Discoid Lupus Erythematosus

Discoid lupus erythematosus (DLE) generally occurs in young adults, with women outnumbering men 2 : 1. Lesions begin as dull-red macules or indurated plaques that develop an adherent scale, then evolve with atrophy, scarring, and pigment changes ( Fig. 8.1 ). In darker-skinned individuals, lesions typically demonstrate areas of both hyperpigmentation and depigmentation. In lighter-skinned patients, the plaques may appear gray or have minimal pigment alteration. The hyperkeratosis characteristically extends into patulous follicles, producing carpet tacklike spines on the undersurface of the scale.

Extensive scarring from discoid lupus erythematosus.

Localized Discoid Lupus Erythematosus.

Discoid lesions are usually localized above the neck, particularly on sun-exposed sites such as the scalp, bridge of the nose, malar areas, lower lip, and ears ( Fig. 8.2 ). The concha of the ear and external canal are frequently involved. Typical lesions are disk-shaped areas of erythema, with follicular plugging, which progress to develop atrophy, scarring, and pigment alteration. Some patients present with periorbital edema and erythema. On the scalp, most lesions begin as erythematous patches or plaques that evolve into white, often depressed, hairless patches. Perifollicular erythema and the presence of easily extractable anagen hairs are signs of active disease. Scarred areas may appear completely smooth or may demonstrate dilated follicular openings in the few remaining follicles. Itching and tenderness are common but rarely severe. On the lips, lesions may be gray or red and hyperkeratotic. They may be eroded and are usually surrounded by a narrow, red inflammatory zone ( Fig. 8.3 ). In one study, 24% of DLE patients had mucosal involvement of the mouth, nose, eye, or vulva. Rarely, aggressive squamous cell carcinoma (SCC) may arise in long-standing lesions of DLE.

Discoid lupus erythematosus.

(Courtesy Steven Binnick, MD.)

Discoid lupus erythematosus.

Patients with cutaneous lupus erythematosus (CLE) may develop systemic disease over time, sometimes with a lengthy delay (8–10 years), though overall only a small percentage (5%–23% reported, though more often the number is less than 15%) of patients with localized DLE will go on to meet criteria for systemic lupus erythematosus (SLE), usually due to cutaneous and mucosal criteria. Although progression from purely cutaneous DLE to SLE occurs infrequently, patients with SLE frequently have discoid lesions. These patients generally have systemic involvement early in the course of their disease, rather than evolving from chronic cutaneous LE to SLE. Fever and arthralgia are common in patients with SLE and discoid lesions. In patients with systemic symptoms, abnormal laboratory tests, such as elevation of antinuclear antibodies (ANAs), antibodies to double-stranded (ds) DNA and C1q, leukopenia, hematuria, and proteinuria, help to identify patients with SLE and suggest a prognosis.

Generalized Discoid Lupus Erythematosus.

Generalized DLE is less common than localized DLE. All degrees of severity are encountered. Most often, the thorax and upper extremities are affected, as well as the head and neck ( Fig. 8.4 ). The scalp may become quite bald with striking patterns of hyperpigmentation and depigmentation. Diffuse scarring may involve the face and upper extremities. Laboratory abnormalities, such as an elevated erythrocyte sedimentation rate (ESR), elevated ANAs, single-stranded (ss) DNA antibodies, and leukopenia, are more common with this form of LE than with localized DLE, and as such patients with generalized DLE are more likely to meet criteria for systemic lupus.

Generalized discoid lupus erythematosus.

Hypertrophic Lupus Erythematosus

Nonpruritic papulonodular lesions may occur on the arms and hands, resembling keratoacanthoma or hypertrophic LP ( Fig. 8.5 ). The lips and scalp may also demonstrate lesions that resemble LP or LPP. Dermoscopy may help distinguish hypertrophic LE from SCC, but biopsy is often needed. Histologic sections of these lesions typically demonstrate lichenoid dermatitis, and a careful examination for other characteristic skin lesions of LE or LP, as well as DIF testing, may be critical in establishing a diagnosis. BMZ thickening, dermal mucin, eccrine coil involvement, and subcutaneous nodular lymphoid infiltrates are features of LE that are not found in LP. Recent reports suggesting the pattern and number of plasmacytoid dendritic cells may be helpful in distinguishing SCC from hypertrophic LE.

Hypertrophic lupus erythematosus.

(Courtesy Steven Binnick, MD.)

Lupus Erythematosus–Lichen Planus Overlap Syndrome

In addition to the cases of hypertrophic LE with lichenoid histology previously discussed, there are patients with a true overlap syndrome with features of both LE and LP. The lesions are usually large, atrophic, hypopigmented, red or pink patches and plaques. Pigment abnormalities become prominent over time, and fine telangiectasia and scaling are usually present. The extensor aspects of the extremities and midline back are typically affected. Prominent palmoplantar involvement is characteristic and tends to be the most troublesome feature for these patients. Nail dystrophy and anonychia may occur. Scarring alopecia and oral involvement have been noted in some patients. The histology of individual lesions has features of LP and/or LE. One study suggested that higher CD3 and CD34 may favor LP over DLE, but this has not been widely examined. DIF may help differentiate the two, but they may share overlapping features. Response to treatment is poor, although potent topical corticosteroids, dapsone, thalidomide, or isotretinoin may be effective. Some patients require immunosuppressive therapy with agents such as mycophenolate mofetil (MMF) or azathioprine. It should also be noted that antimalarials can occasionally produce a lichenoid drug eruption. A rare variant of chronic CLE termed the pigmented macular variant has been described, with lichenoid to gray pigmentation in sun exposed areas; although these patients display interface reaction on biopsy and may have seropositivity, systemic disease is rare, and it is unclear if this represents a rare subtype of lupus or another lichenoid entity. Patients respond to topical steroids, sun protection, and hydroquinone.

Chilblain Lupus Erythematosus

Chilblain LE (Hutchinson) is a chronic, unremitting form of LE affecting the fingertips, rims of ears, calves, and heels, especially in women. It is usually preceded by DLE on the face. Systemic involvement is sometimes seen. Mimicry of sarcoidosis may be striking. Cryoglobulins and antiphospholipid antibody (APLA) should also be sought. Familial chilblain lupus has been linked to mutations in a number of genes, particularly TREX-1, and is considered part of the group of genetic diseases termed interferonopathies.

Tumid Lupus Erythematosus

Tumid LE is a rare but distinctive entity. Patients present with edematous erythematous plaques, usually on the trunk ( Fig. 8.6 ). Histologically, the lesions demonstrate a patchy superficial and deep perivascular and periadnexal lymphoid infiltrate that frequently affects the eccrine coil. Dermal mucin deposition is typical and may be striking. The lesions generally respond readily to antimalarials. Tumid LE shares many features with reticular erythematous mucinosis, and some authorities consider them to be closely related entities.

Tumid lupus.

Lupus Erythematosus Panniculitis (Lupus Erythematosus Profundus)

Patients with the panniculitis type of LE develop subcutaneous nodules that are usually firm, sharply defined, and nontender. The proximal extremities are typically involved. Usually, the overlying skin is normal, but overlying discoid or tumid lesions may occur ( Fig. 8.7 ). Some cases are discovered incidentally when an unrelated lesion is biopsied. The lesions may progress to deep depressions, or “dells,” from loss of the panniculus. LE panniculitis is characteristically chronic and occurs most often in women between ages 20 and 45. Many patients have DLE at other sites or less typically, in the overlying skin.

Lupus panniculitis with overlying discoid lupus erythematosus.

Histologic sections demonstrate lymphoid nodules in the subcutaneous septa, necrosis of the fat lobule, and fibrinoid or hyaline degeneration of the remaining lipocytes. Lipomembranous change, resembling frost on a windowpane, is more typical of stasis panniculitis (lipodermatosclerosis), but it may be noted focally in LE panniculitis. The overlying epidermis may show basal liquefaction and follicular plugging or may be normal. Dermal lymphoid nodules or vertical columns of lymphoid cells may be seen in fibrous tract remnants. Dermal mucin may be prominent, and dermal collagen hyalinization (resembling that seen in morphea) may be present. Continuous granular deposition of immunoglobulin and C3 may be seen at the DEJ. In active cases, abundant fibrin is usually noted in the panniculus.

The most important entity to consider in the differential diagnosis is subcutaneous panniculitis–like T-cell lymphoma (SPTCL). Important clues include the presence of lipocytes, rimmed by atypical lymphocytes with nuclear molding, and the presence of constitutional symptoms. Erythrophagocytosis may be present focally, and T-cell clonality can usually be demonstrated. The infiltrate may be CD8 dominant or may label strongly for CD56, as in natural killer cell lymphoma, or CD30, as in anaplastic lymphoma. CD5 and CD7 expression may be reduced (aberrant loss of pan-T markers). Unfortunately, T-cell clonality, erythrophagocytosis, CD8 predominance, and loss of CD5 or CD7 may also be seen in patients with LE panniculitis who respond to antimalarials or corticosteroids and do not progress to clinical lymphoma. Taken together, these data suggest that some cases of lymphoma may be virtually indistinguishable from LE panniculitis, or that some cases of LE panniculitis represent an abortive lymphoid dyscrasia. Patients diagnosed with lupus panniculitis should be monitored for progression.

Histopathology

Vacuolar interface dermatitis is a universal finding in active SCLE lesions. Mild hyperkeratosis and parakeratosis may be present. Chronic changes of DLE, such as follicular plugging, BMZ thickening, and heavy lymphoid aggregates, are usually lacking. Dermal mucin is variable. DIF is positive in lesional skin in only about one third of cases. A dustlike particulate deposition of immunoglobulin G (IgG) in epidermal nuclei of Ro-positive patients may be present and is a helpful diagnostic finding.

Cutaneous Manifestations

The characteristic butterfly facial erythema seen in patients with SLE is a common manifestation of acute cutaneous LE. The eruption usually begins on the malar area and the bridge of the nose. There may be associated edema. The nasolabial crease if often strikingly spared, unlike in DM. The ears and chest may also be the sites of early lesions. Biopsies at all sites show interface dermatitis and a scant perivascular lymphoid infiltrate. The eruption may last a day to several weeks and resolves without scarring. There may be more widespread erythema in some cases.

Bullous lesions of lupus erythematosus (BLE) occur as single or grouped vesicles or bullae, often widespread, with a predilection for sun-exposed areas ( Fig. 8.10 ). Rarely, the lesions may itch. Most sets of published criteria require that patients with BLE meet ACR criteria for SLE, but some patients have identical bullous lesions and less than four ACR criteria. Histologically, neutrophils accumulate at the DEJ and within dermal papillae. In bullous lesions, there is a subepidermal bulla or superficial dermal edema containing neutrophils. Fluorescence with IgG, IgM, IgA, or C3 is typically present in a continuous, granular pattern at the BMZ on DIF testing. Neutrophils are found in or below the lamina densa on immunofluorescent electron microscopy. Most of these patients are HLA-DR2 positive. The recognition of this subset as distinct is made clear by its often dramatic therapeutic response to dapsone. Epidermolysis bullosa acquisita is histopathologically and immunopathologically identical, because both diseases are mediated by circulating antibodies against type VII collagen. Dapsone is usually ineffective in epidermolysis bullosa acquisita.

Bullous lupus erythematosus.

A variety of vascular lesions occur in 50% of SLE patients. Often, fingertips or toes show edema, erythema, or telangiectasia. Nailfold capillary loops in LE are more likely to show wandering glomeruloid loops, whereas DM and scleroderma capillary loops demonstrate symmetric dilation and dropout of vessels. Capillary loops in the Osler-Weber-Rendu syndrome demonstrate ectasia of half the capillary loop. Erythema multiforme (EM)–like lesions may predominate, termed Rowell syndrome. Rarely, lupus may present with TEN-like lesions due to intense interface inflammation leading to blistering.

In addition to periungual telangiectasia, red or spotted lunulae may be present in patients with SLE, as in RA. The palms, soles, elbows, knees, or buttocks may become persistently erythematous or purplish, sometimes with overlying scale. Diffuse, nonscarring hair loss is common. Short hairs in the frontal region are called “lupus hairs.” These hairs result from a combination of chronic telogen effluvium and increased hair fragility.

Mucous membrane lesions are seen in 20%–30% of SLE patients. Conjunctivitis, episcleritis, and nasal and vaginal ulcerations may occur. Oral mucosal hemorrhages, erosions, shallow angular ulcerations with surrounding erythema, and gingivitis are common ( Fig. 8.11 ). Erythema, petechiae, and ulcerations may occur on the hard palate.

Oral lupus erythematosus.

Multiple eruptive dermatofibromas have been described in SLE. Leg ulcers, typically deeply punched out and with very little inflammation, may be seen on the pretibial or malleolar areas. Many of these patients present with a livedoid pattern, and many have an antiphospholipid antibody. Sneddon syndrome is composed of livedo reticularis and strokes related to a hyalinizing vasculopathy.

Calcinosis cutis is uncommon but may be dramatic. Also seen infrequently are plaquelike or papulonodular depositions of mucin. These reddish purple to skin-colored lesions are often present on the trunk and arms or head and neck ( Fig. 8.12 ). Last, a symmetric papular eruption of the extremities may occur. These skin-colored to erythematous lesions with a smooth, ulcerated or umbilicated surface may show vasculitis or, in older lesions, a palisaded granulomatous inflammation. These occur in patients with SLE, RA, or other immune complex–mediated disease. This eruption has been referred to as palisaded neutrophilic and granulomatous dermatitis of immune complex disease ( Fig. 8.13 ).

Papulonodular mucinosis.

Palisaded neutrophilic granulomatous dermatitis.

Systemic Manifestations

Most organs can be involved in SLE; the symptoms and findings are often caused by immune complex disease, especially vasculitis. The earliest changes noted may be transitory or migratory arthralgia, often with periarticular inflammation. Fever, weight loss, pleuritis, adenopathy, or acute abdominal pain may occur. Arthralgia is often the earliest abnormality and may remain the sole symptom for some time. About 95% of SLE patients will manifest this symptom. Arthralgia, deforming arthropathy, and acute migratory polyarthritis resembling RA may all occur as manifestations of SLE. Avascular necrosis of the femoral head has been observed. Although this is a known complication of systemic corticosteroid therapy, it has also occurred in patients with SLE who have never taken corticosteroids.

Patients with SLE have a higher rate of peripheral arterial disease compared with controls. Thrombosis in vessels of various sizes and thromboembolism may be a recurring event ( Fig. 8.14 ). It may be attributed to a plasma constituent, paradoxically called “lupus anticoagulant” (LA) because it causes prolonged coagulation studies in vitro but thrombosis in vivo. The finding of an LA is usually associated with APLAs. These may be anticardiolipin antibodies, but other APLA types—antiphosphatidylserine, antiphosphatidylinositol, and antiphosphatidylethanolamine—may occur. APLAs and elevated homocysteine may each increase the risk of thrombosis. APLAs are associated with early-onset organ damage. SLE patients with APLAs have higher mortality. Many, but not all, patients have a false-positive blood test for syphilis. In one study, inflammatory lesions of SLE and infections were the most common causes of death during the initial 5 years of disease, whereas thromboses were the most common cause of death after the first 5 years.

Cutaneous thrombosis in antiphospholipid antibody syndrome.

Renal involvement is a predictor of poor prognosis. It may be of either nephritic or nephrotic type, leading in either case to chronic renal insufficiency with proteinuria and azotemia. Patients with lupus who are ANCA positive have higher rates of damage. Active nephritis is unlikely in the absence of anti-dsDNA. Both anti-dsDNA antibody and anti-C1q antibody are of relatively high specificity for active nephritis. Hypercholesterolemia and hypoalbuminemia may occur. Immunoglobulin and complement components have been found localized to the BMZ of glomeruli, where vasculitis produces the characteristic “wire-loop” lesion.

Myocarditis is indicated by cardiomegaly and gallop rhythm, but the electrocardiographic (ECG) changes are usually not specific. Pericarditis, the most frequent cardiac manifestation, and endocarditis also occur. Patients with SLE have accelerated atherosclerosis and elevated risk for cardiovascular morbidity and mortality. Raynaud phenomenon (RP) occurs in about 15% of patients, who have less renal disease and consequently lower mortality rates.

The CNS may be involved with vasculitis, manifested by hemiparesis, convulsions, epilepsy, diplopia, retinitis, and choroiditis. Livedo reticularis is a marker for patients at risk for CNS lesions (Sneddon syndrome; see earlier). Depression and anxiety are common in patients with SLE, and other psychiatric and personality have been reported as well.

Idiopathic thrombocytopenic purpura is occasionally the forerunner of SLE. Coombs-positive hemolytic anemia, neutropenia, and lymphopenia are other hematologic findings. The severity of thrombocytopenia may be a prognostic marker, but can also be followed as a biomarker for response to treatment. Gastrointestinal (GI) involvement may produce symptoms of nausea, vomiting, and diarrhea, and patients may develop intestinal pseudo obstruction. Frequently, the intestinal wall and the mesenteric vessels show vasculitis. Pulmonary involvement with pleural effusions, interstitial lung disease, pulmonary artery hypertension (PAH), and acute lupus pneumonitis may be present. Patients with SLE, pericardial effusions, and anti-RNP antibodies have higher rates of PAH. Sjögren syndrome (keratoconjunctivitis sicca) and Hashimoto thyroiditis are associated with SLE. Overlap with any of the connective tissue diseases may be seen, occurring in approximately 25% of patients. Muscular atrophy may accompany extreme weakness so that DM may be suspected. Myopathy of the vacuolar type may produce muscular weakness, myocardial disease, dysphagia, and achalasia of the esophagus. Steroid myopathy may also occur, and antimalarials may rarely induce myopathy. The serum aldolase level may be elevated with a normal creatine phosphokinase.

A history of exposure to excessive sunlight before the onset of the disease or before an exacerbation is sometimes obtained. Some patients may have only mild constitutional symptoms for weeks or months, but immediately after exposure to strong sunlight, they may develop the facial eruption and severe disease complications.

Hydralazine, procainamide, sulfonamides, penicillin, anticonvulsants, minocycline, and isoniazid have been implicated as causes of drug-induced LE. Penicillamine induces (or unmasks) true SLE. HLA-DR4 individuals, who are slow acetylators, are predisposed to develop hydralazine-induced LE. Antibody to the histone complex H2A-H2B is closely associated with disease. Most drug-induced SLE is associated with a positive ANA, and antibodies directed against histones. Exceptions include penicillamine and etanercept, which may induce or unmask native disease with anti-dsDNA antibodies. l -Canavanine, an amino acid found in alfalfa sprouts and tablets, can also induce or worsen SLE. TNF-inhibitors can induce a variety of types of lupus, with infliximab surpassing etanercept as the most commonly reported culprit. Patients with anti–chimeric antibodies may be ANA positive, and patients with TNF-induced lupus frequently display a malar rash, photosensitivity, and meet ACR criteria for lupus.

Childhood Systemic Lupus Erythematosus

The onset of childhood SLE occurs between ages 3 and 15, with girls outnumbering boys 4 : 1. The skin manifestations may be the typical butterfly eruption on the face and photosensitivity. In addition, there may be morbilliform, bullous, purpuric, ulcerating, or nodose lesions. The oral mucosa is frequently involved. Skin eruptions may be associated with joint, renal, neurologic, and GI disease. Weight loss, fatigue, hepatosplenomegaly, lymphadenopathy, and fever are other manifestations. Pediatric patients with SLE and APLAs, specifically lupus anticoagulants, are at high risk of developing thromboembolic events.

Pregnancy and Female Hormones

Women with LE may have successful pregnancies, but they might have difficulty conceiving, and miscarriages occur with greater frequency, especially among those with APLAs. The course of pregnancy may be entirely normal, with remission of the LE, or the symptoms of LE may become worse. Risk of fetal death is increased in women with a previous history of fetal loss and anticardiolipin or anti-Ro antibodies. For the patient with these antibodies but without a history of previous fetal loss, the risk of fetal loss or neonatal lupus is low. In most cases, the pregnancy itself is well tolerated, although a flare of SLE may occur during the postpartum period. Although several studies failed to demonstrate a clinically significant association between oral contraceptive (OC) use and flares of SLE, recently a UK epidemiologic study found an increased risk of SLE with current use of OC, and the U.S. Nurses’ Health Study suggested that OC and HRT were associated with SLE. There is a high incidence of thromboses in women with APLAs, and OCs containing second- or third-generation progestogens may induce a higher risk. One female-to-male transgender patient experienced significant improvement after testosterone therapy.

Etiology

Genetics plays an important role in LE, with over 100 loci identified in association with sLE. Many of these gene targets are involved in recognition of nucleic acid, type 1 IFN production, and immune signaling. Taken together, these data suggest polygenetic susceptibility to LE. A family history of connective tissue disease is a strong risk factor for all forms of LE. Monozygotic twins, however, display a low concordance rate, with lupus in approximately one fourth of cases. Some skin lesions of LE follow lines of Blaschko, suggesting postzygotic mutation or loss of heterozygosity for a genetic locus. Understanding of lupus genetics is rapidly evolving.

The C-reactive protein (CRP) response is defective in patients with flares of SLE, and the gene locus for CRP maps to 1q23.2 within an interval linked with SLE. Gene polymorphisms in APRIL, a member of the TNF family, have also been linked with SLE. Increased expression of TNF-α and IFN-inducible proteins are noted in cutaneous LE. Polymorphisms of the C1qA gene are associated with both systemic and cutaneous LE. HLA-DR3 confers risk for SLE, and C4 null alleles in Europeans is a specific genetic risk factor for SLE. Linkage varies in different ethnic groups and different clinical subsets of lupus.

Whole exome sequencing has helped identify rare monogenic variants of SLE and SLE-like diseases. CYBB mutations have an X-linked inheritance, and carriers have a higher risk of DLE and SLE. Mutations in DNASE1L3 are associated with SLE with early onset and anti-dsDNA abs. TREX1 mutations are associated with familial chilblain lupus.

Several aspects of the altered immune response are worth particular attention. T-suppressor cell function is reduced in patients with LE. Overproduction of γ-globulins by B cells and reduced clearance of immune complexes by the reticuloendothelial system may contribute to complement-mediated damage. Externalization of cellular antigens, such as Ro/SSA in response to sunlight, may lead to cell injury by way of antibody-dependent cellular cytotoxicity. Abnormal apoptosis or reduced clearance of apoptotic cells may lead to increased exposure of nucleosome antigens and antinucleosome antibodies.

Both ultraviolet (UV) B and UVA can upregulate antigen expression and cytokines, including IL-1, TNF-α, and LFA-1, causing release of sequestered antigens and free radical damage, with UV B felt to be the most pathologically relevant. All these mechanisms may contribute to photosensitivity and UV-induced flares of systemic disease. Air pollutants have been considered a potential trigger, due to increased concentrations of SLE in urban areas and a small Canadian study suggesting a possible link. Tobacco smoke is highly associated with cutaneous LE, but not with systemic LE, and may interfere with the efficacy of antimalarial therapy. Minimal credible data exist regarding other possible aggravating dietary factors, but some reports have implicated excess calories, excess protein, high fat (especially saturated and ω-6 polyunsaturated fatty acids), excess zinc, and excess iron.

Laboratory Findings

There may be hemolytic anemia, thrombocytopenia, lymphopenia, or leukopenia; ESR usually is greatly elevated during active disease but nonspecific. Coombs test may be positive, there is a biologic false-positive test for syphilis, and a rheumatoid factor (RF) may be present. IgG levels may be high, the albumin/globulin ratio is reversed, and serum globulin is increased, especially the γ-globulin or α2 fraction. Albumin, red blood cells, and casts are the most frequent findings in the urine.

Immunologic Findings

• 1.
  

  ANA test. This is positive in 95% of cases of SLE. Human substrates, such as Hep-2 or KB tumor cell lines, are far more sensitive than mouse substrates, and the historical entity “ANA-negative lupus” is quite rare now. ANA pattern has some correlation with clinical subsets, such as a shrunken peripheral pattern in SLE with renal disease, a fine particulate pattern in subacute cutaneous LE, and a homogeneous pattern with antihistone antibodies.

  
  
• 2.
  

  Double-stranded DNA. Anti-dsDNA, anti–native DNA. This is specific, but not very sensitive. It indicates a high risk of renal disease, and correlates with a shrunken peripheral ANA pattern and positive DIF in sun-protected skin.

  
  
• 3.
  

  Anti-Sm antibody. Sensitivity is less than 10%, but specificity is very high.

  
  
• 4.
  

  Antinuclear ribonucleic acid protein (anti-nRNP). Very high titers are present in mixed connective tissue disease (MCTD). Lower titers may be seen in SLE.

  
  
• 5.
  

  Anti-La antibodies. These are common in SCLE and Sjögren syndrome, and occasionally found in SLE.

  
  
• 6.
  

  Anti-Ro antibodies. These are found in about 25% of SLE and 40% of Sjögren patients. They are more common in patients with SCLE (70%), neonatal LE (95%), C2- and C4-deficient LE (50%–75%), late-onset LE (75%), and Asian patients with LE (50%–60%). Photosensitivity may be striking, and externalization of the antigen is seen after UV exposure.

  
  
• 7.
  

  Serum complement. Low levels indicate active disease, often with renal involvement.

  
  
• 8.
  

  Lupus band test. Direct cutaneous immunofluorescence. Continuous granular deposits of immunoglobulins and complement along the DEJ occur in more than 75% of well-established lesions of DLE. In SLE, it usually is positive in sun-exposed skin. A positive test in normal, protected skin correlates with the presence of anti-dsDNA antibodies and renal disease. The lupus band test is seldom performed, because the same population of patients can be detected with anti-dsDNA antibodies.

  
  
• 9.
  

  Anti-ssDNA antibody. This test is sensitive but not specific. Many patients are photosensitive. An IgM isotope seen in DLE may identify a subset of patients at risk for developing systemic symptoms.

  
  
• 10.
  

  Antiphospholipid antibodies. Both the anticardiolipin antibody and the LA are subtypes of APLAs. These are associated with a syndrome that includes venous thrombosis, arterial thrombosis, spontaneous abortions, and thrombocytopenia. Livedo reticularis is a frequent skin finding, and nonfading acral microlivedo, with small, pink cyanotic lesions on the hands and feet, is a subtle clue to the presence of APLAs. These antibodies may occur in association with lupus and other connective tissue disease, or as a solitary event. In the latter case, it is referred to as the primary antiphospholipid syndrome.

Differential Diagnosis

Diagnostically, SLE must be differentiated from DM, EM, polyarteritis nodosa, acute rheumatic fever, RA, pellagra, pemphigus erythematosus (Senear-Usher syndrome), drug eruptions, hyperglobulinemic purpura, Sjögren syndrome, and myasthenia gravis. The SLE patient may have fever, arthralgia, weakness, lassitude, diagnostic skin lesions, increased ESR, cytopenias, proteinuria, immunoglobulin deposition at DEJ, and positive ANA test. Biopsies of skin lesions and involved kidney may also be diagnostic.

Treatment

Some general measures are important for all patients with LE. Exposure to sunlight must be avoided, and broad spectrum, high sun protection factor (SPF) sunscreen should be used daily. Photosensitivity is frequently present even if the patient denies it, and all patients must be educated about sun avoidance and sunscreen use. Smokers should be encouraged and assisted in quitting. The patient should also avoid exposure to excessive cold, to heat, and to localized trauma. Biopsies and scar revision will often provoke a flare of the disease. Women with SLE have an increased risk of osteoporosis, independent of corticosteroid use. Bone density should be monitored and calcium and vitamin D supplementation considered, especially with strict photoprotection. Vitamin D repletion was shown to improve response to some medications. Some women will benefit from bisphosphonate therapy, especially if corticosteroids are used. The most rapid bone loss with corticosteroid therapy occurs at the onset of treatment, so bisphosphonate therapy should not be delayed. Patients who will be treated with immunosuppressive agents should receive a tuberculin skin test, appropriate vaccinations, and thorough physical examination. Aggressive treatment is often necessary for discoid lesions and scarring alopecia. The slowly progressive nature of these lesions, and the lack of systemic involvement, may lead to inappropriate therapeutic complacency. The result is slow, progressive disfigurement.