Discoid lupus erythematosus

 

Discoid lupus erythematosus (DLE) is a chronic, scarring, atrophy producing, photosensitive dermatosis. Discoid lupus erythematosus may occur in patients with systemic lupus erythematosus (SLE), and some patients (<5%) with discoid lupus erythematosus progress to SLE.¹ Some patients also have the lesions of subacute cutaneous lupus erythematosus (SCLE), and some may have a malar rash. Patients with discoid lupus erythematosus rarely fulfill 4 or more of the criteria used to classify SLE. Serologic abnormalities are uncommon. Therapy with sunscreens, topical corticosteroids, and antimalarial agents is usually effective.

Pathophysiology

Discoid lupus erythematosus (DLE) probably occurs in genetically predisposed individuals, but the exact genetic connection has not been determined. The pathophysiology of discoid lupus erythematosus is not well understood. It has been suggested that a heat shock protein is induced in the keratinocyte following ultraviolet (UV) light exposure or stress, and this protein may act as a target for gamma (delta) T-cell–mediated epidermal cell cytotoxicity.²

History

Patients may complain of mild pruritus or occasional pain within the lesions, but most patients are asymptomatic.

Approximately 5% or less discoid lupus erythematosus (DLE) patients have accompanying systemic involvement. Arthralgia or arthritis may occur.

Patients may manifest any symptom of SLE; therefore, the history should include an assessment for symptoms of pleuritis, pericarditis, neurologic involvement, and renal involvement.

Several cutaneous diseases have been reported, perhaps in greater frequency, in patients with discoid lupus erythematosus. Note the following:

• Malignant degeneration of chronic lesions of lupus erythematosus (LE) is possible, although rare, leading to nonmelanoma skin cancer. Dark-skinned individuals may be more prone to skin cancer because of the lack of pigmentation within the chronic lesion, combined with chronic inflammation and continued sun damage.
• Mucin deposition is a factor in the histopathology of LE. Some patients develop such a massive amount of mucin that lesions become raised and assume a different morphology.
• Porphyria cutanea tarda appears to be overrepresented in LE patients. Often, the porphyria is discovered when antimalarials first are administered.
• Lichen planuslike lesions may be part of an overlap between LE and lichen planus or may occur as a result of antimalarial therapy.
• Psoriasis is a common disease, although it is not clear whether it is more common in LE patients.

Physical

Discoid lupus erythematosus lesions (DLE) frequently are characteristic. The primary lesion is an erythematous papule or plaque with slight-to-moderate scaling (see images below). As the lesion progresses, the scale may thicken and become adherent, and pigmentary changes may develop, with hypopigmentation in the central or inactive area and hyperpigmentation at the active border.

Lesions spread centrifugally and may merge. As lesions age, dilation of follicular openings occurs with a keratinous plug, termed follicular plugging or patulous follicles (see image below). Resolution of the active lesion results in atrophy and scarring.

At any time, individual lesions may have any or all of these features. Early lesions may be difficult to distinguish from SCLE. Discoid lupus erythematosus lesions often are photodistributed, but relatively unexposed skin also may be affected. The scalp is a common area of involvement, and permanent alopecia may result

Patients with discoid lupus erythematosus often are divided into 2 subsets: localized and widespread. Localized discoid lupus erythematosus occurs when the head and neck only are affected, while widespread discoid lupus erythematosus occurs when other areas are affected, regardless of whether disease of the head and neck is seen (see image below). Patients with widespread involvement often have hematologic and serologic abnormalities, are more likely to develop SLE, and are more difficult to treat.

Several unusual variants of chronic CLE, other than discoid lupus erythematosus, have been reported. Mucosal surfaces may be affected by lesions that appear identical to discoid lupus erythematosus of the skin or by lesions that may simulate lichen planus. Palms and soles may be affected, but this occurs in less than 2% of patients

Causes

Patients with discoid lupus erythematosus probably have genetic predisposition; however, the precise genetic factors that increase the risk of this disease are unknown. The disease usually manifests following UV light exposure, but other triggers or inciting factors also must contribute. Toll-like receptors are possibly involved in the pathogenesis

Laboratory Studies

Serologic testing is as follows:

• Some patients with discoid lupus erythematosus (DLE) (approximately 20%) manifest a positive antinuclear antibody (ANA) when tested with human substrates. HEp-2 cells currently are the most common substrate used in commercial laboratories.
• Anti-Ro (SS-A) autoantibodies are present in approximately 1-3% of patients.
• Antinative DNA (double-stranded or nDNA) or anti-Sm antibodies usually reflect SLE, and they may occur in some patients (<5%).

Other laboratory findings are as follows:

• Cytopenias may be present.
• Elevated sedimentation rate may occur in some patients.
• Rheumatoid factor may be positive.
• Complement levels may be depressed.
• Urinalysis may reflect the presence of renal involvement with proteinuria.

Other Tests

Immunopathology findings are as follows:

• Deposition of immunoglobulin and/or complement at the dermal-epidermal junction is a characteristic feature of LE referred to in most texts and articles. Tissue may be examined from skin lesions (lesional) or normal skin (nonlesional). Nonlesional biopsies may be from exposed or nonexposed surfaces. Testing of nonlesional, nonexposed skin is termed the lupus band test (LBT).
• The use and interpretation of these tests varies according to the biopsy site. Approximately 90% of patients with discoid lupus erythematosus manifest a positive direct immunofluorescence (DIF) test on lesional skin; however, the presence of immunoreactants in the basement membrane zone of lesional skin is not specific for lupus and can be seen in a variety of inflammatory skin diseases. Older lesions or very early lesions may be more likely to be negative on immunofluorescence microscopy. Only patients with SLE have a positive LBT, defined as the presence of multiple immunoreactants in the basement membrane zone. LBTs are neither sensitive nor specific and mostly have been replaced by advances in serologic testing.

Histologic Findings

The characteristic histopathologic alterations observed in discoid lupus erythematosus include vacuolar alteration of the basal cell layer, thickening of the basement membrane, follicular plugging, hyperkeratosis, atrophy of the epidermis, incontinence of pigment, and inflammatory cell infiltrate (usually lymphocytic) in a perivascular, periappendiceal, and subepidermal location. Often, an abundance of mucin is seen within the dermis. The histopathologic features differ depending upon the type and age of the lesion.

Medical Care

The goals of discoid lupus erythematosus (DLE) management are to improve the patient's appearance, to control existing lesions and limit scarring, and to prevent the development of further lesions. Advise patients that the risk of serious systemic disease is possible, although rare. Regular repeat clinical evaluation accompanied by simple laboratory studies usually is sufficient to evaluate the possible progression from the primary cutaneous disorder to the disorder accompanied by systemic involvement.

Therapy begins with sun-protective measures, including sunscreens, protective clothing, and behavior alteration. Cosmetic measures, such as cover-up makeup or wigs, may be suggested for appropriately selected patients. Makeup used for camouflage includes Covermark and Dermablend.⁷

Smoking appears to decrease the efficacy of antimalarial agents, and efforts regarding smoking cessation are advisable in patients who smoke or are exposed to secondary smoke.^8,9,10

Standard medical therapy includes corticosteroids (topical or intralesional) and antimalarials. Antimalarials appear less effective in patients who smoke; however, discoid lupus erythematosus possibly is worse in these patients. In addition, antimalarial therapy seems to lessen the progression to SLE and to lower the risk of thrombovascular disease.^11,12 Alternative therapies include auranofin, thalidomide,^13,14,15,16 oral or topical retinoids, and immunosuppressive agents.^17,18 Thalidomide is regularly used in antimalarial-resistant patients. In most patients, the antimalarial should be continued during thalidomide therapy, unless a complication due to the antimalarial occurs. In addition, lenalidomide may be useful in some patients.¹⁹

Topical corticosteroids are selected for the type of lesion under treatment and for the site of involvement. For example, lotions or foams are preferred for the scalp, weaker agents are used on the face, and superpotent agents are used for hypertrophic lesions.

Topical calcineurin inhibitors have also been used in patients with cutaneous lesions of LE. In addition, topical retinoids have been reported to be helpful. Lastly, topical imiquimod has been reported to be effective in one patient.

Intralesional injection of corticosteroids (typically, this author uses triamcinolone acetonide 3 mg/mL) is useful as adjunctive therapy for individual lesions. Potential for atrophy relates to the amount of corticosteroid injected in any one area; therefore, dilute concentrations are preferred. In addition, the treating physician must take care to limit the total dose of the injections at any given office/clinic visit to avoid systemic toxicity from the steroids eg, if a patient is given 10 mL of triamcinolone 3 mg/mL, this means that the patient has received a total of 30 mg, and toxicity is the same as if it had been delivered orally or by intramuscular injection.

Among immunosuppressives, methotrexate (MTX) may be considered.²⁰ In this author's experience, azathioprine and, recently, mycophenolate mofetil, have been more successful than MTX, while systemic corticosteroids are rarely effective.²¹

Surgical Care

Excision of burned-out scarred lesions is possible; however, reactivation of inactive lesions has been reported in some patients.

Laser therapy may be useful for lesions with prominent telangiectases. Reactivation also is a consideration with this form of therapy. An open trial in a small group of patients has demonstrated efficacy of pulsed dye laser therapy for discoid lupus erythematosus lesions. However, before using this therapy in additional patients, at a minimum, a test area should be treated to make certain that the discoid lupus erythematosus does not flare.²²

Consultations

Consultation with the following specialists may be helpful:

• Rheumatologist - For joint involvement
• Nephrologist - For renal involvement
• Internist - To evaluate systemic involvement
• Ophthalmologist - To monitor therapy with hydroxychloroquine or chloroquine

Antimalarial agents

May have immunomodulatory properties. Hydroxychloroquine is DOC when a systemic agent is needed for DLE. Chloroquine is second-line therapy.

Hydroxychloroquine (Plaquenil)

For treatment of DLE and SLE. Inhibits chemotaxis of eosinophils, locomotion of neutrophils, and impairs complement-dependent antigen-antibody reactions.
Hydroxychloroquine sulfate 200 mg is equivalent to 155 mg hydroxychloroquine base and 250 mg chloroquine phosphate.

Chloroquine (Aralen)

Inhibits chemotaxis of eosinophils, locomotion of neutrophils, and impairs complement-dependent antigen-antibody reactions.

Leprostatic agents

May modulate the immune system.

Dapsone (Avlosulfon)

Mechanism of action is similar to sulfonamides where competitive antagonists of PABA prevent formation of folic acid, inhibiting bacterial growth. The anti-inflammatory action may relate to suppression of neutrophil function by inhibition of the halide-myeloperoxidase system.

Gold compounds

Have proven effective in the treatment of inflammation with autoimmune etiology.

Auranofin (Ridaura)

Gold is taken up by macrophages, which, in turn, inhibit phagocytosis and lysosomal membrane stabilization. Alters immunoglobulins, decreasing prostaglandin synthesis and lysosomal enzyme activity.

Immunomodulators

Affect factors that regulate the immune system.

Methotrexate (Rheumatrex, Trexall)

Reversibly inhibits dihydrofolate reductase; limits the availability of 1-carbon fragments necessary for synthesis of purines and the conversion of deoxyuridylate to thymidylate in the synthesis of DNA and cell reproduction. Extensively used for cancer treatment, rheumatoid arthritis, psoriasis, and as a steroid-sparing agent in various autoimmune conditions.

Thalidomide (Thalomid)

Immunomodulatory agent that may suppress excessive production of TNF-alpha and may down-regulate selected cell-surface adhesion molecules involved in leukocyte migration.
If <50 kg (110 lb), start at low end of dose regimen.

Azathioprine (Imuran)

Antagonizes purine metabolism and inhibits synthesis of DNA, RNA, and proteins. May decrease proliferation of immune cells, which results in lower autoimmune activity.

Interferon alfa-2a and alfa-2b (Roferon and Intron A)

Protein product manufactured by recombinant DNA technology. Mechanism of antitumor activity is not clearly understood; however, direct antiproliferative effects against malignant cells and modulation of host immune response may be important factors. Has antiviral, antitumor, and immunomodulatory actions.

Mycophenolate (CellCept)

Inhibits inosine monophosphate dehydrogenase and suppresses de novo purine synthesis by lymphocytes, thereby inhibiting their proliferation. Inhibits antibody production.

Corticosteroids

Anti-inflammatory agents that suppress the immune system at several levels including inhibition of inflammatory cells and the production of antibodies.

Triamcinolone (Aristocort)

Can be administered intralesionally in a concentration of 3-5 mg/mL. Amounts injected should be recorded. Systemic adverse effects are uncommon with low doses. Atrophy is possible and is dose dependent.

Retinoids

Have the ability to regulate cell proliferation and regulate immune system.

Acitretin (Soriatane)

Retinoic acid analog, similar to etretinate and isotretinoin. Etretinate is main metabolite and acitretin has demonstrated clinical effects close to those seen with etretinate. Mechanism of action is unknown.

Isotretinoin (Accutane)

Synthetic 13-cis isomer of naturally occurring tretinoin (trans -retinoic acid). Both agents are structurally related to vitamin A.
Decreases sebaceous gland size and sebum production. May inhibit sebaceous gland differentiation and abnormal keratinization.
A US Food and Drug Administration–mandated registry is now in place for all individuals prescribing, dispensing, or taking isotretinoin. For more information on this registry, see iPLEDGE. This registry aims to further decrease the risk of pregnancy and other unwanted and potentially dangerous adverse effects during a course of isotretinoin therapy.