Skin Deep: Cutaneous Lupus. Dr Sarah Sasson Immunology Registrar, Liverpool Hospital 2016

Transcription

1 Skin Deep: Cutaneous Lupus Dr Sarah Sasson Immunology Registrar, Liverpool Hospital 2016

2 Introduction: Cutaneous lupus erythematosus LE is an autoimmune disease with a range of clinical manifestations from limited cutaneous to systemic disease Cutaneous lupus erythematosus (CLE) includes a broad range of dermatologic manifestations Incidence of CLE 4.3/ Similar to SLE F>M Mean age of onset 49 yrs Classifications of subgroups remain a challenge- no uniform definitions Diagnosis relies on clinical and lab findings and skin histology Remains a diagnostic and therapeutic challenge

3 Introduction: Cutaneous lupus erythematosus LE-specific lesions Acute cutaneous LE Subacute cutaneous LE Chronic cutaneous LE Discoid LE Hyperkeratotic LE LE profundus/ panniculitis LE tumidus Chilblain LE

4 Non-specific LE-associated skin lesions Livedo reticularis Periungal telangectasia Reynaud's phenomenon Erythema multiforme Calcinosis cutis

5 Relationship between cutaneous and systemic LE Walling and Sontheimer Am J Clin Derm 2009

6 Acute CLE (ACLE) May be localised Butterfly malar rash May mimic acne rosacea Or generalised as a component of SLE I.e. above and below the neck Photosensitive and transient (daysweeks) Bullous lesions may be present Post inflammatory hyper pigmentation can ensue after active phase of eruption. ACLE flare tend to parallel systemic disease activity Walling and Sontheimer Am J Clin Derm 2009

7 Subacute CLE LE-specific Highly photosensitive Common distribution over upper back, shoulders, neck and anterior chest May be medication induced Symmetric erythematous eruptions of non-indurated macules and papules that soon become surmounted by fine scale. Tends to spare central face and scalp

8 Subacute CLE Over time 1 of 2 morphological forms develop: Scaly annular lesions Scaly papulosquamous plaques

9 Medications associated with Subacute CLE Considered to unmask SCLE in a genetically susceptible individual possibly by photosensitizing mechanism Walling and Sontheimer Am J Clin Derm 2009

10 Chronic CLE LE-specific lesions Classic discoid lupus is the most common form Indurated scaly plaques on scalp (>60%), face, ears, forearms Occurs in 20% of SLE patients at some point Less common forms: hyperkeratotic lupus, lupus tumidis, lupus profundus, chilblain lupus Hejazi and Werth Am J Derm 2016

11 Chronic CLE: Discoid LE Discoid LE may be localised (more common) or generalised Adherent scale often extends into dilated hair follicles leading to follicle plugging >50% of patients will develop significant destructive scarring May be triggered by trauma, UV, cold, infection, dermatitis and burns. Walling and Sontheimer Am J Clin Derm 2009

12 Uncommon forms of chronic CLE: Hyperkeratoitc DLE Thickened lesions on the extensor arms, hands and face May resemble keratoacanthoma or hypertrophic lichen planus

13 Uncommon forms of chronic CLE: LE Panniculitis Involvement of the deep dermis and underlying adipose tissue Presents as firm, depressed nodules Lesions occur on trunk, proximal extremities, face and breasts Lupus mastitis May mimic subcutaneous panniculitis like T-cell lymphoma 1-3% of CLE

14 Uncommon forms of chronic CLE: LE Tumidus Deeply erythematous, urticarial plaques with minimal surface change No follicular plugging and rich mucin deposition histologically More likley to involve face F>M Most photosensitive of all LE types Typically ANA negative and rarely display features of systemic SLE

15 Uncommon forms of chronic CLE: Chilblain LE Violaceous papules and plaques that appear on fingers and/or toes, ears or ace. Triggered by cold, damp environmental exposures 20% will progress to SLE A familial form is characterised by mutations in the TREX1 endonuclease repair gene.

16 CLE: Diagnosis Clinical Findings Comprehensive skin examination SLEDEI and BILAG tools lack sensitivity for CLE Cutaneous Lupus Area and Severity Index (CLASI) tool to measure disease activity Laboratory Findings FBC, EUC, LFT and autoimmune serology should be performed High titre ANA, dsdna and Anti-Sm are more suggestive of SLE (70%) than CLE (25%) Exclusion of APLS

17 CLE: Diagnosis Histopathology Interface dermatitis with mononuclear cell infiltrate at the DEJ and perivascular and peradnexial inflammation Immunohistochemistry less useful. Cutaneous histopathology is similar between subtypes More pronounced dermal oedema and epidermal atrophy in SCLE DLE may demonstrate follicular plugging and inflammation extending in the dermis

18 CLE: Lupus Band test Direct immunofluoresnce of skin showing immunoreactant deposition along the DEJ. May provide support for diagnosis of CLE Demonstrated in lesional and non-lesional skin biopsies from patients with SLE Also demonstrated in sun exposed areas of healthy volunteers Highest sensitivity is in non-lesional non-sun exposed skin biopsies although test has largely been superseded.

19 CLE: Pathogenesis CLE pathogenesis is a multifactorial process that includes genetic risk, environmental triggers innate and adaptive immune responses. Evidence points towards UV light altering cellular content, T-cell dysregulation, B-cell defects and autoab generation as well as chemokine and cytokine imbalances HLA associations with CLE subtypes UV exposure is a common trigger CLE patients can respond to photoprovocation testing Role for IL-1, IL-18and TNFa IFNa and IFNb Autoantibodies SSA present in 47% ACLE, 72% SCLE, 22% DLE Level may correlate with disease activity SSB present in 27% ACLE, 36% SCLE and 7% DLE

20 CLE: Treatment Treatment remains a challenge, no medication approved specifically for CLE Few RCT; widespread off-label use of medications Hejazi and Werth Am J Derm 2016

21 CLE: Treatment In a DBRCT of 25 patients with photosensitive CLE SPF50 sun cream applied 30 min prior to exposure resulted in 100% protection from UV-induced lesions. Vit D supplementation may be required and improves CLASI scores Smoking may induce or aggravate CLE; 60% of patients have smoked Has been correlated to higher disease activity; May interfere with HCQ metabolism Topical Calcineurin inhibitors have emerged as an alternative to steroids for CLE lesions A DBRCT of 20 patients found tacrolimus 0.1% had similar efficacy to clobetasol but resulted in less facial telangectasias. Hydroxychloroquine is generally first line systemic treatment Immunosuppressive agents: AZA MTX Common second line agent; Careful monitoring for BM toxicity MMF

22 CLE: Other treatment options Acitretin and other oral retinoids Hyperlipidemia, hepatoxicity, teratogenic Dapsone Useful in highly inflammatory forms G6PD screening prior to use Hemolysis, hepatoxicity and agranulocytosis IVIG Mixed results for CLE 7-42% response rate High cost Thalidomide and analogues Arguably most uniformly beneficial and rapid acting agents in CLE 80% response rate and 60% remission rate Use limited by toxicity (especially neurotoxicity) profile

23 CLE: Other treatment options Monoclonal Antibodies: Belimumab (BAFF) B-cell inhibitor in clinical trials for SLE only Rituximab (CD20) Inconsistent findings Anti IFNa treatments In trials for SLE with some data suggesting mucocutaenous benefit.

24 Conclusions The pathogenesis involves immune activation secondary to environmental triggers in genetically predisposed individuals CLE occurs at similar frequency to SLE and encompasses a wide range of clinical manifestations. May be cutaneous-limited or associated with systemic disease Diagnosis is involved clinical, laboratory and histopathology parameters and is limited by lack of standardised criteria Treatment ranges from Sun cream UV avoidance Topical steroids Topical Calciurin agent Systemic therapy with hydroxycholroquine as first line Use of IVIG and other Immunosuppresives, oral retinoids, thalidomide and dapsone must be weighed against risk and cost The role of biologics in this conditions remains unclear.

25 Thank You Questions?