RESUMO
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.
Assuntos
Pustulose Exantematosa Aguda Generalizada , Soluções para Diálise , Icodextrina , Diálise Peritoneal , Humanos , Feminino , Pustulose Exantematosa Aguda Generalizada/etiologia , Pustulose Exantematosa Aguda Generalizada/diagnóstico , Soluções para Diálise/efeitos adversos , Adulto , Resultado do Tratamento , Glucanos/efeitos adversos , Falência Renal Crônica/terapia , Falência Renal Crônica/complicações , Glucose , Biópsia , Pele/patologia , Pele/efeitos dos fármacosRESUMO
Acute generalized exanthematous pustulosis (AGEP) is a rare, usually drug-induced, acute pustular rash. Despite the lack of strong data supporting the effectiveness of topical or systemic corticosteroids in this drug reaction, they are widely used. More generally, there is no consensus on the diagnostic modalities and the management of patients with AGEP. We aimed to provide European expert recommendations for the diagnosis and management or patients with AGEP. Members of the ToxiTEN group of the European Reference Network (ERN)-skin, all dermatologists and/or allergologists with expertise in drug reactions, elaborated these recommendations based on their own experience and on a review of the literature. Recommendations were separated into the following categories: professionals involved, assessment of the diagnosis of AGEP, management of the patient and allergological work-up after the acute phase. Consensus was obtained among experts for the list of professionals involved for the diagnosis and management of AGEP, including the minimum diagnostic work-up, the setting of management, the treatments, the modalities and the timing of allergological work-up and follow-up. European experts in drug allergies propose herein consensus on the diagnosis and management of patients with AGEP. A multidisciplinary approach is warranted, including dermatologists, allergologists and pharmacovigilance services.
Assuntos
Pustulose Exantematosa Aguda Generalizada , Consenso , Humanos , Pustulose Exantematosa Aguda Generalizada/diagnóstico , Pustulose Exantematosa Aguda Generalizada/etiologia , Pustulose Exantematosa Aguda Generalizada/terapia , Europa (Continente)RESUMO
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.
Assuntos
Sistemas de Notificação de Reações Adversas a Medicamentos , Inibidores de Checkpoint Imunológico , Síndrome de Stevens-Johnson , United States Food and Drug Administration , Humanos , Inibidores de Checkpoint Imunológico/efeitos adversos , Sistemas de Notificação de Reações Adversas a Medicamentos/estatística & dados numéricos , Estados Unidos , Síndrome de Stevens-Johnson/etiologia , Toxidermias/etiologia , Feminino , Masculino , Síndrome de Hipersensibilidade a Medicamentos/etiologia , Pessoa de Meia-Idade , Pustulose Exantematosa Aguda Generalizada/etiologia , IdosoRESUMO
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.
Assuntos
Pustulose Exantematosa Aguda Generalizada , Síndrome de Stevens-Johnson , Humanos , Estados Unidos , Acetilcisteína , Cicatriz , Fluconazol , Valaciclovir , Síndrome de Stevens-Johnson/etiologia , Pustulose Exantematosa Aguda Generalizada/etiologiaRESUMO
Acute generalized exanthematous pustulosis is a severe adverse skin reaction, usually caused by drugs, but in rare cases it can be associated with infections. Several cases related to COVID-19 have been reported, however, almost all were drug-related. Here we report a case of acute generalized exanthematous pustulosis associated with COVID-19 in a previously healthy 64-year-old woman, with no culprit drugs.
Assuntos
Pustulose Exantematosa Aguda Generalizada , COVID-19 , Humanos , Pustulose Exantematosa Aguda Generalizada/etiologia , Pustulose Exantematosa Aguda Generalizada/patologia , Pustulose Exantematosa Aguda Generalizada/diagnóstico , Feminino , Pessoa de Meia-Idade , COVID-19/complicações , SARS-CoV-2RESUMO
ABSTRACT: Acute generalized exanthematous pustulosis (AGEP) is a rare, pustular rash that occurs most commonly after exposure to a medication (typically antibiotics or diltiazem). This case describes a patient who developed a widespread pustular eruption shortly after beginning empiric antibiotics for community-acquired pneumonia. Diagnosis of AGEP was difficult in this scenario due to the patient's pulmonary infection and atypical skin biopsy results. However, after AGEP was correctly identified, the offending agents were discontinued and the patient had subsequent resolution of her symptoms.
Assuntos
Pustulose Exantematosa Aguda Generalizada , Antibacterianos , Humanos , Pustulose Exantematosa Aguda Generalizada/diagnóstico , Pustulose Exantematosa Aguda Generalizada/etiologia , Feminino , Antibacterianos/efeitos adversos , Infecções Comunitárias Adquiridas/tratamento farmacológico , Infecções Comunitárias Adquiridas/diagnóstico , Pessoa de Meia-IdadeRESUMO
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.
Assuntos
Pustulose Exantematosa Aguda Generalizada , Exantema , Pênfigo Familiar Benigno , Humanos , Feminino , Pessoa de Meia-Idade , Pustulose Exantematosa Aguda Generalizada/tratamento farmacológico , Pustulose Exantematosa Aguda Generalizada/etiologia , Pustulose Exantematosa Aguda Generalizada/diagnóstico , Clindamicina/efeitos adversos , Pênfigo Familiar Benigno/tratamento farmacológico , Exantema/patologia , Pele/patologiaRESUMO
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.
Assuntos
Pustulose Exantematosa Aguda Generalizada , Humanos , Pustulose Exantematosa Aguda Generalizada/diagnóstico , Pustulose Exantematosa Aguda Generalizada/etiologia , Pustulose Exantematosa Aguda Generalizada/terapia , Pele/patologia , Administração CutâneaRESUMO
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.
Assuntos
Pustulose Exantematosa Aguda Generalizada , Humanos , Pustulose Exantematosa Aguda Generalizada/diagnóstico , Pustulose Exantematosa Aguda Generalizada/etiologia , Irmãos , Pele , Administração CutâneaRESUMO
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.
Assuntos
Pustulose Exantematosa Aguda Generalizada , Exantema , Dermatopatias , Vasculite Leucocitoclástica Cutânea , Humanos , Pustulose Exantematosa Aguda Generalizada/diagnóstico , Pustulose Exantematosa Aguda Generalizada/etiologia , Pustulose Exantematosa Aguda Generalizada/patologia , Exantema/etiologia , Exantema/patologia , Dermatopatias/complicações , Vasculite Leucocitoclástica Cutânea/induzido quimicamente , Vasculite Leucocitoclástica Cutânea/complicaçõesRESUMO
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.
Assuntos
Pustulose Exantematosa Aguda Generalizada , Exantema , Síndrome de Stevens-Johnson , Pustulose Exantematosa Aguda Generalizada/diagnóstico , Pustulose Exantematosa Aguda Generalizada/etiologia , Pustulose Exantematosa Aguda Generalizada/patologia , Humanos , Imunoglobulinas Intravenosas/uso terapêutico , Pele/patologia , Síndrome de Stevens-Johnson/diagnóstico , Síndrome de Stevens-Johnson/tratamento farmacológico , Síndrome de Stevens-Johnson/etiologiaRESUMO
is missing (Short communication).
Assuntos
Pustulose Exantematosa Aguda Generalizada , Dermatite Atópica , Pustulose Exantematosa Aguda Generalizada/diagnóstico , Pustulose Exantematosa Aguda Generalizada/tratamento farmacológico , Pustulose Exantematosa Aguda Generalizada/etiologia , Adolescente , Anticorpos Monoclonais Humanizados , China , Dermatite Atópica/diagnóstico , Dermatite Atópica/tratamento farmacológico , Feminino , HumanosRESUMO
BACKGROUND: Acute Generalised Exanthematous Pustulosis (AGEP) is a rash with multiple sterile intraepidermal or subcorneal non-follicular pustules on edematous papules, with a sudden development and rapid evolution, triggered by drugs, vaccination, insect bites, exposure to mercury, and allergens. OBJECTIVES AND METHODS: We describe a female patient who developed extensive and abnormally prolonged AGEP following exposure to terbinafine and SARS-CoV vaccine. A detailed review of terbinafine-induced-AGEP cases was performed, with the aim of evaluating if the AGEP criteria would follow a different pattern when the disease is triggered by this drug. A PubMed search helped retrieve all terbinafine-induced AGEP case reports. AGEP-specific Sideroff criteria were analysed in terbinafine-induced cases and compared to other trigger causes. CONCLUSIONS: When the AGEP causative drug was terbinafine, a delay in recovery was observed, compared to the existing AGEP criteria when other causes are considered. Terbinafine frequently leads to delayed resolution AGEP probably due to the presence of the drug in the skin for several weeks after exposure, even after discontinuation, and the disease severity may be potentialised by additional factors such as concomitant viral infections or vaccination.
Assuntos
Pustulose Exantematosa Aguda Generalizada , Mercúrio , Pustulose Exantematosa Aguda Generalizada/etiologia , Feminino , Humanos , Pele , Terbinafina/efeitos adversosRESUMO
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.
Assuntos
Pustulose Exantematosa Aguda Generalizada , Exantema , Humanos , Feminino , Idoso , Masculino , Pustulose Exantematosa Aguda Generalizada/diagnóstico , Pustulose Exantematosa Aguda Generalizada/tratamento farmacológico , Pustulose Exantematosa Aguda Generalizada/etiologia , Cefalosporinas/efeitos adversos , Estudos Retrospectivos , Ceftriaxona , Exantema/induzido quimicamente , Monobactamas/efeitos adversosRESUMO
Skin tests, including patch tests (PTs), prick tests, and intradermal tests (IDTs), are useful in identifying the culprits of cutaneous adverse drug reactions (CADRs), and determining safer, alternative drugs. PTs have a low sensitivity but are valuable in investigating maculopapular exanthema (MPE), as well as severe CADR, including toxic epidermal necrolysis (TEN), Stevens-Johnson syndrome (SJS), and in particular, acute generalized exanthematous pustulosis (AGEP), and drug reaction with eosinophilia and systemic symptoms (DRESS). To ensure their specificity, at least 10 control tests should be performed. Prick tests are mainly used in the evaluation of immediate-type hypersensitivity and can be performed with all drugs, except opiates. IDTs can be used to explore immediate and delayed-type hypersensitivity, if an injectable form of the drug exists. Except for SJS/TEN, IDTs should be performed by injecting 0.02 mL of the drug. We here provide a practical, up-to-date review on the use of these skin tests in the work-up of CADRs. Numerous negative controls for drug PTs, as well as criteria for the immediate and delayed positivity of prick tests and IDT, are included. It should be emphasized that a negative result never excludes the potential responsibility of a drug in a CADR.
Assuntos
Pustulose Exantematosa Aguda Generalizada , Dermatite Alérgica de Contato , Síndrome de Hipersensibilidade a Medicamentos , Síndrome de Stevens-Johnson , Pustulose Exantematosa Aguda Generalizada/diagnóstico , Pustulose Exantematosa Aguda Generalizada/etiologia , Síndrome de Hipersensibilidade a Medicamentos/diagnóstico , Síndrome de Hipersensibilidade a Medicamentos/etiologia , Humanos , Testes do Emplastro , Testes Cutâneos , Síndrome de Stevens-Johnson/diagnóstico , Síndrome de Stevens-Johnson/etiologiaRESUMO
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.
Assuntos
Pustulose Exantematosa Aguda Generalizada , Dermatite Alérgica de Contato , Pustulose Exantematosa Aguda Generalizada/diagnóstico , Pustulose Exantematosa Aguda Generalizada/tratamento farmacológico , Pustulose Exantematosa Aguda Generalizada/etiologia , Amoxicilina/efeitos adversos , Antibacterianos/efeitos adversos , Dermatite Alérgica de Contato/complicações , Humanos , Testes do Emplastro , Pristinamicina/efeitos adversosRESUMO
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.
Assuntos
Pustulose Exantematosa Aguda Generalizada , Pustulose Exantematosa Aguda Generalizada/diagnóstico , Pustulose Exantematosa Aguda Generalizada/etiologia , Pustulose Exantematosa Aguda Generalizada/terapia , HumanosRESUMO
Rash, photosensitivity, erythema multiforme, and the acute generalized exanthematous pustulosis (AGEP) are relatively uncommon adverse reactions of drugs. To date, the etiology is not well understood and individual susceptibility still remains unknown. Amiodarone, chlorpromazine, amitriptyline, and trimipramine are classified lysosomotropic as well as photosensitizing, however, they fail to trigger rash and pruritic papules in all individuals. Lysosomotropism is a common charcteristic of various drugs, but independent of individuals. There is evidence that the individual ability to respond to external oxidative stress is crosslinked with the elongation of long-chain fatty acids to very long-chain fatty acids by ELOVLs. ELOVL6 and ELOVL7 are sensitive to ROS induced depletion of cellular NADPH and insufficient regeneration via the pentose phosphate pathway and mitochondrial fatty acid oxidation. Deficiency of NADPH in presence of lysosomotropic drugs promotes the synthesis of C16-ceramide in lysosomes and may contribute to emerging pruritic papules of AGEP. However, independently from a lysosomomotropic drug, severe depletion of ATP and NAD(P)H, e.g., by UV radiation or a potent photosensitizer can trigger likewise the collapse of the lysosomal transmembrane proton gradient resulting in lysosomal C16-ceramide synthesis and pruritic papules. This kind of papules are equally present in polymorphous light eruption (PMLE/PLE) and acne aestivalis (Mallorca acne). The suggested model of a compartmentalized ceramide metabolism provides a more sophisticated explanation of cutaneous drug adverse effects and the individual sensitivity to UV radiation. Parameters such as pKa and ClogP of the triggering drug, cutaneous fatty acid profile, and ceramide profile enables new concepts in risk assessment and scoring of AGEP as well as prophylaxis outcome.
Assuntos
Pustulose Exantematosa Aguda Generalizada/tratamento farmacológico , Pustulose Exantematosa Aguda Generalizada/etiologia , Amitriptilina/farmacocinética , Ceramidas/metabolismo , Esfingolipídeos/metabolismo , Pustulose Exantematosa Aguda Generalizada/patologia , Vesícula/induzido quimicamente , Dermatite Atópica/etiologia , Ácidos Graxos/química , Ácidos Graxos/metabolismo , Antagonistas dos Receptores Histamínicos/efeitos adversos , Humanos , Lisossomos/efeitos dos fármacos , Lisossomos/metabolismo , NADP/metabolismo , Transtornos de Fotossensibilidade/etiologia , Transtornos de Fotossensibilidade/metabolismo , Fármacos Fotossensibilizantes/efeitos adversosRESUMO
Notably, enoxaparin has not been described to cause acute localized exanthematous pustulosis (ALEP). Herein, we present a case of a woman with a cutaneous drug reaction consistent with ALEP that occurred after enoxaparin. This case highlights enoxaprin as a novel causative agent for this type of drug reaction.
Assuntos
Pustulose Exantematosa Aguda Generalizada/etiologia , Anticoagulantes/efeitos adversos , Enoxaparina/efeitos adversos , Pustulose Exantematosa Aguda Generalizada/patologia , Adulto , Anticoagulantes/administração & dosagem , Enoxaparina/administração & dosagem , Feminino , Humanos , Injeções Intradérmicas , Trombose Venosa/prevenção & controle , Suspensão de TratamentoRESUMO
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.