How to treat skin lupus erythematosus?

Only for medical professionals to read and reference CLE has a variety of treatment measures, but only some of the plans are supported by high-quality evidence
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Cutaneous lupus erythematosus (CLE) is an autoimmune inflammatory disease with a heavy burden of disease.
It is a disease that dermatologists and rheumatologists are concerned about
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At the end of 2019, the Lupus Erythematosus Research Center of the Dermatology Branch of the Chinese Medical Association issued the latest CLE diagnosis and treatment guidelines in Chinese
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In the past two years, there have been new developments, and more and more new evidence and new opinions need to be included in the guidelines
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To this end, with the joint efforts of the Asian Association of Dermatology (ADA), Asian Society of Dermatology and Venereology (AADV) and the Lupus Erythematosus Research Center of the Chinese Medical Association Dermatology and Venereology Association, 25 people from 16 countries/regions in Asia, the United States and Europe A dermatologist, 7 rheumatologists, 1 scientist in the field of lupus erythematosus and 2 methodologists participated in the formulation of the new guideline "Guideline for the diagnosis, treatment and long-term management of cutaneous lupus erythematosus"
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Just this month, this guide was published online in the classic journal "Journal of Autoimmunity" in the field of autoimmunity
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Among them, Professor Lu Qianjin, Associate Professor Long Hai and Professor Chen Yaolong of China, and Chrang-Shi Lin, vice chairman of the Asian Society of Dermatology, are the co-corresponding authors
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Figure 1.
CLE guide (screenshot from the literature) This guide is comprehensive, including the classification, diagnosis, clinical evaluation, and treatment of CLE
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We focus on sorting out the treatment links of CLE for exchange and learning
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1 Main conclusions The first thing to understand is that CLE has a high degree of clinical heterogeneity, including acute, subacute, chronic and intermittent CLE and other subtypes.
Among them, chronic CLE can be further subdivided into discoid, verrucous, and deep CLE.
In-type, frostbite-like and Blaschko linear lupus erythematosus (Figure 2)
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In terms of treatment, individualized medication is also required
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Figure 2.
Various types of CLE, A~C.
Acute CLE, D.
Bullous SLE, E.
Intermittent CLE, F, G.
Subacute CLE, H, I.
DLE, J.
Disseminated DLE, K, L.
frostbite lupus erythematosus, M.
verrucous lupus erythematosus, N.
deep-type lupus erythematosus, O.
Blaschko linear lupus erythematosus (from the guideline) Although there are few officially approved drugs for the treatment of CLE, it is limited to hydroxychloroquine.
However, the phenomenon of empirical and super-indication therapy is very common, including a variety of local treatments and systemic medications
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For localized CLE lesions, topical glucocorticoids and topical calcineurin inhibitors are the first-line treatment
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For generalized or severe CLE skin lesions and/or cases that are resistant to local treatment, systemic treatment can be added, including antimalarial drugs and/or short-term systemic application of glucocorticoids
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It is worth mentioning that antimalarial drugs are the first-line systemic treatment for all types of CLE and can also be used for pregnant and pediatric patients
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Second-line treatment includes thalidomide, tretinoin, dapsone, and methotrexate
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The third-line treatment is mycophenolate mofetil
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Finally, pulsed dye laser or surgery can be used as a fourth-line treatment for limited and refractory chronic CLE lesions
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Belimumab can also be used as a fourth-line treatment for generalized CLE skin lesions in patients with active SLE or acute CLE that recurs during glucocorticoid tapering
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In addition to treatment, CLE disease management also requires patient education and long-term follow-up in order to achieve better results
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If conditions permit, scholars recommend evaluating disease activity, skin and other organ damage, quality of life, comorbidities, and occurrence of side effects at each follow-up
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2CLE's guidelines for basic protective measures set strict rules for treatment recommendations
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Regarding a certain evidence-based evidence and expert opinion, at least 80% of the 32 doctors with voting rights can agree to be a guideline recommendation
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First, the basic protective measures of CLE are discussed
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Considering that ultraviolet rays can aggravate CLE, the guidelines recommend that all CLE patients be protected from ultraviolet rays and sunlight
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Specific measures include avoiding unprotected outdoor activities, artificial sun protection, wearing protective clothing and applying sunscreen
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In addition, the guidelines also recommend CLE should avoid any form of ultraviolet light therapy, the patient's long-term sunscreen recommended vitamin D
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There are three suggestions for protection in life: It is recommended that all CLE patients quit smoking
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It is recommended to comprehensively evaluate the medication history of CLE patients
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If CLE patients have had Koebner's phenomenon, it is recommended to avoid skin trauma, surgery, cryotherapy and invasive laser treatment if it is not necessary
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Local treatment of 3CLE 1) The glucocorticoid guidelines recommend topical glucocorticoids as a short-term (up to several weeks) first-line treatment for all CLE lesions
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However, scalp lesions are excluded, because scalp lesions may require long-term topical corticosteroids
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In addition, it is recommended to inject corticosteroids into the skin to treat localized and refractory DLE
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2) The calcineurin inhibitor guidelines recommend calcineurin inhibitors as a first-line alternative for the treatment of DLE and other active edematous CLE lesions (especially facial lesions)
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3) Topical tretinoin drugs are recommended as the second-line treatment of verrucous lupus erythematosus and other CLE hyperkeratotic lesions, especially those that are refractory to topical glucocorticoids or topical calcineurin inhibitors Case
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4) Pulsed dye laser When the conventional treatment of local and system medication fails, pulsed dye laser can be used as a fourth-line treatment for refractory and inactive DLE
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It should be noted that the pulsed dye laser must be performed by a dermatologist certified by the committee
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Systemic treatment of 4CLE 1) Antimalarial drugs All experts recommend antimalarial drugs (especially hydroxychloroquine) as the first-line systemic treatment for patients with general or severe CLE skin lesions
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In order to avoid the risk of irreversible retinal damage, it is recommended that the daily dose of hydroxychloroquine is ≤5 mg/kg and the daily dose of chloroquine is ≤2.
3 mg/kg, and the two drugs should be avoided in combination
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In addition, it is recommended to check G6PD activity (if any) before antimalarial treatment; an eye examination should be performed every year before medication and after 5 years of treatment
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If there are risk factors for retinal damage, an eye examination will be performed every year after retreatment
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2) Systemic glucocorticoids For patients with severe skin lesions or generalized active CLE and CLE patients with systemic involvement, in addition to antimalarials, the guidelines recommend systemic glucocorticoids as the first-line treatment
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When CLE is under control, it is recommended to gradually reduce and eventually stop systemic glucocorticoids
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During the tapering period and after stopping systemic glucocorticoids, it is recommended to continue treatment with antimalarial drugs or other hormone replacement drugs
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In order to reduce the risk of glucocorticoid-related side effects, it is recommended that patients with CLE without systemic involvement do not use glucocorticoids for long-term maintenance therapy
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3) Thalidomide and lenalidomide are recommended as the second-line treatment for refractory CLE (especially DLE and subacute CLE), preferably together with antimalarials
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It should be noted that the guidelines recommend that everyone avoid lenalidomide (lenalidomide) for the treatment of CLE
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4) Tretinoin drugs are recommended as the second-line treatment of refractory CLE (especially hyperkeratotic skin lesions and verrucous lupus erythematosus), preferably combined with antimalarials
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5) Dapsone recommends dapsone as a second-line treatment for refractory CLE, especially CLE bullous lesions or bullous systemic lupus erythematosus.
It is best to combine antimalarial drugs and systemic glucocorticoids
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To reduce the risk of serious side effects, it is recommended to check G6PD activity and HLA-B*13:01 alleles before starting dapsone treatment
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In addition, the guidelines recommend starting with a low dose (50 mg/d) dapsone and increasing the dose based on treatment response and side effects
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The dose of dapsone shall not exceed the upper limit of 1.
5 mg/kg/d
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6) Methotrexate (MTX) MTX can be used as a second-line treatment for refractory CLE (especially subacute CLE)
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It is recommended to start with a low dose, usually less than 15 or 20 mg per week, preferably subcutaneously
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At the same time, it is recommended to supplement 5-10 mg of folic acid every week to reduce the side effects during MTX treatment
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It is recommended to regularly monitor blood routine and liver enzyme levels during the long-term use of MTX
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7) Mycophenolate mofetil (MMF) and other immunosuppressive agents suggest MMF as the third-line treatment for refractory CLE, preferably in combination with antimalarials
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The recommended initial dose of MMF is 500 mg twice a day, and the dose should be appropriately increased or decreased according to the treatment response and side effects
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At the same time, mycophenolic acid (MPA) is recommended as an alternative to MMF
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As for other immunosuppressive agents, azathioprine, cyclophosphamide, and cyclosporine are recommended for CLE without systemic involvement
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8) Belimoumab is recommended as the fourth-line treatment for generalized and refractory CLE lesions in patients with active SLE, especially for acute relapses during the gradual reduction of systemic glucocorticoids.
Patients with CLE skin lesions
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5 CLE treatment during pregnancy recommends topical glucocorticoids (excluding strong and super-potent glucocorticoids) as the first-line treatment for CLE skin lesions in pregnant patients
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The guidelines cannot recommend topical calcineurin inhibitors for pregnant patients with CLE
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It is recommended that oral hydroxychloroquine (with or without low-dose prednisone) be taken as the first-line maintenance treatment for CLE patients during pregnancy
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Due to the teratogenic effects of retinoic acid drugs, the use of systemic retinoic acid drugs to treat pregnant patients or patients during pregnancy is prohibited
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During treatment with systemic tretinoin and for a period of time after stopping the drug (isotretinoin: 3 months, acitretin: 2 years), effective contraception is strongly recommended
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Because thalidomide, MTX, MMF and MPA have teratogenic effects, they are contraindicated in pregnant patients or patients during pregnancy
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During the use of these drugs, effective contraception is strongly recommended
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6 Other: Surgical treatment of CLE is in areas that affect beauty.
When the traditional local and system treatment fails or the patient cannot tolerate it, surgical treatment can be considered
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Surgical treatment is suitable for intractable localized chronic CLE skin lesions, especially DLE, verrucous lupus erythematosus and frostbite lupus erythematosus
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It is recommended that the skin lesions be surgically removed first, and then full-thickness skin grafts on the abdomen are used
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It should be noted that surgical treatment must be combined with antimalarial drugs and (or) systemic glucocorticoid drug treatment
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7CLE treatment process combined with the above recommendations, the guide further developed a detailed CLE treatment flow chart (Figure 3)
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Figure 3.
CLE treatment flow chart (from the guide) In order to facilitate understanding, we have translated and arranged according to the original flow chart (Figure 4)
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Figure 4.
CLE treatment flow chart "Chinese version", CLE: skin lupus erythematosus; TCS: topical glucocorticoid; TCI: topical calcineurin inhibitor; HCQ: hydroxychloroquine; CQ: chloroquine; MTX: methotrexate ; MMF: Mycophenolate mofetil; MPA: Mycophenolic acid; DLE: Discoid lupus erythematosus; VLE: Verrucous lupus erythematosus; CHLE: Chilblain-like lupus erythematosus; PDL: Pulsed dye laser (organized from the guide) 8 The summary can be seen from the above CLE has a variety of treatment measures, but only some of the programs are supported by high-quality evidence
.

Combined with the best evidence available, the guidelines believe that for localized CLE lesions, topical glucocorticoids and topical calcineurin inhibitors are the first choice for treatment
.

Antimalarials are the first-line systemic treatment for all types of CLE, and can also be used for pregnant and pediatric patients
.

For generalized or severe CLE skin lesions and/or local treatment resistant cases, systemic treatment can be added to the local treatment, including antimalarials and (or) short-term glucocorticoids
.

Second-line options include thalidomide, tretinoin, dapsone and MTX; MMF is classified as third-line treatment
.

Finally, PDL treatment and surgery can be used as the fourth-line treatment for locally refractory skin lesions; belyumumab can be used as the fourth-line treatment for generalized CLE skin lesions in patients with active SLE, and can also be used in the gradual reduction of glucocorticoids.
ACLE that relapsed during the dose
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References: [1]Lu Q,Long H,Chow S,et al.
Guideline for the diagnosis,treatment and long-term management of cutaneous lupus erythematosus.
J Autoimmun.
2021;123:102707.
Epub ahead of print.