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Background Patients with Stevens-Johnson syndrome (SJS)/toxic epidermal necrolysis (TEN) have high mortality rates. Disseminated intravascular coagulation has been reported in SJS/TEN patients. The influence of this lethal complication in patients with SJS/TEN is not well known. Objective This study aimed to investigate the risk and outcomes of disseminated intravascular coagulation in patients with SJS/TEN. Methods We analyzed the disseminated intravascular coagulation profiles of patients receiving a diagnosis of SJS/TEN between 2010 and 2019. Results We analyzed 150 patients with SJS/TEN (75 with SJS, 22 with overlapping SJS/TEN, and 53 with TEN) and their complete disseminated intravascular coagulation profiles. Disseminated intravascular coagulation was diagnosed in 32 patients (21.3%), primarily those with TEN. It was significantly associated with systemic complications, including gastrointestinal bleeding, respiratory failure, renal failure, liver failure, infection, and bacteremia. Additionally, SJS/TEN patients with disseminated intravascular coagulation had elevated procalcitonin levels. Among patients with SJS/TEN, disseminated intravascular coagulation was associated with a greater than 10-fold increase in mortality (78.1% vs 7%). Limitations The study limitations include small sample size and a single hospital system. Conclusion Disseminated intravascular coagulation is a potential complication of SJS/TEN and associated with higher mortality. Early recognition and appropriate management of this critical complication are important for patients with SJS/TEN.

Bullous skin disorders are induced by different pathomechanisms and several are emergent, including Stevens-Johnson syndrome/toxic epidermal necrolysis (SJS/TEN). Rapid diagnostic methods for SJS/TEN or cytotoxic T-lymphocyte (CTL)-mediated bullous disorders are crucial for early treatment. Granulysin, primarily expressed by CTLs, is a specific cytotoxic protein responsible for SJS/TEN and similar skin reactions.To assess granulysin levels in blister fluids to differentiate SJS/TEN and similar CTL-mediated bullous reactions from other autoimmune bullous disorders.Using ELISA, we measured granulysin in blister fluids from patients with bullous skin disorders, including SJS/TEN, erythema multiforme major, bullous fixed-drug eruption, bullous lupus erythematosus, paraneoplastic pemphigus, pemphigus vulgaris, bullous pemphigoid, purpura fulminans-related bullae, and hand-foot syndrome/hand-foot-skin reactions. We compared serum and blister granulysin levels in patients with SJS/TEN presenting varying severity, monitoring serial granulysin levels from acute to late stages.Overall, 144 patients presenting with bullous skin disorders were enrolled. Blister granulysin levels (mean ± SD) in CTL-mediated disorders, including TEN (n = 28; 3938.7 ± 3475.7), SJS-TEN overlapping (n = 22; 1440.4 ± 1179.6), SJS (n = 14; 542.0 ± 503.2), erythema multiforme major (n = 7; 766.3 ± 1073.7), generalized bullous fixed-drug eruption (n = 10; 720.4 ± 858.3), and localized bullous fixed-drug eruption (n = 16; 69.0 ± 56.4), were significantly higher than in non-CTL-mediated bullous disorders (P.0001), including bullous lupus erythematosus (n = 3; 22.7 ± 20.1), paraneoplastic pemphigus (n = 3; 20.3 ± 8.6), pemphigus vulgaris (n = 3; 4.4 ± 2.8), bullous pemphigoid (n = 18; 4.0 ± 2.7), purpura fulminans (n = 4; 5.9 ± 5.5), and hand-foot syndrome/hand-foot-skin reactions (n = 6; 4.6 ± 3.5). Blister granulysin levels correlated with clinical severity of SJS/TEN (P.0001).Determination of blister granulysin levels is a noninvasive and useful tool for rapid differential diagnosis of SJS/TEN and other similar CTL-mediated bullous skin disorders for treatment selection.

Background Cutaneous lupus erythematosus (CLE) includes a broad range of dermatologic manifestations. Periorbital involvement, however, is a relatively rare clinical presentation of CLE. Objectives This clinical study aimed to investigate the characteristics of this unique presentation of CLE in tertiary medical centers. Methods We enrolled patients with periorbital erythema and swelling as the presenting sign of lupus erythematosus, from January 2003 to November 2017, using the data of 553 pathologically proven CLE cases from the registration database of the Chang Gung Memorial Hospitals in Taiwan. Results We enrolled a total of 25 patients. The mean age was 46.7 years and 68% of the patients were female. Most of the patients (84.0%) presented with unilateral involvement, with the left orbit involved in 15 patients (60%); the upper eyelid was the most frequently involved (72%). Mean duration between the onset of clinical manifestations and the diagnosis of CLE was approximately 59 weeks. Nineteen patients had been previously misdiagnosed. All patients had features compatible with CLE on histopathological examination. In contrast, laboratory analysis of the autoimmune profile often revealed negative results, including those for antinuclear antibodies (25%). Notably, anti-SSA/SSB (45.5%) showed the highest positive rate. During follow-up, six patients developed systemic lupus erythematosus (SLE) and two patients developed Sjögren syndrome. Conclusions The diagnosis of CLE presenting as periorbital erythema and swelling is often delayed because of clinical mimicry and the high proportion of negative results on autoantibody tests. Increased clinical suspicion and prompt histopathological examination are crucial for early diagnosis. Moreover, one-fourth of the patients ultimately developed SLE, which highlights the importance of clinical awareness.

Specific ethnic genetic backgrounds are associated with the risk of Stevens-Johnson syndrome / toxic epidermal necrolysis (SJS/TEN) especially in Asians. However, there have been no large cohort, multiple-country epidemiological studies of medication risk related to SJS/TEN in Asian populations. Thus, we analyzed the registration databases from multiple Asian countries who were treated during 1998-2017. A total 1,028 SJS/TEN cases were identified with the algorithm of drug causality for epidermal necrolysis. Furthermore, those medications labeled by the US Food and Drug Administration (FDA) as carrying a risk of SJS/TEN were also compared with the common causes of SJS/TEN in Asian countries. Oxcarbazepine, sulfasalazine, COX-II inhibitors, and strontium ranelate were identified as new potential causes. In addition to sulfa drugs and beta-lactam antibiotics, quinolones were also a common cause. Only one acetaminophen-induced SJS was identified, while several medications (e.g., oseltamivir, terbinafine, isotretinoin, and sorafenib) labeled as carrying a risk of SJS/TEN by the FDA were not found to have caused any of the cases in the Asian countries investigated in this study.

Introduction: Acute fish liver intoxication, including hypervitaminosis A and hypervitaminosis D, may result from the ingestion of certain fish livers. The typical symptoms of hypervitaminosis A include nausea, headache, blurred vision, and cutaneous manifestations, such as flushing, vesicles formation, and desquamation. Hypervitaminosis D may result in hypercalcemia. We report a case of acute fish liver intoxication with systemic and cutaneous manifestations. Case: A 63-year-old male presented to the clinic with generalized desquamation and multiple clear-fluid filled flaccid vesicles after eating approximately two fist-sized portions (about 300–400 g) of cooked seerfish (Scomberomorus spp.) liver. Laboratory examination showed a high serum level of vitamin A and D, and hypercalcemia. Conclusions: Fish liver consumption from particular fish may result in acute hypervitaminosis A and D. In patients with skin detachment or blister formation, headache, drowsiness, and other symptoms and signs consistent with hypervitaminosis A and/or hypercalcemia, a history of fish intake should be sought, and a serum level of vitamin A and D should be measured.

BACKGROUND. Cytotoxic T lymphocyte–mediated (CTL-mediated) severe cutaneous adverse reactions (SCARs), including Stevens-Johnson syndrome (SJS) and toxic epidermal necrolysis (TEN), are rare but life-threatening adverse reactions commonly induced by drugs. Although high levels of CTL-associated cytokines, chemokines, or cytotoxic proteins, including TNF-α and granulysin, were observed in SJS-TEN patients in recent studies, the optimal treatment for these diseases remains controversial. We aimed to evaluate the efficacy, safety, and therapeutic mechanism of a TNF-α antagonist in CTL-mediated SCARs. METHODS. We enrolled 96 patients with SJS-TEN in a randomized trial to compare the effects of the TNF-α antagonist etanercept versus traditional corticosteroids. RESULTS. Etanercept improved clinical outcomes in patients with SJS-TEN. Etanercept decreased the SCORTEN-based predicted mortality rate (predicted and observed rates, 17.7% and 8.3%, respectively). Compared with corticosteroids, etanercept further reduced the skin-healing time in moderate-to-severe SJS-TEN patients (median time for skin healing was 14 and 19 days for etanercept and corticosteroids, respectively; P = 0.010), with a lower incidence of gastrointestinal hemorrhage in all SJS-TEN patients (2.6% for etanercept and 18.2% for corticosteroids; P = 0.03). In the therapeutic mechanism study, etanercept decreased the TNF-α and granulysin secretions in blister fluids and plasma (45.7%–62.5% decrease after treatment; all P < 0.05) and increased the Treg population (2-fold percentage increase after treatment; P = 0.002), which was related to mortality in severe SJS-TEN. CONCLUSIONS. The anti–TNF-α biologic agent etanercept serves as an effective alternative for the treatment of CTL-mediated SCARs. TRIAL REGISTRATION. ClinicalTrials.gov {"type":"clinical-trial","attrs":{"text":"NCT01276314","term_id":"NCT01276314"}}NCT01276314. FUNDING. Ministry of Science and Technology of Taiwan.

Background Increasing studies reported genetic susceptibility to drug hypersensitivity reactions, as exemplified by the HLA-A*31:01 and HLA-B*15:02 association with carbamazepine (CBZ)-induced hypersensitivity reactions, such as maculopapular exanthema (MPE), drug rash with eosinophilia and systemic symptoms (DRESS), and Stevens–Johnson syndrome (SJS)/toxic epidermal necrolysis (TEN). Objective To carry out a comprehensive analysis on the clinical spectrum and HLA genotype–phenotype correlations in CBZ-induced hypersensitivity reactions. Methods We analyzed the clinical information of 194 patients with CBZ hypersensitivity (51 MPE, 23 DRESS, 112 SJS/TEN, and 8 cases with other phenotypes), and 152 CBZ-tolerant controls. All are Han Chinese. We examined the HLA-A/HLA-B genotypes, gene dosage, and drug dosage effects. Results CBZ-SJS/TEN showed the strongest association with the HLA-B*15:02 allele (Pc=5.8×10 −43 ; odds ratio (OR) (95% CI)=97.6(42.0–226.8)), in which HLA-B*15:02 was identified in all patients (25/25) with SJS/TEN with >5% body surface area (BSA) skin detachment, but lost its 100% association (85.1%, 74/87) in SJS with HLA-B*40:01 showed negative association with CBZ-induced SJS/TEN ((Pc=8.3×10 −5 ; OR (95% CI)=0.22(0.1–0.4)). By comparison, CBZ-induced MPE/DRESS had no association with HLA-B*15:02 , but linked to HLA-A*31:01 (Pc=2.7×10 −3 ; OR (95% CI)=6.86(2.4–19.9), and HLA-B*51:01 (Pc=0.01; OR (95% CI)=4.56(2.0–10.5)). No gene dosage or CBZ dosage effects was observed. Conclusion This study reported the different strength of HLA association with CBZ hypersensitivity in Han Chinese. With the increasing application of pharmacogenetic markers, the HLA genotype–phenotype correlations and the results of the test need to be carefully interpreted for CBZ-induced hypersensitivity reactions.

Objective:To investigate the risk and genetic association of oxcarbazepine-induced cutaneous adverse reactions (OXC-cADRs), including Stevens-Johnson syndrome/toxic epidermal necrolysis (SJS/TEN), in Asian populations (Chinese and Thai).Methods:We prospectively enrolled patients with OXC-cADRs in Taiwan and Thailand from 2006 to 2014, and analyzed the clinical course, latent period, drug dosage, organ involvement, complications, and mortality. We also investigated the carrier rate ofHLA-B*15:02andHLA-A*31:01of patients with OXC-cADRs and compared to OXC-tolerant controls. The incidence of OXC-SJS/TEN was compared with carbamazepine (CBZ)–induced SJS/TEN according to the nationwide population dataset from the Taiwan National Health Insurance Research Database.Results:We enrolled 50 patients with OXC-cADRs, including 20 OXC-SJS/TEN and 6 drug reaction with eosinophilia and systemic symptoms, of Chinese patients from Taiwan and Thai patients from Thailand. OXC-cADRs presented with less clinical severity including limited skin detachment (all ≦5%) and no mortality. There was a significant association betweenHLA-B*15:02and OXC-SJS (p= 1.87 × 10−10; odds ratio 27.90; 95% confidence interval [CI] 7.84–99.23) in Chinese and this significant association was also observed in Thai patients. The positive and negative predictive values ofHLA-B*15:02for OXC-SJS/TEN were 0.73% and 99.97%, respectively.HLA-A*31:01was not associated with OXC-cADRs. The incidence and mortality of OXC-SJS/TEN was lower than CBZ-STS/TEN in new users (p= 0.003; relative risk 0.212; 95% CI 0.077–0.584).Conclusions:Our findings suggest thatHLA-B*15:02is significantly associated with OXC-SJS in Asian populations (Chinese and Thai). However, the severity and incidence of OXC-SJS/TEN are less than that of CBZ-SJS/TEN. The need for preemptiveHLA-B*15:02screening should be evaluated further.

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 (SJS) and toxic epidermal necrolysis (TEN) are life-threatening adverse drug reactions characterized by massive epidermal necrosis, in which the specific danger signals involved remain unclear. Here we show that blister cells from skin lesions of SJS-TEN primarily consist of cytotoxic T lymphocytes (CTLs) and natural killer (NK) cells, and both blister fluids and cells were cytotoxic. Gene expression profiling identified granulysin as the most highly expressed cytotoxic molecule, confirmed by quantitative PCR and immunohistochemistry. Granulysin concentrations in the blister fluids were two to four orders of magnitude higher than perforin, granzyme B or soluble Fas ligand concentrations, and depleting granulysin reduced the cytotoxicity. Granulysin in the blister fluids was a 15-kDa secretory form, and injection of it into mouse skin resulted in features mimicking SJS-TEN. Our findings demonstrate that secretory granulysin is a key molecule responsible for the disseminated keratinocyte death in SJS-TEN and highlight a mechanism for CTL- or NK cell—mediated cytotoxicity that does not require direct cellular contact. Adverse drug reactions (ADRs) account for 6–7% of all hospital admissions and remain a major clinical problem 1 . Among them, SJS

Cutaneous verrucous carcinoma is a rare variant of low-grade squamous cell carcinoma. It usually involves distal extremities and is often misdiagnosed as giant warts. Multiple cutaneous verrucous carcinomas are rare in the English-language literature. We describe a 41-year-old man with multiple verrucous plaques on both feet and ankles, as well as the left thigh. Immunohistochemical study with proliferating cell nuclear antigen revealed positive staining of the basal and suprabasal layers. The patient's condition was successfully treated with systemic acitretin.

TREM-like transcript-1 (TLT-1) was initially characterized as the putative inhibitory receptor within the TREM locus on chromosome 6 and was suggested to play a critical role in modulating TREM-associated immunity. Recently, TLT-1 was found not to function as an inhibiting member of the TREM family; however, it may play a significant role in maintaining vascular hemostasis, coagulation, and inflammation at sites of injury through its location in platelets. In this study, we have successfully generated a monoclonal antibody that can be applied to assays, including enzyme-linked immunosorbent assay (ELISA), Western immunoblotting, immunofluorescence, and Fluorescence-Activated Cell Sorter (Becton-Dickinson) (FACS), for the study of TLT-1 functions in physiological and pathological conditions.

Cutaneous sporotrichosis is a chronic granulomatous fungal infection caused by Sporothrix schenckii with worldwide distribution. Its traditional diagnosis is time-consuming and difficult to differentiate from that of a clinical sporotrichoid lesion caused by various pathogens. In this study, a nested PCR assay for the detection of S. schenckii was evaluated by using a sequence of 18S rRNA gene as a target. For the examination of specificity and sensitivity, five clinical isolates with 1 ATCC 10213 strain of S. schenckii , 10 strains of clinical common fungi, 3 strains of Mycobacterium spp., Staphylococcus aureus , and normal human skin tissue were used. The expected fragment was amplified from six S. schenckii isolates in the first round and nested PCR but not from other microorganisms and human DNA. Their sequences were 100% identical to the S. schenckii 18S rRNA gene sequence deposited in GenBank. A detection limit of 40 fg of S. schenckii DNA extract was determined with ethidium bromide staining. Serial dilution studies demonstrated that the nested PCR could detect a DNA amount of 1 CFU of S. schenckii in tissue samples. We further investigated the nested PCR assay for the detection of S. schenckii from the tail tissues of 5 experimentally infected mice and from the clinical biopsy specimens of 12 patients with sporotrichosis confirmed by culture or histochemical staining. The nested PCR assay was positive in all 5 infected mice and in 11 of the 12 clinical specimens. The high sensitivity and specificity of this nested PCR indicate that the assay can provide rapid diagnosis with sufficient accuracy to be clinically useful for patients with sporotrichosis.

Background. The cutaneous manifestations of human enterovirus (HEV) infection are usually limited, such as hand-foot-mouth disease. By comparison, Stevens-Johnson syndrome (SJS) is a life-threatening severe cutaneous adverse reaction (SCAR), mainly caused by drugs. During the HEV outbreaks in 2010–2012 in Taiwan, we identified 21 patients who developed widespread blistering mucocutaneous reactions without any suspected drug causality. Methods. We screened possible pathogen(s) for detecting human herpes virus (HHV1–HHV7), HEV, or Mycoplasma pneumoniae infections using throat swab virus cultures, real-time PCR, DNA sequencing, immunochemistry and electron microscopy analyses. Results. Coxsackievirus A6 (CVA6) DNA was identified in the blistering skin lesions in 6 of 21 patients. Cytotoxic T lymphocytes and natural killer cells expressing granulysin predominantly infiltrated into the skin lesions, sharing the histopathological features with SJS. Intact CVA6 viral particles were identified in the blister fluids and skin lesions by electron microscopy. The phylogenetic analysis of the viral genome showed the CVA6 DNA sequence sharing higher similarity (97.6%–98.1%) to CVA6 strains reported from Finland at 2008. Conclusions. This study identifies a new variant of CVA6 as the causative agent for severe mucocutaneous blistering reactions mimicking SCAR. An awareness of this unusual presentation of HEV infection is needed in the epidemic area.

Drug rash with eosinophilia and systemic symptoms (DRESS) is a severe cutaneous drug reaction. Although the severity-of-illness score (SCORTEN) has been proposed for toxic epidermal necrolysis (TEN) for 10 years, a prognostic score for DRESS is still lacking. To identify prognostic factors of DRESS patients during hospitalization in one medical health system in Taiwan. We retrospectively reviewed all patients with DRESS diagnosed by dermatologists in Chang Gung Memorial Hospital (CMGH) Health System from 2001 to 2010. To study prognostic factors, we collected data at early disease and maximal disease stages. 91 individuals, including 13 dead patients, were evaluated. Five independent prognostic factors of death were found: heart rate > 90/min, white blood cells >12,000/mm3 and respiratory rate >20/min (at early disease stage), coagulopathy and gastrointestinal bleeding (at maximal disease stage). In addition, systemic inflammatory response syndrome (SIRS) occurred at a much higher percentage among non-survivors throughout hospitalization. We found tachycardia, leukocytosis, tachypnea, coagulopathy, gastrointestinal bleeding and SIRS were associated with a poor outcome in DRESS patients. DRESS patients with persistent SIRS during hospitalization were also associated with a higher mortality risk. Early recognition and prompt intervention in these factors may improve outcome.

Itchy maceration of the toe webs is common in warm and humid weather. Some cases do not respond to treatment for tinea or eczema.Patients with foot intertrigo with a poor response to antifungal or antiinflammatory treatment from 2004 to 2009 were included in this study. Their general characteristics were recorded. Bacterial and fungal cultures as well as potassium hydroxide preparations were performed.We recorded 32 episodes of foot bacterial intertrigo in 17 patients. The disease was more common in men (82%) and the mean age of the patients was 59 years. The main clinical finding was maceration of the toe webs. The majority of bacterial cultures grew mixed pathogens (93%). Pseudomonas aeruginosa, Enterococcus facealis and Staphylococcus aureus were the most common pathogens. Autoeczematization was present in 50% of the 32 disease episodes.Foot bacterial intertrigo is not a rare condition and can easily be confused with interdigital tinea or eczematous dermatitis. Proper identification of bacterial organisms is critical for early effective antibiotic therapy. Patients should be instructed about proper foot hygiene, which is important to prevent recurrent infections.

Background Drug rash with eosinophilia and systemic symptoms (DRESS), a group of non-blistering severe cutaneous adverse drug reactions (SCADRs), is characterized by skin rash and multiorgan involvement. Details of this reaction have not been reported in the literature so far. Aim We investigate clinical and pathological features and prognosis of DRESS and hope this study will provide data concerning this disorder in Taiwan. Methods From January 2001 to June 2006, a total of 30 patients, diagnosed with DRESS, were enrolled and evaluated for demographic characteristics, pathological findings, complications and outcome. Results Patient ages ranged from 13 to 78, with an equal sex ratio. The most common offending drug was allopurinol followed by carbamazepine. Pathologic changes observed were lichenoid dermatitis, erythema multiforme, pseudolymphoma and vasculitis. Impairment of liver and renal functions and blood dyscrasia were frequent complications. Active infection or reactivation of HHV-6 was observed in 7 of 11 patients studied serologically. Two patients developed type 1 diabetes mellitus. The mortality rate was 10% (3 of 30). Conclusions DRESS is a heterogeneous group of life-threatening conditions. The leading drug in DRESS in Taiwan is allopurinol. High eosinophil count and multiple underlying diseases are poor prognostic factors in patients with DRESS.

Background The scalp is a unique anatomic region, in which pilosebaceous follicles are concentrated. Objective We sought to investigate demographic characteristics and histologic distributions of malignant scalp tumors. Methods Primary and metastatic scalp malignancies diagnosed histopathologically between 1983 and 2003 were reviewed. Age at diagnosis, sex, and histologic types were analyzed. Results A total of 398 Taiwanese patients (200 males, 198 females) were selected. Age at diagnosis ranged from 3 to 103 years. Most malignant scalp tumors (69.8%) occurred in those 50 years or older. Basal (41.2%) and squamous (16.6%) cell carcinomas were the most common histologic types. Surprisingly, metastatic tumors (12.8%) came in third, in which lung cancers were the most frequent primary tumor in both male and female patients. Limitations In our series, the case number of metastatic scalp malignancies was underestimated because not all patients with metastatic scalp tumors received a scalp skin biopsy. Conclusion Because a wide spectrum of primary and metastatic malignancies can occur on the scalp, scalp inspection should be included in general screening for either skin or internal cancers.

Stevens-Johnson syndrome and the related disease toxic epidermal necrolysis are life-threatening reactions of the skin to particular types of medication. Here we show that there is a strong association in Han Chinese between a genetic marker, the human leukocyte antigen HLA-B*1502, and Stevens-Johnson syndrome induced by carbamazepine, a drug commonly prescribed for the treatment of seizures. It should be possible to exploit this association in a highly reliable test to predict severe adverse reaction, as well as for investigation of the pathogenesis of Stevens-Johnson syndrome.

Urticarial vasculitis has rarely been described in association with polymyositis. We report the case of a 37-year-old man with dermatomyositis and nasopharyngeal carcinoma who presented initially with urticarial vasculitis. The lesions of urticarial vasculitis were initially photodistributed, indicating photosensitivity. The patient was treated with systemic steroids, chemotherapy (cisplatin and fluorouracil), and radiation therapy. The tumor and urticarial vasculitis completely resolved, and the myositis improved.

We describe a new method for treating livedoid vasculopathy. The typical presentation of livedoid vasculopathy includes chronic, recurrent painful ulcers, satellite scar-like atrophy and telangiectasia involving the lower extremities. Histologically, these lesions show areas of ulceration and dermal vessel occlusion without frank inflammatory cell infiltration. There is currently no satisfactory therapy available for this disease. Hyperbaric oxygen (HBO) has recently established itself as one of the most effective methods of treating ischaemic wounds, including diabetic ulcers. We used this therapy in two patients whose lesions were resistant to multiple therapeutic modalities. Not only did their ulcers respond rapidly to the HBO therapy, but the disturbing wound pain also resolved at the same time. To our knowledge, this is the first successful trial of HBO therapy in livedoid vasculopathy. We believe this to be a very promising new therapy for livedoid vasculopathy and to be worth further investigation.

A 58-year-old man with diabetes had fever and chills 5 days after ingestion of raw seafood. Nausea, vomiting, watery diarrhea, bilateral calf pain, and neck stiffness subsequently developed. Generalized edema and ecchymotic patches with a vesiculobullous eruption appeared on the extremities. Four blood cultures were positive for Vibrio cholerae non-01. The patient was successfully treated with antibiotics. This is the first documented case of V. cholerae non-01 septicemia with cutaneous lesions and meningitis in Taiwan.

Importance The antiepileptic drug phenytoin can cause cutaneous adverse reactions, ranging from maculopapular exanthema to severe cutaneous adverse reactions, which include drug reactions with eosinophilia and systemic symptoms, Stevens-Johnson syndrome, and toxic epidermal necrolysis. The pharmacogenomic basis of phenytoin-related severe cutaneous adverse reactions remains unknown. Objective To investigate the genetic factors associated with phenytoin-related severe cutaneous adverse reactions. Design, Setting, and Participants Case-control study conducted in 2002-2014 among 105 cases with phenytoin-related severe cutaneous adverse reactions (n=61 Stevens-Johnson syndrome/toxic epidermal necrolysis and n=44 drug reactions with eosinophilia and systemic symptoms), 78 cases with maculopapular exanthema, 130 phenytoin-tolerant control participants, and 3655 population controls from Taiwan, Japan, and Malaysia. A genome-wide association study (GWAS), direct sequencing of the associated loci, and replication analysis were conducted using the samples from Taiwan. The initial GWAS included samples of 60 cases with phenytoin-related severe cutaneous adverse reactions and 412 population controls from Taiwan. The results were validated in (1) 30 cases with severe cutaneous adverse reactions and 130 phenytoin-tolerant controls from Taiwan, (2) 9 patients with Stevens-Johnson syndrome/toxic epidermal necrolysis and 2869 population controls from Japan, and (3) 6 cases and 374 population controls from Malaysia. Main Outcomes and Measures Specific genetic factors associated with phenytoin-related severe cutaneous adverse reactions. Results The GWAS discovered a cluster of 16 single-nucleotide polymorphisms in CYP2C genes at 10q23.33 that reached genome-wide significance. Direct sequencing of CYP2C identified missense variant rs1057910 ( CYP2C9*3 ) that showed significant association with phenytoin-related severe cutaneous adverse reactions (odds ratio, 12; 95% CI, 6.6-20; P =1.1 × 10 −17 ). The statistically significant association between CYP2C9*3 and phenytoin-related severe cutaneous adverse reactions was observed in additional samples from Taiwan, Japan, and Malaysia. A meta-analysis using the data from the 3 populations showed an overall odds ratio of 11 (95% CI, 6.2-18; z =8.58; P CYP2C9*3 association with phenytoin-related severe cutaneous adverse reactions. Delayed clearance of plasma phenytoin was detected in patients with severe cutaneous adverse reactions, especially CYP2C9*3 carriers, providing a functional link of the associated variants to the disease. Conclusions and Relevance This study identified CYP2C variants, including CYP2C9*3 , known to reduce drug clearance, as important genetic factors associated with phenytoin-related severe cutaneous adverse reactions.

Stevens-Johnson syndrome and the related disease toxic epidermal necrolysis are life-threatening reactions of the skin to particular types of medication. Here we show that there is a strong association in Han Chinese between a genetic marker, the human leukocyte antigen HLA-B*1502, and Stevens-Johnson syndrome induced by carbamazepine, a drug commonly prescribed for the treatment of seizures. It should be possible to exploit this association in a highly reliable test to predict severe adverse reaction, as well as for investigation of the pathogenesis of Stevens-Johnson syndrome.