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Lupus Erythematosus, Discoid

para>Neonatal LE is a rare autoimmune disorder (caused by transplacental passage of maternal antibodies) that presents with cutaneous lupus skin lesions and/or other systemic manifestations, including congenital heart block. é á

EPIDEMIOLOGY

  • DLE occurs in persons of all ages and ethnicities.
  • All forms of cutaneous LE are most common among women of childbearing age.

Incidence

DLE manifests in up to 25% of patients with systemic lupus erythematosus (SLE) but can occur without systemic involvement: é á

  • Predominant age: 21 to 50 years
  • Predominant sex:Localized DLE: female > male (3:1)Generalized DLE: female > male (9:1)

Prevalence

  • Prevalence of cutaneous LE: 73/100,000
  • Increased prevalence in women and persons of African descent.
  • Between the ages of 21 and 30 years, prevalence is similar among both sexes.

ETIOLOGY AND PATHOPHYSIOLOGY

  • DLE is an autoimmune dysfunction of T cells linked to human leukocyte antigen (HLA) subtypes and environmental triggers.
  • Keratinocyte heat shock protein induction after UV light exposure or stress as a target for T-cell " ômediated epidermal cytotoxicity.

Genetics

  • DLE may occur in genetically predisposed.
  • A haplotype of cytotoxic T-lymphocyte " ôassociated protein 4 (CTLA4) showed association with DLE.

RISK FACTORS

  • Adult women of childbearing age
  • African American
  • SLE

GENERAL PREVENTION

  • Avoid exposure to UV-B and UV-A light sources.
  • Excessive heat, excessive cold, and trauma to the affected skin may worsen DLE.
  • Use broad-spectrum sunscreens, protective clothing (dark colors and closely woven fabrics), and hats.
  • Tobacco exposure may decrease efficacy of antimalarials

COMMONLY ASSOCIATED CONDITIONS

  • SLE
  • Mixed connective tissue disease
  • Antiphospholipid syndrome
  • Porphyria cutanea tarda (PCT)

DIAGNOSIS

  • Diagnosis of discoid lupus is typically clinical.
  • Histopathology of skin biopsies confirms the diagnosis.

HISTORY

  • Localized DLE: Sun-exposed areas of the face, especially the malar areas, bridge of nose, lower lip, lower eyelids, ears, and the scalp most commonly affected.
  • Generalized/disseminated DLE: most commonly presents on the thorax and upper extremities
  • DLE starts as an erythematous papule or plaque, usually on the head or neck, with an adherent scale that spreads outward.
  • Lesions often sting or are mildly pruritic.
  • A latency period of up to 3 weeks is common from time of exposure before lesions develop.

PHYSICAL EXAM

  • Disc-shaped, well-delineated erythematous plaques that become hypertrophic and adherent as they progress and spread centrifugally
  • "Carpet-track " Ł appearance if scale is removed
  • Oral lesions develop in 3 " ô20% of the patients (vermillion border > buccal mucosa > palate).
  • Palms and soles involved in <2% of patients
  • Lesions demonstrate follicular plugging and pigmentary changes; generally hyperpigmentation at the periphery and hypopigmentation with atrophy, scarring, and telangiectasia at the center of the lesion
  • Involvement of the scalp commonly produces a scarring alopecia, which is associated with a prolonged disease course.
  • Potential risk of SLE development in patients with DLE warrants complete skin and joint assessment

DIFFERENTIAL DIAGNOSIS

  • Actinic keratoses
  • Granuloma annulare
  • Cutaneous leishmaniasis
  • Plaque psoriasis
  • Rosacea
  • Eczema
  • Polymorphous light eruption
  • Drug eruptions
  • Lupus vulgaris
  • Seborrheic dermatitis
  • Lichen planus
  • Pemphigus erythematosus
  • Dermatomyositis
  • Squamous cell carcinoma

DIAGNOSTIC TESTS & INTERPRETATION

Initial Tests (lab, imaging)

  • Perform laboratory tests, including antinuclear antibody (ANA), ESR, CBC, and UA regularly in patients with DLE because of risk for SLE.
  • Localized DLE: positive ANAs in low titer (30%)
  • Generalized DLE: may find increased sedimentation rate, positive ANAs (60 " ô80%), positive SS-A (80%) and positive SS-B (40%) autoantibodies, positive double-stranded DNA (dsDNA; <5%), leukopenia, hematuria, and albuminuria if concomitant SLE
  • Disorders that may alter lab results: concomitant SLE

Diagnostic Procedures/Other

Skin biopsy é á

Test Interpretation

  • Hyperkeratosis and parakeratosis with focal epidermal atrophy and degeneration of basal cell layer
  • Edema, mucin, and inflammation of dermis
  • Follicular plugging
  • Mononuclear cell infiltration at the dermal " ôepidermal junction and in the dermis around blood vessels
  • Basement zone thickened with strong periodic acid " ôSchiff reaction staining
  • Biopsied tissue shows immunoglobulin deposits and/or complement at dermal " ôepidermal junction.

TREATMENT

  • Full-spectrum sunscreens, topical steroids, and intralesional glucocorticoids
  • Antimalarial agents, such as hydroxychloroquine, chloroquine, and quinacrine, are indicated when topical or intralesional therapy fails to control skin disease. Quinacrine is available in the United States from compounding pharmacies.
  • Inadequate or late treatment of DLE can lead to permanent scarring.

MEDICATION

First Line

  • Treatment typically begins with topical steroids. If no improvement in 2 to 4 weeks, consider intralesional steroid injections.
  • Localized DLE:Fluocinonide 0.05% cream (a potent topical corticosteroid) is more effective than hydrocortisone 1% cream (a mild corticosteroid).Topical corticosteroids:Start with a potent topical steroid (i.e., fluocinonide 0.05% cream) BID, then switch to a lower potency steroid (e.g., triamcinolone 0.1%) BID once clinical improvement is evident. Tapering steroids reduces side effects (atrophy, telangiectasia, striae, and purpura).Intralesional steroids:Triamcinolone (2.5 to 5.0 mg/mL for the face or 5 to 10 mg/mL elsewhere) is useful for chronic lesions, hyperkeratotic lesions, and lesions not responsive to topical steroids.Recognized side effects of intralesional steroids include cutaneous atrophy and dyspigmentation.Calcineurin inhibitors:Immunomodulator macrolide inhibits T cell activation in skin.Tacrolimus 0.1% or pimecrolimus 1% applied to face BID improves lesions in 4 to 8 weeks; less effective on hyperkeratotic lesions
  • Oral steroids:Generally not beneficial for treatment of DLE, but a prednisone burst (i.e., prednisone 1 mg/kg with a 2- to 4-week taper) may be useful in patients who do not respond to topical measures or individuals with systemic disease.
  • Generalized DLE:Antimalarials (1)[C]:Chloroquine and hydroxychloroquine; hydroxychloroquine is more tolerable and typically the initial therapy of choice.Hydroxychloroquine: 200 mg/day for an adult, increase to 200 mg/day BID if no GI disturbance or other side effects. Start maintenance dose of 200 mg daily once improved clinically.Expect clinical improvement in 4 and 8 weeks.In patients who do not respond to hydroxychloroquine, chloroquine 250 mg/day may be more effective. Do not use together (ocular toxicity)Quinacrine 100 mg/day can be used along with either hydroxychloroquine or chloroquine for increased efficacy.In general, hydroxychloroquine is a safe, well-tolerated drug with few adverse effects (e.g., retinal toxicity).Chloroquine causes macular pigmentation leading to widespread retinal pigment epithelial atrophy, resembling retinitis pigmentosa.Other adverse effects of antimalarials include GI symptoms, pruritus, lichenoid drug reactions, annular erythema, hyperpigmentation, and hematologic disturbances, such as leukopenia and thrombocytopenia.

Second Line

  • Localized DLE:Intralesional triamcinolone: 2.5 mg/mL injected at monthly intervalsPrednisone: 15 mg BID, then tapered after response
  • Generalized DLE:Dapsone: 25 to 100 mg/day (max dose 200 mg/day)Azathioprine: 100 mg/daySystemic retinoid: etretinate 1 mg/kg, acitretin 0.2 to 1.0 mg/kg, isotretinoin 0.5 to 1.0 mg/kg (teratogenic)Thalidomide: 50 to 100 mg/day (teratogenic)Methotrexate: 7.5 to 25.0 mg weekly (folic acid supplementation recommended)Mycophenolate mofetil: 1 to 3 g daily

ISSUES FOR REFERRAL

  • Dermatology referral generally helpful
  • Rheumatology referral for systemic involvement
  • Ophthalmology referral indicated for persons treated with antimalarials to evaluate for ocular toxicity

ADDITIONAL THERAPIES

  • R-salbutamol sulphate
  • IV immunoglobulins

SURGERY/OTHER PROCEDURES

  • Consider laser therapy, cryotherapy, and dermabrasion in patients with persistent DLE lesions.
  • Excision of burned-out scarred lesions may reactivate inactive lesions.

ONGOING CARE

FOLLOW-UP RECOMMENDATIONS

Long-term surveillance is needed during the course of treating DLE to monitor efficacy of medication choice, medication side effects, and signs of systemic disease. é á

Patient Monitoring

  • Initially follow patients once or twice per month, then annually if otherwise asymptomatic.
  • Perform routine laboratory studies to assess for systemic disease.
  • Ophthalmology follow-up at 6-month intervals if taking antimalarials (ocular toxicity).
  • Monitor for Vitamin D deficiency in the setting of strict photoprotection.

PATIENT EDUCATION

  • Use broad-spectrum, water-resistant sunscreens and photo-protective clothing.
  • Discuss symptoms of SLE that may develop during course of DLE.
  • Discuss side effect profile of medications.
  • Tobacco cessation (2)[C]

PROGNOSIS

  • Significant scarring, permanent hair loss, and disfigurement from DLE can cause considerable psychosocial distress and impact quality of life; prompt and early treatment can prevent permanent scarring.
  • 40% of patients may have complete remission; 1 " ô5% develop SLE (these patients usually have generalized DLE).
  • DLE is not life-threatening unless systemic.
  • Some patients may progress through several different subsets of cutaneous lupus during the course of the disease.
  • Small risk of DLE lesions transitioning to squamous cell carcinoma (SCC)

COMPLICATIONS

Cicatricial alopecia, lupoid rash, or SCC é á

REFERENCES

11 Wahie é áS, Daly é áAK, Cordell é áHJ, et al. Clinical and pharmacogenetic influences on response to hydroxychloroquine in discoid lupus erythematosus: a retrospective cohort study. J Invest Dermatol. 2011;131(10):1981 " ô1986.22 Piette é áEW, Foering é áKP, Chang é áAY, et al. Impact of smoking in cutaneous lupus erythematosus. Arch Dermatol. 2012;148(3):317 " ô322.

ADDITIONAL READING

  • Chong é áBF, Song é áJ, Olsen é áNJ. Determining risk factors for developing systemic lupus erythematosus in patients with discoid lupus erythematosus. Br J Dermatol. 2012;166(1):29 " ô35. doi:10.1111/j.1365 " ô2133.2011.10610.x.
  • Cortes-Hern â índez é áJ, Torres-Salido é áM, Castro-Marrero é áJ, et al. Thalidomide in the treatment of refractory cutaneous lupus erythematosus: prognostic factors of clinical outcome. Br J Dermatol. 2012;166(3):616 " ô623.
  • Jessop é áS, Whitelaw é áDA, Delamere é áFM. Drugs for discoid lupus erythematosus. Cochrane Database Syst Rev. 2009;(4):CD002954.
  • Kuhn é áA, Gensch é áK, Haust é áM, et al. Photoprotective effects of a broad-spectrum sunscreen in ultraviolet-induced cutaneous lupus erythematosus: a randomized, vehicle-controlled, double-blind study. J Am Acad Dermatol. 2011;64(1):37 " ô48.
  • Louren â žo é áSV, de Carvalho é áFR, Boggio é áP, et al. Lupus erythematosus: clinical and histopathological study of oral manifestations and immunohistochemical profile of the inflammatory infiltrate. J Cutan Pathol. 2007;34(7):558 " ô564.
  • Panjwani é áS. Early diagnosis and treatment of discoid lupus erythematosus. J Am Board Fam Med. 2009;22(2):206 " ô213.
  • Turan é áE, Sinem Bagci é áI, Turgut Erdemir é áA, et al. Successful treatment of generalized discoid lupus erythematosus with imiquimod cream 5%: a case report and review of the literature. Acta Dermatovenerol Croat. 2014;22(2):150 " ô159.
  • Tzellos é áTG, Kouvelas é áD. Topical tacrolimus and pimecrolimus in the treatment of cutaneous lupus erythematosus: an evidence-based evaluation. Eur J Clin Pharmacol. 2008;64(4):337 " ô341.
  • Winkelmann é áRR, Kim é áGK, Del Rosso é áJQ. Treatment of cutaneous lupus erythematosus: review and assessment of treatment benefits based on Oxford Centre for Evidence-based Medicine criteria. J Clin Aesthet Dermatol. 2013;6(1):27 " ô38.

SEE ALSO

Lupus Erythematosus, Systemic (SLE) é á

CODES

ICD10

  • L93.0 Discoid lupus erythematosus
  • L93.1 Subacute cutaneous lupus erythematosus
  • L93.2 Other local lupus erythematosus

ICD9

695.4 Lupus erythematosus é á

SNOMED

  • Discoid lupus erythematosus (disorder)
  • Discoid lupus erythematosus of face
  • Chronic discoid lupus erythematosus (disorder)
  • disseminated discoid lupus erythematosus (disorder)

CLINICAL PEARLS

  • Patients with cutaneous DLE have a 1 " ô5% chance of developing SLE; screen patients at regular intervals with laboratory testing and physical exam.
  • Early diagnosis and treatment of DLE leads to less clinical and psychosocial morbidity.