Overview of Cutaneous Lupus.pptx

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

18. 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

19. Differential diagnosis Rosacea Sunburn Seborrheic dermatitis Contact dermatitis Erysipelas Flushing Dermatomyositis

20. 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

21. 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)

22. 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

23. 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

24. 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

25. 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

26. 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

27. 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)

28. 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

29. 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

30. 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

31. 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

32. 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

33. 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

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

35. 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

36. 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 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

37. 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

38. 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

39. 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

40. 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

41. 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

42. 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

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

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

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

46. 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

47. 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

48. 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

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

50. 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)

51. 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)

52. 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

53. REFERENCES Watanabe T, Tsuchida T. Classification of lupus erythematosus based upon cutaneous manifestations. Dermatological, systemic and laboratory findings in 191 patients. Dermatology 1995; 190:277. Grönhagen CM, Fored CM, Granath F, Nyberg F. Cutaneous lupus erythematosus and the 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 Sepehr A, Wenson S, Tahan SR. Histopathologic manifestations of systemic diseases: the example of cutaneous lupus erythematosus. J Cutan Pathol 2010; 37 Suppl 1:112 Petersen MP, Möller S, Bygum A, et al. Epidemiology of cutaneous lupus erythematosus and the associated risk of systemic lupus erythematosus: a nationwide cohort study in Denmark. Lupus 2018; 27:1424