations. Among the more common are eczematous, morbilliform, and lichenoid dermatoses, as well as vitiligo and pruritus. Less common adverse events include psoriasiform dermatoses, bullous disorders, and severe cutaneous adverse reactions, including Stevens–Johnson syndrome, toxic epidermal necrolysis, and drug reaction with eosinophilia and systemic symptoms. Because of the immunologic mechanism of ICIs, there are also a variety of rheumatologic adverse reactions with cutaneous manifestations, such as scleroderma, dermatomyositis, cutaneous lupus erythematosus, and various vasculitides. These cutaneous reactions often respond to topical or systemic steroids, although specific toxicities may have alternative treatments available. Conclusions and relevance As they become more widely prescribed, dermatologists will see an increasing number of patients with cutaneous adverse events caused by ICI therapies. Accurately diagnosing and treating these toxicities is paramount to achieving the most favorable outcomes for patients.

Background Corticosteroid injections are a commonly used treatment for dermatologic pathologies. Although the injectable is often prepared with a local anesthetic, we hypothesize that patients receiving an injection with anesthetic will experience no decrease in pain at the time of injection. Methods Patients requiring a corticosteroid injection were prospectively randomized into two cohorts to receive a corticosteroid (triamcinolone acetonide) combined with either lidocaine with epinephrine 1:100 000 (anesthetic) or bacteriostatic normal saline. Both patient and clinician were blinded to the treatment arm. The primary outcome was pain associated with the injection measured using a Visual Analog Scale (VAS) immediately following the injection. Results Thirty-one patients were enrolled with 18 in the saline group and 13 in the lidocaine with epinephrine group. Pain scores were significantly higher for injections containing lidocaine with epinephrine versus saline (VAS 5.0 vs 2.0, p = .0056). Conclusions For various dermatologic pathologies, corticosteroid injections are effective and have relatively little associated pain. Counterintuitively, we found that there is more injection-associated pain when lidocaine with epinephrine is included with the corticosteroid. Therefore, clinicians should omit this anesthetic or dilute corticosteroids with normal saline, rather than with lidocaine and epinephrine. This will minimize injection pain as well as decrease the risk of pharmacologic adverse reactions from an unnecessary additional medication. Due to the small sample size, additional research may be necessary for generalization to other indications. Clinicaltrials.gov listing: NCT03630198.

We report a rare presentation of adult-onset Still disease (AoSD) with flagellate dermatosis and unknown trigger. Atypical skin findings have been increasingly reported for AoSD and may be associated with worse prognosis and systemic complications. Increased awareness of nonclassic skin findings in AoSD may lead to earlier diagnosis and treatment.

Immune checkpoint inhibitors (ICI) are a major class of cancer therapeutics that may cause durable responses in a growing proportion of patients with metastatic cancer. These agents remove negative regulators on T cells and may cause autoimmunelike toxicities that affect all organ systems. Monoclonal antibodies are much less commonly associated with traditional hypersensitivity reactions. Herein, we discuss the pathophysiology, clinical presentation, and management of toxicities of ICI and discuss their broader context within drug hypersensitivity.

Skin cancers remain the most common group of cancers globally, and the incidence continues to rise. Although localized skin cancers tend to have excellent outcomes following surgical excisions, the less common cases that become surgically unresectable or metastatic have been associated with poor prognosis and suboptimal treatment responses to cytotoxic chemotherapy. Development of monoclonal antibodies to programmed cell death-1 receptor and its ligand (PD-1/PD-L1) have transformed the management of metastatic melanoma, squamous cell carcinoma, and Merkel cell carcinoma. These agents, as monotherapies, are associated with response rates of approximately 40-60%, many of which persist durably. Further efficacy is observed with combination immunotherapy in advanced melanoma. Early reports suggest similar activity in locally advanced or metastatic basal cell carcinoma. In this review, we describe common molecular features of skin cancers that may render them particularly susceptible to anti-PD-1/PD-L1 and detail results from key clinical trials of these agents across skin cancers. Overall, the superior response rates of skin cancer to anti-PD-1/PD-L1 compared with other solid tumor types are likely due, at least in part, to a high mutational burden and, in Merkel cell carcinoma, viral etiology. Although melanoma has been rigorously studied in the setting of anti-PD-1/PD-L1 treatment, more research is needed for the other skin cancer types to establish toxicity profiles, responses, and quality-of-life outcomes.

With the rising cost of health care in the United States and an increasingly competitive market, dermatology residents would benefit from business training. We constructed an 8-part questionnaire for dermatology program directors (PDs) to determine the current perceptions of and resources available for business education. Of the 139 surveys distributed, 35 were completed (25.2%). Approximately one half of the respondents said their programs offered business training, primarily through seminars or lectures. Most PDs felt business education during residency was important and that programs should implement more training. The most important topics identified for inclusion in a business curriculum were economics or finance, management, and health care policy or government. Our survey identified a gap between the perceived importance and current supply of business education during dermatology residency training. Future efforts should aim to develop a standardized, dermatology-specific curriculum that is readily available to all programs and residents.

Bullous pemphigoid (BP) is a rare autoimmune blistering disease that classically presents with pruritic, tense bullae on an erythematous base. Approximately 20% of patients with BP never develop bullae.1 In nonbullous pemphigoid (NBP), patients often experience severe pruritus with eczematous patches or urticarial plaques. The diagnosis of NBP represents a diagnostic challenge given its morphologic ambiguity. Clinical, histopathologic, serologic, and immunologic studies are necessary to establish a diagnosis.2 Programmed cell death 1 (PD-1) inhibitors block inhibitory T-cell signals to stimulate an effective antitumor response. This medication class is commonly associated with cutaneous immune-related adverse events, including BP-like eruptions.3, 4 Although sporadic NBP is well described in the dermatologic literature, to our knowledge, NBP developing in the setting of immune checkpoint inhibitors (ICI) has not been described.5 We report 4 cases of NBP in patients receiving PD-1 inhibitors for advanced malignancy.

Kaposi sarcoma (KS) is an angioproliferative mesenchymal neoplasm caused by Kaposi sarcoma-related herpesvirus. This review outlines our current understanding of the epidemiology, pathogenesis, clinical presentation, and staging for this disease. Recent research has informed a more comprehensive understanding of the epidemiology of KS in the post-antiretroviral therapy era, and highlights the continued need to better characterize the African endemic subtype. Advances in clinical oncology, including checkpoint inhibitors and new skin-directed therapies, have translated into exciting new developments for the future of KS treatment options.

Author(s): Dewan, Anna K; Gupta, Sameer; Bach, Daniel Q; Jadeja, Saagar; Granter, Scott; LaCasce, Ann; Joyce, Robin; Davids, Matthew S; Huang, Victor; LeBoeuf, Nicole R

IMPORTANCE: Acute generalized exanthematous pustulosis (AGEP) is a rare, severe cutaneous adverse reaction associated with systemic complications. Currently available data are largely limited to small retrospective case series. OBJECTIVE: To describe the clinical characteristics, disease course, and outcomes of a heterogeneous group of patients with AGEP across the US. DESIGN, SETTING, AND PARTICIPANTS: A retrospective review of a case series of patients was conducted from January 1, 2000, through July 31, 2020. All 340 included cases throughout 10 academic health systems in the US were scored retrospectively using the EuroSCAR scoring system, and patients with a score corresponding to probable or definite AGEP and aged 18 years or older were included. MAIN OUTCOMES AND MEASURES: Patient demographic characteristics, clinical course, suspected causative agent, treatment, and short- and long-term outcomes. RESULTS: Most of the 340 included patients were women (214 [62.9%]), White (206 [60.6%]), and non-Hispanic (239 [70.3%]); mean (SD) age was 57.8 (17.4) years. A total of 154 of 310 patients (49.7%) had a temperature greater than or equal to 38.0 °C that lasted for a median of 2 (IQR, 1-4) days. Of 309 patients, 263 (85.1%) developed absolute neutrophilia and 161 patients (52.1%) developed either absolute or relative eosinophilia. Suspected causes of AGEP were medications (291 [85.6%]), intravenous contrast agents (7 [2.1%]), infection (3 [0.9%]), or unknown (39 [11.5%]). In 151 cases in which a single medication was identified, 63 (41.7%) were β-lactam antimicrobials, 51 (33.8%) were non–β-lactam antimicrobials, 9 (6.0%) were anticonvulsants, and 5 (3.3%) were calcium channel blockers. The median time from medication initiation to AGEP start date was 3 (IQR, 1-9) days. Twenty-five of 298 patients (8.4%) had an acute elevation of aspartate aminotransferase and alanine aminotransferase levels, with a peak at 6 (IQR, 3-9) days. Twenty-five of 319 patients (7.8%) experienced acute kidney insufficiency, with the median time to peak creatinine level being 4 (IQR, 2-5) days after the AGEP start date. Treatments included topical corticosteroids (277 [81.5%], either alone or in combination), systemic corticosteroids (109 [32.1%]), cyclosporine (10 [2.9%]), or supportive care only (36 [10.6%]). All-cause mortality within 30 days was 3.5% (n = 12), none of which was suspected to be due to AGEP. CONCLUSIONS AND RELEVANCE: This retrospective case series evaluation of 340 patients, the largest known study cohort to date, suggests that AGEP onset is acute, is usually triggered by recent exposure to an antimicrobial, may be associated with liver or kidney complications in a minority of patients, and that discontinuation of the triggering treatment may lead to improvement or resolution.

IMPORTANCE: Phosphoinositide 3-kinase (PI3K) inhibitors are a class of small-molecule inhibitors approved for the treatment of certain leukemias and lymphomas. Their dermatologic side effect profile is poorly described. A detailed understanding of the cutaneous adverse events from PI3K inhibitors will help dermatologists and oncologists identify and effectively manage these eruptions. OBJECTIVE: To describe a specific cutaneous side effect reaction pattern from PI3K inhibitors. DESIGN: Retrospective analysis. SETTING: Academic medical center. PARTICIPANTS: Patients receiving PI3K inhibitors referred to the Skin Toxicities Program in The Center for Cutaneous Oncology for dermatologic reactions while on therapy. MAIN OUTCOMES AND MEASURES: Clinical, histopathologic, and laboratory history was obtained and reviewed. RESULTS: Three patients on PI3K inhibitors for treatment of malignancy developed diffuse erythroderma and keratoderma within 4 days to 5 months of initiating therapy. Clinical and histopathologic findings were consistent with pityriasis rubra pilaris-like reactions. All patients improved with topical and oral corticosteroids, oral acitretin, and drug discontinuation. CONCLUSION AND RELEVANCE: Pityriasis rubra pilaris-like cutaneous eruptions may develop secondary to PI3K inhibition. These reactions may be treated based on their specific morphology. Further understanding of the pathophysiology of dermatologic adverse events secondary to small molecule inhibitors may help elucidate the immunologic mechanism of primary, idiopathic dermatoses.

BackgroundImmune checkpoint inhibitors (ICIs) are approved to treat multiple cancers. Retrospective analyses demonstrate acceptable safety of ICIs in most patients with autoimmune disease, although disease exacerbation may occur. Psoriasis vulgaris is a common, immune-mediated disease, and outcomes of ICI treatment in patients with psoriasis are not well described. Thus we sought to define the safety profile and effectiveness of ICIs in patients with pre-existing psoriasis.MethodsIn this retrospective cohort study, patients from eight academic centers with pre-existing psoriasis who received ICI treatment for cancer were evaluated. Main safety outcomes were psoriasis exacerbation and immune-related adverse events (irAEs). We also assessed progression-free survival (PFS) and overall survival.ResultsOf 76 patients studied (50 (66%) male; median age 67 years; 62 (82%) with melanoma, 5 (7%) with lung cancer, 2 (3%) with head and neck cancer, and 7 (9%) with other cancers; median follow-up 25.1 months (range=0.2–99 months)), 51 (67%) received anti-PD-1 antibodies, 8 (11%) anti-CTLA-4, and 17 (22%) combination of anti-PD-1/CTLA-4. All patients had pre-existing psoriasis, most frequently plaque psoriasis (46 patients (61%)) and 15 (20%) with psoriatic arthritis. Forty-one patients (54%) had received any prior therapy for psoriasis although only two (3%) were on systemic immunosuppression at ICI initiation. With ICI treatment, 43 patients (57%) experienced a psoriasis flare of cutaneous and/or extracutaneous disease after a median of 44 days of receiving ICI. Of those who experienced a flare, 23 patients (53%) were managed with topical therapy only; 16 (21%) needed systemic therapy. Only five patients (7%) required immunotherapy discontinuation for psoriasis flare. Forty-five patients (59%) experienced other irAEs, 17 (22%) of which were grade 3/4. PFS with landmark analysis was significantly longer in patients with a psoriasis flare versus those without (39 vs 8.7 months, p=0.049).ConclusionsIn this multicenter study, ICI therapy was associated with frequent psoriasis exacerbation, although flares were manageable with standard psoriasis treatments and few required ICI discontinuation. Patients who experienced disease exacerbation performed at least as well as those who did not. Thus, pre-existing psoriasis should not prevent patients from receiving ICIs for treatment of malignancy.

Ibrutinib is an oral inhibitor of Bruton's tyrosine kinase (BTK) that is FDA-approved for several lymphoproliferative disorders and chronic GVHD.To characterize cutaneous eruptions arising from ibrutinib and highlight overlap with epidermal growth factor receptor inhibitor (EGFRi)-induced dermatologic adverse events (dAEs).Single-center retrospective cohort of patients referred to the Skin Toxicities Program for management of cutaneous eruptions while taking ibrutinib.Among 19 patients, cutaneous eruptions manifested as facial-predominant papulopustular eruptions, petechiae or ecchymoses, photosensitivity, panniculitis, xerosis, and clinical staphylococcal overgrowth. The majority of patients were able to continue ibrutinib therapy with focused management of their cutaneous toxicities.This study represents cases at a single tertiary care center and is limited to patients referred for toxicity.With the exception of petechiae, the cutaneous toxicities of ibrutinib overlap with those associated with selective EGFR inhibitors. We observed that these reactions can be successfully managed using approaches for EGFR inhibitor-induced cutaneous adverse events.

We report the case of an infant born with perioral vesicles that rapidly spread to involve his mouth and the majority of his body. Histopathology, immunofluorescence, and enzyme-linked immunohistochemistry assays confirmed a diagnosis of epidermolysis bullosa acquisita (EBA). His mother had no history of EBA, and serum indirect immunofluorescence was negative. The patient improved rapidly with local wound care and oral dapsone.

Little is known about the anatomic distribution of cutaneous chronic graft-versus-host disease (cGVHD). Using data from the cGVHD Consortium Improving Outcomes Assessment Study, we describe the frequency and extent of erythema and superficial and deep sclerosis in 8 anatomic sites in patients with incident disease (ie, new cGVHD diagnosis within 3 months of study entry) receiving systemic therapy. Of 339 patients with incident disease, 182 (54%) had skin involvement. When an extremity was involved, the same type of disease was present contralaterally in 92% of cases, revealing a high level of symmetry. As anticipated, erythema was the most common incident feature; however, sclerotic skin involvement at the time of cGVHD diagnosis was more common than has been suggested by previous studies. Erythema occurred in 155 (85%) and sclerosis in 53 (29%) of the patients with skin involvement (46% and 16%, respectively, of the entire cohort of 339 incident cGVHD cases). Erythema was least common on the lower extremities (n = 71; 39% of patients with skin involvement). Moveable sclerosis was rare on the head, neck, and scalp (n = 4; 2%). Deep sclerosis did not occur in this region, and instead was most likely to occur on the upper extremities (n = 14; 8%) and lower extremities (n = 14; 8%). More than one-half of patients with erythema (n = 107; 58.7%) had diffuse involvement (4 or more of 8 sites involved), compared with less than one-third of those with sclerosis (n = 16; 30.2%).

This cohort study of patients with advanced melanoma treated with anti–programmed cell death 1 with or without ipilimumab assessed whether cutaneous toxic effects were associated with superior clinical outcomes.

Background We previously demonstrated that dermatology consultation substantially reduces the rates of misdiagnosis of cellulitis; however, broad implementation of dermatology consultation is impractical on account of existing practice patterns and reimbursement systems. Meanwhile, efforts to improve diagnostic accuracy have culminated in point-of-care tools, including the ALT-70 predictive model for lower extremity cellulitis and thermal imaging. Objective To prospectively evaluate the performance of the ALT-70 predictive model and thermal imaging in diagnosing lower extremity cellulitis in a head-to-head comparison. Methods We collected ALT-70 and thermal imaging data from patients with presumed lower extremity cellulitis and compared classification measures and accuracy for the ALT-70 predictive model, thermal imaging, and combination testing (ALT-70 predictive model plus thermal imaging). Results We enrolled 67 patients with ALT-70 and thermal imaging data. The ALT-70 predictive model conferred the highest sensitivity (97.8%) and negative predictive value (90.9%), whereas combination testing had the highest specificity (71.4%) and positive predictive value (86.6%). The ALT-70 predictive model had improved classification measures compared with thermal imaging. Combination testing conferred a marginal benefit compared with the ALT-70 predictive model alone. Limitations Single-center design may limit generalizability. Conclusion The ALT-70 predictive model outperformed thermal imaging in diagnosing lower extremity cellulitis. The accuracy of the ALT-70 predictive model was high and consistent with its performance in previously published literature. Broad implementation of the ALT-70 predictive model in clinical practice may decrease the rates of misdiagnosis of lower extremity cellulitis.

Importance Many inflammatory skin dermatoses mimic cellulitis (pseudocellulitis) and are treated with antibiotics and/or hospitalization, leading to unnecessary patient morbidity and substantial health care spending. Objective To evaluate the impact of early dermatology consultation on clinical and economic outcomes associated with misdiagnosed cellulitis. Design, Setting, and Participants This prospective cohort study enrolled patients with presumed diagnosis of cellulitis in the emergency department, in the emergency department observation unit, or within 24 hours of admission to an inpatient unit of a large urban teaching hospital between February and September 2017. Patients were provided with telephone and clinic follow-up during the 30-day postdischarge period. We screened 165 patients with the primary concern of cellulitis. Of these, we excluded 44 who required antibiotics for cutaneous, soft-tissue, and deeper-tissue and/or bone infections irrespective of cellulitis status, and 5 who were scheduled to be discharged by the emergency department. Interventions Early dermatology consultation for presumed cellulitis. Main Outcomes and Measures Primary outcomes were patient disposition and rates of antibiotic use. Results Of 116 patients (63 [54.3%] women; 91 [78.4%] non-Hispanic white; mean [SD] age, 58.4 [19.1] years), 39 (33.6%) were diagnosed with pseudocellulitis by dermatologists. Of these, 34 (87.2%) had started using antibiotics for presumed cellulitis as prescribed by the primary team at the time of enrollment. The dermatology team recommended antibiotic discontinuation in 28 of 34 patients (82.4%), and antibiotics were stopped in 26 of 28 cases (92.9%). The dermatologists also recommended discharge from planned observation or inpatient admission in 20 of 39 patients with pseudocellulitis (51.3%), and the primary team acted on this recommendation in 17 of 20 cases (85.0%). No patients diagnosed with pseudocellulitis experienced worsening condition after discharge based on phone and clinic follow-up (30 of 39 [76.9%] follow-up rate). Extrapolating the impact of dermatology consultation for presumed cellulitis nationally, we estimate 97 000 to 256 000 avoided hospitalization days, 34 000 to 91 000 patients avoiding unnecessary antibiotic exposure, and $80 million to $210 million in net cost savings annually. Conclusions and Relevance Early consultation by dermatologists for patients with presumed cellulitis represents a cost-effective intervention to improve health-related outcomes through the reduction of inappropriate antibiotic use and hospitalization.