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Severe cutaneous adverse drug reactions are uncommon but potentially critical clinical situations demanding prompt diagnosis and treatment. We report a rare and severe case of terbinafine-induced acute generalized pustulosis. The patient was directly referred to a Burn Unit where she underwent diagnostic confirmation, systemic supportive care, and wound care treatments. Clinical and histopathological differential diagnosis of severe cutaneous adverse drug reactions is fundamental due to their significantly different management and prognosis.

Contrast media (CM) are an indispensable part of modern medical imaging. Adverse reactions to CM are uncommon, but frequently involve cutaneous symptoms. This two-part article reviews adverse events secondary to CM that are relevant to the practising dermatologist. Part 1 covers the classification of CM, immediate hypersensitivity reactions to CM and the newly described condition, gadolinium deposition disease. Given that there has only been two case reports to our knowledge of a delayed adverse reaction to gadolinium-based CM, this second part will focus on cutaneous delayed reactions caused by iodinated CM (ICM). Delayed hypersensitivity reactions to ICM commonly present as maculopapular exanthems, but more rarely, they can manifest as fixed drug eruptions, acute generalized exanthematous pustulosis, drug-related eosinophilia and systemic symptoms, Stevens-Johnson syndrome/toxic epidermal necrolysis, symmetrical drug-related intertriginous and flexural exanthema, graft-versus-host disease, vasculitis and iododerma. Delayed reactions to ICM may be underdiagnosed, as cutaneous symptoms may be attributed to oral medications, particularly if patients are on multiple drugs.

We present a returning traveler with acute generalized exanthematous pustulosis after atovaquone/proguanil prophylaxis. Diagnosis was confirmed with biopsy and allergy testing, symptoms resolved after steroid treatment. Atovaquone/proguanil prophylaxis is generally well tolerated, however, some patients may present severe adverse events that require prompt medical evaluation and treatment.

A male in early adolescence born to non-consanguineous parents was brought to dermatology outpatient department services with multiple pustular lesions over penis since 2 days. There was fever associated with chills and rigours. The patient is a known case of Lennox-Gastaut syndrome (multiple seizure types, electroencephalogram changes, intellectual impairment) on sodium valproate since 10 years. The patient was started on tablet lamotrigine 50 mg once daily in addition to sodium valproate 4 days prior to the lesions for the new onset of seizure episode. There was no history of irritant application. On cutaneous examination, there were multiple grouped non-follicular pustules on prepuce, shaft of penis with erythematous and oedematous background, at places coalescing to form lakes of pus (figure 1). Tzanck smear was …

Beta-lactam allergy is commonly diagnosed in paediatric patients, but over 90% of individuals reporting this allergy are able to tolerate the medications prescribed after evaluation by an allergist. Beta-lactam allergy labels are associated with negative clinical and administrative outcomes, including use of less desirable alternative antibiotics, longer hospitalizations, increasing antibiotic-resistant infections, and greater medical costs. Also, children with true IgE-mediated allergy to penicillin medications are often advised to avoid all beta-lactam antibiotics, including cephalosporins, which is likely unnecessary in greater than 97% of those reporting penicillin allergies. Most patients can be safely treated with penicillin or amoxicillin if they do not have a history compatible with IgE-mediated or systemic, delayed reactions such as Stevens-Johnson syndrome (SJS), serum sickness-like reactions, drug reaction with eosinophilia and systemic symptoms (DRESS) syndrome, or acute generalized exanthematous pustulosis (AGEP). Guidance is provided on how to stratify risk of beta-lactam allergy, and on test dosing and monitoring in the outpatient setting for patients deemed low risk. Guidance for patients at higher risk of beta-lactam allergy includes criteria for appropriate referral to allergists and the use of alternative antimicrobials, such as cephalosporins, while awaiting specialist assessment.

Acute generalized exanthematous pustulosis (AGEP) and Stevens-Johnson syndrome (SJS)/toxic epidermal necrolysis (TEN) are rare but severe cutaneous adverse drug reactions. Especially in TEN, large areas of the skin and mucosae may become detached. Although AGEP and SJS/TEN are distinct entities with a different clinical picture, pathogenesis, prognosis and treatment, they may share some features, raising the hypothesis of overlap between both entities. We present a severe case of AGEP, caused by flucloxacillin, clinically presenting with TEN-like features and pronounced systemic symptoms with haemodynamic and respiratory instability. Furthermore, we present a review of the literature on cases of AGEP with features resembling SJS/TEN or a supposed overlap with SJS/TEN.

Background Systemic antibiotics are a major cause of severe cutaneous adverse reactions (SCARs). The selection of alternative antibiotics and management for SCARs patients with underlying infections can be challenging. Methods We retrospectively analyzed 74 cases of SCARs, including Stevens-Johnson syndrome (SJS), toxic epidermal necrolysis (TEN), drug rash with eosinophilia and systemic symptoms (DRESS), and acute generalized exanthematous pustulosis (AGEP), related to use of systemic antibiotics in Taiwan from January 2006 to January 2012. We analyzed the causative antibiotics, clinical features, organ involvements, and mortality. We also assessed patient tolerability to alternative antibiotics after the development of antibiotic-related SCARs. Results The most common causes of SCARs were penicillins and cephalosporins for SJS/TEN and AGEP; glycopeptides for DRESS. Fatality was more frequent in the SJS/TEN group. In patients with SJS/TEN, higher mortality was associated with old age and underlying sepsis before the development of SCARs. The majority of patients with penicillin- or cephalosporin-related SCARs were able to tolerate quinolones, glycopeptides, and carbapenems. Conclusions Complicated underlying conditions and infections may increase mortality in patients with antibiotic-related SCARs. The selection of structurally different alternative drugs is important to avoid recurrence.

Summary Background Drug patch tests (PTs) can reproduce delayed hypersensitivity to drugs and entail a moderate re-exposure of patients to offending drugs. Objectives To determine the value of PTs for identifying the responsible drug in severe cutaneous adverse drug reactions (SCARs) such as acute generalized exanthematous pustulosis (AGEP), drug reaction with eosinophilia and systemic symptoms (DRESS) and Stevens–Johnson syndrome/toxic epidermal necrolysis (SJS/TEN). Methods In a multicentre study, PTs were conducted on patients referred for DRESS, AGEP or SJS/TEN within 1 year of their SCAR. All drugs administered in the 2 months prior to and the week following the onset of the SCAR were tested. Results Among the 134 patients included (48 male, 86 female; mean age 51·7 years), positive drug PTs were obtained for 24 different drugs. These included positive tests for 64% (46/72) of patients with DRESS, 58% (26/45) of those with AGEP and 24% (4/17) of those with SJS/TEN, with only one relapse of AGEP. The value of PTs depended on the type of drug and the type of SCAR (e.g. carbamazepine was positive in 11/13 DRESS cases but none of the five SJS/TEN cases). PTs were frequently positive for beta lactams (22 cases), pristinamycin (11 cases) and in DRESS with pump proton inhibitors (five cases), but were usually negative for allopurinol and salazopyrin. Of 18 patients with DRESS, eight had virus reactivation and positive PTs. In DRESS, multiple drug reactivity was frequent (18% of cases), with patients remaining sensitized many years later. Conclusions PTs are useful and safe for identifying agents inducing SCAR.

Summary Background Rashes are a frequent conundrum in clinical practice as they may be reactive, drug induced or disease specific. Identification of the culprit drug is important as re-exposure may be harmful or even life-threatening and unnecessary avoidance of ‘innocent’ drugs leads to limitations of treatment options. Objective To objectify the cause of suspected cutaneous drug reactions in a large patient population. Method Over 5 years (2006–10), 612 patients with suspected cutaneous drug reactions were evaluated. Histology was assessed. About 200 patients were invited for complete work-up with skin tests (prick/intracutaneous testing and scratch/patch as indicated) and, if necessary, lymphocyte transformation tests (LTT). In special cases, drug provocation tests were conducted. Results A total number of 141 cases with suspected drug reaction underwent full work-up (age 6–86 years; 75% female, 25% male). In 107 cases (76%) a drug was identified whereas 34 (24%) were reactive rashes or had other causes. Mostly, cutaneous drug reactions were maculopapular rashes, urticaria/angio-oedema; less frequently, acute generalized exanthematous pustulosis, drug reaction with eosinophilia and systemic symptoms, systemic drug-related intertriginous and flexural exanthema, toxic epidermal necrolysis and fixed drug eruptions were present. Of all the cutaneous drug reactions investigated, 39·8% were caused by antibiotics, 21·2% by anti-inflammatories, 7·6% by contrast media and 31·4% by others (oral antidiabetics, antimycotics, antipsychotics, antiepileptics and others). Conclusion Clinical assessment overestimates the role of drug allergies in cutaneous reactions. Assessment of suspected drug reactions can be greatly improved by thorough evaluation including dermatological and allergological work-up with skin testing and assays such as LTT.

A 72-year-old man developed a generalized erythematous pustular eruption 11 weeks after commencing terbinafine. Clinically and histologically, the appearance was that of acute generalized exanthematous pustulosis (AGEP), and the disease was managed with topical preparations. Initial improvement was marred by relapse of acute pustulosis, now more in keeping with terbinafine-induced pustular psoriasis (PP), which was successfully treated with acitretin. This case highlights the difficulty of differentiating between AGEP and PP.

Background Acute generalized exanthematous pustulosis (AGEP) is a rare severe pustular reaction pattern with a typical clinical picture. Objectives To characterize the histopathological features of AGEP in a large series of cases with a validated diagnosis. Methods A multinational retrospective histopathological study was conducted. It included 102 hospitalized patients (recruited within the EuroSCAR and RegiSCAR studies) with a validated diagnosis of probable or definite AGEP. A systematic description of the histopathological features in AGEP was done based on a standardized grading system. Results Sub/intracorneal pustules (41%), intraepidermal pustules (20%) or combinations of them (38%) were observed in 102 cases. The pustules were usually large (> 15 keratinocytes) (82% and 89%, respectively) and regularly contained eosinophils (36% and 32%, respectively). Spongiform features were less prominent in the sub/intracorneal pustules compared with the intraepidermal pustules (44% and 95%, respectively). The main epidermal features were necrotic keratinocytes (67%), including incidental segmental necrosis (7%), and spongiosis (80%) with neutrophil exocytosis (77%). The main dermal features were papillary oedema (88%) and mixed superficial (100%), interstitial (93%), and mid/deep-dermal infiltrates (95%) containing neutrophils (100%) and eosinophils (81%). Follicular pustules were also seen (23%), but vasculitis generally was absent. Classical features of plaque-type psoriasis were infrequent and usually mild. No significant differences were observed between a subgroup of 16 cases with and 86 cases without psoriasis. Conclusions The present histopathological study concerns a large series of cases with a validated diagnosis of AGEP. It provides diagnostic clues in favour of AGEP in patients with a pustular eruption.

Background Acute generalized exanthematous pustulosis (AGEP) is a disease characterized by the rapid occurrence of many sterile, nonfollicular pustules usually arising on an oedematous erythema often accompanied by leucocytosis and fever. It is usually attributed to drugs. Objectives To evaluate the risk for different drugs of causing AGEP. Patients and methods A multinational case-control study (EuroSCAR) conducted to evaluate the risk for different drugs of causing severe cutaneous adverse reactions; the study included 97 validated community cases of AGEP and 1009 controls. Results Strongly associated drugs, i.e. drugs with a lower bound of the 95% confidence interval (CI) of the odds ratio (OR) > 5 were pristinamycin (CI 26-infinity), ampicillin/amoxicillin (CI 10-infinity), quinolones (CI 8.5-infinity), (hydroxy)chloroquine (CI 8-infinity), anti-infective sulphonamides (CI 7.1-infinity), terbinafine (CI 7.1-infinity) and diltiazem (CI 5.0-infinity). No significant risk was found for infections and a personal or family history of psoriasis (CI 0.7-2.2). Conclusions Medications associated with AGEP differ from those associated with Stevens-Johnson syndrome or toxic epidermal necrolysis. Different timing patterns from drug intake to reaction onset were observed for different drugs. Infections, although possible triggers, played no prominent role in causing AGEP and there was no evidence that AGEP is a variant of pustular psoriasis.

Cutaneous drug reactions occur with a frequency of 1-8% and can be higher for certain classes of drugs. They can range from mild morbilliform eruptions to more severe forms such as drug-hypersensitivity syndrome, toxic epidermal necrolysis or anaphylaxis. Acute generalized exanthematous pustulosis (AGEP) is considered to be a clinical reaction pattern, which is induced in over 90% of the cases by systemic drugs. It is a rare presentation of an adverse drug reaction most frequently triggered by anti-infectious drugs. A high proportion of these cases have been attributed to aminopenicillins and macrolides. We report a terbinafine-induced AGEP in a 68-year-old male confirmed by lymphocyte stimulation in vitro, and review the published cases induced by antimycotic drugs with special emphasis on terbinafine-triggered cases.

Acute generalized exanthematous pustulosis (AGEP) is an uncommon skin disorder most often caused by drugs. Few adverse reactions to sympathomimetic drugs have been reported, despite their extensive use. Although the aetiology of AGEP remains uncertain, recent data have reported involvement of drug-specific T cells and interleukin (IL)-8 production. We characterized an adverse reaction to pseudoephedrine both clinically and immunologically. Histological analysis of skin biopsies confirmed the clinical entity as AGEP, while epicutaneous tests confirmed the specificity of the reaction to the drug. Moreover, immunohistochemical studies showed a mononuclear infiltrate consisting of activated memory T cells in addition to polymorphonuclear cells. Reverse transcription-polymerase chain reaction revealed an increased expression of IL-8 in AGEP-affected skin.

We report the first case, to the best of our knowledge, of a woman suffering from cystic echinococcosis of the liver, who consequently developed urticaria and acute generalized exanthematous pustolosis (AGEP). Serum immunoglobulin (Ig)E and IgG4 specific to Echinococcus granulosus antigens were detected by immunoblotting. Furthermore, the intracellular cytokine analysis revealed a prevalent T-helper 2 polarization. It can be reasoned that, while the presence of IgE specific to various E. granulosus allergens may be responsible for the chronic urticarial manifestations, the detection of IgG4 specific for E. granulosus antigens, forming immunocomplexes, may be related to the development of the AGEP.

Summary Acute generalized exanthematous pustulosis (AGEP) is an uncommon disease, whichpresents as a nonfollicular erythematous sterile pustular eruption. More than 90% ofthe cases are induced by adverse drug reactions, often triggered by anti-infectioussystemic drugs. We report a case of itraconazole-induced AGEP in a 22-year-old man,with an assessment of his cytokine ⁄chemokine production and drug-specific cellreactivity. We found that AGEP, like other T cell-mediated drug eruptions, alters theimmunological status of the patient, probably favouring T-cell activation, recruitmentand regulation. Few cases of itraconazole-induced AGEP have been described in theliterature, and to our knowledge, this is the first report in which the cellularimmunological features are assessed.Acute generalized exanthematous pustulosis (AGEP)is an uncommon phenomenon, often triggered byanti-infectious systemic drugs, 1 which presents as anonfollicular erythematous sterile pustular eruption.The clinical presentation typically includes: fever>38 C, nonfollicular intra-epidermal or subcornealsterile pustules arising on a widespread erythema, andblood neutrophil levels > 7 · 10

Acute generalized exanthematous pustulosis (AGEP) is a rare cutaneous reaction, which in most cases, is related to medication. Pemetrexed is an antifolate drug, approved for treatment of metastatic non-small-cell lung cancer (NSCLC) and malignant pleural mesothelioma (MPM). We present a case of AGEP caused by pemetrexed, and a recurrence of this eruption after re-introduction of pemetrexed despite use of corticosteroids.

Skin testing with the suspected compound has been reported to be helpful in determining the cause of cutaneous adverse drug reactions (ADRs), but the value and specificity of these tests need to be determined. In this study, 72 patients with presumed drug eruptions (27 maculopapular, 18 urticarial, seven erythrodermic, nine eczematous, four photosensitivity, three fixed drug eruptions, three with pruritus and one with acute generalized exanthematous pustulosis) were assessed. All had drug patch tests; 46 also had prick tests and 30 had intradermal tests (performed on hospitalized patients using a sterile solution of the suspected drug, diluted sequentially) with immediate and delayed readings. Among these patients, 52 (72%) had a positive skin test reaction, 43%, 24% and 67% in patch, prick and intradermal skin tests, respectively. The results of skin tests varied with the drug tested and with the clinical type of cutaneous ADR, as a significantly higher number of positive patch tests was observed in maculopapular rashes than in urticarial reactions (P = 0.001). This study supports the value of careful sequential drug skin testing in establishing the cause of cutaneous ADR. Guidelines are proposed for performing these tests, and these include the use of appropriate negative control patients to avoid false-positive results.

We report three cases of acute generalized exanthematous pustulosis (AGEP) following oral administration of nystatin. All cases showed similar clinical features and histopathological findings, and a delayed-type hypersensitivity to nystatin could be demonstrated in patch and prick testing. Drug eruptions to nystatin are extremely rare, and, to our knowledge. AGEP has not been reported previously.

Pustulation is a major feature in several different dermatoses, and it may also occur as a manifestation of drug hypersensitivity. Acute generalized exanthematous pustulosis (AGEP) is an uncommon eruption characterized by acute, extensive formation of sterile pustules, fever and peripheral blood leucocytosis. It shares several clinical and histological features in common with pustular psoriasis. Most reported cases have been triggered by ingestion of broad spectrum antibiotics, particularly betalactams and macrolides. There is usually rapid resolution of the eruption on drug withdrawal. We report the case of a 58 year-old woman who developed AGEP shortly after commencing treatment with the calcium channel blocker diltiazem hydrochloride. The eruption followed a biphasic course, and improved following treatment with systemic corticosteroids and methotrexate. AGEP appears to be a rare adverse cutaneous reaction to diltiazem, whereas a wide range of other skin eruptions have been reported more commonly with this drug.

We report a patient with acute generalized exanthematous pustulosis (AGEP), which occurred 3 days after ingesting paracetamol and bromhexine. Both were immediately stopped and the rash resolved rapidly. To determine the offending drug responsible for AGEP, an in vitro drug-induced interferon (IFN)-gamma release test was performed using an ELISA technique. Increased IFN-gamma release was observed following in vitro challenge of the patient's lymphocytes with paracetamol or bromhexine (110% and 157% increase, respectively). In vitro challenge with paracetamol or bromhexine in a control patient, treated with paracetamol and bromhexine, did not induce an increase in IFN-gamma. These findings suggest that the patient with AGEP may have polysensitivity to both drugs. The ELISA assessment also demonstrates the relevance of in vitro cytokine release tests in the investigation of such dermatoses.