British Association of Dermatologists guidelines for the management of people with cutaneous lupus erythematosus 2021

Abstract

The guideline is presented as a detailed review with highlighted recommendations for practical use in primary care and secondary care (see section 3.0), in addition to an updated patient information leaflet (available on the BAD Skin Health Information website, https://www.skinhealthinfo.org.uk/a-z-conditions-treatments/). The guideline does not cover Jessner lymphocytic infiltrate or nonspecific cutaneous manifestations of lupus such as vasculitis and Raynaud phenomenon. This set of guidelines has been developed using the BAD’s recommended methodology.1 Further information can be found in Appendix M (see Supporting Information) with reference to the Appraisal of Guidelines Research and Evaluation (AGREE II) instrument (www.agreetrust.org)2 and the Grading of Recommendations Assessment, Development and Evaluation (GRADE; http://www.gradeworkinggroup.org/). Recommendations were developed for implementation in the UK National Health Service (NHS). The Guideline Development Group (GDG), which consisted of six consultant dermatologists, a consultant rheumatologist, two patient representatives and a technical team (consisting of an information scientist, a guideline research fellow and a project manager providing methodological and technical support), established several clinical questions pertinent to the scope of the guideline and a set of outcome measures of importance to patients, ranked according to the GRADE methodology (see section 2.1 and Appendix A; see Supporting Information). A systematic literature search of PubMed, MEDLINE, Embase and the Cochrane databases was conducted by the technical team to identify key articles on CLE up to December 2020; search terms and strategies are detailed in Appendix N (see Supporting Information). Additional references relevant to the topic were also isolated from citations in reviewed literature. Data extraction and critical appraisal for question 1 were carried out by two clinicians and for questions 2 and 3 by the technical team. Data synthesis, evidence summaries, lists of excluded studies and the PRISMA diagram were prepared by the technical team. Overall certainty of the evidence from included studies was rated according to the GRADE system (high, moderate, low or very low). The recommendations are based on the evidence drawn from systematic reviews of the literature pertaining to the clinical questions identified following discussions with the entire GDG and factoring in all four factors that would affect its strength rating according to the GRADE approach (i.e. balance between desirable and undesirable effects, overall certainty of the evidence, patient values and preferences and resource allocation). All GDG members contributed towards drafting and reviewing the guideline and supporting information. Where there was insufficient evidence from the literature, informal consensus was reached based on the experience of the GDG. The Supporting Information contains the summary of findings with forest plots (Appendix B), clinical evidence summary (Appendix C), tables Linking the Evidence To the Recommendations (Appendix D), GRADE evidence profiles indicating the overall certainty of the evidence (Appendix E), summary of included studies (Appendices F and G), narrative findings for within-patients studies (Appendix H) and noncomparative studies (Appendix I), PRISMA flow diagram (Appendix J), critical appraisal of included systematic reviews (Appendix K) and list of excluded studies (Appendix L). The strength of recommendation is expressed by the wording and symbols as shown in Table 1. The GDG established a number of clinical questions pertinent to the scope of the guideline; see Appendix A for the full review protocol. The GDG also established a set of outcome measures of importance to patients for each clinical question, which were agreed with and ranked according to the GRADE methodology by the patient representatives.3 This uses a 9-point scale, with outcomes that the patient representatives considered most important ranked 9. Outcomes ranked 9, 8 or 7 are critical for decision making; those ranked 6, 5 or 4 are important but not critical for decision making, and those ranked 3, 2 or 1 are the least important for decision making. Data on these outcome measures were extracted from included studies (Appendices B, C, E and G). The GDG decided that an initial review of the available literature was needed to define a change in Cutaneous Lupus Erythematosus Disease Area and Severity Index (CLASI) that is clinically relevant in order to inform the outcomes for the other two clinical questions.4 Review question 1: CLASI In people with CLE how effective is the CLASI score in determining the impact of therapy on disease activity and damage? After a review of the literature (see Appendices D and F) the following outcomes were agreed. (↑↑) Use CLASI-50 (proportion of participants achieving at least a 50% reduction in the CLASI score) as a critical outcome (for decision making) in the systematic reviews Q2 and Q3. (↑↑) Use CLASI-20 (proportion of participants achieving at least a 20% reduction in the CLASI score) as an important outcome (for decision making) in the systematic reviews Q2 and Q3. Review question 2: local and systemic therapies In people with CLE what is the clinical effectiveness and safety of local and systemic therapies compared with each other and/or placebo? Review question 3: other interventions In people with CLE, what is the clinical effectiveness and safety of other interventions compared with each other and/or placebo? The following recommendations and ratings were agreed upon unanimously by the core members of the GDG and patient representatives. For further information on the wording used for recommendations and strength of recommendation ratings, see Table 1. The evidence for recommendations is based on the studies as listed (for details and discussion of the evidence see Appendices B–I). Good practice point (GPP) recommendations are derived from informal consensus. The GDG acknowledges that a number of the recommended treatment options are used off licence in CLE. Where recommendations relate to specific subtypes of CLE: acute (ACLE), subacute (SCLE) or chronic [CCLE, which includes discoid (DLE)], this has been indicated. There is a paucity of evidence relating to the treatment of CLE in young people and children. The GDG is mindful that the presentation of CLE before adulthood is rare and therefore treatment decisions are typically based on available evidence in adults and physicians’ own experience in children and young people with CLE or other inflammatory diseases (see section 8). Throughout this guideline, drug doses refer to adults and adjustment of all systemic drugs is required in children. General R1 (↑) Consider the presence of SLE in people with CLE using history, examination and targeted laboratory investigations. R2 (GPP) People with CLE in the setting of SLE should be managed jointly with rheumatology. R3 (GPP) Where the psychological impact of CLE on an individual patient is significant, consider referral to available psychological support services (such as a psychiatrist, clinical psychologist or patient support group). R4 (↑) Consider the possibility of drug-induced CLE (particularly in people with SCLE) and discontinue any potential causative drug. R5 (↑↑) Discuss with people with CLE the importance of lifestyle changes on disease activity and treatment response, such as smoking cessation and the need for a range of photoprotective measures, including the use of a broad-spectrum sunscreen. R6 (↑) Consider vitamin D supplementation in people with CLE.5 R7 (GPP) Caution people with CLE against herbal supplements and traditional medicines as some may contain corticosteroids or induce disease exacerbation by immune stimulation. R8 (↑↑) Offer those of child-bearing potential a pregnancy test prior to commencing methotrexate, mycophenolate mofetil, acitretin, rituximab, belimumab, cyclophosphamide, thalidomide or lenalidomide therapy for their CLE (see individual drug’s summary of product characteristics).6-8 Counsel them regarding the risk of teratogenicity, advise pregnancy prevention and instigate the pregnancy prevention programme. R9 (↑↑) As a precautionary measure, advise sexually active males to use reliable contraception during methotrexate, mycophenolate mofetil, thalidomide and lenalidomide therapy for their CLE, during dose interruption (where applicable) and for periods of time following the cessation of treatment (see individual drug’s summary of product characteristics).6 R10 (GPP) Additional monitoring by the obstetric team is required to identify congenital heart block in the fetuses of females with CLE with anti-Ro/SSA and/or anti-La/SSB antibodies who become pregnant. R11 (GPP) Consider hydroxychloroquine (HCQ) at standard dosing (see R22) as a first-line systemic therapy for CLE during pregnancy. R12 (GPP) Consider dapsone as a second-line systemic agent for CLE during pregnancy when the response to HCQ is suboptimal. Co-prescription of folic acid 5 mg daily is necessary. Local therapies Topical therapy R13 (↑↑) Offer very potent/potent topical corticosteroids as a first-line monotherapy option to people with localized CLE (including the face) for up to 4 weeks, and as an adjuvant to systemic therapy when there is widespread cutaneous and/or SLE involvement. R14 (↑↑) Offer topical calcineurin inhibitors as a first-line monotherapy option to people with localized CLE for up to 12 weeks, and as an adjuvant to systemic therapy when there is widespread cutaneous and/or SLE involvement. R15 (GPP) Consider reducing to a twice-weekly dose for maintenance in people with CLE who respond to topical corticosteroids or calcineurin inhibitors, reviewing the effectiveness after 3–6 months. R16 (↑) Consider the early addition of systemic therapy to topical therapy in people with severe or disseminated CLE. R17 (GPP) Consider intralesional triamcinolone (0.1 mL per 1 cm2 field, starting at 2.5–5 mg mL–1 for sites at higher risk of atrophy including the face and 10 mg mL–1 for other sites) as a local treatment option in people with localized DLE or as an adjunctive therapy for persistent lesions. Θ There is insufficient evidence to support the use of pulsed dye laser in CLE. Systemic therapies Antimalarials R18 (↑↑) Offer antimalarials, either alone or with adjunctive topical corticosteroids (see R13–R17), as the first-line systemic treatment option to people with CLE (see R22–R39). R19 (GPP) Consider higher, initial antimalarial doses in people with severe or disseminated CLE, or subtypes at the greatest risk of scarring (e.g. DLE and lupus profundus). R20 (GPP) Consider concomitant systemic corticosteroids initially in people with severe or disseminated CLE, or subtypes at the greatest risk of scarring (see R32–R33). R21 (GPP) Consider intermittent use of antimalarials in people with seasonal CLE (e.g. summer flares in photosensitive lupus erythematosus and winter flares in chilblain lupus erythematosus) (see R22–R31). Hydroxychloroquine R22 (↑↑) Offer HCQ at doses of 200–400 mg daily to people with CLE. The daily maintenance dose of HCQ should not exceed 5 mg kg–1 (actual body weight). R23 (↑↑) Screen people with CLE receiving HCQ for retinopathy, following current guidelines by the Royal College of Ophthalmologists:9 Mepacrine R24 (↑) Consider mepacrine (50–100 mg daily) as an alternative, first-line antimalarial option in people with CLE in may be a (GPP) Consider mepacrine to mg daily) in people with CLE to standard dosing (see when antimalarials or other therapies are (↑) Consider as a antimalarial option in people with CLE. (↑↑) an in all people with CLE on after 1 of following the current Royal College of (GPP) care when as the dosing on the used and is expressed in reference to for mg is to mg and to antimalarials (↑) Consider mepacrine in with HCQ as a second-line antimalarial option in patients with CLE to HCQ (↑↑) not HCQ in with to the risk of (GPP) when using doses of and when used in with to the the safety of antimalarial corticosteroids (GPP) Consider concomitant of or in people with severe or disseminated CLE, or subtypes with the greatest risk of scarring (e.g. patients with DLE with a risk of disease (GPP) people receiving corticosteroids 3 and those or four per are during the of treatment to identify and and (GPP) Consider in people with CLE and the prior to commencing systemic (↑) Consider to mg in people with CLE with an response to topical therapy and antimalarials (see R8 and (GPP) Consider in with antimalarials in people with CLE with response to topical therapy and antimalarials (see R8 and (GPP) Consider from an to a of when the treatment response is or in the of (↑) Consider mycophenolate at mg daily and to on response and in people with CLE with an response to topical therapy and antimalarials (see R8 and (GPP) Consider mycophenolate in with antimalarials in people with CLE with a response to topical therapy and antimalarials (see R8 and Consider a to mycophenolate mg to mg of mycophenolate in the of (GPP) Consider dapsone at mg daily and to mg on response and as a first-line systemic treatment option in people with and (↑) Consider dapsone as a second-line systemic treatment option in people with CLE. (↑↑) for and of and in people with CLE receiving in the 3 of (↑) Consider mg daily) as a second-line systemic treatment option in people with CLE (see (GPP) Consider in people with DLE to topical therapy and antimalarials (see (↑↑) in those of child-bearing potential in to the risk of during and up to 3 after treatment (see Θ There is insufficient evidence to support the use of in CLE. Θ has shown in the of there is insufficient evidence to support its use in CLE. (↑) Consider on a in people with CLE systemic therapies (see is by for use in Θ There is insufficient evidence to support the use of in people with CLE. (↑) Consider in people with SLE with cutaneous systemic therapies (see is by to people with active SLE score with antibodies and low (↑) consider on a in people with CLE systemic therapies (see treatment to the be required as are not by the National for Health and for the treatment of SLE or CLE. and Θ There is insufficient evidence to support the use of or in the treatment of CLE. Θ has evidence for use in the of severe SLE with there is insufficient evidence to support its use in the treatment of CLE is see R8 and on the risk of (↑) Consider mg daily) as a systemic treatment option in people with CLE with or (GPP) of and antimalarials in people with CLE as drugs can (↑) Consider thalidomide in people with CLE as a treatment option for disease (see R8 and (GPP) Consider the addition of of thalidomide to antimalarial therapy in people with CLE as a therapy for disease (see R8 and (↑↑) Use thalidomide with in people with risk of and other (see R8 and (↑↑) for and of in people with CLE receiving thalidomide (see R8 and (↑) Consider lenalidomide in people with CLE as a treatment option for may be to (see R8 and of research recommendations The following list research recommendations to the safety and of established and therapies in CLE (e.g. a outcome for CLE. SLE should CLE as a and with of the cutaneous using CLASI and a to the clinically important CLE using with to identify what a clinically important as by CLASI and a of the effectiveness of CLASI in disease and response to treatment in the subtypes of and core and outcome measures in CLE to of and and of A disease safety and of for CLE. The discussions in the Linking Evidence To Recommendations (see Appendix and consensus experience were used to inform the of care CLE to a of cutaneous that laboratory and The is with and to disease and CLE can or in with SLE with CLE subtypes of risk of systemic The most used system for CLE disease and the most as as lupus and chilblain A intermittent has been for lupus which clinical and and a clinical risk of CLE and is with anti-Ro/SSA the and the risk of and in are also with The of in CLE is 1 and an of including and in has been can be in CLE, their to disease and is is in of patients with and its presence in to risk of the in CLE to and of that on their and of and may the for and of and the inflammatory immune response may to cutaneous antibodies are also in in and anti-Ro/SSA and/or anti-La/SSB in people a risk of lupus and congenital heart The presence of other antibodies including and are with an risk of smoking is in patients with CLE with a of disease activity and and a on that smoking with antimalarial in CLE, is that this disease activity in this The of to induce or CLE is with on CLE in and studies that the can between patients or and may also in the disease In not cutaneous in CLE, but also systemic including and of CLE can be by effective In a broad-spectrum and flares of CLE in response to and on CLE developed in the patients at sites of to and to to photoprotective measures (including and are in CLE. the between and a CLE can be several weeks, in the impact of on disease flares In CLE developed following in of patients with CLE who any of to activity of their Additional to identified in a from time and to of CLE has clinical typically as a the of the is is by is with flares of SLE and activity is typically DLE as with on the in scarring and with the scarring and are is typically photosensitive and as and/or on the and but the of the two or CLE subtypes in up to of The of CLE as an disease is to SLE and per There is a of in the of and CLE is as in CLE is and typically in the CLE DLE is the most by and CLE is rare in and of of DLE before 10 of The impact of CLE on is other (including and with or of and with CLE to regarding their and a of by the of their All of these factors to A the and that CLE and the required photoprotective on with CLE on a daily The of CLE is clinical and based on a in the setting of Where there is or with other (see section and can be an by of and is in all of CLE there is involvement. in early in can be in established DLE and and are typically the can or of and and at the in in isolated CLE and in and in these changes are nonspecific and is therefore not recommended in CLE. of patients with SLE CLE at some The risk of SLE based on the CLE For is as a cutaneous of SLE and therefore of patients with systemic 50% of patients with the College of for clinically systemic The risk of SLE in patients with DLE is and on the of disease for localized and for The risk of to SLE to be in children with The risk in lupus is to localized the risk in lupus erythematosus is There are for SLE and should not be used to a patient with CLE for the of a number of factors can be The most important is a full clinical with a detailed and for evidence of involvement. with of or are to the are the and The presence of and are with to The of and inflammatory and systemic such as and systemic such as with a low and the of including and which are specific for and low should a referral to a or other on the clinical CLE should be from cutaneous findings as severe and are all of are of been to a drug and the of has in as a of and of There are a range of of including (including and (including and inhibitors, several antibodies and In patients with (particularly when is a should be when an drug has been In most is on the can up to 3 and therapies may be required during this of and is rare and with inhibitors and has been that of females may experience a of their SLE during obstetric are in people with SLE that of the when the disease is active at time of or in the presence of The impact of pregnancy on CLE as an disease or in with is review of patients with DLE a of disease and the most in identified obstetric outcomes in people with CLE and those in the anti-Ro/SSA and/or anti-La/SSB in females a risk of lupus and congenital heart is to the safety of the and to from and the use of topical and systemic during pregnancy is by from and The UK Information Service and its Use of in are for and patients on the safety of during pregnancy. Where safety are an individual decision should be based on the risk of a to an Where are to teratogenicity, advise as a to before to any drug. A Cochrane review on the safety of topical corticosteroids in pregnancy identified between use of topical corticosteroids of any and pregnancy There is a between low and topical systemic in pregnancy is with an risk of and of Where systemic corticosteroids are required for CLE in with the dose of is recommended (i.e. 10 mg on studies of HCQ in there is evidence that HCQ HCQ is considered a first-line systemic to active CLE or in patients with a of severe CLE in pregnancy (including when cessation of other systemic is other antimalarial there is evidence to that is in based on As there is insufficient literature regarding the use of mepacrine in during pregnancy is the other systemic used to CLE, dapsone is considered for use in active disease in of folic acid at 5 mg daily is in and to a higher risk of SLE to be for and drug-induced are rare in children. is considered a of and is in of anti-Ro/SSA to of is with a of systemic including congenital heart SLE has a to disease but is with a severe clinical in up to and higher of manifestations are also may be required to the used in adults as the to early and in children. The and point for in has consensus guidelines to the and of SLE in The guidelines the of evidence regarding treatment of SLE in and specific other are in the guidelines regarding the of CLE in children and young on consensus and evidence from the guidelines that all children with SLE should be with Where systemic corticosteroids are required with HCQ and clinical activity of the addition of other should be The risk of with a dose in patients is In there are of HCQ in children and evidence for monitoring patients for drug is Throughout this guideline, drug doses refer to adults and adjustment of all recommended systemic drugs is required in children. In of the paucity of literature on CLE in children and young treatment should by a team with experience of lupus in children. decisions should to disease and systemic which is relevant with systemic in children. The recommendation of per is to in the to a patient and to for between to this recommendation may to all in the 12 months. Appendix in Supporting The was available to the BAD the Group the the for the Health for in the for the Royal College of and the Royal College of and Health the Royal College of the Royal College of General the for the of the Lupus UK the Lupus Group and Lupus for which were considered by the GDG. further the was for review by the of the BAD up of the Guidelines prior to for This has been prepared on of the BAD and is based on the available when the was is that may be to from the guidelines and that the of studies may some of the recommendations to be to to these guidelines should not be considered should to these recommendations a against a of the review to references was a but the this may some important information in other The for this set of recommendations is for important changes be updated on the BAD are very to of of for on CLASI and to the patient representatives and for their in the clinical of the reviewing the evidence and the as as all those who on the during the Appendix A Review protocol. Appendix Appendix evidence Appendix D Linking Evidence To Appendix E GRADE evidence Appendix F of Cutaneous Lupus Erythematosus Disease Area and Severity Index Appendix of included Appendix findings for Appendix findings for noncomparative Appendix PRISMA diagram Appendix appraisal of included systematic reviews Appendix excluded from Appendix M Appendix N Appendix and The is not for the or of any supporting information by the should be to the for the