Lupus Erythematosus Prognosis and Treatment

Background

The treatment of lupus erythematosus must be individualized for each patient and the type of lupus. Tremendous advancements have been made in immunomodulatory agents.

OUTLINE

Prognosis

Treatment DLE
SCLE
SLE

Commonly Used Terms

Internet Links

PROGNOSIS AND TREATMENT CHARACTERIZATION

PROGNOSIS

SLE
Arch Dermatol 1975;111:1448
Patients with classical discoid lesions may have a more indolent form and rarely die of internal organ complications
These DLE lesions may develop in the background of longstanding SLE

SCLE

DLE
SLE develops in 5-10% of patients

Photoprovocation
Br J Dermatol 1997;136:230
These studies were positive in:
SCLE 100%
SLE 70%
DLE 64%

Survival

SLE

SCLE
J Am Acad Dermatol 1998;38:405
These patients do better than SLE patients

DLE

Anti-Ro/SSA associated SLE
Medicine 1995;74:109
65% of patients (65/100 patients)with progressive disease with 20% dead at 10 year follow-up

TREATMENT FOR DLE

GENERAL

Drugs for discoid lupus erythematosus (Cochrane Review).

Jessop S, Whitelaw D, Jordaan F.

Dermatology, Groote Schuur Hospital, Observatory 7195, Cape Town, SOUTH AFRICA.

Cochrane Database Syst Rev 2001;1:CD002954 Abstract quote

BACKGROUND: Discoid lupus erythematosus is a chronic form of cutaneous (skin) lupus which can cause permanent scarring if treatment is inadequate. Many drugs have been used to treat this disease and some of these are potentially very toxic.

OBJECTIVES: To assess the effects of drugs for discoid lupus erythematosus.

SEARCH STRATEGY: We searched the Cochrane Clinical Trials Register (December 1999), MEDLINE (January 1966 to December 1999), EMBASE (January 1980 to January 2000), and the reference lists of relevant reviews. Index Medicus (1956 to 1966) was handsearched and 7 experts in the field were approached for information about unpublished trials.

SELECTION CRITERIA: Randomised trials of drugs to treat people with discoid lupus erythematosus. Drugs included in the search were azathioprine, chloroquine, clofazimine, corticosteroids, (oral and topical), dapsone, gold, interferon alpha-2a, methotrexate, phenytoin, retinoids, sulphasalazine and thalidomide.

DATA COLLECTION AND ANALYSIS: Two reviewers independently examined each retrieved study for eligibility.

MAIN RESULTS: Two trials involving 136 participants were included. In a cross-over study of twelve weeks duration fluocinonide 0.05% cream (a potent topical corticosteroid), appeared to be markedly better than hydrocortisone 1% cream ( a mild corticosteroid). Clearing or excellent improvement was seen in 27% of people using fluocinonide and in 10% of those using hydrocortisone, giving a 17% absolute benefit in favour of fluocinonide (95% CI 4.5 to 29.5% and NNT 6). In the second trial, hydroxychloroquine was compared with acitretin in 58 people. There was marked improvement or clearing in 46% of people using acitretin and in 50% of those on hydroxychloroquine, a nonsignificant 4% absolute gain with hydroxychloroquine (95%CI -23% to 30%). The adverse effects were more frequent and more severe in the acitretin group.

REVIEWER'S CONCLUSIONS: Fluocinonide cream may be more effective than hydrocortisone in treating people with discoid lupus erythematosus. Hydroxychloroquine and acitretin appear to be of equal efficacy, although adverse effects are more frequent and more severe with acitretin. There is not enough reliable evidence about other drugs used to treat discoid lupus erythematosus

EFALIZUMAB

Efalizumab in the Treatment of Discoid Lupus Erythematosus
Naila Usmani, MBChB, MRCP; Mark Goodfield, MBChB, MD

Author Affiliations: Department of Dermatology, Leeds General Infirmary, Leeds, England.

Arch Dermatol. 2007;143:873-877. Abstract quote

Background Discoid lupus erythematosus is a chronic inflammatory condition in which the pathogenesis and the role of cell-mediated immunity remains unclear. Currently, the most effective treatments for severe disease are thalidomide, methotrexate, and cyclosporin, although the evidence for this is limited. Efalizumab is a monoclonal antibody directed against CD11a, the ${alpha}$ -subunit of the leukocyte-functioning antigen 1, with a current license for use in psoriasis. Because discoid lupus erythematosus is known to be predominantly T-cell mediated, our aim was to use efalizumab as a T-cell modulator in patients with recalcitrant disease.

Observations Thirteen patients received efalizumab, with treatment responses varying from good to excellent in 12 of 13 patients. There was a significant reduction in the cutaneous lupus activity and severity score (CLASS) score after therapy with efalizumab (P = .002).

Conclusions We have presented efalizumab as a novel alternative treatment for patients with difficult discoid lupus erythematosus. The response to treatment in 12 patients was very encouraging, with the mean time to response being 5.5 weeks. However, patient numbers were small, and many remain in the early stages of therapy. A prospective randomized study with a long-term follow-up is required, especially in light of recent findings to evaluate both the effectiveness and safety profile of this monoclonal antibody.

LASER

Successful treatment of discoid lupus erythematosus with argon laser.

Kuhn A, Becker-Wegerich PM, Ruzicka T, Lehmann P.

Department of Dermatology, Heinrich Heine University, Dusseldorf, Germany.

Dermatology 2000;201(2):175-7 Abstract quote

Vascular lesions with telangiectasias on visible areas, such as the face, are common in discoid lupus erythematosus (DLE); however, an efficient management of these skin lesions can sometimes be difficult. Since argon laser light is able to specifically coagulate vascular structures, it has been used in the treatment of various vascular skin malformations.

Therefore, we addressed the issue whether argon laser treatment could be a therapeutic alternative for this disease. Here, we report on a patient with DLE, who suffered from long-standing erythematous, telangiectatic plaques on the face refractory to standard regimens of therapy. After 2 laser applications, a significant improvement was observed and after 5 sessions of argon laser therapy the treated skin lesions had completely resolved with an excellent cosmetic result. The patient tolerated the laser treatment well without any short-term side effects.

These data indicate that argon laser therapy might be a powerful alternative approach in the treatment of vascular skin lesions of DLE.

THALIDOMIDE

Thalidomide in the treatment of the cutaneous manifestations of lupus erythematosus: experience in sixteen consecutive patients.

Stevens RJ, Andujar C, Edwards CJ, Ames PR, Barwick AR, Khamashta MA, Hughes GR.

Department of Rheumatology, Rayne Institute, St Thomas Hospital, London.

Br J Rheumatol 1997 Mar;36(3):353-9 Abstract quote

We review the efficacy, tolerability and safety of low-dose thalidomide in the treatment of refractory disfiguring rash in 16 patients with cutaneous manifestations of lupus. Rashes, which included discoid lupus erythematosus (DLE), subacute cutaneous lupus (SCLE), photosensitive malar rash and non-specific chronic erythema, were diagnosed on clinical grounds, supported by skin biopsy in 11/16 patients.

Using starting doses of 50-100 mg/day, 7/16 (44%) patients gained complete or near-complete remission of skin disease and 6/16 (37%) partial remission. Three out of 16 patients failed to respond. Maximum benefit was achieved within 16 weeks in all patients. Doses of 25-50 mg/day were effective in maintaining response. Rapid relapse occurred in 6/8 (75%) patients following drug withdrawal, but the response to thalidomide in those requiring repeat courses appeared to be maintained. There was no detectable improvement in systemic disease. One patient developed symptoms of mild peripheral neuropathy which resolved on drug withdrawal.

Our experience suggests that thalidomide is effective in the treatment of severe skin manifestations of lupus refractory to other treatment and can be used safely in specialist rheumatological practice.

TREATMENT FOR SCLE
J Am Acad Dermatol 1998;38:405
Mild cases, especially in elderly may be managed with sunblockers alone

METHOTREXATE

Methotrexate treatment for refractory subacute cutaneous lupus erythematosus.

Kuhn A, Specker C, Ruzicka T, Lehmann P.

Departments of Dermatology and Rheumatology, Heinrich-Heine-University Dusseldorf, and the Department of Dermatology, University of Witten-Herdecke, Wuppertal.
J Am Acad Dermatol 2002 Apr;46(4):600-3 Abstract quote
Methotrexate is beneficial in rheumatoid arthritis and has been used in small studies of patients with systemic lupus erythematosus.

We describe a patient with severe subacute cutaneous lupus erythematosus refractory to therapy with antimalarials and corticosteroids.

Treatment with methotrexate resulted in complete clearing of the skin lesions without any side effects.

THALIDOMIDE

Low-dose thalidomide therapy for refractory cutaneous lesions of lupus erythematosus.

Housman TS, Jorizzo JL, McCarty MA, Grummer SE, Fleischer AB Jr, Sutej PG.

Department of Dermatology, Wake Forest University School of Medicine, Medical Center Blvd, Winston-Salem, NC 27157-1071.
Arch Dermatol 2003 Jan;139(1):50-4 Abstract quote
BACKGROUND: Thalidomide is an anti-inflammatory agent and an immunomodulator that inhibits the production of tumor necrosis factor alpha. It has shown promise as a treatment option for the cutaneous manifestations of lupus erythematosus (LE).

OBJECTIVE: To assess the degree of clinical response per subtype of cutaneous lupus, the duration of therapy before documented clinical improvement, and the incidence of adverse effects, including peripheral neuropathy, with low-dose thalidomide therapy at 100 mg daily in the treatment of refractory cutaneous lesions of LE.

METHODS: This retrospective medical record review of patients with refractory cutaneous manifestations of LE is one of the largest modern series in the literature. There were 29 patients seen at the Department of Dermatology, Wake Forest University School of Medicine (Winston-Salem, NC), who were unresponsive to conventional agents including antimalarial agents, and who started treatment between 1998 and 2000. Twenty-three patients who took the drug for 1 month or more were included in the analysis. Clinical responses were assessed by the investigators based on statements of improvement listed in the clinic notes and were categorized as "no response," "partial response," and "complete response." Partial response was classified as either 75% or greater or less than 75% improvement. The incidence of adverse effects including peripheral neuropathy was determined.

RESULTS: Of the 23 patients, 17 (74%) demonstrated complete resolution of the cutaneous manifestations of LE, whereas 3 patients (13%) demonstrated 75% or greater partial improvement; 3 patients (13%) had less than 75% partial clinical improvement; and 21 patients (91%) who demonstrated a complete or partial response did so within 8 weeks of initiating thalidomide therapy.

CONCLUSIONS: Based on the results of this case series, we believe that thalidomide should be given prime consideration as a treatment for antimalarial drug-resistant interface lesions of LE. The design of prospective, randomized, double-blind, placebo-controlled trials for this indication is warranted.

Thalidomide in the treatment of cutaneous lupus refractory to conventional therapy.

Ordi-Ros J, Cortes F, Cucurull E, Mauri M, Bujan S, Vilardell M.

Internal Medicine Department, Vall d'Hebron Hospital, Autonoma University of Barcelona, Spain.

J Rheumatol 2000 Jun;27(6):1429-33 Abstract quote

OBJECTIVE: We describe a prospective treatment study of thalidomide in a series of 22 patients with cutaneous lupus refractory to other treatments.

METHODS: From 1992 to 1998, 22 patients with cutaneous lupus (9 with discoid lupus erythematosus, 7 with subacute cutaneous lupus, 4 with profundus lupus, 2 with nonspecific rash) were treated with thalidomide. Initial treatment was started at 100 mg daily. If the cutaneous lesions vanished, the dose was lowered to 50-25 mg daily as a maintenance therapy and it was considered a complete remission. If the lesions improved but remained, this was considered a partial response and treatment was continued until the lesions were not further modified. Periodically, adverse effects were evaluated.

RESULTS: Three patients discontinued treatment because of side effects such as vertigo, persistent drowsiness, or paresthesia. Rash improved in 16/19 patients (84%). Complete remission occurred in 12/16 (75%). In 9 (65%) the rash resolved, but recurred 4-16 weeks after withdrawal of thalidomide; when it was used again, they improved. Partial response was achieved in 4/16 (25%) patients. No response occurred in 3/19 (16%). Many patients noted improvement within 2 weeks after starting thalidomide and maximum benefit was achieved within 3 months. Five of the 14 women had amenorrhea during the treatment with thalidomide.

CONCLUSION: Thalidomide is effective in the treatment of cutaneous lupus refractory to other treatments. However, only some patients had a remission; the remainder relapsed when treatment was withdrawn, or required low doses of thalidomide to preserve inactive lesions. Amenorrhea was observed as a new secondary effect of thalidomide.

TREATMENT FOR SLE Steroid and immunosuppressive agents are the mainstay
Additional therapy is directed at affected organs

KIDNEY

Mycophenolate mofetil combined with a cyclooxygenase-2 inhibitor ameliorates murine lupus nephritis.

Zoja C, Benigni A, Noris M, Corna D, Casiraghi F, Pagnoncelli M, Rottoli D, Abbate M, Remuzzi G.

Mario Negri Institute for Pharmacological Research, Bergamo, Italy

Kidney Int 2001 Aug;60(2):653-63 Abstract quote

BACKGROUND: Approaches to the treatment of lupus nephritis include immunosuppressants associated with anti-inflammatory drugs, mainly steroids, which, however, cause major side effects. Mycophenolate mofetil (MMF) has been described as being less toxic than conventional immunosuppressants, and it was effective in preventing progressive nephritis in lupus mice. Our study evaluated the therapeutic effect of MMF in NZB/W F1 hybrid mice with established disease. We also examined the combination of MMF with a selective cyclooxygenase-2 (COX-2) inhibitor, DFU, based on previous findings of excessive renal production of COX-2-derived thromboxane A2 (TXA2) in lupus nephritis.

METHODS: Four groups of NZB/W mice (N = 30 each group), starting at five months of age, were given daily by gavage the following: vehicle, MMF 60 mg/kg, DFU 3 mg/kg, or MMF + DFU. Fifteen mice for each group were used for the survival studies, and the remaining mice were sacrificed at nine months.

RESULTS: MMF or DFU alone partially delayed the onset of proteinuria compared with vehicle. Combined therapy was significantly (P < 0.05) more effective than single drugs. Animal survival was partially ameliorated by MMF and significantly improved by the drug combination in comparison with the vehicle (P = 0.005) and DFU alone (P < 0.03). At nine months, serum blood urea nitrogen (BUN) levels were lower in all of the treated groups than in the vehicle group. Renal damage was also limited, but to a greater extent in mice given the combined therapy. In untreated mice, renal COX-2 mRNA expression was up-regulated, and generation of TXB(2), the stable breakdown product of TXA(2), increased. DFU prevented the abnormal renal TXB(2) production, confirming the COX-2 origin of this eicosanoid, whereas renal 6-keto-PGF(1 alpha) and prostaglandin E(2) (PGE(2)) were not affected substantially.

CONCLUSIONS: These results offer a strong case for exploring the possibility that in humans MMF combined with COX-2 inhibitors has a role in the treatment options for lupus nephritis. This combined drug therapy may be at least as effective as steroids but without the obvious nephrotoxicity of the latter.

Combination therapy with pulse cyclophosphamide plus pulse methylprednisolone improves long-term renal outcome without adding toxicity in patients with lupus nephritis.

Illei GG, Austin HA, Crane M, Collins L, Gourley MF, Yarboro CH, Vaughan EM, Kuroiwa T, Danning CL, Steinberg AD, Klippel JH, Balow JE, Boumpas DT.

Arthritis and Rheumatism Branch, National Institute of Arthritis and Musculoskeletal and Skin Diseases, National Institutes of Health, 10 Center Drive, Building 10, Room 9S-205, Bethesda, MD 20892, USA.

Ann Intern Med 2001 Aug 21;135(4):248-57 Abstract quote

BACKGROUND: Controlled trials in lupus nephritis have demonstrated that cyclophosphamide therapy is superior to corticosteroid therapy alone. The long-term effectiveness and side-effect profiles of pulse immunosuppressive regimens warrant further study.

OBJECTIVE: To define the long-term risk and benefit of monthly treatment with boluses of methylprednisolone, cyclophosphamide, or both. DESIGN: Extended follow-up (median, 11 years) of a randomized, controlled trial.

SETTING: U.S. government research hospital.

PATIENTS: 82 patients with proliferative lupus nephritis.

MEASUREMENTS: Rates of treatment failure (defined as need for supplemental immunosuppressive therapy or doubling of serum creatinine concentration, or death) and adverse events.

RESULTS: In an intention-to-treat survival analysis, the likelihood of treatment failure was significantly lower in the cyclophosphamide (P = 0.04) and combination therapy (P = 0.002) groups than in the methylprednisolone group. Combination therapy and cyclophosphamide therapy alone did not differ statistically in terms of effectiveness or adverse events. Of patients who completed the protocol (n = 65), the proportion of patients who had doubling of serum creatinine concentration was significantly lower in the combination group than in the cyclophosphamide group (relative risk, 0.095 [95% CI, 0.01 to 0.842]).

CONCLUSION: With extended follow-up, pulse cyclophosphamide continued to show superior efficacy over pulse methylprednisolone alone for treatment of lupus nephritis. The combination of pulse cyclophosphamide and methylprednisolone appears to provide additional benefit over pulse cyclophosphamide alone and does not confer additional risk for adverse events.

Outcome after transplantation of young patients with systemic lupus erythematosus: a report of the North American pediatric renal transplant cooperative study.

Bartosh SM, Fine RN, Sullivan EK.

Department of Pediatrics, University of Wisconsin Medical School, 600 Highland Avenue, H4/474, Madison, WI 53792-4108, USA.

Transplantation 2001 Sep 15;72(5):973-8 Abstract quote

BACKGROUND: The risk of progressing to end-stage renal disease in children with lupus glomerulonephritis is 18% to 50%. Published reports of transplantation secondary to end-stage renal failure in adult patients with systemic lupus erythematosus (SLE) demonstrate equivalent patient and graft survival. The purpose of this analysis is to compare patient and graft outcomes of pediatric SLE renal transplant recipients with an age-, race-, and gender-matched control group.

METHODS: A retrospective analysis of the North American Pediatric Renal Transplant Cooperative Study (NAPRTCS) database identified 100 renal transplants performed in 94 young SLE patients. A control group of 470 children having received 501 renal transplants was identified.

RESULTS: The SLE cohort was primarily female (82%), non-Caucasian (61%), adolescents and differed from the control group in being less likely to be preemptively transplanted, in receiving longer pretransplant dialysis, and in being likely to have received more than five pretransplant transfusions. After transplantation, there were no differences seen in patient survival at 3 years (89% vs. 95%, SLE vs. control) or in overall graft failure rates (31% vs. 29%, SLE vs. control). There was a trend toward poorer graft survival in non-white SLE patients receiving living donor grafts compared with white SLE patients. An increased graft failure rate was seen among those SLE cadaveric transplant recipients receiving peritoneal dialysis before transplant compared with controls and compared with SLE patients receiving hemodialysis. No differences were seen in rates of acute tubular necrosis or overall acute rejection incidence, although there was a significant increase in the percentage of living donor SLE patients who experienced greater than four rejection episodes. There were nonsignificant trends toward increased graft loss due to patient death with a functioning graft as well as increased mortality secondary to infection in the SLE patients.

CONCLUSIONS: The results of renal transplantation in young SLE patients are comparable to those seen in an age-, race- and gender-matched control group. The similar patient and graft survival is seen despite the SLE patients having an underlying disease with multiorgan involvement and despite receiving immunosuppression for potentially prolonged periods before transplantation. No outcome differences were seen except for an unexplained increase in the incidence of recurrent rejections (> or =4) in the living donor SLE patients as well as increased graft failure rate in those patients receiving cadaveric renal transplants after a period of peritoneal dialysis. The nonsignificant trends toward increased graft failures in non-white SLE patients receiving living donor grafts, increased graft loss secondary to death with a functioning graft, as well as the increased mortality due to infection deserve recognition and further study.

Macpherson and Pincus. Clinical Diagnosis and Management by Laboratory Methods. Twentyfirst Edition. WB Saunders. 2006.
Rosai J. Ackerman's Surgical Pathology. Ninth Edition. Mosby 2004.
Sternberg S. Diagnostic Surgical Pathology. Fourth Edition. Lipincott Williams and Wilkins 2004.
Robbins Pathologic Basis of Disease. Seventh Edition. WB Saunders 2005.
DeMay RM. The Art and Science of Cytopathology. Volume 1 and 2. ASCP Press. 1996.
Weedon D. Weedon's Skin Pathology Second Edition. Churchill Livingstone. 2002
Fitzpatrick's Dermatology in General Medicine. 6th Edition. McGraw-Hill. 2003.
Weiss SW and Goldblum JR. Enzinger and Weiss's Soft Tissue Tumors. Fourth Edition. Mosby 2001.

Commonly Used Terms

Basic Principles of Disease
Learn the basic disease classifications of cancers, infections, and inflammation

Commonly Used Terms
This is a glossary of terms often found in a pathology report.

Diagnostic Process
Learn how a pathologist makes a diagnosis using a microscope

Surgical Pathology Report
Examine an actual biopsy report to understand what each section means

Special Stains
Understand the tools the pathologist utilizes to aid in the diagnosis

How Accurate is My Report?
Pathologists actively oversee every area of the laboratory to ensure your report is accurate

Got Path?
Recent teaching cases and lectures presented in conferences

Internet Links

Last Updated July 17, 2007

Send mail to The Doctor's Doctor with questions or comments about this web site.
Read the Medical Disclaimer.

Copyright © The Doctor's Doctor

TREATMENT FOR DLE
GENERAL
Drugs for discoid lupus erythematosus (Cochrane Review). Jessop S, Whitelaw D, Jordaan F. Dermatology, Groote Schuur Hospital, Observatory 7195, Cape Town, SOUTH AFRICA.	Cochrane Database Syst Rev 2001;1:CD002954 Abstract quote BACKGROUND: Discoid lupus erythematosus is a chronic form of cutaneous (skin) lupus which can cause permanent scarring if treatment is inadequate. Many drugs have been used to treat this disease and some of these are potentially very toxic. OBJECTIVES: To assess the effects of drugs for discoid lupus erythematosus. SEARCH STRATEGY: We searched the Cochrane Clinical Trials Register (December 1999), MEDLINE (January 1966 to December 1999), EMBASE (January 1980 to January 2000), and the reference lists of relevant reviews. Index Medicus (1956 to 1966) was handsearched and 7 experts in the field were approached for information about unpublished trials. SELECTION CRITERIA: Randomised trials of drugs to treat people with discoid lupus erythematosus. Drugs included in the search were azathioprine, chloroquine, clofazimine, corticosteroids, (oral and topical), dapsone, gold, interferon alpha-2a, methotrexate, phenytoin, retinoids, sulphasalazine and thalidomide. DATA COLLECTION AND ANALYSIS: Two reviewers independently examined each retrieved study for eligibility. MAIN RESULTS: Two trials involving 136 participants were included. In a cross-over study of twelve weeks duration fluocinonide 0.05% cream (a potent topical corticosteroid), appeared to be markedly better than hydrocortisone 1% cream ( a mild corticosteroid). Clearing or excellent improvement was seen in 27% of people using fluocinonide and in 10% of those using hydrocortisone, giving a 17% absolute benefit in favour of fluocinonide (95% CI 4.5 to 29.5% and NNT 6). In the second trial, hydroxychloroquine was compared with acitretin in 58 people. There was marked improvement or clearing in 46% of people using acitretin and in 50% of those on hydroxychloroquine, a nonsignificant 4% absolute gain with hydroxychloroquine (95%CI -23% to 30%). The adverse effects were more frequent and more severe in the acitretin group. REVIEWER'S CONCLUSIONS: Fluocinonide cream may be more effective than hydrocortisone in treating people with discoid lupus erythematosus. Hydroxychloroquine and acitretin appear to be of equal efficacy, although adverse effects are more frequent and more severe with acitretin. There is not enough reliable evidence about other drugs used to treat discoid lupus erythematosus
EFALIZUMAB
Efalizumab in the Treatment of Discoid Lupus Erythematosus Naila Usmani, MBChB, MRCP; Mark Goodfield, MBChB, MD Author Affiliations: Department of Dermatology, Leeds General Infirmary, Leeds, England.	Arch Dermatol. 2007;143:873-877. Abstract quote Background Discoid lupus erythematosus is a chronic inflammatory condition in which the pathogenesis and the role of cell-mediated immunity remains unclear. Currently, the most effective treatments for severe disease are thalidomide, methotrexate, and cyclosporin, although the evidence for this is limited. Efalizumab is a monoclonal antibody directed against CD11a, the ${alpha}$ -subunit of the leukocyte-functioning antigen 1, with a current license for use in psoriasis. Because discoid lupus erythematosus is known to be predominantly T-cell mediated, our aim was to use efalizumab as a T-cell modulator in patients with recalcitrant disease. Observations Thirteen patients received efalizumab, with treatment responses varying from good to excellent in 12 of 13 patients. There was a significant reduction in the cutaneous lupus activity and severity score (CLASS) score after therapy with efalizumab (P = .002). Conclusions We have presented efalizumab as a novel alternative treatment for patients with difficult discoid lupus erythematosus. The response to treatment in 12 patients was very encouraging, with the mean time to response being 5.5 weeks. However, patient numbers were small, and many remain in the early stages of therapy. A prospective randomized study with a long-term follow-up is required, especially in light of recent findings to evaluate both the effectiveness and safety profile of this monoclonal antibody.
LASER
Successful treatment of discoid lupus erythematosus with argon laser. Kuhn A, Becker-Wegerich PM, Ruzicka T, Lehmann P. Department of Dermatology, Heinrich Heine University, Dusseldorf, Germany.	Dermatology 2000;201(2):175-7 Abstract quote Vascular lesions with telangiectasias on visible areas, such as the face, are common in discoid lupus erythematosus (DLE); however, an efficient management of these skin lesions can sometimes be difficult. Since argon laser light is able to specifically coagulate vascular structures, it has been used in the treatment of various vascular skin malformations. Therefore, we addressed the issue whether argon laser treatment could be a therapeutic alternative for this disease. Here, we report on a patient with DLE, who suffered from long-standing erythematous, telangiectatic plaques on the face refractory to standard regimens of therapy. After 2 laser applications, a significant improvement was observed and after 5 sessions of argon laser therapy the treated skin lesions had completely resolved with an excellent cosmetic result. The patient tolerated the laser treatment well without any short-term side effects. These data indicate that argon laser therapy might be a powerful alternative approach in the treatment of vascular skin lesions of DLE.
THALIDOMIDE
Thalidomide in the treatment of the cutaneous manifestations of lupus erythematosus: experience in sixteen consecutive patients. Stevens RJ, Andujar C, Edwards CJ, Ames PR, Barwick AR, Khamashta MA, Hughes GR. Department of Rheumatology, Rayne Institute, St Thomas Hospital, London.	Br J Rheumatol 1997 Mar;36(3):353-9 Abstract quote We review the efficacy, tolerability and safety of low-dose thalidomide in the treatment of refractory disfiguring rash in 16 patients with cutaneous manifestations of lupus. Rashes, which included discoid lupus erythematosus (DLE), subacute cutaneous lupus (SCLE), photosensitive malar rash and non-specific chronic erythema, were diagnosed on clinical grounds, supported by skin biopsy in 11/16 patients. Using starting doses of 50-100 mg/day, 7/16 (44%) patients gained complete or near-complete remission of skin disease and 6/16 (37%) partial remission. Three out of 16 patients failed to respond. Maximum benefit was achieved within 16 weeks in all patients. Doses of 25-50 mg/day were effective in maintaining response. Rapid relapse occurred in 6/8 (75%) patients following drug withdrawal, but the response to thalidomide in those requiring repeat courses appeared to be maintained. There was no detectable improvement in systemic disease. One patient developed symptoms of mild peripheral neuropathy which resolved on drug withdrawal. Our experience suggests that thalidomide is effective in the treatment of severe skin manifestations of lupus refractory to other treatment and can be used safely in specialist rheumatological practice.

TREATMENT FOR SCLE	J Am Acad Dermatol 1998;38:405 Mild cases, especially in elderly may be managed with sunblockers alone
METHOTREXATE
Methotrexate treatment for refractory subacute cutaneous lupus erythematosus. Kuhn A, Specker C, Ruzicka T, Lehmann P. Departments of Dermatology and Rheumatology, Heinrich-Heine-University Dusseldorf, and the Department of Dermatology, University of Witten-Herdecke, Wuppertal.	J Am Acad Dermatol 2002 Apr;46(4):600-3 Abstract quote Methotrexate is beneficial in rheumatoid arthritis and has been used in small studies of patients with systemic lupus erythematosus. We describe a patient with severe subacute cutaneous lupus erythematosus refractory to therapy with antimalarials and corticosteroids. Treatment with methotrexate resulted in complete clearing of the skin lesions without any side effects.
THALIDOMIDE
Low-dose thalidomide therapy for refractory cutaneous lesions of lupus erythematosus. Housman TS, Jorizzo JL, McCarty MA, Grummer SE, Fleischer AB Jr, Sutej PG. Department of Dermatology, Wake Forest University School of Medicine, Medical Center Blvd, Winston-Salem, NC 27157-1071.	Arch Dermatol 2003 Jan;139(1):50-4 Abstract quote BACKGROUND: Thalidomide is an anti-inflammatory agent and an immunomodulator that inhibits the production of tumor necrosis factor alpha. It has shown promise as a treatment option for the cutaneous manifestations of lupus erythematosus (LE). OBJECTIVE: To assess the degree of clinical response per subtype of cutaneous lupus, the duration of therapy before documented clinical improvement, and the incidence of adverse effects, including peripheral neuropathy, with low-dose thalidomide therapy at 100 mg daily in the treatment of refractory cutaneous lesions of LE. METHODS: This retrospective medical record review of patients with refractory cutaneous manifestations of LE is one of the largest modern series in the literature. There were 29 patients seen at the Department of Dermatology, Wake Forest University School of Medicine (Winston-Salem, NC), who were unresponsive to conventional agents including antimalarial agents, and who started treatment between 1998 and 2000. Twenty-three patients who took the drug for 1 month or more were included in the analysis. Clinical responses were assessed by the investigators based on statements of improvement listed in the clinic notes and were categorized as "no response," "partial response," and "complete response." Partial response was classified as either 75% or greater or less than 75% improvement. The incidence of adverse effects including peripheral neuropathy was determined. RESULTS: Of the 23 patients, 17 (74%) demonstrated complete resolution of the cutaneous manifestations of LE, whereas 3 patients (13%) demonstrated 75% or greater partial improvement; 3 patients (13%) had less than 75% partial clinical improvement; and 21 patients (91%) who demonstrated a complete or partial response did so within 8 weeks of initiating thalidomide therapy. CONCLUSIONS: Based on the results of this case series, we believe that thalidomide should be given prime consideration as a treatment for antimalarial drug-resistant interface lesions of LE. The design of prospective, randomized, double-blind, placebo-controlled trials for this indication is warranted.
Thalidomide in the treatment of cutaneous lupus refractory to conventional therapy. Ordi-Ros J, Cortes F, Cucurull E, Mauri M, Bujan S, Vilardell M. Internal Medicine Department, Vall d'Hebron Hospital, Autonoma University of Barcelona, Spain.	J Rheumatol 2000 Jun;27(6):1429-33 Abstract quote OBJECTIVE: We describe a prospective treatment study of thalidomide in a series of 22 patients with cutaneous lupus refractory to other treatments. METHODS: From 1992 to 1998, 22 patients with cutaneous lupus (9 with discoid lupus erythematosus, 7 with subacute cutaneous lupus, 4 with profundus lupus, 2 with nonspecific rash) were treated with thalidomide. Initial treatment was started at 100 mg daily. If the cutaneous lesions vanished, the dose was lowered to 50-25 mg daily as a maintenance therapy and it was considered a complete remission. If the lesions improved but remained, this was considered a partial response and treatment was continued until the lesions were not further modified. Periodically, adverse effects were evaluated. RESULTS: Three patients discontinued treatment because of side effects such as vertigo, persistent drowsiness, or paresthesia. Rash improved in 16/19 patients (84%). Complete remission occurred in 12/16 (75%). In 9 (65%) the rash resolved, but recurred 4-16 weeks after withdrawal of thalidomide; when it was used again, they improved. Partial response was achieved in 4/16 (25%) patients. No response occurred in 3/19 (16%). Many patients noted improvement within 2 weeks after starting thalidomide and maximum benefit was achieved within 3 months. Five of the 14 women had amenorrhea during the treatment with thalidomide. CONCLUSION: Thalidomide is effective in the treatment of cutaneous lupus refractory to other treatments. However, only some patients had a remission; the remainder relapsed when treatment was withdrawn, or required low doses of thalidomide to preserve inactive lesions. Amenorrhea was observed as a new secondary effect of thalidomide.

Prognosis
Treatment	DLE SCLE SLE
Commonly Used Terms
Internet Links

PROGNOSIS AND TREATMENT	CHARACTERIZATION
PROGNOSIS
SLE	Arch Dermatol 1975;111:1448 Patients with classical discoid lesions may have a more indolent form and rarely die of internal organ complications These DLE lesions may develop in the background of longstanding SLE
SCLE
DLE	SLE develops in 5-10% of patients
Photoprovocation	Br J Dermatol 1997;136:230 These studies were positive in: SCLE 100% SLE 70% DLE 64%
Survival
SLE
SCLE	J Am Acad Dermatol 1998;38:405 These patients do better than SLE patients
DLE
Anti-Ro/SSA associated SLE	Medicine 1995;74:109 65% of patients (65/100 patients)with progressive disease with 20% dead at 10 year follow-up