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Antibody-drug conjugates (ADCs) are an emerging class of anticancer agents that combine targeting antibodies with potent cytotoxic agents. Their molecular configuration allows for increased therapeutic efficacy and reduced adverse-effect profiles compared to monoclonal antibodies or cytotoxic chemotherapy alone. ADCs cause off-target toxicities through several mechanisms, including premature deconjugation of the cytotoxic agent in the serum and the presence of the targeted antigen on normal tissues. Given cutaneous adverse events comprise 31.3% of all-grade adverse events in clinical trials involving ADCs, dermatologists are increasingly called upon to manage the cutaneous toxicities caused by these drugs. In this review, we summarize known cutaneous toxicities of the ADCs that have been approved for use by the US Food and Drug Administration to date. Dermatologists can play a key role in recognizing cutaneous reactions associated with ADCs, contributing to guidelines for their management, and aiding during clinical trials to generate detailed morphologic and histopathologic descriptions of cutaneous toxicities caused by ADCs. [ABSTRACT FROM AUTHOR]

Abstract Henoch–Schönlein purpura (HSP) is an immunoglobulin A (IgA)‐mediated small‐vessel vasculitis mostly observed in children and rarely in adults. It can affect many organs, mainly the skin, kidneys, joints, and gastrointestinal tract. We report a case of HSP occurring after COVID‐19 vaccine (Pfizer‐BioNTech).

Programmed cell death-1 (PD1) inhibitors, a form of immune checkpoint inhibitor, are efficacious for metastatic melanoma but are associated with cutaneous adverse reactions (CARs). Studies in Europe and North America showed that CARs are associated with an increased overall survival. However, studies from Asia showed mixed results. There is a paucity of data regarding the efficacy of PD1 inhibitors and the effect of CARs on overall survival from Southeast Asia. A retrospective study of patients in the National Cancer Centre Singapore who were diagnosed with melanoma between 2015 and 2020 was conducted. Patients were included in the study if they had stage IV melanoma (advanced melanoma). Sixty-two patients were included in the study. The median age was 62.5 years and acral melanoma was the commonest subtype. Forty-three patients received PD1 inhibitors. Comparing patients who did not receive PD1 inhibitors to patients who received PD1 inhibitors, the former had a median overall survival of 6 months (95% CI: 5.07, 6.93), whereas the latter had a median overall survival of 21 months (95% CI: 13.33, 28.67; p < 0.001) (Hazard ratio 0.32; 95% CI: 0.16, 0.63; p = 0.001). Amongst patients who received PD1 inhibitors, patients who developed CARs had a greater median overall survival of 33 months (95% CI: 17.27, 48.73) compared to 15 months (95% CI: 9.20, 20.80; p = 0.013) for patients who did not (HR 0.29; 95% CI: 0.098, 0.834; p = 0.022). This study provides insight into the outcomes of metastatic melanoma in Singapore, and adds to the body of evidence supporting the use of PD1 inhibitors in Asians. [ABSTRACT FROM AUTHOR]

This article discusses the use of in vivo and ex vivo tests for identifying adverse drug reactions to non-beta lactam antibiotics. The study found that patient history alone has a high misdiagnosis rate for non-immediate hypersensitivity reactions. The researchers conducted intradermal tests, ELISpot assays, and oral provocation tests on 26 participants with a history of non-severe hypersensitivity to non-beta lactam antibiotics. The combined use of intradermal tests and ELISpot assays had a higher positive rate than either test alone, and the oral provocation test identified additional positive cases. The study suggests that integrating these tests can accurately diagnose non-immediate hypersensitivity to non-beta lactam antibiotics. [Extracted from the article]

Programmed cell death-1 (PD1) inhibitors, a form of immune checkpoint inhibitor, are efficacious for metastatic melanoma but are associated with cutaneous adverse reactions (CARs). Studies in Europe and North America showed that CARs are associated with an increased overall survival. However, studies from Asia showed mixed results. There is a paucity of data regarding the efficacy of PD1 inhibitors and the effect of CARs on overall survival from Southeast Asia. A retrospective study of patients in the National Cancer Centre Singapore who were diagnosed with melanoma between 2015 and 2020 was conducted. Patients were included in the study if they had stage IV melanoma (advanced melanoma). Sixty-two patients were included in the study. The median age was 62.5 years and acral melanoma was the commonest subtype. Forty-three patients received PD1 inhibitors. Comparing patients who did not receive PD1 inhibitors to patients who received PD1 inhibitors, the former had a median overall survival of 6 months (95% CI: 5.07, 6.93), whereas the latter had a median overall survival of 21 months (95% CI: 13.33, 28.67; p < 0.001) (Hazard ratio 0.32; 95% CI: 0.16, 0.63; p = 0.001). Amongst patients who received PD1 inhibitors, patients who developed CARs had a greater median overall survival of 33 months (95% CI: 17.27, 48.73) compared to 15 months (95% CI: 9.20, 20.80; p = 0.013) for patients who did not (HR 0.29; 95% CI: 0.098, 0.834; p = 0.022). This study provides insight into the outcomes of metastatic melanoma in Singapore, and adds to the body of evidence supporting the use of PD1 inhibitors in Asians.

We presents an unique and significant case of Acute Generalized Exanthematous Pustulosis (AGEP) associated with the use of tadalafil, a phosphodiesterase type 5 inhibitor for erectile dysfunction. AGEP, typically linked to antibiotics and antiepileptics, had not been previously reported with tadaladil in the MEDLINE database. The case involved a 40-year-old male who developed an erythematous rash, fever and sterile pustules after starting tadalafil. A skin biopsy confirmed AGEP. Discontinuation of the drug and treatment with prednsiolone cleared the dermatosis. This case emphasizes the need for awareness among healthcare providers regarding this potential adverse reaction, considering the growing use of tadalafil.

Here, we report an 86‐year‐old Japanese woman presenting with confluent maculopapular erythema, which developed following the second dose of COVID‐19 Messenger RNA (mRNA) vaccine (BNT162b2). Her skin lesions spread over time and persisted for more than 3 months. Surprisingly, immunohistochemical staining of the lesion 100 days after the disease onset revealed the COVID‐19 spike protein expressed by vascular endothelial cells and eccrine glands in the deep dermis. As she had no episode of COVID‐19 infection, it is highly likely that the spike protein was derived from the mRNA vaccine and it might be the cause of the development and persistence of her skin lesions. Her symptoms were prolonged and intractable until oral prednisolone was given. [ABSTRACT FROM AUTHOR]

Background: Human leukocyte antigen (HLA) is associated with drug-induced cutaneous adverse reactions, including antiepileptic drugs (AEDs). HLA gene polymorphism has a regional discrepancy, and it is therefore important to study it in different populations.Objective: To investigate the role of HLA in AED-induced mild cutaneous adverse drug reactions (cADRs) in a Northeast Han Chinese population.Methods: A case-control study was performed in the First Hospital of Jilin University between August 2016 and March 2017. In total, 26 patients with mild cADRs induced by AEDs and 23 AED-tolerant control patients were included. Sequence-based typing (SBT) was used to detect HLA-A and HLA-B genotypes. Differences in genotype frequencies between groups were assessed using Fisher's exact test.Results: In the mild cADRs group, 22 patients (84.6%) presented with maculopapular exanthema (MPE) and four patients (15.4%) presented with an isolated itch. The median duration between the AED exposure and cADRs was 7.5 days (IQR, 3 - 14 days). We failed to find statistically significant differences in HLA alleles between the cADRs group and the control group when considering all the drugs included in our study together or when considering oxcarbazepine (OXC), carbamazepine (CBZ), and levetiracetam (LEV) alone (P > 0.05).Conclusions: Our findings indicated that there was no correlation between HLA alleles and AED-induced mild cADRs in the Northeast Han Chinese population. [ABSTRACT FROM AUTHOR]

Background: An increasing number of cutaneous adverse reactions (CARs) to SARS-CoV-2 vaccines have been reported, but their incidence is debated. Objective: To estimate the pooled incidence of CARs to SARS-CoV-2 vaccines in the general adult population. Methods: A systematic review and meta-analysis of original articles published on MEDLINE via PubMed and Web Of Science from 1 January 2020 to 18 July 2022 was undertaken. Studies reporting the incidence proportion of CARs (defined as number of new cases of CARs on the total of vaccinated people) were included. All types of SARS-CoV-2 vaccine were included. People receiving at least one dose were considered eligible. Local cutaneous reactions were excluded. Results: A total of 970 records were identified and screened by title and abstract; 22 observational studies were included with aggregate data on 93,165 participants. The pooled incidence of overall CARs was 5% (95%CI 4–6%; I2 = 99%; p < 0.001), ranging from <0.01 to 19.00%. Most CARs were new onset dermatitis including rash, urticaria and vascular lesions; one case of Steven–Johnson syndrome and six cases of erythema multiforme were reported. In the sensitivity analysis we found that the incidence of CARs after the first and second dose was similar, i.e., 3% (95%CI 2–3%; I2 = 96%; p < 0.001) and 3% (95%CI 2–4%; I2 = 97%; p < 0.001), respectively. The magnitude of incidence of CARs remained unchanged independently of vaccine platform and in the general population versus healthcare workers. Conclusions: CARs associated with SARS-CoV-2 vaccines are frequent but mild and self-remitting, whereas severe CARs are rare. [ABSTRACT FROM AUTHOR]

Background: Tumor necrosis factor alpha (TNF-α) inhibitors, such as adalimumab, have significantly advanced the treatment of inflammatory diseases. However, these therapies are associated with various cutaneous adverse reactions., Case Presentation: We describe two rare instances of isolated facial hyperpigmentation induced by adalimumab. Both patients presented with asymptomatic, isolated brown macules on the cheeks following adalimumab treatment for ankylosing spondylitis. The hyperpigmentation appeared shortly after starting the medication in both cases. In one case, the hyperpigmentation persisted despite stopping the medication, while in the second case, it completely resolved within one month after discontinuation. However, in the second patient, the hyperpigmentation recurred after switching to certolizumab, another TNF-α inhibitor. No skin biopsies were performed, and both patients were otherwise healthy, with normal laboratory evaluations., Conclusion: Hyperpigmentation is an uncommon adverse reaction of this class of drugs, with only a few reported cases in the literature. The recurrence of hyperpigmentation after switching to another TNF-α agent, certolizumab, further suggests that this reaction may be a class effect, adding new insights into the spectrum of cutaneous side effects associated with TNF-α inhibitors. Clinicians should consider this potential side effect in patients presenting with hyperpigmentation, and sun protection should be recommended as a preventive measure., (Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.net.)

Competing Interests: Dr Foley has received grant support, and/or served on advisory boards, and/or served as a consultant, and/or has received travel grants, and/or has served as a speaker for or received honoraria from AbbVie, Akaal, Amgen, Arcutis, Argenx, Aslan, AstraZeneca, Boehringer Ingelheim, Botanix, Bristol Myers Squibb, Celgene, Celtaxsys, CSL, Cutanea, Dermira, Evelo, Galderma, GenesisCare, Genentech, GlaxoSmithKline, Hexima, Incyte, Janssen, Kymab, Leo Pharma, Lilly, Mayne Pharma, MedImmune, Melaseq/Geneseq, Merck, Novartis, Pfizer, Regeneron, Reistone, Roche, Sanofi, SunPharma, Takeda, Teva, UCB Pharma, Valeant, and ZaiLab. Drs Punchihewa, Lee, and Tan have no conflicts of interest to declare.

Introduction: Biological medications have significantly improved the prognosis of psoriasis patients. All biological drugs (except infliximab) for psoriasis require subcutaneous (SC) administration. Adverse events of biologic drug treatment include injection site reactions. ISRs are a local phenomenon characterized by swelling, erythema, pruritus, and pain around the injection site., Areas Covered: We conducted a review to analyze the differences between the ISRs of various biologics approved for psoriasis. Specifically, the review focused on anti-TNF-α, anti-IL12/23, anti-IL-17, and anti-IL-23 drugs., Expert Opinion: Etanercept and adalimumab have reported ISR rates of 37% and 20%, respectively, with erythema, pruritus, pain, and irritation being the most common. Citrate free (CF) solution and thinner needles have reduced ISR associated with adalimumab. Ustekinumab showed a low risk of ISR. Regarding secukinumab and ixekizumab, pain was found to be the most common ISR. The introduction of CF ixekizumab formulation has shown promise in reducing ISRs associated with ixekizumab. The risk of ISR appears insignificant with bimekizumab, brodalumab, and anti-IL23 drugs, with ISR rates ranging from less than 1% to 7.1%. The choice of biologic agent should consider ISR risk. Education on injection techniques and the use of single-dose autoinjectors/pens can mitigate ISR risk.

Background: Cutaneous drug eruptions are a significant source of morbidity, mortality, and cost to the healthcare system. Identifying the culprit drug is essential; however, despite numerous methods being published, there are no consensus guidelines. Objectives: Conduct a scoping review to identify all published methods of culprit drug identification for cutaneous drug eruptions, compare the methods, and generate hypotheses for future causality assessment studies. Eligibility criteria: Peer-reviewed publications involving culprit drug identification methods. Sources of evidence: Medline, Embase, and Cochrane Central Register of Controlled Trials. Charting methods: Registered PRISMA-ScR format protocol on Open Science Forum. Results: In total, 109 studies and 26 reviews were included comprising 656,635 adverse drug events, most of which were cutaneous. There were 54 methods of culprit drug identification published, categorized as algorithms, probabilistic approaches, and expert judgment. Algorithms had higher sensitivity and positive predictive value, but lower specificity and negative predictive value. Probabilistic approaches had lower sensitivity and positive predictive value, but higher specificity and negative predictive value. Expert judgment was subjective, less reproducible, but the most frequently used to validate other methods. Studies suggest that greater accuracy may be achieved by specifically assessing cutaneous drug eruptions and using combinations of causality assessment categories. Conclusions: Culprit drug identification for adverse drug reactions remains a challenge. Many methods have been published, but there are no consensus guidelines. Using causality assessment methods specifically for cutaneous drug eruptions and combining aspects of the different causality assessment categories may improve efficacy. Further studies are needed to validate this hypothesis. [ABSTRACT FROM AUTHOR]

Le vaccin chinois Sinopharm-CoronaVac®, est sûr et bien toléré, ses réactions cutanées sont rarement rapportées. Nous rapportons le cas d'une toxidermie secondaire à la prise de la 1re dose du vaccin Sinopharm-CoronaVac®. Une patiente âgée de 32 ans sans antécédents médicaux remarquables. Elle a été admise pour une éruption maculo-papuleuse généralisée et prurigineuse apparue 4 jours après l'administration de la première dose du vaccin Sinopharm-CoronaVac®. La causalité a révélé une association possible entre la prise du vaccin et la survenue de la réaction médicamenteuse. Des données publiées provenant d'essais randomisés de phase I et II ont montré que le vaccin type Sinopharm-CoronaVac® présente une bonne immunogénicité, une bonne sécurité et une bonne tolérance chez la majorité des patients, avec peu d'effets indésirables signalés. Dans la littérature, un seul cas de réactions cutanées a été mentionné avec le vaccin Sinopharm-CoronaVac® mais sans précisions. Nous rapportons un premier cas de toxidermie médicamenteuse de type exanthème maculo-papuleux suite à l'administration d'une première dose de vaccin SinopharmCoronaVac®. Chinese Sinopharm-CoronaVac® vaccine is safe and well tolerated, its skin reactions are rarely reported. We report the case of a cutaneous adverse reaction due to this vaccine. A 32-year-old female with no remarkable medical history. She was admitted for a generalized itchy maculo-papular rash appearing 4 days following the administration of the first dose of the Sinopharm-CoronaVac®. The causality reveals a possible association between the vaccine and the drug reaction. Published data from randomized trials Phase I and II trials have shown that the Sinopharm-CoronaVac® has good immunogenicity, safety and tolerability in the majority of patients with few reported adverse events. In literature, we found only one case that developed a cutaneous rash due to Sinopharm-CoronaVac® vaccine but without any precisions. We report the first case of a cutaneous adverse reaction type Maculopapular rash after the first dose of the Sinopharm-CoronaVac® vaccine. [ABSTRACT FROM AUTHOR]

Background: As more people become vaccinated against the SARS‐CoV‐2 virus, reports of delayed cutaneous hypersensitivity reactions are beginning to emerge. Methods: In this IRB‐approved retrospective case series, biopsy specimens of potential cutaneous adverse reactions from the Pfizer‐BioNTech or Moderna mRNA vaccine were identified and reviewed. Clinical information was obtained through the requisition form, referring clinician, or medical chart review. Results: Twelve cases were included. Histopathological features from two injection‐site reactions showed a mixed‐cell infiltrate with eosinophils and a spongiotic dermatitis with eosinophils. Three biopsy specimens came from generalized eruptions that showed interface changes consistent with an exanthematous drug reaction. Three biopsy specimens revealed a predominantly spongiotic pattern, consistent with eczematous dermatitis. Small‐vessel vascular injury was seen in two specimens, which were diagnosed as urticarial vasculitis and leukocytoclastic vasculitis, respectively. There were two cases of new‐onset bullous pemphigoid supported by histopathological examination and direct immunofluorescence studies. Eosinophils were seen in 10 cases. Conclusions: Dermatopathologists should be aware of potential cutaneous adverse reactions to mRNA‐based COVID‐19 vaccines. Histopathological patterns include mixed‐cell infiltrates, epidermal spongiosis, and interface changes. Eosinophils are a common finding but are not always present. Direct immunofluorescence studies may be helpful for immune‐mediated cutaneous presentations such as vasculitis or bullous pemphigoid. [ABSTRACT FROM AUTHOR]

Competing Interests: None disclosed.

An in‐depth characterization of the incidence, morphology, and onset of COVID‐19‐vaccines cutaneous adverse reactions is currently lacking. The existing literature on COVID‐19 vaccination‐related cutaneous adverse reactions largely focused on messenger RNA vaccines and mainly included type 1 hypersensitivity reactions, such as urticaria and angioedema. Other cutaneous manifestations are still poorly characterized and have been classified as delayed hypersensitivity rash. Our prospective observational study on a sample of 2740 subjects who underwent the COVID‐19 vaccination aimed at defining the prevalence of cutaneous adverse reactions and at identifying their timing of onset and their correlation with the administered dose. Vaccine‐related cutaneous adverse reactions occurred in 50 subjects. Patients were asked to complete a questionnaire on the type of COVID‐19 vaccine received, the time of onset of cutaneous reactions, and the dates of administration. Out of 2740 individuals who received the COVID‐19 vaccination, 50 were diagnosed with cutaneous adverse reactions to vaccine, after the first dose in 28 patients, after the second in 20, and after both in two. We reported localized injection site erythema in 12 patients and generalized cutaneous reactions in 38 patients. Our study shows that cutaneous adverse reactions to COVID‐19 vaccination are not common and most often occur after the first dose, recurring infrequently after the second dose. These reactions are usually easily manageable and, even in severe generalized cases, oral antihistamines and corticosteroids were sufficient for resolution. Therefore, except for immediate hypersensitivity reactions, cutaneous adverse reactions do not represent a contraindication to the completion of the vaccination cycle. [ABSTRACT FROM AUTHOR]

Drug reaction with eosinophilia and systemic symptoms (DRESS) is a distinct part of severe cutaneous adverse reactions (SCARs). It is characterized by fever, rash, hematologic abnormalities, lymphadenopathy, or/and different degrees of visceral organ involvement. Its diagnosis is particularly challenging due to the variability of its clinical presentations and its long latency period (2–6 weeks). Allopurinol, an uric acid‐lowering drug, has been incriminated in several cases of allopurinol‐induced DRESS syndrome. Through this paper, we present a case of allopurinol‐induced DRESS syndrome with initial oral mucosal involvement. A 69‐year‐old female patient presented with an erosive cheilitis that started 1 week prior to his presentation. The cheilitis was associated with maculopapular rash and fever. She started taking allopurinol, as treatment of Gout, 6 weeks before hospitalization. The histologic findings obtained from skin biopsy were consistent with a toxic drug reaction. A complete blood count (CBC) showed a moderate eosinophilia. Alteration of renal function was also noted, and the diagnosis of allopurinol‐induced DRESS syndrome was made. Systemic corticosteroid therapy was therefore started. The patient completely recovered and had been healthy for 3 years before developing a recurrence after re‐challenge with allopurinol. [ABSTRACT FROM AUTHOR]

Abstract Drug reaction with eosinophilia and systemic symptoms (DRESS) is a distinct part of severe cutaneous adverse reactions (SCARs). It is characterized by fever, rash, hematologic abnormalities, lymphadenopathy, or/and different degrees of visceral organ involvement. Its diagnosis is particularly challenging due to the variability of its clinical presentations and its long latency period (2–6 weeks). Allopurinol, an uric acid‐lowering drug, has been incriminated in several cases of allopurinol‐induced DRESS syndrome. Through this paper, we present a case of allopurinol‐induced DRESS syndrome with initial oral mucosal involvement. A 69‐year‐old female patient presented with an erosive cheilitis that started 1 week prior to his presentation. The cheilitis was associated with maculopapular rash and fever. She started taking allopurinol, as treatment of Gout, 6 weeks before hospitalization. The histologic findings obtained from skin biopsy were consistent with a toxic drug reaction. A complete blood count (CBC) showed a moderate eosinophilia. Alteration of renal function was also noted, and the diagnosis of allopurinol‐induced DRESS syndrome was made. Systemic corticosteroid therapy was therefore started. The patient completely recovered and had been healthy for 3 years before developing a recurrence after re‐challenge with allopurinol.

Background: An increasing number of cutaneous adverse reactions (CARs) to SARS-CoV-2 vaccines have been reported, but their incidence is debated. Objective: To estimate the pooled incidence of CARs to SARS-CoV-2 vaccines in the general adult population. Methods: A systematic review and meta-analysis of original articles published on MEDLINE via PubMed and Web Of Science from 1 January 2020 to 18 July 2022 was undertaken. Studies reporting the incidence proportion of CARs (defined as number of new cases of CARs on the total of vaccinated people) were included. All types of SARS-CoV-2 vaccine were included. People receiving at least one dose were considered eligible. Local cutaneous reactions were excluded. Results: A total of 970 records were identified and screened by title and abstract; 22 observational studies were included with aggregate data on 93,165 participants. The pooled incidence of overall CARs was 5% (95%CI 4–6%; I2 = 99%; p < 0.001), ranging from 2 = 96%; p < 0.001) and 3% (95%CI 2–4%; I2 = 97%; p < 0.001), respectively. The magnitude of incidence of CARs remained unchanged independently of vaccine platform and in the general population versus healthcare workers. Conclusions: CARs associated with SARS-CoV-2 vaccines are frequent but mild and self-remitting, whereas severe CARs are rare.

AGEP induced by hydroxychloroquine usually has a latency period of 2-3 weeks.7 In this patient, the rash was initiated 12 days after the first administration of generic hydroxychloroquine, which was consistent with the latency period described above. During his most recent hospitalization, he did not continue to receive the original hydroxychloroquine treatment but instead received the generic hydroxychloroquine (Hydroxychloroquine Sulfate Tablets, 100 mg per tablet) on the advice of a local physician, no other medications were administered. Keywords: acute generalized exanthematous pustulosis; cutaneous adverse reaction; hydroxychloroquine; treatment EN acute generalized exanthematous pustulosis cutaneous adverse reaction hydroxychloroquine treatment 3608 3610 3 08/09/22 20220801 NES 220801 CONFLICT OF INTEREST The authors declare that they have no conflict of interest. [Extracted from the article]

Trimebutine is a spasmolytic agent with antimuscarinic effects that is used for the treatment of irritable bowel syndrome (IBS) and lower gastrointestinal tract motility disorders. Lichenoid drug eruptions (LDE) to trimebutine maleate have not been previously reported. Here we present the case of a 50-year-old male patient who developed an extensive lichenoid eruption on his upper and lower extremities and trunk 4 weeks after starting treatment with trimebutine maleate 300 mg once daily for IBS. Two months after discontinuation of the drug and administration of topical treatment with emollients and corticosteroids, the LDE cleared completely with no recurrence. The diagnosis of LDE due to trimebutine was made, based upon the clinical features resembling lichen planus, the histological findings of interface dermatitis, the evidence of a temporal relationship between drug intake and the development of skin lesions, and resolution upon discontinuation of the drug. To the best of the authors’ knowledge, LDE following trimebutine maleate intake has not been previously reported. Management of trimebutine-induced LDE includes withdrawal of the causative agent and treatment with potent topical corticosteroids.

The use of the humanized monoclonal anti-programmed cell death 1 antibodies pembrolizumab and nivolumab as potent anticancer therapies is rapidly increasing. However, since their approval, numerous cases of cutaneous reactions have been reported. Cutaneous adverse reactions to these agents have yet to be fully characterized and range from nonspecific eruptions to recognizable skin manifestations, which may be localized and vary from mild to life threatening. This systematic review article provides an overview of the various adverse cutaneous reactions to pembrolizumab and nivolumab therapy and offers suggestions for their management. [ABSTRACT FROM AUTHOR]

The clinical classification of cutaneous adverse reactions by drugs should be clearly distinguished to avoid conceptual confusion and inconsistency. Although dermatologists appear to have established a roughly common consensus for cutaneous adverse reactions, some types are more rigorously defined than other, possibly misleading classifications. To assess the consensus on the clinical classifications, we investigated the concordance rate of diagnosis by Japanese experts through a snap visual inspection of various clinical pictures exhibiting erythema multiforme and maculopapular eruption types of cutaneous adverse reactions. The experts were shown images on a screen and were then asked to decide whether to classify cases as maculopapular eruption or erythema multiforme type, and the concordance rates were calculated. Overall, the mean concordance rate was 71.6% (standard deviation, 17.3%), and only 33.8% of cases had a 90% or more concordance rate. Our study shows that the determinations of erythema multiforme and maculopapular eruption types by the existing classification criteria were confusing even among experts, which prompted us to standardize the terminology. We propose clinically defining erythema multiforme type as generalized macules mainly of 1 cm or more with a tendency of elevation and coalescence, and maculopapular eruption type as generalized erythema other than erythema multiforme type. Currently, the clinical definitions of cutaneous adverse reactions are poorly described, which may be problematic upon analyzing large volumes of data. Our proposal for a new terminology will enhance the accuracy and consistency of information for the correct analysis of cutaneous adverse reactions. [ABSTRACT FROM AUTHOR]

Acute generalized exanthematous pustulosis (AGEP) is a dramatic generalized pustular rash of severe onset, which is considered a serious cutaneous adverse reaction to drugs. However, even though the clinical features are impressive and are often accompanied by systemic inflammation, it can be controlled quickly and safely by topical steroids subsequent to interruption of the offending drug. Here, we describe the management of a case and the evolution of the pustular rash. An elderly woman consulted with a generalized crop of 2–3 mm, nonfollicular pustules on erythematous background. In the 4 preceding weeks, she had been using amoxicillin/clavulanic acid for a bacterial implant infection and rivaroxaban. The clinical EuroSCAR criteria including the histology confirmed AGEP. Her medication was stopped and topical clobetasol propionate was used. Within 24 h, the development of new pustules ceased and the patient was discharged after 7 days of hospitalization with only a faint, diffuse erythema and focal desquamation remaining. This and many other cases in the literature suggest that topical steroids should be considered as a first-line treatment option, especially as systemic steroids themselves can sometimes induce generalized pustulosis.

This study aimed to investigate the association between HLA genotypes and antiepileptic drug-induced cutaneous adverse reactions (AEDs-cADRs) among patients with epilepsy in Ningxia Hui Autonomous Region of Northwest China. Fifteen patients with AEDs-cADRs and 30 matched AEDs tolerant controls from anested case-control study were tested the HLA-A, HLA-B, and HLA-DRB1 genotype using the polymerase chain reaction sequence-based typing (PCR-SBT). Significant difference was not observed between AEDs-cADRs and AEDs tolerant groups in terms of HLA-A, HLA-B, and HLA-DRB1 genotype frequencies. Future studies using larger cohorts are needed to verify this observation.

This study aimed to investigate the association between HLA genotypes and antiepileptic drug-induced cutaneous adverse reactions (AEDs-cADRs) among patients with epilepsy in Ningxia Hui Autonomous Region of Northwest China. Fifteen patients with AEDs-cADRs and 30 matched AEDs tolerant controls from anested case-control study were tested the HLA-A, HLA-B, and HLA-DRB1 genotype using the polymerase chain reaction sequence-based typing (PCR-SBT). Significant difference was not observed between AEDs-cADRs and AEDs tolerant groups in terms of HLA-A, HLA-B, and HLA-DRB1 genotype frequencies. Future studies using larger cohorts are needed to verify this observation. [ABSTRACT FROM AUTHOR]

The article focuses on findings of a study on clinical significance of cutaneous adverse reaction to mogamulizumab in relapsed or refractory adult T-cell leukaemia-lymphoma. It states that mogamulizumab is a humanized monoclonal antibody against CC chemokine receptor 4, and mentions that in the patients who received more than 4 cycles of mogamulizumab, the overall survival for the patients who developed cutaneous adverse reactions (CARs).

Purpose Cutaneous adverse reactions (cADRs) from carbamazepine (CBZ) have been associated with human leukocyte antigens (HLA). Our aims were to assess the clinical usefulness of HLA-A*31:01 as a predictor of CBZ-induced cADRs in the Norwegian population and to explore whether cADRs from aromatic antiepileptic drugs (AEDs) in general might be linked with a common HLA-A-marker. Materials and methods 86 ethnic Norwegians with a history of non-bullous cADRs from aromatic AEDs were included. 114 subjects tolerant to at least one aromatic AED were used as drug-specific controls. Complete HLA-A genotyping was performed. 1026 blood donors were used as population controls. Results Comparing all cADR subjects with controls and blood donors, there were no statistical differences for any HLA-A allele, except for HLA-A*24 ( p = 0.022 vs. controls and p = 0.014 vs. blood donors). When comparing tolerant controls with patients having had a cADR to one of the two most used drugs, CBZ ( n = 48) and lamotrigine ( n = 28), we found no significant associations for CBZ to HLA-A*31:01 or HLA-A*24:02 , but for lamotrigine there was an association with HLA-A*24:02 ( p = 0.027). In patients developing cross-reactivity ( n = 14) to aromatic AEDs, the presence of HLA-A*31:01 or HLA-A*24:02 was not different compared to patients with a single cARD tolerant to at least one other drug. Conclusion We question the clinical usefulness of HLA-A*31:01 as a marker for CBZ rash in the Norwegian population. A previously suggested protective effect of aromatic AED cross-reactivity from HLA-A*24:02 was not confirmed. The association between HLA-A*24:02 and lamotrigine-induced rash should be further investigated. [ABSTRACT FROM AUTHOR]

The use of lamotrigine ( LTG) can be limited by the occurrence of cutaneous adverse drug reactions (c ADRs) that range from maculopapular eruption ( MPE) to the more severe Stevens-Johnson syndrome and toxic epidermal necrolysis. A few human leukocyte antigen ( HLA)-related genetic risk factors for carbamazepine-induced cADR have been identified. However, the HLA-related genetic risk factors associated with LTG-induced cADR are not yet well known. We performed HLA genotyping in 50 Korean patients with epilepsy, including 21 patients presenting LTG-induced MPE and 29 LTG-tolerant patients. A significant association between the HLA-A*2402 allele and LTG-induced MPE was identified, in comparison with the LTG-tolerant group (odds ratio [ OR] 4.09, p = 0.025) and the general Korean population ( OR 3.949, p = 0.005). The frequencies of the Cw*0102 or Cw*0702 alleles were significantly higher in the LTG- MPE group than in the Korean population, whereas the frequency of the A*3303 allele was lower. The coexistence of the A*2402 and Cw*0102 alleles was significantly associated with the LTG- MPE group when compared to the LTG-tolerant group ( OR 7.88, p = 0.007). In addition, the Cw*0701 allele was more frequent in the LTG-tolerant group than in the Korean population. These findings suggest the presence of HLA-related genetic risk factors for LTG-induced MPE in the Korean population. [ABSTRACT FROM AUTHOR]

Adult T-cell leukemia/lymphoma (ATLL) is a peripheral T-cell lymphoma caused by latent infection of human T-cell lymphotropic virus type 1. The outcome for ATLL is very poor, with a 3-year overall survival of approximately 24% with conventional chemotherapy; thus, there is an unmet need for developing new treatment options. Defucosylated humanized anti-CC chemokine receptor 4 (CCR4) antibody (KW-0761, mogamulizumab) has been clinically available for the treatment of relapsed or refractory ATLL in Japan since 2012, and a Phase II study of mogamulizumab for patients with relapsed CCR4+ ATLL demonstrated a 50% objective response, a 30.8% complete response, and an acceptable safety profile. Allogeneic hematopoietic stem cell transplantation has been used to treat patients with ATLL, and mogamulizumab in combination with allogeneic hematopoietic stem cell transplantation has been used successfully in a limited number of patients to treat refractory or relapsed ATLL. The efficacy of combining mogamulizumab with standard chemotherapy (mLSG15) for patients with ATLL has also been examined, and the results have shown higher rates of complete response with the combined therapy (52%) compared with for chemotherapy alone (33%). Mogamulizumab also has potential application in the treatment of human T-cell lymphotropic virus type 1-associated myelopathy/tropical paraparesis, Epstein-Barr virus-associated T-cell and natural killer-cell lymphoproliferative diseases, and peripheral and cutaneous T-cell lymphomas. Possible adverse events of mogamulizumab have been reported, such as cutaneous adverse reactions (including Stevens-Johnson syndrome), diffuse panbronchiolitis, reactivation of hepatitis B, and opportunistic infections. The treatment outcome of patients with ATLL might be improved by further optimizing the use of mogamulizumab and managing severe adverse events. In this review, we provide an overview of the current treatment options for patients with ATLL and a focused review on the use, application, and adverse events associated with mogamulizumab. [ABSTRACT FROM AUTHOR]

Background: Stevens-Johnson syndrome (SJS) or toxic epidermal necrolysis (TEN) may develop in susceptible patients after administration of different drugs. Only mild cutaneous reactions have been related to lomefloxacin. A correlation between human leucocyte antigen (HLA) and cutaneous adverse reaction has been identified. Case Report: Twenty-four hours after intake of lomefloxacin, a 30-year-old Caucasian woman developed a severe skin reaction with symptoms suggesting SJS/TEN. The fast onset reaction worsened with skin blisters and 20% body surface area skin detachment within 48 h. Burn unit admittance was required; corticosteroids and human immunoglobulins were administered. Complete recovery occurred within 3 months, except for epidermal discoloration. Molecular studies showed a peculiar profile characterized by HLA class I genotype rich of ligands for natural killer cell immunoglobulin-like receptors (KIR) and HLA class II haplotype, HLA-DRB1*03:01,DQB1*02:01, prone to autoimmunity. Conclusion: While the HLA profile approaches our case to other well-documented drug-induced SJS/TEN, KIR involvement still remains puzzling. © 2014 S. Karger AG, Basel [ABSTRACT FROM AUTHOR]

Background: Pompholyx and eczematous reactions are known adverse reactions to intravenous immunoglobulins (IVIg) infusion, but little is known about their clinical characteristics, associated outcomes and management., Objective: To describe IVIg-induced eczematous skin reactions., Methods: We conducted a retrospective study on cases of delayed skin reactions post-IVIg infusion notified to the French Regional Pharmacovigilance Centre from 1985 to 2020., Results: A total of 27 patients were identified, of whom 85% were male. IVIg infusions were given in a neurological indication in 82% of cases. Eczematous skin reactions occurred in two-thirds of cases after the first infusion, with a median time to onset of 11 days. Palmoplantar pompholyx was the most common presentation, being seen in 63% of patients. Other eruptions were erythemato-squamous or maculopapular. Eight patients were classified as severely affected and developed extensive lesions (>50% BSA). One third of the 27 patients required hospitalization. All of the severe eczematous reactions involved males receiving high doses of IVIg for neurological diseases. Biopsies of severe cases revealed a common non-specific eczematous pattern. Relapses were frequent and more severe than the initial reaction. Reintroduction of the same IVIg product consistently resulted in relapse, whereas switching IVIg type produced relapse in only 53% of patients., Conclusion: We present the largest retrospective study of delayed skin reactions after IVIg infusions. This side-effect may be severe and have a polymorphic presentation. Relapse occurs frequently but less consistently after IVIg switch., (Copyright © 2022 Elsevier Masson SAS. All rights reserved.)

Purpose: High initial serum concentrations increase the risk of cutaneous adverse reactions. Genetic variants of the main metabolizing isoenzyme, uridine diphosphate glucuronosyltransferase (UGT) 1A4 influence the elimination of lamotrigine (LTG). Our aim was to investigate the potential association between the two best studied variants, *2 (P24T) and *3 (L48V), and the occurrence non-bullous skin reactions from LTG.Method: The study included 29 patients of Caucasian ethnicity with a history of non-bullous skin reactions from LTG. 184 subjects tolerant to LTG for at least three months were used as controls. UGT1A4 genotyping was performed in all patients and controls by sequencing of the first part of exon 1. Six controls were excluded due to rare genetic variants.Results: Two of 29 subjects (7%) with rash from LTG were heterozygous for UGT1A4 *2, compared to 23 of 178 (13%) tolerant controls (p=0.54). Four of 29 subjects (14%) with rash from LTG were heterozygous for UGT1A4 *3 compared to 25 of 178 (14%) tolerant controls (p=0.97).Conclusion: It is unlikely that heterozygosity of the UGT1A4 genetic variants *2(P24T) or *3(L48V) influences the risk of non-bullous skin reactions in patients treated with LTG. [ABSTRACT FROM AUTHOR]