Chapter 155. Lupus Erythematosus

Lupus erythematosus (LE) is the root designation for a diverse array of illnesses that are linked together by the development of autoimmunity directed predominantly at the molecular constituents of nucleosomes and ribonucleoproteins. Some patients present with life-threatening manifestations of systemic LE (SLE); whereas others, who are affected with what likely represents the same basic underlying disease process, express little more than discoid LE (DLE) skin lesions throughout their illness. It is convenient to conceptualize LE as a clinical spectrum ranging from mildly affected patients with only localized DLE skin lesions to those at risk of dying from the systemic manifestations of LE such as nephritis, central nervous system disease, or vasculitis. The pattern of skin involvement expressed by an individual patient with LE can provide insight about the position on the spectrum where the patient's illness might best be placed.

The nomenclature and classification system originally devised by James N. Gilliam divides the cutaneous manifestations of LE into those lesions that show characteristic histologic changes of LE (LE-specific skin disease) and those that are not histopathologically distinct for LE and/or may be seen as a feature of another disease process (LE-nonspecific skin disease). Within this context, the term “LE-specific” relates to those lesions displaying an interface dermatitis. The term cutaneous LE (CLE) is often used synonymously with “LE-specific skin disease” as an umbrella designation for the three major categories of LE-specific skin disease: acute cutaneous LE (ACLE), subacute cutaneous LE (SCLE), and chronic cutaneous LE (CCLE). This will be the framework used in our discussion of the extraordinarily diverse set of cutaneous lesions that occur in patients with LE (Table 155-1).

The essence of LE is in its heterogeneity, and the challenge for those who treat it is to recognize clinically useful patterns within the mosaic of features that constitute this protean illness. An overview of the systemic manifestations of LE can be seen in the American College of Rheumatology's (ACR) classification criteria for SLE,1 which are presented in Table 155-2, and from the outline of the systemic manifestations of SLE presented in Table 155-3.

The epidemiology and socioeconomic impact of LE in general,2 and CLE specifically,3 have been reviewed. Skin disease is the second most frequent clinical manifestation of LE after joint inflammation. As many as 45% of patients with CLE experience some degree of vocational handicap. A recent quality of life study suggested that the impact of skin manifestations in patients with SLE was preceded only by pain and fatigue related to their disease.4 The Dermatology Life Quality Index and SF-36 have been used to measure quality of life in patients with CLE. Both questionnaires showed that patients with active skin lesions had lower quality of life and that patients with associated alopecia were particularly impacted.5

Malar, or butterfly rash (localized ACLE), has been reported in 20%–60% of large cohorts of patients with LE. Limited data suggest that the maculopapular or SLE rash of generalized ACLE is present in about 35%–60% of patients with SLE. ACLE, like SLE in general, is much more common in women than men (8:1). All races are affected; however, the early clinical manifestations of ACLE can be overlooked in a dark-skinned individual.

Patients presenting with SCLE lesions constitute 7%–27% of LE patient populations. SCLE is primarily a disease of white females, with the mean age of onset in the fifth decade. Drug-induced SCLE patients are somewhat older at disease onset, perhaps reflecting greater exposure to drugs for age-related medical problems (hypertension, cardiovascular disease).

The most common form of CCLE, a classic DLE skin lesion, is present in 15%–30% of SLE populations selected in various ways. Approximately 5% of patients presenting with isolated localized DLE subsequently develop SLE. Rheumatologists have estimated that SLE patients are sevenfold more common than isolated cutaneous LE patients. However, dermatologists have estimated that isolated cutaneous LE patients may be 2-3 times more common that SLE patients. Recently published population-based data have argued strongly that the incidence and prevalence of isolated forms of cutaneous LE are equivalent to those of SLE.6 Although DLE can occur in infants and the elderly, it is most common in individuals between 20 and 40 years of age. DLE has a female-male ratio of 3:2 to 3:1, which is much lower than that of SLE. All races are affected, but investigations suggest that DLE might be more prevalent in blacks.

The cause(s) of and pathogenetic mechanisms responsible for LE-specific skin disease are not fully understood, although recent work has provided many new insights. The pathogenesis of LE-specific skin disease is inextricably intertwined with SLE pathogenesis. Simply put, SLE is a disorder in which the interplay between host factors (susceptibility genes, hormonal milieu, etc.) and environmental factors [ultraviolet (UV) radiation, viruses, and drugs] leads to loss of self-tolerance, and induction of autoimmunity. This is followed by activation and expansion of the immune system, and eventuates in immunologic injury to end organs and clinical expression of disease7 (eFig. 155-0.1). Recent work has highlighted the important role of interferon-α signaling in the pathogenesis of both SLE and LE-specific skin disease.

Genetic Factors

Environmental Factors

Genetic predisposition for a lupus diathesis does not, in itself, produce disease. Rather, it appears that induction of autoimmunity in such patients is triggered by some inciting event, likely an environmental exposure. Drugs, viruses, UV light, and, possibly, tobacco, have been shown to induce development of SLE.

Ultraviolet radiation (UVR) is probably the most important environmental factor in the induction phase of SLE and especially of LE-specific skin disease. UV light likely leads to self-immunity and loss of tolerance because it causes apoptosis of keratinocytes, which in turn, makes previously cryptic peptides available for immunosurveillance. UVB radiation has been shown to displace autoantigens such as Ro/SS-A and related autoantigens, La/SS-B, and calreticulin, from their normal locations inside epidermal keratinocytes to the cell surface.13 UVB irradiation induces the release of CCL27 (cutaneous T cell-attracting chemokine), which upregulates the expression of chemokines that activate autoreactive T cells and interferon-α (IFN-α), producing dendritic cells (DCs), which likely play a central role in lupus pathogenesis.14,15

A recent, large, case-control study reported that smokers are at a greater risk of developing SLE than are nonsmokers and former smokers. A cross-sectional analysis of a collaborative Web-based database established by Werth and colleagues documented that patients with treatment resistant CLE were much more likely to smoke.16 Several authors have shown that patients with LE-specific skin disease who smoke are less responsive to antimalarial treatment.17–19

Numerous drugs have been implicated in inducing various features of SLE (Table 155-3). The drugs that induce CLE can be linked by their photosensitizing properties. It has been suggested that these drugs cause an increase in keratinocyte apoptosis, exposure of previously intracellular peptides on epidermal cell surfaces, and enhance proinflammatory cytokines such as TNF-α and IFN-α.20,21

There has been much speculation about the role of infectious agents, particularly viruses, in the induction of SLE and CLE. Seroconversion to Epstein-Barr virus (EBV) among patients with SLE is nearly universal, and recent data have demonstrated that patients with SLE have defective control of latent EBV infection that probably stems from altered T-cell responses against EBV.

Interferon‐a and Dendritic Cells

Neutrophils

Toll-Like Receptors

Cell-Mediated Immunity in the Pathogenesis of Lupus

Tumor Necrosis Factor-α

T Cells

B Cells

(eFig. 155-0.2)

Cutaneous Lesions

eTable 155-3.1 compares the key clinical, histopathologic, and laboratory features of patients presenting with ACLE, SCLE, and CCLE (classic DLE) skin lesions. It is important to distinguish among the subtypes of LE-specific skin disease, because the type of skin involvement in LE can reflect the underlying pattern of SLE activity. In fact, the designations acute, subacute, and chronic, in regard to CLE, refer to the pace and severity of any associated SLE and are not necessarily related to how long individual lesions have been present. For example, ACLE almost always occurs in the setting of acutely flaring SLE, whereas CCLE often occurs in the absence of SLE or in the presence of mild smoldering SLE. SCLE occupies an intermediate position in this clinical spectrum. Subclassification, although important for assigning risk, is sometimes difficult, as it is not uncommon to see more than one subtype of LE-specific skin disease in the same patient, especially in patients with SLE.

Acute Cutaneous Lupus Erythematosus

Although ACLE localized to the face is the usual pattern of presentation, ACLE can assume a generalized distribution. Localized ACLE has commonly been referred to as the classic butterfly rash or malar rash of SLE (Fig. 155-1). In localized ACLE, confluent symmetric erythema and edema are centered over the malar eminences and bridges over the nose (unilateral involvement with ACLE has been described). The nasolabial folds are characteristically spared. The forehead, chin, and V area of the neck can be involved, and severe facial swelling may occur. Occasionally, ACLE begins as small macules and/or papules on the face that later may become confluent and hyperkeratotic. Generalized ACLE presents as a widespread morbilliform or exanthematous eruption often focused over the extensor aspects of the arms and hands and characteristically sparing the knuckles (Fig. 155-2A). Although perivascular nail fold erythema and telangiectasia can occur (see Fig. 155-2B), they are considerably more common and occur in more exaggerated forms in dermatomyositis (see Fig. 157-5). Generalized ACLE has been indiscriminately referred to as the maculopapular rash of SLE, photosensitive lupus dermatitis, and SLE rash. An extremely acute form of ACLE is rarely seen that can simulate toxic epidermal necrolysis (TEN). This form of LE-specific vesiculobullous disease results from widespread apoptosis of epidermal keratinocytes, and eventuates in areas of full-thickness epidermal skin necrosis, which is subsequently denuded. It can be differentiated between true TEN because it occurs on predominantly sun-exposed skin and has a more insidious onset.30 The mucosa may or may not be involved, as in TEN.

ACLE is typically precipitated or exacerbated by exposure to UV light. This form of CLE can be quite ephemeral, lasting only hours, days, or weeks; however, some patients experience more prolonged periods of activity. Postinflammatory pigmentary change is most prominent in patients with heavily pigmented skin. Scarring does not occur in ACLE unless the process is complicated by secondary bacterial infection.

Subacute Cutaneous Lupus Erythematosus

A disease presentation dominated by SCLE lesions marks the presence of a distinct subset of LE having characteristic clinical, serologic, and genetic features. Although a finding of circulating autoantibodies to the Ro/SS-A ribonucleoprotein particle strongly supports a diagnosis of SCLE, the presence of this autoantibody specificity is not required to make a diagnosis of SCLE.

SCLE initially presents as erythematous macules and/or papules that evolve into hyperkeratotic papulosquamous or annular/polycyclic plaques (Fig. 155-3). Whereas most patients have either annular or papulosquamous SCLE, a few develop elements of both morphologic varieties. SCLE lesions are characteristically photosensitive and occur in predominantly sun-exposed areas (i.e., upper back, shoulders, extensor aspects of the arms, V area of the neck, and, less commonly, the face). SCLE lesions typically heal without scarring but can resolve with long-lasting, if not permanent, vitiligo-like leukoderma, and telangiectasias.

Several variants of SCLE have been described. On occasion, SCLE lesions present initially with an appearance of erythema multiforme. Such cases are similar to Rowell syndrome (erythema multiforme-like lesions occurring in patients with SLE in the presence of La/SS-B autoantibodies). As a result of intense injury to epidermal basal cells, the active edge of an annular SCLE lesion occasionally undergoes a vesiculobullous change that can subsequently produce a strikingly crusted appearance. Such lesions can mimic Stevens-Johnson syndrome/TEN. Pathogenesis is similar to that described above for TEN-like ACLE. Rarely, SCLE presents with exfoliative erythroderma or displays a curious acral distribution of annular lesions. Pityriasiform and exanthematous variants of SCLE have been reported. The skin lesions of neonatal LE (transient, photosensitive, nonscarring LE-specific skin lesions in neonates who have received IgG anti-Ro/SS-A, and, occasionally, other autoantibody specificities transplacentally) share many features with SCLE.

Unlike ACLE skin lesions, SCLE lesions tend to be less transient than ACLE lesions and heal with more pigmentary change. They are also less edematous and more hyperkeratotic than ACLE lesions. SCLE more commonly involves the neck, shoulders, upper extremities, and trunk, whereas ACLE more commonly affects the malar areas of the face. When the face is involved with SCLE, it is most often the lateral face, with sparing of the central, malar regions. In comparison to SCLE lesions, DLE lesions are generally associated with a greater degree of hyper- and hypopigmentation, atrophic dermal scarring, follicular plugging, and adherent scale. A consistent clinical difference is that DLE lesions are characteristically indurated, whereas SCLE lesions are not; this difference reflects the greater depth of inflammation seen histopathologically in DLE lesions.

Approximately one-half of patients with SCLE meet the ACR's revised criteria for the classification of SLE. However, manifestations of severe SLE, such as nephritis, central nervous system disease, and systemic vasculitis, develop in only 10%–15% of patients with SCLE. It has been suggested that the papulosquamous type of SCLE, leu-kopenia, high titer of antinuclear antibody (ANA) (>1:640), and anti-dsDNA antibodies are risk factors for the development of SLE in a patient presenting with SCLE lesions.

SCLE can overlap with other autoimmune diseases, including Sjögren's syndrome, rheumatoid arthritis, and Hashimoto's thyroiditis. Other disorders that have been anecdotally related to SCLE are Sweet syndrome, porphyria cutanea tarda, gluten-sensitive enteropathy, and Crohn's disease. There has also been the suggestion that SCLE can be associated with internal malignancy (breast, lung, gastric, uterine, hepatocellular, and laryngeal carcinomas as well as with Hodgkin lymphoma).31

Chronic Cutaneous Lupus Erythematosus

Classic DLE

Classic DLE lesions, the most common form of CCLE, begin as red-purple macules, papules, or small plaques and rapidly develop a hyperkeratotic surface. Early classic DLE lesions typically evolve into sharply demarcated, coin-shaped (i.e., discoid) erythematous plaques covered by a prominent, adherent scale that extends into the orifices of dilated hair follicles (Fig. 155-4).

DLE lesions typically expand with erythema and hyperpigmentation at the periphery, leaving hallmark atrophic central scarring, telangiectasia, and hypopigmentation (Fig. 155-5). DLE lesions at this stage can merge to form large, confluent, disfiguring plaques. DLE in persons of certain ethnic backgrounds, such as Asian Indians, can present clinically as isolated areas of macular hyperpigmentation. When present on hair-bearing skin (scalp, eyelid margins, and eyebrows), DLE causes scarring alopecia, which can lead to disfigurement and markedly impact quality of life. Follicular involvement in DLE is a prominent feature. Keratotic plugs accumulate in dilated follicles that soon become devoid of hair. When the adherent scale is lifted from more advanced lesions, keratotic spikes similar in appearance to carpet tacks can be seen to project from the undersurface of the scale (i.e., the “carpet tack” sign). DLE lesions can be difficult to diagnose in Caucasian patients because the characteristic peripheral hyperpigmentation is often absent. Such lesions are often confused with actinic keratoses, squamous cell carcinoma, or acne.

DLE lesions are most frequently encountered on the face, scalp, ears, V area of the neck, and extensor aspects of the arms. Any area of the face, including the eyebrows, eyelids, nose, and lips, can be affected. A symmetric, hyperkeratotic, butterfly-shaped DLE plaque is occasionally found over the malar areas of the face and bridge of the nose. Such lesions should not be confused with the more transient, edematous, minimally scaling ACLE erythema reactions that occur in the same areas. Facial DLE, like ACLE and SCLE, usually spares the nasolabial folds. It may be difficult to distinguish early lesions of malar DLE from ACLE, but induration and recalcitrance to topical steroids/calcineurin inhibitors favors the former diagnosis. When DLE lesions occur periorally, they resolve with a striking acneiform pattern of pitted scarring. DLE characteristically affects the external ear, including the outer portion of the external auditory canal (Fig. 155-6A). Such lesions often present initially as dilated, hyperpigmented follicles. The scalp is involved in 60% of patients with DLE; irreversible, scarring alopecia resulting from such involvement has been reported in one-third of patients (see Fig. 155-6B). The irreversible, scarring alopecia resulting from DLE differs from the reversible, nonscarring alopecia that patients with SLE often develop during periods of systemic disease activity. This type of hair loss, so-called lupus hair, may be telogen effluvium occurring as the result of flaring systemic disease.

Localized DLE lesions occur only on the head or neck, whereas generalized DLE lesions occur both above and below the neck. Generalized DLE is more commonly associated with underlying SLE and is often more recalcitrant to standard therapy, frequently requiring layering of antimalarial and immunosuppressive medications. DLE lesions below the neck most commonly occur on the extensor aspects of the arms, forearms, and hands, although they can occur at virtually any site on the body. The palms and soles can be the sites of painful, and at times disabling, erosive DLE lesions. On occasion, small DLE lesions occurring only around follicular orifices appear at the elbow and elsewhere (follicular DLE). We have observed that elbow/extensor arm lesions seem to cooccur with acral finger lesions of DLE, and that patients with this combination of findings more frequently have active systemic disease. DLE activity can localize to the nail unit. The nail can be impacted by other forms of CLE as well as SLE, producing nail fold erythema and telangiectasia, red lunulae, clubbing, paronychia, pitting, leukonychia striata, and onycholysis.

DLE lesions can be potentiated by sunlight exposure but to a lesser extent than ACLE and SCLE lesions. DLE, as well as other forms of LE skin disease activity, can be precipitated by any form of cutaneous trauma (i.e., the Koebner phenomenon or isomorphic effect).

The relationship between classic DLE and SLE has been the subject of much debate.32 The following summary points can be made: (1) 5% of patients presenting with classic DLE lesions subsequently develop unequivocal evidence of SLE and (2) patients with generalized DLE (i.e., lesions both above and below the neck) have somewhat higher rates of immunologic abnormalities, a higher risk for progressing to SLE, and a higher risk for developing more severe manifestations of SLE than patients with localized DLE.

Roughly one-fourth of patients with SLE develop DLE lesions at some point in the course of their disease, and such patients tend to have less severe forms of SLE. Figure 155-7 illustrates the relative risks for systemic disease activity that are associated with the clinical varieties of LE-specific skin disease.

Aside from Classic DLE, there are several other less common variants of CCLE, which are subclasssified as such because of their overlapping histologies and tendency to occur in a low frequency in association with underlying SLE.

Hypertrophic DLE

Hypertrophic DLE, also referred to as hyperkeratotic or verrucous DLE, is a rare variant of CCLE in which the hyperkeratosis normally found in classic DLE lesions is greatly exaggerated. The extensor aspects of the arms, the upper back, and the face are the areas most frequently affected. Overlapping features of hypertrophic LE and lichen planus have been described under the rubric lupus planus. The entity lupus erythematosus hypertrophicus et profundus appears to represent a rare form of hypertrophic DLE, affecting the face with the additional features of violaceous/dull red, indurated, rolled borders and striking central, crateriform atrophy. The name for this clinical entity is ambiguous because LE panniculitis is not characteristic of its histopathology. Patients with hypertrophic DLE probably do not have a greater risk for developing SLE than do patients with classic DLE lesions.

Mucosal DLE

Mucosal DLE occurs in approximately 25% of patients with CCLE. The oral mucosa is most frequently affected; however, nasal, conjunctival, and genital mucosal surfaces can be targeted. In the mouth, the buccal mucosal surfaces are most commonly involved, with the palate (see Fig. 155-6C), alveolar processes, and tongue being sites of less frequent involvement. Lesions begin as painless, erythematous patches that evolve to chronic plaques that can be confused with lichen planus. Chronic buccal mucosal plaques are sharply marginated and have irregularly scalloped, white borders with radiating white striae and telangiectasia. The surfaces of these plaques overlying the palatal mucosa often have a honeycomb appearance. Central depression often occurs in older lesions, and painful ulceration can develop. Rarely, oral mucosal DLE lesions can degenerate into squamous cell carcinoma, similar to longstanding cutaneous DLE lesions. Any degree of nodular asymmetry within a mucosal DLE lesion should be evaluated for the possibility of malignant degeneration. Chronic DLE plaques also appear on the vermilion border of the lips. At times, DLE involvement of the lips can present as a diffuse cheilitis, especially on the more sun-exposed lower lip.

DLE lesions may present on the nasal, conjunctival, and anogenital mucosa. Perforation of the nasal septum is more often associated with SLE than DLE. Conjunctival DLE lesions affect the lower lid more often than the upper lid. Lesions begin as focal areas of nondescript inflammation most commonly affecting the palpebral conjunctivae or the lid margin. Scarring becomes evident as lesions mature, and the permanent loss of eyelashes and ectropion can develop, producing considerable disability.

LE Profundus/LE Panniculitis

LE profundus/LE panniculitis (Kaposi-Irgang disease) is a rare form of CCLE typified by inflammatory lesions in the lower dermis and subcutaneous tissue. Approximately 70% of patients with this type of CCLE also have typical DLE lesions, often overlying the panniculitis lesions. Some have used the term LE profundus to designate those patients who have both LE panniculitis and DLE lesions, and LE panniculitis to refer to those having only subcutaneous involvement. Typical subcutaneous lesions present as firm nodules, 1–3 cm in diameter. The overlying skin often becomes attached to the subcutaneous nodules and is drawn inward to produce deep, saucerized depressions (Fig. 155-8). The head, proximal upper arms, chest, back, breasts, buttocks, and thighs are the sites frequently affected. LE panniculitis, in the absence of overlying DLE, may produce breast nodules that can mimic carcinoma clinically and radiologically (lupus mastitis). Confluent facial involvement can simulate the appearance of lipoatrophy. Dystrophic calcification frequently occurs in older lesions of LE profundus/LE panniculitis, and pain associated with such calcification can, at times, be the dominant clinical problem. Roughly 50% of patients with LE profundus/panniculitis have evidence of SLE. However, the systemic features of patients with LE panniculitis/profundus tend to be less severe, similar to those of patients with SLE who have DLE skin lesions.

Chilblain LE

Chilblain LE lesions initially develop as purple-red patches, papules, and plaques on the toes, fingers, and face, which are precipitated by cold, damp climates and are clinically and histologically similar to idiopathic chilblains (pernio) (see Chapter 94). As they evolve, these lesions usually assume the appearance of scarred atrophic plaques with associated telangiectases. They may resemble old lesions of DLE or may mimic acral lesions of small vessel vasculitis. Histologic findings include a superficial and deep lymphocytic vascular reaction in addition to fibrin deposition in reticular, dermal-based blood vessels. Patients with chilblain LE often have typical DLE lesions on the face and head. It is possible that chilblain LE begins as a classic acral, cold-induced lesion that then koebnerizes DLE lesions, thus explaining the spectrum of clinico-histologic findings, which seem to vary based on when, in the course of the lesion, the biopsy sample is taken.

Chilblain LE appears to be associated with anti-Ro/SS-A antibodies,33 and is linked to Raynaud's phenomenon in many cases.34 Persistence of lesions beyond the cold months, a positive ANA, or presence of one of the other ACR criteria for SLE at the time of diagnosis of chilblain lesions helps to distinguish chilblain LE from idiopathic chilblains.35 Approximately 20% of patients presenting with chilblain LE later develop SLE. Chilblain LE is an underrecognized entity, yet it is likely that it is one of the most common causes of digital lesions in patients with LE. It is sometimes misdiagnosed as vasculitis and may overlap with acral DLE as mentioned above. An autosomal dominant, familial form of Chilbalin LE has recently been described, and is caused by a missense mutation in the TREX 1 (endonuclease repair) gene.36

Lupus Erythematosus Tumidus

Lupus erythematosus tumidus (LET; tumid LE) is a variant of CCLE in which the dermal findings of DLE, namely, excessive mucin deposition and superficial perivascular and periadnexal inflammation, are found on histologic evaluation. The characteristic epidermal histologic changes of LE-specific skin disease are only minimally expressed, if at all. This results in succulent, edematous, urticaria-like plaques with little surface change (Fig. 155-9). Annular urticaria-like plaques can also be seen. The paucity of epidermal change often produces confusion concerning the diagnosis of LET as a form of CCLE.37,38

There have been several recent reports that support this subclassification and further characterize this subtype of CCLE.39–44 Although described to occur in some patients with SLE, most patients with LET have a negative ANA and a benign disease course. LET appears to be the most photosensitive subtype of cutaneous lupus, and typically demonstrates a good response to antimalarials. Additionaly, LET lesions tend to resolve completely without either scarring or atrophy.

There continues to be debate about the validity of LET as an authentic form of LE-skin disease. Some argue that LET lesions may in fact not be a form of CLE45 while others feel that LET deserves to be recognized as a distinct type of CLE (intermittent cutaneous LE) equivalent in importance to acute cutaneous LE, subacute cutaneous LE, and chronic cutaneous LE.46

Other Variants

Other rare forms of chronic cutaneous LE have been described. These include LE hypertrophicus et profundus, lichenoid DLE, LE vermiculatus, LE telangiectaticus, linear CLE, and LE edematous (probably a historical designation for urticaria-like plaque DLE. Further information on these clinical entities has recently been presented.47

Vesiculobullous Skin Change in Lupus Erythematosus

The cutaneous entity described as bullous SLE appears to be a distinct entity, with formation of tense blisters of varying size in the setting of a patient with systemic disease, particularly nephritis. Histopathologically, marked neutrophilic infiltration with dermal papillary microabscess formation is present similar to that of dermatitis herpetiformis (DH) and the inflammatory variant of epidermolysis bullosa acquisita. However, the direct immunofluorescence findings are more typical of those of LE. Type VII collagen autoantibodies are present in some patients.

Drug-Induced Cutaneous Lupus Erythematosus

Lupus Erythematosus-Nonspecific Skin Lesions

Lupus Erythematosus-Nonspecific Lesions as Diagnostic Criteria for Systemic Lupus Erythematosus

Cutaneous Vascular Reactions

Other Lupus Erythematosus-Nonspecific Skin Lesions

eTable 155-3.1 summarizes the major laboratory findings associated with the varieties of LE-specific skin disease, and Table 155-5 presents the autoantibody associations of SLE. Because of the strong association between ACLE and SLE, the laboratory features of ACLE are those associated with SLE (high-titer ANA, anti-dsDNA, anti-Sm, and hypocomplementemia).

The laboratory markers for SCLE are the presence of anti-Ro/SS-A (70%–90%) and, less commonly, anti-La/SS-B (30%–50%) autoantibodies. ANA are present in 60%–80% of patients with SCLE, and rheumatoid factor is present in approximately one-third. Other autoantibodies in patients with SCLE include false-positive serologic tests for syphilis (VDRL rapid plasma reagin) (7%–33%), anticardiolipin (10%–16%), antithyroid (18%–44%), anti-Sm (10%), anti-ds-DNA (10%), and anti-U1 ribonucleoprotein (10%). Patients with SCLE, particularly those with systemic involvement, may have a number of laboratory abnormalities, including anemia, leukopenia, thrombocytopenia, elevated erythrocyte sedimentation rate, hypergammaglobulinemia, proteinuria, hematuria, urine casts, elevated serum creatine and blood urea nitrogen, and depressed complement levels (resulting from genetic deficiency or increased complement consumption).

ANA are present in low titer in 30%–40% of patients with DLE; however, fewer than 5% have the higher ANA levels that are characteristic of patients with overt SLE (>1:320). Antibodies to single-stranded DNA are not uncommon in DLE, but antibodies to dsDNA are distinctly uncommon. Precipitating antibodies to U1RNP are sometimes found in patients whose disease course is dominated by DLE lesions; however, such patients usually have only mild manifestations of SLE or overlapping connective tissue disorders such as mixed connective tissue disease. Precipitating Ro/SS-A and La/SS-B autoantibodies are rare in patients with DLE; low levels of anti-Ro/SS-A antibody detected by enzyme-linked immunoassay are more common. A small percentage of patients with DLE have low-grade anemia, biologic false-positive serologic tests for syphilis (VDRL rapid plasma reagent), positive rheumatoid factor tests, slight depressions in serum complement levels, modest elevations in γ globulin, and modest leukopenia. It has been suggested that such findings are risk factors for the development of SLE. ANA are present in 70%–75% of patients with LE profundus/panniculitis, but anti-dsDNA antibodies are rare.

The laboratory findings associated with SLE, as well as with CLE, in both adults and newborns, have been reviewed.71,72

The LE-specific skin disease histopathology is a distinctive constellation of hyperkeratosis, epidermal atrophy, vacuolar basal cell degeneration, dermal-epidermal junction basement membrane thickening, dermal edema, dermal mucin deposition, and mononuclear cell infiltration of the dermal-epidermal junction and dermis, focused in a perivascular and periappendageal distribution (eFig. 155-9.1). Variable degrees of these features are encountered in the different forms of LE-specific skin disease (see Chapter 6). Differences of opinion exist as to whether ACLE, SCLE, and DLE lesions can be distinguished reliably on the basis of their histopathologic appearances alone.72–74

Acute Cutaneous Lupus Erythematosus

The histopathologic changes in ACLE lesions are generally less impressive than those in SCLE and DLE lesions, and are mainly those of a cell-poor interface dermatitis. The lymphohistiocytic cellular infiltrate is relatively sparse. Some authors have noted an increase in the number of neutrophils in the infiltrate. A mild degree of focal vacuolar alteration of basal keratinocytes can be seen, in addition to telangiectases and extravasation of erythrocytes. One may see individually necrotic keratinocytes, and in its most severe form, ACLE can display extensive epidermal necrosis similar to TEN. The upper dermis usually shows pronounced mucinosis and may be very helpful in distinguishing ACLE from other causes of a cell-poor interface dermatitis. It is uncommon to see basement membrane zone thickening, follicular plugging, or alteration of epidermal thickness in ACLE, although epidermal atrophy is sometimes present.73,74

Subacute Cutaneous Lupus Erythematosus

SCLE also frequently presents as an interface dermatitis, with foci of vacuolar alteration of basal keratinocytes alternating with areas of lichenoid dermatitis. Pronounced epidermal atrophy is often present. SCLE is in the differential diagnosis of atrophic lichenoid dermatitis, along with atrophic lichen planus and lichenoid drug eruptions. Dermal changes include edema, prominent mucin deposition, and sparse mononuclear cell infiltration usually limited to areas around blood vessels and periadnexal structures in the upper one-third of the dermis. Lesser degrees of hyperkeratosis, follicular plugging, mononuclear cell infiltration of adnexal structures, and dermal melanophages might help distinguish SCLE lesions from DLE lesions. It has not been possible to differentiate papulosquamous from annular SCLE by histopathologic criteria alone.72

Chronic Cutaneous Lupus Erythematosus

In classic DLE lesions, epidermal changes include hyperkeratosis, variable atrophy, and interface changes similar to those described for SCLE. The epidermal basement membrane is markedly thickened. Dermal changes include a dense mononuclear cell infiltrate composed primarily of CD4 T lymphocytes and macrophages predominantly in the periappendageal and perivascular areas, melanophages, and dermal mucin deposition. The infiltrate is often quite dense and typically extends well into the deeper reticular dermis and/or subcutis, which may help to distinguish it from ACLE or SCLE. In chronic scarring DLE lesions, the dense inflammatory cell infiltrate subsides and is replaced by dermal fibroplasia. A folliculotropic variant of DLE, in which the inflammatory infiltrate is predominantly around hair follicles, has been described, as have lymphomatoid variants, in which there are extremely dense infiltrates that may contain atypical lymphoid cells.73

Less Common Sub-Types of Lupus Erythematosus-Specific Skin Disease

Immunohistology is often helpful in confirming a diagnosis of LE-specific skin disease and has been shown to boost the sensitivity and specificity of diagnosis.73 Because it is not uncommon to see negative immunofluorescence studies in patients with acute, subacute, and chronic LE, and false-positive studies in healthy individuals, immunohistology must be interpreted in the context of clinical and histologic findings in a given patient.

IgG, IgA, IgM, and complement components (C3, C4, Clq, properdin, factor B, and the membrane attack complex C5b-C9) deposited in a continuous granular or linear band-like array at the dermal-epidermal junction have been observed in the lesional and nonlesional skin of patients with LE since the early 1960s (Fig. 155-10). However, debate about terminology in this area continues to cloud the field. Some restrict the use of the term lupus band test to refer to the examination of nonlesional skin biopsies for the presence of this band-like array of immunoreactants at the dermal-epidermal junction. Others qualify the LBT as being either “lesional” or “nonlesional.” Less confusion might exist if the terms lesional LBT (lesional lupus band) and nonlesional LBT (nonlesional lupus band) were uniformly adopted.

Acute Cutaneous Lupus Erythematosus

The sparse data that exist suggest that 60%–100% of ACLE lesions display a lesional lupus band. However, the realization that sun-damaged skin from otherwise healthy individuals can display similar immunopathology has diluted the clinical value of this finding.

Subacute Cutaneous Lupus Erythematosus

Initial studies indicated that approximately 60% of patients with SCLE had lesional lupus bands. A “dust-like particle” pattern of IgG deposition focused around epidermal basal keratinocytes has been suggested to be more specific for SCLE by reflecting the presence of in vivo bound Ro/SS-A autoantibody.

Chronic Cutaneous Lupus Erythematosus

Early reports suggested that more than 90% of classic DLE lesions had lesional immunoreactants at the dermal-epidermal junction, often extending along the basement membrane of the hair follicle, but subsequent studies report somewhat lower rates. Lesions on the head, neck, and arms are positive more frequently (80%) than those on the trunk (20%). The lesional lupus band also appears to be a function of the age of the lesion being examined, with older lesions (>3 months) being positive more often than younger ones. Ultrastructural localization of immunoglobulin at the dermal-epidermal junction confirms that these proteins are deposited on the upper dermal collagen fibers and along the lamina densa of the epidermal basement membrane zone.

In LE profundus, immunoglobulin and complement deposits are usually found in blood vessel walls of the deep dermis and subcutis. Immunoglobulin deposits at the dermal-epidermal junction may or may not be present, depending on the site biopsied, the presence or absence of accompanying SLE, and the presence or absence of overlying changes of DLE at the dermal-epidermal junction.

Nonlesional Lupus Band Test

There has been much debate over the past three decades regarding the diagnostic and prognostic significance of an immunoglobulin/complement band at the dermal-epidermal junction of nonlesional skin taken from patients with LE.72 When totally sun-protected nonlesional skin (e.g., buttocks) is sampled, the diagnostic specificity for SLE appears to be very high when three or more immunoreactants are present at the dermal-epidermal junction. Prospectively ascertained follow-up data also suggest that the presence of a nonlesional LBT correlates positively with risk for developing LE nephritis. However, the nonlesional LBT has fallen out of favor as a clinical tool largely because the information gained has not been proven to be of significantly greater value than the results of more readily available serologic assays such as antibody to dsDNA.

The differential diagnosis of CLE is outlined in Box 155-1 and eBox 155-1.1. In addition, reticulated erythematosus mucinosis (REM) has been suggested by some to be a form of photosensitive cutaneous LE perhaps related to LE tumidus. REM presents as a reticulated array of macules and/or papules on the upper chest and back.

Acute Cutaneous Lupus Erythematosus

Both localized and generalized forms of ACLE lesions flare and abate in parallel with underlying SLE disease activity. Therefore, the prognosis for any given patient with ACLE is dictated by the pattern of the underlying SLE. Both 5-year (80%–95%) and 10-year (70%–90%) survival rates for SLE have progressively improved over the past four decades as a result of earlier diagnosis made possible by more sensitive laboratory testing and improved immunosuppressive treatment regimens. Ominous prognostic signs in SLE are hypertension, nephritis, systemic vasculitis, and central nervous system disease.

Subacute Cutaneous Lupus Erythematosus

Because SCLE has been recognized as a separate disease entity for only two decades, the long-term outcome associated with SCLE lesions has yet to be determined. It is the authors’ experience that most patients with SCLE have intermittent recurrences of skin disease activity over long periods of time without significant progression of systemic involvement (we are aware of only one death directly attributable to SLE in approximately 150 patients with SCLE). Other patients enjoy long-term if not permanent remissions of their skin disease activity. A few patients have experienced unremitting cutaneous disease activity.

It has also been the authors’ experience that approximately 15% of the patients with SCLE develop active SLE, including lupus nephritis. This subgroup of patients is marked by the presence of papulosquamous SCLE, localized ACLE, high-titer ANA, leukopenia, and/or antibodies to dsDNA. Long-term follow-up studies of SCLE are required to determine the true risk of severe systemic disease progression in patients presenting with SCLE skin lesions. CCLE lesions, typically classic DLE, have also arisen in patients initially presenting with SCLE.

Evidence suggests that overlap occurs between SCLE and Sjögren's syndrome. Patients with SCLE who develop Sjögren's syndrome are at risk for developing the extraglandular systemic complications associated with Sjögren's syndrome, including vasculitis, peripheral neuropathy, autoimmune thyroiditis, renal tubular acidosis, myositis, chronic hepatitis, primary biliary cirrhosis, psychosis, lymphadenopathy, splenomegaly, and B-cell lymphoma.

Chronic Cutaneous Lupus Erythematosus

Most patients with untreated classic DLE lesions suffer indolent progression to large areas of cutaneous dystrophy and scarring alopecia that can be psychosocially devastating and occupationally disabling. However, with treatment, skin disease can be largely controlled. Spontaneous remission occurs occasionally, and the disease activity can recrudesce at the sites of older, inactive lesions. Rebound after discontinuation of treatment is typical, and slower taper of medications during periods of inactivity is recommended. Squamous cell carcinoma occasionally develops in chronic smoldering DLE lesions.

Death from SLE is distinctly uncommon in patients who present initially with localized DLE. As discussed in Section “Epidemiology,” patients presenting with localized DLE have only a 5% chance of subsequently developing clinically significant SLE disease activity. Generalized DLE and persistent, low-grade laboratory abnormalities appear to be risk factors for such disease progression. Unrecognized squamous-cell carcinoma developing within a longstanding DLE skin lesion could be a cause of morbidity and mortality.

Outcomes Measures

The recent development of a validated instrument to measure activity of CLE, the Cutaneous Lupus Erythematosus Area and Severity Index (CLASI), has made it possible to objectively follow patients’ disease course and response to therapy. The instrument has separate scores for damage (scarring) and activity which is important, because one would not expect a “burned-out” scarred area to normalize with drugs that were meant to abate LE activity.76 It has been validated as a useful tool to measure clinical response.77

The initial management of patients with any form of CLE should include an evaluation to rule out underlying SLE disease activity at the time of diagnosis. All patients with CLE should receive instruction about protection from sunlight and artificial sources of UVR and should be advised to avoid the use of potentially photosensitizing drugs such as hydrochlorothiazide, tetracycline, griseofulvin, and piroxicam. With regard to specific medical therapy, local measures should be maximized and systemic agents used if significant local disease activity persists or systemic activity is superimposed.

ACLE lesions usually respond to the systemic immunosuppressive measures required to treat the underlying SLE disease activity that so frequently accompanies this form of CLE (e.g., systemic glucocorticoids, azathioprine, and cyclophosphamide). Increasing evidence suggests that aminoquinoline antimalarial agents such as hydroxychloroquine can have a steroid-sparing effect on SLE, and these drugs can be of value in ACLE. The local measures discussed in Local Therapy below can also be of value in treating ACLE. Because the lesions of SCLE and CCLE are often found in patients who have little or no evidence of underlying systemic disease activity, unlike the lesions of ACLE, nonimmunosuppressive treatment modalities are preferred for SCLE and CCLE (Table 155-6). For the most part, SCLE and CCLE lesions respond equally to such agents.

Local Therapy

Sun Protection

Advise patients to avoid direct sun exposure, wear tightly woven clothing and broad-brimmed hats, and regularly use broad-spectrum, water-resistant sunscreens [SPF ≥30 with an efficient UVA blocking agent such as a photostabilized form of avobenzone (Parsol 1789), micronized titanium dioxide, micronized zinc oxide, or Mexoryl SX]. UV-blocking films should be applied to home and automobile windows, and acrylic diffusion shields should be placed over fluorescent lighting. Corrective camouflage cosmetics such as Dermablend® and Covermark® offer the dual benefit of being highly effective physical sunscreens as well as aesthetically pleasing cosmetic masking agents. An in-depth discussion of practical and theoretical photoprotection and local therapy for autoimmune connective tissue skin disease has been discussed in detail (see Chapter 223).78

Local Glucocorticoids

Although some prefer intermediate-strength preparations, such as triamcinolone acetonide 0.1%, for sensitive areas such as the face, superpotent topical class I agents, such as clobetasol propionate 0.05% or betamethasone dipropionate 0.05%, produce the greatest benefit in CLE. Twice-daily application of the superpotent preparations to lesional skin for 2 weeks followed by a 2-week rest period can minimize the risk of local complications such as steroid atrophy and telangiectasia. Alternatively, a topical calcineurin inhibitor can be used daily during the 2-week rest period from topical corticosteroids. Ointments are more effective than creams for more hyperkeratotic lesions such as hypertrophic DLE. Occlusive therapy with glucocorticoid-impregnated tape (e.g., flurandrenolide) or glucocorticoids with plastic food wrap (e.g., Saran or Glad Press-N-Seal) can potentiate the beneficial effects of topical glucocorticoids but also carries a higher risk of local side effects. Class I or class II topical glucocorticoid solutions and gels are best for treating the scalp. Unfortunately, even the most aggressive regimen of topical glucocorticoids by itself does not provide adequate improvement for most patients with SCLE and CCLE.

Topical Calcineurin Inhibitors

Pimecrolimus 1% cream and tacrolimus 0.1% ointment have demonstrated efficacy in the treatment of ACLE, DLE, and SCLE.79–81 A double blind, placebo controlled pilot study showed that pimecrolimus 1% cream had equal efficacy with betamethasone valerate 0.1% cream in treating facial DLE,82 and a different study demonstrated the efficacy of topical tacrolimus 0.3% compound in clobetasol propionate 0.05% for recalcitrant CLE.83

Intralesional Glucocorticoids

Intralesional glucocorticoids (e.g., triamcinolone acetonide suspension, 2.5–5.0 mg/mL for the face with higher concentrations allowable in less sensitive sites) are more useful in the management of DLE than SCLE. Intralesional glucocorticoids themselves can produce cutaneous and subcutaneous atrophy (deep injections into the subcutaneous tissue enhances this risk). A 30-gauge needle is preferred because it produces only mild discomfort on penetration, especially when injected perpendicularly to the skin. The active borders of lesions should be thoroughly infiltrated. Intralesional therapy is indicated for particularly hyperkeratotic lesions or lesions that are unresponsive to topical glucocorticoids, but most patients with CLE have too many lesions to be managed exclusively by intralesional glucocorticoid injections.

Systemic Therapy

Antimalarials

One or a combination of the aminoquinoline antimalarials can be effective for approximately 75% of patients with CLE who have failed to benefit adequately from the local measures described in Section “Local Therapy.”84 The risks of retinal toxicity should be discussed with the patient, and a pretreatment ophthalmologic examination should be performed. However, the risk of antimalarial retinopathy is extremely rare, particularly in the first 10 years of therapy, if recommended daily dose maximum levels of these agents are not exceeded (hydroxychloroquine, 6.5 mg/kg/day based on ideal body weight; chloroquine, 3 mg/kg/day). Patients should have follow-up ophthalmologic evaluations every 6–12 months while on therapy.

Hydroxychloroquine sulfate (Plaquenil), 6–6.5 mg/kg, should be given daily, either once daily or in two divided doses to prevent GI side effects. Patients should be informed about 2–3 month delayed onset of therapeutic benefit. If no response is seen after 8–12 weeks, quinacrine hydrochloride, 100 mg/day (currently available in the United States only through compounding pharmacies), can be added to the hydroxychloroquine without enhancing the risk of retinopathy (quinacrine does not cause retinopathy). If, after 4–6 weeks, adequate clinical control has not been achieved, consideration should be given to replacing the hydroxychloroquine with chloroquine diphosphate (Aralen), 3 mg/kg to prevent retinopathy. Doses may need to be adjusted for patients with decreased renal or hepatic function. In Europe, chloroquine is generally felt to be more efficacious than hydroxychloroquine in treating CLE, perhaps due to the earlier therapeutic responses that might occur as a result of the shorter time period required to reach steady state blood levels with chloroquine as compared to hydroxychloroquine. Hydroxychloroquine and chloroquine should not be used simultaneously because of enhanced risk for retinal toxicity. There is some evidence that chloroquine may be more retinotoxic than hydroxychloroquine.

Multiple side effects other than retinal toxicity are associated with the use of antimalarials. Quinacrine is associated with a higher incidence of side effects, such as headache, gastrointestinal intolerance, hematologic toxicity, pruritus, lichenoid drug eruptions, and mucosal or cutaneous pigmentary deposition, than is either hydroxychloroquine or chloroquine. Quinacrine commonly produces a yellow discoloration of the entire skin and sclera in fair-skinned individuals, which is completely reversible when the drug is discontinued. Quinacrine can produce significant hemolysis in patients with glucose-6-phosphate dehydrogenase deficiency (this adverse effect has also been reported to occur rarely with hydroxychloroquine and chloroquine). Each of the aminoquinoline antimalarials can produce bone marrow suppression, including aplastic anemia, although this effect is exceedingly rare with the current dosage regimens. Toxic psychosis, grand mal seizures, neuromyopathy, and cardiac arrhythmias occurred with the use of high doses of these drugs in the past; these reactions are uncommon with the lower daily dose regimens used today.

Before therapy with hydroxychloroquine and chloroquine is begun, complete blood cell counts, as well as liver and renal function tests, should be performed; these tests should be repeated 4–6 weeks after therapy has been initiated, and every 4–6 months thereafter. A screen for hematologic toxicity when quinacrine is used is recommended more often. Patients with overt or subclinical porphyria cutanea tarda are at particularly high risk for developing acute hepatotoxicity, which often simulates an acute surgical abdomen, when treated with therapeutic doses of antimalarials for CLE. It is also recommended to check urine levels of β-human chorionic gonadotropin initially in women with childbearing potential, although recent evidence indicates that the risk to pregnant women of currently recommended dose regimens of antimalarials is minimal.

Nonimmunosuppressive Options for Antimalarial-Refractory Disease

Some patients with refractory CLE (SCLE more than DLE) respond to diaminodiphenylsulfone (dapsone).85 An initial dose of 25 mg by mouth twice daily can be increased up to 200–400 mg/day, if necessary. Significant dose-related hemolysis and/or methemoglobinemia can result from the use of dapsone, especially in individuals deficient in glucose-6-phosphate dehydrogenase activity, and, therefore, complete blood counts and liver function tests should be performed regularly. Isotretinoin, 0.5–2.0 mg/kg/day, and acitretin, 10–50 mg/day, have also been used in this setting, but their efficacy is limited by their side effects (teratogenicity, mucocutaneous dryness, and hyperlipidemia). In addition, breakthrough of CLE activity has been a problem with the long-term use of retinoids.

Thalidomide (see Chapter 235) (50–200 mg/day) is strikingly effective for CLE that is refractory to other medications. Numerous studies have cited response rates between 85% and 100%, with many patients experiencing complete remission.86 However, strict prescribing regulations put in place in the United States in 1998 because of severe teratogenicity, make thalidomide challenging to dispense to women of childbearing potential. Sensory neuropathy is another toxicity associated with thalidomide, and 25%–75% of patients with CLE develop peripheral neuropathy while taking the drug. Most cases are reversible when therapy is stopped. Neuropathy seems to correlate with total treatment times so that short courses are preferred. Relapses after the drug is stopped are common. Excess somnolence as well as constipation and other minor side effects sometimes limit its use, although these effects usually abate with lower daily doses.87 Thromboembolism is a serious adverse event that may occur in patients with a preexisting hypercoagulable state (e.g., presence of antiphospholipid antibodies). Oncologists who use thalidomide for multiple myeloma frequently initiate concomitant anticoagulation therapy to prevent this side effect. Lenalidomide (Revlamid, Celgene) is a thalidomide analog that is more efficacious but has similar rates of teratogenicity, peripheral neuropathy, thromboembolism, and also has the additional potential side effect of profound leukopenia.88

Other drugs reported to be of value in the treatment of refractory CLE are gold and clofazimine; however, the benefit varies from case to case and both of these agents are associated with the risk of significant side effects. Vitamin E, phenytoin, sulfasalazine, danazol, DHEA, and phototherapy (UVAI phototherapy, photopheresis) have also been reported in uncontrolled trials to be of value in CLE.

Systemic Glucocorticoids

Every effort should be made to avoid the use of systemic glucocorticoids in patients with LE limited to the skin. However, in occasional patients who have especially severe and symptomatic skin disease, intravenous pulse methylprednisolone has been used. In less acute cases, moderate daily doses of oral glucocorticoids (prednisone, 20–40 mg/day, given as a single morning dose) can be used as supplemental therapy during the loading phase of therapy with an antimalarial agent. The dose should be reduced at the earliest possible time because of the complications of long-term glucocorticoid therapy, especially avascular (aseptic) bone necrosis, a side effect to which patients with LE are particularly susceptible.

Because steroid-induced bone loss occurs most rapidly in the first 6 months of use, all patients who do not have contraindications should begin agents to prevent osteoporosis with the initiation of steroid therapy. An excellent review describing current recommendations for prevention of bone loss and other side effects of systemic glucocorticoids has been published.89 When the disease activity is controlled, the daily dosage should be reduced by 5- to 10-mg decrements until activity flares again or until a daily dosage of 20 mg/day is achieved. The daily dose should then be lowered by 2.5-mg decrements (some physicians prefer to use 1-mg dose decrements below 10 mg/day). Alternate-day glucocorticoid therapy has not been successful in suppressing disease activity in most patients with CLE or SLE. Prednisolone rather than prednisone should be used in patients who have significant underlying liver disease, because prednisone requires hydroxylation in the liver to become biologically active. Any amount of prednisone given as a single oral dose in the morning has less adrenal-suppressing activity than the same amount given in divided doses throughout the day. However, any given amount of this drug, taken in divided doses, has a greater LE-suppressing activity than does the same amount of drug given as a single morning dose.

Other Immunosuppressives

Biologic Therapies

Surgical and Cosmetic Therapy

Predicting and preventing the initial clinical manifestation of LE, whether it is skin disease or systemic, is not feasible at this time. However, as many LE patients exhibit worsening of their skin disease activity with UV light exposure, physical protection from sunlight and artificial sources of UV light as well as the regular use of broad-spectrum sunscreens having a SPF of 30 or greater should be encouraged.