892 Case reports J AM ACAD DERMATOL

MAY 2006

Treatment of refractory subacute cutaneous lupus

erythematosus with efalizumab
Timothy H. Clayton, MB CHB, MRCPCH(UK), Stephanie Ogden, MB CHB, MRCP,
and Mark D. J. Goodfield, MB CHB, MD, FRCP
Leeds, United Kingdom

We report the case of a 47-year-old woman who first presented with erythematous plaques on the upper
portion of her right arm, which developed into an annular eruption involving the face, upper portion of the
trunk, and limbs in a predominantly photosensitive distribution. Findings from histopathologic evaluation
of a lesion from her arm were consistent with the clinical diagnosis of SCLE. After years of unsuccessful
treatment with conventional medications for SCLE, she began therapy with efalizumab and experienced
dramatic improvement in her cutaneous lesions after 6 weeks. ( J Am Acad Dermatol 2006;54:892-5.)

S ubacute cutaneous lupus erythematosus (SCLE)

is a specific form of lupus that usually carries a
good prognosis. SCLE was described originally
by Sontheimer1 in 1979 and affects predominantly
adults who exhibit mainly cutaneous disease. SCLE
presents with photosensitive, nonscarring lesions
typically involving the neck, trunk, and limbs.
Patients may have either nonscarring papulosqua-
mous lesions, annular polycylic lesions, or a combi-
nation of both.2 Antibodies to the Ro/SS-A antigen
are found in most cases. Systemic involvement may
occur, but the potential for severe systemic disease is
low. Standard treatments include the use of sun-
screens, topical and oral corticosteroids or dapsone
for acute exacerbations, and antimalarials and/or
immunosuppressive agents such as cyclosporin to
reduce the frequency of flareups. We report a patient
with chronic refractory SCLE that had failed to
respond to conventional therapies, and whose cuta-
neous manifestations improved dramatically with
efalizumab.
Efalizumab is a recombinant, humanized, mono-
clonal IgG1 antibody directed against CD11a, the
alpha subunit of leukocyte function-associated anti-
gen1 (LFA-1). (2) LFA-1 is an adhesion molecule that
is expressed on the surface of T cells and is involved
in T-cell activation and trafficking.3
From the Department of Dermatology, Leeds General Infirmary.
Funding sources: None.
Conflicts of interest: None identified.
Reprint requests: Dr Timothy Howel Clayton, MB CHB, MRCPCH(UK),
Department of Dermatology, Leeds General Infirmary, Great
George St, Leeds LS1 3EX, United Kingdom; E-mail: timhclayton@
hotmail.com.
0190-9622/$32.00
2006 by the American Academy of Dermatology, Inc.
doi:10.1016/j.jaad.2005.08.025
Abbreviations used:
LFA-1:
ICAM-1:
SLCE:
leukocyte function-associated antigen 1
intercellular adhesion molecule 1
subacute cutaneous lupus erythematosus
TNF: tumor necrosis factor
CASE REPORT
A 47-year-old lady first presented in 1997 with
3 erythematous plaques on the upper part of her
right arm. She was a nonsmoker and had an unre-
markable past medical history apart from suffer-
ing from Bartters syndrome (a potassium-wasting
syndrome) for which she was taking potassium
supplementation. She was on no other medication.
The lesions on her arm later developed into an
annular eruption involving the face, upper portion of
the trunk, and limbs in a predominantly photosen-
sitive distribution. These appearances were consis-
tent with a clinical diagnosis of SCLE. (Fig 1, A-C ).
Serum immunology was negative for antinuclear
antibody and positive for extractable nuclear anti-
gens Ro and La. Complete blood count and a
biochemical profile were normal. Histopathologic
evaluation of a lesion from the upper portion of her
arm revealed epidermal atrophy, vacuolar degener-
ation of the basal cell layers, numerous civatte
bodies, pilosebaceous atrophy, and a moderately
dense perivascular lymphohistiocytic infiltrate
within the upper dermis, findings in keeping with
the clinical diagnosis of SCLE. The patient was
treated with a number of agents that resulted
in either a poor response or the development of
side effects that necessitated discontinuation of
treatment; these treatments are summarized in
Table I.
J AM ACAD DERMATOL Case reports 893
VOLUME 54, NUMBER 5

Table I. Responses to treatment received and side effects

Treatment Response Duration of therapy Side effects
Topical clobetasol propionate Poor 1 mo
Hydroxychloroquine 200 mg twice daily Poor 2 mo
Qinacrine 200 mg/d Poor 2 mo
Chloroquine 200 mg twice daily Poor 2 mo
Combination antimalarials No response
Prednisolone 40 mg/d Partial response; flare Periodic use to gain
on reducing dose control of disease
Dapsone 50 mg twice daily Poor 3 mo
Auranofin 3 mg twice daily Poor 3 mo
Azathioprine 50 mg twice daily No response 3 mo
Thalidomide 50 mg twice daily Rapid response 4 mo Neuropathy
IV methyl prednisolone 1 g and Partial response; flare 3 mo GI upset and severe
cyclophosphamide 50 mg, after completing malaise
33 pulsed therapy treatment
Methotrexate 15 mg/wk Partial control 4 mo GI upset, abnormal
liver function
Clofazimine 100 mg/d Poor 2 mo; used in combination
with isotretinoin and
mycophenolate
Isotretinoin 20 mg/d Poor 2 mo; used in combination
with clofazimine and
mycophenolate
Mycophenolate 1g 3 times daily Poor 2 mo; used in combination
with clofazimine and
isotretinoin
Leflunomide 20 mg/d No response 2 mo

GI, Gastrointestinal; IV, intravenous.

Fig 1. Patient before treatment with efaluzimab. A, face. B, back. C, torso.

She became clinically depressed and withdrawn
after several years of unsuccessful treatments, and
her quality of life had suffered severely. Only corti-
costeroids were able to offer some control of her
symptoms. In January 2005, she began treatment
with subcutaneous efalizumab at a dose of 100 mg
per week (1mg/kg/week). She was not receiving
any medication before initiating treatment with
efazilumab that may have been capable of precipi-
tating SCLE disease activity, such as thiazides,
calcium channel blockers, terbinafine, and so forth.
Within 6 weeks of beginning this therapy, her cuta-
neous manifestations began to improve dramatically
(Fig 2, A-C ). The treatment with efalizumab was
well-tolerated with no adverse effects. Despite
continued weekly subcutaneous therapy with
894 Case reports
Fig 2. Patient after treatment with efaluzimab. A, face.
B, back. C, torso.
efalizumab, she developed a slight flare of her
cutaneous disease in April 2005, which was con-
trolled by increasing the efalizumab dose to 125 mg
per week (1.25mg/kg/week). At present, she has
minimal activity in her cutaneous disease after 5
months of weekly subcutaneous therapy with
J AM ACAD DERMATOL
MAY 2006
efalizumab. She is delighted with the marked im-
provement in her condition. The therapy with
efalizumab also has improved the quality of her life
significantly.
DISCUSSION
This case reports the use of efalizumab in the
treatment of SCLE. This condition usually has a
relatively benign prognosis, and a number of thera-
peutic options, including: topical and oral steroids,4
antimalarials,5 methotrexate,6 mycophenloate,7 iso-
tertinoin,8 thalidomide,9 auranofin,10 and clofazi-
mine,11 are available to patients with this disease.
However, the patient in this case had particularly
severe cutaneous disease. She had failed to respond
to conventional therapies, and she also had experi-
enced severe side effects from several of the treat-
ments that she had received.
Systemic lupus erythematosus (SLE) is an autoan-
tibody- and immune complex-mediated disease that
results in inflammation in all affected areas. Tumor
necrosis factor (TNF) has been found to be markedly
increased and appears to be bioactive in the sera of
patients with active SLE; levels of TNF have been
shown to correlate with SLE disease activity.12-16
Anti-TNF therapy has been proven to be effective in
SLE, although it remains controversial. The primary
concerns derive from data reporting the induction
of antinuclear antibodies and anticardiolipin anti-
bodies, and some rare cases of drug-induced lupus-
like syndromes in patients treated with anti-TNF
agents.17,18 There have been reports of patients
developing SCLE while on etanercept, a recombinant
human TNF receptor fusion protein.19 There also has
been a report in which SCLE skin disease activity in a
patient with rheumatoid arthritis responded remark-
ably to treatment with etanercept.20
With this in mind, treatment with efalizumab was
initiated. Efalizumab is a recombinant, humanized,
monoclonal IgG1 antibody directed against CD11a,
the alpha subunit of LFA-1. LFA-1 is an adhesion
molecule expressed on the surface of T lymphocytes
and is involved in T-lymphocyte activation and
trafficking of T cells from the circulation into the
skin. Efalizumab has been used successfully to treat
psoriasis.21 When this medication binds to CD11a,
the interaction of LFA-1 with intercellular adhesion
molecule 1 (ICAM-1) is disrupted. ICAM-1 is an
important cell surface adhesion molecule, which is
upregulated on keratinocytes and endothelial cells
within psoriatic plaques. LFA-1 also is found on the
cell surface of antigen-presenting cells. By disturbing
LFA-1/ICAM-1 binding, efalizumab interferes with
3 important events in the inflammatory process: It
J AM ACAD DERMATOL
VOLUME 54, NUMBER 5
decreases the efficiency of initial T-cell activation in
lymph nodes, it disrupts the trafficking of T lympho-
cytes to the target tissue (eg, the skin), and decreases
reactivation of memory T cells in the sites of inflam-
mation. We believe that efalizumab may exert a
similar effect within the lesions of SCLE, resulting in
suppression of the inflammatory process and sub-
sequent clinical improvement, as observed in this
case.
In conclusion, efalizumab is an interesting novel
alternative treatment for SCLE when standard thera-
pies have failed or contraindicated. However, the use
of this drug must be monitored carefully. There are
still some questions about safety and whether this
treatment might elevate antinuclear antibodies, and
antiedouble-stranded DNA and anticardiolipin anti-
bodies. There have been reported cases of drug-
induced lupuslike syndromes in patients treated with
similar anticytokine therapies. Finally, a prospective
study with long-term follow-up is required to eval-
uate the usefulness of efalizumab in the treatment of
subacute cutaneous lupus erythematosus.
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