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      Intravenous N-acetylcysteine in severe cutaneous drug reaction treatment: A case series

      case-report

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          Abstract

          Drug-induced serious adverse reaction is an unpleasant event with high rate of mortality. Stevens–Johnson Syndrome and toxic epidermal necrolysis are most common among the serious adverse drug reactions. There is no selective drug therapy for the management of serious adverse drug reactions-associated mucocutaneous blisters. The use of N-acetylcysteine in the treatment of mucocutaneous blisters has limited evidence worldwide. Three cases of toxic epidermal necrolysis or Stevens–Johnson Syndrome-associated mucocutaneous blisters are presented in this study where intravenous N-acetylcysteine (600 mg, every 8 h) was given in early hospitalization hours for the treatment of mucocutaneous fluid-filled blisters. Here, one patient with toxic epidermal necrolysis received intravenous immunoglobulin along with intravenous N-acetylcysteine and the other two patients (toxic epidermal necrolysis/Stevens–Johnson Syndrome) received only N-acetylcysteine intravenously. In response, mucocutaneous fluid-filled blisters stopped progressing within 48 h and were healed within 2 weeks of admission in the intensive care unit. Thus, intravenous N-acetylcysteine with or without having intravenous immunoglobulin in the treatment of serious adverse drug reactions-associated mucocutaneous blisters may be an effective therapeutic option for better clinical outcome.

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          Most cited references13

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          Current Perspectives on Stevens-Johnson Syndrome and Toxic Epidermal Necrolysis.

          Stevens-Johnson syndrome (SJS) and toxic epidermal necrolysis (TEN) are considered a delayed-type hypersensitivity reaction to drugs. They represent true medical emergencies and an early recognition and appropriate management is decisive for the survival. SJS/TEN manifest with an "influenza-like" prodromal phase (malaise, fever), followed by painful cutaneous and mucous membrane (ocular, oral, and genital) lesions, and other systemic symptoms. The difference between SJS, SJS/TEN overlap, and TEN is defined by the degree of skin detachment: SJS is defined as skin involvement of  30%, and SJS/TEN overlap as 10-30% skin involvement. The diagnosis of different degrees of epidermal necrolysis is based on the clinical assessment in conjunction with the corresponding histopathology. The mortality rates for SJS and TEN have decreased in the last decades. Today, the severity-of-illness score for toxic epidermal necrolysis (SCORTEN) is available for SJS/TEN severity assessment. Drugs with a high risk of causing SJS/TEN are anti-infective sulfonamides, anti-epileptic drugs, non-steroidal anti-inflammatory drugs of the oxicam type, allopurinol, nevirapine, and chlormezanone. Besides conventional drugs, herbal remedies and new biologicals should be considered as causative agents. The increased risk of hypersensitivity reactions to certain drugs may be linked to specific HLA antigens. Our understanding of the pathogenesis of SJS/TEN has improved: drug-specific T cell-mediated cytotoxicity, genetic linkage with HLA- and non-HLA-genes, TCR restriction, and cytotoxicity mechanisms were clarified. However, many factors contributing to epidermal necrolysis still have to be identified, especially in virus-induced and autoimmune forms of epidermal necrolysis not related to drugs. In SJS/TEN, the most common complications are ocular, cutaneous, or renal. Nasopharyngeal, esophageal, and genital mucosal involvement with blisters, erosions as well as secondary development of strictures also play a role. However, in the acute phase, septicemia is a leading cause of morbidity and fatality. Pulmonary and hepatic involvement is frequent. The acute management of SJS/TEN requires a multidisciplinary approach. Immediate withdrawal of potentially causative drugs is mandatory. Prompt referral to an appropriate medical center for specific supportive treatment is of utmost importance. The most frequently used treatments for SJS/TEN are systemic corticosteroids, immunoglobulins, and cyclosporine A.
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            Expression of cytokines and chemokine receptors in the cutaneous lesions of erythema multiforme and Stevens-Johnson syndrome/toxic epidermal necrolysis.

            Erythema multiforme (EM) and Stevens-Johnson syndrome/toxic epidermal necrolysis (SJS/TEN) are caused by a dysregulation of cellular immunity. 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. 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. 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. 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.
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              Cutaneous adverse drug reactions in a tertiary care teaching hospital: A North Indian perspective

              Background: Cutaneous manifestations of adverse drug reactions are a common occurrence and need to be differentiated from other causes of similar manifestations. Active search is essential for identification of these as patients may tend to downplay the causal association between drug use and the subsequent cutaneous manifestation. Purpose: To study the incidence of Cutaneous Adverse Drug Reactions (CADRs) in a tertiary care teaching hospital in North India. Methods: A prospective, observational study was conducted over a period of 6 months; using self-reporting method for selection of cases. The CADRs were graded as definite, possible and probable. Results: During the study period, 91 cases of CADRs were observed. Maximum incidence of CADRs was seen with antimicrobials (48.30%), followed by nonsteroidal anti-inflammatory drugs (21.90%). Maculopapular rash was the most common cutaneous manifestation of ADRs (42.85%). Conclusion: CADRs are a common occurrence and awareness about the same is essential for diagnosis and prevention.
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                Author and article information

                Journal
                SAGE Open Med Case Rep
                SAGE Open Med Case Rep
                SCO
                spsco
                SAGE Open Medical Case Reports
                SAGE Publications (Sage UK: London, England )
                2050-313X
                20 June 2020
                2020
                : 8
                : 2050313X20934708
                Affiliations
                [1 ]Clinical Pharmacy Services, Department of Pharmacy, Square Hospitals Ltd., Dhaka, Bangladesh
                [2 ]Department of Internal Medicine and ICU, Square Hospitals Ltd., Dhaka, Bangladesh
                Author notes
                [*]Md Jahidul Hasan, Clinical Pharmacist, Clinical Pharmacy Services, Department of Pharmacy, Square Hospitals Ltd., 18/F, Bir Uttam Qazi Nuruzzaman Sarak, West Panthapath, Dhaka 1205, Bangladesh. Email: jahidul@ 123456squarehospital.com
                Author information
                https://orcid.org/0000-0001-7038-6437
                Article
                10.1177_2050313X20934708
                10.1177/2050313X20934708
                7307482
                d049a73b-6933-447e-8615-ae6ca1c3cd8c
                © The Author(s) 2020

                This article is distributed under the terms of the Creative Commons Attribution-NonCommercial 4.0 License ( https://creativecommons.org/licenses/by-nc/4.0/) which permits non-commercial use, reproduction and distribution of the work without further permission provided the original work is attributed as specified on the SAGE and Open Access page ( https://us.sagepub.com/en-us/nam/open-access-at-sage).

                History
                : 16 December 2019
                : 25 May 2020
                Categories
                Case Report
                Custom metadata
                January-December 2020
                ts1

                serious adverse drug reactions,stevens–johnson syndrome,toxic epidermal necrolysis,mucocutaneous blister,n-acetylcysteine

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