We report two cases of recalcitrant epidermolysis bullosa aquisita with associated systemic lupus erythematosus treated with combination rituximab and belimumab therapy. This resulted in the complete resolution of cutaneous lesions and a partial response of the mucosal lesions. These cases support the use of combined rituximab and belimumab for the treatment of recalcitrant immunobullous disease.

The authors declare no conflicts of interest.

Background There is a growing literature reporting the association between proton pump inhibitor (PPI) use and subacute cutaneous lupus erythematosus (SCLE). Aims To compare the clinical characteristics of a cohort of patients with PPI-induced SCLE, their clinical course and treatment with a control group of primary SCLE patients not exposed to PPI. Methods We conducted a matched case–control study in a tertiary referral setting at the Louise Coote Lupus Unit. There were 64 SCLE patients: 36 with PPI-induced SCLE and 28 patients with primary SCLE. Results Twenty-six patients (72%) had pre-existing SLE in the PPI-induced SCLE group. Lower limb skin lesions were significantly more prevalent in the PPI group ( p < 0.0001). The prevalence of anti-Ro and anti-Ro-52 antibodies was numerically higher in the PPI group (64% and 60%), respectively, compared with 46% and 42% in the primary SCLE group. Peripheral blood eosinophils were normal in all patients in the PPI group. Thirteen patients underwent skin biopsy in the PPI group and 12 had histology in keeping with SCLE. The median time to presentation was 8 months with a median resolution period of 6 weeks. PPIs were stopped in 34 patients, while 2 patients continued treatment for other clinical indications. Twelve patients received concurrent oral corticosteroids. Two patients had severe SCLE in the form of Toxic Epidermal Necrolysis requiring critical care admission and were managed with corticosteroids, IV immunoglobulin and/or belimumab. Conclusion Lower limb involvement is a pointer to PPI-induced SCLE which is likely a class effect with all PPI.

Drug-induced lupus erythematosus (LE) has been associated with multiple causative medications, but the risk of developing lupus varies greatly among culprit agents. Skin rashes are less common in drug-induced systemic LE (SLE) than in idiopathic SLE with a low incidence of malar rash, discoid lesions, alopecia and photosensitivity. However, drug-induced subacute cutaneous lupus erythematosus (SCLE) is clinically similar to the idiopathic form of SCLE. The pathophysiology of drug-induced LE involves the interplay between genetic factors, drug metabolism and immunogenicity. Pathogenetic pathways include neutrophil extracellular trap (NET) formation and the induction of T cell DNA hypomethylation with increased lymphocyte function associated antigen-1 (LFA-1), both of which are associated with autoreactivity. Immune-mediated damage triggered by medication has also been implicated in the initiation of drug-induced forms of dermatomyositis and scleroderma.

British Journal of DermatologyEarly View GuidelinesFree Access British Association of Dermatologists guidelines for the management of people with cutaneous lupus erythematosus 2021 D. O'Kane, Corresponding Author donal.okane@belfasttrust.hscni.net orcid.org/0000-0003-0190-6114 Department of Dermatology, Belfast Health & Social Care Trust, Belfast, BT9 7AB UK Correspondence Donal O'Kane. Emails: donal.okane@belfasttrust.hscni.net; guidelines@bad.org.ukSearch for more papers by this authorC. McCourt, orcid.org/0000-0002-1822-3486 Department of Dermatology, Belfast Health & Social Care Trust, Belfast, BT9 7AB UKSearch for more papers by this authorS. Meggitt, Department of Dermatology, Newcastle upon Tyne Hospitals NHS Foundation Trust, Newcastle, NE1 4LP UKSearch for more papers by this authorD.P. D'Cruz, orcid.org/0000-0002-6983-8421 Louise Coote Lupus Unit, Guy's & St Thomas' NHS Foundation Trust, London, SE1 9RT UKSearch for more papers by this authorC.H. Orteu, Department of Dermatology, Royal Free London NHS Foundation Trust, London, NW3 2QG UKSearch for more papers by this authorE. Benton, St John's Institute of Dermatology, Guy's & St Thomas' NHS Foundation Trust, London, SE1 9RT UKSearch for more papers by this authorS. Wahie, Department of Dermatology, County Durham and Darlington NHS Foundation Trust, Durham, DH1 5TW UKSearch for more papers by this authorS. Utton, Patient representativeSearch for more papers by this authorM. Hashme, Clinical Standards Unit, British Association of Dermatologists, London, W1T 5HQ UKSearch for more papers by this authorM.F. Mohd Mustapa, orcid.org/0000-0003-4070-0696 Clinical Standards Unit, British Association of Dermatologists, London, W1T 5HQ UKSearch for more papers by this authorL.S. Exton, orcid.org/0000-0003-0073-1885 Clinical Standards Unit, British Association of Dermatologists, London, W1T 5HQ UKSearch for more papers by this authorthe British Association of Dermatologists' Clinical Standards Unit, Search for more papers by this author D. O'Kane, Corresponding Author donal.okane@belfasttrust.hscni.net orcid.org/0000-0003-0190-6114 Department of Dermatology, Belfast Health & Social Care Trust, Belfast, BT9 7AB UK Correspondence Donal O'Kane. Emails: donal.okane@belfasttrust.hscni.net; guidelines@bad.org.ukSearch for more papers by this authorC. McCourt, orcid.org/0000-0002-1822-3486 Department of Dermatology, Belfast Health & Social Care Trust, Belfast, BT9 7AB UKSearch for more papers by this authorS. Meggitt, Department of Dermatology, Newcastle upon Tyne Hospitals NHS Foundation Trust, Newcastle, NE1 4LP UKSearch for more papers by this authorD.P. D'Cruz, orcid.org/0000-0002-6983-8421 Louise Coote Lupus Unit, Guy's & St Thomas' NHS Foundation Trust, London, SE1 9RT UKSearch for more papers by this authorC.H. Orteu, Department of Dermatology, Royal Free London NHS Foundation Trust, London, NW3 2QG UKSearch for more papers by this authorE. Benton, St John's Institute of Dermatology, Guy's & St Thomas' NHS Foundation Trust, London, SE1 9RT UKSearch for more papers by this authorS. Wahie, Department of Dermatology, County Durham and Darlington NHS Foundation Trust, Durham, DH1 5TW UKSearch for more papers by this authorS. Utton, Patient representativeSearch for more papers by this authorM. Hashme, Clinical Standards Unit, British Association of Dermatologists, London, W1T 5HQ UKSearch for more papers by this authorM.F. Mohd Mustapa, orcid.org/0000-0003-4070-0696 Clinical Standards Unit, British Association of Dermatologists, London, W1T 5HQ UKSearch for more papers by this authorL.S. Exton, orcid.org/0000-0003-0073-1885 Clinical Standards Unit, British Association of Dermatologists, London, W1T 5HQ UKSearch for more papers by this authorthe British Association of Dermatologists' Clinical Standards Unit, Search for more papers by this author First published: 25 June 2021 https://doi.org/10.1111/bjd.20597Citations: 1 The author affiliations can be found in the Appendix. Funding sources None. Conflicts of interest D.O'K. has received sponsorship to attend meetings from Janssen, Galderma and Novartis (nonspecific) and invited speaker fees from Janssen (nonspecific), and has participated in advisory boards for AbbVie, Janssen and Novartis (nonspecific). C.M. has received travel and accommodation expenses from AbbVie, Almirall and Janssen (nonspecific) and invited speaker fees from Almirall (nonspecific). S.W. has received travel and accommodation expenses from AbbVie, Almirall, Janssen and Novartis (nonspecific), and has been awarded a research grant from Lupus UK (specific). D.D'C. has participated in advisory boards for Eli Lilly (specific), has received sponsorship to attend meetings from Eli Lilly and GSK/Human Genome Sciences (specific), has received departmental grant support from Aspreval/Vifor Pharma (specific), is a British Society for Rheumatology Heberden Committee member (specific), a British Society for Rheumatology GDG for SLE member (specific) and a Clinical Reference Group for Specialised Rheumatology representing London member (specific). C.H.O. is Chair of the Clinical Reference Group for Specialised Dermatology (specific). Produced in 2021 by the British Association of Dermatologists This is a new guideline prepared for the British Association of Dermatologists (BAD) Clinical Standards Unit, which includes the Therapy & Guidelines subcommittee. Members of the Clinical Standards Unit who have been involved are N.J. Levell (Chair, Therapy & Guidelines subcommittee), B. McDonald (BAD Assistant Honorary Secretary), A. Bardhan, S.L. Chua, A. Daunton, H. Frow, P. Laws, I. Nasr, G. Petrof, A. Salim, M.C. Ezejimofor (BAD Guideline Research Fellow), M. Hashme (BAD Information Scientist), L.S. Exton (BAD Senior Guideline Research Fellow) and M.F. Mohd Mustapa (Director Clinical Standards). NICE has renewed accreditation of the process used by the British Association of Dermatologists to produce clinical guidelines. The renewed accreditation is valid until 31 May 2026 and applies to guidance produced using the processes described in Updated guidance for writing a British Association of Dermatologists clinical guideline – the adoption of the GRADE methodology 2016. The original accreditation term began on 12 May 2010. More information on accreditation can be viewed at www.nice.org.uk/accreditation. AboutSectionsPDF ToolsRequest permissionExport citationAdd to favoritesTrack citation ShareShare Give accessShare full text accessShare full-text accessPlease review our Terms and Conditions of Use and check box below to share full-text version of article.I have read and accept the Wiley Online Library Terms and Conditions of UseShareable LinkUse the link below to share a full-text version of this article with your friends and colleagues. Learn more.Copy URL Share a linkShare onEmailFacebookTwitterLinked InRedditWechat 1 Purpose and scope The overall objective of the guideline is to provide up-to-date, evidence-based recommendations for the management of cutaneous lupus erythematosus (CLE) in the presence or absence of systemic lupus erythematosus (SLE) in adults, young people and children. The document aims to: offer an appraisal of all relevant literature up to December 2020, focusing on any key developments address important, practical clinical questions relating to the primary guideline objective provide guideline recommendations and, if appropriate, research recommendations. 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/). 1.1 Exclusions The guideline does not cover Jessner lymphocytic infiltrate or nonspecific cutaneous manifestations of lupus such as vasculitis and Raynaud phenomenon. 2 Methodology 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. Table 1. Strength of recommendation ratings Strength Wording Symbols Definition Strong recommendation for the use of an intervention 'Offer' (or similar, e.g. 'use', 'provide', 'take', 'Investigate', etc.) ↑↑ Benefits of the intervention outweigh the risks; most patients would choose the intervention while only a small proportion would not; for clinicians, most of their patients would receive the intervention; for policymakers, it would be a useful performance indicator Weak recommendation for the use of an intervention 'Consider' ↑ Risks and benefits of the intervention are finely balanced; most patients would choose the intervention, but many would not; clinicians would need to consider the pros and cons for the patient in the context of the evidence; for policymakers it would be a poor performance indicator where variability in practice is expected No recommendation Θ Insufficient evidence to support any recommendation Strong recommendation against the use of an intervention 'Do not offer' ↓↓ Risks of the intervention outweigh the benefits; most patients would not choose the intervention whilst only a small proportion would; for clinicians, most of their patients would not receive the intervention 2.1 Clinical questions and outcomes 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? Critical Sensitive and specific for disease activity/damage severity Sensitive and specific to clinically relevant changes in disease activity/damage Important Correlation with physician-assessed disease measures Correlation with patient-reported health outcomes 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? Critical Clear/nearly clear (proportion of participants with complete resolution of skin lesions) Improvement in quality of life (QoL) measures [e.g. Dermatology Life Quality Index (DLQI) – mean change from baseline] CLASI-50 (proportion of participants achieving at least a 50% reduction in the CLASI score) Drug withdrawal due to serious adverse event (e.g. ocular toxicity) Important Improvement in the skin component of a validated lupus activity score [e.g. British Isles Lupus Assessment Group (BILAG) index; Systemic Lupus Erythematosus Disease Activity Index (SLEDAI); Systemic Lupus Activity Measure (SLAM); European Consensus Lupus Activity Measurement (ECLAM); Systematic Lupus International Collaborating Clinics/American College of Rheumatology-Damage index (SLICC/ACR-DI); and SLE Disease Activity Index-2000 (SLEDAI-2K)] CLASI-20 (proportion of participants achieving at least a 20% reduction in CLASI score) Improvement in disease severity [Physician Global Assessment (PGA), Patients' Global Self-Assessment (PGSA)] Time to flare Reduction in number of flares Less important Mild adverse event (e.g. gastrointestinal upset) 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? Critical Clear/nearly clear (proportion of participants with complete resolution of skin lesions) Improvement in QoL measures (e.g. DLQI – mean change from baseline) CLASI-50 (proportion of participants achieving at least a 50% reduction in CLASI score) Drug withdrawal due to serious adverse event (e.g. ocular toxicity) Important Improvement in the skin component of a validated lupus activity score (e.g. BILAG, SLEDAI, SLAM, ECLAM, SLICC/ACR-DI and SLEDAI-2K) CLASI-20 (proportion of participants achieving at least a 20% reduction in CLASI score) Improvement in disease severity (PGA and PGSA) Time to flare Reduction in number of flares Less important Mild adverse event (e.g. gastrointestinal upset) 3 Summary of recommendations 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 Annual screening is recommended in all patients who have taken HCQ for > 5 years. This should include spectral domain optical coherence tomography and fundus autofluorescence imaging photography. Annual screening may be commenced after 1 year of treatment if additional risk factors for retinal toxicity exist, such as concomitant tamoxifen therapy or impaired renal function (estimated glomerular filtration rate < 60 mL min–1 1.73 m–2) or if the daily dose of HCQ is > 5 mg kg–1. Mepacrine R24 (↑) Consider mepacrine (50–100 mg daily) as an alternative, first-line antimalarial option in people with CLE in whom retinal toxicity may be a concern. R25 (GPP) Consider mepacrine (up to 200 mg daily) in people with CLE resistant to standard dosing (see R24), when combination antimalarials or other therapies are contraindicated. Chloroquine R26 (↑) Consider chloroquine (CQ) as a third-line antimalarial option in people with CLE. R27 (↑↑) Conduct an annual retinal assessment in all people with CLE on CQ after 1 year of therapy, following the current Royal College of Ophthalmologists guidelines.9 R28 (GPP) Take care when prescribing CQ as the dosing depends on the salt used and is generally expressed in reference to chloroquine base, for example chloroquine phosphate 250 mg is approximately equivalent to chloroquine sulfate 200 mg and to chloroquine base 155 mg. Combination antimalarials R29 (↑) Consider mepacrine in combination with HCQ as a second-line antimalarial option in patients with CLE refractory to HCQ monotherapy. R30 (↑↑) Do not offer HCQ in combination with CQ owing to the combined risk of retinopathy. R31 (GPP) Exercise caution when using maximum doses of HCQ/CQ, and when used in combination with mepacrine, due to the uncertainty around the retinal safety of antimalarial combinations. Oral/intravenous corticosteroids R32 (GPP) Consider concomitant tapering courses of oral or intravenous corticosteroids, e.g. methylprednisolone, in people with severe or disseminated CLE, or subtypes with the greatest risk of scarring (e.g. patients with DLE with a high risk of permanent damage, high disease burden, etc.). R33 (GPP) Ensure people receiving long-term oral corticosteroids (> 3 weeks' duration) and those needing frequent courses (three or four per year) are regularly monitored during the course of corticosteroid treatment to identify and help prevent steroid-induced osteoporosis and adrenal insufficiency.10, 11 R34 (GPP) Consider comorbidities in people with CLE and the risk/benefit ratio prior to commencing systemic corticosteroids. Methotrexate R35 (↑) Consider methotrexate (up to 25 mg once weekly) in people with CLE with an inadequate response to topical therapy and antimalarials (see R8 and R9). R36 (GPP) Consider methotrexate in combination with antimalarials in people with CLE with partial response to topical therapy and antimalarials (see R8 and R9). R37 (GPP) Consider switching from an oral to a subcutaneous preparation of methotrexate when the treatment response is suboptimal or in the event of significant gastrointestinal side-effects. Mycophenolate R38 (↑) Consider oral mycophenolate mofetil (typically commenced at 500 mg twice daily and escalated to 1.5 g twice daily, dependent on response and tolerability) in people with CLE with an inadequate response to topical therapy and antimalarials (see R8 and R9). R39 (GPP) Consider mycophenolate mofetil in combination with antimalarials in people with CLE with a partial response to topical therapy and antimalarials (see R8 and R9). R40 (GGP) Consider a switch to enteric-coated mycophenolate sodium (360 mg equivalent to 500 mg of mycophenolate mofetil) in the event of significant gastrointestinal side-effects. Dapsone R41 (GPP) Consider dapsone (typically commenced at 50 mg daily and escalated to 150 mg daily, depending on response and tolerability) as a first-line systemic treatment option in people with SCLE and bullous SLE. R42 (↑) Consider dapsone as a second-line systemic treatment option in people with CLE. R43 (↑↑) Monitor for signs and symptoms of haemolytic anaemia, methaemoglobinaemia and agranulocytosis in people with CLE receiving dapsone, particularly in the first 3 months of treatment. Retinoids R44 (↑) Consider acitretin (25–50 mg daily) as a second-line systemic treatment option in people with CLE (see R8). R45 (GPP) Consider acitretin in people with hyperkeratotic DLE resistant to topical therapy and antimalarials (see R8). R46 (↑↑) Only offer acitretin in those of child-bearing potential in exceptional circumstances owing to the risk of teratogenicity during and up to 3 years after treatment (see R8).8 Θ There is insufficient evidence to support the use of alitretinoin in CLE. Biologics Θ While rituximab has shown benefit in the management of SLE, there is insufficient evidence to support its routine use in CLE. R47 (↑) Consider rituximab on a case-by-case basis in people with treatment-resistant CLE where conventional systemic therapies have failed (see R8). (Rituximab is approved by NHS England for use in SLE.) Θ There is insufficient evidence to support the use of belimumab in people with CLE. R48 (↑) Consider belimumab in eligible people with SLE with cutaneous involvement where conventional systemic therapies have failed (see R8). [Belimumab is currently restricted by NHS England to people with active seropositive SLE (SLEDAI score > 10, with positive anti-double-stranded (ds)DNA antibodies and low complement)]. Intravenous immunoglobulins R49 (↑) Only consider intravenous immunoglobulins (IVIg) on a case-by-case basis in people with treatment-resistant CLE where conventional systemic therapies have failed (see treatment algorithm). Individual funding requests to the NHS will be required as IVIg are not approved by the National Institute for Health and Care Excellence (NICE) for the treatment of SLE or CLE. Azathioprine and ciclosporin Θ There is insufficient evidence to support the use of azathioprine or ciclosporin in the treatment of CLE. Cyclophosphamide Θ While cyclophosphamide has robust evidence for use in the management of severe SLE with major organ involvement, there is insufficient evidence to support its use in the treatment of CLE specifically. However, if it is used, see R8 and provide additional counselling on the risk of infertility. Clofazimine R50 (↑) Consider clofazimine (100 mg daily) as a third-line systemic treatment option in people with CLE with or without SLE. R51 (GPP) Avoid co-prescription of clofazimine and antimalarials in people with CLE as both drugs can independently cause skin discoloration. Thalidomide R52 (↑) Consider thalidomide in people with CLE as a third-line treatment option for treatment-resistant disease (see R8 and R9). R53 (GPP) Consider the addition of short courses of thalidomide to antimalarial therapy in people with CLE as a third-line therapy for treatment-resistant disease (see R8 and R9). R54 (↑↑) Use thalidomide with caution in people with increased risk of thromboembolic events and other comorbidities (see R8 and R9). R55 (↑↑) Monitor for signs and symptoms of peripheral neuropathy in people with CLE receiving thalidomide (see R8 and R9). Lenalidomide R56 (↑) Consider lenalidomide in people with CLE as a third-line treatment option for treatment-resistant disease. Availability may be restricted due to cost (see R8 and R9). Summary of future research recommendations The following list outlines future research recommendations

P48 Growing burden of dermatophytosis in southern region of Nepal R. Tripathi, V. Paudel, M. Pradhan and B.R. Pandey Grande International Hospital, Kathmandu, Nepal and National Medical College, Birgunj, Nepal Dermatophytosis is becoming challenging to treat, particularly because of its chronicity and recurrence. Studies from India have suggested significant distress being caused to patients socially, emotionally and financially. The aim of the study was to quantify the magnitude of the problem being faced by patients with dermatophytosis in the southern region of Nepal. A cross-sectional, single-time assessment prospective observational study was conducted in the Dermatology and Venereology Department of National Medical College, Birgunj, Nepal (March–April 2019). Of 100 patients, a preponderance of dermatophytosis was found in males (male-to-female ratio 1 5 : 1). Mean patient age was 29 5 years (range 4–75). Mean duration of disease at presentation was 5 months. On average, patients travelled a distance of 28 65 km to hospital. Clinical diagnoses in these patients, in descending order, were tinea corporis (78%), tinea cruris (55%), tinea faciei (22%) and others, with more than one diagnosis in 54%. Body surface area involvement ranged from 1% to 40%. The presence of chronic/recurrent dermatophytosis was noted in one-fourth of patients. Ninety-two per cent of patients were using topical treatment prior to their visit, with the use of a topical overthe-counter steroid in 54%. Ten per cent were using irritant medications such as salicylic acid and 27% had used multiple topicals. Other measures applied by 9% of the studied population included chloroxylenol, ayurvedic ointments, cactus extract, garlic paste and neem oil. Of 87% who gave an estimate of treatment cost, the average was $48. Absence from work (range 1–6 days) was reported by 6%. Moderate-to-severe pruritus affecting sleep was reported by 56%. Complications noted in the study were tinea incognito (15%), lichenification (7%), irritant contact dermatitis, striae, pseudoimbricata and scaling. Positive family history was present in 42%, with 1–6 family members being affected. Fifteen per cent had one or more family members with chronic/recurrent dermatophytosis. The burden of dermatophytosis is high at both personal and societal level in terms of the high cost of treatment, availability and abuse of topical steroid, distress due to pruritus and complications of improper treatment. P49 Toxic epidermal necrolysis in the setting of systemic lupus erythematosus: a case series J. Oldham, A. Ryan, M. Steyn, R. Adams, E. Agius, G. Sanna, M. Fernando, E. Calonje, H. Malhomme de la Roche, E. Benton and D. D’Cruz Guy’s and St Thomas’ NHS Foundation Trust, London, UK There is increased recognition of a characteristic presentation of toxic epidermal necrolysis (TEN) associated with systemic lupus erythematosus (SLE). We present a case series of three patients and discuss aspects of their presentation and outcome. A 35-year-old woman who had SLE since 2017 was admitted with a new-onset rash. Recent medication included prednisolone, esomeprazole and flucloxacillin. She had annular erythematous macules on the trunk, arms and face, evolving to bullous lesions with epidermal detachment of 80% of her body surface area (BSA). She had markers of active lupus and was treated with methylprednisolone, intravenous immunoglobulins (IVIG) and granulocyte colony-stimulating factor. She was discharged and started on belimumab for treatment-resistant SLE. Our second case, a previously well 26year-old woman, was admitted with a skin rash. A toothache was treated with co-codamol, amoxicillin and metronidazole, and she developed a macular erythema to her face, trunk and thighs. This recurred 2 months later and she was treated with penicillin V, flucloxacillin and metronidazole (for Clostridium difficile infection). She was found to have a high antinuclear antibody, double-stranded DNA and low complement, was diagnosed with SLE and treated with steroids, lansoprazole and hydroxychloroquine, and developed a widespread bullous eruption. On transfer to the intensive treatment unit (ITU) she had 70% BSA epidermal detachment. She was treated with intravenous methylprednisolone and IVIG. Her recovery was complicated by recurrent sepsis. Our third case, a 68-year-old woman who had SLE and Sjogren syndrome since 2012, had experienced multiple bullous drug reactions to antibiotics and was on haemodialysis. She presented following a seizure and was treated for pneumonia with clarithromycin. She developed bullae on her buttocks, with multiple dusky patches on her lower limbs. There was no mucosal involvement, with subsequent 20% BSA epidermal detachment. The culprit drugs were thought to be clarithromycin or omeprazole. She was transferred to ITU. Her skin re-epithelialized, but she died of an acute abdomen. It is interesting to note the similarities of presentation in these patients; two had had previous rashes. Proton pump inhibitors and antibiotics were implicated as drug culprits in all. There was no mucosal involvement in any patient. All patients had a skin biopsy, which showed fullthickness epidermal necrosis consistent with TEN, with negative direct immunofluorescence in two patients. In the third patient only, immunofluorescence was consistent with lupus. These patients had a protracted ITU stay of 18, 43 and 16 days, respectively, vs. an average stay of 12 days in our hospital for patients with TEN.

Primary Sjögren’s syndrome (SS) is an autoimmune condition characterized by sicca symptoms affecting mucosal surfaces with or without a spectrum of systemic manifestations. The skin acts as a remarkable window for the diagnosis of systemic autoimmune disease. SS has many diverse cutaneous manifestations, which occur in approximately 16% of patients, making skin involvement one of the most common extra-glandular manifestations of the disease. However, cutaneous manifestations of SS remain understudied. The most common cutaneous manifestations of SS are thought to be xerosis, cutaneous vasculitis, and annular erythema, the clinical and histopathological of which will be described in the chapter. Clinicians managing patients with SS should be mindful that cutaneous manifestations, such as purpura, are an important sign of systemic complications of the disease. It is therefore important for clinicians to undertake a full skin examination at each clinic visit.

SAQs and answers are ONLINE for RCP fellows and collegiate members Format Candidates are asked to choose the best answer from the five possible answers. This best of five format is used in many medical examinations; however, the questions are not intended to be representative of those used in

PD01 Homocysteine levels in blood and the severity of vitiligo before and after narrowband ultraviolet B phototherapy J. Taneja, T.C. Arora, V. Ramesh and C. Kaur Safdarjung Hospital, Delhi, India Vitiligo is a common multifactorial pigmentary disorder with a complex pathogenesis. Recently, it has been seen that serum homocysteine may interfere with normal melanogenesis and play a role in the pathogenesis of vitiligo. It has been found that vitamin D3 influences cellular homocysteine levels 1 by direct regulation of cystathionine b-synthase (Kriebitzsch C, Verlinden L, Eelen G et al. 1,25-Dihydroxyvitamin D3 influences cellular homocysteine levels in murine preosteoblastic MC3T3-E1 cells by direct regulation of cystathionine b-synthase. J Bone Miner Res 2011; 26: 2991–3000). Narrowband ultraviolet B (NB-UVB), by causing an increase in vitamin D3 levels, may cause a reduction in serum homocysteine. Our study included a total of 50 patients with vitiligo and 50 healthy controls. The patients were administered NB-UVB for 6 months, three times a week. Serum homocysteine and Vitiligo Area Scoring Index (VASI) score were determined at 0 and 6 months of NB-UVB phototherapy. We found that the mean serum level of homocysteine was significantly higher in patients with vitiligo than in controls (18 09 9 97 vs. 10 79 5 74 μmol L ). The correlation between mean serum homocysteine and mean VASI score was strongly positive (r = 0 82). Mean homocysteine levels were significantly higher in patients with unstable vitiligo than stable vitiligo. NB-UVB phototherapy resulted in a significant decrease in the levels of serum homocysteine. The correlation between mean percentage reduction in homocysteine levels and mean percentage improvement in VASI score was statistically significant. Hence, it can be concluded that elevation in serum homocysteine may be a precipitating factor in the pathogenesis of vitiligo. Serum homocysteine is a good marker for severity, extent and progression of vitiligo. Homocysteine-lowering agents should be added to the vitiligo treatment protocol.

Clinical and Experimental DermatologyVolume 40, Issue 7 p. 808-809 Viewpoints in dermatology ● Correspondence Proton pump inhibitor-induced subcutaneous lupus erythematosus in a patient with systemic lupus erythematosus R. Hung, R. Hung The Louise Coote Lupus Unit, Gassiot House, St Thomas' Hospital, Westminster Bridge Road, London, UKSearch for more papers by this authorS. R. Sangle, S. R. Sangle The Louise Coote Lupus Unit, Gassiot House, St Thomas' Hospital, Westminster Bridge Road, London, UKSearch for more papers by this authorE. Benton, E. Benton The Louise Coote Lupus Unit, Gassiot House, St Thomas' Hospital, Westminster Bridge Road, London, UKSearch for more papers by this authorD. P. D'Cruz, D. P. D'Cruz david.dcruz@kcl.ac.uk The Louise Coote Lupus Unit, Gassiot House, St Thomas' Hospital, Westminster Bridge Road, London, UKSearch for more papers by this authorD. McGibbon, D. McGibbon The Louise Coote Lupus Unit, Gassiot House, St Thomas' Hospital, Westminster Bridge Road, London, UKSearch for more papers by this author R. Hung, R. Hung The Louise Coote Lupus Unit, Gassiot House, St Thomas' Hospital, Westminster Bridge Road, London, UKSearch for more papers by this authorS. R. Sangle, S. R. Sangle The Louise Coote Lupus Unit, Gassiot House, St Thomas' Hospital, Westminster Bridge Road, London, UKSearch for more papers by this authorE. Benton, E. Benton The Louise Coote Lupus Unit, Gassiot House, St Thomas' Hospital, Westminster Bridge Road, London, UKSearch for more papers by this authorD. P. D'Cruz, D. P. D'Cruz david.dcruz@kcl.ac.uk The Louise Coote Lupus Unit, Gassiot House, St Thomas' Hospital, Westminster Bridge Road, London, UKSearch for more papers by this authorD. McGibbon, D. McGibbon The Louise Coote Lupus Unit, Gassiot House, St Thomas' Hospital, Westminster Bridge Road, London, UKSearch for more papers by this author First published: 21 March 2015 https://doi.org/10.1111/ced.12592Citations: 4 Conflict of interest: the authors declare that they have no conflicts of interest. Read the full textAboutPDF ToolsRequest permissionExport citationAdd to favoritesTrack citation ShareShare Give accessShare full text accessShare full-text accessPlease review our Terms and Conditions of Use and check box below to share full-text version of article.I have read and accept the Wiley Online Library Terms and Conditions of UseShareable LinkUse the link below to share a full-text version of this article with your friends and colleagues. Learn more.Copy URL Share a linkShare onFacebookTwitterLinked InRedditWechat No abstract is available for this article.Citing Literature Volume40, Issue7October 2015Pages 808-809 RelatedInformation

British Journal of DermatologyVolume 171, Issue 6 p. 1567-1570 Correspondence Two cases of bilateral earlobe cutaneous pseudolymphoma Z. Laftah, Z. Laftah zainablaftah@nhs.net St John's Institute of Dermatology, Guy's and St Thomas' Hospital, Westminster Bridge Road, London, SE1 7EH U.K.Search for more papers by this authorE. Benton, E. Benton St John's Institute of Dermatology, Guy's and St Thomas' Hospital, Westminster Bridge Road, London, SE1 7EH U.K.Search for more papers by this authorK. Bhargava, K. Bhargava St John's Institute of Dermatology, Guy's and St Thomas' Hospital, Westminster Bridge Road, London, SE1 7EH U.K.Search for more papers by this authorJ. Ross, J. Ross University Hospital Lewisham, Lewisham High Street, London, SE13 6LH U.K.Search for more papers by this authorT. Millard, T. Millard Gloucestershire Royal Hospital, Great Western Road, Gloucester, GL1 3NN U.K.Search for more papers by this authorP. Craig, P. Craig Cheltenham General Hospital, Sandford Road, Cheltenham, GL53 7AN U.K.Search for more papers by this authorE. Calonje, E. Calonje St John's Institute of Dermatology, Guy's and St Thomas' Hospital, Westminster Bridge Road, London, SE1 7EH U.K.Search for more papers by this author Z. Laftah, Z. Laftah zainablaftah@nhs.net St John's Institute of Dermatology, Guy's and St Thomas' Hospital, Westminster Bridge Road, London, SE1 7EH U.K.Search for more papers by this authorE. Benton, E. Benton St John's Institute of Dermatology, Guy's and St Thomas' Hospital, Westminster Bridge Road, London, SE1 7EH U.K.Search for more papers by this authorK. Bhargava, K. Bhargava St John's Institute of Dermatology, Guy's and St Thomas' Hospital, Westminster Bridge Road, London, SE1 7EH U.K.Search for more papers by this authorJ. Ross, J. Ross University Hospital Lewisham, Lewisham High Street, London, SE13 6LH U.K.Search for more papers by this authorT. Millard, T. Millard Gloucestershire Royal Hospital, Great Western Road, Gloucester, GL1 3NN U.K.Search for more papers by this authorP. Craig, P. Craig Cheltenham General Hospital, Sandford Road, Cheltenham, GL53 7AN U.K.Search for more papers by this authorE. Calonje, E. Calonje St John's Institute of Dermatology, Guy's and St Thomas' Hospital, Westminster Bridge Road, London, SE1 7EH U.K.Search for more papers by this author First published: 29 May 2014 https://doi.org/10.1111/bjd.13145Citations: 3 Funding sources: none. Conflicts of interest: none declared. Read the full textAboutPDF ToolsRequest permissionExport citationAdd to favoritesTrack citation ShareShare Give accessShare full text accessShare full-text accessPlease review our Terms and Conditions of Use and check box below to share full-text version of article.I have read and accept the Wiley Online Library Terms and Conditions of UseShareable LinkUse the link below to share a full-text version of this article with your friends and colleagues. Learn more.Copy URL Share a linkShare onFacebookTwitterLinked InRedditWechat Citing Literature Volume171, Issue6December 2014Pages 1567-1570 RelatedInformation