U.K. guidelines for the management of Stevens–Johnson syndrome/toxic epidermal necrolysis in adults 2016

The overall objective of the guidelines is to provide up‐to‐date, evidence‐based recommendations for the diagnosis and management of the full spectrum of Stevens–Johnson syndrome (SJS), toxic epidermal necrolysis (TEN) and SJS–TEN overlap in adults during the acute phase of the disease. The document aims to: (i) offer an appraisal of all relevant literature up to February 2016, focusing on any key developments; (ii) address important, practical clinical questions relating to the primary guideline objective, i.e. accurate diagnosis and identification of cases and suitable treatment; (iii) provide guideline recommendations; and (iv) discuss areas of uncertainty, potential developments and future directions SJS/TEN is rare and few healthcare professionals are confident in the recognition and management of the disorder. There is widely divergent practice among different specialities and healthcare settings, and limited information on outcomes. These guidelines aim to provide recommendations on the diagnosis and management of SJS/TEN, to inform clinical decision‐making and, when justified by evidence, to standardize practice. The breadth of this document should be sufficient to assist clinicians of all relevant specialities in the management of patients with SJS/TEN. The recommendations will also inform pathways of care to optimize healthcare delivery and highlight key areas of uncertainty for future research. In these guidelines, the term SJS/TEN encompasses the full spectrum of the disease, i.e. SJS, TEN and SJS–TEN overlap (see section section 10 for clinical definition of the separate entities). The guideline is presented as a detailed review with highlighted recommendations for practical use (see section section 64), in addition to the development of a new patient information leaflet available on the British Association of Dermatologists’ (BAD) website, www.bad.org.uk. Unless otherwise specified, recommendations apply to all forms of the disease. This guideline does not cover paediatric patients. An addendum to this guideline addressing the needs of paediatric patients with SJS/TEN is planned. The evidence for treatment of children differs from that of adult patients, and will be considered separately. The management of long‐term sequelae of SJS/TEN is not considered in this document. The guideline development group (GDG) consisted of consultant dermatologists (D.C., S.A.W., H.Y.L., J.S., C.B.B., M.R.A.‐J., K.M.T.W., G.A.E.W., C.H.S.), including oral (J.S.) and urogenital specialists (S.A.W., C.B.B.), a histopathologist (M.P.), burns/plastic surgeon specialists (P.D., G.W., M.S.), a burns anaesthestist (R.V.M.), intensive care specialists (A.V., R.V.M.), an ophthalmologist (J.K.G.D.), a dermatological clinical nurse specialist (D.B.) and a patient (P.W.). The draft document went out for consultation to the BAD membership, British Dermatological Nursing Group, Primary Care Dermatological Society, British Burn Association, British Association of Plastic, Reconstructive and Aesthetic Surgeons, Royal College of Ophthalmologists, Association of Anaesthetists of Great Britain and Ireland, Intensive Care Society and SJS Awareness U.K. The comments received were actively considered by the GDG. Following further review, the amended draft was recirculated to the stakeholders for comments and the finalized version peer‐reviewed by the Clinical Standards Unit of the BAD (made up of the Therapy for each question, PubMed, MEDLINE and Embase, and the Cochrane Library were searched for meta‐analyses, randomized and nonrandomized controlled clinical trials, open studies and case series to February 2016. The literature was searched for evidence to address the questions. The search terms and strategies are detailed online (Data S1; see Supporting Information). Additional relevant references were also isolated from citations in the reviewed literature, as well as specific targeted searches for hypersensitivity testing, causative drugs, diagnostic and prognostic indicators, topical treatments, oral/mouth, growth factors and granulocyte colony‐stimulating factor (G‐CSF), and analgesia. The lead authors screened the identified titles, and those relevant for first‐round inclusion were selected for further scrutiny. All co‐authors then reviewed the abstracts for the shortlisted references and the full papers of relevant material were obtained; disagreements in the final selections were resolved by discussion with the entire GDG. In section section 47, active interventions were assessed only if studies recruited at least eight patients with SJS/TEN into the treatment group. The structure of the guidelines was then discussed, with headings and subheadings decided; different co‐authors were allocated separate subsections. Each co‐author then performed a detailed appraisal of the selected literature, and all subsections were subsequently collated and edited to produce the final guideline. This document has been prepared on behalf of the BAD and is based on the best data available when the document was prepared. It is recognized that under certain conditions it may be necessary to deviate from the guidelines and that the results of future studies may require some of the recommendations herein to be changed. Failure to adhere to these guidelines should not necessarily be considered negligent, nor should adherence to these recommendations constitute a defence against a claim of negligence. The proposed revision date for this set of recommendations is scheduled for 2021; where necessary, important interim changes will be updated on the BAD website. SJS and TEN are severe mucocutaneous reactions, usually to drugs, characterized by blistering and epithelial sloughing.3 The two terms describe phenotypes within a severity spectrum, in which SJS is the less extensive and TEN the more extensive form. The incidence of SJS/TEN is approximately 1–2 cases per million per year.4 5 Although rare, SJS/TEN is a devastating disease; in severe cases the acute phase may be by a of including The for SJS is with the to for overall SJS/TEN is well as an of the acute long‐term SJS/TEN is characterized by epithelial and a process by to of which the factors including factor and may to Although and all been in evidence as the key of in A by the of of in TEN of into SJS/TEN is an severe characterized by epidermal and by A by of patients in a specialist a detailed of the clinical in In a of and the by may also the is a in SJS/TEN, and the of this should the to epidermal Clinical in the series of a in the of and of The are and of are the and to the of the and of the and is areas of in severe cases is to will the to This is by the in which to to the Although not specific for SJS/TEN is also in the is a clinical of epidermal areas and a in which from necrolysis results in the of of areas of and of the of the and is usually an and to an and 10 In the series by of patients with SJS/TEN, developed oral was in of patients, in in and all in epithelial necrolysis in and necrolysis of to to and acute acute may in the phase of SJS/TEN. of is is the of this patient with Stevens–Johnson epidermal necrolysis are are characterized by a by a In some the are This patient with Stevens–Johnson epidermal necrolysis developed on the and a few the to produce areas of in Stevens–Johnson epidermal necrolysis may be widely the and In this the patient developed and blistering on the and also has severe and is a of of and in Stevens–Johnson epidermal necrolysis be and, as at may is the are areas of epidermal on the The within an of on this has developed on the of this Stevens–Johnson epidermal necrolysis In case was epidermal of of necrolysis results in the of of and of areas of This patient with toxic epidermal necrolysis epidermal of in the acute phase of Stevens–Johnson epidermal necrolysis is a and The patient is and of and is may at any within the as in this the of the is with on the and of the In this the also the the clinical of SJS/TEN, a of with blistering of the and the clinical diagnosis and (see diagnosis of Stevens–Johnson epidermal necrolysis diagnosis of Stevens–Johnson epidermal necrolysis In a by a group of in SJS/TEN reviewed the clinical of patients and the cases to of and of epidermal (i) SJS (ii) overlap SJS–TEN of (iii) TEN with (iv) TEN with of epidermal There is that these are not cases with from two more of the may the less severe of the spectrum, of SJS from be In is and blistering with epidermal of in to SJS, the in of on the and from SJS/TEN has is to and to SJS/TEN is usually by a by an SJS is and in some may be characterized by a of with This of SJS has been Although a diagnosis of SJS/TEN is by the of a is necessary to the clinical and blistering (see is epidermal from to epidermal changes are with and as and are the is only a of and with of in some cases of Stevens–Johnson epidermal There are the full of the and a a There is a within the SJS/TEN is any potential The patient should an of the Clinical an appraisal to any as well as specific to SJS/TEN. of an management is necessary as as the patient has been a detailed from the patient with specific reference to the (i) of SJS/TEN, including a of a on the and and of (ii) the date when the and document of the (iii) of the and (iv) and the date of of the by when the patient developed the of the for and a of and all the including and document the date were and the when of document the date when were if has been a any any of including of the of severe characterized by blistering and of (see a full the and with a for and areas of epidermal all for and the of and the of epidermal on a for each the of using the and should as well as it is this the of that has prognostic of in SJS/TEN. of of epidermal of of epidermal The should be (i) full and and (ii) (iii) a from to a for and a from should be for to an (iii) from for (iv) of the to of and of a primary management (i) any potential SJS/TEN (see (ii) where the if (see section section A should be (iii) if the patient and if this is not a and (see section section (iv) a when urogenital is A will also accurate to assist Stevens–Johnson epidermal necrolysis Stevens–Johnson epidermal necrolysis SJS/TEN is a with a in approximately of of the causative may be in cases where a is are by a patient has been to of the is as this the of The should be of specific in SJS/TEN be from which are in a studies the from to cases and the out and consisted of cases and a of that are with the of SJS/TEN has been these are for of all cases (see and an are to be to of SJS/TEN. An of in has been developed to in is as a for of and not for use in the acute phase of the key in be as a for in clinical practice. all by the patient a of prior to the of to a full a for each the date the was and, when to as A the and of SJS/TEN is the is a of a to the in which case the may be the that the was in the at the of the by into of the any and which lead to of in the each by the document any and any of a is more if the patient a of a hypersensitivity with the each by the to SJS/TEN (see a causative be as In severe cases of SJS/TEN the acute sequelae lead to and potential prognostic in SJS/TEN identified factors with including to a specialist patient of and of In a prognostic for SJS/TEN, which clinical to of (see and In is to each of the with A of patients that during with a and the of the by of SJS/TEN case series has to should be in all patients with SJS/TEN within the of epidermal in SJS/TEN is by and sequelae of acute and the the of It is recommended that patients with areas of epidermal are to a specialist intensive care for care management and specialist (see the in SJS/TEN is to a patients are to a that intensive management and and in a burns are well for the management of and extensive studies and a review of TEN cases that to a burns is with is by Stevens–Johnson epidermal necrolysis of intensive care of the specialist necessary for SJS/TEN cases a for The SJS/TEN should be by a specialist in usually and should clinicians from intensive and an the patient should be in a to and to the to be in burns patients at by of with of at by of The in extensive epidermal necrolysis and a is necessary in SJS/TEN patient care to and with SJS/TEN with epidermal should be to a to an with of patients with SJS/TEN and to the of extensive The SJS/TEN should be by a specialist in usually and should clinicians from intensive and specialist Additional clinical to the may be from oral and with SJS/TEN be in a controlled for on a with the to and In SJS/TEN, is to from of the in these patients is In care be to to the when and the patient care is by specialist with are with the of epidermal should be the in SJS/TEN at to of There are to management of with evidence as to which is In the is in to as a for the In cases where are should be and the to the of a to the is during the acute phase of SJS/TEN to and The use of an on will and and the may also active blistering and epidermal may within a few may be and a of to A of to material by using This more be considered of characterized by clinical of epidermal and of into a in SJS/TEN and with The and as a for by and by from the will and may lead to which is the of in SJS/TEN. of may with should only be if are clinical of The SJS/TEN process may be by a which of patients should be for of as and may be by an in The of may also be by a in and a of is on of from which this that of is and the of of in areas that are to in and oral The are to all patients with SJS/TEN and in all (i) to (ii) of the and of will the of epidermal (iii) epidermal by the use of and identification (iv) for and from areas of on the acute phase of if is only if are clinical of of should be by in patients with and are a management to of to and management may a based on the specialist review of the needs of the patient a in all patients as (i) and by using an as (ii) a as with the including using to with topical (iii) a topical to areas The of topical should be by to of use of should be limited if extensive areas are (iv) The may be in to as a should be by and of to Health A should be to & to a in patients with TEN epidermal and evidence of the clinical of epidermal In a may be with a (i) and using a topical under (ii) with (iii) with & in patients with and A of care in SJS/TEN is to and epidermal will in which is by oral to of the In patients with burns the of is to the of the is with in adults at In SJS/TEN, are those by may be with and A by and of patients with TEN with extensive epidermal the of and that be by the epidermal and and if if be by and (see management should be on a necessary, use a to of is in patients, use and based on of may also to oral of should be if SJS/TEN is characterized by a with approximately the epidermal is also with of of and from in SJS/TEN cases with areas of a be to and in intensive care is to to and of in SJS/TEN oral with a should be when of intensive care are and these are in The Society for Clinical and the acute phase of SJS/TEN, by the oral if the is by up to during the phase of SJS/TEN. the the aim should be to provide and SJS/TEN is characterized by which is severe at of epidermal There are studies different in SJS/TEN. In the of evidence, patient should be using the of the Health should to at with the addition of as by of the of the by SJS/TEN may the of the patient to a the patient is in which is by then an using should be of of and is for delivery of Additional is to address with patient changes and be for more limited of and use of these including may an of may of and a to in all patients at least a the is with should be if with oral as a as should be of the potential for and the to severe then by may be in with In patients should be using the on a and prior to any the acute as changes and may require analgesia. may be for this when the of is with areas of epidermal will require for in should this in a as an to patients may require in care patients with SJS/TEN are to and, if at of with a is in the in be with is necessary, and are of the acute phase of SJS/TEN. will the of and of has been to It has also been that the use of in SJS/TEN may be and with SJS/TEN are in should as against the acute phase of SJS/TEN, patients in be may from a to against with SJS/TEN are may from the of in SJS/TEN usually with may the of A by of patients with SJS/TEN that during the acute phase of the of the of the and is by and and epithelial a for SJS/TEN, which the acute (see the patients in the by and in the of patients was acute of acute with TEN more not more acute patients with of those with acute went on to also the to the of patients with SJS/TEN of acute This was in in and severe in patients a of of developed of which the were severe and There was in the severity of acute when patients with SJS and TEN were In the severity of the acute was not a factor for The that be from these studies are that the severity of the nor the of the acute are for the may not the acute clinicians should be of this and management of in the acute of SJS/TEN, in will acute and may the severity of the disease. of acute in Stevens–Johnson epidermal necrolysis of acute in Stevens–Johnson epidermal necrolysis a for has been The is to factors for severe and to of and It to be more the of for acute severity of Stevens–Johnson epidermal necrolysis from for acute severity of Stevens–Johnson epidermal necrolysis from These long‐term which constitute the sequelae of SJS/TEN, and severe to to of the and as well as to and with require management for and of the acute of SJS/TEN the of and the management and of and the identification and management of of and are and and be the acute a patients with SJS/TEN in an a is of is of are for the use of a topical are to A of SJS/TEN cases patients topical during the acute phase with patients with information was the of treatment of topical assessed at an the acute were in the group topical with the The should be by an ophthalmologist as a of the of a patient with SJS/TEN. review is necessary during the acute A to provide and a for is of a should be and the acute to and be out each by an ophthalmologist and be performed using a and may be when are well developed and be with of the with a is not recommended and may The of a topical is necessary prior to the In the of is to the of and a with should be to epithelial be to the care be if is of the All and should in topical is recommended by the authors in the of when has been The of should be by of which widely in different In the U.K. a is as which has a of against and U.K. on and by the which may as in the of an treatment is use of topical to and may be by results when these is in patients with that for and are The use of topical by an may in the acute phase of SJS/TEN. the of and should be with in the of a epithelial to topical are these are available in the U.K. for all the studies to the of on in SJS/TEN. A by patients with acute SJS/TEN by a of oral was group. was at a of SJS/TEN the was was in was evidence of epithelial In a case series from the in eight patients with TEN with were with a group of eight of received oral The patients in the group were all were from A of of patients were and severe All patients received In received oral prior to received a of oral The were and There was in severity of the and A further the of treatment on in patients from with with and care only This that the prognostic for that not from the use of treatment to the in the acute phase of SJS/TEN, is evidence for the of to outcomes. studies are to the of There are a of and during the acute phase of The of of and less case of that may provide from the National Health Service and is available in a 5 as well as The is for the entire may be the usually under The is by a also by the that not require a further for and by a and which to the that may be are to the are in the available case and the is not It to on each and is to out in an under as with it be out under the a may be and are available in the U.K. use and has been performed at the under topical has been in of eight SJS/TEN In these patients, was using a and the into a It is to of in the using The be performed at the A the results of in and in in A from patients with SJS/TEN with patients with performed in the acute phase of the assessed within of treatment in the patients in is and in those with extensive of to the use of should be It may if this is out in cases with severe using a and performed at the is a for this in SJS/TEN is characterized by with blistering and of the of the to with the development of The and are in severe may to the and and are usually by oral in acute SJS/TEN. to be and in usually to be and a (see section section A long‐term of acute oral is and which may and with by to as a in up to of for oral in acute SJS/TEN are and with of the and should be to topical and topical In an series of patients with a of blistering conditions the including SJS/TEN, topical were to oral are widely in oral SJS/TEN, is limited evidence for The should be as a of the of a patient with SJS/TEN. oral review is necessary during the acute to the and then the acute with a a the with an oral the in the and to the of an oral is controlled with then a topical per may be as an be for severe oral an oral to of the available 10 10 by up to will the that this and should be if is should be with oral for oral oral & in the for of the oral may using a topical in 10 as a A more in with be to the during the acute There are controlled of in the management of in are by oral in severe In a series eight cases and cases of SJS, patients were with in a of for during the acute a of in all patients of is evidence to for the treatment of the oral of acute SJS/TEN. There are studies of oral in acute SJS/TEN with of the urogenital in SJS/TEN is characterized by blistering and the acute phase is and is by is a of urogenital may also of the may for the acute phase has with In the in the of and of the in and in with and for urogenital in acute SJS/TEN are and with of the urogenital should be to and topical may be to urogenital the urogenital as a of the of a patient with SJS/TEN. In by a specialist is recommended for of to needs to be with that all be patients should be for urogenital review is necessary during the acute to the urogenital and and the acute Health to areas in the and to and A in should be into the to of a topical to the urogenital all patients to in the There are studies of urogenital in patients with acute SJS/TEN with are an of SJS/TEN, and may be a of severity and does not to with the of epidermal A characterized in SJS/TEN into based on and were and the of the development of during the acute phase and of patients presented with characterized by and an were on with in of these patients, and a of of in the with epithelial by epithelial There was evidence of in this and to at the as in was in of and a was In patients with epithelial may and and A of patients with on to which and The is with a of approximately in of cases and consisted of a group of including and the of epithelial in these was for in this and all patients and on should discussion with an and to the as is should be as to the prognostic of this