Type Skin Reactions Research Articles

Apalutamide-induced lichenoid reaction in a patient with non-metastatic castrate-resistant prostate cancer.

Apalutamide is an oral selective androgen receptor inhibitor, approved by the FDA for the treatment of patients with non-metastatic, castration-resistant prostate cancer (M0 CRPC) at high risk of developing metastases and for patients with metastatic castration-sensitive prostate (mHSPC) in association with androgen deprivation therapy (ADT). In the registration studies, skin reactions were reported among the most common side effects and as an adverse event of special interest. Apalutamide-induced rash includes a wide spectrum of different types of skin reactions, but few cases reports and case series have described this adverse event. Here, we report an M0 CRPC patient who experienced a rare skin adverse event, a lichenoid reaction. After 4 months of therapy with apalutamide, the patient reported dorsal pricking and dry skin. Lichenoid reaction was confirmed histologically and its correlation to the drug was demonstrated after pursuing a multidisciplinary approach. To our knowledge, this is one of the first cases of Apalutamide-related lichenoid reaction and this clinical case showed the relevance of a multidisciplinary management when assessing drug-related adverse events. A broader knowledge of the spectrum of drug-related reactions would allow for a better diagnosis and therapy management by both physicians and patients.

Skin Reactions Following Primary Total Knee Arthroplasty With an Adhesive Superficial Closure System: A Case Series

BackgroundWe investigated a skin adhesive closure device consisting of a self-adhesive polyester mesh placed over the surgical incision, followed by a liquid adhesive that is spread over the mesh and surrounding the skin. It is intended to reduce wound closure times, scarring, and skin complications associated with traditional closure with sutures or staples. The aim of this study was to report on skin reactions in patients who underwent primary total knee arthroplasty (TKA) using the skin adhesive closure system. MethodsA retrospective review of patients who underwent TKA using adhesive closure between 2016 to 2021 at a single institute was performed. A total of 1,719 cases were analyzed. Patient demographics were collected. The primary outcome was any postoperative skin reaction. Skin reactions were classified as allergic dermatitis, cellulitis, or other. Treatment(s), duration of symptoms, and surgical infections were also collected. ResultsA total of 5.0% (86) of patients were found to have any type of skin reaction following their TKA. Of these 86, 39 (2.3%) had symptoms of allergic dermatitis (AD), 23 (1.3%) had symptoms of cellulitis, and 24 (1.4%) had other symptoms. A total of 27 (69%) allergic dermatitis patients were treated with a topical corticosteroid cream only; their symptoms resolved within an average of 25 days. There was only 1 case of superficial infection (<0.001%). No prosthetic joint infections were observed. ConclusionDespite skin reactions appearing in 5.0% of cases, the rate of infection was low. A patient-specific preoperative workup and effective treatment strategies can minimize complications associated with adhesive closure system and increase patient satisfaction following TKA.

A systematic review on treatment-related mucocutaneous reactions in COVID-19 patients.

Most of drugs could have certain mucocutaneous reactions and COVID‐19 drugs are not an exception that we focused. We systematically reviewed databases until August 15, 2020 and among initial 851 articles, 30 articles entered this study (20 case reports, 4 cohorts, and 6 controlled clinical trials). The types of reactions included AGEP, morbiliform drug eruptions, vasculitis, DRESS syndrome, urticarial vasculitis, and so on. The treatments have been used before side effects occur, included: antimalarial, anti‐viral, antibiotics, tocilizumab, enoxaparin and and so on. In pandemic, we found 0.004% to 4.15% of definite drug‐induced mucocutaneous reactions. The interval between drug usage and the eruption varied about few hours to 1 month; tightly dependent to the type of drug and hydroxychloroqine seems to be the drug with highest mean interval. Antivirals, antimalarials, azithromycin, and tocilizumab are most responsive drugs for adverse drug reactions, but antivirals especially in combination with antimalarial drugs are in the first step. Types of skin reactions are usually morbilliform/exanthematous maculopapular rashes or urticarial eruptions, which mostly may manage by steroids during few days. In the setting of HCQ, specific reactions like AGEP should be considered. Lopinavir/ritonavir is the most prevalent used drug among antivirals with the highest skin adverse reaction; ribarivin and remdisivir also could induce cutaneous drug reactions but favipiravir has no or less adverse effects. Logically the rate of dermatologic adverse effects among anivirals may relate to their frequency of usage. Rarely, potentially life‐threatening reactions may occur. Better management strategies could achieve by knowing more about drug‐induced mucocutaneous presentations of COVID‐19.

Severe Cutaneous Adverse Drug Reactions : a Prospective Study of Epidemiology and Clinical Pattern.

BACKGROUND:Cutaneous adverse drug eruptions are the most common adverse reactions attributed to drugs in which any type of skin reaction can be mimicked, induced, or aggravated. Cutaneous drug reactions are of wide range from mild to moderate to severe life threatening reactions. The term severe cutaneous adverse drug reactions encompasses Steven– Johnson syndrome (SJS), toxic epidermal necrolysis (TEN), drug reaction with eosinophilia and systemic symptoms (DRESS), and acute generalized exanthematous pustulosis (AGEP). Aims: The aims of this study are to evaluate the clinical and epidemiological aspects of severe cutaneous adverse drug reactions (SCADRS) at a tertiary care center from gujarat. Methods : This is a prospective study which was conducted over period from September 2014 to December 2016. A total 31 patients were included in the study which included outpatients as well as inpatients admitted after written informed consent.The diagnosis of SJS, TEN ,AGEP were made on clinical grounds and according to standard definitions while in case of DRESS REGISCAR score was used to establish the diagnosis. Results : In the study, a total of 31 patients were included in the study,in which 18 were males and 13 were females, and maximum patients were in the age group of 31-40 years. SJS 14(45.16%) was the most common SCADR. Antiepileptic class of drug was found to be most commonly implicated. Conclusion : Patients can be educated to avoid re-administration of the offending drug(s) to reduce the morbidity associated with CADRs. Early identification of SCADRs can reduce the morbidity and mortality rates.

Sentinel lymph node mapping in early breast cancer using methylene blue dye

Background: With the introduction of the concept of sentinel lymph node biopsy (SLNB), the surgical management of the axilla has undergone a paradigm change in clinically node-negative early breast cancer, and complete axillary dissection is avoided if the sentinel lymph node (SLN) is negative for metastasis. Aim: The purpose of this study was to identify the reliability, accuracy, and safety of using methylene blue dye (MBD) in SLNB for early-stage carcinoma of the breast. Materials and Methods: A prospective study was conducted among 151 early breast carcinoma patients (T1/2N0M0) from December 2012 to February 2016. Intraoperative identification of the SLN was done by injecting 5 ml of 1% MBD into the subareolar region of the breast. All the blue-stained lymph nodes were then surgically excised and sent for frozen section examination. Results: The mean age of presentation was 54.10 years. Thirty out of 151 cases had SLN metastasis and 115 cases were negative for malignancy on the frozen section. On the final histopathological examination, 36 cases had metastasis and 115 cases were negative for malignancy. The false-negative rate was 5%. No patients developed anaphylactic/allergic or any type of skin reaction following MBD injection. The accuracy, positive predictive value, and negative predictive value of sentinel node identification using MBD were 96.02%, 100%, and 95.04%, respectively. After a mean follow-up of 10 months, no patient was found to be with ipsilateral axillary or supraclavicular recurrence. Conclusion: The use of MBD in SLNB for the diagnosis of axillary metastasis is reliable, accurate, and safe.

A Study of Cutaneous Adverse Drug Reactions in a Tertiary Care Center in Punjab.

Context:Cutaneous adverse drug eruptions are the most common adverse reactions attributed to drugs in which any type of skin reaction can be mimicked, induced, or aggravated.Aims:To study the pattern of various types of cutaneous adverse drug reactions (CADRs), to find out the causative drug(s) involved and to determine the response to treatment and outcome in patients with CADRs.Patients and Methods:This prospective study was done in the department of dermatology. Patients with suspected drug rash, of either sex and all age groups were included in the study.Statistical Analysis:Frequencies and proportions were calculated using Chi-square test and t-test as the tests of significance. Data was analyzed using SPSS version 21.Results:A total of 258 patients were enrolled in the study. The most common CADR observed in the study was exanthematous drug eruption in 42.63% patients followed by drug induced urticaria in 21.32% patients. Antimicrobials were the most common offending drugs in 64.73% of patients, followed by non-steroidal anti-inflammatory drugs (NSAIDs) in 15.50% patients. In the study, 12 patients (4.65%) were found to have severe cutaneous adverse drug reactions (SCADRs). Stevens–Johnson syndrome (SJS) - Toxic epidermal necrolysis (TEN) was the most common SCADR (50%) and antituberculous drugs were the most common causative group of drugs causing SCADRs.Conclusion:The most common CADR observed in the study was exanthematous drug eruption and antimicrobials were the most common causative drugs.

Differentiation of irradiation and cetuximab induced skin reactions in patients with locally advanced head and neck cancer undergoing radioimmunotherapy: the HICARE protocol (Head and neck cancer: ImmunoChemo and Radiotherapy with Erbitux) – a multicenter phase IV trial

BackgroundIn order to improve the clinical outcome of patients with locally advanced squamous cell carcinoma of the head and neck (LASCCHN) not being capable to receive platinum-based chemoradiation, radiotherapy can be intensified by addition of cetuximab, a monoclonal antibody that blocks the epidermal growth factor receptor (EGFR). The radioimmunotherapy with cetuximab is a feasible treatment option showing a favourable toxicity profile. The most frequent side effect of radiotherapy is radiation dermatitis, the most common side effect of treatment with cetuximab is acneiform rash. Incidence and severity of these frequent, often overlapping and sometimes limiting skin reactions, however, are not well explored. A clinical and molecular differentiation between radiogenic skin reactions and skin reactions caused by cetuximab which may correlate with outcome, have never been described before.Methods/designThe HICARE study is a national, multicenter, prospective phase IV study exploring the different types of skin reactions that occur in patients with LASCCHN undergoing radioimmun(chemo)therapy with the EGFR inhibitor cetuximab. 500 patients with LASCCHN will be enrolled in 40 participating sites in Germany. Primary endpoint is the rate of radiation dermatitis NCI CTCAE grade 3 and 4 (v. 4.02). Radioimmunotherapy will be applied according to SmPC, i.e. cetuximab will be administered as loading dose and then weekly during the radiotherapy. Irradiation will be applied as intensity-modulated radiation therapy (IMRT) or 3D-dimensional radiation therapy.DiscussionThe HICARE trial is expected to be one of the largest trials ever conducted in head and neck cancer patients. The goal of the HICARE trial is to differentiate skin reactions caused by radiation from those caused by the monoclonal antibody cetuximab, to evaluate the incidence and severity of these skin reactions and to correlate them with outcome parameters. Besides, the translational research program will help to identify and confirm novel peripheral blood based molecular predictors and surrogates for treatment response and resistance.Trial registrationClinical Trial Identifier, NCT01553032 (clinicaltrials.gov)EudraCT number: 2010-019748-38

Natural killer cells and T cells induce different types ofskin reactions during recall responses to haptens

The role of T cells in contact hypersensitivity (CHS) to haptens has been well described. However, recent reports demonstrated that CHS-like reactions to experimental haptens could be induced in mice deficient in T cells and B cells, as a result of adaptive-like features of NK cells. Here, we compared hapten-specific inflammatory reactions induced by memory T cells or NK cells. Classical CHS protocols were applied to WT or T- and B-cell deficient mice. Adoptive transfers of hapten-specific T cells and NK cells were also performed. Liver NK cells from hapten-primed mice induced specific recall responses to haptens upon transfer in CD3ε-deficient mice, thus confirming the existence of "memory" NK cells in the liver. We investigated the nature of the inflammation generated in these transfer conditions and found that hapten-induced skin inflammation mediated by CD8(+) T cells or "memory" NK cells are different. Indeed, ear swelling induced by memory NK cells was transient and not associated with cellular infiltrate and inflammation markers, characteristic for T-cell-mediated responses. Thus, NK cells and T cells mediate distinct forms of skin inflammation. NK cell-mediated pathogenesis does not rely on cellular infiltrate and could be involved in atypical forms of adverse drug reactions.

Radiation recall dermatitis induced by Amol during tamoxifen therapy –

In the course of radiation therapy different types of adverse reactions of the skin are observed in approximately 95% of patients. Among the various complications encountered after radiotherapy, radiation recall dermatitis (RRD) deserves special attention. Radiation dermatitis is a form of delayed hypersensitivity of irradiated skin, and the direct trigger factors are medicines – most chemotherapeutics. The reaction is an inflammatory dermatosis. It is limited to previously irradiated skin and appears a number of months after radiotherapy. The aetiology of RRD is still unclear. Its clinical presentation may vary from mild erythema to necrosis and ulceration. The article presents the case of a 50-year-old patient, who after radiotherapy for breast cancer, during the hormonal therapy (tamoxifen), developed RRD type skin reactions after skin application of Amol. The article presents a detailed differential diagnosis of skin changes of RRD type, and discusses the principles of treatment and prevention.

Docetaxel extravasation resulting in vesicant type skin reaction: case report

Docetaxel extravasation resulting in vesicant type skin reaction: case report

Skin and Systemic Manifestations of Jellyfish Stings in Iraqi Fishermen

Background: Jellyfish stings are common worldwide with an estimated 150 million cases annually, and their stings cause a wide range of clinical manifestations from skin inflammation to cardiovascular and respiratory collapse. No studies on jellyfish stings have been carried out in Basra, Iraq. Objectives: To describe the immediate and delayed skin reactions to White Jellyfish (Rhizostoma sp.) stings and the types of local treatment used by fishermen. Methods and Materials: 150 fishermen were enrolled at three Marine stations in Basra, Iraq. Demographic data, types of skin reactions, systemic manifestations and kinds of treatments were collected. Results: Overall, 79% of fishermen in all three Marine stations gave a history of having been stung. The common sites of sings were the hands and arms followed by the legs. Most fishermen claimed that stings led to skin reactions within 5 minutes. The presenting complaints were itching, burning sensation, and erythematic wheals. A few days after the sting, new groups of painless and itchy erythematous monomorphic papular rashes developed at the site of the sting in 62% of cases as a delayed type of skin reaction that resolved spontaneously. The local remedies commonly used by the fishermen were seawater, tap water and ice. A few fishermen considered stings as insignificant and did not think there was a need to seek medical help. Conclusions: We conclude that jellyfish causes many stings among fishermen in the Basra region. Their stings lead to immediate and delayed skin reactions. Self-treatment by topical remedies is common.

Secretome analysis of novel IgE‐binding proteins from Penicillium citrinum

The Penicillium genus of fungi is a frequently reported cause of allergic reactions. However, only a limited number of allergens have been reported. In Penicillium spp., many allergens show higher IgE-binding activity in culture filtrate extracts than in cellular extracts. In order to investigate the IgE-reactive profile of mold-sensitized patients, secreted IgE-reactive proteins from Penicillium citrinum were identified by 2-DE, serum immunoblotting, and nanoLC-MS/MS. Among the IgE-reactive spots, one known allergen, Pen c 13, and four novel allergens were identified. The cDNAs coding for Pen c 32 and Pen c 30 were cloned using designed primers based on nanoLC-MS/MS analysis. The amino acid sequences of Pen c 32 and Pen c 30 were, respectively, found to have extensive similarity with those of pectate lyases and catalases from various fungi. Native Pen c 30 was shown to have catalase activity and to bind to serum IgE from 48% of mold-allergic patients and induced immediate type skin reactions in a sensitized patient. Here, we present a proteome approach which resulted in the identification of four novel secreted allergens. These novel allergens might be useful in allergy diagnosis and in the treatment of mold-allergic disorders.

Praktische Tipps für die Betreuung von Patienten mit Urtikaria

Urticaria (hives), one of the most common inflammatory skin conditions, is relatively easy to diagnose because of its characteristic skin symptoms, i.e. wheal and flare type skin reactions and/or angioedema. Urticaria, however, actually comprises 12 distinct conditions and it is important and often difficult, to determine which urticaria subform(s) individual patients are afflicted with. The most challenging task in diagnosing urticaria is to identify the underlying causes in chronic urticaria. Yet, this is important as many patients with chronic urticaria can be successfully treated by eliminating the reason for their condition. In contrast, the treatment of virtually all other urticarias is primarily aimed at achieving symptom control, e.g. by avoiding accountable triggers and/or by using symptomatic treatment.

Diagnostic algorithm and management of immune-mediated complications associated with subcutaneous insulin therapy.

Immune mediated complications associated with subcutaneous insulin therapy such as insulin neutralizing antibodies and/or skin reactions are rare conditions since human insulin is in general use. Nevertheless, if it occurs, a stepwise diagnostic approach is essential for differential diagnosis and consecutive treatment of these complications. Here we suggest a diagnostic algorithm to deal with e.g. insulin antibody formation of the IgG and/or IgE type and/or severe skin reactions resulting in poor metabolic control and often "brittle diabetes" in affected patients. This diagnostic algorithm includes step 1: Intradermal skin testing with positive and negative controls, additives and different insulin preparations; step 2: Quantification of insulin specific IgG and IgE in the serum, and step 3: Analysis of the time dependent binding/dissociation curves of the insulin neutralizing antibodies in an ex vivo/in vitro assay to assess the clinical significance of these antibodies. Based on 158 insulin treated control subjects and four patients with typical symptoms and signs representing the spectrum of immune-mediated complications subsequent to subcutaneous insulin therapy we demonstrate that the proposed stepwise approach leads to a definite diagnosis as a prerequisite for individual and successful therapy.

Occupational dermatoses.

All terms referring to job-related (occupational) rashes are clearly defined. Ranking as the second most common occupational disorder, the importance of occupational dermatoses is illustrated. 90-95% of occupational dermatoses result from a contact-type dermatitis. Until recently, 4/5 cases were believed to be of the irritant, rather than allergic type of contact dermatitis, however, with more extensive patch testing, more than half the cases were found to be allergic. The direct causes of occupational dermatoses: chemical, mechanical, physical, and biological in nature are presented. The implications of assigning the degree and type of occupational dermatoses are explained. Workmans compensation is based on a no-fault arrangement, stating that unrestricted treatment and compensation is allowable only when negligence on the part of the employer is proven. Employee benefits are then determined by the duration and degree of disability sustained - all of which becomes litigational. Predisposing host factors, i.e. intellectual ability, anatomic site, atopy, skin pigmentation, age of skin, and immunosuppression (by disease or medication) are usually ignored. Environmental factors at the workplace must be considered conducive to occupational diseases. The full spectrum of irritant contact dermatitis is discussed with examples of each described. Allergic contact dermatitis and patch testing - the gold standard for identification of putative allergens is extensively discussed. Differentiating irritant contact dermatitis from allergic contact dermatitis is elucidated. The other non-contact type skin reactions are briefly mentioned.

Proteomics and immunological analysis of a novel shrimp allergen, Pen m 2.

Shellfish are a common cause of adverse food reactions in hypersensitive individuals and shrimp is one of the most frequently reported causes of allergic reactions. A novel allergen from Penaeus monodon, designated Pen m 2, was identified by two-dimensional immunoblotting using sera from subjects with shrimp allergy, followed by matrix-assisted laser desorption ionization time-of-flight mass spectrometry analysis of the peptide digest. This novel allergen was then cloned and the amino acid sequence deduced from the cDNA sequence. The cloned cDNA encoded a 356-aa protein with an acetylated N terminus at Ala2, identified by postsource decay analysis. Comparison of the Pen m 2 sequence with known protein sequences revealed extensive similarity with arginine kinase (EC 2.7.3.3) from crustaceans. Pen m 2 was purified by anion exchange chromatography and shown to have arginine kinase activity and to react with serum IgE from shrimp allergic patients and induce immediate type skin reactions in sensitized patients. Using Pen m 2-specific antisera and polyclonal sera from shrimp-sensitive subjects in a competitive ELISA inhibition assay, Pen m 2 was identified as a novel cross-reactive Crustacea allergen. This novel allergen could be useful in allergy diagnosis and in the treatment of Crustacea-derived allergic disorders.

Purification, structural and immunological characterization of a timothy grass (Phleum pratense) pollen allergen, Phl p 4, with cross-reactive potential.

Almost 500 million people worldwide suffer from Type I allergy, a genetically determined immunodisorder which is based on the production of IgE antibodies against per se harmless antigens (allergens). Due to their worldwide distribution and heavy pollen production, grasses represent a major allergen source for approximately 40% of allergic patients. We purified Phl p 4, a major timothy grass (Phleum pratense) pollen allergen with a molecular mass of 61.3 kDa and a pl of 9.6 to homogeneity. Circular dichroism spectroscopical analysis indicates that Phl p 4 contains a mixed alpha-helical/beta-pleated secondary structure and, unlike many other allergens, showed no reversible unfolding after thermal denaturation. We show that Phl p 4 is a major allergen which reacts with IgE antibodies of 75% of grass pollen allergic patients (n=150) and induces basophil histamine release as well as immediate type skin reactions in sensitized individuals. Phl p 4-specific IgE from three patients as well as two rabbit-anti Phl p 4 antisera cross-reacted with allergens present in pollen of trees, grasses, weeds as well as plant-derived food. Rabbit antibodies raised against Phl p 4 also inhibited the binding of allergic patients IgE to Phl p 4. Phl p 4 may thus be used for diagnosis and treatment of sensitized allergic patients.

Molecular characterization of human IgG monoclonal antibodies specific for the major birch pollen allergen Bet v 1. Anti-allergen IgG can enhance the anaphylactic reaction

We report the molecular characterization of five human monoclonal antibodies, BAB1–5 (BAB1: IgG 1; BAB4: IgG 2; BAB2, 3, 5: IgG 4), with specificity for the major birch pollen allergen, Bet v 1. BAB1–5 were obtained after immunotherapy and contained a high degree of somatic mutations indicative of an antigen-driven affinity maturation process. While BAB1 inhibited the binding of patients IgE to Bet v 1, BAB2 increased IgE recognition of Bet v 1, and, even as Escherichia coli-expressed Fab, augmented Bet v 1-induced immediate type skin reactions. The demonstration that IgG antibodies can enhance allergen-induced allergic reactions is likely to explain the unpredictability of specific immunotherapy.

Molecular, Immunological, and Structural Characterization of Phl p 6, a Major Allergen and P-Particle-Associated Protein from Timothy Grass (Phleum pratense) Pollen

AbstractDue to the wide distribution and heavy pollen production of grasses, ∼50% of allergic patients are sensitized against grass pollen allergens. cDNAs coding for two isoforms and four fragments of a major timothy grass (Phleum pratense) pollen allergen, Phl p 6, were isolated by IgE immunoscreening from a pollen expression cDNA library. Recombinant Phl p 6 (rPhl p 6), an acidic protein of 11.8 kDa, was purified to homogeneity as assessed by mass spectrometry and exhibited almost exclusive α-helical secondary structure as determined by circular dichroism spectroscopy. Phl p 6 reacted with serum IgE from 75% of grass pollen-allergic patients (n = 171). IgE binding experiments with rPhl p 6 fragments indicated that the N terminus of the allergen is required for IgE recognition. Purified rPhl p 6 elicited dose-dependent basophil histamine release and immediate type skin reactions in patients allergic to grass pollen. A rabbit antiserum raised against purified rPhl p 6 identified it as a pollen-specific protein that, by immunogold electron microscopy, was localized on the polysaccharide-containing wall-precursor bodies (P-particles). The association of Phl p 6 with P-particles may facilitate its intrusion into the deeper airways and thus be responsible for the high prevalence of IgE recognition of Phl p 6. Recombinant native-like Phl p 6 can be used for in vitro as well as in vivo diagnoses of grass pollen allergy, whereas N-terminal deletion mutants with reduced IgE binding capacity may represent candidates for immunotherapy of grass pollen allergy with a low risk of anaphylactic side effects.

Skin reactions to carbamazepine

Abbreviations. CBZ: carbamazepine; EEM: erythema exsudativum multiforme; TEN: toxic epidermal necrolysis. . Carbamazepine (CBZ) is an important drug used mainly in the treatment of epilepsy, paroxysmal trigeminal neuralgia, and affective disorders. Skin eruptions caused by CBZ occur in 2±4% of the patients on this therapy and include pruritic and erythematous rashes, urticaria, photosensitivity reactions, alterations in skin pigmentation, exfoliative dermatitis, and toxic epidermal necrolysis (TEN) (1). Patch tests with CBZ 1% and 5% pet. seem to be useful for diagnostic con®rmation purposes in patients with generalized maculopapular hypersensitivity reactions to CBZ (2). A double bond between positions 10 and 11 of the azepine ring of CBZ seems to be critical for skin reactivity. This bond is lost in CBZ metabolites and in its analog oxcarbazepine, which usually does not cross-react with CBZ (3). Two patients with different skin reactions to carbamazepine are described. Thirteen days after starting CBZ therapy, patient no. 1 (age 36; female) developed a pruritic erythematous maculopapular eruption with some target lesions on the extremities characteristic of erythema exsudativum multiforme (EEM). The lesions progressed to TEN with 50% epidermolysis, accompanied by oral and genital ulcers. Patient no. 2 (age 47; female) developed maculopapular exanthema with erythrodermia about 91 days after starting CBZ therapy. In both patients, CBZ therapy was discontinued, and systemic corticosteroids were initiated. A skin cell suspension obtained from lesional skin was prepared by enzymatic digestion, by the method of Sager et al. (4). To select for CBZ-speci®c T cells, the suspension was cocultured with 10 irradiated (20 Gy) peripheral blood-derived mononuclear cells in culture medium (RPMI 1640; Gibco, Grand Island, NY, USA) supplemented with 10% human AB serum (Bloedbank, Utrecht, The Netherlands), and IL-2 and IL-4 (both 50 U/ml; Novartis Research Institute, Vienna, Austria) and CBZ (Tegretol). T-cell cultures were phenotypically characterized by ow cytometry in order to assess relative expressions of CD4 and CD8. Speci®city for CBZ was examined in lymphocyte stimulation tests in which, in triplicates, 40310 T cells were cocultured with equal numbers of autologous, irradiated (40 Gy), EBV-transformed B cells and increasing concentrations of CBZ. H-labeled thymidine incorporation was the measure of T-cell proliferation. In patient no. 1, the T-cell culture consisted of CD8 T cells mostly (94%). No CBZ speci®city was detected in this culture (Fig. 1A). Patient no. 1 had a negative patch test to CBZ, a fact which may be explained by the exclusive presence of CD8 T cells. Indeed, Friedmann et al. previously reported the predominant presence of CD8 T cells in the lesional skin of drug-induced EM/TEN by immunohistochemistry (5). These authors did not detect speci®city for CBZ in blood-derived T cells. In patient no. 2, the T cells cultured with CBZ were nearly all CD4 (98%) and showed speci®city for CBZ (Fig. 1B). Patient no. 2 had a positive patch test reaction to CBZ after 48 h, suggesting a type IV, cell-mediated skin reaction. We hypothesize that the way a drug is presented as an antigen is re ected in the type of skin reaction induced by that drug: activation of CD8 T cells (cytotoxicity) in TEN, and CD4 T cells (delayed-type reaction) in erythrodermia.