Causes and Management of Cutaneous Adverse Drug Reactions: A Comprehensive Review.

Cutaneous adverse drug reactions (CADRs) are one of the most broadly studied and rigorously researched conditions in recent dermatological advancements. Also termed as "toxidermia," they are heavily involved and are of utmost importance to be understood and studied in the modern healthcare industry. In simple terms, they are dermatological manifestations which result from systemic drug administration to patients. Since allopathy is influenced by the medicines and drugs provided to the patients, cutaneous skin eruptions are a common occurrence in recent times. It is a need of the hour to understand the causative factors for such skin eruptions and the correct management and handling of such disorders to provide better healthcare to patients. The withdrawal of the causative drug which induces the reaction plays a key role in treatment. The risk factors are to be thoroughly studied, and dosages must be in accordance with the patient's situation. They are some of the common public health problems. The age group which is affected is highly variable as people from all age groups can be affected. Those who are affected comprise approximately 10% of all hospitalized patients, and it is also observed in about 1-4% of people who are on multiple medications.

Cefepime-Induced Generalized Fixed Drug Eruption With Morbilliform Rash.

Fixed drug eruption (FDE) is a cutaneous reaction that characteristically recurs in the same locations upon re-exposure to the offending drug(s). The typical presentation of FDEs is single or multiple violaceous plaques with hyperpigmentation due to inflammation. The causative agents for FDEs include antibiotics, nonsteroidal anti-inflammatory drugs (NSAIDs), acetaminophen, barbiturates, and anticonvulsants. We present an interesting case of a generalized fixed drug eruption secondary to cefepime that resolved with the cessation of the offending drug and the institution of antihistamines and topical steroids.

Eritema fijo pigmentado generalizado por ARAII / Generalized fixed pigmented erythema due to ARBS

RESUMEN El eritema fijo pigmentado es una toxicodermia que puede afectar la piel o las mucosas. Tiende a recurrir en las mismas localizaciones tras la administración repetida del agente desencadenante. Los principales grupos farmacológicos asociados han sidoanalgésicos, antiepilépticos y AINES. Clínicamente, hayaparición de placaseritemato-edematosas redondas u ovaladas, definidas. Existen diferentes variantes;la generalizada es una de las menos frecuentes. Se reporta el caso de un paciente de mediana edad, quien presentó un cuadro deeritema fijo pigmentadogeneralizado, asociado al uso de ARA II. Es el primer caso reportado de esta patología secundaria al uso de dicho grupo farmacológico.

SUMMARY Pigmented fixed erythema is a toxicoderma, it can affect the skin or mucous membranes. It tends to recur in the same locations after repeated administration of the triggering agent.1 The main associated pharmacological groups have been: analgesics, antiepileptics and NSAIDs. Clinically, there is the appearance of defined round or oval erythematous-edematous plaques. There are different variants, the generalized is one of the least frequent. The case of a middle-aged patient is reported, who presented a generalized fixed pigmented erythema, associated with ARBS, it is the first reported case of this pathology secondary to the use of said pharmacological group.

Dupilumab-induced psoriasiform dermatitis in two pediatric cardiac transplant patients.

Dupilumab is an interleukin-4 receptor antagonist important in the treatment of refractory atopic dermatitis (AD), particularly among pediatric patients. Two boys with a history of AD and cardiac transplant who developed psoriasiform dermatitis in response to dupilumab therapy are reported. These patients paradoxically developed an immune-mediated adverse drug reaction despite taking systemic immunosuppressive agents. While the literature suggests possible pathomechanisms for psoriasiform dermatitis despite immunosuppression, further research is necessary to better characterize this unique and unexpected phenomenon.

Exantema en enfermedad por virus de inmunodeficiencia humana, ¿manifestación de infección o reacción alérgica?

Paciente varón que presentó exantema maculopapular, no pruriginoso, sin afectación palmoplantar, luego de recibir tratamiento con trimetoprim/sulfametoxazol por siete días debido a sintomatología gastrointestinal. Tras realizar historia clínica completa y con pruebas de cuarta generación se confirmó infección por VIH. Al quinto día de tratamiento antirretroviral presentó nuevas lesiones eritematosas con descamación gruesa, pruriginosas, edema facial y eosinofilia. Se realizó una biopsia de piel que reportó una dermatitis liquenoide, con espongiosis, degeneración vacuolar de la capa basal, queratinocitos necróticos e infiltrado de eosinófilos, características que favorecen la reacción por drogas. El tratamiento consistió en interrumpir la terapia combinada, uso de corticoides sistémicos, antihistamínicos y ya que, no se trató de un cuadro severo, se reinició el tratamiento antirretroviral sin complicaciones.

A male patient presented with a maculopapular, non-pruritic rash, without palmoplantar involvement, after receiving treatment with trimethoprim/sulfamethoxazole for seven days due to gastrointestinal symptoms. After taking a complete medical history and using fourth-generation tests confirmed HIV infection. On the fifth day of antiretroviral treatment, he presented new erythematous lesions with thick, pruritic scaling, facial edema and eosinophilia. A skin biopsy reported lichenoid dermatitis, with spongiosis, vacuolar degeneration of the basal layer, necrotic keratinocytes and eosinophil infiltrate, characteristics that favor drug reaction. The treatment consisted of interrupting the combined therapy, using systemic corticosteroids, antihistamines and since it was not a severe condition, antiretroviral treatment restarted without complications.

Fixed Drug Eruption in a Patient Taking Valacyclovir without Cross-Reactivity to Acyclovir.

Fixed drug eruption (FDE) is a well-defined hyperpigmented patch that recurs in a fixed location each time a particular drug is taken. Common causative agents of FDE are non-steroidal anti-inflammatory drugs, non-narcotic analgesics, sedatives, anticonvulsants, sulfonamides, and tetracycline. We report a 33-year-old male who presented with a recurrent, localized, brownish-to-erythematous macule and papules on the peri-philtrum area two hours after taking valacyclovir. Three episodes of valacyclovir ingestion for treatment of Herpes simplex virus infection provoked a similar skin rash at the same site. Histopathology results showed vacuolar degeneration in the basal layer of the epidermis, pigmentary incontinence, and perivascular inflammatory cell infiltration in the papillary dermis. Although patch test and skin prick test showed negative responses to acyclovir and valacyclovir, an intradermal test showed a positive reaction only to valacyclovir. The oral provocation test to acyclovir and valacyclovir showed a positive reaction only to valacyclovir. Through drug history, histopathological examination, patch test, intradermal test, and oral provocation test, we established a final diagnosis of FDE due to valacyclovir without cross-reactivity to acyclovir. To find alternative therapeutic drugs, we suggest diagnostic tests with not only the suspected drugs, but also other drugs in the same class.

The Impact of the COVID-19 Pandemic on Cutaneous Drug Eruptions in a Swedish Health Region without Lockdown.

The incidence of severe cutaneous drug eruptions during the COVID-19 period in Sweden has not been studied previously. Our aim was to compare the incidence of these skin reactions in a Swedish health region during the COVID-19 pandemic period with that of the year after: we conducted a retrospective, observational cohort study using data from a national registry of patients diagnosed with cutaneous drug eruptions during the pandemic in Sweden. We included the number of patients diagnosed with severe cutaneous drug eruptions at the Department of Dermatology in the Jonkoping health region during the COVID-19 pandemic (1 April 2020 to 31 March 2021) and the reference period (1 April 2021 to 31 March 2022). We examined the monthly occurrences of cutaneous drug eruptions in three dermatology clinics within the Jonkoping health region. The frequency of these eruptions was determined for two distinct time periods: during the pandemic and post-pandemic. The study included 102 patients with cutaneous drug eruptions: 29 patients were diagnosed during the COVID-19 pandemic period and 73 were diagnosed during the reference period. The difference in the number of cutaneous drug eruptions cases (p-value = 0.0001, 95% CI 1.4995-3.5500, OR 2.3072) during the pandemic period compared to the post-pandemic period was significant. To our knowledge, the impact of the pandemic on cutaneous drug eruptions has not been investigated in EU countries. The increasing and differentiation of the number of diagnosed cutaneous drug eruptions cases after the pandemic could be explained by the removal of COVID-19 restrictions and the more frequent health-seeking behavior during the post-pandemic period.

Epidemiology of Stevens-Johnson syndrome and toxic epidermal necrolysis in the United States and factors predictive of outcome.

Background: Stevens-Johnson syndrome (SJS), toxic epidermal necrolysis (TEN), and SJS-TEN overlap syndrome are rare severe cutaneous adverse reactions associated with high mortality. Objectives: To estimate incidence and describe trends of SJS/TEN hospitalizations in the United States and to describe the clinical, demographic, and geographic characteristics of affected patients and risk factors for mortality. Methods: We utilized hospitalization data from the 2010 to 2020 National Inpatient Sample. SJS, SJS-TEN overlap syndrome, and TEN were identified by International Classification of Diseases, 9th Revision and International Classification of Diseases, 10th Revision codes and analyzed by logistic regression. Results: We identified 51,040 hospitalizations involving SJS/TEN. Amog those, 37,283 (73.0%) were for SJS only, 7818 (15.3%) were for SJS-TEN overlap syndrome, and 7160 (14.0%) were for TEN only. Overall, SJS/TEN hospitalization rates declined over time, 2010 to 2020 (P < .05). Mortality rates of the SJS group, SJS-TEN overlap syndrome group, and TEN group were 5.4%, 14.4%, and 15.3%, respectively. Increasing age, chronic kidney disease, pneumonia, sepsis, and malignant neoplasm were all significantly associated with increased odds of mortality (P < .05). Non-Hispanic White racial/ethnic identification was associated with decreased odds of mortality (P < .05). Limitations: Lack of standardization for diagnostic criteria. Conclusions: Risk factors identified in this study lay the groundwork for improvement in SJS/TEN mortality prediction scoring.

Dermatologic complications in transplantation and cellular therapy for acute leukemia.

Adoptive cellular immunotherapy, mainly hematopoietic stem cell transplant and CAR-T cell therapy have revolutionized treatment of patients with acute leukemia. Indications and inclusion criteria for these treatments have expanded in recent years. While these therapies are associated with significant improvements in disease response and overall survival, patients may experience adverse events from associated chemotherapy conditioning, engraftment, cytokine storm, supportive medications, and post-transplant maintenance targeted therapies. Supportive oncodermatology is a growing specialty to manage cutaneous toxicities resulting from the anti-cancer therapies. In this review, we summarize diagnosis and management of the common cutaneous adverse events including drug eruptions, graft-versus-host disease, neoplastic and paraneoplastic complications in patients undergoing cellular therapies.

[Identification of cutaneous adverse drug reactions]. / Identification des toxidermies médicamenteuses.

IDENTIFICATION OF CUTANEOUS ADVERSE DRUG REACTIONS. Cutaneous adverse drug reactions are common. The most common are maculopapular exanthemas, which heal within a few days. However, clinical and biological signs of severity should be ruled out. Severe drug reactions include acute generalized exanthematous pustulosis, DRESS (drug reaction with eosinophilia and systemic symptoms), and epidermal necrolysis (Stevens-Johnson and Lyell syndromes). The search for the suspect drug is based on the questioning of the patient or his entourage and a chronological timeline. The treatment of drug eruption depends on its nosological type and the patient's background. For any severe drug reaction, hospitalization in a specialized units is necessary. Follow-up of epidermal necrolysis should be prolonged due to the frequency of disabling sequelae. All drug reactions, in particular the severe forms, must be declared to the pharmacovigilance services.

IDENTIFICATION DES TOXIDERMIES MÉDICAMENTEUSES. Les toxidermies sont des effets indésirables fréquents des médicaments. Les plus fréquentes sont les exanthèmes maculopapuleux, qui guérissent en quelques jours. Il convient toutefois d'éliminer des signes de gravité cliniques et biologiques. Les toxidermies graves comprennent la pustulose exanthématique aiguë généralisée, la drug reaction with eosinophilia and systemic symptoms (DRESS) et la nécrolyse épidermique (syndromes de Stevens-Johnson et de Lyell). La recherche du médicament suspect repose sur l'interrogatoire du patient ou de son entourage et l'élaboration d'une frise chronologique. Le traitement des toxidermies dépend du type nosologique et du terrain du patient. Pour toute toxidermie grave, une hospitalisation en service spécialisé est nécessaire. Le suivi de la nécrolyse épidermique doit être prolongé en raison de la fréquence des séquelles invalidantes. Toutes les toxidermies, notamment les formes graves, doivent être déclarées au système de pharmacovigilance.

Acute generalized exanthematous pustulosis complicated by cutaneous small vessel vasculitis: A case report and literature review.

Acute generalized exanthematous pustulosis (AGEP) is a rare skin eruption characterized by widespread erythematous lesions covered with numerous pustules. Leukocytoclastic vasculitis is now considered an uncommon but possible histopathological feature within the clinical and pathological spectrum of AGEP. Our report describes a rare case of AGEP overlapping with cutaneous small vessel vasculitis, a condition that has only been reported once in the literature.

A Case of Vancomycin-Induced Drug Reaction with Eosinophilia, Systemic Symptoms and Multiorgan Involvement Proven Using Lymphocyte Transformation Test.

Drug-induced hypersensitivity syndrome (DiHS), also referred to as drug reaction with eosinophilia and systemic symptoms (DRESS), is a rare but potentially life-threatening condition induced by drug hypersensitivity that leads to significant morbidity and mortality and often occurs in patients undergoing combination antibiotic therapy. Due to a recent increase in the incidence of methicillin-resistant Staphylococcus aureus infections, the occurrence of vancomycin-induced DiHS/DRESS has increased rapidly. However, because of insufficient pharmacogenetic data on vancomycin-induced drug eruptions in Asians coupled with the risk of re-eliciting the symptoms by provocation tests, confirmation of the culprit drug in vancomycin-induced DiHS/DRESS is often challenging. Here, we report a case of vancomycin-induced DiHS/DRESS, where the causal relationship was confirmed using a lymphocyte transformation test (LTT). A 51-year-old woman was treated with combination antibiotics, including vancomycin, for infective pericarditis. The patient subsequently developed fever, facial edema, generalized rash followed by multiple internal organ involvement, including the kidney, lung, liver, and heart. Thus, based on the International Registry of Severe Cutaneous Adverse Reaction (RegiSCAR) criteria, the case was diagnosed as 'definite' DiHS/DRESS, although the culprit drug was obscured by combination antibiotic therapy. The LTT confirmed that vancomycin, but not other glycopeptide antibiotics, specifically induced T-cell proliferation in this case. Collectively, our case suggests that clinicians can utilize LTT to identify the causative medication of DiHS/DRESS when the clinical information is limited to defining the culprit drug.

Concurrent acute generalized exanthematous pustulosis in siblings.

Acute generalized exanthematous pustulosis (AGEP) is a rare severe cutaneous adverse reaction triggered in most cases by drugs. It is characterized by abrupt onset and rapid evolution of fields of sterile pustules on an erythematous background. The role of genetic predisposition in this reactive disorder is being explored. We report the simultaneous occurrence of AGEP in two siblings after being exposed to the same drug.

Lichenoid Lesions of the Oral Mucosa.

Lichenoid lesions involving the oral cavity present with an array of complex clinical manifestations and etiologies. The etiology ranges from local factors, systemic entities, and even autoimmune conditions. Several different types of lichenoid lesions may affect the oral cavity, and it is imperative that these are correctly diagnosed to ensure effective patient care. Lichenoid lesions such as chronic ulcerative stomatitis prove to be challenging as these are recalcitrant, present with overlapping features, require unique treatment and patients suffer a long time if not promptly diagnosed.

Hair loss after drug reaction with eosinophilia and systemic symptoms (DRESS): A multicentric retrospective case series.

Drug reaction with eosinophilia and systemic symptoms (DRESS) is a severe cutaneous drug adverse reaction characterized by various cutaneous and systemic manifestations. However, reports on the various patterns of alopecia after DRESS are lacking. Thus, we aimed to describe cases of alopecia after DRESS and review the literature. This multicentric retrospective study reviewed the records of 182 patients diagnosed with DRESS from 2009 to 2021; of these, 10 who had alopecia after DRESS were included. Patients were diagnosed with permanent alopecia (n = 4), telogen effluvium (n = 5), and alopecia areata (n = 1), and were treated with topical minoxidil or alfatradiol (6; 60%), topical corticosteroids (3; 30%), dietary supplements (6; 60%), systemic corticosteroids (1; 10%), and intralesional corticosteroid injection (2; 20%). Although patients with permanent alopecia did not show hair regrowth after 6 months, those with telogen effluvium and alopecia areata experienced marked clinical improvement within 6 months. Various types of alopecia can persist over an extended period, even after the resolution of an acute episode of DRESS.