Exanthematous Pustulosis Research Articles

TEASING OUT ALLERGY VERSUS INFECTION IN A PATIENT WITH SEPTIC SHOCK

Introduction In ill patients, it can be particularly difficult to determine whether physical examination or laboratory abnormalities are due to one or the other. We present a critically ill patient whose drug reaction (with end organ involvement) was initially misdiagnosed, despite having signs and symptoms of hypersensitivity. Case Description A 73-year old African American male was admitted for septic shock due to Klebsiella pneumoniae urosepsis. He received one dose of vancomycin and four days of piperacillin-tazobactam and was then switched to ceftriaxone. Within 14 hours of starting ceftriaxone, he developed pustules on his chest, neck, and back. These lesions were initially thought to be milia secondary to infection. However, further investigation revealed diffuse erythroderma, which was more easily discernible on his lower extremities as they were of lighter complexion. In addition, within 48 hours of starting ceftriaxone, he had worsening fevers, leukocytosis, neutrophilia, and transaminase levels. Based on these findings, his diagnosis was changed to Acute Generalized Exanthematous Pustulosis (AGEP) due to ceftriaxone. Discussion AGEP is a severe cutaneous drug hypersensitivity characterized by rapid development of pustules, fever, and leukocytosis with neutrophilia. It can also present with erythroderma, which can be easily missed in darker-pigmented patients. A thorough integumentary exam is paramount in suspected drug hypersensitivity reactions, as some areas will reveal erythroderma more easily. In ill patients, it can be particularly difficult to determine whether physical examination or laboratory abnormalities are due to one or the other. We present a critically ill patient whose drug reaction (with end organ involvement) was initially misdiagnosed, despite having signs and symptoms of hypersensitivity. A 73-year old African American male was admitted for septic shock due to Klebsiella pneumoniae urosepsis. He received one dose of vancomycin and four days of piperacillin-tazobactam and was then switched to ceftriaxone. Within 14 hours of starting ceftriaxone, he developed pustules on his chest, neck, and back. These lesions were initially thought to be milia secondary to infection. However, further investigation revealed diffuse erythroderma, which was more easily discernible on his lower extremities as they were of lighter complexion. In addition, within 48 hours of starting ceftriaxone, he had worsening fevers, leukocytosis, neutrophilia, and transaminase levels. Based on these findings, his diagnosis was changed to Acute Generalized Exanthematous Pustulosis (AGEP) due to ceftriaxone. AGEP is a severe cutaneous drug hypersensitivity characterized by rapid development of pustules, fever, and leukocytosis with neutrophilia. It can also present with erythroderma, which can be easily missed in darker-pigmented patients. A thorough integumentary exam is paramount in suspected drug hypersensitivity reactions, as some areas will reveal erythroderma more easily.

ACUTE LOCALIZED EXANTHEMATOUS PUSTULOSIS: A RARE CUTANEOUS DRUG ERUPTION

Introduction Acute localized exanthematous pustulosis (ALEP) is a rare, likely T-cell-mediated immune processes (type-IV-reaction), characterized by pustules typically localized to the face, neck or chest, usually in response to medications. We present a case with cutaneous drug reaction consistent with ALEP following administration of antibiotics. Case Description A 33-year-old woman presented with 3-4 days of painless pustules mostly on her right forehead, but slightly crossing the midline. She denied new topical exposures. However, she reported receiving intravenous ampicillin-sulbactam 4 days prior for purulent cellulitis of the hand, followed by oral amoxicillin-clavulanate. Based on wound culture sensitivities, the antibiotic was later changed to trimethoprim-sulfamethoxazole, of which she had only taken 2 doses of. Initially, her rash was believed to be shingles versus MRSA cellulitis, for which she was started on valacyclovir and vancomycin. However, the patient was afebrile without leukocytosis. On examination, she had multiple superficial pustules without significant erythema, warmth or edema. Due to the lack of typical signs of cellulitis and considering recent antibiotic exposure, the patient was eventually diagnosed with ALEP, with ampicillin-sulbactam or amoxicillin-clavulanate as the most likely culprits. All antibiotics were discontinued. The patient had spontaneous resolution of the rash several weeks following discharge. Discussion ALEP is a rare drug eruption occurring 3-5 days after drug commencement, most commonly associated with aminopenicillins. Major differentials include shingles, acne or bacterial infections. Key differentiating features include acute course, history of recent drug administration and spontaneous resolution following drug cessation. Once ALEP is confirmed, the patient should avoid further use of the trigger medication.

ACUTE GENERALIZED EXANTHEMATOUS PUSTULOSIS PRESENTING AS DISTRIBUTIVE SHOCK WITH MULTI-ORGAN FAILURE

SESSION TITLE: Critical Care 3 SESSION TYPE: Med Student/Res Case Rep Postr PRESENTED ON: 10/09/2018 01:15 PM - 02:15 PM INTRODUCTION: Acute Generalized Exanthematous Pustulosis (AGEP), or Pustular Drug Eruption, is a rare cutaneous condition most commonly induced by drug or toxin exposure. AGEP is manifested pathologically by acute sterile intraepidermal pustular eruptions and is a rare presentation of febrile drug reaction. Prior cases have described this pathology as similar in presentation to septic shock or toxic epidermal necrolysis. Vancomycin, antiepileptic agents, non-steroidal anti-inflammatory medications, antibiotics, and diltiazem have all been identified as possible etiologies of AGEP. Here we present a rare case of AGEP in a patient with no prior medication exposures presenting with shock and multisystem organ failure. CASE PRESENTATION: An 86 year-old woman presented to the Emergency Department (ED) with report of recurrent high grade fevers and progressive maculopapular rash for one week. The patient had previously been evaluated by outpatient dermatology. Biopsy was performed and results were pending at the time of initial ED evaluation. Symptoms were additionally refractory to topical steroid therapy. ED course was significant for tachycardia (110 beats per minute), hypotension (84/48 mmHg), fever (103˚F), bandemia (15%) and acute kidney injury (AKI). The patient was admitted to the Intensive Care Unit with distributive shock of unclear etiology. The patient received intravenous fluid resuscitation, norepinephrine infusion, vancomycin, and piperacillin/tazobactam. She subsequently developed multiorgan failure involving the renal, hepatic, cardiac and respiratory systems. Prior skin biopsy results were obtained and revealed intraepidermal neutrophilic pustules with no evidence of infection. Findings were consistent with AGEP. An extensive evaluation for an infectious etiology was unremarkable. Antibiotic therapy was discontinued and the patient was treated with pulse methylprednisolone therapy with a prolonged prednisone taper. The patient improved on steroid therapy and resolution of multiorgan failure was noted. The patient was subsequently discharged to a rehabilitation facility. DISCUSSION: AGEP is a rare cutaneous condition typically associated with medication or toxin exposure. We present a unique case of idiopathic AGEP in a patient with no prior infectious, toxic or medication exposures. This case is likewise unique with respect to disease severity and only four prior case reports describe AGEP progressing to multiorgan failure and shock. CONCLUSIONS: This is the first case, to our knowledge, describing the use of pulse dose steroids in the treatment of severe AGEP. Pulse therapy, in this setting, led to complete resolution of multiorgan dysfunction. Determination of the etiology of distributive shock is essential for the prompt and appropriate treatment of patients in the critical care setting. Reference #1: Mohyuddin GR, Al Asad M, Scratchko L, Khaleeq G. Acute generalized exanthematous pustulosis with multiple organ dysfunction syndrome. Am J Crit Care. 2013;22(3):270-3. Reference #2: Lesterhuis WJ, Tjioe M, Stumpenhausen GA, van Crevel R. Acute generalized exanthematous pustulosis mimicking septic shock. Am J Med. 2004;116(8):574-5. Reference #3: Shim K, Choi Y, Lee S, Lee H, Choi G, Kim H, Suh K. A case of acute generalized exanthematous pustulosis with patterns of septic shock. Korean J Med. 2011; 81(6):802-806. DISCLOSURES: No relevant relationships by George Elkomos-Botros, source=Web Response No relevant relationships by Mina Makaryus, source=Web Response No relevant relationships by Nirvi Shah, source=Web Response

Cephalexin-induced acute generalized exanthematous pustulosis.

Cephalexin is a cephalosporin antibiotic that is commonly used in the treatment of infectious diseases. We report a patient exhibiting a rare adverse effect of cephalexin: drug-induced Acute Generalized Exanthematous Pustulosis (AGEP). We present this case because of the scarcity of reports associating cephalexin with AGEP in hopes that clinicians will consider AGEP in their differential diagnosis in the appropriate clinical setting.

LB1568 Role of IL-36 in acute generalized exanthematous pustulosis

LB1568 Role of IL-36 in acute generalized exanthematous pustulosis

Acute generalized exanthematous pustulosis caused by fexofenadine

Acute generalized exanthematous pustulosis caused by fexofenadine

Acute generalized exanthematous pustulosis caused by lincomycin: a case report

A 28-year-old male patient with coughing was treated with intramuscular injection of lincomycin, oral Kesouting granules and erythromycin in a local clinic. One day later, erythema occurred on the head and face, and rapidly spread to the trunk and limbs. Three days later, a large number of densely distributed needle tip- to millet-sized pustules occurred on the generalized erythema all over the body with fever and burning pain sensation of the skin. Skin examination revealed diffuse edematous erythema with obvious hyperemia on more than 90% of the body, a large number of needle tip- to millet-sized white-yellowish pustules on the erythema on the hair line, face, flexor aspect of the extremities and flexural site of the trunk (axillary and inguinal regions) , and bilateral lower-extremity swelling. No erythema or erosion was observed on the oral mucosa or genital mucosa. Histopathological examination of skin lesions on the right elbow showed local intraepidermal and subcorneal pustules, necrotic keratinocytes and neutrophil aggregation in the pustules, and infiltration of lymphocytes and eosinophils in the superficial dermis. Laboratory examination showed elevated white blood cell counts (26.9 × 109/L) , neutrophils proportion (Segment, 0.88) , C-reactive protein level (127.89 mg/L) , aspartate aminotransferase level (44.2 U/L) and alanine transarninase level (77.3 U/L) , but decreased proportion of lymphocytes (0.08) . The patient was diagnosed with acute generalized exanthematous pustulosis. After admission, the patient was treated with intravenous drips of methylprednisolone at a dose of 60 mg/d. Then, the condition was rapidly relieved, and the dosage was rapidly reduced. The patient was discharged on day 7. Key words: Acute generalized exanthematous pustulosis; Lincomycin; Drug eruptions; Drug-induced liver injury

DILI Associated with Skin Reactions

Adverse drug reactions (ADR) frequently involve the liver and skin in the form of drug-induced liver injury or cutaneous drug eruption. Skin ADR can range from harmless rash to severe skin manifestations such as drug rash with eosinophilia and systemic symptom syndrome (DRESS syndrome), Stevens-Johnson syndrome (SJS), toxic epidermal necrolysis (TEN), and acute generalized exanthematous pustulosis (AGEP), all of which can be associated with severe outcome, including a 30% mortality rate in case of TEN. The association with co-occurring liver injury varies and in DRESS and SJS/TEN can contribute to substantial morbidity and mortality. Liver and skin ADR are frequent but rarely severe; however, if severe, they are not uncommonly fatal.

Analysis of HLA-B Allelic Variation and IFN-γ ELISpot Responses in Patients with Severe Cutaneous Adverse Reactions Associated with Drugs

The prevention and confirmation of drug-induced severe cutaneous adverse reactions (SCARs) are difficult. To determine the benefit of HLA-B allele prescreening and the measurement of drug-specific IFN-γ-releasing cells in the prevention and identification of the culprit drug in patients with SCARs. A total of 160 patients with SCARs were recruited from 6 university hospitals in Thailand over a 3-year period. HLA-B alleles were genotypically analyzed. The frequencies of drug-specific IFN-γ-releasing cells in patients with SCARs were also measured. The drugs commonly responsible for SCARs were anticonvulsants, allopurinol, beta-lactams, antituberculosis agents, and sulfonamides. If culprit drugs had been withheld in patients carrying known HLA-B alleles at risk, it would have prevented 21.2% of SCAR cases, mainly allopurinol- and carbamazepine-related SCARs. Culprit drug-specific IFN-γ-releasing cells could be identified in 45.7% (53 of 116) of patients with SCARs caused by 5 major drug groups, particularly in patients diagnosed with drug reactions with eosinophilia andsystemic symptoms (DRESS) (50.0%), followed by Stevens-Johnson syndrome/toxic epidermal necrolysis (46.0%), and acute generalized exanthematous pustulosis (31.3%). According to our study, high frequencies of drug-specific IFN-γ-releasing cells were significantly demonstrated in patients who suffered from DRESS phenotype, having anticonvulsants or the drugs belonging to the "probable" category based on the Naranjo algorithm scale, as the culpritdrugs. HLA-B prescreening would succeed in preventing only a minority of SCAR victims. Drug-specific IFN-γ-releasing cells are detectable in almost half of patients. Better strategies are required for better SCAR prevention and culprit drug confirmation.

Severe cutaneous adverse reactions induced by targeted anticancer therapies and immunotherapies.

With the increasing use of targeted anticancer drugs and immunotherapies, there have been a substantial number of reports concerning life-threatening severe cutaneous adverse reactions (SCARs), including Stevens–Johnson syndrome (SJS), toxic epidermal necrolysis (TEN), drug rash with eosinophilia and systemic symptoms, drug-induced hypersensitivity syndrome, and acute generalized exanthematous pustulosis. Although the potential risks and characteristics for targeted anticancer agent- and immunotherapy-induced SCAR were not well understood, these serious adverse reactions usually result in morbidity and sequela. As a treatment guideline for this devastating condition is still unavailable, prompt withdrawal of causative drugs is believed to be a priority of patient management. In this review, we outline distinct types of SCARs caused by targeted anticancer therapies and immunotherapies. Also, we discuss the clinical course, latency, concomitant medication, tolerability of rechallenge or alternatives, tumor response, and mortality associated with these devastating conditions. Imatinib, vemurafenib, and rituximab were the top three offending medications that most commonly caused SJS/TEN, while EGFR inhibitors were the group of drugs that most frequently induced SJS/TEN. For drug rash with eosinophilia and systemic symptoms/drug-induced hypersensitivity syndrome and acute generalized exanthematous pustulosis, imatinib was also the most common offending drug. Additionally, we delineated 10 SCAR cases related to innovative immunotherapies, including PD1 and CTLA4 inhibitors. There was a wide range of latency periods: 5.5–91 days (median). Only eight of 16 reported patients with SCAR showed clinical responses. Targeted anticancer drugs and immunotherapies can lead to lethal SCAR (14 deceased patients were identified as suffering from SJS/TEN). The mortality rate of TEN was high: up to 52.4%. The information compiled herein will serve as a solid foundation to formulate ideas for early recognition of SCAR and to discontinue offending drugs for better management.

Acute generalized exanthematous pustulosis due to hydroxychloroquine after a prolonged latent period

Acute generalized exanthematous pustulosis due to hydroxychloroquine after a prolonged latent period

Severe Cutaneous Adverse Drug Reactions: Presentation, Risk Factors, and Management.

Immune-mediated adverse drug reactions occur commonly in clinical practice and include mild, self-limited cutaneous eruptions, IgE-mediated hypersensitivity, and severe cutaneous adverse drug reactions (SCAR). SCARs represent an uncommon but potentially life-threatening form of delayed T cell-mediated reaction. The spectrum of illness ranges from acute generalized exanthematous pustulosis (AGEP) to drug reaction with eosinophilia with systemic symptoms (DRESS), to the most severe form of illness, Stevens-Johnson syndrome (SJS) and toxic epidermal necrolysis (TEN). There is emerging literature on the efficacy of cyclosporine in decreasing mortality in SJS/TEN. The purpose of our review is to discuss the typical presentations of these conditions, with a special focus on identifying the culprit medication. We review risk factors for developing SCAR, including HLA alleles strongly associated with drug hypersensitivity. We conclude by discussing current strategies for the management of these conditions.

The genetic basis for most patients with pustular skin disease remains elusive.

Rare variants in the genes IL36RN, CARD14 and AP1S3 have been identified to cause or contribute to pustular skin diseases, primarily generalized pustular psoriasis (GPP). To better understand the disease relevance of these genes, we screened our cohorts of patients with pustular skin diseases [primarily GPP and palmoplantar pustular psoriasis (PPP)] for coding changes in these three genes. Carriers of single heterozygous IL36RN mutations were screened for a second mutation in IL36RN. Coding exons of IL36RN, CARD14 and AP1S3 were sequenced in 67 patients - 61 with GPP, two with acute generalized exanthematous pustulosis and four with acrodermatitis continua of Hallopeau. We screened IL36RN and AP1S3 for intragenic copy-number variants and 258 patients with PPP for coding changes in AP1S3. Eleven heterozygous IL36RN mutations carriers were analysed for a second noncoding IL36RN mutation. Genotype-phenotype correlations in carriers/noncarriers of IL36RN mutations were assessed within the GPP cohort. The majority of patients (GPP, 64%) did not carry rare variants in any of the three genes. Biallelic and monoallelic IL36RN mutations were identified in 15 and five patients with GPP, respectively. Noncoding rare IL36RN variants were not identified in heterozygous carriers. The only significant genotype-phenotype correlation observed for IL36RN mutation carriers was early age at disease onset. Additional rare CARD14 or AP1S3 variants were identified in 15% of IL36RN mutation carriers. The identification of IL36RN mutation carriers harbouring additional rare variants in CARD14 or AP1S3 indicates a more complex mode of inheritance of pustular psoriasis. Our results suggest that, in heterozygous IL36RN mutation carriers, there are additional disease-causing genetic factors outside IL36RN.

Management of severe drug reactions: a retrospective monocentric analysis

In contrast to the classic frequently seen drug eruptions, the rare severe drug reactions such as acute generalized exanthematous pustulosis (AGEP), erythema multiforme (EM), Stevens–Johnson syndrome (SJS), toxic epidermal necrolysis (TEN, Lyell’s syndrome), and drug reaction with eosinophilia and systemic symptoms (DRESS) are frequently associated with increased mortality. Neither their acute management nor their further allergy diagnostic testing to avoid re-exposure and enable restriction of substances prohibited due to the event are standardized. The management of severe adverse drug reactions was investigated in a 10-year monocentric retrospective study. TEN (43.5%) and EM (29.0%) were the two most common subtypes of severe adverse drug reactions, while AGEP (3.2%), SJS (6.5%), and DRESS (17.7%) were less frequent. The acute management of 62 patients with severe adverse drug reactions was generally performed using systemic glucocorticoids (58.1%) or as a combination therapy consisting of glucocorticoids and intravenous immunoglobulins (IVIG, 41.9%), which were usually used in severe clinical courses. The most commonly suspected triggers were beta-lactam antibiotics (28.8%), followed by metamizole (19.4%) and sulfonamide antibiotics (17.7%). Due to the rarity and heterogeneity of this patient population, there is scant reliable data on the systemic treatment of SJS/TEN. Therefore, whether it confers an evident benefit remains unclear. Although the allergy diagnostic testing of severe adverse drug reactions is complex, it is often able to yield important insights and should be performed.

A case of intractable acute generalized exanthematous pustulosis induced by hydroxychloroquine

A case of intractable acute generalized exanthematous pustulosis induced by hydroxychloroquine

Acute Generalised Exanthematous Pustulosis: An Update.

Acute generalised exanthematous pustulosis (AGEP) is a severe cutaneous adverse reaction and is attributed to drugs in more than 90% of cases. It is a rare disease, with an estimated incidence of 1–5 patients per million per year. The clinical manifestations characterised by the rapid development of sterile pustular lesions, fever and leucocytosis. Number of drugs has been reported to be associated with AGEP, most common being the antibiotics. Histopathologically there is intraepidermal pustules and papillary dermal oedema with neutrophilic and eosinophilic infiltrations. Systemic involvement can be present in more severe cases. Early diagnosis with withdrawal of the causative drug is the most important step in the management. Treatment includes supportive care, prevention of antibiotics and use of a potent topical steroid.

Ciprofloxacin-induced Acute Generalized Exanthematous Pustulosis

Acute generalized exanthematous pustulosis (AGEP) is a cutaneous eruption characterized by sterile non-follicular pustules located on erythematous skin. This case report describes a rare instance of ciprofloxacin-induced AGEP in a patient initially admitted to the hospital for treatment of acute diverticulitis.

Acute Generalized Exanthematous Pustulosis during Puerperal Period Induced by Azithromycin: Case Report

Background: The use of antibiotics, especially beta-lactams and macrolides, may be associated with dermatopathies, such as Acute Generalized Exanthematous Pustulosis (AGEP), which is an uncommon cutaneous adverse reaction. Case: We report a case of AGEP, in a 36-year-old multiparous (G5P3C1A1) woman, with 38 weeks of gestation, admitted to the hospital to induce labor. Due to cephalopelvic disproportion, the cesarean section was indicated. In the postoperative period, the patient evolved with cutaneous rash, accompanied by productive cough and dyspnea. Because it was a fever of obscure origin, the treatment with antibiotics, including azithromycin, was initiated. On subsequent days, she presented pustules on the back, abdomen and extremities. Such reaction was attributed to the use of azithromycin. When the drug was discontinued, the lesions regressed significantly. Conclusion: The clinical picture of AGEP may occur with persistent high fever and therefore could be confused with systemic infections, consequently, being treated with wrong medications capable of aggravating the adverse cutaneous reaction, worsening the course of the disease that could be easily treated by stopping the use of the causative drug. This case shows the importance of including AGEP as a differential diagnosis of dermatopathies in the pregnancy-puerperal cycle, especially in women who are using various medications, including antibiotics.

Clinicopathologic retrospective analysis of annular pustular psoriasis

Annular pustular psoriasis (APP) is a rare form of pustular psoriasis with a chronic relapsing course and a good prognosis. The clinical picture is characterized by erythematous lesions, usually polycyclic, with the presence of small, sterile pustules on the circumference of the lesions and fine peeling. We present two cases of APP with diagnostic problems: a 65-year-old woman that suffered from intermittent APP with remission and exacerbation for many years, and an 83-year-old man with lesions that developed after atenolol treatment. In both cases, the patients were thought to have drug provocation, and therefore acute generalized exanthematous pustulosis (AGEP) was diagnosed. Only a thorough analysis of the course of the disease and histopathological examination allowed correct diagnosis. The clinical picture of APP is similar to AGEP, generalized pustular psoriasis (GPP), also known as von Zumbusch pustular psoriasis, and subcorneal pustular disease, and it requires accurate differential diagnosis.

Cefixime-associated acute generalized exanthematous pustulosis: Rare cases in India.

BACKGROUND:Cefixime is a widely used third-generation cephalosporin schedule H1 drug, which is prescribed for the treatment of otitis media, respiratory tract infections, and uncomplicated urinary tract infections and is effective against infections caused by Enterobacteriaceae and Haemophilus influenzae species in India. The National Coordination Centre (NCC)-Pharmacovigilance Programme of India (PvPI), Indian Pharmacopoeia Commission (IPC), has received rare individual case safety reports (ICSRs) for acute generalized exanthematous pustulosis (AGEP) associated with the use of cefixime.MATERIALS AND METHODS:IPC, NCC-PvPI also acts as a national collaborating center for pharmacovigilance activities under the aegis of Ministry of Health and Family Welfare, Government of India; moreover, it is a member country in global pharmacovigilance system, World Health Organization-Uppsala Monitoring Centre, Sweden. There are more than 250 government/corporate medical colleges and hospitals acting as regional adverse drug reaction monitoring centers, actively functioning under PvPI. Furthermore, various stakeholders including consumers and pharmaceutical industries also play a significant contribution. NCC-PvPI receives spontaneous ICSRs from various stakeholders.RESULTS:NCC-PvPI, IPC has received a total of four spontaneous ICSRs for cefixime-induced AGEP. After clinical evaluation of reported ICSRs, a strong causal relationship was established between AGEP and cefixime and was supported by published literature and histopathological examination of skin. Based on the statistics with positive information component (IC025 Value: 0.17) and proportionality relative risk (PRR:3.4), PvPI considered cefixime-associated AGEP may be a potential signal.CONCLUSION:Hence, initially, AEGP is considered by PvPI as drug safety alert in July 2016. Therefore, to enhance the safety of population in rational usage of medication, as a result, there is a need for physicians and health-care professionals to sensitize about serious adverse reaction while prescribing the cefixime as signal in India.