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1.
Reduction of interleukin‐10 production by B cells in intractable toxic epidermal necrolysis
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Amiko Hakuta Hiroyuki Fujita Miwa Kanaoka Midori Watanabe Kanako Izumi Tomoya Watanabe Noriko Komitsu Munenari Itoh Katsumi Tanito Yukitoshi Takahashi Michiko Aihara 《The Journal of dermatology》2015,42(8):804-808
Several interleukin (IL)‐10 producing B‐cell subsets have been identified recently. However, few studies have examined the role of them in toxic epidermal necrolysis (TEN). We describe a 41‐year‐old woman with TEN who had B‐cell lymphoma and a history of treatments including B‐cell depletion therapy. Her re‐epithelization was still ongoing after 7 months, despite treatments. To investigate her immune system, we compared cytokine and chemokine production from B cells and non‐B cells isolated from the patient and another non‐lymphoma TEN patient. IL‐10 production from B cells decreased in the patient compared with the control TEN‐only patient. Cytokine and chemokine levels from non‐B cells involved in inflammation were elevated in the patient compared with the control patient. In conclusion, this study demonstrates that IL‐10 from B cells as well as regulatory T cells is critical in the pathogenesis of TEN, and that B‐cell dysfunction based on B‐cell lymphoma and B‐cell depletion therapy may be involved in the intractability of TEN. 相似文献
2.
Hikaru Takeda Yoshihiko Mitsuhashi Shigeo Kondo Yu-ichi Kato Katsufumi Tajima 《The Journal of dermatology》1997,24(10):635-641
Toxic epidermal necrolysis (TEN) is a severe blistering skin disease of high mortality. TEN may occur after bone marrow transplantation (BMT). In such cases, TEN have been attributed to graft-versus-host disease (GVHD) or an adverse drug reaction. It is very difficult to distinguish the causes of TEN after BMT. We report a 21-year-old Japanese man who developed TEN eight days after BMT, evaluate the differential diagnosis of hyperacute GVHD and an adverse drug reaction, and deduce that hyperacute GVHD was the more likely pathogenesis of TEN in this patient. 相似文献
3.
Fang Wang Xuemei Gao Xiaohong Chen Xuhua Tang Haihong Chen Jiande Han 《The Journal of dermatology》2019,46(11):1035-1038
Interstitial lung disease (ILD) is a rare complication of Stevens–Johnson syndrome/toxic epidermal necrolysis (SJS/TEN). In this study, we present the case of a 33‐year‐old woman who was diagnosed with ILD related to SJS/TEN overlap syndrome. Surprisingly, the patient did not respond to combination therapy with steroids and i.v. immunoglobulin, but rapidly improved after two doses of etanercept treatment. To our knowledge, this is the first case of SJS/TEN‐induced ILD that was successfully treated with etanercept. We reviewed another two cases of ILD associated with SJS/TEN, and found that unlike the other cases, in the present case, ILD occurred early in the course of the disease and rapidly improved after etanercept injection. We discovered that in the present patient, the serum interleukin‐6 level increased during the progressive stage and declined after the initiation of treatment with etanercept. 相似文献
4.
Tomoko Nomiyama M.D. Akiko Arakawa M.D. Sayoko Hattori M.D. Keisuke Konishi M.D. Hideya Takenaka M.D. Norito Katoh M.D. 《Pediatric dermatology》2013,30(1):105-108
Abstract: Treatment of infantile acute lymphocytic leukemia (ALL) may cause failure to thrive and hypogonadism due to hypopituitarism induced by chemotherapy and whole‐brain radiotherapy. We report the case of a 22‐year‐old girl with a genetic predisposition to pattern hair loss who developed inveterate diffuse alopecia. The patient had onset of ALL at 8 years old and underwent bone marrow transplantation (BMT). Diffuse alopecia gradually advanced over her whole body. Her vellus scalp hair gradually came out, and hair loss progressed again at 8 years, after BMT. She later developed iatrogenic failure of secretion of estrogen and was treated with estrogen substitution therapy for 14 months from the age of 20. There was a small increase in the volume of hair during therapy, but alopecia returned to the former level after the therapy was suspended. Histopathologic examinations of the scalp performed during estrogen substitution therapy and 2 years after suspension of the therapy showed a 60% decrease in the number of hair follicles and prominent development of vellus hair. We conclude that estrogen influenced hair growth in the context of a genetic predisposition for pattern hair loss in this case. 相似文献
5.
Toxic epidermal necrolysis (TEN) is a rare life-threatening disease characterized by blister formation and erosion over the entire body surface resulting from extensive keratinocyte death. We reported a case of TEN that developed in a 68-year-old man with hepatitis C virus liver cirrhosis three weeks after treatment with allopurinol. Exanthema developed as multiple target-like lesions, and erythroderma within five days without forming visible erosive lesions or obvious mucous membrane involvement. Reactivation of human herpes virus-6 or other herpes virus was not detected by polymerase chain reaction or serologic studies, and drug-induced hypersensitivity syndrome was ruled out. The finding of panepidermal necrosis on histopathological examination led to a diagnosis of TEN. Exanthema, fever and renal dysfunction responded to oral prednisolone, but the patient died of liver failure. Cases of TEN with histopathologically proven panepidermal necrosis without apparent blisters or erosions have rarely been reported because they do not fulfill the previously proposed diagnostic criteria for TEN. This finding, the discrepancy between the clinical and the histopathological manifestations, should not be overlooked in a case suspicious of TEN, and the importance of the histopathological examination should be emphasized in the differential diagnosis of TEN. 相似文献
6.
Stevens–Johnson syndrome (SJS) and toxic epidermal necrolysis (TEN) are rare but life threatening cutaneous reactions that are most commonly caused by exposure to medications. This review assesses the efficacy and safety of cyclosporine therapy for SJS, TEN, and SJS/TEN overlap. A literature review was conducted in PubMed using the MeSH terms TEN, SJS, and cyclosporine. Five case series and one meta‐analysis were analyzed. From review of the existing literature, cyclosporine appears to not only have a mortality benefit in the treatment of SJS/TEN, but also a relatively safe side effect profile. 相似文献
7.
Grgurević I Pejsa V Morović-Vergles J Dobrić I Gasparović V Tudorić N 《Acta dermatovenerologica Croatica : ADC》2008,16(3):133-137
Toxic epidermal necrolysis (TEN) is one of the most threatening adverse reactions to various drugs. No case of concomitant occurrence TEN and severe granulocytopenia following the treatment with cefuroxime has been reported to date. Herein we present a case of TEN that developed eighteen days of the initiation of cefuroxime axetil therapy for urinary tract infection in a 73-year-old woman with chronic renal failure and no previous history of allergic diathesis. The condition was associated with severe granulocytopenia and followed by gastrointestinal hemorrhage, severe sepsis and multiple organ failure syndrome development. Despite intensive medical treatment the patient died. The present report underlines the potential of cefuroxime to simultaneously induce life threatening adverse effects such as TEN and severe granulocytopenia. Further on, because the patient was also taking furosemide for chronic renal failure, the possible unfavorable interactions between the two drugs could be hypothesized. Therefore, awareness of the possible drug interaction is necessary, especially when given in conditions of their altered pharmacokinetics as in case of chronic renal failure. 相似文献
8.
Karina L. Vivar Maria Deschaine Jane Messina Jennifer M. Divine Alejandro Rabionet Nishit Patel Michael A. Harrington Lucia Seminario‐Vidal 《Journal of cutaneous pathology》2017,44(4):381-384
Nivolumab is a programmed cell death receptor‐1 (PD‐1) antibody used in the treatment of metastatic or unresectable melanoma. Cutaneous reactions are the most common adverse events reported with these agents and are rarely severe or life‐threatening. Here we present a case report describing the clinicopathological findings of a patient with a fatal toxic epidermal necrolysis (TEN) eruption associated with use of nivolumab for treatment of metastatic melanoma. The patient developed a pruritic, morbiliform eruption, which slowly progressed over 3 months to a tender, exfoliative dermatosis. Histology initially showed interface dermatitis and subsequently revealed full thickness epidermal necrosis. The diagnosis of TEN was made. From initial biopsy to TEN presentation, there was an increase in the number of CD8+ lymphocytes within the dermal–epidermal junction and an increase of programmed death ligand 1 (PD‐L1) expression in both lymphocytes and keratinocytes. Despite treatment with infliximab, high‐dose steroids and intravenous immunoglobulin, the patient expired. Herein we describe what we believe is the second case of TEN associated with anti‐PD1 therapy reported in the literature. Increased expression of PD‐L1 by immunohistochemistry was observed as the eruption progressed to TEN. Early diagnosis and treatment is necessary in these fatal TEN reactions secondary to the anti‐PD‐1 antibody therapies. 相似文献
9.
C.‐H. Hu N.‐J. Chang E.K.‐W. Liu S.‐S. Chuang W.‐H. Chung J.‐Y. Yang 《Journal of the European Academy of Dermatology and Venereology》2013,27(5):628-633
Background Toxic epidermal necrolysis syndrome (TEN) is a rare, life‐threatening, drug‐related skin reaction with a high mortality rate. To date, only a few studies with insufficient sample sizes have been conducted to analyse SCORTEN in Asian populations with TEN. Objective To analyse SCORTEN and other related factors that affect TEN patients in Taiwan. Methods A retrospective review of medical records of 101 patients with TEN from 1992 to 2009. Results There were 62 cases of adverse reactions to a single medication and 39 cases of idiopathic reaction, from multiple medications, or infectious pathogens, of 101 TEN patients. Of the seven individual SCORTEN parameters, only associate malignancy, detached or compromised body surface area >10%, serum urea and bicarbonate were statistically significant in the multivariate analysis. Factors such as 1.5 times baseline serum creatinine levels, urine output of less than 0.5 mL/kg for 6 h and acute renal failure were connected with subsequent mortality. Conclusion The SCORTEN score is effective in predicting the outcome in Taiwanese TEN patients. A number of factors are predictors of mortality. In our study, we determine renal insufficiency and failure to be a marker for predicting a poor outcome. 相似文献
10.
Kamada N Kinoshita K Togawa Y Kobayashi T Matsubara H Kohno M Igari H Kuriyama T Nakamura M Hirasawa H Shinkai H 《The Journal of dermatology》2006,33(9):616-622
Patients with toxic epidermal necrolysis (TEN) have been known to have various complications. Though pulmonary complications are often observed, they usually show an acute form; however, chronic complications are quite rare and little is known about either their incidences or clinical manifestations. We herein report a 33‐year‐old man who presented with chronic pulmonary complications after a recovery from TEN. At the onset of TEN, he had severe respiratory failure and artificial ventilation was instituted. Despite being extubated successfully, respiratory failure reappeared 1 month later. A diagnosis of chronic bronchitis with severe obstructive ventilatory impairment and bronchiectasis was made and he was treated with steroids, bronchodilators and antibiotics, however, he died 1.5 years after the onset of TEN. There have been 13 reported cases of chronic pulmonary complications with TEN or Stevens–Johnson syndrome (SJS) in the English published work. Such cases are usually classified into chronic bronchitis/bronchiolitis with obstructive change (including bronchiolitis obliterans and bronchiolitis obliterans organizing pneumonia), respiratory tract obstruction and bronchiectasis. Approximately 40% of all such patients die while the surviving continue to suffer from these complications because no curative therapy yet exists. As a result, the prognosis seems to be poor. The relationship between TEN and these chronic pulmonary complications remains to be elucidated. Interestingly, our patient was asymptomatically anti‐Ro/SS‐A positive at the onset of TEN. In addition, eccrine gland involvement and an extremely high level of serum salivary amylase were observed at the onset of TEN, furthermore, Sjögren‐like symptoms occurred after recovery from TEN. These findings suggested that the Sjögren‐like autoimmune abnormalities induced by anti‐Ro/SS‐A correlated with the development of chronic pulmonary complications in our patient. 相似文献
11.
The association of HLA B*15:02 allele and Stevens–Johnson syndrome/toxic epidermal necrolysis induced by aromatic anticonvulsant drugs in a South Indian population
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Background
The presence of HLA‐B*15:02 allele is considered a risk factor for development of Stevens–Johnson syndrome/toxic epidermal necrolysis (SJS/TEN) in patients taking aromatic anticonvulsant drugs like carbamazepine and phenytoin. The genetic association is ethnicity specific. Testing for HLA‐B*15:02 allele is suggested as a prerequisite before starting carbamazepine in certain ethnic groups. There are only a few/no studies from south India on HLA association of SJS/TEN.Aims
To identify any association between HLA‐B*15:02 allele and SJS/TEN induced by carbamazepine/phenytoin among native population.Methods (including settings, design, and statistical analysis used)
A case–control study done in a tertiary care center at Kottayam in Kerala state of south India. Cases were 12 native patients who developed SJS/TEN owing to aromatic anticonvulsant drugs (phenytoin – 8; carbamazepine – 4), and controls were 11 persons tolerant to these drugs from unrelated families of the same ethnic group. HLA‐B typing was done by PCR SSP method.Results
There was only one HLA‐B*15:02 carrier among cases and controls. He/she had SJS/TEN induced by carbamazepine.Conclusions
Association of HLA‐B*15:02 with phenytoin‐induced SJS/TEN is rare in the population studied. The one limitation of the study was the small sample size. 相似文献12.
Amanda Leal Rocha Alessandra Figueiredo De Souza Laiz Fernandes Mendes Nunes Nayara Dias de Souza Cunha Clia Regina Moreira Lanza Denise Vieira Travassos Tarcília Aparecida da Silva 《Pediatric dermatology》2019,36(1):e27-e30
Drug‐induced reactions are complications associated with high mortality and significant morbidity. Stevens–Johnson Syndrome (SJS) and toxic epidermal necrolysis (TEN) are examples of these conditions, which are characterized by skin and mucous lesions. Here, we report a case of a 9‐year‐old girl who presented with blisters associated with an extensive vesicular rash and multiple ulcerations on the lips and oral cavity. A drug‐induced hypersensitivity reaction to antibiotics was suspected, and a diagnosis of TEN was made. The patient was managed with withdrawal of the suspected causative agent, and the oral lesions were treated with low‐level laser therapy (LLLT) and oral hygiene. This case highlights that TEN requires interdisciplinary intervention with dental assistance and follow‐up to improve symptoms, nutrition, systemic condition, and quality of life. 相似文献
13.
A. De Sica‐Chapman G. Williams N. Soni C.B. Bunker 《The British journal of dermatology》2010,162(4):860-865
Background: Toxic epidermal necrolysis (TEN) is a rare but life‐threatening, allergic drug reaction. Skin blistering with epidermal and mucosal necrolysis with subsequent detachment from an inflamed underlying dermis is a hallmark of the condition. The pathogenesis of TEN is not well understood, accounting for controversies about its management and significant delay in initiating potentially beneficial therapy. There are no management protocols based on a robust evidence base. Objectives: Prompt recognition of the diagnosis and consensus on early management initiatives are necessary in order to improve outcomes and survival in TEN. To date, TEN management has been directed at arresting the allergic reaction and treating the complications. We have identified a need for specific medical interventions to accelerate wound regeneration. This approach has not previously been adopted in the management of TEN. Methods: We observed that in two cases of severe TEN, dramatic re‐epithelialization and recovery coincided with the introduction of granulocyte colony‐stimulating factor (G‐CSF) for neutropenia. We explain how addition of the G‐CSF promotes recovery from TEN by enhanced bioregeneration of the damaged tissues through accelerated re‐epithelialization. Conclusion: G‐CSF has been used for severe neutropenia in TEN, but we recommend and explain why, as in our Chelsea and Westminster protocol, G‐CSF should be considered in treating severe TEN irrespective of the severity of neutropenia. 相似文献
14.
Adalimumab administration after infliximab therapy is a successful treatment strategy for generalized pustular psoriasis
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Ai Matsumoto Mayumi Komine Masaru Karakawa Megumi Kishimoto Mamitaro Ohtsuki 《The Journal of dermatology》2017,44(2):202-204
We report a case of a 70‐year‐old woman with generalized pustular psoriasis (GPP) who responded well to infliximab therapy and adalimumab therapy after secondary failure of infliximab therapy, but did not respond to ustekinumab therapy. We speculate that the pathogenic factor in this case favored anti‐tumor necrosis factor (TNF)‐α therapy to anti‐interleukin‐12/23 therapy. Herein, we also briefly present three additional cases of treatment with adalimumab after secondary failure of infliximab. GPP is often difficult to treat, and no placebo‐controlled trials have been conducted to guide the use of biologics against it because of a paucity of cases. Infliximab and adalimumab are anti‐TNF‐α antibodies that specifically block the interaction of TNF‐α with its receptors. Infliximab has been reported to be effective, with a rapid clearance of symptoms, even in cases of severe GPP. Adalimumab could be a good biologic candidate that can be administrated after secondary failure of infliximab therapy. 相似文献
15.
Emanuela GUBINELLI Flora CANZONA Tiziano TONANZI Desanka RASKOVIC Biagio DIDONA 《The Journal of dermatology》2009,36(3):150-153
Toxic epidermal necrolysis (TEN) is a rare and acute severe adverse reaction to drugs, characterised by massive apoptosis and widespread epidermal and mucosal detachment. Although no gold standard therapy exists, human i.v. immunoglobulins have recently been described as an effective treatment for this disease. We report a case of phenobarbital-induced TEN in a 59-year-old white woman where the epidermal detachment stopped 48 h after beginning the etanercept treatment with complete healing after 20 days. To the best of our knowledge, this is only the second reported case of TEN successfully treated with etanercept. 相似文献
16.
Sugiyama A Takeuchi S Fukagawa S Moroi Y Yoshimoto G Miyamoto T Akashi K Furue M 《The Journal of dermatology》2012,39(2):172-175
A 50-year-old female patient, who had had a long-term history of myelodysplastic syndrome and type II diabetes mellitus, had developed acute myelogenous leukemia and received allogeneic bone marrow transplantation (BMT). She was being treated with tacrolimus, methotrexate and prednisolone for prophylaxis and treatment of graft-versus-host disease, and with intensive insulin therapy for better glycemic control. The patient suddenly developed marked leg edema at 27 days after starting intensive insulin therapy (on day 40 after BMT) without coexistence or exacerbation of apparent causes such as renal failure, cardiac dysfunction or leg thrombosis around the onset of leg edema. Interestingly, the leg edema regressed soon after daytime hyperglycemia and intensive insulin therapy were performed. Histopathological examination revealed slight dermal edema and small bullae with little inflammatory infiltration but no signs of autoimmune blistering diseases or vasculitis. These findings indicate that the present case may be considered a form of so-called insulin edema occurring during intensive insulin therapy after BMT. 相似文献
17.
Yongsheng Yang MSc Jinhua Xu MD Feng Li MD Xiaohua Zhu MD 《International journal of dermatology》2009,48(10):1122-1128
Background Toxic epidermal necrolysis (TEN) and Stevens–Johnson Syndrome (SJS) are drug‐induced diseases with no well‐established treatments. The application of corticosteroid therapy is controversial. Intravenous immunoglobulin (IVIG) therapy is emerging as a promising new method for the treatment of these two diseases. The efficacy of combination therapy of IVIG and corticosteroid in the treatment of TEN/SJS has seldom been reported. Methods Sixty‐five consecutive patients with either TEN or SJS, admitted over a 14‐year period from January 1993 to October 2007, were treated with corticosteroid and analyzed retrospectively using SCORTEN, a severity‐of‐illness scoring system for TEN/SJS prognosis, to evaluate efficacy. For patients admitted after January 2001, additional therapy with a dose of 0.4 g/kg/day of IVIG for 5 days was applied. Results In the 45 patients with TEN treated without IVIG, 8.63 patients were expected to die based on the SCORTEN system, but 10 deaths were observed. Standardized mortality ratio (SMR) analysis [(Σobserved deaths/Σexpected deaths) × 100] suggested that patients with TEN treated with systemic corticosteroid were 16% more likely to die than those treated with routine therapy (SMR = 1.16; 95% confidence interval, 0.56–2.13). In the further study of combination therapy, 12 patients with TEN and eight patients with SJS were admitted. There were two deaths in the TEN group and one death in the SJS group, with 3.51 deaths expected on the basis of the SCORTEN system. SMR analysis showed that combination therapy had a tendency to reduce the mortality rate of TEN (SMR = 0.85; 95% confidence interval, 0.18–2.50). Nevertheless, in both the TEN and SJS groups, the difference in mortality rate between the two therapies was not statistically significant (P = 0.651 and P = 1, respectively). In patients with TEN, combination therapy also reduced significantly the time of arrested progression (P = 0.019) and the total hospitalization time (P = 0.043), but could not reduce the time to the tapering of corticosteroid (P = 0.96). In SJS patients, the times of arrested progression and hospitalization were also reduced significantly (P = 0.019 and P = 0.0475, respectively). Likewise, the time to the tapering of corticosteroid was not reduced (P = 0.122). Conclusion Combination therapy with corticosteroid and IVIG exhibited a tendency to reduce the mortality rate in comparison with the solo administration of corticosteroid. The decrease in the mortality rate, however, was not statistically significant. Combination therapy also arrested progression earlier and decreased the hospitalization time, meaning that the total dose of corticosteroid may be reduced. Combination therapy, however, did not lead to earlier tapering of corticosteroid. No severe adverse effects of IVIG were found during treatment. 相似文献
18.
Ignacio Torres-Navarro Álvaro Briz-Redón Gonzalo Botella-Casas Antonio Sahuquillo-Torralba Anaid Calle-Andrino Blanca de Unamuno-Bustos Jennifer Piqueras-García Juncal Roca Ginés Jorge Magdaleno Tapial Víctor Alegre de Miquel Rafael Botella-Estrada 《The Journal of dermatology》2020,47(10):1182-1186
Epidermal necrolysis (EN) compromises a spectrum of life-threatening dermatoses (Stevens–Johnson Syndrome [SJS], overlap syndrome and toxic epidermal necrolysis [TEN]). Currently, no active therapeutic regimen with unequivocal benefit exists for SJS/TEN. SCORTEN is the widely-used prognostic scale specific for SJS/TEN. Nevertheless, a new prognostic scale, the ABCD-10, has been recently proposed. In this context, acute renal failure (ARF) seems to be an important comorbidity that could influence prognosis in SJS/TEN patients more than it is assumed by these two scales. Our objectives were to compare the accuracy of the SCORTEN and ABCD-10 scales in predicting the mortality in SJS/TEN, and to investigate the influence of renal failure on prognosis. The prognostic results of 18 patients with EN treated in two referral centers between 2013 and 2018 are presented. SCORTEN, ABCD-10 and renal function values were retrospectively collected for all patients. Out of the 18 patients who were analyzed, nine (50%) received only supportive therapy, four were treated with etanercept 50 mg in a single dose (22.2%) and five with corticosteroids (27.8%). Five patients developed ARF. Predicted mortality was 3.48 for SCORTEN and 2.33 for ABCD-10. Eventually, four patients died (22.2%), all had ARF and none of them received active treatment. Despite study limitations and in the absence of active treatment of choice, SCORTEN behaved as a reliable predictor of mortality in patients with EN, outperforming the newer ABCD-10. ARF was an early event associated with a poor prognosis, which could represent a prognostic marker to consider in the future. 相似文献
19.
R. Pahk M. C. Azu B. R. Taira S. Sandoval 《Clinical and experimental dermatology》2009,34(8):e775-e777
Stevens–Johnson syndrome (SJS) and toxic epidermal necrolysis (TEN) are two variants on a spectrum of severe systemic hypersensitivity characterized by blistering maculopapular lesions and desquamation of the skin and mucus membranes. Although several causative agents, including infections, have been reported for SJS/TEN, medications remain the most common cause. We report the case of a 42‐year‐old man with human immunodeficiency virus (HIV) who developed TEN 4 months after starting treatment with darunavir and abacavir. The patient presented with upper body lesions, oral mucosal ulcerations, and impending airway compromise. He was intubated and admitted to the burns unit. Score for Toxic Epidermal Necrolysis (SCORTEN) was 5, with > 90% predicted mortality. However, after intravenous immunoglobulin and supportive treatment, the patient made a remarkable recovery. Abacavir and darunavir may be associated with SJS/TEN. TEN should be considered a risk for patients with HIV and should be monitored for cutaneous eruptions for several months after changes in treatment regimen. 相似文献
20.
We describe a 44‐year‐old woman with an 18‐year‐history of Behçet's disease (BD) in whom heterotopic ossification (HO) developed as a complication of toxic epidermal necrolysis (TEN). The patient presented with high fever, a progressive erythematous rash including target‐like lesions, flaccid blister formations, and severe detachment. The patient was diagnosed with TEN, and methylprednisolone therapy was started. In the 2nd month of her hospital course, painful limitation developed in both her elbow and shoulder joints. Laboratory and radiographic findings confirmed HO of these areas. BD associated with TEN and HO is a previously unreported entity. In such a condition, determination of underlying genetic abnormality is important. Additionally, HO should be considered as a potential cause of the symptoms related to the joints. 相似文献