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STUDENT PROJECT
CUTANEOUS DISCOID LUPUS
CREATED BY:
PT. GEDE YUDI DARMA WIJAYA SUPARTA (0802005060)
I GST AYU PREMA YANI SIDEMEN (0802005006)
I GEDE YUHANA DHARMA SASMITA (0802005075)
FARADILLA NOVITA ANGGREINI (0802005008)
THANATHAN R. SANTHERANATHAN (0802005168)
MYELONE THARMASEELAN (0802005164)
POONEETHAWATHI SANTRAN (0802005169)
SUBA KAMARASAMY (0802005165)
KEREN KARUNYA SINGAM (0802005200)
YOJENETHA SUBRAMANIAM (0802005177)
SGD B.1 ENGLISH CLASS
7TH
SEMESTER
FACULTY OF MEDICINE UDAYANA UNIVERSITY
DENPASAR
2011
ii
PREFACE
We would like to say thanks to the Lord for His charity, because of Him, we can
finish this scientific writing as our student project on the time that have been
given to us.
Scientific writing based on the literatur titled “Cutaneous Discoid Lupus” was
made in order to complete and pass student project of skin and disorders block in
7th
semester. Wishes that we can be able and applicate our ability to compile
scientific writing systematically which comes from valid literatures.
In this chance, I would thank to:
1. dr. I G. N. Darmada, Sp. KK as our block coordinator of Skin and
Disorder Block,
2. All the planners team and lecturers in Skin and Disorder Block,
3. All the supervisors team of student project in Skin and Disorder Block,
4. dr. Ida Ayu Ika Wahyuniari, M. Kes as our facilitator, and
5. All parties that have given supports for us in compiling this scientific
writing neither morally or materially.
We recognize that this writing still far away from perfection. Accordingly, we
wish more suggestions and critics for making this writing better. Finally, we also
hope this scientific writing can give positive contribution for the development of
knowledge, especially in medical field.
Denpasar, 24th
of October 2011
Writers
iii
CONTENTS
Content Page
REPORT COVER ........................................................................................ i
PREFACE ..................................................................................................... ii
CONTENTS .................................................................................................. iii
FIGURE LISTS ............................................................................................ iv
TABLE LISTS .............................................................................................. v
ABBREVIATIONS ...................................................................................... vi
SECTION I INTRODUCTION .............................................................. 1
SECTION II CUTANEOUS DISCOID LUPUS .................................... 3
2.1 Etiology and Epidemiology of Cutaneous Discoid Lupus 3
2.2 Pathophysiology of Cutaneous Discoid Lupus ............ 3
2.3 Clinical Features of Cutaneous Discoid Lupus .............. 7
2.4 Diagnosis of Cutaneous Discoid Lupus ........................ 10
2.4.1 Diagnostic Strategies ........................................ 10
2.4.2 Differential Diagnosis ...................................... 13
2.5 Management for Cutaneous Discoid Lupus ................. 15
2.5.1 Topical Corticosteroids .................................... 15
2.5.2 Antimalarials .................................................... 16
2.5.3 Excision and Laser Therapy ............................. 17
2.5.4 Long-term Monitoring ...................................... 17
2.5.5 Other Drugs Used for the Treatment of DLE ... 17
2.5.6 Education .......................................................... 19
2.6 Complication and Prognosis of Cutaneous Discoid Lupus 19
SECTION VI CONCLUSION ................................................................... 20
REFERENCES ............................................................................................. 21
iv
FIGURE LISTS
Figure 1. Pathophysiology of Systemic Lupus Erythematosus ............... 4
Figure 2. DLE: erythema, hyperkeratosis, and scarring alopecia (a);
peripheral erythema, central hyperkeratosis and scarring
(upper arm) (b) ......................................................................... 8
Figure 3. Discoid Lupus Erythematosus on the face and oral mucosa ..... 11
Figure 4. Lupus erythematosus: histopathological aspects and immuno
fluorescence of oral lesions. (A) Hyperkeratosis, acanthosis
and intense lichenoid infiltrate, (B) Spongiosis, lymphocyte
exocystosis and basal layer destruction, (C) Colloid body,
(D) Intense perivascular chronic inflammatory infiltrate,
(E) Basement membrane thickening and perivascular infiltrate,
(F) DIF showing thickening of epithelial basement membrane 12
v
TABLE LISTS
Table 1. Demographic data of 130 Thai patient with DLE ..................... 8
Table 2. Other manifestation detected in 130 Thai patient with DLE ..... 9
Table 3. Laboratory abnormalities of 130 Thai patient with DLE ........... 9
Table 4. Differences between SLE, SLCE, and DLE .............................. 13
vi
ABBREVIATIONS
AICD = Activation Induced Cell Death
ARA = American College of Rheumatology
CBC = Complete Blood Count
CCLE = Chronic Cutaneous Lupus Erythematosus
CLE = Cutaneous Lupus Erythematosus
COX = Cyclooxygenase
DLE = Discoid Lupus Erythematosus
DNA = Deoxyribonucleic Acid
IFN = Interferon
iNOS = Inducible Nitric Oxide Synthase
LBT = Lupus Band Test
LE = Lupus Erythematosus
NO = Nitric Oxide
PABA = Para-aminobenzoic Acid
PDC = Plasmacytoid Dendritic Cells
PGE2 = Prostaglandin E2
SCLE = Subacute Cutaneous Lupus Erythematosus
SLE = Systemic Lupus Erythematosus
TNF = Tumor Necrosis Factor
UV = Ultra Violet
1
SECTION I
INTRODUCTION
Discoid Lupus Erythematosus (DLE) is a chronic, scarring, atrophy producing,
photosensitive dermatosis. Patients with DLE rarely fulfil four or more of the
criteria used to classify Systemic Lupus Erythematosus (SLE). DLE may occur in
patients with SLE, and some patients <5% with DLE progress to SLE.1 DLE
lesions are frequently fairly characteristic. It is characterized by erythema;
telangiectasia; adherent scale which varies from fine to thick; follicular plugging;
dyspigmentation; atrophy; and scarring. It usually sharply demarcated and can be
round, thereby giving rise to the term “discoid” (disc like).2
The DLE lesion
localized in 80% of patients to the face, scalp and ears, and in 20% of cases to the
upper trunk and extremities.3
The prevalence of cutaneous lupus varies from 14.6 to 68 per 100 000 people,
with a female predominance of 3:1.3
The usual age of onset is between 20 and 40
years, which is about 20 years younger than SLE.1 DLE may be more common in
African-Americans.4 Although DLE is an autoimmune disease, it is thought to
result from interplay of certain genetic factors, environmental factors like
ultraviolet light, and hormonal factors with antibodies.1
In addition to a routine
history and physical examination, the workup for DLE should include a complete
blood count, antinuclear antibody levels, anti-Ro, anti-La, hepatic and renal
function tests, and urinalysis. Patient with DLE lesion should be consider a
diagnosis of SLE by using the American College of Rheumatology (ARA)
criteria. A biopsy for histopathology of a fresh lesion or a biopsy for
immunofluorescence of an old lesion can confirm the diagnosis.5
Effective early therapies for DLE are available, but patients who do not respond
appropriately may end up with deep scars, alopecia, and pigmentary changes that
are considerably disfiguring. Therefore, the goal of treatment is not only to
improve the appearance of the skin by minimizing the scarring and preventing
further lesions, but also to prevent future complications.5 The primary therapeutic
approach is to educate patients regarding exposure to sunlight. Sunprotective
1
2
measures include the use of high-SPF sunscreen lotions and protective clothing,
such as baseball caps without vent holes and wide-brimmed hats. Current
treatment options for DLE include antimalarial agents such as chloroquine, topical
and intralesional glucocorticoids, and thalidomide. The use of potent topical
steroids may prevent significant scarring and deformity, especially of the face.
Common side effects include steroid withdrawal syndrome, perioral dermatitis,
steroid acne, and rosacea. All of these side effects can be treated and result in less
long-term deformity than untreated.5
3
SECTION II
CUTANEOUS DISCOID LUPUS
2.1 Etiology and Epidemiology of Cutaneous Discoid Lupus
Cutaneous discoid lupus or Discoid Lupus Erythematosus (DLE) is an
autoimmune inflammatory disorder of the skin that often leads to scarring and
alopecia. It may be localized to sun-exposed areas such as the face, ears, and scalp
but occasionally is much more extensive, involving the trunk and extremities.
Most patients are otherwise healthy, and DLE may be the only clinical finding.5
The prevalence of cutaneous lupus varies from 14.6 to 68 per 100 000 people,
with a female predominance of 3:1.3 The usual age of onset is between 20 and 40
years, which is about 20 years younger than SLE.1 DLE may be more common in
African-Americans.4 While about 15% to 20% of patients with systemic lupus
erythematosus (SLE) manifest DLE lesions, only about 5% to 10% of patients
with DLE go on to develop SLE.5
Like SLE, DLE is believed to be an autoimmune disorder. Unlike SLE, however,
DLE patients do not have similar serologic abnormalities. Skin trauma and
ultraviolet light exposure have been reported to induce or exacerbate the lesions of
DLE. Sex hormones may also play a role: exacerbation may occur during
pregnancy, during menstrual or premenstrual periods, or while taking oral
contraceptives. Drugs such as procainamide, hydralazine, isoniazid,
diphenylhydantoin, methyldopa, penicillamine, guanides, and lithium may also
precipitate DLE lesions.5 Environmental factors including ultraviolet radiation,
viruses, hormones, medications, and stress have been suggested as initiating
factors of cutaneous LE.6
2.2 Pathophysiology of Cutaneous Discoid Lupus
Due to the polygenic and multifactorial nature of Lupus Erythematosus, the
pathogenesis of the disease remains unclear.7 Pathophysiology of DLE is thought
to be similar to SLE in which autoimmune response attack the skin tissue. In SLE,
interactions between susceptibility genes and environmental factors result in
3
4
abnormal immune responses: production of pathogenic autoantibodies (Figure 1)
and immune complexes, which bind to target tissues, with activation of
complement and phagocytic cells that recognize Ig-coated circulating blood cells.
Activation of complement and immune cells leads to release of inflammatory
mediators. In the setting of chronic inflammation, accumulation of growth factors
and products of chronic oxidation contribute to irreversible tissue damage as in
skin and other tissue.8
Figure 1. Pathophysiology of Systemic Lupus Erythematosus.8
Abnormal apoptosis, the presence of autoantibodies, and infiltration by
plasmacytoid dendritic cells (PDCs), T cells as well as B cells are important
factors for the induction and maintenance of Cutaneous Lupus Erythematosus
(CLE) in SLE patients.6 From this point of view, the pathophysiology of DLE in
CLE, might be include several mechanisms:
a. Photosensitivity (Ultraviolet Radiation)
Photosensitivity shows a strong association with manifestation of all CLE
subtypes, and abnormal reactivity to ultraviolet (UV) light is an important factor
in the pathogenesis of this disease. It has been demonstrated that broadband
sunscreens are able to suppress the induction of skin lesions on UV irradiation in
patients with CLE.9
5
b. Accumulation of PDCs, T and B Cells
PDC is the natural IFN-α/β producing cells, results in an increased expression of
IFN-α/β inducible protein. The IFN-α subsequently induces activation of
autoreactive T cells, CXCR3+ lymphocytes, CXCL9
+ and CXCL10
+ keratinocytes
and endothelial cells in cutaneous LE, therefore bringing on peripheral intolerance
and inflammation. However, up-regulation of IFN-α in DLE lesions has never
been demonstrated in cutaneous LE patients without SLE.6 It is known that
autoimmune T helper cells drive pathogenic autoantibody production in LE, but
the mechanisms maintaining those pathogenic T cells are unknown.10
Velez et al.
found that T cells and neutrophil activated, downstream cell signaling molecules
seem to play significant roles in the pathophysiology of DLE in skin adnexal
structures and dermal blood vessels. In DLE lesion, the presence of COX-2
(marker of immune activation), an inducible enzyme that is normally absent in
skin cells; however, in response to growth factors, tumor promoters and some
cytokines, it exhibits a rapid and transient expression.10
c. Role of Regulatory T Cells and Chemokines for Lymphocyte Recruitment
Naturally occurring CD4+CD25
+ regulatory T cells (Treg) have emerged as an
important factor in our understanding of self tolerance and mechanisms in
autoimmune diseases. Recently, a decreased number of peripheral Treg were
found in SLE patients. Whether the number of Treg is also impaired in patients
with CLE. Recently, a superfamily of small chemotactic proteins has been shown
to regulate lymphocyte trafficking under inflammatory conditions, and it has been
demonstrated that UV exposure induces the expression of T-cell attracting
chemokines. Furthermore, the CXCR3 ligands CXCL9, CXCL10 and CXCL11
have been identified as the most abundantly expressed genes in patients with CLE.
Additionally, it has been reported that the CCR4 ligand TARC/CCL17 is strongly
expressed in skin lesions and elevated in the serum of patients with CLE.9
d. Aberrant Expression of Inducible Nitric Oxide Synthase
Nitric oxide (NO) is an important regulator of apoptosis and has an implication in
the course of various autoimmune diseases. Interestingly, this molecule has also
different effects on the various cell types within the skin, and it has been shown
that NO can protect against UVA-induced apoptosis by increasing Bcl-2
6
expression and inhibiting UVA-induced overexpression of Bax protein in
endothelial cells. Furthermore, UV (A and B) exposure has also been shown to
modulate local NO production, inducible nitric oxide synthase (iNOS), which is
expressed by epidermal keratinocytes after endogenous and/or exogenous stimuli
up to 48 hours. In striking contrast, an iNOS-specific signal appeared only 72
hours after UV exposure and persisted in the evolving skin lesions up to 25 days
in patients with CLE. It has further been reported that NO production is increased
in patients with SLE possibly due to upregulated iNOS expression in activated
endothelial cells and keratinocytes.9
e. Abnormal Apoptosis
Daldon and Lage suggest that apoptosis of keratinocytes has been indicated as a
key event in triggering cutaneous lupus lesions through various apoptotic
pathways such as p53, tumor necrosis factor-alpha (TNF-α) and Fas/FasL. It is
speculated that the aberrant keratinocytes may be unable to express the essential
proteins required to regulate apoptosis, and are hence unable to prevent the
apoptosis induced by UV radiation. Another mechanism that has been suggested
is that these keratinocytes may have an anomalous major histocompatibility
complex (MHC) or may release abnormal cytokines.11
Autoreactive T cells are normally eliminated by 1) functional inactivation
(anergy), 2) activation induced cell death (AICD; directed apoptosis) through
death receptor (Fas) signaling, and 3) apoptosis by markedly upregulating and
sustaining COX-2 expression. Inhibition of COX-2 caused apoptosis of the
anergy-resistant lupus T cells by augmenting Fas signaling and markedly
decreasing the survival molecule c-FLIP (cellular homolog of viral FLICE
inhibitory protein). It also found that selected COX-2 inhibitors were able to
suppress the production of pathogenic autoantibodies to DNA by causing
autoimmune T-cell apoptosis, an effect that was independent of prostaglandin E2
(PGE2). Based on this findings, the T cells and the cell signaling cascades are
actively targeting not only the base membrane, but also skin adnexal structures;
thus, the process may the result in dermal scarring and hair loss in some patients
with LE.10
7
f. Impaired Clearance of Apoptotic Cells
In several reports, a potentially crucial role in the initiation of the autoimmune
reaction cascade has been attributed to UV-induced keratinocyte apoptosis.
Interestingly, a significantly higher number of apoptotic nuclei in the epidermis
has been described in primary and UV-induced skin lesions of CLE patients
compared with normal healthy donors. It has been reported that apoptotic cells
accumulate in the germinal centres of lymph nodes from patients with SLE, which
might be due to impaired phagocytic activity or caused by the absence of tingible
body macrophages. Further, recent data support the hypothesis that a defective or
delayed clearance leads to the accumulation of apoptotic cells and cellular debris
in tissue culture and circulation. Consequently, these results indicate that
apoptotic cells accumulate and subsequently enter late stages of apoptotic cell
death including secondary necrosis in various tissues of patients with this disease.9
2.3 Clinical Features of Cutaneous Discoid Lupus
DLE is the most common form of Chronic Cutaneous Lupus Erythematosus
(CCLE). Characteristic lesions are sharply-bordered, erythematous, keratotic
plaques that grow peripherally and show a coin-shaped (“discoid”)
appearance.12,13
The center of the lesion often contains firmly attached areas of
white, follicular hyperkeratosis with hyperesthesia; these are painful if lifted
manually (the “carpet tack sign”). Over the course of disease, DLE plaques
become atrophic and scar with central depigmentation and peripheral
hyperpigmentation. Hair follicles are irreversibly damaged and hair-bearing areas
such as the scalp, eyebrows, and bearded region of the face develop scarring
alopecia (Figure 2a).12
The sites of predilection of DLE are the face and scalp (localized form), especially
the cheeks, forehead, ears, nose, and upper lip. Characteristic pitting scars can
result periorally. Especially in men with involvement of the nose or ears scarring
can lead to mutilation with considerable disfigurement. DLE, involving the upper
part of the trunk and the extensor surfaces of the extremities (disseminated form)
(Figure 2b) is less common. Involvement of palmar and plantar regions in DLE
8
causes heavy pain. Painful lesions of the oral mucosa, especially the buccal
mucosa, are relatively uncommon. Often lesions of the buccal mucosa resemble
lichen planus, but tend to have a radial, brush-like appearance and usually radiate
from a central inflammatory erythema or erosion. Exposure to the sun or irritating
stimuli (Köbner phenomenon) can provoke or exacerbate disease. DLE can co-
exist with all other subtypes of CLE.12
Figure 2. DLE: erythema, hyperkeratosis, and scarring alopecia (a); peripheral
erythema, central hyperkeratosis and scarring (upper arm) (b).12
Retrospective research from Insawang et al. showed that 58% patient DLE
presented with a localized form of classic DLE with the primarily involved
location on the face (52.3%) (Table 1) with common other manifestation is malar
rash (16.2%) (Table 2) and positive ANA result 68.5% (Table 3); 45.4% fulfilled
SLE criteria; 45.7% had DLE which preceded the diagnosis of SLE with 50% of
these patient would progress to develop SLE 2 years from the disease onset;
54.6% had only cutaneous lesions without fulfilling the criteria of SLE.14
Table 1. Demographic data of 130 Thai patient with DLE14
9
DLE lesions have well-defined pathognomonic histological features, which help
in confirming the diagnosis of chronic discoid erythematosus in majority of the
patients. The principal immunologic finding of clinical relevance in CLE is the
presence of immune deposits at dermoepidermal junction (DEJ) of the lesional
skin i.e. the lupus band test (LBT).13
Histopathological findings include
hyperkeratosis, parakeratosis, follicular plugging, telangiectasias, and atrophy of
the epidermis. Liquefaction or hydropic degeneration of the basal layer leads to
pigmentary incontinence. A perivascular and perifollicular mononuclear
inflammatory cell infiltrate is present in the superficial and deep dermis. Direct
immunofluorescence demonstrates immunoglobulins and complement deposits at
the dermoepidermal junction.5
Table 2. Other manifestation detected in 130 Thai patient with DLE14
Table 3. Laboratory abnormalities of 130 Thai patient with DLE14
10
2.4 Diagnosis of Cutaneous Discoid Lupus
2.4.1 Diagnostic Strategies
Diagnosis involves differentiating DLE from SLE, as the skin lesions may be the
same or very similar. Tests include:
a. Medical History
Patients may complain of mild pruritus or occasional pain within the lesions, but
most patients are asymptomatic. Approximately 5% or less of patients with DLE
have accompanying systemic involvement. Arthralgia or arthritis may occur.
Patients may manifest any symptom of SLE. Therefore, the history should include
an assessment for symptoms of pleuritis, pericarditis, neurologic involvement, and
renal involvement. Malignant degeneration of chronic lesions of lupus LE is
possible, although rare, leading to nonmelanoma skin cancer. Mucin deposition is
a factor in the histopathology of LE. Some patients develop such a massive
amount of mucin that lesions become raised and assume a different morphology.
Porphyria cutaneatarda appears to be overrepresented in LE patients. Often, the
porphyria is discovered when antimalarials first are administered. Lichen planus ̶
like lesions may be part of an overlap between LE and lichen planus or may occur
as a result of antimalarial therapy. Psoriasis is a common disease, although it is
not clear whether it is more common in LE patients.15
b. Physical Examination
DLE lesions frequently are characteristic. The primary lesion is an erythematous
papule or plaque with slight to moderate scaling (Figure 3). As the lesion
progresses, the scale may thicken and become adherent, and pigmentary changes
may develop, with hypopigmentation in the central or inactive area and
hyperpigmentation at the active border.12,15
Lesions spread centrifugally and may
merge. As lesions age, dilation of follicular openings occurs with a keratinous
plug, termed follicular plugging or patulous follicles. Resolution of the active
lesion results in atrophy and scarring. Early lesions may be difficult to distinguish
from those of Subacute Cutaneous Lupus Erythematosus (SCLE). DLE lesions
often are photodistributed, but relatively unexposed skin also may be affected.
11
The scalp is a common area of involvement, and permanent alopecia may
result.15,16
Patients with DLE often are divided into 2 subsets: which is localized and
widespread. Localized DLE occurs when the head and neck only are affected,
while widespread DLE occurs when other areas are affected, regardless of
whether disease of the head and neck is seen. Patients with widespread
involvement often have hematologic and serologic abnormalities, are more likely
to develop SLE, and are more difficult to treat. Mucosal surfaces may be affected
by lesions that appear identical to DLE of the skin or by lesions that may simulate
lichen planus. Palms and soles may be affected, but this occurs in less than 2% of
patients. DLE lesions may become hypertrophic or verrucous. This subset is
manifested by wartlike lesions, most often on the extensor arms. Hypertrophic
lesions of LE must be differentiated from warts, keratoacanthomas, or squamous
cell carcinoma. These lesions are more difficult to treat.15
Figure 3. Discoid Lupus Erythematosus on the face and oral mucosa.16
c. Blood Tests
A complete blood count, basic metabolic panel, hepatic function profile,
prothrombin time, and partial thromboplastin time were normal. Urinalysis may
contained leukocytes. C-reactive protein was 15mg/dL. Anti-nuclear antibody titer
was less than 40. Anti-double-stranded DNA, SS-A, SS-B, Smith, and
ribonucleoprotein antibodies were not detected. Complement levels and aldolase
were normal. A rapid plasma regain test was non-reactive.15
d. Biopsy of a Skin Lesion
Deposition of immunoglobulin and/or complement at the dermal-epidermal
junction is a characteristic feature of LE. Tissue may be examined from skin
12
lesions (lesional) or normal skin (nonlesional). Testing of nonlesional,
nonexposed skin is termed the lupus band test (LBT). Approximately 90% of
patients with DLE manifest a positive direct immunofluorescence (DIF) test on
lesional skin; however, the presence of immunoreactants in the basement
membrane zone of lesional skin is not specific for lupus and can be seen in a
variety of inflammatory skin diseases. Older lesions or very early lesions may be
more likely to be negative on immunofluorescence microscopy. Only patients
with SLE have a positive LBT, defined as the presence of multiple
immunoreactants in the basement membrane zone. LBTs are neither sensitive nor
specific and mostly have been replaced by advances in serologic testing.13
Figure 4. Lupus erythematosus: histopathological aspects and
immunofluorescence of oral lesions. (A) Hyperkeratosis, acanthosis
and intense lichenoid infiltrate, (B) Spongiosis, lymphocyte
exocystosis and basal layer destruction, (C) Colloid body, (D) Intense
perivascular chronic inflammatory infiltrate, (E) Basement membrane
thickening and perivascular infiltrate, (F) DIF showing thickening of
epithelial basement membrane.17
There is epidermal thinning with hyperkeratosis, vacuolar alteration of the basal
layer, and a superficial and deep, perivascular and periadnexal lymphocytic
infiltrate (Figure 4). A periodic acid-Schiff stain shows a thick basement
13
membrane, and a colloidal iron stain shows increased deposits of connective-
tissue mucin. Histopathologic features include an interface dermatitis with a
superficial and deep, perivascular and periadnexal infiltrate that is composed
primarily of lymphocytes. Liquefaction degeneration of basal keratinocytes with
melanin incontinence, increased dermal deposition of mucin, and diffuse
thickening of the basement membrane are observed.13,17
Follicular plugs may be prominent in discoid lesions. Immunoglobulins and
complement proteins are deposited in a granular distribution along the dermal-
epidermal junction of lesional skin in up to 90 percent of cases of chronic
cutaneous lupus erythematosus In photosensitive cutaneous lupus, ultraviolet light
is hypothesized to induce apoptosis of keratinocytes, which results in increased
autoantigen display, increased local cytokine release, activation of dendritic cells
and T-lymphocytes, and autoantibody-mediated tissue injury Other proposed
mechanisms for the development of lupus erythematosus include molecular
mimicry and epitope spreading in response to exposure to infectious agents.13,17
2.4.2 Differential Diagnosis
Differential diagnosis is wide. The differential diagnosis of DLE is extensive and
includes actinic keratosis, dermatomyositis, granuloma annulare, granuloma
faciale, keratoacanthoma, lichen planus, subacute cutaneous lupus erythematosus,
psoriasis, rosacea, sarcoidosis, squamous cell carcinoma, syphilis, and nongenital
warts.5
Table 4. Differences between SLE, SLCE, and DLE7
Feature SLE SCLE DLE
Lesional character
Scale Fine, easily detached Fine, easily detached Thick, adherent
Follicular atrophy Absent Absent Present
Photodistribution Present Marked Present
Scarring Absent Absent Present
Atrophy Absent-usually Absent-usually Present-often
marked
Pigmentary
alteration Slight Slight Often marked
Telangectasia Present Present Present
Positive Lupus Band Test
Lesional skin >50% 50% 90%
Nonlesional skin 90% (active)
30% (inactive) 30% 0-10%
SLE criteria
14
Presence of 4/11
criteria
At least 4 present in
all SLE patient
40% will have 4
criteria
10% will have 4
criteria
Histopathology examination
Poor inflammatory
interface dermatitis
Slight to no
epidermal atrophy
Normal BM
thickness
No follicular
plugging
Prominent papillary
dermal edema and
dermal mucin
Dyskeratosis in
upper spinous layer
Prominent epidermal
atrophy
Normal BM or mild
thickening
Follicular plugging
Mild to moderate
superficial dermal
mononuclear
infiltrate
Lymphocyte rich
interface dermatitis
Less epidermal
atrophy
Prominent BM
thickness
Prominent follicular
plugging and
degeneration
Dense superficial
and deep
perivascular and
periadnexal infiltrate
Dermal fibrosis
a. Systemic Lupus Erythematosus (SLE)
Skin manifestations are a common presentation of SLE. The photosensitive malar
or butterfly rash is characteristic. This erythematous rash extends from the cheeks
over the bridge of the nose, sparing the nasolabial folds. It can be painful and
pruritic, usually lasts a few days, heals without scarring, but often recurs after sun
exposure.For a diagnosis of SLE, ≥4 of the following 11 criteria are requiredsuch
as malar rash, discoid rash, photosensitivity, oral ulcers, arthritis, serositis, renal
disorder, neurological disorder,haematological disorder, immunological disorder,
ANA.2
b. Subacute Cutaneous Lupus Erythematosus (SCLE)
SCLE lesions begin as small, erythematous, slightly scaly papules that evolve into
either psoriasiform (papulosquamous) or annular forms. The lesions typically
have erythematous crusted margins, usually sparing the face and mostly affecting
the neck, arms, and upper torso. Although telangiectasia may be seen, permanent
pigment changes and scarring are absent.7
c. Psoriasis
Lesions are red, inflamed, silvery-white scaly and circumscribed papules and
plaques on elbows, knees, extensor limbs, and scalp. Psoriatic nails have a pitted
surface and/or hypertrophic (subungual) changes.2
d. Rosacea
15
Common chronic disorder of the skin characterised by redness, flushing, and other
cutaneous findings that often include telangiectasias, roughened skin, rhinophyma,
and general inflammation that can resemble acne.Typically affects the convexities
of the central face, including the nose, cheeks, eyelids, and forehead. Papules
and/or pustules occur in crops.2
e. Polymorphous Light Eruption (PMLE)
Considered an exclusively photo-triggered dermatosis that can express several
clinical forms. PMLE lesions are usually itchy papules, eczematous plaques, or
vesicles, often with associated urticaria, and develop within 24 hours of sun
exposure.2
f. Lichen Planus
Refers to lichen planus of the hair follicles. Presents with alopecia associated with
hyperkeratotic papules and perifollicular erythema. Typical lichen planus lesions
affecting skin, nails, and buccal mucosa may also be present.2
2.5 Management for Cutaneous Discoid Lupus
DLE is a scarring autoimmune disease that can linger on for a prolonged period,
not surprisingly, the psychological impact is considerable. Consequently there is a
need for treatment, often prolonged, that incurs considerable expenditure for
health facilities. Early effective treatment may lead to total clearing of skin
lesions, but failure of treatment results in permanent scarring, the depressed scars,
hair loss, and pigmentary changes are often extremely disfiguring, particularly in
darker-skinned people.16
2.5.1 Topical Corticosteroids
Topical steroids are the mainstay of treatment of DLE. Patients usually start with
a potent topical steroid applied twice a day, then switch to a lower potency steroid
as soon as possible. The minimal use of steroids reduces the recognized side
effects like atrophy, telengiaectasiae, striae, and purpura. Intralesional steroids are
particularly useful to treat chronic lesions, hyperkeratotic lesions, and those that
do not respond adequately to topical steroids. Recognized side effects of
16
intralesional steroids include cutaneous atrophy and dyspigmentation, which are
not significant risks in experienced hands.18
Intralesional injection of corticosteroids (typically, this author uses triamcinolone
acetonide 3 mg/mL) is useful as adjunctive therapy for individual lesions.
Potential for atrophy relates to the amount of corticosteroid injected in any 1 area;
therefore, dilute concentrations are preferred with limit the total dose to avoid
systemic toxicity. For patients with progressive or disseminated disease or in
those with localized disease that does not respond to topical measures, the
addition of systemic agents should be considered.16
2.5.2 Antimalarials
Treatment with antimalarial drugs constitutes first line systemic therapy for DLE.
Therapy with antimalarials, either used single or in combination, is usually
effective. The three commonly used preparations include chloroquine,
hydroxychloroquin, and mepacrine. It is customary to start hydroxychloroquine at
a dose of 200 mg per day for an adult and, if there are no untoward
gastrointestinal or other side effects, to increase the dose to twice a day. No more
than 6.5 mg/kg/day should be administered. It is important to emphasize to the
patient that it may take between 4 to 8 weeks for any clinical improvement.19
An
ophthalmological evaluation is advisable before starting antimalarial treatment,
and should repeat it at 4 to 6 month intervals during treatment.5
In general, hydroxychloroquine and mepacrine are safe, well-tolerated drugs and
adverse effects are relatively few, the most widely recognized being retinal
toxicity. Chloroquine causes macular pigmentation that progresses to a typical
bull’s eye lesion and then to widespread retinal pigment epithelial atrophy
resembling retinitis pigmentosa which is dose related. The side effect spectrum
between chloroquine and hydroxychloroquine is different, with ocular toxicity
being mainly, although perhaps not exclusively, seen after chloroquine use. Other
adverse effects of antimalarials include gastrointestinal symptoms, such as nausea
and vomiting, and cutaneous side effects including pruritus, lichenoid drug
reactions, annular erythema, hyperpigmentation, and hematological disturbances
like leukopenia and thrombocytopenia.16,19
17
Hemolysis is reported in individuals who are deficient in the enzyme glucose-6-
phosphate-dehydrogenase. Hydroxychloroquine has caused toxic psychosis when
used for the treatment of discoid lupus. Prolonged mepacrine therapy mayproduce
a yellow discoloration of the skin and urine. Hepatitis and aplastic anemia have
also been reported. Thalidomide may provide one of the most useful therapeutic
alternatives for chronic refractory DLE, although its distribution is limited to a
few countries because of the risk of teratogenicity and polyneuropathy. Research
found low-dose thalidomide treatment was efficacious with good tolerance, with
the most frequent side effect being usually mild asthenia.19
2.5.3 Excision and Laser Therapy
Excision of burned-out, scarred lesions is possible; however, reactivation of
inactive lesions has been reported in some patients. Laser therapy may be useful
for lesions with prominent telangiectases. Reactivation also is a consideration in
this form of therapy.16
2.5.4 Long-Term Monitoring
Follow patients with discoid lupus erythematosus (DLE) at regular intervals.
Response to therapy varies from several weeks to several months. At each visit,
question the patient about new symptoms that may reflect systemic disease. At
regular intervals, perhaps annually in otherwise asymptomatic patients, perform
routine laboratory studies for assessment, including complete blood count (CBC),
renal function tests, and urinalysis. Repeat antibody testing is needed only if a
change in symptomatology is noted.4
2.5.5 Other Drugs Used for the Treatment of DLE
a. Methotrexate
Methotrexate may be of help to patients with DLE resistant to conventional
treatment. Full blood count and liver function along with renal function need to be
checked before commencing treatment with methotrexate and regularly thereafter
because it can cause myelosuppresion and hepatic-renal impairment.18
b. Cyclosporin A
This is a potent immunosuppressant because of its immunomodulating effect on
helper T-cell function, inhibiting lymphocyte activation and proliferation. Because
18
DLE is an inflammatory dermatosis with T-cell infiltrate, it should not be
surprising if cyclosporine is effective in the management of the condition. It was
effective at a dose of 4 to 5mg/kg/day. Blood pressure and kidney function need to
be monitored, and hypertension is a common side effect. It can also cause gingival
hyperplasia and hirsutism. Lipid disturbances can also occur and therefore serum
cholesterol and triglycerides have to be monitored.18
c. Tacrolimus and Pimecrolimus
Tacrolimus is a macrolide derived from the fungus Streptomyces tsukubaensis.
When used as an ointment it acts as a local immunosuppressive agent. It found
that tacrolimus 0.1% was as efficient as clobetasol 0.05% in treating cutaneous
LE.20
Pimecrolimus (SDZASM 981) is the most recent member of a triad of
calcineurin inhibitors: cyclosporin A, tacrolimus and pimecrolimus. Pimecrolimus
1% cream was specifically developed for the treatment of inflammatory skin
diseases such as atopic dermatitis. Tlacuilo-Parra et al. have proved that
pimecrolimus cream for DLE seems to be a safe and clinically effective option.3
d. Mycophenolatemofetil
This is an immunosuppressive agent that has been added relatively recently to the
other drugs in this group and has been used increasingly in recent years for the
treatment of various dermatoses that are inflammatory or autoimmune in origin.
Mycophenolateis an ester prodrug of mycophenolic acid, initially isolated from
Penicillium species.2
e. Azathioprine
Azathioprine, a potentially toxic drug, has been used in refractory cases of discoid
lupus, with particular success among those with the involvement of the palms of
the hands and the soles of the feet. It is a synthetic derivative of 6-mercaptopurine
and is an immunosuppressive drug.18
f. Dapsone
Dapsone's mechanism of action is similar to that of sulfonamides, in which
competitive antagonists of para-aminobenzoic acid (PABA) prevent the formation
of folic acid, inhibiting bacterial growth. The anti-inflammatory action may relate
19
to suppression of neutrophil function by inhibition of the halide-myeloperoxidase
system.16
g. Lenalidomide
Therapy at a dosage of 5 mg/d with increased dosage to 10 mg/d useful as an
alternative or adjunctive systemic therapy for patients with severe recalcitrant
DLE with minimal or no systemic involvement or for patients who are not able to
tolerate thalidomide. An additional known adverse effect of lenalidomide therapy
is increased risk of deep vein thrombosis, and antimalarial or anticoagulant agents
such as aspirin should be prescribed as prophylaxis to decrease the risk of such
events.21
2.5.6 Education
Because cutaneous lesions of lupus are known to be induced or exacerbated by
exposure to ultraviolet light, a logical approach in the management of discoid
lupus must include sun avoidance and the liberal application of sunscreens.
Patients should be educated about the use of sunscreens and protective clothing
and behavior modification to avoid sun exposure, particularly between 10 am and
4 pm.16
2.6 Complication and Prognosis of Cutaneous Discoid Lupus
Patients with DLE generally have a favorable prognosis with regards to morbidity
and mortality. Because DLE is usually self-limited, the course is most often
benign; therefore, early recognition and adequate therapy may prevent clinical
complications.5 DLE tends to run a less severe course than SLE and has a better
prognosis. Early referral and institution of treatment by dermatologists increases
the hope of minimizing the progression of the disease and consequent
socioeconomic impact on the individual.1 Many patients with DLE go on to
develop destructive or deforming scarring or pigmentary disturbances,14
especially in the spring and summer months when the sun is the strongest.5
Infection may worsen the course of DLE. Renal failure is a serious complication
of DLE when immune system begin to attack kidney.4
20
SECTION III
CONCLUSION
Cutaneous discoid lupus or Discoid Lupus Erythematosus (DLE) is an
autoimmune inflammatory disorder of the skin that often leads to scarring and
alopecia. It may be localized to sun-exposed areas such as the face, ears, and scalp
but occasionally is much more extensive, involving the trunk and extremities. .
Patients with DLE rarely fulfil four or more of the criteria used to classify
Systemic Lupus Erythematosus (SLE). Abnormal apoptosis, the presence of
autoantibodies, and infiltration by plasmacytoid dendritic cells (PDCs), T cells as
well as B cells are important factors for the induction and maintenance of CLE.
Characteristic lesions of DLE are sharply-bordered, erythematous, keratotic
plaques that grow peripherally and show a coin-shaped (“discoid”) appearance.
Histopathological findings include hyperkeratosis, parakeratosis, follicular
plugging, telangiectasias, and atrophy of the epidermis. Current treatment options
for DLE include antimalarial agents such as chloroquine, topical and intralesional
glucocorticoids, and thalidomide. Patients with DLE generally have a favorable
prognosis and it usually self-limited disease. Complication of DLE is
development of destructive or deforming scarring or pigmentary disturbances and
skin infection.
20
21
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