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INTRODUCTION: Brodalumab is a human interleukin-17 receptor A antagonist indicated for the treatment of moderate-to-severe plaque psoriasis in adult patients who are candidates for systemic therapy or phototherapy and have failed to respond or have lost response to other systemic therapies. Although the US prescribing information for brodalumab includes a boxed warning regarding suicidal ideation and behavior, no causal association has been demonstrated. Here, we summarize 5 years of pharmacovigilance data, from August 15, 2017, through August 14, 2022, reported to Ortho Dermatologics by US patients and healthcare providers. METHODS: Prevalence of the most common adverse events (AEs) listed in the brodalumab package insert (incidence ≥ 1%) and AEs of special interest are described. Brodalumab exposure was estimated as the time from the first to last prescription-dispensing authorization dates. Data were collected from 4744 patients in the USA, with an estimated exposure of 5815 patient-years. RESULTS: Over 5 years, 11 cases of adjudicated major adverse cardiovascular events were reported (0.23 events/100 patients), a rate lower than that experienced by patients in the international Psoriasis Longitudinal Assessment and Registry. There were 106 serious infections. No serious fungal infections were reported. There were 40 confirmed and 2 suspected COVID-19 cases, with no new COVID-19-related deaths. Of 49 reported malignancies among 42 patients, 3 were deemed possibly related to brodalumab. No completed suicides and no new suicidal attempts were reported. CONCLUSION: Five-year pharmacovigilance data are consistent with the established safety profile reported in long-term clinical trials and previous pharmacovigilance reports, with no new safety signals.

Leflunomide can be used in management of psoriatic disease. Leflunomide's active metabolite, teriflunomide, is used in the treatment of multiple sclerosis and has unexpectedly been rarely reported to induce pustular psoriasis. In this report, we present a patient with multiple sclerosis who developed inverse psoriasis after starting teriflunomide.

ABSTRACT Background Methods Results Conclusions Binimetinib and selumetinib are two mitogen‐activated protein kinase kinase (MEK) inhibitors used to treat low‐grade gliomas and plexiform neurofibromas. Cutaneous toxicities are commonly associated with MEK inhibitors; however, limited studies have examined cutaneous effects in a pediatric population or whether toxicities vary between MEK inhibitors.We conducted an IRB‐approved, single‐center, retrospective review of pediatric neuro‐oncology patients on binimetinib or selumetinib who presented to NYU from April 2016 through July 2022.Forty‐six children met inclusion criteria (23 females, 23 males) with a mean age of 11.7 years. Thirty‐three were treated with binimetinib and 13 with selumetinib. Dermatologic adverse events were encountered in 97.8% of the cohort, and the most common were acneiform eruption (63.0%), paronychia (58.7%), and xerosis (54.3%). Children 12 years and older were more likely to have acneiform eruption (p < 0.001) and seborrheic dermatitis (p < 0.001), while children under 12 were more likely to have xerosis (p = 0.037). The incidence of cutaneous adverse events was significantly different between MEK inhibitors for folliculitis and hair pigment dilution (39.4% binimetinib, 0% selumetinib, p = 0.009). Significantly, more patients required MEK inhibitor dose reduction/hold on binimetinib (87.9%) than selumetinib (46.2%) (p = 0.006). Severity of cutaneous disease was not associated with tumor response.Our study confirms dermatologic adverse events are common in children on MEK inhibitors. Age appears to be associated with increased likelihood of certain cutaneous reactions. Overall, the selumetinib patients in our cohort presented with less severe adverse events and decreased risk of MEK inhibitor dose reduction/hold. Our results will aid clinicians in providing appropriate counseling, treatments, and improved preventive care. [ABSTRACT FROM AUTHOR]

This study aims to characterize the timeline and clinical features of onset, progression, and management of drug‐induced epidermal necrolysis in pediatric patients. Sixteen pediatric patients were retrospectively identified and selected if under age 18 years at admission with one identified culprit drug exposure. Culprit drugs were antiepileptics (12/16, 75%) and antibiotics (4/16, 25%). Notably, anti‐epileptic drugs (AED) had delayed onset and reported dose escalations that precipitated symptom onset; thus, patients prescribed AED with or without planned dose escalations should be monitored for prodromal symptoms longer than the typical onset window. [ABSTRACT FROM AUTHOR]

Copyright of Journal der Deutschen Dermatologischen Gesellschaft is the property of Wiley-Blackwell and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)

Summary: Stevens‐Johnson syndrome and toxic epidermal necrolysis (SJS/TEN) are rare, predominantly drug‐induced, acute life‐threatening diseases of skin and mucosae. SJS and TEN are nowadays considered as variants of one disease entity with varying degrees of severity called epidermal necrolysis (EN). EN is associated with high morbidity and mortality and constitutes a major disease burden for affected patients. The guideline "Diagnosis and treatment of epidermal necrolysis (Stevens‐Johnson syndrome and toxic epidermal necrolysis)" was developed under systematic consideration of existing scientific literature and in a formal consensus process according to regulations issued by the Association of Scientific Medical Societies in Germany (AWMF) to establish an evidence‐based framework to support clinical decision‐making. The interdisciplinary guideline commission consisted of representatives from various specialist societies and of patient representatives. The guideline is aimed at specialists in the fields of dermatology, ophthalmology, plastic surgery, intensive care, and pediatrics in hospitals and offices, as well as other medical specialties involved in the diagnosis and treatment of EN. The guideline is also aimed at patients, their relatives, insurance funds, and policymakers. The second part is concerned with the topics of supportive therapy in the acute phase of EN and outpatient follow‐up treatment. [ABSTRACT FROM AUTHOR]

Introduction: Perioperative hypersensitivity and allergic reactions can result in significant morbidity and mortality. For routine anesthetic care, allergies are determined from a review of the electronic medical record supplemented by a detailed patient history. Although the electronic medical record is generally assumed to be accurate, it may be that allergies are erroneously listed or not based on sound medical practice. The purpose of the current study is to evaluate allergies listed in the electronic medical record of children presenting for surgery and determine their origin, authenticity, and impact on perioperative care. Methods: Eligible patients included those presenting for a surgical procedure in the main operating room, who were ≤ 21 years of age, with a drug allergy listed on the EMR. Prior to intraoperative care, an electronic survey questionnaire containing questions related to medication allergies was provided to a guardian or parent. Two anesthesiology physicians reviewed the survey responses to determine the validity of any reported allergies. A second electronic survey was given postoperatively to the attending anesthesiologist to determine whether the documented allergy impacted anesthetic care. Results: The study cohort included 250 patients, ranging in age from 5 to 14 years (median age 9 years). All of the patients had at least one allergy listed on the electronic medical record. Seventy of the 250 patients (28%) had more than one drug allergy listed for a total of 351 medication allergies. The majority of the listed allergies were related to antibiotics including 155 (44%) from the penicillin family, 26 (7%) cephalosporins, 16 (5%) sulfonamides, and 36 (10%) other antimicrobial agents. Other commonly listed allergies were 27 (8%) nonsteroidal anti‐inflammatory agents and 15 (4%) opioids. The remaining 76 (22%) included a miscellaneous list of other medications. On further review of the allergies, the survey was completed for 301 medications. After physician review, 135 of 301 (45%) responses were considered consistent with IgE reactions "true allergy," 73 (24%) were deemed less relevant to IgE reactions "unlikely true allergy," and 93 (31%) were not related to IgE reactions "not an allergy." Care alterations during surgery were uncommon regardless of whether the issue was assessed as a true allergy (11%), unlikely to be a true allergy (3%), or not a true allergy (13%). Conclusion: A significant portion of the documented allergies in children are not true allergies, but rather recognized adverse effects (apnea from an opioid, renal failure from an NSAIDs) or other nonallergic concerns (gastrointestinal upset such as nausea). Erroneously listed allergies may lead to unnecessary alterations in patient care during perioperative care. A careful analysis of the allergy list on the EMR should be supplemented by a thorough patient history with specific questions related to the drug allergy. Once this is accomplished, the allergy listed should be updated to avoid its erroneous impact on perioperative care. [ABSTRACT FROM AUTHOR]

Copyright of Journal der Deutschen Dermatologischen Gesellschaft is the property of Wiley-Blackwell and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)

Summary: Stevens‐Johnson syndrome and toxic epidermal necrolysis (SJS/TEN) are rare, predominantly drug‐induced, acute, life‐threatening diseases of skin and mucosae. SJS and TEN are nowadays considered variants of one disease entity with varying degrees of severity called epidermal necrolysis (EN). EN is associated with high morbidity and mortality and constitutes a major disease burden for affected patients. The guideline "Diagnosis and treatment of epidermal necrolysis (Stevens‐Johnson syndrome and toxic epidermal necrolysis)" was developed under systematic consideration of existing scientific literature and in a formal consensus process according to regulations issued by the Association of Scientific Medical Societies in Germany (AWMF) to establish an evidence‐based framework to support clinical decision‐making. The interdisciplinary guideline commission consisted of representatives from various specialist societies and patient representatives. The guideline is aimed at specialists in the fields of dermatology, ophthalmology, plastic surgery, intensive care, and pediatrics in hospitals and offices, as well as other medical speciallved in the diagnosis and treatment of EN. The guideline is also aimed at patients, their relatives, insurance funds, and policymakers. This first part focuses on the diagnostic aspects, the initial management as well as the immunomodulating systemic therapy. [ABSTRACT FROM AUTHOR]

Copyright of Zeitschrift für Rheumatologie is the property of Springer Nature and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)

Steven Johnson Syndrome (SJS) and Toxic Epidermal Necrolysis (TEN), grouped together under the terminology of epidermal necrolysis (EN), are a spectrum of life-threatening dermatologic conditions. A lack of standardization and validation for existing endpoints has been identified as a key barrier to the comparison of these therapies and development of evidenced-based treatment. Following PRISMA guidelines, we conducted a systematic review of prospective studies involving systemic or topical treatments for EN, including dressing and ocular treatments. Outcomes were separated into mortality assessment, cutaneous outcomes, non-cutaneous clinical outcomes, and mucosal outcomes. The COSMIN Risk of Bias tool was used to assess the quality of studies on reliability and measurement error of outcome measurement instruments. Outcomes across studies assessing treatment in the acute phase of EN were varied. Most data came from prospective case reports and cohort studies representing the lack of available randomized clinical trial data available in EN. Our search did not reveal any EN-specific validated measures or scoring tools used to assess disease progression and outcomes. Less than half of included studies were considered “adequate” for COSMIN risk of bias in reliability and measurement error of outcome measurement instruments. With little consensus about management and treatment of EN, consistency and validation of measured outcomes is of the upmost importance for future studies to compare outcomes across treatments and identify the most effective means of combating the disease with the highest mortality managed by dermatologists. [ABSTRACT FROM AUTHOR]

PD-1/PD-L1 inhibitors have increasingly been associated with the occurrence of subacute cutaneous lupus erythematosus (SCLE), but the clinical characteristics and outcomes remain under-explored. Literature on PD-1/PD-L1 inhibitors induced SCLE was retrieved from Chinese and English databases until June 31, 2024, and clinical data of patients were extracted for retrospective analysis. Twenty-nine patients participated, with a median age of 63 years (range 43, 80). The most frequently reported drugs were Nivolumab (51.7%) and pembrolizumab (31.0%). The median time from treatment initiation to SCLE onset was 3 months (range 0.5, 47). Cutaneous manifestations presented primarily as papulosquamous lesions (65.5%) and erythema annulare (31.0%), predominantly occurring on the trunk (51.7%) and arms (51.7%). Serological analysis revealed positive anti-Ro antibodies in 91.7% of patients, positive antinuclear antibodies in 75.0%, and positive anti-La antibodies in 50.0%. Skin biopsies showed interface dermatitis in 65.5% of cases and lymphocyte infiltration in 82.8%. Treatment with topical corticosteroids, systemic corticosteroids, and hydroxychloroquine led to gradual improvement or resolution of the rash, with a median recovery time of 1 month (range 0.5, 11). As the use of PD-1/PD-L1 inhibitors in oncology increases, SCLE should be recognized as a rare cutaneous adverse effect. Histological and serological evaluations play a critical role in diagnosing SCLE. Typically, SCLE resolves on its own with appropriate local and systemic treatment. [ABSTRACT FROM AUTHOR]

Abstract Andexanet alfa is a recombinant, modified factor Xa (FXa) molecule that is used for the reversal of the anticoagulant effect of oral anti‐FXa anticoagulants in patients with major haemorrhage. Here, we present a case of an 85‐year‐old man taking rivaroxaban for atrial fibrillation, who presented with an acute, upper gastrointestinal bleed. He was stabilised with red cell transfusion and then received a 400 mg bolus of andexanet alfa. Within minutes of this, he developed chest tightness, shortness of breath, ischaemic electrocardiographic changes and then cardiac arrest from which he could not be resuscitated. The onset of symptoms was clearly temporally related to andexanet alfa administration and the differential diagnosis includes anaphylaxis with Kounis syndrome, or myocardial infarction. Although infusion site reactions have been reported and are relatively common, this is to date the first case of a fatal drug reaction andexanet alfa. This knowledge can be factored into physicians’ risk–benefit decisions when treating patients with oral anti‐FXa anticoagulant‐associated major haemorrhage.

A 9‐month‐old mixed‐breed dog developed generalised pustular dermatitis, accompanied by lethargy and hyperthermia, 7 days after oral fluralaner administration. Dermatopathological and microbiological evaluations were consistent with a pustular acantholytic dermatitis. A 4‐month course of immunosuppressive therapy resulted in complete remission of lesions, which did not recur after therapy was withdrawn. [ABSTRACT FROM AUTHOR]

Immune checkpoint inhibitor (ICI) therapies carry the risk of major immune-related adverse events (irAEs). Among the most severe irAEs is epidermal necrosis that may clinically mimic Stevens-Johnson syndrome (SJS) and toxic epidermal necrosis (TEN). The aim of this study was to provide a summary of the clinical and histological features of ICI-associated epidermal necrosis, with a special focus on factors associated with fatal outcomes in cases of extensive disease. A total of 98 cases, 2 new cases and 96 reported on PubMed and in the literature, of ICI-associated epidermal necrosis were assessed. Development of epidermal necrosis occurred between 1 day and 3 years after starting ICI therapy, with an average onset of 13.8 weeks for patients with limited (< 30% BSA) and 11.3 weeks for those with extensive (≥ 30% BSA) involvement, and a median onset of 5.8 weeks and 4 weeks respectively. A preceding rash was seen in 52 cases and was more common in extensive cases. Mucosal involvement was only reported in 65% of extensive cases but was significantly associated with fatal reactions. Co-administration of cytotoxic chemotherapy was associated with more extensive disease. Recovery was observed in 96% and 65% of those with limited and extensive involvement respectively and no specific therapy was associated with improved survival. Young age was significantly associated with poor outcomes in extensive disease, the average age of surviving patients was 64.5 years old versus 55.1 years old for deceased patients, p < 0.01. Both superficial perivascular and interface/lichenoid inflammatory infiltrates were commonly seen. These findings suggest that ICI-associated epidermal necrosis should be considered a distinct clinical entity from drug-induced SJS/TEN. [ABSTRACT FROM AUTHOR]

Toxic erythema of chemotherapy is a broad but useful diagnosis used to summate the non‐infectious, non‐allergic, and reproducible reaction of certain chemotherapeutics. Due to overlapping chemotherapy side effects and often multiple drug exposures, identification of a singular culprit drug is challenging for dermatologists. Herein, we report a patient with 6‐mercaptopurine (6‐MP) toxic erythema confirmed via toxic metabolite markers secondary to increased levels of thiopurine methyltransferase activity, or so called "super shunting." Consulting dermatologists should be aware of "super shunting" in pediatric patients and consider testing for metabolites in patients with toxic acral erythema and mucositis in the setting of 6‐MP. [ABSTRACT FROM AUTHOR]

Adverse drug reactions, multiple drug allergy syndrome, and multiple drug intolerance syndrome, are common terms used in clinical practice worldwide. Here we present a 61-year-old Caucasian female, who is diabetic and hypertensive, and started receiving doxycycline for an upper respiratory tract infection. Simultaneously, she selfprescribed Advil.®. The patient has had a previous episode of drug intolerance. In this episode, she presented with a skin rash included bullae on her arms, legs and in part of her abdomen along with some systemic symptoms such fever, cough, and upset stomach. Biopsies for hematoxylin and eosin (H&E), direct immunofluorescence (DIF), and immunohistochemistry (IHC) stain analysis were performed. The diagnosis was made based upon interpretation of the histology in the context of drug reaction with alterations on the dermal lymphatics. DIF showed significant deposits of fibrinogen, complement/C3c and IgA around the dermal vessels, and at the endothelial-mesenchymal dermal cell junctions. IHC staining showed lymphangiectases with strong staining of the lymphatic junctions to the adjacent upper dermis using D2-40 marker. In this case, it is possible that the drug reaction could be causing previously unreported damage in lymphatics, including fragmentation and dilatation. These channels are stimulated inhibited, contracted, and relaxed by interactions with multiple receptors and the inflammation could cause dysregulation in those including their shape. [ABSTRACT FROM AUTHOR]

With the increasing number of young breast cancer (BC) patients worldwide, concerns about hair loss and skin change persist among BC survivors. This study aimed to evaluate the hair loss and skin changes in Asian BC patients and to compare them according to the treatment regimens. This study enrolled 322 patients scheduled to undergo BC surgery. Hair loss and skin changes were assessed at the following two time points: one day before surgery and 6 months after surgery. Patients who had received systemic anticancer treatment before surgery were assigned to the neoadjuvant treatment group, while patients who were scheduled to receive systemic anticancer treatment were assigned to the adjuvant treatment group. In the adjuvant treatment group, patients with taxane‐based chemotherapy had significantly higher odds of increased hair loss, a higher melanin index, and an increased volume of wrinkles (p < 0.0001, p = 0.0110, and p = 0.0371, respectively). In the neoadjuvant treatment group, hair loss was reversed in most patients at 6 months after surgery. Clinicians should inform BC patients about the potential for hair loss and skin changes and provide supportive care to mitigate the effects on the patients' quality of life. [ABSTRACT FROM AUTHOR]

Background: Diagnosing drug reaction with eosinophilia and systemic symptoms (DRESS) can be challenging. Objectives: We sought to identify clinical and laboratory features outside of the Registry of Severe Cutaneous Adverse Reaction (RegiSCAR) criteria that distinguish patients with probable DRESS (RegiSCAR ≥ 4) from those with drug rash and eosinophilia (DRE). Methods: Using international coding classifications of drug-induced fever, generalized skin eruption due to medications, and eosinophilia, a retrospective audit from 2008 to 2023 of hospitalized patients was performed. Results: Forty-four cases of DRESS were compared to 80 cases of DRE. In addition to the RegiSCAR distinguishing factors for DRESS were longer drug latency before symptom onset (median 21 vs 5 days, P < .001) and higher alanine transaminase levels (increase by a factor of 2.49 [95% confidence interval, 1.56, 4.00; P = .009]). Follow-up (mean 5.67 years) revealed a low rate of statewide drug alert reporting (29.6%) and drug allergy testing in DRESS (20.5%). Inadvertent reexposure to a culprit or structurally related drug resulted in recurrent DRESS in 3 patients (7.5%), and tolerance of structurally related drugs occurred in 8 patients (17.5%). Conclusion: In this large study evaluating DRE patients whose disease does not meet the RegiSCAR criteria for DRESS, we found that additional factors outside the RegiSCAR criteria may help clinicians differentiate DRESS, which is critical for optimal and timely patient management. Our study also highlights the need for development of local protocols to ensure appropriate allergy labeling and testing are performed to prevent recurrent DRESS.

An identical group of disorders has been called “interstitial granulomatous dermatitis” and “palisaded neutrophilic and granulomatous dermatitis.” In addition, a drug-induced subset of this condition has been named “interstitial granulomatous drug reaction (IGDR).” More recently, “reactive granulomatous dermatitis (RGD)” has been proposed as an umbrella term encompassing these three disorders. A considerable number of RGD cases are associated with systemic conditions, including autoimmune diseases, such as rheumatoid arthritis and systemic lupus erythematosus, inflammatory bowel disease, and malignancies. IGDR has also been shown to be caused by certain medications. We present a case of a 74-year-old Japanese man showing an asymptomatic, well-demarcated erythema eruption on the bilateral inguinal region extending to the lower abdomen and proximal thigh area. He had hyperlipidemia and had been taking pravastatin for 4 years. A biopsy specimen taken from the erythematous lesion revealed infiltration of lymphocytes and histiocytes in the upper and lower dermis. Interstitial infiltrates of histiocytes and lymphocytes were found as they were dispersed between collagen bundles. Immunostaining showed CD68+ macrophages intermingled with CD4+ and CD8+ T cells. Based on the clinical and histologic findings, the eruption was diagnosed as RGD. Because of the possibility of IGDR, pravastatin was stopped. His eruption completely disappeared within 6 months after the discontinuation. The list of drugs that cause RGD includes angiotensin-converting enzyme inhibitors, antihistamines, β-blockers, antidepressants, anticonvulsants, tocilizumab and ustekinumab. In addition, various statins have been reported to induce drug eruptions. The eruption types are mainly eczematous or lichenoid reactions, with psoriasiform or ichthyosiform reactions occurring rarely. There was only one report documenting that RGD occurred in patients administered rosuvastatin, with annular, violaceous plaques distributed on the extremities, proximal trunk and intertriginous areas. Pravastatin induces lichenoid eruption, but RGD has not been documented. Our case suggests that RGD is underestimated as an adverse effect of statins possibly because of its unusual cutaneous manifestations.

The article discusses a case of a 63-year-old male patient with enteropathy-associated T-cell lymphoma who developed keratoacanthomas (KAs) from a PD-1 inhibitor and was successfully treated with topical 5-fluorouracil (5-FU) without halting immunotherapy. The patient underwent allogeneic transplant (allo-HSCT) from his son and achieved a third complete remission after resolving the lesions with 5-FU. The use of 5-FU in treating nivolumab-induced KAs highlights its potential as a valuable tool for managing immune-related adverse events and enabling uninterrupted cancer treatment. [Extracted from the article]

Drug reaction with eosinophilia and systemic symptoms (DRESS) syndrome is a severe, potentially life-threatening, drug-induced hypersensitivity reaction that involves hematological abnormalities (atypical lymphocytosis, eosinophilia), lymphadenopathy, skin eruption, and internal organ involvement (lung, liver, kidney). The 36-year-old female patient was followed by bloody diarrhea, diffuse skin rashes and hepatitis. She was diagnosed with psoriatic arthritis, and Leflunomide 20 mg was added to the treatment six weeks ago. Upon developing hepatic encephalopathy and deepening the fulminant liver failure during the follow-up, a living donor liver from her son was transplanted on the 4th day of hospitalization. The patient had deceased on the second day after liver transplantation due to multiple organ failures. In the literature, mortality in DRESS syndrome is mostly secondary to hepatic failure. Liver transplantation cannot be effective due to systemic involvement and recurrence in the transplanted liver. [ABSTRACT FROM AUTHOR]

Abstract Introduction Brodalumab is a human interleukin-17 receptor A antagonist indicated for the treatment of moderate-to-severe plaque psoriasis in adult patients who are candidates for systemic therapy or phototherapy and have failed to respond or have lost response to other systemic therapies. Although the US prescribing information for brodalumab includes a boxed warning regarding suicidal ideation and behavior, no causal association has been demonstrated. Here, we summarize 5 years of pharmacovigilance data, from August 15, 2017, through August 14, 2022, reported to Ortho Dermatologics by US patients and healthcare providers. Methods Prevalence of the most common adverse events (AEs) listed in the brodalumab package insert (incidence ≥ 1%) and AEs of special interest are described. Brodalumab exposure was estimated as the time from the first to last prescription-dispensing authorization dates. Data were collected from 4744 patients in the USA, with an estimated exposure of 5815 patient-years. Results Over 5 years, 11 cases of adjudicated major adverse cardiovascular events were reported (0.23 events/100 patients), a rate lower than that experienced by patients in the international Psoriasis Longitudinal Assessment and Registry. There were 106 serious infections. No serious fungal infections were reported. There were 40 confirmed and 2 suspected COVID-19 cases, with no new COVID-19-related deaths. Of 49 reported malignancies among 42 patients, 3 were deemed possibly related to brodalumab. No completed suicides and no new suicidal attempts were reported. Conclusion Five-year pharmacovigilance data are consistent with the established safety profile reported in long-term clinical trials and previous pharmacovigilance reports, with no new safety signals.

Tebentafusp is a bispecific protein that recently underwent FDA approval for the treatment of metastatic uveal melanoma that functions by redirecting cytotoxic T cells to glycoprotein-100, a protein highly expressed in melanoma. Although clinical trials have demonstrated that rashes are common in the first few days of treatment, little is known about skin reactions that develop later in the treatment course. Herein, we describe a type IV hypersensitivity reaction and vitiligo-like depigmentation that developed six weeks into treatment and discuss the possible mechanisms underlying these reactions. The type IV hypersensitivity reaction resolved without intervention within seven weeks of onset, suggesting that tebentafusp can be safely continued in select patients who develop this cutaneous reaction.

We describe a particularly severe case of drug reaction with eosinophilia and systemic symptoms (DRESS) syndrome with hemodynamic instability, erythroderma, profound eosinophilia, and severe organ dysfunction. We attribute the severity in part to a delay in diagnosis due to patient's skin of color, as the erythroderma was not noticed until a dermatologist was consulted. This case highlights how even severe skin disease can present less conspicuously in patients with darker skin types. We outline several strategies that can help clinicians to recognize DRESS and other skin disease phenotypes in patients of color, thereby avoiding delays in diagnosis as seen in this case.

Introduction: Iron deficiency is the most common cause of anemia in both sexes, although it is more common in women. Intravenous (IV) iron replacement is preferred in patients who cannot tolerate oral treatment or when iron stores need to be replenished rapidly. In this study, we wanted to share the ferric carboxymaltose (FCM) desensitization protocol that we self-created and successfully applied. Methods: This retrospective cross-sectional study included patients with a history of hypersensitivity reactions (HSRs) to IV or oral iron replacement and patients who were planned to receive IV iron replacement but were referred to the allergy clinic because of have risk factors (atopic diseases, history of HSR to other drugs, high serum tryptase levels, etc.) for HSRs. Before desensitization, some of the patients underwent skin tests (skin prick test and intradermal test) with FCM, and the results were recorded. Skin tests were not performed in patients with a history of drug use (antihistamine, systemic steroid, omalizumab, etc.) that affected the results of skin tests. All patients underwent a one-bag 8-step desensitization protocol with 500 mg FCM and were observed for 2 h after desensitization. Results: A total of 15 patients (14 females and 1 male) with a mean age of 41.13 ± 11.18 years were included in the study. When the patients were evaluated in terms of the risk of allergic reactions according to their clinical history, 8 patients had a history of anaphylaxis with iron preparations (FCM, n = 4; ferric hydroxide sucrose, n = 2; iron [II] glycine sulfate, n = 1; and iron [III] hydroxide polymaltose, n = 1), and 7 patients had a history of HSR other than anaphylaxis with iron preparations (urticaria, n = 6 [FCM, n = 2; iron (II) glycine sulfate, n = 2; and iron (III) hydroxide polymaltose, n = 2] and urticaria + angioedema [ferric hydroxide sucrose, n = 1]). Desensitization was successfully completed in all patients. No HSR was observed during or after the procedure in any of the patients. Conclusion: IV iron replacement is a very effective method, especially in cases where iron stores need to be replenished more rapidly. In patients with a history of iron HSR or at risk of developing HSR, replacement can be safely performed without an allergic reaction with successful desensitization protocols. [ABSTRACT FROM AUTHOR]

Drug-induced hypersensitivity syndrome (DiHS), also known as drug reaction with eosinophilia and systemic symptoms (DRESS), is a severe cutaneous adverse reaction (SCAR) characterized by an exanthem, fever, and hematologic and visceral organ involvement. Anticonvulsants, antibiotics, and allopurinol are the most common triggers. The pathogenesis involves a complex interplay between drugs, viruses, and the immune system primarily mediated by T-cells. DiHS/DRESS typically presents with a morbilliform eruption 2-6 weeks after drug exposure, and is associated with significant morbidity, mortality, and risk of relapse. Long-term sequelae primarily relate to organ dysfunction and autoimmune diseases. Part I of this continuing medical education activity on DiHS/DRESS provides an update on epidemiology, novel insights into pathogenesis, and a description of clinicopathological features and prognosis. [ABSTRACT FROM AUTHOR]

Drug-induced hypersensitivity syndrome, also known as drug reaction with eosinophilia and systemic symptoms, is a severe cutaneous adverse reaction characterized by an exanthem, fever, and hematologic and visceral organ involvement. The differential diagnosis includes other cutaneous adverse reactions, infections, inflammatory and autoimmune diseases, and neoplastic disorders. Three sets of diagnostic criteria have been proposed; however, consensus is lacking. The cornerstone of management is immediate discontinuation of the suspected drug culprit. Systemic corticosteroids remain first-line therapy, but the literature on steroid-sparing agents is expanding. Longitudinal evaluation for sequelae is recommended. Adjunctive tests for risk stratification and drug culprit identification remain under investigation. Part II of this continuing medical education activity begins by exploring the differential diagnosis and diagnosis of drug-induced hypersensitivity syndrome/drug reaction with eosinophilia and systemic symptoms and concludes with an evidence-based overview of evaluation and treatment. [ABSTRACT FROM AUTHOR]

A subtype of cutaneous lupus erythematosus known as lupus erythematosus tumidus (LET) is characterized by sun-exposed areas that typically display urticaria-like papules and plaques. For LET, systemic therapy with antimalarials – particularly hydroxychloroquine (HCQ) – is the first line of treatment. Even though the safety profile of these medications appears to be high, there have been very few reports of side effects in the literature, including hemolytic anemia, retinal toxicity, maculopapular rash, gastrointestinal disturbance, and blue-gray discoloration of the skin or mucous membranes. Here, we report a unique instance of a 46- year-old LET smoker who, following HCQ treatment, developed a generalized myopathy. [ABSTRACT FROM AUTHOR]

A 29‐year‐old Caucasian woman presented with a 3‐month history of bilateral lower limb swelling with painful erythematous nodules on shins without ulceration. She had been taking minocycline for acne vulgaris for 3 years. Biochemical investigations showed deranged liver function test with positive ANA and mixed antinuclear factor (ANF) pattern. A skin biopsy was in keeping with a diagnosis of nodular vasculitis. Her skin lesions and liver function test improved within 3 months of stopping the minocycline treatment. This case report raises the awareness that minocycline could be a potential cause of nodular vasculitis, patients on minocycline should be closely monitored and minocycline should ideally not be prescribed for more than 12 weeks, given the possible adverse effects. [ABSTRACT FROM AUTHOR]

Drug reaction with eosinophilia and systemic symptoms (DRESS) syndrome is rare but carries significant mortality and morbidity, making early identification and definitive management crucial. The diagnosis of DRESS is made clinically and involves consideration of a broad list of differential diagnoses. Given variable clinical presentations among patients with DRESS syndrome, clinicians should look for common findings and other hallmarks of the syndrome while monitoring for known complications. Additionally, clinicians should maintain a high index of suspicion to avoid missing more mild presentations, such as in this case patient with DRESS syndrome minor. [ABSTRACT FROM AUTHOR]

Drug reaction with eosinophilia and systemic symptoms (DRESS) syndrome is a severe cutaneous adverse drug eruption characterized by rash, fever, lymphadenopathy, hematologic abnormalities, and organ dysfunction. Identifying causative agents and monitoring disease course in DRESS syndrome is crucial to prevent end-organ damage. The temporal relationship between causative medications including vancomycin and laboratory abnormalities in DRESS has not been studied, limiting the utility of laboratory data in monitoring disease course. Our study aims to investigate associations between medication class and peak serum laboratory values using simple linear regression (absolute eosinophils, creatinine, alanine aminotransferase [ALT] and aspartate aminotransferase [AST]). We found a significant difference between timing of peak AST values among vancomycin-triggered DRESS compared to other trigger groups. These findings draw attention to the increased role of AST as a diagnostic and monitoring tool in DRESS. [ABSTRACT FROM AUTHOR]

Erythema Multiforme Major (EMM) is a rare hypersensitivity reaction that primarily affects the skin and mucosa, typically self-limiting. This case discusses a patient who developed severe EMM lesions after consuming nimesulide, a non-steroidal anti-inflammatory drug (NSAID), for abdominal discomfort. Patient was admitted to the hospital, the drug was discontinued, and supportive measures such as pain management and fluid replacement were initiated. This case, being the first to identify nimesulide as a possible trigger for EMM, aims to contribute to the growing body of knowledge on this topic. It emphasizes the need for vigilance and swift intervention for unusual drug reactions.

Drug reaction with eosinophilia and systemic symptoms (DRESS)/drug-induced hypersensitivity syndrome (DIHS) is a life-threatening, multi-organ adverse drug reaction with a mortality rate of approximately 10 %–20 %. The most common culprit drugs are anticonvulsants, some antibiotics such as dapsone and minocycline, salazosulfapyridine, allopurinol and some antiretroviral molecules such as abacavir and nevirapine. Only one case of DRESS induced by sildenafil has been reported in the literature. Here we report a new case.

Fixed drug eruption (FDE) is a common entity encountered in our day-to-day clinical practice. It is a T-cell-dependent pathway with induction of interferon-gamma-producing CD8+ T-cells in the dermis and epidermis. It is not just a drug that causes a fixed eruption but has also been described with food known as fixed food eruption and also with other agents. The article describes the common causes and pathomechanism of FDE.

Introduction: Adalimumab (ADM) is a recombinant human monoclonal antibody (anti-TNFα) used to treat inflammatory bowel diseases. It can cause kidney injury (KI). Case diagnosis/treatment: We describe two pediatric patients with Crohn's disease (CD) in whom ADM therapy was associated with kidney injury (KI). The drug was discontinued in both cases. For the first patient, changes were irreversible despite intensive glucocorticosteroid (GCS) therapy. For the second patient, discontinuation of ADM led to an improvement in kidney function. Conclusions: Due to the risk of KI in patients undergoing ADM therapy, careful assessment of kidney function and early specialist referral are required. Timely withdrawal of ADM can significantly reduce kidney damage, but in some cases, the kidney damage can be irreversible. [ABSTRACT FROM AUTHOR]

Allopurinol-induced drug reaction syndrome with eosinophilia and systemic symptoms (A-DRESS) is a welldescribed condition in adults, whereas it is uncommon among children. We describe a case of A-DRESS in a 16-year-old male with steroid-dependent nephrotic syndrome. He presented a life-threatening clinical course with persisting fever, skin rash, eosinophilia, lymphadenopathy, distributive shock, and herpesvirus 6 detection. The withdrawal of allopurinol and a combination of intravenous immunoglobulins (IVIGs) and systemic corticosteroids led to the patient's recovery without sequelae. Drug reaction with eosinophilia and systemic symptoms (DRESS) in pediatrics is rare and can present in a severe form. Early diagnosis and timely treatment are critical for prognostic purposes. This report suggests the potentially crucial role of IVIG in the treatment of patients with A-DRESS. [ABSTRACT FROM AUTHOR]

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Background: A previously unreported systemic reaction to Galcanezumab (Emgality) is described. Galcanezumab is a humanized monoclonal antibody designed to bind to calcitonin gene-related peptide, a neuropeptide associated with neurogenic inflammation during migraine attacks. Although clinical trials showed that Galcanezumab had few adverse reactions (injection site related erythema, pruritus, and swelling), no systemic drug reactions have been noted. Case report: A 50-year-old female with chronic migraine, mast cell disorder, Hashimoto’s disease, positive antinuclear antibody and positive anti-cyclic citrullinated peptide antibody not on immune modulators received the initial dose of galcanezumab 240 mg after failing multiple migraine treatments. The following day, she developed injection site reaction, malar erythema and flu-like symptoms. Symptoms progressed the second day after injection, and she developed swelling in her lips and throat. Intravenous steroid and antihistamines improved airway symptoms, and the remaining symptoms improved after a course of oral steroids. Conclusions: Delayed system allergic reaction to Galcanezumab requiring emergency intervention may occur. A history of autoimmune disorder may be a predisposing factor. [ABSTRACT FROM AUTHOR]

Posterior reversible encephalopathy syndrome (PRES) is a neurotoxic state which is characterized by seizures, headache, visual disturbances, paresis, and altered mental status. Golimumab is anti-tumor necrosis factor-α inhibitor (anti-TNF-α) that can be used in the treatment of rheumatologic diseases. Here, we present a patient who had developed PRES after golimumab treatment for ankylosing spondylitis (AS). A 45-year-old female patient was admitted to the emergency service with a newly onset severe headache, loss of vision in both eyes, and two generalized tonic–clonic seizures that lasted for 3 to 4 min. The patient had the diagnoses of AS for 12 years and hypertension for 3 years and receiving golimumab and carvedilol. The patient was diagnosed with PRES based on the current clinical and diffusion cranial magnetic resonance imaging (MRI) findings. On suspicion of being the trigger of this situation, golimumab was stopped. After starting anti-convulsant therapy and controlling blood pressure, the neurological findings recovered rapidly and no seizures were seen. Control MRI images, in the first month's visit, were normal. Although chemotherapeutic agents are well-known causes of PRES, there are few reported cases with anti-TNF-α agents in the literature. To our knowledge, this is the first case that developed PRES after golimumab. Demyelinating diseases are the most frightening neurologic complication of anti-TNF-α treatment; however, PRES should come to mind in patients presenting with neurological symptoms. [ABSTRACT FROM AUTHOR]