The CD40/CD40 ligand system is expressed in the cutaneous lesions of erythema multiforme and Stevens-Johnson syndrome/toxic epidermal necrolysis spectrum

Background Erythema multiforme (EM) and Stevens–Johnson syndrome (SJS)/toxic epidermal necrolysis (TEN) are determined by a dysregulation of cellular immunity. Objectives To evaluate the effector role of cellular immunity and the involvement of the CD40/CD40 ligand (CD40L) system in the pathogenesis of EM and SJS/TEN. Methods Biopsy specimens from eight patients with EM and six with SJS/TEN were stained for immunohistochemical examination using the alkaline phosphatase/antialkaline phosphatase method. The monoclonal antibodies used included those to CD1a, CD4, CD8, CD40, CD40L, CD68, Fas, Fas ligand (FasL) and myeloperoxidase. Results The cellular infiltrate in both EM and SJS/TEN lesions was composed mainly of T lymphocytes and CD68+ macrophages. We also detected large amounts of neutrophils. Fas and FasL were very highly expressed in SJS and TEN, but weakly in EM. CD40 staining was strong in all tissue sections; there were numerous CD40L+ cells in SJS/TEN but much fewer in EM. Conclusions Activated T lymphocytes and macrophages, but also neutrophils, are presumably the main triggers of mucocutaneous damage in the SJS/TEN disease spectrum. The Fas/FasL system is significantly expressed in SJS/TEN lesions, but not in EM, where this apoptotic pathway presumably does not play a pivotal role in the epidermal damage. We suggest that the CD40/CD40L system may represent an important pathway of induction of SJS/TEN lesions, while in EM it would contribute to the immunoinflammation only as a second‐line mechanism.     

Expression of cytokines and chemokine receptors in the cutaneous lesions of erythema multiforme and Stevens-Johnson syndrome/toxic epidermal necrolysis

BACKGROUND: Erythema multiforme (EM) and Stevens-Johnson syndrome/toxic epidermal necrolysis (SJS/TEN) are caused by a dysregulation of cellular immunity. OBJECTIVES: To evaluate further the potential role of certain cytokines and chemokine receptors in cutaneous lesions of patients affected by EM and SJS/TEN and to establish whether such diseases are polarized preferentially towards a T-helper (Th) 1 or Th2 pattern. METHODS: Biopsy specimens from eight patients with EM, six with SJS/TEN and three healthy controls were stained for immunohistochemical examination using the alkaline phosphatase-antialkaline phosphatase method. The monoclonal antibodies used included those to tumour necrosis factor (TNF)-alpha, interferon (IFN)-gamma, interleukin (IL)-2, IL-5, IL-13, receptor 3 for C-C chemokines (CCR3), receptor 3 for C-x-C chemokines (CXCR3) and CXCR4. RESULTS: The SJS/TEN specimens showed significantly higher expression of all the cytokines and chemokine receptors (except CXCR3) tested than the EM specimens. Both lesional series showed significantly higher expression of all the receptors tested than the healthy control specimens, with the sole exception of a lower expression of CCR3 in EM specimens. Comparison between molecules associated with a Th1 or Th2 response revealed a predominance of Th1 response in EM and no significant imbalance between Th1 and Th2 in SJS/TEN. CONCLUSIONS: We have provided further evidence that TNF-alpha is strongly expressed in SJS/TEN lesions and therefore it may be involved in the epidermal necrosis featured in such diseases. IFN-gamma may play an important role both in EM and SJS/TEN. IL-2, IL-5 and IL-13 may contribute to the cutaneous immunoinflammation in these diseases. Chemokine receptors may be involved strongly in the recruitment of inflammatory cells in lesional skin. In our cases we found a sharp polarization towards a Th1 pattern in EM, while the SJS/TEN lesions showed a mixed Th1/Th2 pattern.     

Oral manifestations of erythema multiforme

Erythema multiforme is a reactive mucocutaneous disorder in a disease spectrum that comprises a self-limited, mild, exanthematic, cutaneous variant with minimal oral involvement (EM minor) to a progressive, fulminating, severe variant with extensive mucocutaneous epithelial necrosis (SJS and TEN). Significant differences exist among EM minor, EM major, SJS, and TEN with regards to severity and clinical expression; however, all variants share two common features: typical or less typical cutaneous target lesions and satellite-cell or more widespread necrosis of the epithelium. These features are considered to be sequelae of a cytotoxic immunologic attack on keratinocytes expressing non-self-antigens. These antigens are primarily microbial (viruses) or drugs and in rare instances histocompatibility antigens [5]. Although the precise pathogenesis is unknown, there is a tendency to consider EM both minor and major as part of one spectrum that is most often triggered by viral infections, and SJS and TEN as a separate one most often elicited by drugs with EM major and SJS representing a bridge in the continuum of EM. The oral manifestations of the spectrum of EM range from tender superficial erythematous and hyperkeratotic plaques to painful deep hemorrhagic bullae and erosions. Other mucosal surfaces including ocular, nasal, pharyngeal, laryngeal, upper respiratory, and anogenital may be involved. Scarring sequelae from ocular and pharyngeal involvement cause morbidity. The oral EM variant is an underrecognized form of EM. Most patients have chronic or recurrent oral lesions only, but one third have oral and lip lesions and one quarter have oral, lip, and skin lesions. This variant is a reaction pattern similar to EM minor, EM major, SJS, and TEN. The diagnosis of oral EM is one of exclusion. Careful clinical evaluation for other chronic mucocutaneous diseases, such as pemphigus, paraneoplastic pemphigus, mucous membrane pemphigoid, and lichen planus, is a necessary component of the diagnosis. The value of a biopsy specimen studied by both routine histopathologic and immunopathologic methods is fundamental to excluding the other causes for this variant of EM.     

Retrospective analysis of stevens-johnson syndrome and toxic epidermal necrolysis over a period of 10 years

Background:

Stevens-Johnson syndrome (SJS), and toxic epidermal necrolysis (TEN), are the acute emergencies in dermatology practice. Prompt diagnosis and management may reduce the morbidity and mortality in SJS/TEN patients. Early identification of the offending drug is necessary for early withdrawal and to prevent the recurrences of such a devastating illness.

Aims

To study the demography, offending agents, clinical and laboratory features, treatment, complications, morbidity and mortality of SJS/TEN in our hospital.

Materials and Methods:

In this retrospective study, we reviewed the medical records of SJS, TEN, SJS/TEN overlap of inpatients over a period of 10 years

Results:

Maximum number of SJS/TEN cases were in the age group of 11-30 years. Males predominated in the SJS group with a ratio of 1.63:1, whereas females predominated the TEN group with a ratio of 1:2.57.Nonsteroidal anti-inflammatory drugs (NSAIDs) were the commonest group of drugs among the SJS group in 5/21 patients (23.8%). Antimicrobials were the commonest group of drugs causing TEN in 11/25 patients (44%). Mucosal lesions preceded the onset of skin lesions in nearly 50%. Our study had one patient each of SJS/TEN due to amlodipine and Phyllanthus amarus, an Indian herb. The most common morbidity noted in our study was due to ocular sequelae and sepsis leading to acute renal failure respectively. Kaposi''s varicelliform eruption was found in three of our patients.

Conclusion:

Antimicrobials and NSAIDS are the common offending agents of SJS/TEN in our study.     

Erythema multiforme,Stevens–Johnson syndrome and toxic epidermal necrolysis: Frozen‐section diagnosis

Stevens–Johnson syndrome (SJS) and toxic epidermal necrolysis (TEN) may be fatal. Although classified by body surface area skin detachment, initial stages of both may present with erythema multiforme (EM)‐like lesions. To diagnose and predict disease activity adequately as early as possible for patients revealing EM‐like lesions, we performed frozen‐section diagnosis. Thirty‐five patients clinically diagnosed as EM, SJS or TEN were biopsied to diagnose and predict disease progression within the initial‐visit day. Half of a histological section taken from a lesion was snap‐frozen and immediately cryostat‐sectioned, acetone‐fixed and stained with hematoxylin–eosin. Specimens were examined with light microscopy for presence of epidermal necrosis. A section from unaffected sites was also examined for 11 patients. Specimens were examined with light microscopy for presence of graft‐versus‐host reaction (GVHR)‐like findings: apoptotic keratinocytes and satellite cell necrosis. Epidermal necrosis was seen in nine patients. Initial diagnosis of the nine was one of overlap SJS‐TEN, four of SJS and four of EM, and final diagnosis of those was one of TEN, one of overlap SJS–TEN, four of SJS and three of EM. Dissociation between initial and final diagnosis was seen in three cases. GVHR‐like findings in the epidermis were observed in two patients finally diagnosed as overlap SJS–TEN and TEN. Frozen sections are useful not only to make a diagnosis of erythema multiforme but to assess a potential to exhibit more aggressive clinical behaviors (SJS or TEN).     

重症多形红斑与中毒性表皮坏死松解症患者的临床对比研究

目的探讨重症多形红斑(SJS)与中毒性表皮坏死松解症(TEN)的临床特点与临床治疗。方法对9例SJS和4例TEN住院患者的临床资料进行回顾性分析。结果 SJS组和TEN组患者中药物为最常见病因。TEN组的皮损范围、损害程度、粘膜病变均较SJS组更广泛、更严重。TEN患者主要表现为全身表皮松解,而SJS患者以靶形红斑为特征。TEN患者较SJS患者更易出现并发症。TEN患者病程急性期和恢复期时间均长于SJS患者。9例SJS和4例TEN患者早期均予以足量糖皮质激素治疗,TEN患者同时联用免疫球蛋白,13例患者均获痊愈。结论药物是SJS和TEN发病最主要的原因。TEN患者较SJS患者病变广泛且严重。药物诱发的SJS和TEN患者早期使用足量激素十分必要,TEN患者尚需静脉联用免疫球蛋白,提高抢救成功率。     

IgA-lineare Dermatose im Erwachsenenalter mit klinischen Zeichen eines Stevens-Johnson-Syndroms

Immunohistologically linear IgA disease presents with unambiguous features, whereas clinical manifestations are variable. It sometimes shows similarity to other bullous dermatoses such as bullous pemphigoid and dermatitis herpetiformis. A 73 year old female patient was referred with the diagnosis of bullous pemphigoid. One day after admission clinical examination revealed the classical features of Stevens-Johnson syndrome (SJS): widespread confluent atypical target lesions, partly raised, partly flat with central blisters, and erythematous spots, but few typical targets, as well as blisters and large areas of skin detachment on her back and buttocks, accompanied by erosions of the oral and genital mucosa. Direct immunofluorescence performed on peri-lesional skin showed linear deposition of IgA along the basement membrane zone, leading to the diagnosis of linear IgA disease of adults. Our case report shows that linear IgA disease may present with the clinical pattern of SJS.     

Erythema multiforme, Stevens–Johnson syndrome and toxic epidermal necrolysis in northeastern Malaysia

Background Previous studies have reported that drugs and infections are common causes of erythema multiforme (EM) and Stevens–Johnson syndrome (SJS). Toxic epidermal necrolysis (TEN) is mainly related to drugs. No study has been conducted in Kelantan, the northeastern state of Malaysia, to assess these cutaneous reactions. Methods A retrospective study of all hospitalized cases of EM, SJS, and TEN was conducted covering an 8-year period from 1987 to 1994. Results There were four cases (13.8%) of EM, 22 cases (75.9%) of SJS, and three cases (10.3%) of TEN. Drugs as a definitive cause was observed in one case (25%) of EM, 12 cases (54.5%) of SJS, and two cases (66.7%) of TEN. Drugs as a probable cause was observed in seven cases (31.8%) of SJS and one case (33.3%) of TEN. The male to female ratio was equal in EM and SJS. Antiepileptics were the commonest culprits, followed by antibiotics. One patient died of SJS and one patient died of TEN, giving mortality rates of 4.5% and 33.5% respectively. Fever was noted in 18 patients (62.1%). Leukocytosis was noted in 10 patients (34.5%), and nine patients (31.0%) had elevated liver transaminase enzymes. No significant correlation was noted between these biochemical changes and cutaneous eruption. Secondary infections were observed in 11 patients (37.9%): Staphylococcus aureus was the commonest isolated organism. Conclusions This study shows that drugs remain the commonest culprit in SJS and TEN. Despite adequate treatment, the mortality rate remains high, especially in TEN. These findings are similar to those of other reported studies.     

The incidence of erythema multiforme, Stevens-Johnson syndrome, and toxic epidermal necrolysis. A population-based study with particular reference to reactions caused by drugs among outpatients

We carried out a study to estimate the incidence of erythema multiforme (EM), Stevens Johnson syndrome (SJS), and toxic epidermal necrolysis (TEN) requiring hospitalization and to determine which drug therapies were associated with these reactions. We reviewed the clinical records of all patients who were hospitalized with these discharge diagnoses at Group Health Cooperative (GHC) of Puget Sound, Seattle, Wash, from 1972 through 1986. During this 14-year period, an average of about 260,000 persons, with demographic characteristics similar to those of the general population, received their care from GHC, and there were about 25,000 admissions to hospitals per year at the GHC hospitals. Based on International Classification of Diseases-Adapted coding, a total of 61 suspect cases of EM, SJS, or TEN were identified from the computerized hospital discharge file. Based on record review and the application of a uniform set of diagnostic criteria, a total of 37 patients (61%) were classified as having EM, SJS, or TEN. Of these, 16 cases (43%) were attributed to drugs administered to these patients prior to hospitalization. The overall incidence of hospitalization for EM, SJS, or TEN due to all causes was 4.2 per 10(6) person-years. The incidence of TEN alone due to all causes was 0.5 per 10(6) person-years. The incidence of EM, SJS, or TEN associated with drug use were 7.0, 1.8, and 9.0 per 10(6) person-years, respectively, for persons younger than 20 years of age, 20 to 64 years of age, and 65 years of age and older. Drug therapies with reaction rates in excess of 1 per 100,000 exposed individuals include phenobarbital (20 per 100,000), nitrofurantoin (7 per 100,000), sulfamethoxazole and trimethoprim, and ampicillin (both 3 per 100,000), and amoxicillin (2 per 100,000). Overall, our data suggest that cases of EM, SJS, and TEN sufficiently severe to require hospitalization are infrequent among outpatients using well-established drug therapies. A continuing challenge is the evaluation of these severe cutaneous reactions that are associated with newly marketed or less frequently prescribed drug therapies.     

Erythema multiforme,Stevens‐Johnson syndrome/toxic epidermal necrolysis – diagnosis and treatment

Prior to the first international consensus classification published in 1993, the clinical distinction between erythema multiforme (EM), Stevens‐Johnson syndrome (SJS) and toxic epidermal necrolysis (TEN) had been subject to uncertainty and controversy for more than a century. Based on this classification, the three conditions are defined by the morphology of the individual lesions and their pattern of distribution. Etiopathogenetically, the majority of EM cases is caused by infections (primarily herpes simplex virus and Mycoplasma pneumoniae), whereas SJS/TEN are predominantly triggered by drugs. The SCORTEN (score of toxic epidermal necrolysis) can and should be used to assess disease prognosis in patients with SJS/TEN. While supportive treatment is generally considered sufficient for EM, there is still uncertainty as to the type of systemic therapy required for SJS/TEN. Given the lack of high‐quality therapeutic trials and (in some cases) conflicting results, it is currently impossible to issue definitive recommendations for any given immunomodulatory therapy. While there is always a trade‐off between rapid onset of treatment‐induced immunosuppression and an uptick in infection risk, there has been increasing evidence that cyclosporine in particular may be able to halt disease progression (i.e. skin detachment) and lower mortality rates. Assistance in diagnosis and management of the aforementioned conditions may be obtained from the Center for the Documentation of Severe Skin Reactions (dZh) at the Department of Dermatology, University Medical Center, Freiburg, Germany.     

Critical factors differentiating erythema multiforme majus from Stevens-Johnson syndrome (SJS)/toxic epidermal necrolysis (TEN)

Erythema multiforme majus (EMM) and Stevens-Johnson syndrome (SJS)/toxic epidermal necrolysis (TEN) are severe cutaneous reactions characterised by targetoid erythematous lesions and mucocutaneous involvement. The initial skin manifestations are similar, making early diagnosis difficult. We retrospectively reviewed 36 cases of EMM and 18 cases of SJS/TEN and also evaluated 6 patients with unclassified EMM. 13 patients in the EMM group and 16 patients in the SJS/TEN group presented with a high fever (>38.5?C; p<0.001). Two or more mucous membranes were affected in 6 patients in the EMM group and 18 patients in the SJS/TEN group. Significantly more SJS/TEN than EMM patients had high levels of C-reactive protein and severe hepatic dysfunction. Thirteen EMM and 13 SJS/TEN cases were caused by medications/drugs. Skin biopsy samples showed stronger mononuclear cell infiltration in the EMM than in the SJS/TEN group (p<0.001). The mean dose of initial systemic corticosteroid used to treat EMM was lower than that used to treat SJS/TEN. No patients died in either group. Clinically, the unclassified cases mostly behaved like EMM. The results of our investigation suggest that EMM and SJS/TEN are distinct conditions and they help in differentiating these syndromes at an early stage.     

Severe cutaneous reactions caused by barbiturates in seven Iranian children

Background  The severe adverse cutaneous reactions of erythema multiforme (EM), Stevens–Johnson syndrome (SJS) and toxic epidermal necrolysis (TEN) are rare mucocutaneous diseases associated with significant morbidity and mortality. The most common cause is antiepileptic drugs, particularly carbamazepine and lamotrigine, as well as the barbiturates group (phenobarbital and phenytoin). In this article, we present seven children with severe adverse cutaneous reactions caused by barbiturates.
Case Reports  The age of the affected children was between 2 and 11 years and they all had a history of taking barbiturates. Their symptoms started 1–3 weeks after the initiation of barbiturates, including a prodrome characterized by 2–3 days of malaise, fever, cough and anorexia, after which the skin and mucosal lesions appeared and worsened. The skin lesions varied from rash to large bullae, plus different forms of mucous membrane involvement. The offending drugs (barbiturates) were stopped immediately and care was largely supportive.
Conclusion  As a result of the morbidity and/or mortality associated with EM, SJS and TEN, physicians should keep in mind their differential diagnosis when cutaneous reactions are observed in patients undergoing barbiturate therapy. Furthermore, although TEN and SJS are life-threatening diseases, early detection and appropriate care can lead to a decrease in the incidence of death. The strategies described here seem to be successful and safe because, despite the serious conditions, our patients responded well. All survived.     

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.     

Toxic epidermal necrolysis and Stevens-Johnson syndrome. An epidemiologic study from West Germany

Little work has been carried out on the epidemiology of the two serious skin reactions--toxic epidermal necrolysis (TEN) and Stevens-Johnson syndrome (SJS). We collected details of all the hospitalized cases of TEN and SJS in the Federal Republic of Germany for the years 1981 through 1985 inclusive. Inquiries by telephone, letter, and personal visits produced an overall response of 91%; 259 cases of TEN and 315 cases of SJS were identified. From these data, we were able to calculate an overall annual risk of 0.93 and 1.1 per million for TEN and SJS, respectively. The average age group was higher for TEN (63 years) than for SJS (25 years). Women are markedly more at risk for TEN in the ratio of 2:1, these figures being reversed for SJS. The mortality was 34% (87/259) for TEN and only 1% (2/315) for SJS. An association with previous medication defined as "definite, probable, possible" could be established for 89% of cases of TEN and 54% of cases of SJS. The drugs most commonly involved were antibiotics (TEN, 40%; SJS, 34%), followed by the analgesics (TEN, 23%; SJS, 33%). As with the drug groups, the incidences being based on the defined daily doses, were high for sulfonamides, beta-lactam antibiotics, and some nonsteroidal anti-inflammatory drugs.     

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.     

Anti-desmoplakin antibodies in erythema multiforme and Stevens-Johnson syndrome sera: pathogenic or epiphenomenon?

The pathophysiology of erythema multiforme (EM), Stevens-Johnson syndrome (SJS), and toxic epidermal necrolysis (TEN) is unclear. Whether autoantibodies against desmoplakin (Dp) I and II play a pathogenic role or result from an epitope spreading phenomenon is uncertain. Our aim was to characterize the keratinocyte antigens recognized in EM, TEN and SJS. Of 33 patients studied, 2 had TEN, 1 SJS, 9 EM major and 21 EM minor, according to Roujeau's criteria. All sera were studied by indirect immunofluorescence (IIF), immunoblotting and immunoprecipitation. Twenty normal sera were used as controls. 10/33 sera reacted with polypeptides of 215 and/or 250-kDa molecular mass, which co-migrate with Dp I and II as assessed by an anti-Dp I and II monoclonal antibody on IB. In IP, none of the anti-Dp I and -Dp II 10 patient sera immunoprecipitated Dp I and/or II from radiolabeled keratinocyte extracts. Two of 10 patient sera (SJS, EM minor) reacted with DpI and II when denaturated by the IB procedure. The reactivity against intracellular antigens DpI and II as denaturated proteins may result from the epidermal damage produced by aggressive autoreactive T cells, playing therefore only a secondary role in the pathogenesis of the disease.     

Drug-Induced Stevens-Johnson Syndrome/Toxic Epidermal Necrolysis

Stevens-Johnson syndrome/toxic epidermal necrolysis (SJS/TEN) is a rare (occurring in approximately 2 to 3 people/million population/year in Europe and the US), life-threatening, intolerance reaction of the skin. It is most often caused by drugs (most commonly sulfonamides, nonsteroidal anti-inflammatory drugs, antimalarials, anticonvulsants, and allopurinol). SJS/TEN is characterized by a macular exanthema (‘atypical targets’) which focusses on the face, neck, and the central trunk regions. Lesions show rapid confluence, a positive Nikolsky’s sign, and quickly result in widespread detachment of the epidermis and erosions. Mucosal, conjunctival, and anogenital mucous membranes are prominently involved. Histopathology shows satellite cell necrosis in the early stages progressing to full thickness necrosis of the epidermis, contrasting with rather inconspicuous inflammatory infiltrates of the dermis. Damage to the skin is thought to be mediated by cytotoxic T lymphocytes and mononuclear cells which induce apoptosis in keratinocytes expressing drug-derived antigens at their surfaces. No guidelines for the treatment of SJS/TEN exist since no controlled clinical trials have ever been performed. The controversy over whether systemic corticosteroids should be used to curtail progression is still unresolved; while many authors agree that corticosteroids do in fact suppress progression, it is obvious that they also greatly enhance the risk of infection, the complication which most frequently leads to a fatal outcome. It appears reasonable to only administer corticosteroids in the phase of progression and to withdraw them as soon as possible, and to add antibacterials for prophylaxis. Recently, in a small series of patients, intravenous immunoglobulins were presumed to be effective by the blockade of lytic Fas ligand-mediated apoptosis in SJS/TEN. However, these results have to be confirmed by large clinical trials. Supportive treatment and monitoring of vital functions is of utmost importance in SJS/TEN, and out-patient treatment is unacceptable. Recovery is usually slow, depending on the extent and severity and the presence of complications, and may take 3 to 6 weeks. Skin lesions heal without scars as a rule, but scarring of mucosal sites is a frequent late complication, potentially leading to blindness, obliteration of the fornices and anogenital strictures. There is no reliable laboratory test to determine the offending drug; diagnosis rests on the patient’s history and the empirical risk of drugs to elicit skin SJS/TEN. Provocation tests are not indicated since re-exposure is likely to elicit a new episode of SJS/TEN of increased severity.     

Clinical Pattern of Cutaneous Drug Eruption among Children and Adolescents in

Abstract: Various types of cutaneous drug eruptions and the Incriminating drugs were analyzed tn 50 children and adolescents up to 18 years of age (34 or 65% boys, 16 or 32% girls). Thirteen (26%) patients had a maculopapular rash, 11 (22%) a fixed drug eruption (FDE), 10 erythema multiforme (EM), 6 (12%) toxic epidermal necrolysis (TEN), 5 (10%) Stevens-Johnson syndrome (SJS), 3 (6%) urticaria, and 2 (4%) erythroderma. The Incubation period for maculopapular rashes, SJS and TEN due to commonly used antibiotics and sulfonamides was short, a few hours to two to three days, reflecting reexposure, and for drugs used sparingly such as antiepileptics and antitubereulosis agents, was approximately one week or more, suggesting a first exposure. Antibiotics were responsible for cutaneous eruptions in 27 patients, followed by antlepileptics In 17, analgin in 4, and metronidazole and albendazole in 1 each. Cotrimoxazole, a combination of sulfamethoxazole and trimethoprim, was the most common antibacterial responsible for eruptions (11 patients), followed by penicillin and its semisynthetlc derivatives (8 patients), sulfonamide alone (3 patients), and other antibiotics (4 patients). Antiepileptics were the most frequently incriminated drugs in EM, TEN, and SJS. The role of systemic corticosteroids in the management of SJS and TEN is controversial. We administered prednisolone or an equivalent corticosteroid 2 mg/kg/day for 7 to 14 days. With this dosage the mortality rate in the combined patients with TEN and SJS was 18.2%. Our limited experience suggests that these drugs might still have a role in the management of SJS and TEN In children and adolescents.     

Stevens-Johnson syndrome and toxic epidermal necrolysis in patients with lupus erythematosus: a descriptive study of 17 cases from a national registry and review of the literature

Background Stevens–Johnson syndrome (SJS) and toxic epidermal necrolysis (TEN) are severe cutaneous adverse reactions with high morbidity and mortality. Some expressions of lupus erythematosus (LE) may cause enormous difficulties in differentiating them from SJS and TEN by showing large areas of sheet‐like epidermal necrosis. Objective To evaluate clinically and histopathologically probable or definite cases of SJS/TEN with a history of systemic or other LE [(S)LE]. Methods This was a retrospective analysis of validated cases of SJS/TEN with a history of (S)LE, based on a large population‐based national registry. Results Among 1366 patients with SJS/TEN, 17 with a sufficiently documented history of (S)LE and representative histological material could be identified, suggesting a considerable over‐representation of LE in patients with SJS/TEN. Eight of these showed clinically and/or histopathologically some LE‐characteristic features interfering with the diagnosis of SJS/TEN. Differentiation could be elaborated on clinical and histopathological grounds: four patients were classified as SJS/TEN with a preceding (S)LE exacerbation and/or LE‐typical histopathological features, and four as ‘TEN‐like’ (S)LE. Conclusion Most patients with SJS/TEN and a history of (S)LE demonstrate clinical and histopathological properties allowing clear differentiation. However, occasionally acute cutaneous manifestations of (S)LE and SJS/TEN can be phenotypically similar, caused by extensive epidermal necrosis. Although no feature by itself is conclusive, a combination of recent (S)LE exacerbation, evident photodistribution, annular lesions and absent or only mild focal erosive mucosal involvement may favour LE over SJS/TEN clinically. Histopathologically, in particular, junctional vacuolar alteration, and the presence of solitary necrotic keratinocytes at lower epidermal levels, combined with moderate to dense periadnexal and perivascular lymphocytic infiltrates with a variable presence of melanophages, and mucin point to a LE‐related origin.