This topic talks about the overview of cutaneous lupus and system lupus erythematosus(SLE) from acute to subacute and discoid, clinical features and management. pictures illustration and references for further reading

1. Overview of Cutaneous
Lupus
Abubakar Ghali Abduljalil

2. Outline
• Introduction
• Epidemiology
• Pathogenesis
• Classification
• Management
• Conclusion
• Reference

3. INTRODUCTION
Cutaneous lupus erythematosus (cutaneous LE) includes three categories of
LE-specific skin diseases:
• Acute cutaneous lupus erythematosus (ACLE)
• Subacute cutaneous lupus erythematosus (SCLE)
• Chronic cutaneous lupus erythematosus (CCLE)
The designations "acute," "chronic," and "subacute" do not necessarily or
strictly reflect the duration of activity of the skin disease

4. INTRODUCTION
• The "acute" in ACLE reflects the often transient and recurrent course of
ACLE and the tendency for exacerbations of ACLE to occur during acute
flares of SLE
• Cutaneous LE can occur as a manifestation of systemic lupus
erythematosus (SLE) or independent of SLE
• the terminology was originally coined in reference to a lack of residual
long-term skin damage, dyspigmentation, or scarring

5. INTRODUCTION
• The "chronic" in CCLE reflects both the often prolonged course of CCLE and the
resulting chronic skin changes of dyspigmentation and scarring that occur in DLE
• SCLE may lead to longstanding skin dyspigmentation but typically does not cause
scarring
• Patients with SLE may also develop a variety of LE-nonspecific skin diseases,
cutaneous disorders that lack histologic features of LE, but occur with increased
frequency in patients with SLE

6. Epidemiology
• Cutaneous disease is common in systemic lupus erythematosus (SLE)
• Approximately 80 percent of patients develop skin disease at some point in their
disease course. However, cutaneous LE frequently exists independently of SLE
and may be two to three times more prevalent than SLE
• The association with SLE varies among the subtypes of cutaneous LE and mainly
has been estimated from cross-sectional studies and retrospective studies

7. Epidemiology
Studies evaluating cross-sectional percent prevalence of underlying SLE in patients
with cutaneous LE have suggested the following levels of association with SLE
• ACLE – >90%
• SCLE – 48 to 50%
• Localized DLE – 5 to 10%
• Generalized DLE – 15 to 28%
• Lupus profundus/panniculitis – 5 to 10%
• Lupus erythematosus tumidus – Rarely associated with SLE

8. Pathogenesis
• The pathogenesis of cutaneous LE is complex, and it involves an interaction
between genetic and environmental factors
• The latter include ultraviolet radiation (UVR), medications, cigarette smoking, and
possibly viruses
• This interplay triggers a complex inflammatory cascade of cytokine, chemokine
and inflammatory cell responses
• LE is driven by dysfunction within the adaptive and innate immune system
• Beginning with a loss of self-tolerance in the adaptive immune system through
the production of autoantibodies

9. Pathogenesis (cont’d)
• These antibodies inappropriately react to the self-antigens resulting in activation
and recruitment of T and B cells
• This leads to production of immune complexes which cause direct tissue injury
• Both ultraviolet B (UVB) and ultraviolet A (UVA) radiation have been implicated in
exacerbation of cutaneous LE
• UVR induces apoptosis, which leads to translocation of cellular and nuclear
antigens
• A number of proinflammatory cytokines, including TNF-α, IL-1, IFN-γ, IL-18 are
induced by UVR

10. Pathogenesis (cont’d)
• Adhesion molecules ICAM-1, VCAM-1 and E-selectin are also involved
• Proinflammatory signaling pathways are upregulated and these results in
increased cytokine activity
• Overall, a lichenoid tissue reaction, defined as epidermal basal cell damage and a
bandlike lymphocytic infiltrate in the upper dermis results
• The end result is cytotoxic keratinocyte apoptosis

11. CLASSIFICATION
The modified Gilliam grouping system for cutaneous manifestations of LE provides
a helpful organizational framework for the related but distinct clinical entities that
comprise
• Lupus Erythematosus Specific Skin diseases
• Lupus Erythematosus Nonspecific skin diseases

12. CLASSIFICATION cont’d
Lupus Specific Cutaneous LE
• Acute CLE
• Sub acute CLE
• Chronic CLE (Discoid lupus)
Lupus Nonspecific Cutaneous LE
• Livedo reticularis
• Raynaud phenomenon
• Urticarial Vasculitis
• Non scarring Alopecia
• Mucosal Involvement
• Bullous CLE

13. Lupus Erythematosus Specific
• The key characteristic that unites the LE-specific skin diseases is histopathology
• Common shared histopathologic features include a vacuolar interface dermatitis
(liquefactive degeneration of the basal layer of the epidermis),hyperkeratosis,
epidermal atrophy, a superficial, perivascular, and perifollicular mononuclear cell
inflammatory infiltrate, thickening of the basement membrane and pigment
incontinence

14. Lupus Erythematosus Specific
Acute cutaneous lupus erythematosus (ACLE):
• Localized ACLE (ie, malar rash, butterfly rash)
• Generalized ACLE
• Toxic epidermal necrolysis-like ACLE

15. Acute cutaneous lupus erythematosus
• ACLE is a manifestation of systemic lupus erythematosus (SLE) that may present
as a characteristic localized facial eruption, less commonly as a generalized
eruption, and rarely as a toxic epidermal necrolysis (TEN)-like presentation
• Localized ACLE appears in approximately one-half of patients with SLE
• Almost all patients with ACLE have SLE

16. Clinical Manifestations
• The facial eruption of localized ACLE (also known as "malar rash" or "butterfly
rash") is characterized by erythema in a malar distribution (cheeks and bridge of
the nose)
• Localized ACLE may precede other symptoms of SLE by months or even years or
may be accompanied by other symptoms and signs of acute SLE
• The involved skin feels warm and appears slightly edematous. The erythema may
last for hours, days, or weeks and often recurs, particularly with sun exposure

17. Clinical Manifestations
• Generalized ACLE presents as an erythematous maculopapular (morbilliform)
eruption involving primarily sun-exposed skin
• The extensor surfaces of the arms and hands are common sites
• The skin overlying the knuckles often is spared, a feature that contrasts with
dermatomyositis
• Occasionally, the inflammatory infiltrate is severe enough to produce vesicles or
bullae

19. Histopathology
The classic histologic findings of localized and generalized ACLE are consistent with
interface dermatitis and include:-
• Apoptotic keratinocytes
• Vacuolization of the basal cell layer of the epidermis
• Lymphohistiocytic infiltrate in the superficial dermis and dermal mucin deposition

20. Differential diagnosis
• Rosacea
• Sunburn
• Seborrheic dermatitis
• Contact dermatitis
• Erysipelas
• Flushing
• Dermatomyositis

21. Subacute cutaneous lupus erythematosus
• SCLE frequently is associated with SLE
• Approximately 50 percent of affected patients meet the 1997 American College
of Rheumatology (ACR) classification criteria for SLE
• Subsequent studies have revealed that approximately 10 to 15 percent of
patients presenting with SCLE go on to develop severe clinical manifestations of
SLE

22. Subacute cutaneous lupus erythematosus
• The ACR classification criteria are known to have inherent limitations, which
include classifying SLE too readily in patients with SCLE
• Based upon SCLE features alone, at least 3 or 4 of 11 criteria are often met (ie,
patients with SCLE may have photosensitivity, positive antinuclear antibodies
[SSA/Ro+], mild arthralgias, and/or oral ulcers, which could suggest the diagnosis
of SLE)

23. Subacute cutaneous lupus erythematosus
• However, these patients may have no other systemic end-organ involvement or
other SLE features
• In 2012, the Systemic Lupus International Collaborating Clinics (SLICC) proposed
revised classification criteria that addressed some of these limitations regarding
the cutaneous disease manifestations
• There is a strong association between SCLE, human leukocyte antigen (HLA)-DR3,
antibodies to Ro/SSA, and polymorphisms in the tumor necrosis factor (TNF)-
alpha promoter gene More than 80 percent of patients with SCLE are positive for
anti-Ro/SSA antibodies

24. Clinical Manifestations
• SCLE begins as small, erythematous, slightly scaly papules that evolve into either
psoriasiform plaques (papulosquamous SCLE) or annular plaques (annular SCLE)
• The latter often coalesce to form polycyclic or figurative patterns. The plaques are
typically erythematous with variable amounts of overlying scale
• The most common sites of involvement are somewhat photodistributed and
include the shoulders, forearms, neck, and upper torso

26. Clinical Manifestations
• Despite a photo aggravated nature of the condition, the face is often spared
Dyspigmentation at sites of resolved SCLE is common and may resemble vitiligo
• Scarring usually does not occur
• Less common variants include vesiculobullous annular, poikilodermatous,
erythrodermic, and erythema multiforme-like (Rowell syndrome) SCLE

27. Histopathology
• Less follicular plugging
• Hyperkeratosis
• Perivascular and appendageal lymphocytic infiltrates tend to be more superficial
• Vacuolization of the basement membrane and mucin deposition in the dermis
• Basement membrane thickening is generally absent or minimal

28. Differential Diagnosis
The differential diagnosis of SCLE includes other disorders that may exhibit
erythematous papules or plaques such as:-
• Psoriasis
• Tinea corporis
• Nummular eczema
• Dermatomyositis
• Cutaneous T cell lymphoma

30. Chronic cutaneous lupus erythematosus
CCLE encompasses:
• Discoid lupus erythematosus (DLE)
• Lupus erythematosus tumidus (LE tumidus)
• Lupus profundus (also known as lupus panniculitis)
• Chilblain lupus erythematosus (chilblain LE)
• Lichenoid cutaneous lupus erythematosus-lichen planus overlap syndrome (LE-LP
overlap syndrome)

31. Discoid Lupus Erythematosus
• The most common type of CCLE is DLE, accounting for 73 to 85 percent of CCLE
• It is estimated that 15 to 30 percent of patients with SLE develop DLE
• The presence of DLE lesions among patients with SLE may modify the risk of
specific SLE features
• Compared with SLE patients without DLE, those with DLE have increased risk for
photosensitivity and leukopenia but decreased risk for serositis and arthritis

32. Discoid Lupus Erythematosus
• There is no obvious change in risk of nephritis despite variable reports of a "renal-
protective effect" of the presence of discoid lesions among SLE patients
• Data on the risk for progression of DLE to SLE are limited
• Retrospective cohort studies showed progression to SLE has occurred in 0 to 28
percent of patients initially presenting with DLE
• Progression to SLE appears to occur most often in the first few years after a DLE
diagnosis

33. Discoid Lupus Erythematosus
• Risk factors for progression include an increasing number of clinical and serologic
features of SLE:
• More widespread DLE lesions
• Arthralgias and arthritis
• High Antinuclear Antibody (ANA) titers
• Leukopenia
• High erythrocyte sedimentation rates

34. Clinical Manifestations
• The classic findings of DLE are discrete, erythematous, somewhat indurated
plaques covered by a well-formed adherent scale that extends into dilated hair
follicles (follicular plugging)
• The plaques tend to expand slowly with active inflammation at the periphery and
then heal, leaving depressed central scars, atrophy, telangiectasias, and
hyperpigmentation and/or hypopigmentation
• DLE most often involves the face, neck, and scalp but may also occur on the ears
(particularly conchal bowls) and less frequently on the upper torso

36. Clinical Manifestations
• Localized DLE is limited to sites above the neck
• Generalized DLE refers to DLE occurring both above and below the neck.
• Hypertrophic DLE is an uncommon clinical variant of DLE characterized by the
development of hyperkeratotic, verrucous plaques

37. Histopathology
• Pathologic examination of DLE typically reveals hyperkeratosis
• Follicular plugging
• Basal layer vacuolar changes
• Mononuclear cell infiltrate (predominantly T cells) near the dermal-epidermal
junction, dermal blood vessels, and appendages

38. Differential Diagnosis
• Lupus vulgaris (cutaneous tuberculosis)
• Cutaneous leishmaniasis (eg, lupoid leishmaniasis, leishmaniasis recidivans)
• Tuberculoid leprosy
• Tinea faciei
• Granuloma faciale
• Sarcoidosis

40. Less common subtypes of CCLE
• LE tumidus
• Lupus profundus (lupus panniculitis)
• Chilblain LE
• Lupus erythematosus-lichen planus (LE-LP) overlap syndrome are additional
manifestations of CCLE

42. LUPUS NONSPECIFIC SKIN DISEASE
Cutaneous disorders that occur with increased frequency among patients with
systemic lupus erythematosus (SLE), but are not specific to SLE and lack
histopathologic features of cutaneous LE this include
1. Periungual erythema – Periungual erythema is due to dilated tortuous loops of
capillaries and a prominent subcapillary venous plexus along the base of the
nail. Similar findings have been noted along the edges of the upper eyelid

43. LUPUS NONSPECIFIC SKIN DISEASE
• Livedo reticularis – Livedo reticularis refers to a reddish-cyanotic, reticular pattern
on the skin of the arms, legs, and torso, particularly with cold exposure. In SLE,
livedo reticularis is induced by vasospasm of the dermal ascending arterioles
• Raynaud phenomenon – Raynaud phenomenon in SLE is a vasospastic process
that occurs in approximately 15 to 30 percent of patients It is characterized by
blanching of the nail beds, fingers, and toes (and occasionally ears, nose, tongue,
and nipples) with accompanying pain

44. Urticarial Vasculitis
• Vasculitis develops in approximately 11 to 20 percent of patients with SLE. The
most common form, occurring in 10 to 15 percent of cases, is urticarial vasculitis
• In contrast to urticaria, lesions of urticarial vasculitis may persist for more than
24 hours and frequently evolve into painful petechiae or purpura that may heal
with hyperpigmentation

45. Nonscarring Alopecia
• Nonscarring alopecia (reversible) hair loss in patients with SLE may reflect telogen
effluvium or "lupus hair." Nonscarring hair loss usually responds well to treatment
of SLE
• Telogen effluvium is characterized by a shift in follicular cycling that leads to
premature shedding of hair
• Lupus hair" is generally seen during exacerbations of SLE. It is characterized by
thin, unruly hair that easily fractures, Lupus hair usually occurs along the frontal
hairline

46. Mucosal Manifestations
• Mucous membrane involvement can occur in the setting of cutaneous LE or SLE
Mucosal involvement occurs in 12 to 45 percent of patients with SLE
• Oral involvement may manifest as white plaques, areas of erythema, or
punched-out erosions or ulcers with surrounding erythema on the soft or hard
palate or buccal mucosa
• The oral ulcers are usually painless, Oral ulcers may be the first sign of SLE
• There is no apparent association between the presence of oral ulcers and
systemic activity

47. Mucosal Manifestations
• Nasal ulcers occur in some patients with SL, They are usually in the lower nasal
septum and tend to be bilateral
• The appearance of nasal ulcers tends to parallel other features of active SLE
• Involvement of the mucosa of the upper airway may also occur and may cause
hoarseness
• Oral mucous membrane lesions may respond to topical corticosteroids,
tacrolimus 0.1% ointment, intralesional corticosteroids, and systemic antimalarial
drugs

49. Bullous Cutaneous Lupus Erythematosus
• Bullous cutaneous lupus erythematosus (bullous CLE) is a rare and distinct
complication of SLE characterized by the development of autoantibodies against
type VII collagen and subepidermal blistering
• Affected patients develop a vesicular or bullous eruption that may affect any
body site, including oral mucosa
• There is a predilection for the upper trunk, upper extremities, and neck. Bullae
may arise on normal or erythematous skin
• Pruritus is usually absent and scarring does not usually occur
• Dyspigmentation may occur in sites of resolved bullae

51. Additional Disorders
Sclerodactyly
Rheumatoid nodules
Calcinosis cutis
Urticaria
Cutis laxa/anetoderma
Acanthosis nigricans
Erythema multiforme

52. Management
Non Specific investigation include:-
• FBC
• ESR
• CRP
• Urinanalysis
• UPCr
• Clothing profile

53. Management
Specific investigations:-
• Biopsy
• Lupus Band Test
• Autoantibodies
• Serum complement level
• Photoprovocation test
• Dermoscopy

54. Management
• The approach to the treatment of LE-specific skin disease is influenced by
the subtype of disease and the presence of underlying SLE
• In all cases, photoprotection and use of appropriate broad-spectrum
sunscreens are recommended, given the known photoexacerbation of
cutaneous LE
• Patients should also be monitored for the development of signs or
symptoms suggestive of progression to SLE

55. First-Line Therapy
• Photoprotection :- sun avoidance, sun screens, protective clothing
• Use of topical or intralesional corticosteroids, topical calcineurin inhibitors,
and/or systemic glucocorticoids depending on the extent of involvement
and subset of disease
• Systemic antimalarial agents (treatment with either hydroxychloroquine or
chloroquine, or with the addition of quinacrine to either of these agents

56. Second-line therapy
• Methotrexate (oral or subcutaneous) – Additional benefits may include treatment
of SLE with inflammatory arthritis component
• Mycophenolate mofetil – May be of dual benefit to patients with underlying
lupus nephritis, interstitial lung disease variants

57. Third-line Therapy
• Thalidomide
• Lenalidomide
• Belimumab
• Systemic retinoids
• Oral dapsone (particularly for bullous lupus)
• Intravenous immunoglobulin (IVIG), or azathioprine

58. Conclusion
• Cutaneous lupus erythematosus (cutaneous LE) may occur as an independent
disorder or in association with systemic lupus erythematosus (SLE)
• Cutaneous LE includes three categories of LE-specific skin disease: acute
cutaneous lupus erythematosus (ACLE), subacute cutaneous lupus
erythematosus (SCLE), and chronic cutaneous lupus erythematosus (CCLE)
• A variety of non-LE cutaneous disorders may also occur in patients with SLE (LE-
nonspecific skin diseases)

59. Conclusion
• The different types of LE-specific skin disease have varying strengths of
association with SLE
• ACLE almost always occurs in association with SLE, other types of lupus-specific
skin disease are less strongly associated with SLE
• Other types of lupus-specific skin disease are less strongly associated with SLE
• Cutaneous LE is largely a clinical diagnosis supported by contextual clinical
features (such as the presence of known underlying SLE)

60. Conclusion
• Confirmatory histopathologic examination is indicated when diagnostic
uncertainty remains
• The approach to the management of cutaneous LE is influenced by the extent of
disease, subtype of cutaneous LE, response to initial therapy, and the presence of
underlying SLE
• Photoprotection, topical corticosteroids, topical calcineurin inhibitors, and oral
antimalarials are common first-line treatments

61. REFERENCES
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association with systemic lupus erythematosus: a population-based cohort of 1088
patients in Sweden. Br J Dermatol 2011; 164:1335
• Chong BF, Song J, Olsen NJ. Determining risk factors for developing systemic lupus
erythematosus in patients with discoid lupus erythematosus. Br J Dermatol 2012; 166:29
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example of cutaneous lupus erythematosus. J Cutan Pathol 2010; 37 Suppl 1:112
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and the associated risk of systemic lupus erythematosus: a nationwide cohort study in
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