STUDENT PROJECT

CUTANEOUS DISCOID LUPUS

CREATED BY: PT. GEDE YUDI DARMA WIJAYA SUPARTA I GST AYU PREMA YANI SIDEMEN I GEDE YUHANA DHARMA SASMITA FARADILLA NOVITA ANGGREINI THANATHAN R. SANTHERANATHAN MYELONE THARMASEELAN POONEETHAWATHI SANTRAN SUBA KAMARASAMY KEREN KARUNYA SINGAM YOJENETHA SUBRAMANIAM (0802005060) (0802005006) (0802005075) (0802005008) (0802005168) (0802005164) (0802005169) (0802005165) (0802005200) (0802005177)

SGD B.1 ENGLISH CLASS 7TH SEMESTER

FACULTY OF MEDICINE UDAYANA UNIVERSITY DENPASAR 2011

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 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. Skin and

Denpasar, 24th of October 2011

Writers

ii

CONTENTS
Content REPORT COVER PREFACE CONTENTS Page ........................................................................................ i ii

.....................................................................................................

.................................................................................................. iii ............................................................................................ iv .............................................................................................. v

FIGURE LISTS TABLE LISTS

ABBREVIATIONS SECTION I

...................................................................................... vi .............................................................. .................................... 1 3 3 3 7

INTRODUCTION

SECTION II CUTANEOUS DISCOID LUPUS

2.1 Etiology and Epidemiology of Cutaneous Discoid Lupus 2.2 Pathophysiology of Cutaneous Discoid Lupus 2.3 Clinical Features of Cutaneous Discoid Lupus 2.4 Diagnosis of Cutaneous Discoid Lupus 2.4.1 Diagnostic Strategies 2.4.2 Differential Diagnosis ............ ..............

........................ 10

........................................ 10 ...................................... 13 ................. 15

2.5 Management for Cutaneous Discoid Lupus 2.5.1 Topical Corticosteroids 2.5.2 Antimalarials

.................................... 15

.................................................... 16 ............................. 17

2.5.3 Excision and Laser Therapy 2.5.4 Long-term Monitoring

...................................... 17 ... 17

2.5.5 Other Drugs Used for the Treatment of DLE 2.5.6 Education

.......................................................... 19

2.6 Complication and Prognosis of Cutaneous Discoid Lupus 19 SECTION VI CONCLUSION REFERENCES ................................................................... 20

............................................................................................. 21

iii

FIGURE LISTS
Figure 1. Figure 2. Pathophysiology of Systemic Lupus Erythematosus ............... 4

DLE: erythema, hyperkeratosis, and scarring alopecia (a); peripheral erythema, central hyperkeratosis and scarring (upper arm) (b) ......................................................................... 8

Figure 3. Figure 4.

Discoid Lupus Erythematosus on the face and oral mucosa 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,

..... 11

(E) Basement membrane thickening and perivascular infiltrate, (F) DIF showing thickening of epithelial basement membrane 12

iv

TABLE LISTS
Table 1. Table 2. Table 3. Table 4. Demographic data of 130 Thai patient with DLE ..................... ..... 8 9 9

Other manifestation detected in 130 Thai patient with DLE Laboratory abnormalities of 130 Thai patient with DLE Differences between SLE, SLCE, and DLE

...........

.............................. 13

ABBREVIATIONS
AICD ARA CBC CCLE CLE COX DLE DNA IFN iNOS LBT LE NO PABA PDC PGE2 SCLE SLE TNF UV = Activation Induced Cell Death = American College of Rheumatology = Complete Blood Count = Chronic Cutaneous Lupus Erythematosus = Cutaneous Lupus Erythematosus = Cyclooxygenase = Discoid Lupus Erythematosus = Deoxyribonucleic Acid = Interferon = Inducible Nitric Oxide Synthase = Lupus Band Test = Lupus Erythematosus = Nitric Oxide = Para-aminobenzoic Acid = Plasmacytoid Dendritic Cells = Prostaglandin E2 = Subacute Cutaneous Lupus Erythematosus = Systemic Lupus Erythematosus = Tumor Necrosis Factor = Ultra Violet

vi

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

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

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

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

b. Accumulation of PDCs, T and B Cells PDC is the natural IFN-/ producing cells, results in an increased expression of IFN-/ inducible protein. The IFN- 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- 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

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-) 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

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
12,13

grow

peripherally

and

show

coin-shaped

(discoid)

appearance.

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

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 (Kbner phenomenon) can provoke or exacerbate disease. DLE can coexist 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 DLE 14

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 DLE 14

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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 connectivetissue 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 dermalepidermal 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 Lesional character Scale Follicular atrophy Photodistribution Scarring Atrophy Pigmentary alteration Telangectasia Positive Lupus Band Test Lesional skin Nonlesional skin SLE criteria SLE Fine, easily detached Absent Present Absent Absent-usually Slight Present >50% 90% (active) 30% (inactive) SCLE Fine, easily detached Absent Marked Absent Absent-usually Slight Present 50% 30% DLE Thick, adherent Present Present Present Present-often marked Often marked Present 90% 0-10%

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Presence of 4/11 At least 4 present in criteria all SLE patient Histopathology examination

40% will have 4 criteria

10% will have 4 criteria

Lymphocyte rich interface dermatitis Poor inflammatory Dyskeratosis in Less epidermal interface dermatitis upper spinous layer atrophy Slight to no Prominent epidermal Prominent BM epidermal atrophy atrophy thickness Normal BM Normal BM or mild Prominent follicular thickness thickening plugging and No follicular Follicular plugging degeneration plugging Mild to moderate Dense superficial superficial dermal Prominent papillary and deep dermal edema and mononuclear perivascular and dermal mucin infiltrate 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 bulls eye lesion and then to widespread retinal pigment epithelial atrop hy 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-6phosphate-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.

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REFERENCES
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11) Daldon P. E. C. and Lage R. Linear chronic Discoid Lupus Erythematosus following the lines of blaschko. An Bras Dermatol 2011; 86(3):553-556. 12) Kuhn A., Sticherling M., Bonsmann G. Clinical Manifestation of cutaneous lupus erythematosus. JDDG 2007; 5:1124-1140. 13) Naqqash S., Asad F., Pal S. S. Direct immunofluorescence and histopathology in chronic Discoid Lupus Erythematosus. Journal of Pakistan Association of Dermatologist 2011; 21:98-101. 14) Insawang M., Kulthanan K., Chularojanamontri L., Tuchinda P., Pinkaew S. Discoid Lupus Erythematosus: Description of 130 cases and review of their natural history and clinical course. Journal of Clinical Immunology and Immunopathology Research 2010; 2(1):1-8. 15) Spann C. R., Callen J. P., Klein J. B., Kulick K. B. Clinical, serologic and immunogenetic studies in patients with chronic cutaneous (discoid) lupus erythematosus who have verrucous and/or hypertrophic skin lesions. J Rheumatol 1988; 15(2):256-261. 16) Callen J. P. Cutaneous lupus erythematosus: a personal approach to management. Australasian Journal of Dermatology 2006; 47:13-27. 17) Lourenco S. V., de Carvalho F. R. G., Boggio P., Sotto M. N., Vilela M. A. C., E. Rivitti A., et al. Lupus erythematosus: clinical and histopathological study of oral manifestation and immunohistochemical profile of the inflammatory infiltrate. Journal of Cutaneous Pathology 2007; 34:558-564. 18) Panjwani S. Early diagnosis and treatment of discoid lupus erythematosus. JABFM 2009; 2:30-35. 19) Jung H., Bobba R., Su J., Shariati-Sarabi Z., Gladman D. D., Urowitz M., et al. The protective effect of antimalarial drugs on thrombovascular events in systemic lupus erythematosus. Arthritis Rheum 2010; 62(3):863-868. 20) Atra E. and Sato E. I. Treatment of the cutaneous lesions of systemic lupus erythematosus with thalidomide. Clin Exp Rheumatol 1993; 11(5):487-493. 21) Shah A., Albrecht J., Bonilla-Martinez Z., Okawa J., Rose M., Rosenbach M., Werth V. P. Lenalidomide for the Treatment of Resistant Discoid Lupus Erythematosus. Arch Dermatol 2009; 145(3):303-306.