Discoid LE= الذئبة الحمامية القرصية |
Discoid lupus erythematosus (DLE)
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.
Patients may complain of mild pruritus or occasional pain within the lesions, but most patients are asymptomatic.
PhysicalDiscoid 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 . Discoid lupus erythematosus lesions may become hypertrophic or verrucous (see image below). This subset is manifested by wartlike lesions, most often on the extensor arms. Hypertrophic lesions of LE must be differentiated from warts, keratoacanthomas, or squamous cell carcinoma. These lesions are more difficult to treat
Lupus panniculitis is a form of chronic CLE that may be accompanied by typical DLE lesions or may occur in patients with SLE.6 CausesPatients 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 StudiesSerologic testing is as follows:
Other laboratory findings are as follows:
Other TestsImmunopathology findings are as follows:
Histologic FindingsThe 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 CareThe 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.
Surgical CareExcision of burned-out scarred lesions is possible; however, reactivation of inactive lesions has been reported in some patients. 21
MedicationThe goals of pharmacotherapy are to reduce morbidity and to prevent complications. Hydroxychloroquine and chloroquine phosphate have shown beneficial effects in treating DLE. Alternative therapies, anecdotal reports, and small open-label trials (as reported by Callen23 ) suggest that the following agents may be useful in some patients: dapsone, auranofin, quinacrine, thalidomide, isotretinoin,24 acitretin, azathioprine, mycophenolate mofetil, phenytoin, interferon, and chimeric monoclonal antibody.25 Antimalarial agentsMay 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. Adult200-400 mg/d PO; not to exceed 6.5 mg/kg/d; 310 mg PO qd or bid for several wk depending on response; 155-310 mg/d for prolonged maintenance therapy Pediatric6.5 mg/kg/d PO; 3-5 mg base/kg/d PO qd or divided bid; not to exceed 7 mg/kg/d Penicillamine levels may increase; serum levels increase with cimetidine; magnesium trisilicate may decrease absorption Documented hypersensitivity; psoriasis; retinal and visual field changes attributable to 4-aminoquinolones
PregnancyC - Fetal risk revealed in studies in animals but not established or not studied in humans; may use if benefits outweigh risk to fetus PrecautionsCrosses placenta and may cause ocular, CNS, or ototoxicity in the fetus; do not use if breast-feeding; limit pediatric use to established safe doses to avoid potential fatality; ocular toxicity is possible for hydroxychloroquine and chloroquine but not quinacrine; perform regular ophthalmologic examinations during therapy Chloroquine (Aralen)Inhibits chemotaxis of eosinophils, locomotion of neutrophils, and impairs complement-dependent antigen-antibody reactions.
Adult250-500 mg PO qd Pediatric10 mg/kg PO d 1, then 5 mg/kg 6 h later, followed by 5 mg/kg d 2 and 3
Cimetidine may increase serum levels of chloroquine (possibly other 4-aminoquinolones); magnesium trisilicate may decrease absorption of 4-aminoquinolones Documented hypersensitivity; psoriasis, retinal and visual field changes attributable to 4-aminoquinolones
PregnancyC - Fetal risk revealed in studies in animals but not established or not studied in humans; may use if benefits outweigh risk to fetus PrecautionsCaution in hepatic disease, G-6-PD deficiency, psoriasis, porphyria; not recommended for long-term use in children; perform periodic ophthalmologic examinations; test for muscle weakness Leprostatic agentsMay 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. Adult100-200 mg PO qd PediatricNot established May inhibit anti-inflammatory effects of clofazimine; hematologic reactions may increase with folic acid antagonists, eg, pyrimethamine (monitor for agranulocytosis during second and third mo of therapy); probenecid increases dapsone toxicity; trimethoprim with dapsone may increase toxicity of both; because of increased renal clearance, dapsone levels may significantly decrease when administered concurrently with rifampin
Documented hypersensitivity; G-6-PD deficiency PregnancyC - Fetal risk revealed in studies in animals but not established or not studied in humans; may use if benefits outweigh risk to fetus PrecautionsPerform weekly or biweekly blood counts (first mo), then perform WBC counts monthly (6 mo), then semiannually; discontinue if significant reduction in platelets, leukocytes, or hematopoiesis is seen; caution in methemoglobin reductase deficiency, G-6-PD deficiency, or hemoglobin M because of high risk for hemolysis and Heinz body formation; caution in patients exposed to other agents or conditions (eg, infection, diabetic ketosis) capable of producing hemolysis; peripheral neuropathy can occur (rare); phototoxicity may occur when exposed to UV light Gold compoundsHave 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.
Adult6 mg/d PO qd or divided bid; after 3 mo, may increase to 9 mg/d divided tid; then, if no response, discontinue drug PediatricInitial dose: 0.1 mg/kg/d PO divided bid
Penicillamine, hydroxychloroquine, and antimalarials may increase toxicity
PregnancyB - Fetal risk not confirmed in studies in humans but has been shown in some studies in animals PrecautionsDiscontinue therapy if platelet counts fall <100,000/µL, WBC count <4,000/µL, granulocyte count <1,500/µL ImmunomodulatorsAffect 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.
AdultIn autoimmune conditions: 7.5-25 mg/wk as a single dose PO/SC Pediatric5-15 mg/m2/wk as a single dose PO/SC
Oral aminoglycosides may decrease absorption and blood levels of concurrent oral MTX; charcoal lowers levels; coadministration with etretinate may increase hepatotoxicity; folic acid or its derivatives contained in some vitamins may decrease response to MTX Documented hypersensitivity; alcoholism; hepatic insufficiency; documented immunodeficiency syndromes; preexisting blood dyscrasias (eg, bone marrow hypoplasia, leukopenia, thrombocytopenia, significant anemia); renal insufficiency PregnancyX - Contraindicated; benefit does not outweigh risk PrecautionsMonitor CBC counts monthly, and liver and renal function q1-3mo during therapy (monitor more frequently during initial dosing, dose adjustments, or when risk of elevated MTX levels, eg, dehydration); has toxic effects on hematologic, renal, GI, pulmonary, and neurologic systems; discontinue if significant drop in blood counts occurs; fatal reactions reported when administered concurrently with NSAIDs 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. Adult100-300 mg PO hs aq, and >1 h pc PediatricNot established May increase sedation effects of alcohol, barbiturates, chlorpromazine, and reserpine; because of teratogenic effects, women must use 2 additional methods of contraception or abstain from intercourse
Documented hypersensitivity
PregnancyX - Contraindicated; benefit does not outweigh risk PrecautionsPerform pregnancy test within 24 h prior to initiating therapy (weekly during first mo, followed by monthly tests in women with regular menstrual cycles or q2wk with irregular menstrual cycles); bradycardia may occur; use protective measures (eg, sunscreens, protective clothing) against exposure to sunlight or UV light (eg, tanning beds) 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.
Adult1 mg/kg/d PO for 6-8 wk; increase by 0.5 mg/kg q4wk until response is seen or dose reaches 2.5 mg/kg/d PediatricInitial dose: 2-5 mg/kg/d PO/IV
Toxicity increases with allopurinol; concurrent use with ACE inhibitors may induce severe leukopenia; may increase levels of MTX metabolites and decrease effects of anticoagulants, neuromuscular blockers, and cyclosporine Documented hypersensitivity PregnancyD - Fetal risk shown in humans; use only if benefits outweigh risk to fetus PrecautionsIncreases risk of neoplasia; caution with liver disease and renal impairment; hematologic toxicities may occur 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. Adult2 million U/m2 SC 3 times/wk for 30 d PediatricNot established Theophylline may increase toxicity; cimetidine may increase antitumor effects; zidovudine and vinblastine may increase toxicity Documented hypersensitivity PregnancyC - Fetal risk revealed in studies in animals but not established or not studied in humans; may use if benefits outweigh risk to fetus PrecautionsCaution in brain metastases, severe hepatic or renal insufficiencies, seizure disorders, multiple sclerosis, or compromised CNS Mycophenolate (CellCept)Inhibits inosine monophosphate dehydrogenase and suppresses de novo purine synthesis by lymphocytes, thereby inhibiting their proliferation. Inhibits antibody production. Adult1 g PO bid PediatricNot established; 15-23 mg/kg PO bid suggested May elevate levels of acyclovir and ganciclovir; antacids and cholestyramine decrease absorption, reducing levels (do not administer together); probenecid may increase levels of mycophenolate; salicylates may increase toxicity of mycophenolate Documented hypersensitivity PregnancyD - Fetal risk shown in humans; use only if benefits outweigh risk to fetus PrecautionsIncreases risk for infection; increases toxicity in patients with renal impairment; caution in active peptic ulcer disease CorticosteroidsAnti-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. Adult3-5 mg/mL; not to exceed 2 mL at any single setting PediatricNot established Rare for intralesional, but if administered IM or in sufficient dosage, potential adverse effects may occur with coadministration with barbiturates, phenytoin, and rifampin, which decrease effects of triamcinolone Documented hypersensitivity; fungal, viral, and bacterial skin infections PregnancyC - Fetal risk revealed in studies in animals but not established or not studied in humans; may use if benefits outweigh risk to fetus PrecautionsAdverse effects of intralesional corticosteroids include atrophy and hypopigmentation; significant systemic exposure to corticosteroids may result in multiple complications (eg, severe infections, hyperglycemia, edema, osteonecrosis, myopathy, peptic ulcer disease, hypokalemia, osteoporosis, euphoria, psychosis, myasthenia gravis, and growth suppression); abrupt discontinuation of glucocorticoids may cause adrenal crisis RetinoidsHave 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. AdultInitial dose: 25 or 50 mg/d PO single dose with main meal PediatricNot established Increases toxicity of MTX (avoid concomitant use); interferes with effects of microdosed progestin minipill; coadministration with alcohol may enhance synthesis of etretinate, which has much longer half-life than acitretin (>120 d)
PregnancyX - Contraindicated; benefit does not outweigh risk PrecautionsDo not use in severe obesity; women of childbearing age must be able to comply with effective contraceptive measures, abstain from alcohol intake, and continue contraceptive measures for a minimum of 3 y following cessation of therapy; perform AST, ALT, and LDH tests prior to initiation of acitretin therapy at 1- to 2-wk intervals until stable and thereafter, at intervals as indicated clinically Isotretinoin (Accutane)Synthetic 13-cis isomer of naturally occurring tretinoin (trans -retinoic acid). Both agents are structurally related to vitamin A. Adult40-60 mg/d PO for 4 mo PediatricNot established |