RESUMEN
Icodextrin has been widely prescribed for peritoneal dialysis (PD) patients with inadequate ultrafiltration, but icodextrin induced acute generalized exanthematous pustulosis (AGEP) has been not well recognized in clinical practice. We described a young-aged female with IgA nephropathy and end stage kidney disease under continuous automated peritoneal dialysis. She developed skin erythema with exfoliation over the groin 7th day after initiation of icodextrin based PD dialysate. Initially, her scaling skin lesion with pinhead-sized pustules affected the bilateral inguinal folds, and then it extended to general trunk accompanied by pruritus. She was admitted because of deterioration of skin lesion on 14th day of icodextrin exposure. She was afebrile and physical examination was notable for widespread erythematous papules with pruritus extending over her groins and trunk. Pertinent laboratory examination showed leukocytosis of 18 970 cells/µL with neutrophile count of 17 642 cells/µL (92.3%), and c-reactive-protein: 3.39 mg/dL. Skin biopsy revealed multifocal sub corneal abscess with papillary dermal edema, and upper-dermal neutrophilia with perivascular accentuation, consistent with the diagnosis of AGEP. After discontinuation of PD, she underwent temporary high-flux haemodialysis with treatment of steroid and antihistamine. Her dermatologic lesion resolved without any skin sequalae completely within 4 days, and she underwent icodextrin-free peritoneal dialysis at 17th day. This case highlighted the fact that icodextrin-induced AGEP should be early recognized to avoid inappropriate management.
Asunto(s)
Pustulosis Exantematosa Generalizada Aguda , Soluciones para Diálisis , Icodextrina , Diálisis Peritoneal , Humanos , Femenino , Pustulosis Exantematosa Generalizada Aguda/etiología , Pustulosis Exantematosa Generalizada Aguda/diagnóstico , Soluciones para Diálisis/efectos adversos , Adulto , Resultado del Tratamiento , Glucanos/efectos adversos , Fallo Renal Crónico/terapia , Fallo Renal Crónico/complicaciones , Glucosa , Biopsia , Piel/patología , Piel/efectos de los fármacosRESUMEN
BACKGROUND/OBJECTIVES: The immune checkpoint inhibitors (ICIs) have been increasingly associated with severe cutaneous adverse reactions (SCARs). These reactions, including Stevens-Johnson syndrome (SJS), toxic epidermal necrolysis (TEN), drug reaction with eosinophilia and systemic symptoms (DRESS) and acute generalized exanthematous pustulosis (AGEP) are uncommon but potentially lethal. Despite the severity of these reactions and growing association with the ICIs, their specific risk and mortality rates have been largely unexplored. METHODS: A case/non-case analysis was performed using data from the United States Food and Drug Administration (FDA) Adverse Event Reporting System (FAERS) to examine the reporting odds ratios (RORs) for ICI-associated SCARs cases under two conditions: (1) ICIs compared with all drugs in FAERS and (2) ICIs compared with a reference group of pooled anticancer drugs to control for underlying malignancy. RESULTS: A statistically significant ROR for SJS (ROR: 5.44), TEN (ROR: 5.81) and DRESS (ROR: 1.38) were identified under Condition 1. Under Condition 2, this significance was maintained for SJS (ROR: 7.31), TEN (ROR: 7.40) and DRESS (ROR: 3.90), and mild significance was identified for AGEP (ROR: 1.89). Mortality rates for the ICIs were increased compared with the anticancer medications (28.5% vs. 24.5% for SJS, 55.3% vs. 46% for TEN, 3.0% vs. 2.1% for AGEP and 7.1% vs. 6.1% for DRESS). CONCLUSIONS: Our results suggest an association between SCARs and the ICIs independent of cancer status.
Asunto(s)
Sistemas de Registro de Reacción Adversa a Medicamentos , Inhibidores de Puntos de Control Inmunológico , Síndrome de Stevens-Johnson , United States Food and Drug Administration , Humanos , Inhibidores de Puntos de Control Inmunológico/efectos adversos , Sistemas de Registro de Reacción Adversa a Medicamentos/estadística & datos numéricos , Estados Unidos , Síndrome de Stevens-Johnson/etiología , Erupciones por Medicamentos/etiología , Femenino , Masculino , Síndrome de Hipersensibilidad a Medicamentos/etiología , Persona de Mediana Edad , Pustulosis Exantematosa Generalizada Aguda/etiología , AncianoRESUMEN
BACKGROUND: Stevens-Johnson syndrome (SJS), toxic epidermal necrolysis (TEN), drug reaction with eosinophilia and systemic symptoms (DRESS), and acute generalized exanthematous pustulosis (AGEP) are potentially life-threatening severe cutaneous adverse reactions (SCARs). Although the classical causal agents of SCARs (antibiotics, anticonvulsants, nonsteroidal anti-inflammatory drugs, and allopurinol) are well characterized, there has been little update to this list to account for newly marketed medications. OBJECTIVE: To provide an updated and stratified list of medications with significant reporting odds ratios (RORs) of SCARs. METHODS: A case/non-case analysis using the United States FDA Adverse Event Reporting System was performed. RESULTS: As expected, the prototypical medication classes made up the majority of reported cases of SJS, TEN, AGEP, and DRESS (77%, 64%, 75%, and 72%, respectively). In addition, several infrequently or previously undescribed classes/medications implicated in SCARs were identified to have significant ROR signals, including acetylcysteine, anticoagulants, diuretics, immunotherapies, proton pump inhibitors, antivirals, and antifungals. Among these reported for SJS were acetylcysteine (ROR: 64.38) and fluconazole (ROR: 17.13). For TEN, we identified furosemide (ROR: 26.32), spironolactone (ROR: 14.45), fluconazole (ROR: 30.21), amphotericin B (39.06), and acetylcysteine (ROR: 93.12). For AGEP, we identified acyclovir (ROR: 61.72), valacyclovir (ROR: 30.76), and enoxaparin (ROR: 27.37). For DRESS, we identified vemurafenib (ROR: 17.35), acyclovir (ROR: 30.63), abacavir (ROR: 26.62), raltegravir (ROR: 23.27), and valacyclovir (ROR: 21.77) to have strong reporting odds. CONCLUSION: Our analysis provides an updated tool for physicians to reference when identifying suspected SCARs and a basis for future studies to investigate atypical medication causality.
Asunto(s)
Pustulosis Exantematosa Generalizada Aguda , Síndrome de Stevens-Johnson , Humanos , Estados Unidos , Acetilcisteína , Cicatriz , Fluconazol , Valaciclovir , Síndrome de Stevens-Johnson/etiología , Pustulosis Exantematosa Generalizada Aguda/etiologíaRESUMEN
The identification of disease alleles underlying human autoinflammatory diseases can provide important insights into the mechanisms that maintain neutrophil homeostasis. Here, we focused our attention on generalized pustular psoriasis (GPP), a potentially life-threatening disorder presenting with cutaneous and systemic neutrophilia. Following the whole-exome sequencing of 19 unrelated affected individuals, we identified a subject harboring a homozygous splice-site mutation (c.2031-2A>C) in MPO. This encodes myeloperoxidase, an essential component of neutrophil azurophil granules. MPO screening in conditions phenotypically related to GPP uncovered further disease alleles in one subject with acral pustular psoriasis (c.2031-2A>C;c.2031-2A>C) and in two individuals with acute generalized exanthematous pustulosis (c.1705C>T;c.2031-2A>C and c.1552_1565del;c.1552_1565del). A subsequent analysis of UK Biobank data demonstrated that the c.2031-2A>C and c.1705C>T (p.Arg569Trp) disease alleles were also associated with increased neutrophil abundance in the general population (p = 5.1 × 10-6 and p = 3.6 × 10-5, respectively). The same applied to three further deleterious variants that had been genotyped in the cohort, with two alleles (c.995C>T [p.Ala332Val] and c.752T>C [p.Met251Thr]) yielding p values < 10-10. Finally, treatment of healthy neutrophils with an MPO inhibitor (4-Aminobenzoic acid hydrazide) increased cell viability and delayed apoptosis, highlighting a mechanism whereby MPO mutations affect granulocyte numbers. These findings identify MPO as a genetic determinant of pustular skin disease and neutrophil abundance. Given the recent interest in the development of MPO antagonists for the treatment of neurodegenerative disease, our results also suggest that the pro-inflammatory effects of these agents should be closely monitored.
Asunto(s)
Enfermedades Neurodegenerativas/genética , Peroxidasa/genética , Psoriasis/genética , Enfermedades de la Piel/genética , Ácido 4-Aminobenzoico/administración & dosificación , Adulto , Anciano , Anciano de 80 o más Años , Línea Celular/efectos de los fármacos , Femenino , Genotipo , Humanos , Mutación con Pérdida de Función/genética , Enfermedades Neurodegenerativas/tratamiento farmacológico , Enfermedades Neurodegenerativas/patología , Neutrófilos/efectos de los fármacos , Peroxidasa/antagonistas & inhibidores , Fenotipo , Psoriasis/tratamiento farmacológico , Psoriasis/patología , Piel/efectos de los fármacos , Piel/patología , Enfermedades de la Piel/tratamiento farmacológico , Enfermedades de la Piel/patologíaRESUMEN
A 61-year-old African-American female with moderately controlled Hailey-Hailey disease (HHD) presents to the emergency department with a rash and fever. One day prior to her presentation, she was started on oral clindamycin for a tooth extraction procedure. Her physical examination shows diffuse erythema on the trunk and extremities with multiple nonfollicular pustules. A punch biopsy of her upper extremity revealed intraepidermal acantholysis, neutrophilic spongiosis, and subcorneal pustules. The perivascular and interstitial superficial dermal infiltrate is mixed and composed of predominantly neutrophils, with lymphocytes and rare eosinophils. These findings suggest a superimposed acute generalized exanthematous pustulosis (AGEP) in the background of HHD. AGEP is a potentially severe cutaneous condition characterized by the abrupt onset of numerous nonfollicular pustules in a background of pruritic edematous erythroderma. To date, only two case reports have described AGEP in patients with HHD. Early diagnosis of AGEP is essential to initiate prompt and aggressive systemic therapy, prompt medication cessation, close monitoring for end-organ damage, and improve overall morbidity and mortality.
Asunto(s)
Pustulosis Exantematosa Generalizada Aguda , Exantema , Pénfigo Familiar Benigno , Humanos , Femenino , Persona de Mediana Edad , Pustulosis Exantematosa Generalizada Aguda/tratamiento farmacológico , Pustulosis Exantematosa Generalizada Aguda/etiología , Pustulosis Exantematosa Generalizada Aguda/diagnóstico , Clindamicina/efectos adversos , Pénfigo Familiar Benigno/tratamiento farmacológico , Exantema/patología , Piel/patologíaRESUMEN
BACKGROUND: Acute generalized exanthematous pustulosis (AGEP) is a potentially severe adverse cutaneous drug reaction, which typically occurs within 24-48 h after the intake of the culprit drug. SUMMARY: AGEP is characterized by numerous sterile subcorneal pustules on erythematous skin and in less than a third of cases it can be associated with organ manifestations possibly leading to life-threatening symptoms (e.g., cholestasis, nephritis, and lung and bone marrow involvement). In contrast to generalized pustular psoriasis, it can involve mucosal regions and typically resolves rapidly if the culprit drug is removed, and adequate therapy with topical or systemic steroids administered. Diagnosis based on patient history, clinical signs, and characteristic cutaneous histology is rarely challenging. Identification of the culprit drug may be aided by patch testing or lymphocyte transformation tests that are of limited value. KEY MESSAGES: Recent experimental data reviewed herein are supportive of an early role of drug-induced innate immune activation and innate cytokines such as interleukin (IL)-1, IL-36, and IL-17 in the pathogenesis of AGEP. This explains the rapid onset and neutrophilic character of the cutaneous inflammation, but also provides new avenues for in vitro tests aimed at better identifying the culprit drug.
Asunto(s)
Pustulosis Exantematosa Generalizada Aguda , Humanos , Pustulosis Exantematosa Generalizada Aguda/diagnóstico , Pustulosis Exantematosa Generalizada Aguda/etiología , Pustulosis Exantematosa Generalizada Aguda/terapia , Piel/patología , Administración CutáneaRESUMEN
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.
Asunto(s)
Pustulosis Exantematosa Generalizada Aguda , Humanos , Pustulosis Exantematosa Generalizada Aguda/diagnóstico , Pustulosis Exantematosa Generalizada Aguda/etiología , Hermanos , Piel , Administración CutáneaRESUMEN
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.
Asunto(s)
Pustulosis Exantematosa Generalizada Aguda , Exantema , Enfermedades de la Piel , Vasculitis Leucocitoclástica Cutánea , Humanos , Pustulosis Exantematosa Generalizada Aguda/diagnóstico , Pustulosis Exantematosa Generalizada Aguda/etiología , Pustulosis Exantematosa Generalizada Aguda/patología , Exantema/etiología , Exantema/patología , Enfermedades de la Piel/complicaciones , Vasculitis Leucocitoclástica Cutánea/inducido químicamente , Vasculitis Leucocitoclástica Cutánea/complicacionesRESUMEN
Cyclin-dependent kinase (CDK) 4/6 inhibitors (palbociclib, ribociclib and abemaciclib) have revolutionized the treatment of metastatic breast carcinoma. They currently form the first-line treatment, in combination with endocrine agents, for the management of locally advanced or metastatic hormone receptor-positive (HRâ¯+â¯), human epidermal growth factor receptor 2-negative (HER2-) breast cancer, the largest subtype of breast carcinoma. CDK 4/6 inhibitors have shown comparable efficacy outcomes with predictable and manageable adverse events. In this setting, dermatologic toxicity appears to be relatively frequent, accounting for up to 15% of all reported adverse events. It is usually mild to moderate in intensity and does not normally constitute a dose-limiting toxicity. The range of dermatologic adverse events includes both non-specific entities (maculopapular rash, pruritus, alopecia) and more characteristic toxicities related to CDK4/6 inhibitors, such as vitiligo-like lesions or cutaneous lupus erythematosus. Finally, more severe or life-threatening skin reactions can occasionally occur. The main dermatologic manifestations associated with CDK4/6 inhibitors, as well as management thereof, are described in this comprehensive review.
Asunto(s)
Neoplasias de la Mama , Humanos , Femenino , Neoplasias de la Mama/tratamiento farmacológico , Neoplasias de la Mama/patología , Quinasas Ciclina-Dependientes/uso terapéutico , Quinasa 4 Dependiente de la Ciclina/uso terapéutico , Inhibidores de Proteínas Quinasas/efectos adversosRESUMEN
Acute generalized exanthematous pustulosis (AGEP) is a severe cutaneous adverse reaction (SCAR) characterized by sterile nonfollicular pustules on an erythematous base that form rapidly after drug exposure. AGEP is mediated by numerous cytokines produced by drug-specific T cells that mediate neutrophilic intracorneal, subcorneal, or intraepidermal pustule development. Though genetic susceptibility is not fully understood, individuals with mutations in IL-36RN may be at increased risk of AGEP development. AGEP commonly presents with leukocytosis and fever in the acute pustular phase and follows a self-limited desquamative recovery phase upon removal of offending drug. Severe cases of AGEP may have multisystem organ involvement. Atypical presentations of AGEP include localized eruptions and cases with overlapping clinical and histopathologic features associated with Stevens-Johnson syndrome/toxic epidermal necrolysis, drug reaction with eosinophilia and systemic symptoms, and generalized pustular psoriasis. Most cases of AGEP clear rapidly with systemic corticosteroids, but severe or recalcitrant cases may require other systemic therapies, such as cyclosporine, and intravenous immunoglobulin.
Asunto(s)
Pustulosis Exantematosa Generalizada Aguda , Exantema , Síndrome de Stevens-Johnson , Pustulosis Exantematosa Generalizada Aguda/diagnóstico , Pustulosis Exantematosa Generalizada Aguda/etiología , Pustulosis Exantematosa Generalizada Aguda/patología , Humanos , Inmunoglobulinas Intravenosas/uso terapéutico , Piel/patología , Síndrome de Stevens-Johnson/diagnóstico , Síndrome de Stevens-Johnson/tratamiento farmacológico , Síndrome de Stevens-Johnson/etiologíaRESUMEN
WHAT IS KNOWN AND OBJECTIVE: Acute generalized exanthematous pustulosis (AGEP) is a serious and rare adverse reaction of cephalosporins. We aimed to describe the clinical features of cephalosporin-induced AGEP and provide a reference for rational clinical use of cephalosporins. METHODS: We systematically searched Chinese and English databases for cephalosporin-induced TGEP-related case reports, retrospective studies, clinical studies, and review articles published before May 2022. RESULTS AND DISCUSSION: A total of 43 patients from 35 articles were eligible, of which 28 (65.1%) were female, with a median age of 69 years. A total of 11 cephalosporins were suspected, the most commonly involved were ceftriaxone (41.9%), cephalexin (16.3%), and cefepime (9.3%). AEGP erupted primarily within 14 days after administration, manifested as nonfollicular pustules on an erythematous base, distributed favourably to the extremities (44.2%), trunk (23.3%), face (23.3%), and could involve the oral mucosa (11.6%). During AGEP resolution, the affected area had desquamation (39.5%). The acute phase of the disease may be accompanied by fever (>38.0°C) and elevated neutrophil count (>7500/mm3 ). Histology of AGEP showed subcorneal pustules (56.3%), intraepidermal cavernous pustules (37.5%), with papillary dermal edema (37.5%), containing neutrophils and eosinophilic infiltration (71.9%). After drug discontinuation, the median time to resolution of AGEP symptoms was 10 days (range 2, 90). WHAT IS NEW AND CONCLUSION: Cephalosporin-induced AGEP is rare and should be properly diagnosed. This serious cutaneous adverse reaction is self-limiting and has a favourable prognosis, usually resolves with drug interruption, and may require additional interventions, such as topical steroids.
Asunto(s)
Pustulosis Exantematosa Generalizada Aguda , Exantema , Humanos , Femenino , Anciano , Masculino , Pustulosis Exantematosa Generalizada Aguda/diagnóstico , Pustulosis Exantematosa Generalizada Aguda/tratamiento farmacológico , Pustulosis Exantematosa Generalizada Aguda/etiología , Cefalosporinas/efectos adversos , Estudios Retrospectivos , Ceftriaxona , Exantema/inducido químicamente , Monobactamas/efectos adversosRESUMEN
The literature on positive patch-test results in acute generalized exanthematous pustulosis (AGEP) is reviewed. Ninety-three drugs were identified that have together caused 259 positive patch tests in 248 patients with AGEP. The drug classes causing the highest number of reactions are beta-lactam antibiotics (25.9%), other antibiotics (20.8%), iodinated contrast media (7.3%), and corticosteroids (5.4%), together accounting for nearly 60% of all reactions. The highest number of reactions to individual drugs was to amoxicillin (n = 36), followed by pristinamycin (n = 25), diltiazem (n = 14), amoxicillin-clavulanic acid (n = 13), clindamycin (n = 11), and iomeprol (n = 8); 59 of the 93 drugs each caused a single case only. The "Top-10" drugs together caused over 50% of all reactions. The sensitivity of patch testing (percentage of positive reactions) in patients with AGEP is largely unknown, but may generally be ~50%, which also applies to pristinamycin. Patch testing in AGEP appears to be safe, although mild recurrence of AGEP skin symptoms or other rashes may occur occasionally. Clinical aspects of AGEP, including epidemiology, etiology and pathophysiology, clinical features, histology, treatment, and prognosis are briefly presented, as are diagnosing the disease and identifying the culprit drugs with patch tests, intradermal tests, in vitro tests, and challenge tests.
Asunto(s)
Pustulosis Exantematosa Generalizada Aguda , Dermatitis Alérgica por Contacto , Pustulosis Exantematosa Generalizada Aguda/diagnóstico , Pustulosis Exantematosa Generalizada Aguda/tratamiento farmacológico , Pustulosis Exantematosa Generalizada Aguda/etiología , Amoxicilina/efectos adversos , Antibacterianos/efectos adversos , Dermatitis Alérgica por Contacto/complicaciones , Humanos , Pruebas del Parche , Pristinamicina/efectos adversosRESUMEN
BACKGROUND/PURPOSE: Taiwan Drug-Injury Relief System (TDRS) has been implemented since 1999. More than 60% of the approved applications were associated with severe cutaneous adverse reactions (SCARs). Studies assessing SCARs using real-world evidence are very limited. TDRS offers abundant case information as a source of real-world evidence to investigate the characteristics of SCARs in Taiwan. The purpose of this study is to understand the trends and characteristics of SCARs in Taiwan. METHODS: Applications from Drug-Injury Relief Database (TDRD) from 1999 to 2016 were retrospectively analyzed. RESULTS: A declining trend in SCARs application was noticed after 2012, and 952 applications of SCARs were identified. The most common subtypes of SCARs were SJS/TEN (n = 455/206), DRESS (n = 228), GBFDE (n = 34) and AGEP (n = 18). The most common culprit drugs were allopurinol, carbamazepine, phenytoin, diclofenac and lamotrigine for SJS/TEN; allopurinol, phenytoin, co-trimoxazole, carbamazepine and phenobarbital for DRESS; mefenamic acid for GBFDE; non-steroidal anti-inflammatory drugs (NSAIDs) and beta-lactam antibacterials for AGEP. The proportions of mortality cases were 28.9% for SJS/TEN; 36% for DRESS; 11.8% for GBFDE and 5.6% for AGEP. The mean latent period of SJS/TEN, DRESS, GBFDE and AGEP were 21.8 days, 29.2 days, 3.3 days and 6.7 days, respectively. CONCLUSION: The approved drug-injury relief applications associated with SCARs were mainly SJS, TEN and DRESS. The most common culprit drugs were antiepileptics, antibacterials, antigout agents, and NSAIDs. The latent periods showed some distinct features for different types of SCARs. In light of the high mortality rate, public awareness and vigilance of SCARs are crucial for the patient safety.
Asunto(s)
Fenitoína , Síndrome de Stevens-Johnson , Alopurinol/efectos adversos , Antibacterianos/efectos adversos , Antiinflamatorios no Esteroideos/efectos adversos , Anticonvulsivantes/efectos adversos , Carbamazepina/efectos adversos , Cicatriz/inducido químicamente , Humanos , Estudios Retrospectivos , Síndrome de Stevens-Johnson/tratamiento farmacológico , Síndrome de Stevens-Johnson/etiología , Taiwán/epidemiologíaRESUMEN
Acute generalized exanthematous pustulosis (AGEP) is a severe cutaneous drug reaction. Bullous pemphigoid (BP) is an acquired autoimmune disease that might be associated with drugs. There is currently no report of tripterygium glycosides (TG)-induced AGEP-like lesions combined with BP. A 66-year-old male with a 20-year history of psoriasis was prescribed oral TG at 1 mg/kg, three times a day, due to aggravated psoriasis. Seven days later, erythemas, and blisters appeared. After another 3 days, there were two types of blisters: (1) numerous small tension blisters with a lot of neutrophils on the top similar to AGEP combined with BP; (2) a BP. After intravenous injection of methylprednisolone and gamma globulin, the lesions were controlled. This patient developed two types of lesions, including one similar to AGEP combined BP (AGEP-like) and a BP. It is a rare drug reaction induced by TG.
Asunto(s)
Pustulosis Exantematosa Generalizada Aguda , Penfigoide Ampolloso , Preparaciones Farmacéuticas , Anciano , Glicósidos/efectos adversos , Humanos , Masculino , Penfigoide Ampolloso/inducido químicamente , Penfigoide Ampolloso/diagnóstico , Penfigoide Ampolloso/tratamiento farmacológico , TripterygiumRESUMEN
Acute localized exanthematous pustulosis (ALEP) is a rare disease characterized by the acute onset of multiple localized non-follicular, pinhead-sized pustules. ALEP is considered a localized form of acute generalized exanthematous pustulosis but its pathogeny is not well identified. We performed a systematic review of the literature of all publications regarding ALEP cases using the term "acute localized exanthematous pustulosis," to provide an update on this disease and its management. Results and conclusion ALEP is an uncommon skin condition attributed primarily to a hypersensitivity reaction to a systemic drug (classical or herbal); though a contact mechanism has been reported. It may be misdiagnosed as infectious or inflammatory disease but the clinico-pathological correlation in addition to the rapid response to withdrawal of the culprit agent supports this diagnosis. The pathogenesis of ALEP is still unclear, and there are no standardized treatment guidelines to manage this disease. Both AGEP and ALEP have a good prognosis if an early diagnosis is made.
Asunto(s)
Pustulosis Exantematosa Generalizada Aguda , Pustulosis Exantematosa Generalizada Aguda/diagnóstico , Pustulosis Exantematosa Generalizada Aguda/etiología , Pustulosis Exantematosa Generalizada Aguda/terapia , HumanosRESUMEN
BACKGROUND AND OBJECTIVE: Severe cutaneous adverse reactions to drugs (SCARs) are associated with high morbidity and mortality and with sequelae. Objective: To characterize patients with SCARs in 8 health care institutions in Latin America. METHODS: We performed a cross-sectional, descriptive, multicenter study of patients diagnosed with SCARs in Latin America between January 2009 and December 2018. The analysis was carried out using a database in BD Clinic. RESULTS: We collected 70 patients, of whom 42 (60%) were women. Mean age was 38.7 years. Forty-two patients (60%) had DRESS-DIHS, 12 (17.1%) TEN, 5 (7.1%) SJS, 6 (8.5%) AGEP, 4 (5.7%) other reactions not classified as SCARs, and 1 (1.4%) overlapping SJS-TEN. The main causative drugs were aromatic anticonvulsants in 31 cases (44.3%), ß-lactam antibiotics in 11 cases (15.7%), and non-ß-lactam antibiotics in 6 cases (8.6%). In all of the cases, the suspected drug was withdrawn at the first sign of a SCAR. Sixty-six patients (94.2%) received anti-inflammatory treatment, mostly systemic corticosteroids. Complications occurred in 53 cases (75.7%), and 3 patients died (4.3%). Thirteen patients (18.6%) had sequelae. CONCLUSIONS: This is the first multicenter report on SCARs in Latin America. DRESS-DIHS was the most frequently reported clinical entity, and anticonvulsants were the main triggers. Most of the patients received systemic corticosteroids. Complications were frequent, and 3 patients died.
Asunto(s)
Corticoesteroides/uso terapéutico , Alérgenos/efectos adversos , Anticonvulsivantes/efectos adversos , Efectos Colaterales y Reacciones Adversas Relacionados con Medicamentos/epidemiología , Piel/patología , beta-Lactamas/efectos adversos , Adulto , Estudios Transversales , Efectos Colaterales y Reacciones Adversas Relacionados con Medicamentos/tratamiento farmacológico , Efectos Colaterales y Reacciones Adversas Relacionados con Medicamentos/mortalidad , Femenino , Humanos , América Latina/epidemiología , Masculino , Análisis de SupervivenciaRESUMEN
Acute generalized exanthematous pustulosis (AGEP) is a rare severe cutaneous adverse reaction usually caused by drugs. The annual incidence is one to five cases per million. It is characterized by an acute febrile episode, accompanied by numerous small primarily non-follicular, sterile pustules arising within large areas of edematous erythema. There have been several case reports to date of AGEP following exposure to antifungals. Terbinafine is most commonly implicated in AGEP. We report a case of 7-year-old boy who developed AGEP shortly after commencing oral fluconazole for Tinea capitis. To our knowledge, this is the fourth reported case of AGEP due to fluconazole.
Asunto(s)
Pustulosis Exantematosa Generalizada Aguda/diagnóstico , Pustulosis Exantematosa Generalizada Aguda/etiología , Antifúngicos/efectos adversos , Fluconazol/efectos adversos , Niño , Humanos , MasculinoRESUMEN
We present a severe case of acute generalized exanthematous pustulosis (AGEP) secondary to trimethoprim-sulfamethoxazole complicated by non-infectious circulatory shock in a 16-year-old boy. Hemodynamic instability has been reported as a complication of AGEP in adults, but is rarely observed in pediatric patients. The patient we present demonstrated characteristic cutaneous findings of AGEP including isolated non-follicular, sterile pustules on a background of erythema with involvement at intertriginous areas and subsequently developed non-infectious circulatory shock. This case expands the spectrum of possible clinical presentations for AGEP in pediatric patients.
Asunto(s)
Pustulosis Exantematosa Generalizada Aguda , Pustulosis Exantematosa Generalizada Aguda/diagnóstico , Pustulosis Exantematosa Generalizada Aguda/etiología , Adolescente , Adulto , Niño , Humanos , MasculinoRESUMEN
BACKGROUND: Acute generalized exanthematous pustulosis (AGEP) is a rare, severe, cutaneous adverse reaction. Although most commonly caused by drugs, it can also be triggered by infections, especially in children. METHODS: This is a retrospective study involving children and adolescents aged 16 years or younger, diagnosed with AGEP between January 2010 and March 2020 in our tertiary pediatric hospital. Information pertaining to the patient's demographics, clinical presentation and progress, biochemical, microbiological, and histopathological investigations, treatment, and outcomes was analyzed. RESULTS: Eight patients were diagnosed with AGEP with mean age 8.2 years (range: 1.7-16.0 years). None of the patients had a personal or family history of psoriasis. Almost all patients had fever (n = 7, 87.5%). Although all 8 patients had intercurrent illness, 5 cases were attributed to infection, while the other 3 were likely precipitated by drugs. Abnormal hematological and biochemical parameters included a raised absolute neutrophil count (mean: 11.5 × 109 /L, range: 5.0-30.9 × 109 /L), C-reactive protein (mean: 52.5 mg/L, range: 5.0-143.7 mg/L), and erythrocyte sedimentation rate (mean: 38.6 mm/h, range: 6-64 mm/h). All patients developed post-pustular desquamation and subsequently recovered. The mean duration from onset to cessation of acute pustulation was 5.6 days (range: 3.0-10.0 days). One patient developed a recurrent episode of AGEP. CONCLUSION: AGEP is rare and may be more commonly caused by infections in children. The condition is self-limiting with overall good outcomes in this age-group. In cases with concomitant infection and drug use, formal allergy testing should be arranged after resolution of the infection to confirm the underlying etiology.
Asunto(s)
Pustulosis Exantematosa Generalizada Aguda , Psoriasis , Pustulosis Exantematosa Generalizada Aguda/diagnóstico , Pustulosis Exantematosa Generalizada Aguda/epidemiología , Pustulosis Exantematosa Generalizada Aguda/etiología , Adolescente , Niño , Comorbilidad , Humanos , Estudios Retrospectivos , Singapur/epidemiologíaRESUMEN
The similarity between pustular psoriasis (PP) and acute generalized exanthematous pustulosis (AGEP) poses problems in the diagnosis and treatment of these two conditions. Significant clinical and histopathologic overlap exists between PP and AGEP. PP is an inflammatory disorder that has numerous clinical subtypes, but all with sterile pustules composed of neutrophils. AGEP is a severe cutaneous adverse reaction that is also characterized by non-follicular sterile pustules. Clinical features that suggest a diagnosis of PP over AGEP include a history of psoriasis and the presence of scaling plaques. Histologically, eosinophilic spongiosis, vacuolar interface dermatitis, and dermal eosinophilia favor a diagnosis of AGEP over PP. Importantly, PP and AGEP vary in clinical course and treatment. PP treatment involves topical steroids, oral retinoids, and systemic immunosuppressants. Newer therapies targeting IL-36, IL-23, IL-1, and PDE-4 have been investigated. The removal of the offending agent is a crucial part of the treatment of AGEP.