Professional Documents
Culture Documents
DOI: 10.1111/j.1365-2133.2004.06196.x
TOPICAL REVIEW
Summary
This paper reviews the latest treatments for cutaneous lupus erythematosus. It focuses on evidencebased guidance for the management of cutaneous lupus erythematosus, with identification of the
strength of evidence available at this time. In addition, I have briefly reviewed the epidemiological
aspects, diagnosis and evaluation of patients with cutaneous lupus erythematosus. This review
reflects data available from the Cochrane Library, Medline, literature searches, and the experience
of the author managing patients with cutaneous lupus erythematosus for over 25 years.
Definition
Epidemiology
The prevalence of cutaneous lupus varies from 146 to
68 per 100 000 people.2 The rate may be increasing or
the recognition of LE may be increasing. Regardless, it
appears that more cases are diagnosed now than in the
past. Systemic LE is more common in women, and most
cutaneous subsets of LE also are more prevalent in
women, but the ratio is not as high. All races are
affected.
Diagnosis
The diagnosis of cutaneous LE is based upon the
presence of compatible clinical lesions which on biopsy
demonstrate a characteristic pathological picture.
Immunofluorescence microscopy and serological testCorrespondence: Professor Jeffrey P. Callen, MD, 310 East Broadway,
Suite 200, Louisville, KY 40202, U.S.A.
E-mail: jefca@aol.com
2004 British Association of Dermatologists
Treatment
The therapy of cutaneous lesions of LE involves both an
empirical as well as a scientific approach.3 Unfortunately, there are few double-blind, placebo-controlled
trials of drugs used in the treatment of cutaneous LE.4
The author generally approaches patients with specific
cutaneous lesions of LE [e.g. subacute cutaneous LE
(SCLE), discoid LE (DLE) or lupus panniculitis] in a
similar manner (Table 1). The annotated table includes
levels of evidence for each of the therapies which will
not be repeated within the body of the article because
although there are several randomized, controlled
trials, they involve small numbers of patients.
The goals of management of the patient with DLE or
SCLE are to improve the patients appearance and to
prevent the development of deforming scars, atrophy or
dyspigmentation. In addition, the majority of patients
with chronic cutaneous LE (CCLE) or SCLE have disease
that primarily affects their skin and may be reassured
that their prognosis is relatively benign. A complete list
of the patients medications will assist in the exclusion
of drug-induced cutaneous LE.510 Also, patients who
731
732
J.P.CALLEN
733
hydroxychloroquine or chloroquine.24 It is not associated with ocular toxicity, but has other toxicity
associated with antimalarial use.
In difficult cases, many other approaches have been
advocated for the treatment of cutaneous LE. In the
authors experience, low-dose systemic corticosteroids
(< 1 mg prednisone per day or its equivalent) are
rarely effective for DLE, and only partially effective for
SCLE lesions. Corticosteroids are effective for the acute
lesions of photosensitivity, the malar rash, or for the
vasculitic lesions that may complicate LE. The chronic
use of oral or intramuscular corticosteroids for patients
with cutaneous disease should be avoided.
Dapsone, given in doses of 25200 mg daily, has
been useful for patients with the vasculitic lesions that
may accompany LE, SCLE lesions, bullous LE and oral
ulceration.25 In open-label clinical trials, dapsone has
resulted in improvement in some patients with DLE or
SCLE; however, the level of benefit has been judged as
excellent in only about 25% of patients. In contradistinction, clofazimine failed to demonstrate efficacy in all
but one report.26 There are several special circumstances in which dapsone may be useful. The first is
bullous LE. In addition, those patients with urticarial
vasculitis in combination with SCLE lesions may benefit
from the use of dapsone. The author has only once
observed benefit from dapsone therapy, and therefore it
is only the first line of therapy for a minority of patients.
A variety of other antibiotics have been used for the
treatment of cutaneous LE. Recently, Rudnicka et al.27
reported that the antibiotic cefuroxime axetil resulted
in the clearing of skin lesions in three patients with
SCLE at a dose of 500 mg daily. Cefuroxime axetil is a
second-generation b-lactamase oral cephalosporin.
Others must replicate this observation before it can be
recommended for widespread use; however, it is a
relatively benign form of treatment. Another group has
reported the successful use of sulfasalazine in eight of
11 patients.28 Sulfasalazine is used for inflammatory
bowel disease and various forms of arthritis. These
authors administered 2 g daily, but noted that the
minimal effective daily dose was 15 g. The eight
patients who responded were all rapid acetylators,
while the three who failed to respond were all slow
acetylators. No serious toxicity was noted in this small
open-label case series. In contrast, Lagrange et al. noted
a drug eruption in five of six patients whom they
treated with sulfasalazine and in only two patients did
they feel that there was a beneficial effect.29
Auranofin (RidauraTM, Yamanouchi, West Byfleet,
U.K.), an oral form of gold, has been used in cutaneous
734
J.P.CALLEN
Recommendations
Cutaneous LE is a chronic or recurrent disease that may
occur at any age. It is more common in women, but men
are also affected. It may be induced or exacerbated by
drugs and therefore a careful history and intervention
such as discontinuation or substitution of a drug may
induce a remission. Tobacco smoking seems to worsen
the disease or render antimalarial therapy less effective
and when possible this behaviour should be stopped. DLE
and SCLE are exacerbated by sunlight and appropriate
sun-protective measures should be used on a daily basis.
Topical corticosteroids, intralesional corticosteroids and
oral antimalarial therapies are the standard therapies
and are effective in a majority of patients. Alternative
topical therapies while available are not proven. Various
systemic therapies beyond antimalarial agents are based
on anecdotal reports or small case series. The approach
to therapy should follow a course as outlined: (i) remove
any exacerbating factors; (ii) photoprotection; (iii) topical corticosteroids or other immunomodulating agents;
(iv) oral antimalarialhydroxychloroquine with or
without quinacrine or chloroquine with or without
quinacrine; (v) consider thalidomide, with careful monitoring to prevent pregnancy and monitoring for neur-
735
References
1 Gilliam JN, Sontheimer RD. Distinctive cutaneous subsets in the
spectrum of lupus erythematosus. J Am Acad Dermatol 1981; 4:
4715.
2 Bongu A, Chang E, Ramsey-Goldman R. Can morbidity and
mortality of SLE be improved? Best Pract Res Clin Rheumatol 2002;
16: 31332.
3 Callen JP. Management of skin disease in patients with lupus
erythematosus. Best Prac Res Clin Rheumatol 2002; 16: 24560.
4 Jessop S, Whitelas D, Jordaan F. Drugs for discoid lupus erythematosus (Cochrane Review). In: The Cochrane Library, Issue 1.
Oxford: Update Software, 2002.
5 Reed BR, Huff JC, Jones SK et al. Subacute cutaneous lupus
erythematosus associated with hydrochlorothiazide therapy. Ann
Intern Med 1985; 103: 4951.
6 Crowson AN, Magro CM. Subacute cutaneous lupus erythematosus arising in the setting of calcium channel blocker therapy.
Hum Pathol 1997; 28: 6773.
7 Bonsmann G, Schiller M, Luger TA, Stander S. Terbinafine-induced subacute cutaneous lupus erythematosus. J Am Acad Dermatol 2001; 44: 92531.
8 Callen JP, Kulp-Shorten CL, Hughes AP. Subacute cutaneous
lupus erythematosus associated with terbinafine therapy. Arch
Dermatol 2001; 137: 11968.
9 Bleumink GS, ter Borg EJ, Ramselaar CGCh, Stricker BH. Etanercept-induced subacute cutaneous lupus erythematosus. Rheumatology 2001; 40: 131719.
10 Srivastava M, Rencic A, Diglio G et al. Drug-induced, Ro SSApositive cutaneous lupus erythematosus. Arch Dermatol 2003;
139: 459.
11 Gallego H, Crutchfield CE III, Lewis EJ, Gallego HJ. Report of an
association between discoid lupus erythematosus and smoking.
Cutis 1999; 63: 2314.
12 Ueki H. Kobner-Phanomen bei lupus erythematodes. Hautarzt
1994; 45: 15460.
13 Rubin AI, Stiller MJ. A listing of skin conditions exhibiting the
Koebner and pseudo-Koebner phenomena with eliciting stimuli.
J Cutan Med Surg 2002; 6: 2934.
14 Millard TP, Hawk JLM, McGregor JM. Photosensitivity in lupus.
Lupus 2000; 9: 310.
15 Stege H, Budde MA, Grether S, Krutmann J. Evaluation of the
capacity of sunscreens to photoprotect lupus erythematosus patients by employing the photoprovocation test. Photodermatol
Photoimmunol Photomed 2000; 16: 2569.
16 Yoshimasu T, Ohtani T, Sakamoto T et al. Topical FK506 (tacrolimus) therapy for facial erythematous lesions of cutaneous
lupus erythematosus and dermatomyositis. Eur J Dermatol 2002;
12: 502.
17 Walker SL, Kirby B, Chalmers RJG. The effect of topical tacrolimus
on severe recalcitrant chronic discoid lupus erythematosus. Br J
Dermatol 2002; 147: 4056.
18 Zabawski E. Treatment of cutaneous lupus with Elidel. Dermatol
Online J 2002; 8: 25 (Letter).
19 Tebbe B, Lauy M, Gollnick H. Therapy of cutaneous lupus
erythematosus with recombinant interferon alfa-2a. Eur J Dermatol 1992; 2: 2535.
736
J.P.CALLEN
37
38
39
40
41
42
43
44
45
46
47
48
49
50