Severe drug‐induced skin reactions: clinical features,diagnosis, etiology,and therapy

Drugs can induce severe skin reactions that differ in clinical presentation, prognosis, and therapy. The spectrum of these reactions not only includes bullous reactions such as Stevens‐Johnson syndrome (SJS), toxic epidermal necrolysis (TEN), and generalized bullous fixed drug eruption (GBFDE) but also acute generalized exanthematous pustulosis (AGEP) and drug reaction with eosinophilia and systemic symptoms (DRESS). If AGEP or DRESS is suspected, the diagnosis should be confirmed by thorough clinical examination, a skin biopsy, and specific laboratory tests. Crucial for the patient's prognosis, the causative agent should be rapidly identified and discontinued. It is therefore important to know the most frequent triggers of severe drug reactions, some of which may induce various reaction patterns. Depending on the clinical diagnosis, symptomatic and adequate supportive therapy, as well as systemic immunomodulatory treatments are used. The prognosis in SJS/TEN is often poor and depends on the patient's age and underlying conditions as well as the extent of skin detachment. The prognosis of GBFDE is somewhat better, but recurrences may lead to more severe disease manifestations. In DRESS, protracted and recurrent courses have been described, whereas AGEP usually resolves without problems.     

Piperacillin/Tazobactam-Associated Hypersensitivity Syndrome with Overlapping Features of Acute Generalized Exanthematous Pustulosis and Drug-Related Rash with Eosinophilia and Systemic Symptoms Syndrome

Acute generalized exanthematous pustulosis (AGEP) is a rare disorder characterized by acute onset of erythematous and edematous eruptions with sterile pustules, accompanied by fever, and a self-limiting condition thought to be caused by drugs, in particular, antibiotics. Drug-related rash with eosinophilia and systemic symptoms (DRESS) syndrome is a severe adverse drug-induced reaction, characterized by a generalized skin rash associated with hypereosinophilia, lymphocytosis, and internal organ involvement. These reactions differ in causative agents, as well as clinical presentation, prognosis, and treatment. Therefore, appropriate diagnostic measures should be rapidly undertaken. Herein, we described a patient who developed overlapping features of hypersensitivity syndromes, AGEP and DRESS, with the use of piperacillin and the beta-lactamase inhibitor sodium tazobactam. Coexistence of AGEP and DRESS in the same patient is quite rare. To the best of our knowledge, there have been no previous reports on the coexistence of AGEP and DRESS associated with piperacillin/tazobactam.     

Severe Cutaneous Adverse Reactions: A Single-Center Retrospective Study of 173 Patients in China

BackgroundSevere cutaneous adverse reactions (SCAR) to drugs are a crucial public health issue and the use of systemic corticosteroids in SCAR has been controversial.ObjectiveTo analyze clinical features, causative drugs, treatment, outcomes, and prognostic factors of SCAR in the case-series of 173 patients, and add more information to the debate of using systemic corticosteroids in SCAR management.MethodsA retrospective study of 173 SCAR patients diagnosed with drug reaction with eosinophilia and systemic symptoms (DRESS), Stevens-Johnson syndrome (SJS)/toxic epidermal necrolysis (TEN) or acute generalized exanthematous pustulosis (AGEP) at a tertiary care institution in China between January 2014 and December 2017 was conducted.ResultsOf 173 patients, allopurinol, carbamazepine, and antibiotics are the most frequently implicated drugs for DRESS (40.4%), SJS/TEN (26.0%), and AGEP (40.0%) respectively. Moreover, there is a strongly negative correlation between early corticosteroids use and the progression (p=0.000) and severity (p=0.01) of skin lesions. However, there is no association between early corticosteroids use and the mortality of SCAR (odds ratio: 1.01, 95% confidence interval: 0.95~1.08). In addition, lymphadenopathy, eosinophilia, and interval from onset to corticosteroids treatment were correlated with SCAR prognosis.ConclusionPrompt short-course systemic corticosteroids use is associated with early-stage skin lesions remission without influencing the disease mortality. Lymphadenopathy and eosinophilia were the independent poor prognostic factors of SCAR.     

Pustular‐type drug‐induced hypersensitivity syndrome/drug reaction with eosinophilia and systemic symptoms due to carbamazepine with systemic muscle involvement

Drug‐induced hypersensitivity syndrome (DIHS)/drug reaction with eosinophilia and systemic symptoms (DRESS) is a severe reaction usually associated with maculopapular eruptions and systemic involvement. Here we report the first case, to our knowledge, of DIHS/DRESS due to carbamazepine with acute generalized pustular bacterid‐like (AGPB‐like) eruptions and skeletal muscle involvement. Reviewing our case and the published work, we discuss pustular‐type DIHS/DRESS which, in most cases, involves acute generalized exanthematous pustulosis (AGEP)‐like skin eruptions in response to carbamazepine. Pustular eruptions may appear in relatively few cases of DIHS/DRESS, in particular, when the causative drug is carbamazepine and, even in cases of intractable pustular bacterid‐like eruptions, a reaction to a drug should be suspected. Skeletal muscle involvement may be associated with DIHS/DRESS as one of its systemic manifestations.     

Severe flucloxacillin‐induced acute generalized exanthematous pustulosis (AGEP), with toxic epidermal necrolysis (TEN)‐like features: does overlap between AGEP and TEN exist? Clinical report and review of the literature

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.     

A multicentre study to determine the value and safety of drug patch tests for the three main classes of severe cutaneous adverse drug reactions

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.     

Long-term outcome of patients with severe cutaneous adverse reactions

Visceral involvement associated with Stevens-Johnson syndrome/toxic epidermal necrolysis (SJS/TEN) and drug-induced hypersensitivity syndrome/drug reaction with eosinophilia and systemic symptoms (DIHS/DRESS) is well documented. However, little is known about the long-term outcomes of severe drug eruptions due to a lack of long-term follow-up. Long-term sequelae may arise in patients who survive the acute complications of severe drug reactions. In SJS/TEN, extensive scarring that result from the healing of mucocutaneous ulcerative lesions may interfere with organ function. Severe sequelae include visual impairment and pulmonary obliterative disease that impair patients' quality of life. In DIHS/DRESS, recent observations suggest that fulminant type 1 diabetes mellitus (FT1D) and autoimmune diseases such as autoimmune thyroiditis and lupus erythematosus can occur after a disease-free period of several months to years. Thus, DIHS/DRESS may lead to the development of autoimmune diseases, which may be overlooked. Dermatologists need to be aware of the sequelae that may arise following resolution of severe cutaneous adverse reactions and should be vigilant for manifestations of autoimmune disease during follow-up.     

Schwere Arzneimittelreaktionen der Haut

Toxic epidermal necrolysis (TEN) and Stevens-Johnson syndrome (SJS) are severe drug-induced bullous skin reactions. They are rare, but often life-threatening and have a high mortality rate. Acute generalized exanthematous pustulosis (AGEP) is a severe cutaneous adverse reaction, but after the suspected drug is withdrawn, the skin heals rapidly and mortality is low. The clinical pattern, histology and inducing drugs differ substantially between AGEP and the SJS/TEN group.     

Prognosis of generalized bullous fixed drug eruption: comparison with Stevens–Johnson syndrome and toxic epidermal necrolysis

Background Generalized bullous fixed drug eruption (GBFDE) is a rare cutaneous adverse reaction to drugs, and may resemble Stevens–Johnson syndrome (SJS) or toxic epidermal necrolysis (TEN), but is usually considered less severe. Objectives To compare the severity and mortality rate in cases of GBFDE and control cases of SJS or TEN of similar extent of skin detachment. Methods This was a case–control analysis of 58 patients with GBFDE matched by age and extent of skin detachment to 170 control patients with a validated diagnosis of SJS or SJS/TEN overlap. Data for cases and controls were extracted from the EuroSCAR and RegiSCAR databases resulting from two population‐based studies of severe cutaneous adverse reactions conducted in Europe. Preselected outcome criteria were death (primary), and fever, duration of hospitalization and transfer to an intensive care or burn unit (secondary). Results GBFDE affected mainly older patients (median age 78 years, interquartile range 68–84 years); 13 of 58 cases died (22%). The mortality rate was slightly but not significantly lower for patients with GBFDE than controls [28%, multivariate odds ratio 0·6 (95% confidence interval 0·30–1·4)]. Patients with GBFDE and controls did not differ in other preselected criteria for severity. Conclusions Although our study featured limited statistical power, we were not able to confirm that GBFDE had better prognosis than SJS or SJS/TEN of similar disease extent in older patients. Severe cases of GBFDE deserve the attention and active management given to patients with SJS or TEN.     

A patch testing and cross‐sensitivity study of carbamazepine‐induced severe cutaneous adverse drug reactions

Background The usefulness of the drug patch testing for Stevens–Johnson syndrome and toxic epidermal necrolysis (SJS/TEN) is still controversial. Recent studies have shown that HLA‐B*1502 is strongly associated with CBZ‐SJS/TEN in Chinese and Southeast Asian populations. Objective To evaluate the usefulness of patch tests for patients with carbamazepine (CBZ)‐induced SJS, TEN and drug reaction with eosinophilia and systemic symptoms (DRESS) and the cross‐reactivity in patch tests among the aromatic antiepileptic drugs. Methods We measure the frequency of positive patch test reactions and cross‐sensitivity to structure‐related aromatic anti‐epileptic drugs (AEDs) for patients after SJS/TEN or DRESS episodes caused by CBZ. CBZ and other structure‐related AEDs used for patch testing were prepared in 10% and 30% petrolatum. Secondary measures included the association of HLA‐B*1502 genotype and frequency of possible side effects from the patch tests. Results Positive patch test reactions to 30% CBZ in the CBZ‐SJS/TEN were 62.5% (10/16), and 70% (7/10) in the CBZ‐DRESS. None of the 10 healthy controls displayed a positive reaction to tested agents. Cross‐sensitivity to other aromatic AEDs was observed in both the CBZ‐SJS/TEN and the CBZ‐DRESS. Only the HLA‐B*1502 genotype was present and strongly associated with the CBZ‐SJS/TEN, but not with the CBZ‐DRESS. Conclusion Drug patch testing is a safe and useful method for the identification of CBZ as the culprit drug of SJS/TEN as well as DRESS. Testing of chemically or pharmacologically related AEDs may provide information on cross‐reactivity for these patients.     

Stevens‐Johnson syndrome and toxic epidermal necrolysis in children: a review of the experience with paediatric patients in a University Hospital

Background Stevens‐Johnson syndrome (SJS) and toxic epidermal necrolysis (TEN) are life‐threatening drug reactions considered to be part of the spectrum of a single pathological process. Objective To describe the clinical and epidemiological characteristics of SJS/TEN in children attended at our hospital. Materials and methods Retrospective study of children diagnosed with SJS/TEN between 1999 and 2009 in a University Hospital provided with regional‐level burn and paediatric intensive care units. Results We found 14 paediatric patients (eight SJS and six TEN). They presented an average of 60% of the body surface area affected and 31% of epidermal sloughing. The average of suspected drugs was 1.7 per patient, anticonvulsants (carbamazepine, phenytoin and lamotrigine) and antibiotics (penicillin and macrolides) being the most frequent ones. Silver sulfadiazine was the topical treatment most frequently used, 86% of patients received systemic steroids and 28.5% intravenous immunoglobulins. One patient died. Conclusions The SJS/TEN complex is a true dermatological critical condition that also affects children. Any drug can be the causative agent, more frequently anticonvulsants and antibiotics. Depending on the extension of the affected body surface, patients should be rapidly admitted to a critical care area with experience in the care of burn patients. Discontinuation of the suspected offending drugs is mandatory. Optimal supportive care and management of denuded skin areas are still the mainstay of treatment. The use of specific therapies remains controversial. Compared with adults, the disease in children seems to be milder with lower mortality.     

Differential diagnosis of severe cutaneous drug eruptions

Adverse cutaneous reactions to drugs are frequent, mostly secondary to antibacterials, however, serious adverse cutaneous reactions are infrequent. Stevens-Johnson syndrome (SJS) and toxic epidermal necrolysis (TEN) are a spectrum of the same disease. They are the more severe drug eruptions, with a mortality around 30% for TEN. The confusion between erythema multiforme major and SJS means that erythema multiforme major is the main differential diagnosis. Skin disorders involving desquamation, in particular after pustulosis, are also common differential diagnoses. Mechanical or autoimmune blistering are also potential misdiagnoses of TEN/SJS. Hypersensitivity Syndrome (HSS) or Drug Rash with Eosinophilia and Systemic Symptoms (DRESS) is a severe cutaneous drug reaction with often a long duration of eruption and serious other organ involvement. Exfoliative dermatitis, whether caused by psoriasis, dermatitis or lymphoma, can be thought of as a differential diagnosis of DRESS/HSS. Angio-immunoblastic lymphadenopathy, viral eruption and vasculitis are other differential diagnoses of DRESS/HSS. Prompt recognition of a severe drug reaction and withdrawal of the culprit drug is often the most important therapeutic action. Alternatively, a delay in starting a specific treatment for a disease misdiagnosed as a drug eruption could be deleterious.     

Drug reaction with eosinophilia and systemic symptoms (DRESS): a clinical update and review of current thinking

Summary Drug reaction with eosinophilia and systemic symptoms (DRESS) describes a severe medication-induced adverse reaction, which has cutaneous, haematological and solid-organ features. It is one of the triad of life-threatening drug hypersensitivity dermatoses, along with acute generalized exanthematous pustulosis (AGEP) and Stevens-Johnson syndrome/toxic epidermal necrolysis (SJS/TEN). In this article, we discuss several controversies that surround DRESS, including problems with nomenclature and the lack of consensus in diagnostic criteria.     

Koebnerization of Hailey–Hailey disease into a cutaneous drug eruption of acute generalized exanthematous pustulosis associated with systemic symptoms

We describe a 65‐year‐old Caucasian female with well‐controlled Hailey–Hailey disease (HHD) who developed acute generalized exanthematous pustulosis (AGEP) with severe systemic symptoms. Despite sparing of the patient's intertriginous skin, histopathologic evidence of HHD was observed in all biopsies, suggestive of a unique koebernization phenomenon of HHD to areas of cutaneous drug eruption. While internal organ involvement is less commonly reported in AGEP, there are an increasing number of patients with signs and symptoms suggestive of an AGEP/drug reaction with eosinophilia and systemic symptoms (DRESS) spectrum of cutaneous drug disorders. Early diagnosis of patients with AGEP and systemic symptoms is critical so that these patients may receive prompt and aggressive systemic therapy to decrease the risk of end organ damage and improve overall morbidity and mortality.     

3 Severe cutaneous adverse reactions time latency between beginning of drug use and onset of reaction

Background Toxic epidermal necrolysis (TEN) and Stevens–Johnson syndrome (SJS) are acute life‐threatening severe cutaneous adverse reactions (SCAR) with an unclear pathogenesis mainly caused by drugs. Allopurinol and trimethoprim/sulphamethoxazole (TMS) are both well known to be associated with these conditions. In addition, TMS is known to induce generalized bullous fixed drug eruption (GBFDE), a less severe condition with a very short induction period that is clinically often confused with SJS or TEN. Aim We want to further investigate the risk profile of allopurinol and TMS for inducing SCAR, as the hazard functions of these substances are different. Furthermore, the re‐review of cases using more specific criteria to differentiate between SCAR and GBFDE should allow us to detect misclassification of cases. Methods 984 cases of SJS, SJS/TEN overlap and TEN were ascertained by a population‐based registry between 1990 and 1999. The following analysis is based on a random sample of 115 cases earlier accepted as SJS or TEN, which were exposed to either allopurinol or TMS, and 38 cases excluded in the previous review. An independent expert committee blinded for possible causes re‐reviewed these cases in clinical terms, as the original review process took place over a period of 10 years. In this analysis special emphasis is given to the time latency between beginning of drug use and onset of SCAR. Results Before re‐review 162/984 patients with SCAR reported the use of allopurinol and 131/984 the use of TMS within 2 weeks prior to the onset of the adverse reaction. After the re‐review the percentage of doubtful cases was higher for TMS (28/57) than for allopurinol (30/83). For definite cases of SJS or TEN the range between the lower and upper quartile of the time latency between beginning of drug use and onset of SCAR was 14–34 days for allopurinol, in contrast to 5–15 days for TMS. The time latency for doubtful and excluded cases after the use of TMS was much shorter (2.5 and 2 days, respectively). Conclusions The high numberof doubtful cases after the re‐review reveals the difficulty of applying approved detailed definitions to the variety of clinical patterns of cutaneous adverse reactions. We could confirm a high correlation of time latency between beginning of drug use and onset of SCAR and GBFDE for allopurinol and TMS, which may have an important impact on the risk profile of these and other suspected drugs, as well as on pathogenetic and therapeutic considerations of severe adverse events. When drug exposure occurs outside the relevant interval of time latency for SJS and TEN, other risk factors and/or differential diagnoses such as GBFDE should be considered.     

Drug rash with eosinophilia and systemic symptoms vs toxic epidermal necrolysis: the dilemma of classification

According to contemporary vernacular, when the cutaneous manifestations of drug rash with eosinophilia and systemic signs (DRESS) syndrome are those of Stevens-Johnson syndrome (SJS) or toxic epidermal necrolysis (TEN), the condition is defined as "DRESS syndrome with severe cutaneous reactions". In this article, we have presented arguments for and against including patients with skin lesions of the SJS/TEN syndromes who also have fever (practically all of the patients) and internal organ involvement (most of the patients) under the definition of DRESS syndrome. After weighing the arguments for and against this alteration of definition, we conclude that it makes more sense for patients with SJS/TEN to be classified as such and not be lumped together under the misleading label of DRESS syndrome.     

Fixed-drug eruption: A retrospective study in a single referral center in northern Taiwan

Background/ObjectiveFixed drug eruption (FDE) is a dermatosis characterized by recurrent patches or plaques at exactly the same sites with each administration of the causative drug. Vesicles or bullae may sometimes be found, and generalized bullous fixed drug eruption (GBFDE) may be confused with Stevens-Johnson syndrome (SJS) or toxic epidermal necrolysis (TEN). This study aimed to investigate the clinical and pathologic features of FDE in Taiwan.MethodsA retrospective analysis evaluated patients with FDE in a referral center in Taiwan covering a period of 11 years. Clinical data, suspected etiologies, and pathology/patch test results were collected. We also compared the GBFDE cases with SJS/TEN overlap or TEN cases to find differentiating clues.ResultsThere were 39 FDE patients, including nine GBFDE cases. The most frequent causative drugs were non-steroidal anti-inflammatory drugs (five cases, 12.8%) and antibiotics (four cases, 10.3%). Extremities other than the hands (71.8%) were the most frequently affected sites, followed by the trunk (51.3%), mucosa (38.5%), and hands (33.3%). The average age of FDE patients was 52.2 years (median, 56 years; range, 4–86 years). Patients with GBFDE were significantly older than non-GBFDE patients (69.1 ± 19.7 vs. 47.2 ± 23.6, p = 0.0124) and the trunk was more likely to be involved in GBFDE cases (88.9% vs. 40.0%, p = 0.0197). GBFDE cases also showed tendency to have more mucosal involvement (66.7% vs. 30.0%, p = 0.0631). Although similar to SJS/TEN, GBFDE cases had fewer constitutional symptoms, less mucosal involvement but had previous episodes. Histopathologically, the presence of more than two aggregated dyskeratotic keratinocytes (fire flag sign) in the epidermis was more frequently observed in SJS/TEN, whereas GBFDE had superficial and deep dermal infiltration of eosinophils and melanophages.ConclusionFDE is one of the specialized cutaneous drug reactions and GBFDE should be kept in mind and differentiated from SJS/TEN.     

Cutaneous adverse drug reactions seen in a tertiary hospital in Johor,Malaysia

Background Adverse drug reactions are most commonly cutaneous in nature. Patterns of cutaneous adverse drug reactions (ADRs) and their causative drugs vary among the different populations previously studied. Objective Our aim is to determine the clinical pattern of drug eruptions and the common drugs implicated, particularly in severe cutaneous ADRs in our population. Materials and Methods This study was done by analyzing the database established for all adverse cutaneous drug reactions seen from January 2001 until December 2008. Results A total of 281 cutaneous ADRs were seen in 280 patients. The most common reaction pattern was maculopapular eruption (111 cases, 39.5%) followed by Stevens‐Johnson Syndrome (SJS: 79 cases, 28.1%), drug reaction with eosinophilia and systemic symptoms (DRESS: 19 cases, 6.8%), toxic epidermal necrolysis (TEN: 16 cases, 5.7 %), urticaria/angioedema (15 cases, 5.3%) and fixed drug eruptions (15 cases, 5.3%). Antibiotics (38.8%) and anticonvulsants (23.8%) accounted for 62.6% of the 281 cutaneous ADRs seen. Allopurinol was implicated in 39 (13.9%), carbamazepine in 29 (10.3%), phenytoin in 27 (9.6%) and cotrimoxazole in 26 (9.3%) cases. Carbamazepine, allopurinol and cotrimoxazole were the three main causative drugs of SJS/TEN accounting for 24.0%, 18.8% and 12.5% respectively of the 96 cases seen whereas DRESS was mainly caused by allopurinol (10 cases, 52.6%) and phenytoin (3 cases, 15.8%). Discussion The reaction patterns and drugs causing cutaneous ADRs in our population are similar to those seen in other countries although we have a much higher proportion of severe cutaneous ADRs probably due to referral bias, different prescribing habit and a higher prevalence of HLA‐B*1502 and HLA‐B*5801 which are genetic markers for carbamazepine‐induced SJS/TEN and allopurinol‐induced SJS/TEN/DRESS respectively. Conclusion The most common reaction pattern seen in our study population was maculopapular eruptions. Antibiotics, anticonvulsants and NSAIDs were the most frequently implicated drug groups. Carbamazepine and allopurinol were the two main causative drugs of severe ADRs in our population.     

Patch testing in severe cutaneous adverse drug reactions, including Stevens-Johnson syndrome and toxic epidermal necrolysis

Patch testing may help to assess the culpability of a drug in an adverse reaction. Our aim was to study patch testing in severe cutaneous ad verse drug reactions [ADRs] (Stevens-Johnson syndromeitoxic epidermal necrolysis (SJS/TEN). acute genera exanthematous pustulosis (AGEP), and other cutaneous ADRs). 59 patients with cutaneous ADRs were included: 22 had SJS/TEN. 14 AGEP, and 23 other cutaneous ADRs. Patients were patch tested with the suspect drug and with H standard series of drugs. 2 patients among the 22 SJSTEN cases had a relevant positive test. 7 patients among the 14 AGEP cases had a relevant positive test. 6 patients among the 23 other cutaneous ADRs had a relevant positive test. Our results suggest that patch testing has a weak sensitivity in SJS'TEN and is not appropriate in these diseases. Patch testing seems more adapted to other cutaneous ADRs, such as AC it: P. in which the proportion of positive patch tests was significantly higher (P<0.02). Nevertheless, the difference of sensitivity of patch testing in SJS TEN, AGEP or other cutaneous ADRs could be linked not only to the clinical type of eruption, but also lo the different spectrum of culprit drugs in each type of eruption.     

Stevens–Johnson syndrome and toxic epidermal necrolysis due to anticonvulsants share certain clinical and laboratory features with drug‐induced hypersensitivity syndrome,despite differences in cutaneous presentations

Background. Drug‐induced hypersensitivity syndrome (DIHS)/drug rash with eosinophilia and systemic symptoms (DRESS) syndrome is characterized by late disease onset, fever, rash, hepatic dysfunction, haematological abnormalities, lymphadenopathy and often, human herpesvirus (HHV) reactivation. The diagnosis of DIHS is based on the combined presence of these findings. Anticonvulsants are a major cause of DIHS and may also cause Stevens–Johnson syndrome (SJS) and toxic epidermal necrolysis (TEN). We examined whether SJS/TEN due to anticonvulsants display similar clinical and laboratory features seen in DIHS. Methods. Patients diagnosed with SJS or TEN due to anticonvulsants (n = 8) were examined and their clinical features and laboratory findings were compared with patients with anticonvulsant‐related DIHS (n = 6). Results. Seven of the eight patients with SJS/TEN developed symptoms > 3 weeks after starting anticonvulsants. Hepatic dysfunction was present in six patients with SJS/TEN and five patients with DIHS. Leucocytosis and/or eosinophilia was noted in seven patients with SJS/TEN and four patients with DIHS. Only one patient in the SJS/TEN group had atypical lymphocytosis; this was present in four patients with DIHS. Reactivation of HHV‐6 was detected in one of the four patients tested in the SJS/TEN group, although it was seen in five of the six patients with DIHS. Conclusions. TSJS/TEN due to anticonvulsants may exhibit some clinical and laboratory features of DIHS. The nature of the cutaneous involvement should be emphasized in the diagnosis of DIHS.