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Lupus

Key Points

  • Lupus is a disease that presents across a broad spectrum of cutaneous and systemic manifestations. It may be cutaneous-only or systemic with cutaneous manifestations; some patients with systemic lupus do not have cutaneous involvement. Diagnostic evaluation of a patient with lupus should be aimed at understanding which form of lupus the patient has; the specific diagnosis should inform appropriate treatment.
  • Since the faces of patients with the classic facial eruption of systemic lupus erythematosus usually clear with treatment of their systemic disease, only the management of more common forms of cutaneous lupus will be discussed here. The four forms of cutaneous lupus discussed are: discoid lupus, subacute cutaneous lupus, lupus profundus, and bullous lupus.
  • Subcutaneous lupus may be drug-induced in etiology.

Introduction

Clinically, the cutaneous presentation of systemic lupus erythematosus (SLE) may have specific or non-specific features. Specific cutaneous signs include malar (butterfly) facial rash, discoid skin lesions, oral ulcers, and photosensitivity, especially in combination with systemic symptoms. Non-specific skin signs of systemic lupus include chilblains (pernio), livedo reticularis, vasculitis, and other (non-oral) ulcerations.

Cutaneous lupus erythematosus (CLE) may be divided into four subtypes: discoid lupus, subacute cutaneous lupus, lupus profundus, and bullous lupus. These subtypes can usually be distinguished by characteristic cutaneous features (see Table 1). Of note, these specific forms of cutaneous lupus may also occur in association with systemic lupus erythematosus. It is also important to note that some patients with cutaneous-only lupus may meet criteria for systemic lupus erythematosus.

The diagnosis of cutaneous lupus may be confirmed by skin biopsy, which in general reveals a vacuolar interface dermatitis, often in association with a lymphocytic infiltrate with plasma cells, epidermal atrophy, and mucin. Variants exist, such as bullous lupus, which is marked by the presence of bullous lesions clinically and histologically, the infiltrate of which may be comprised of neutrophils rather than lymphocytes. Lupus profundus has less epidermal and interface involvement, with the focus of inflammation in the subcutaneous fat. A direct immunofluorescence testing of the skin biopsy will reveal characteristic patterns, depending on the form of cutaneous lupus.

The goal of treatment for cutaneous lupus is directed at inflammation of the skin, and often requires systemic therapy. Prevention of cutaneous flares is essential, and avoidance of sun exposure and any exacerbating medications are key elements. Medications associated with subacute cutaneous lupus include: anti-fungal medications (terbinafine more commonly than griseofulvin), hydrochlorothiazide, calcium channel blockers, angiotensin-converting enzyme inhibitors, beta-blockers, interferons, anticonvulsants (carbamazepine, phenytoin), glyburide, penicillamine, spironolactone, statins, psoralen, sulfonylurea, NSAIDs (piroxicam, naproxen), diltiazem, biologics (etanercept, efalizumab), antihistamines (ranitidine), and chemotherapy (docetaxel). Stopping the triggering medication will lead to resolution, but only over several months.
Table 1. Subtypes of cutaneous lupus

Sub-type Characteristic features of cutaneous presentation Notes
Discoid lupus Photosensitive, annular plaques with central scarring (hypopigmented or depigmented) rimmed with peripheral hyperpigmentation Common involvement of scalp, face, conchal bowl of ear, neck Heal with pigmentary changes, scarring and alopecia (if scalp involvement is present) Rare cases progress to systemic lupus erythematosus Patients with systemic lupus erythematosus may have discoid lesions
Subacute cutaneous lupus Photosensitive, papulosquamous eruption or annular violaceous to erythematous scaly plaques 80% ANA+ Many patients are also Ro/SSA+ May be drug-induced
Lupus profundus Minimal epidermal change Subcutaneous warmth, nodules, and/or atrophy Cheeks, chest, shoulders, hips, buttocks, face Disfiguring
Bullous lupus Bullous lesions, often photosensitive
Neonatal lupus Violaceous to erythematous scaly plaques, often with periocular involvement (raccoon eyes) Female patients (newborns) Anti-Ro/SSA (87%)+ Anti-La/SSB (50%)+ Born to mothers who are Ro/SSA+ but may be asymptomatic Association with congenital heart block in up to 50% patients, also cardiomyopathy

Initial Evaluation

Discoid lupus erythematosus

Subacute lupus erythematosus

Systemic lupus erythematosus

Neonatal lupus erythematosus

Lupus profundus

Differential diagnosis

Rosacea, face

Tinea faciei

Psoriasis

Dermatomyositis

Treatment

First-line treatment: Photoprotection is critical for all patients with cutaneous lupus erythematosus (CLE). Inflammation should be targeted via topical, intralesional, or systemic immunosuppression, or a combination therapeutic approach. Treatment requires monitoring and adjustment according to the activity of cutaneous disease.

Patients with cutaneous lupus lesions should undergo diagnostic evaluation for possible systemic lupus erythematosus. All patients with CLE should have laboratory parameters checked for the development of SLE at routine intervals.

Initial therapy

  • Topical corticosteroids: Prescribe a potent topical corticosteroid such as desonide 0.05% or triamcinolone 0.1% ointment b.i.d. (face) or superpotent such as fluocinonide 0.05% or clobetasol 0.05% ointment b.i.d. (body), to be applied b.i.d. to areas of active disease.
  • Intralesional corticosteroids: Intralesional triamcinolone acetonide (such as Kenalog, 10 mg/cc) diluted 1:1 or 1:2 with lidocaine 1% (final steroid concentration 3.33-5 mg/cc) can be administered to active lesions or deeper (i.e., dermal or subcutaneous) lesions. Do not perform this therapy more often than once every 3-4 weeks to minimize atrophy.
  • All patients with CLE should practice strict photoprotection and sun avoidance, as even minimal sun exposure can result in further spread or reactivation of quiescent disease. Photoprotection should include physical barriers (hats, protective clothing, gloves), as well as broad spectrum UVA/UVB-blocking sunscreens for exposed areas of skin. Sunscreens should contain UVA-blocking agents such as mineral sunscreens (zinc oxide), mexoryl (SX or XL), and/or parsol 1789. As a result of photoprotection and sun avoidance, patients may become deficient in vitamin D levels; vitamin D should be supplemented in the diet and levels monitored.

Alternative therapy

  • Antimalarials (such as hydroxychloroquine 4-6.5 mg/kg/day and chloroquine 250 mg daily) are an effective therapeutic option. Baseline and screening ophthalmologic exams should be performed, as this therapy can be associated with some irreversible ocular toxicities. These antimalarials may be used in combination with quinacrine (50-100 mg daily), a third antimalarial not associated with ocular toxicity.
  • Systemic corticosteroids are sometimes effective for patients in whom antimalarials are contraindicated. A typical regimen consists of prednisone 0.5 mg/kg daily for 2-3 weeks, followed by tapering if a response occurs. A more prolonged 4-6 week course with tapering may be used if the response is slow.
  • Alternative treatments for refractory cases of CLE that do not respond to antimalarials include azathioprine, mycophenolate mofetil, or thalidomide. Systemic retinoids and methotrexate may also lead to resolution of symptoms and is in the therapeutic ladder for CLE.
  • Dapsone 50-200 mg/day usually leads to a rapid resolution of the bullous lesions.

Ancillary therapy

Camouflage techniques are particularly helpful in dark-skinned patients with DLE. Several lines of cosmetics are designed to mask pigmentary abnormalities such as those in DLE (e.g., Dermablend, Covermark). These cosmetics often are available only in cosmetic departments of large department stores.

Pitfalls

  • Topical and intralesional steroids may cause epidermal or dermal atrophy and can themselves produce pigmentary abnormalities. Prolonged or excessive usage can worsen the disfigurement in CLE. Intralesional steroids may be associated with exacerbation of lupus profundus lesions and should be used with caution.
  • Antimalarials may be associated with both reversible and irreversible ocular toxicity. Baseline and monitoring ophthalmological evaluation (every 6-12 months) is recommended.
  • Antimalarials can cause acute hemolysis in G6PD-deficient patients; hence, a screen for this enzyme must be obtained prior to initiation of therapy.
  • Quinacrine (Atabrine) can cause a yellow discoloration of the skin.
  • The most common side effects of dapsone therapy are hemolysis and a hypersensitivity syndrome.
  • Cosmetic surgical correction of lesions of lupus profundus, even when inactive, may be associated with exacerbation of disease and should be undertaken with caution.

When to refer to a dermatologist

  • If the diagnosis of lupus is not clear
  • If the form of cutaneous lupus cannot be distinguished
  • For patients who fail topical steroids, especially for management of systemic immunosuppression or antimalarial medication dosing and monitoring

Clinical Cases

Case 1

  • 31-year-old woman with recurrent lesions on cheeks and scalp
  • Negative workup for systemic lupus erythematosus (recent)
  • Lesions are itchy, exacerbated by sun exposure
  • No current treatment

Initial evaluation

  • Diagnosis: Discoid lupus (confirmed by biopsy)
  • Desonide 0.05% ointment b.i.d. (face)
  • Clobetasol 0.05% ointment b.i.d. (scalp)
  • Counseling on photoprotection and sun avoidance
  • Vitamin D supplementation is recommended

4-week follow-up evaluation

  • Clinically improved
  • Ongoing photoprotection emphasized
  • Annual follow-up for clinical evaluation, medication refill, and screening for systemic lupus erythematosus

Case 2

  • 20-year-old woman with slightly pruritic annular, violaceous plaques for two months on back, chest, abdomen, and arms
  • No current medications
  • Negative workup for systemic lupus erythematosus (recent)

Initial evaluation

  • Diagnosis: Subacute cutaneous lupus (confirmed by skin biopsy)
  • Fluocinonide 0.05% ointment b.i.d.
  • Counseling on photoprotection and sun avoidance
  • Vitamin D supplementation is recommended

4-week follow-up evaluation

  • No clinical improvement
  • Patient is referred for ophthalmologic evaluation and started on hydroxychloroquine 5 mg/kg/day
  • Ongoing photoprotection emphasized
  • Follow-up in 6 weeks

6 weeks later

  • Patient is noting clinical improvement
  • Quarterly follow-up for clinical evaluation, medication refill, screening for systemic lupus erythematosus, and ophthalmology exam

Case 3

  • Female newborn infant born at 37 weeks gestational age
  • Presents with neonatal-onset annular violaceous scaly plaques on the face, scalp, and trunk
  • Bilateral periocular lesions (raccoon eyes)
  • Anti-Ro/SSA+ (mother is also anti-Ro+), Anti-La/SSB+
  • ANA+ (speckled pattern)
  • Diagnosis: Neonatal cutaneous lupus (confirmed by skin biopsy)

Initial evaluation

  • Electrocardiogram, transthoracic echocardiogram recommended
  • Lab studies recommended: liver transaminases, bilirubin, alkaline phosphatase, renal function, complete blood count
  • Low potency topical corticosteroid (desonide 0.05% ointment) b.i.d. recommended

1-week follow-up

  • Cardiac studies are normal
  • All lab studies are normal
  • No systemic immunosuppression or cardiac medications are indicated
  • Skin lesions are improving
  • Continue topical corticosteroids

1-month follow-up

  • Repeat lab studies are normal
  • Lesions are fading with telangiectasias and mild skin atrophy
  • Topical corticosteroids are discontinued
  • Dermatologic, rheumatologic, and cardiac follow-up evaluation is recommended

References

Clarke JT, Werth VP (2010) Rheumatic manifestations of skin disease, Curr Opin Rheum, 22:78-84.

Gammon B, Hansen C, Costner MI (2011) Efficacy of mycophenolate mofetil in antimalarial-resistant cutaneous lupus erythematosus, JAAD, Epub ahead of print.

Kuhn A, Ruland V, Bonsmann G (2010) Cutaneous lupus erythematosus: Update of therapeutic options (part I and II), JAAD, Epub ahead of print.

Lowe G, Henderson CL, Grau RH, Hansen CB, Sontheimer RD (2009) A systematic review of drug-induced subacute cutaneous lupus erythematosus, BJD, 164:465-472.

Wisuthsarewong W, Soongswang J, Chantorn R (2011) Neonatal lupus erythematosus: clinical character, investigation, and outcome, Ped Derm, 28:115-121.