British Association of Dermatologists guidelines for the management of people with cutaneous lupus erythematosus 2021
Authors: D. O’Kane, C. McCourt, S. Meggitt, D.P. D’Cruz, C.H. Orteu, E. Benton, S. Wahie, S. Utton, M. Hashme, M.F. Mohd Mustapa, L.S. Exton
Journal: British Journal of Dermatology (2021)

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 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 (FRRs). FRR1 Head-to-head randomized controlled trials (RCTs) to compare the safety and efficacy of established and emerging therapies in CLE (e.g. baricitinib). FRR2 Establish a validated patient-reported outcome measure (PROM) for CLE. FRR3 Trials involving SLE should include CLE as a primary/secondary stratum and with stratification of the cutaneous results using CLASI and a validated PROM to determine the minimal clinically important difference. FRR4 Trials involving CLE using treatments with proven efficacy to help identify what constitutes a minimum clinically important difference as measured by CLASI and a validated PROM. FRR5 Assessment of the effectiveness of CLASI in measuring disease severity and response to treatment in the different subtypes of disease. FRR6 Optimal and standardized core patient- and physician-reported outcome measures in CLE to reduce heterogeneity of reported data and allow comparisons and pooling of data. FRR7 A UK-wide disease registry capturing real-world safety and efficacy of treatments for CLE. The recommendations, discussions in the Linking Evidence To Recommendations (see Appendix D) and consensus specialist experience were used to inform the algorithm/pathway of care (Figure 1). CLE refers to a spectrum of cutaneous disorders that share common clinical, laboratory and histological findings. The pathogenesis is multifactorial, with genetics, autoantibodies and environmental exposures contributing to disease onset and severity. CLE can occur independently or in association with SLE with different CLE subtypes conferring differing levels of risk of systemic disease. The most commonly used classification system for CLE divides lupus-specific skin disease into three subtypes: ACLE, SCLE and CCLE.12 CCLE encompasses the most common subtype, DLE, as well as lupus profundus/panniculitis and chilblain lupus. A fourth subtype – intermittent (ICLE) – has been proposed for lupus tumidus, which displays distinct clinical and histological features and follows a relatively benign clinical course.13 Major histocompatibility complex alleles conferring increased risk of CLE include human leucocyte antigen (HLA)-B8, HLA-DR3, HLA-DQA1 and HLA-DRB1. HLA-DR3 is associated with anti-Ro/SSA antibody positivity, the tumour necrosis factor (TNF)-α promoter polymorphism –308A and SCLE, whereas HLA-DQA1 increases the risk of DLE. IRF5, TYK2 and CTLA4, single nucleotide polymorphisms previously implicated in SLE, are also associated with CLE.14 The pattern of inflammation in CLE is T helper cell 1 predominant and an upregulation of cytokines including interleukin (IL)-6 and IL-17 in affected skin has been demonstrated. Several autoantibodies can be overexpressed in CLE, although their contribution to disease onset and severity is poorly understood. Anti-Ro/SSA positivity is seen in approximately 80% of patients with SCLE and its presence in ACLE appears to confer increased risk of photosensitivity. Keratinocytes within the epidermis in CLE demonstrate increased susceptibility to ultraviolet (UV)-induced apoptosis.15 Increased generation and reduced clearance of apoptotic keratinocytes that express Ro/SSA on their surface, and UV-induction of proinflammatory cytokines, chemokines and adhesion molecules, may represent the triggers necessary for UV-induced autoimmunity. Subsequently, recruitment and activation of effector memory T cells and plasmacytoid dendritic cells amplifying the inflammatory immune response may lead to UV-induced cutaneous LE lesions.16, 17 Anti-La/SSB antibodies are also more commonly seen in SCLE than in ACLE and CCLE. Importantly, anti-Ro/SSA and/or anti-La/SSB positivity in pregnant people confers a risk of neonatal lupus and congenital heart block.17 The presence of other antibodies including anti-dsDNA and anti-Sm are associated with an increased risk of SLE. Cigarette smoking is more common in patients with CLE than healthy controls, with a prevalence of 60–80%. Current smokers demonstrate increased disease activity and damage, and a more pronounced effect on QoL.18 Despite previous reports that smoking interferes with antimalarial efficacy in CLE, it is more likely that this reflects increased disease activity in this group.19 The ability of UV radiation (UVR) to induce or exacerbate CLE is widely recognized, with varying susceptibility dependent on CLE subtype (more common in SCLE and ACLE than DLE).20 Photoprovocation studies have demonstrated that the culpable UVR wavelength can differ between patients (UVA, UVB or both). UVA and UVB may also have distinct roles in the disease pathogenesis.21 In addition, UVR not only aggravates cutaneous involvement in CLE, but also exacerbates systemic symptoms, including joint pains, fatigue and QoL scores. Flares of CLE can be reduced by effective photoprotection measures. In one RCT, a broad-spectrum (UVA and UVB) sunscreen prevented flares of CLE in response to UVA and UVB photoprovocation on three consecutive days, whereas typical CLE lesions developed in the same patients at sites of vehicle application (n = 14/25 to UVA and n = 14/25 to UVB).22 Despite this, adherence to photoprotective measures (including applying suitable sunscreen, avoiding sun exposure and wearing appropriate clothing) are often suboptimal in CLE. Importantly, the latency period between UV exposure and a CLE flare can be several weeks, resulting in the impact of UV on disease flares being underappreciated.23 In one study, CLE lesions developed following photoprovocation in 71% of patients with CLE who denied any contribution of sun exposure to activity of their disease. Additional barriers to adequate photoprotection identified in a recent study include unclear advice from clinicians, cost, tolerability, time constraints and conforming to social norms.24 Each subtype of CLE has characteristic clinical features. ACLE typically presents as a macular erythematous rash involving the malar region of the face. Less commonly, more generalized involvement is seen. ACLE is frequently accompanied by oral ulceration. ACLE is strongly correlated with flares of SLE and activity is typically transient, resolving without scarring. DLE characteristically presents as erythematous, indurated plaques with overlying scale extending into hair follicles (follicular plugging) on the face, ears, scalp (resulting in scarring alopecia) and neck (localized DLE; 70%) with concurrent involvement below the neck less commonly (generalized DLE). Central atrophic scarring and dyspigmentation are characteristic. SCLE is typically highly photosensitive and usually presents as annular and/or psoriasiform plaques on the upper torso, neck and arms. Lesions heal without scarring, but dyspigmentation often persists. Despite the contrasting appearance of the different subtypes, two or more CLE subtypes coexist in up to 30% of patients.25 The incidence of CLE as an independent disease is similar to SLE and approximately 4–5 per 100 000.26 There is a peak age of onset in the fourth decade of life, and CLE is twice as common in females. Overall, CLE is more prevalent and typically more aggressive in darker skin types. Of the CLE subtypes, DLE is the most common (68%), followed by SCLE (18%) and ACLE (6%). CLE is rare in childhood and < 3% of cases of DLE present before 10 years of age.27 The impact of CLE on emotional well-being is greater than other common dermatological conditions (including acne and alopecia), with equivalent or worse scores of mental health status than hypertension, diabetes and congestive cardiac failure.28 Patients with CLE describe pressures conforming to societal norms, distress regarding their appearance and a feeling of helplessness aggravated by the chronicity of their disease. All of these factors contribute to social isolation. A recent publication provides in-depth insight into the disruption and additional burden that CLE and the required photoprotective practices place on individuals with CLE on a daily basis.24 The diagnosis of CLE is clinical and based on a characteristic appearance, particularly in the setting of underlying SLE. Where there is diagnostic uncertainty or overlap with other dermatoses, serum autoantibodies (see section 6.2) and skin biopsy can be useful. On routine histology, an interface dermatitis characterized by varying degrees of basal layer degeneration (keratinocyte apoptosis and vacuolization) is seen in all types of CLE where there is epidermal involvement. Histology in early lesions, particularly in ACLE, can be nonspecific, whereas in established DLE hyperkeratosis, basement membrane zone thickening, follicular plugging, and perivascular and periadnexal inflammation are typically seen. Direct immunofluorescence (DIF; historically termed the 'lupus band test') can demonstrate linear or granular deposits of immunoglobulin (IgG, IgM and IgA) and complement at the dermal–epidermal junction in lesional skin in isolated CLE and in both lesional and nonlesional skin in SLE.29 However, these changes are nonspecific and DIF is therefore not routinely recommended in CLE. Approximately 80% of patients with SLE will develop CLE at some stage. The risk of SLE differs based on the CLE subtype. For example, ACLE is regarded as a cutaneous manifestation of SLE and therefore 90–100% of patients with ACLE have systemic disease.30 Approximately 50% of patients with SCLE meet the 1997 American College of Rheumatologists (ACR) classification criteria for SLE; however, only 10% will develop clinically significant systemic disease.31 The risk of SLE in patients with DLE is lower and dependent on the extent of disease (5% for localized and 15% for generalized disease).32, 33 The risk of progression to SLE appears to be greater in children with CCLE (25–40%).34 The risk in lupus profundus/panniculitis is similar to localized DLE, whereas the risk in lupus erythematosus tumidus is negligible. There are no diagnostic criteria for SLE and classification criteria should not be used to diagnose SLE. When assessing a patient with CLE for the development of SLE, a number of factors can be considered.35 The most important is a full clinical evaluation with a detailed history and physical examination, searching for evidence of internal organ involvement. Women with DLE, especially of African or Asian ancestry, are more likely than men to develop SLE, especially if the skin lesions are below the head and neck. The presence of nailfold lesions and periungual telangiectasias are associated with progression to SLE. The development of mucocutaneous and inflammatory musculoskeletal symptoms, and systemic features such as malaise, fevers and new proteinuria strongly suggest systemic disease. Laboratory abnormalities such as raised erythrocyte sedimentation rate, especially with a low C-reactive protein, cytopenias and the development of autoantibodies, including antinuclear, anti-dsDNA and extractable nuclear antibodies, especially Sm antibodies, which are highly specific for SLE, and low complement levels, should prompt a referral to a rheumatologist or other specialist, depending on the clinical presentation. Drug-induced (DI) CLE should be distinguished from DI-SLE where cutaneous findings (as well as severe renal and haematological sequelae) are much less common than idiopathic SLE.36 Almost all reported cases of DI-CLE are DI-SCLE. Approximately one-quarter of SCLE cases have been attributed to a drug trigger and the frequency of DI-SCLE has increased in recent years as a result of