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      The Role of Frozen Section in the Rapid Diagnosis of Severe Cutaneous Adverse Drug Reactions

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          Abstract

          Context:

          Early diagnosis is the mainstay in the management of severe cutaneous adverse reactions (SCARs) to drugs.

          Aims:

          To study the role of frozen section in the rapid diagnosis of SCARs and the impact on outcome of the affected patients.

          Settings and Design:

          A single-blind, hospital-based study was conducted from December 2014-July 2016.

          Methods and Material:

          We biopsied 32 adults with SCARs diagnosed by clinical features and standard criteria. The histopathological features seen on frozen sections were compared to that of paraffin blocks. The impact of rapid diagnosis on the clinical outcome was studied in toxic epidermal necrolysis (TEN), Stevens-Johnson syndrome (SJS), drug rash with eosinophilia and systemic symptoms (DRESS) and acute generalized exanthematous pustulosis (AGEP).

          Statistical Analysis:

          Z test was used to compare two proportions. Kappa statistic, sensitivity, specificity, positive predictive value, and negative predictive value of the frozen section diagnosis were calculated in TEN/SJS and DRESS using MedCalc software.

          Results:

          Frozen and paraffin sections were done in TEN/SJS spectrum (13), DRESS (17), and AGEP (2). The sensitivity, specificity and kappa values for frozen section diagnosis in SJS/TEN and DRESS were 91.7%, 95%, 0.867 and 94.4%, 100%, 0.937 respectively. The concordance between frozen and paraffin section diagnosis was 100% in TEN, SJS, DRESS and AGEP. All the 6 patients with TEN and 2 with AGEP survived. Taking the worst-case scenario, the mortality in SJS was 28.6%. The mortality among patients with DRESS was 11.8%.

          Conclusions:

          Frozen section helps in the rapid diagnosis and early treatment of SCARs and differentiates it from diseases that mimic it.

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          Most cited references18

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          Clinical classification of cases of toxic epidermal necrolysis, Stevens-Johnson syndrome, and erythema multiforme.

          To conduct a prospective case-control study about causative factors of severe bullous erythema multiforme, Stevens-Johnson syndrome, and toxic epidermal necrolysis, we needed to define criteria for classifying the cases and standardize the collection of data so that cases could be reliably diagnosed according to this classification. Based on review of case histories and photographs of patients, a group of experts proposed a classification based on the pattern of erythema multiforme-like lesions (categorized as typical targets, raised or flat atypical targets, and purpuric macules) and on the extent of epidermal detachment. An atlas illustrating this classification that included photographs and schematic drawings was developed. We compared the evaluations of 28 cases by four nonphysicians relying on the atlas with the evaluations of the same cases by five experts not using the atlas to determine the usefulness of this atlas for classifying cases according to our nosologic schema. The following consensus classification in five categories was proposed: bullous erythema multiforme, detachment below 10% of the body surface area plus localized "typical targets" or "raised atypical targets"; Stevens-Johnson syndrome, detachment below 10% of the body surface area plus widespread erythematous or purpuric macules or flat atypical targets; overlap Stevens-Johnson syndrome-toxic epidermal necrolysis, detachment between 10% and 30% of the body surface area plus widespread purpuric macules or flat atypical targets; toxic epidermal necrolysis with spots, detachment above 30% of the body surface area plus widespread purpuric macules or flat atypical targets; and toxic epidermal necrolysis without spots, detachment above 10% of the body surface area with large epidermal sheets and without any purpuric macule or target. Using the atlas, the nonexperts showed excellent agreement with the experts. This study suggests that an illustrated atlas is a useful tool for standardizing the diagnosis of acute severe bullous disorders that are attributed to drugs or infectious agents. Whether the five categories proposed represent distinct etiopathologic entities will require further epidemiologic and laboratory investigations.
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            Acute generalized exanthematous pustulosis (AGEP)--a clinical reaction pattern.

            A wide range of diseases or reactions can cause pustular eruptions of the skin. In this spectrum there seems to be a subgroup with characteristic clinical features and a typical course which is mostly caused by drugs for which the term acute generalized exanthematous pustulosis (AGEP) has been established. To describe the clinical features of AGEP. The authors' experience from a multinational epidemiological study on severe cutaneous adverse reactions and a comprehensive review of the literature were used to provide an overview of the disease and it's possible causes. An algorithm for validating cases which was established for this study is also presented. AGEP typically presents with at least dozens of non follicular sterile pustules occurring on a diffuse, edematous erythema predominantly in the folds and/or on the face. Fever and elevated blood neutrophils are common. Histopathology typically shows spongiform subcorneal and/or intraepidermal pustules, a marked edema of the papillary dermis, and eventually vasculitis, eosinophils and/or focal necrosis of keratinocytes. Onset is acute, most often following drug intake, but viral infections can also trigger the disease. Pustules resolve spontaneously in less than 15 days. The diagnosis AGEP should be considered in cases of acute pustular rashes and detection of the causative drug should be strived for. Knowledge of the clinical features and usual course of this disease can often prevent unnecessary therapeutical measures.
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              Severe cutaneous adverse reactions to drugs.

              During the past decade, major advances have been made in the accurate diagnosis of severe cutaneous adverse reactions (SCARs) to drugs, management of their manifestations, and identification of their pathogenetic mechanisms and at-risk populations. Early recognition and diagnosis of SCARs are key in the identification of culprit drugs. SCARS are potentially life threatening, and associated with various clinical patterns and morbidity during the acute stage of Stevens-Johnson syndrome and toxic epidermal necrolysis, drug reactions with eosinophilia and systemic symptoms, and acute generalised exanthematous pustulosis. Early drug withdrawal is mandatory in all SCARs. Physicians' knowledge is essential to the improvement of diagnosis and management, and in the limitation and prevention of long-term sequelae. This Seminar provides the tools to help physicians in their clinical approach and investigations of SCARs.
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                Author and article information

                Journal
                Indian Dermatol Online J
                Indian Dermatol Online J
                IDOJ
                Indian Dermatology Online Journal
                Wolters Kluwer - Medknow (India )
                2229-5178
                2249-5673
                Jan-Feb 2021
                16 January 2021
                : 12
                : 1
                : 78-83
                Affiliations
                [1] Department of Dermatology, Venereology and Leprosy, Christian Medical College, Vellore, Tamil Nadu, India
                [1 ] Department of General Pathology, Christian Medical College, Vellore, Tamil Nadu, India
                [2 ] Department of Biostatistics, Christian Medical College, Vellore, Tamil Nadu, India
                Author notes
                Address for correspondence: Professor Renu George (Retired), Department of Dermatology, Venerology and Leprosy, Christian Medical College, Vellore, Tamil Nadu, India. E-mail: renuegeorge@ 123456gmail.com
                Article
                IDOJ-12-78
                10.4103/idoj.IDOJ_397_20
                7982049
                33768026
                c48851f2-d2a0-4fa6-97c0-9407af8c869c
                Copyright: © 2021 Indian Dermatology Online Journal

                This is an open access journal, and articles are distributed under the terms of the Creative Commons Attribution-NonCommercial-ShareAlike 4.0 License, which allows others to remix, tweak, and build upon the work non-commercially, as long as appropriate credit is given and the new creations are licensed under the identical terms.

                History
                : 20 May 2020
                : 07 August 2020
                : 24 September 2020
                Categories
                Original Article

                Dermatology
                scars,frozen section,outcome,rapid diagnosis
                Dermatology
                scars, frozen section, outcome, rapid diagnosis

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