Cutaneous Adverse Events Research Articles

Clinical Experience of External Application of Clearing Heat and Removing Dampness in Relieving Grade 2 to 3 Rash Caused by Programed Cell Death Protein 1 (PD-1)/Programed Cell Death Ligand 1 (PD-L1) Inhibitors: A Single-Center Retrospective Study.

In China, grade 2 to 3 immune-related rash will probably lead to the interruption of immunotherapy. Corticosteroid (CS) is the main treatment, but not always effective. The external application of clearing heat and removing dampness, which is represented by Qing-Re-Li-Shi Formula (QRLSF), has been used in our hospital to treat immune-related cutaneous adverse events (ircAEs) for the last 5 years. The purpose of this study was to discuss its efficacy and safety in the treatment of grade 2 to 3 rash. A retrospective study of patients with grade 2 to 3 immune-related rash in our hospital from December 2019 to December 2022 was conducted. These patients received QRLSF treatment. Clinical characteristics, treatment outcome, and health-related quality of life (HrQoL) were analyzed. Thirty patients with grade 2 to 3 rash (median onset time: 64.5 days) were included. The skin lesions of 24 cases (80%) returned to grade 1 with a median time of 8 days. The accompanying symptoms were also improved with median time of 3 to 4 days. The addition of antihistamine (AH) drug didn't increase the efficacy of QRLSF (AH + QRLSF: 75.00% vs QRLSF: 83.33%, P = .66). No significant difference was observed in the efficacy of QRLSF treatment regardless of whether patients had previously received CS therapy (untreated population: 88.24% vs treated population: 69.23%, P = .36). During 1-month follow-up, 2 cases (8.33%) underwent relapses. In terms of HrQoL, QRLSF treatment could significantly reduce the median scores of all domains of Skindex-16, including symptoms (39.58 vs 8.33, P < .0001), emotions (58.33 vs 15.48, P < .0001), functioning (46.67 vs 13.33, P < .0001) and composite (52.60 vs 14.06, P < .0001). External application of clearing heat and removing dampness was proven to be an effective and safe treatment for such patients. In the future, high-quality trials are required to determine its clinical application in the field of ircAEs.

A unique dermatologic adverse event from enfortumab vedotin

Enfortumab vedotin (EV) is a novel chemotherapeutic agent used in the treatment of metastatic urothelial cancer. Although rashes are reported as a common adverse event from this therapy, a paucity of literature is available on dermatologic toxicities to EV, especially with respect to bullous dermatoses. This case report will review a unique bullous dermatosis in the setting of EV therapy, including the diagnostic workup and management. Because cutaneous adverse events to chemotherapy and immunotherapy are common and can often result in dose reduction and treatment withdrawal for cancer patients, awareness of these manifestations and understanding how to manage them is crucial to providing quality care to this patient population.

Skin reactions to tyrosine kinase inhibitors in pediatric patients with chronic myeloid leukemia.

Cutaneous adverse events are commonly reported in adult patients with chronic myeloid leukemia (CML) receiving tyrosine kinase inhibitors (TKIs); however, little is known about the cutaneous reactions in children receiving TKIs for CML. As pediatric patients may require lifelong TKI therapy, it is essential to understand the wide range of potential cutaneous toxicities. We examined all case studies, cohort studies, and clinical trials in PubMed/MEDLINE and Embase that reported cutaneous reactions to first-, second-, and third-generation TKIs in children 18 years or younger with CML. This review article focuses on the TKI drug types and doses, patient demographic characteristics, features of skin reactions, and clinical outcomes.

Integrated sun protection advice for the South African population.

Exposure to solar ultraviolet radiation (UVR) is associated with several cutaneous adverse effects. However, to the best of our knowledge, in South Africa there are no formal guidelines on sun protection. A group of South African dermatologists and researchers convened over the course of 1 year to deliberate on integrated advice for sun protection among the multi-ethnic South African population. For people with light skin and those with genetic skin disorders (e.g., oculocutaneous albinism), sun protection was identified as critical to prevent sunburn, skin cancer, and photoaging. The evidence is less clear for people with medium and darker skin types, especially the latter, in whom melanin may confer a degree of protection against some parts of the solar spectrum. Recent studies have demonstrated that visible light can cause pigmentary changes in individuals with darker skin types in particular. Sun protection for people of all skin colors is beneficial to protect against photoaging and ocular damage. Herein sun protection advice is suggested for South Africans of all skin colors to reduce morbidity and mortality from sun exposure, particularly relating to skin cancer. Several knowledge gaps are identified as future research priorities.

Signal mining study of severe cutaneous adverse events of valaciclovir or acyclovir based on the FAERS database

ABSTRACT Objective This study aimed to explore a comprehensive empirical investigation and assess SCARs related to valaciclovir or acyclovir based on FAERS database from FDA, thus providing a theoretical foundation for the rational application of drugs in clinic. Methods SCARs reports relevant to valaciclovir or acyclovir were searched in FAERS database from the 2004 Q1 to 2023 Q2. These data were further mined by a proportional analysis and Bayesian approach to detect signals of SCARs caused by two drugs. Meanwhile, the clinical characteristics, onset time, correlation, and stratification analysis of the two drugs in SCARs were analyzed. Results Both drugs exhibited positive signals for drug reaction with DRESS, AGEP, TEN, SJS-TEN overlap and SJS. The median onset time of SCARs caused by valaciclovir or acyclovir was 30 days vs 10 day for DRESS, 11 days vs 9 days for AGEP, 17 days vs 12 days (TEN) and 12 days vs 8 days (SJS). Excluding the effect of combinational drugs, there was an association between the two antiviral drugs and SCARs. Conclusion By analyzing the FAERS database, the risk trends of SCARs caused by valaciclovir or acyclovir have been identified, providing valuable insights to recognize various types of SCARs in clinics.

Adverse events from topical corticosteroid use in chronic hand eczema — Findings from the Danish Skin Cohort

BackgroundTopical corticosteroids (TCS) are used to treat most patients with chronic hand eczema (CHE), but knowledge about TCS-related adverse events in CHE is limited. ObjectivesTo investigate patient-reported adverse events to TCS in CHE patients. MethodsData on adverse events related to TCS use in CHE patients were analyzed from the Danish Skin Cohort; a prospective survey of a hospital cohort. We assessed patients’ knowledge about TCS use and adverse event risks, and preference of TCS vs. a non-steroidal topical alternative. ResultsOf 724 adults with CHE (64.0% women; mean age 57.5 [standard deviation 12.8] years), 64.1% reported skin atrophy, 41.4% cracks/fissures, 23.9% bleeding, 45.9% pain/stinging sensation, 40.0% reduced hand dexterity, and 40.2% worsening of CHE signs or symptoms from using TCS. We observed CHE-severity-dependent associations (all groups; p<0.0001). Most patients (76.4%) would prefer a non-steroidal option, 10.9% were neutral/indifferent, and 12.7% would prefer TCS for CHE. The median numerical rating scale-score (ranging from 0-10) was 10 (interquartile range 6-10) for preferring a non-steroidal topical treatment. LimitationsDifferences across TCS formulations were unexplored. ConclusionTCS-related cutaneous adverse events were common. There is a desire from patients for novel steroid-free topical alternatives for CHE treatment.

2371. A study to describe the pattern of cutaneous adverse effects of COVID-19 vaccines (Covishield and Covaxin )

Abstract Background Vigorous administration of Covid-19 vaccines to tackle the ongoing pandemic has led to increasing research on adverse effects including both systemic and cutaneous. A prospective observational study to delineate cutaneous adverse effects of two vaccines namely Covishield and Covaxin administered in two doses in northern India. Methods The study was conducted in a tertiary hospital in northern India wherein patients were asked to report voluntarily any cutaneous adverse effects after covid-19 vaccination to the dermatology department. The data was collected using excel sheets and later analysed taking into consideration the age, vaccine types, and duration of onset of adverse effects. Results Out of the 19672 vaccination jabs, 296 (1.5%) developed cutaneous adverse effects out of which the incidence was higher in Covishield vaccinees compared to Covaxin vaccinee group. The incidence of side effects was more with the first dose of either vaccine compared to the second dose. All the side effects were benign and were managed symptomatically or were self-limiting. Conclusion Rampant administration of vaccines along with widespread advertisement of vaccine-induced side effects via social media has created apprehension in the general population. This warrants studies improving awareness about the most vital preventive measure available to halt and eventually end the Covid-19 pandemic. Disclosures All Authors: No reported disclosures

Cutaneous immune-related adverse event burden and effect on immunotherapy: A retrospective review of the experience at a tertiary care immunotherapy center

Cutaneous immune-related adverse event burden and effect on immunotherapy: A retrospective review of the experience at a tertiary care immunotherapy center

Safety of Immunomodulatory Systemic Therapies Used in the Management of Immune-Related Cutaneous Adverse Events

Immune-related cutaneous adverse events (ircAEs) commonly occur in patients on treatment with immune checkpoint inhibitors and can significantly reduce patient quality of life. These are often treated with immunomodulatory agents, including glucocorticoids, immunosuppressants, and biologics. While often effective at managing symptoms, these therapies can cause several adverse events which may limit their use. In addition, immunomodulatory agents should be used with particular caution in patients receiving immunotherapy, as the efficacy of the oncologic regimen may potentially be undermined. In this review, we summarize the safety of systemic therapies that are used in the management of ircAEs, with a particular focus on the resultant risk of secondary tumor progression in patients with active cancer.

Cutaneous adverse effects induced by tebentafusp in patients with metastatic uveal melanoma: a case series and treatmentinsights.

Tebentafusp, recently approved by the FDA as an immunotherapy agent, has shown great promise in improving outcomes for metastatic uveal melanoma. In this case series, we present six patients treated with tebentafusp at our institution, focusing on the associated cutaneous adverse reactions and their management. A better understanding of the cutaneous adverse reactions associated with tebentafusp is important because, given its promising treatment outcomes, the use of tebentafusp will likely become more widespread. This study highlights the range of possible outcomes and effective treatment regimens for mild-to-severe cutaneous reactions, ensuring that patients can continue tebentafusp treatment without interruption in most cases.

IL12/23 Blockade with Ustekinumab as a Treatment for Immune-Related Cutaneous Adverse Events.

Background: Immune-related cutaneous adverse events (ircAEs) are frequent and may reduce quality of life and consistent dosing. IL12/23 has been implicated in psoriasis, which is reminiscent of the psoriasiform/lichenoid ircAE phenotype. We report the use of ustekinumab as a therapeutic option. Methods: Patients at Memorial Sloan Kettering Cancer Center, New York, who received immune checkpoint inhibitors and were treated with ustekinumab or had the keywords "ustekinumab" or "Stelara" in their clinical notes between 1 March 2017 and 1 December 2022 were retrospectively identified via a database query. Documentation from initial and follow-up visits was manually reviewed, and response to ustekinumab was categorized into complete cutaneous response (CcR, decrease to CTCAE grade 0), partial cutaneous response (PcR, any decrease in CTCAE grade exclusive of decrease to grade 0), and no cutaneous response (NcR, no change in CTCAE grade or worsening). Labs including complete blood count (CBC), cytokine panels, and IgE were obtained in a subset of patients as standard of care. Skin biopsies were reviewed by a dermatopathologist. Results: Fourteen patients with psoriasiform (85.7%), maculopapular (7.1%), and pyoderma gangrenosum (7.1%) ircAEs were identified. Ten (71.4%) receiving ustekinumab had a positive response to treatment. Among these 10 responders, 4 (40%) demonstrated partial cutaneous response and 6 (60%) demonstrated complete cutaneous resolution. Six patients (42.9%) experienced interruptions to their checkpoint inhibitor treatment as a result of intolerable ircAEs, and following ircAE management with ustekinumab, two (33.3%) were successfully rechallenged with their checkpoint inhibitors. On histopathology, patients primarily had findings of interface or psoriasiform dermatitis. No patients reported an adverse event related to ustekinumab. Conclusions: Ustekinumab showed a benefit in a subset of patients with psoriasiform/lichenoid ircAEs. No safety signals were identified. However, further prospective randomized controlled trials are needed to confirm our findings.

INDIVIDUAL ARTICLE: USCOM Algorithm for the Prevention and Management of Cutaneous Immunotherapy-Related Adverse Events.

In 2023, nearly 2 million patients will be diagnosed with cancer in the United States and at least 40% will be eligible for treatment with an immune checkpoint inhibitor (ICI). Cutaneous immune related adverse events (cirAEs) from ICIs are common and include pruritus as well as maculopapular, eczematous, bullous, lichenoid, and psoriasiform reactions. All clinicians interfacing with cancer patients must expedite proper evaluation and diagnosis, treatment, and/or consultation that supports the need for evidence-directed guidelines. A panel of advisors was selected, and a systematic literature review generated foundational evidence to develop a treatment algorithm for cirAEs via a modified Delphi process. Iterations of the algorithm were performed until the group met consensus. An algorithm that tailors the management of cirAEs was developed based on the CTCAE v.5 grading of skin disorders. Representative clinical images and suggested diagnostic measures, supplement the algorithm. Recognition and treatment of cirAEs guided through a multidisciplinary, physician-developed algorithm will limit disruption of immunotherapy, optimize quality of life, and enhance overall outcomes in patients treated with ICIs. J Drugs Dermatol. 2023;22:11(Suppl 1):s3-10.

Cutaneous lesions and clinical outcomes in five cats after frunevetmab injections.

This case series describes five cats with cutaneous adverse events after subcutaneous administration of frunevetmab, a felinised anti-nerve growth factor monoclonal antibody, including histopathological findings in one case. All cats displayed moderate to severe pruritus resulting in self-trauma to the neck and/or head, causing lesions ranging from superficial dermatitis to alopecia and ulcerations. There were no reactions at the injection sites. In one cat, clinical signs developed after the second frunevetmab dose the cat received, with no reaction noted after the first dose. For the remaining cats, clinical signs were observed after their first dose of frunevetmab. The onset of the first episode of pruritus and self-trauma was 3-18 days after the most recent frunevetmab injection. Three cats had one or more additional frunevetmab injections after the original adverse event and all had subsequent reactions. Subsequent reactions were either similar in time frame or occurred more rapidly, with similar or more severe pruritus compared with the original reactions. Treatments and outcomes varied between cases. Frunevetmab is a novel, monthly injectable monoclonal antibody for the management of pain associated with osteoarthritis in cats. This is the first published report detailing the nature of cutaneous adverse events associated with this treatment, and the first report of the histopathological findings.

Prevalence of Cutaneous and Oral Immune-Related Adverse Events Related to Immune Checkpoint Inhibitor Therapy in a Single Institution

Prevalence of Cutaneous and Oral Immune-Related Adverse Events Related to Immune Checkpoint Inhibitor Therapy in a Single Institution

Tocilizumab Treatment in COVID-19 Patients: Comparing Cutaneous Disease and Adverse Drug Effects

Tocilizumab Treatment in COVID-19 Patients: Comparing Cutaneous Disease and Adverse Drug Effects

An Analysis of Risk Factors for the Development of Acneiform Eruptions in Patients on Monoclonal Antibody Epidermal Growth Factor Receptor Inhibitors

Acneiform eruptions occur frequently and early in patients on epidermal growth factor receptor inhibitors (EGFRi). Identification of baseline patient risk factors would prompt earlier referral to dermatology to optimize prevention and management. The primary objective of this retrospective study is to determine the association between clinical and demographic characteristics and the development of acneiform eruptions. A retrospective chart review was conducted on patients diagnosed with colon and head and neck cancers who started EGFRi between January 2017 and December 2021. Patients were followed until death or September 2022. Baseline demographic and clinical parameters were documented and patients were followed from the time of diagnosis to most recent visit for the development and management of an acneiform eruption. Regression analyses were performed to determine the association between baseline characteristics and the development of acneiform eruptions. A total of 66 patients were treated with cetuximab or panitumumab between 2017-2021 were included in the analysis. Forty-seven of the sixty-six patients developed an acneiform eruption while on EGFRi therapy (71.2%). Combination cancer therapy with another chemotherapeutic agent was associated with a lower risk of acneiform eruption (OR 0.03, P = .027). No other baseline features were statistically associated with a lower risk of acneiform eruption. Acneiform eruptions are a common cutaneous adverse event of EGFRi therapy. Ongoing research is required to elucidate risk factors for the development of acneiform eruptions, to improve the quality of life of oncology patients.

Literature analysis of cutaneous adverse reactions induced by tislelizumab

Objective Tislelizumab may induce immune-related adverse events, especially adverse skin events. Early detection and timely intervention of cutaneous adverse events are crucial to improve patients’ quality of life and reduce the disruption of therapeutic regimens. This study aimed to determine the clinical characteristics of cutaneous adverse reactions to tislelizumab and offer a reference for its rational clinical use. Methods Case reports of cutaneous adverse reactions induced by tislelizumab were collected from the relevant databases (up to 31 March 2023). Patient age, sex, primary disease, medication use, occurrence of adverse skin conditions, treatment, and outcomes were recorded and descriptively analysed. Results A total of 13 patients were enrolled, including six males and seven females, aged 55–79 years, with a median age of 75 years and a mean age of 70.92 ± 8.84 years. The original disease was lung carcinoma in none patients, cervical carcinoma in two, and urothelial carcinoma and squamous cell carcinoma in one each. The time from the initiation of medication use to the occurrence of cutaneous adverse reactions ranged from 7 to 177 days. Among the 13 patients, 10 showed improvement after drug withdrawal or symptomatic treatment. Two patients died (one died of disease progression and multiorgan failure, one died of acute coronary syndrome), and one patient’s adverse skin reactions persisted without treatment. Conclusions Tislelizumab-related cutaneous adverse reactions mostly occur after several days to months of treatment. In clinical practice, evaluation and monitoring should be strengthened. More attention should be paid to erythema and rashes, which may be signs of serious adverse skin reactions. Early detection and intervention can ensure the safe use of drugs and provide greater clinical benefits to patients.

Clinicopathological characteristics of cutaneous complications following COVID-19 vaccination: A case series.

Several vaccine-related cutaneous adverse events occurred following the widespread use of vaccines to prevent coronavirus disease 2019 (COVID-19). This case series reports 25 patients with de novo or accentuated dermatologic conditions after receiving the Sinopharm, Sputnik V, AstraZeneca, or BIV1-CovIran vaccine in Iran. Twenty-five eligible patients with a mean age of 46.80 years were investigated. The cutaneous adverse events included pityriasis rosea, zoster, viral exanthema, urticaria, bullous pemphigoid, pemphigus vulgaris, and acute generalized exanthematous pustulosis. The manifestations appeared 14.45 ± 6.98 and 20.79 ± 22.18 days following injection of the first and second doses of COVID-19 vaccines, respectively. All patients experienced new cases of cutaneous disease other than two who developed flare-ups of lichen planus and psoriasis. Several cutaneous reactions, ranging from allergic events to skin diseases, have been reported following the injection of COVID-19 vaccines. Focal injection-site reactions are the most common cutaneous adverse events; however, de-novo skin diseases and a flare-up of preexisting cutaneous disorders have also been described. Although many cases of COVID-19 vaccine-related cutaneous diseases have been published, our zoster/lichen planus and AGEP cases after vaccination are interesting. A more detailed understanding of cutaneous adverse events following COVID-19 vaccination will facilitate better diagnosis and management.

Two cases of COVID-19 vaccine-related erythema multiforme under the administration of immune checkpoint inhibitors

The COVID-19 pandemic has increased mRNA vaccine usage and revealed various cutaneous adverse events, such as injection site reactions, urticaria, and morbilliform eruptions. Multiple centers have reported erythema multiforme (EM) as a COVID-19 vaccine-associated adverse event. Our center observed two cases of EM in patients receiving immune checkpoint inhibitors (ICI) after COVID-19 vaccination. Notably, ICI administration is known to cause cutaneous adverse events, including EM. A previous report indicated that administering COVID-19 vaccination to patients receiving ICI treatment could promote severe systemic symptoms. This raise concerns that COVID-19 vaccination might rapidly worsen skin rashes in these patients. Our report demonstrates that skin rash related to COVID-19 vaccine-induced EM in ICI-treated patients does not significantly differ from that of COVID-19 vaccine-related EM. Additionally, in both cases, the skin rash resolved without exacerbation. Further research is necessary to determine optimal management strategies. However, our findings provide reassurance that COVID-19 vaccination is safe in ICI-treated patients and should not be avoided.

Cutaneous adverse effects associated with LAG-3 inhibitor use in cancer treatment: A systematic review.

Immunotherapy has become a mainstay of treatment for many cancers. Multiple immune checkpoint inhibitors have been used to treat malignancies, including anti-programed death-1 (PD1) and anti-cytotoxic T-lymphocyte-associated protein (anti-CTLA4). However, a significant percentage of patients develop resistance to these immunotherapy drugs. Therefore, novel strategies were developed to target other aspects of the immune response. Lymphocyte activation gene-3 (LAG-3) is a cell-surface molecule found on natural killer cells and activated T-cells which negatively regulates T-cell proliferation and function. LAG-3 inhibitors interact with LAG-3 ligands on the surface of T-cells to block T-regulatory (Treg) cell activity, suppress cytokine secretion and restore dysfunctional effector T-cells which subsequently attack and destroy cancer cells. This review reports the dermatologic side effects associated with LAG-3 inhibitors used in the treatment of melanomas. Using PRISMA 2022 guidelines, a comprehensive literature review of PubMed, Google Scholar, Embase, Cochrane, and Web of Science databases was conducted. Three studies were identified that demonstrated that the use of LAG-3 inhibitors, whether as a single agent or in combination with other immune checkpoint inhibitors, resulted in stomatitis, pruritus, rash, dry skin, erythema, and vitiligo. Further research is warranted to assess the cutaneous adverse events observed with LAG-3 inhibitors in treating melanoma and to identify populations most vulnerable to such side effects.