discoid lupus

28
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 7 TH SEMESTER FACULTY OF MEDICINE UDAYANA UNIVERSITY DENPASAR 2011

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discoid lupus erythematosus is one of autoimmune disease in skin

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Page 1: Discoid Lupus

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

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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

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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

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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

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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

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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

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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

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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

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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

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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

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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

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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

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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

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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

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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

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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.

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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

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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

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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

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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

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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

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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

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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

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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

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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

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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

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