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 intervals
- Prednisone: 15 mg BID, then tapered after response
- Generalized DLE:
- Dapsone: 25 to 100 mg/day (max dose 200 mg/day)
- Azathioprine: 100 mg/day
- Systemic 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.