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.
eTable 155-3.1 Comparison of the Major Types of Lupus Erythematosus-Specific Skin Disease ||Download (.pdf)
eTable 155-3.1 Comparison of the Major Types of Lupus Erythematosus-Specific Skin Disease
Clinical features of skin lesions
Thickened basement membrane
Antidouble-stranded DNA antibodies
Risk for developing systemic lupus erythematosus
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.
Localized acute cutaneous lupus erythematosus. Erythematous, slightly edematous, sharply demarcated erythema is seen on the malar areas in a “butterfly” distribution.
Generalized acute cutaneous lupus erythematosus. A. Well-demarcated patches of erythema with fine overlying scale on the dorsal aspect of the hands, fingers, and periungual areas. Note the characteristic sparing of the knuckles, which are preferentially involved in dermatomyositis. B. Closeup view of periungual erythema and grossly visible telangiectasia. Although these lesions can be seen in lupus erythematosus, they are more typical of dermatomyositis.
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.
Subacute cutaneous lupus erythematosus (SCLE). A. Annular SCLE on the upper back of a 38-year-old woman. Note the central areas of hypopigmentation in which no dermal atrophy is present. B. Papulosquamous SCLE over the extensor aspect of the forearm of a 26-year-old woman.
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 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).
Classic discoid lupus erythematosus. Typical early erythematous plaque on the forehead demonstrating hyperkeratosis and accentuation of follicle orifices in a 60-year-old man with a 25-year history of cutaneous lupus erythematosus. The lesion had been present for 3 months; no dermal atrophy was present at this stage.
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.
Classic discoid lupus erythematosus. Sharply demarcated, round-to-ovoid slightly indurated, erythematous plaques on the neck and face. Most plaques show a mild degree of hyperkeratosis, and some show dermal atrophy. Noninflamed areas of hypopigmentation and scarring mark the sites of prior lesions that have resolved.
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.
Classic discoid lupus erythematosus (DLE) and mucosal DLE in a 45-year-old African-American woman with a 20-year history of untreated cutaneous lupus erythematosus. A. Characteristic involvement of the ear shows lesions with atrophy and postinflammatory hyperpigmentation as well as inflammatory red plaques on the scalp with postinflammatory hypopigmentation. B. Confluent lesions on the scalp have resulted in extensive scarring alopecia. C. Plaques of DLE on the palatal mucosa showing morphologic features similar to those of cutaneous lesions.
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.
Relative risk for coexistence of or progression to systemic lupus erythematosus in patients presenting with various forms of lupus erythematosus (LE)-specific skin disease. The spectrum of LE is depicted as a disease continuum ranging from skin disease alone to life-threatening systemic disease. ACLE = acute cutaneous lupus erythematosus; DLE = discoid lupus erythematosus; SCLE = subacute cutaneous lupus erythematosus.
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, 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 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.
Lupus erythematosus panniculitis. Lupus panniculitis has resulted in large, sunken areas of overlying skin; erythema and atrophy of the skin are present.
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
Lupus erythematosus tumidus. Note succulent, indurated plaques.
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 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 existing nomenclature surrounding vesiculobullous skin change in LE is also a source of potential confusion. Bullae may develop in ACLE and SCLE as a manifestation of particularly aggressive liquefactive degeneration of the epidermal basal layer, resulting in basal cell dissolution and simulating the clinical and histopathologic appearance of TEN. Vesiculo-bullous changes can develop at the active edge of annular SCLE lesions, and subepidermal bullous changes occasionally develop in DLE lesions.
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
Drug-induced lupus shares symptoms and laboratory characteristics with idiopathic SLE, and numerous drugs have been implicated in inducing various features of SLE, e.g., procainamide
, and most recently, anti-TNF medications. Classic drug-induced SLE is associated with antihistone antibodies and manifests similarly to SLE but without cutaneous involvement.
Drugs can also induce or exacerbate lupus-specific skin lesions, especially SCLE (see Table 155-4
). Many medications have been implicated, including ACE inhibitors, calcium channel blockers, thiazide diuretics, sulfonylureas, antiepilepticcs, antimalarials, tetracyclines, antifungals, and NSAIDS. These medications likely unmask SCLE in an immunogenetically susceptible individual, perhaps via photosensitizing mechanisms. SCLE has recently been reported with the use of leflunomide
for rheumatoid arthritis, and Sjogren's syndrome. Anti-TNF medications and interferon-α have been reported to induce both SCLE and DLE skin lesions, likely by interfering with homeostasis between these molecules.48,49
Table 155-4 Causes of Drug-Induced Lupus
Lupus Erythematosus-Nonspecific Skin Lesions
A large number of cutaneous lesions that are found in LE patients are not specific for LE, that is, they also occur in patients that do not have or never develop LE (Table 155-1
) and do not share the histologic features of LE-specific skin disease. Such skin lesions are usually found in the patients with underlying SLE or a significant risk thereof. Nonspecific skin findings in LE include vasculitis, photosensitivity reactions, alopecia, Raynaud's phenomenon, livedo reticularis, soft-tissue calcification, bullous lesions, urticaria, cutaneous mucinosis, skin necrosis, ulcerations, and nail changes.
Lupus Erythematosus-Nonspecific Lesions as Diagnostic Criteria for Systemic Lupus Erythematosus
As with some forms of LE-specific skin disease (e.g., ACLE), the presence of nonspecific skin lesions may be an indicator of underlying SLE activity. In studies looking at skin lesions in patients with SLE, higher activity scores were seen in association with photosensitivity, Raynaud's phenomenon, oral ulcers, nonscarring alopecia (all lupus nonspecific lesions), in addition to malar rash and cicatricial alopecia.50–53
The high prevalence rates of these conditions in SLE has led to their past and/or present inclusion in the ACR criteria for diagnosis of SLE. Photosensitivity, defined clinically as an abnormal response to UVR
, appears to be a relatively sensitive indicator of SLE. Several different studies have documented between 50% and 93% incidence rates of photosensitivity in patients with SLE. Because of the frequency of photosensitivity in SLE, all patients should be taught the importance of protecting skin from UVR. Oral ulcers are present in roughly 25%–45% of SLE patients54,55
and up to 25% of DLE patients.56
Although these lesions can show LE-specific histopathologic changes on biopsy, particularly in DLE patients, they often are nonspecific. LE-nonspecific alopecia, diffuse nonscarring alopecia that is different than the scarring alopecia associated with DLE, has been referred to as lupus hair
and presents as coarse, dry hair that has increased fragility. It often results in broken hairs and may be more prominent over the frontal hairline. This likely has considerable overlap with a diffuse nonscarring alopecia caused by telogen effluvium.
Cutaneous Vascular Reactions
Reactions that are focused on the cutaneous vasculature are important to recognize in patients with SLE, as they can frequently indicate underlying systemic vascular pathology. Raynaud's phenomenon is the most common vascular reaction in lupus patients: one study documented Raynaud's phenomenon in 39.6% of patients with SLE.57
Additionally, it has been shown that Raynaud's phenomenon seems to herald a worse prognosis and is associated with higher disease activity scores.50,52
The presence of Raynaud's phenomenon in patients with SLE may correlate with an increase risk in DLE lesions on the hands. Skin changes that can be seen in association with chronic severe Raynaud's phenomenon include focal ulcerations on the fingertips and periungual areas that result in pitted scarring on resolution, prominent nail fold capillary ectasia and drop out, punctate cuticular hemorrhage due to incompetent nail fold capillaries, fingertip tuft atrophy, digital calcinosis, and pterygium inversus unguium (see Chapter 170
Patients with SLE often develop vessel pathology in the form of vasculitis. In SLE, all sizes of vessels may be affected.58
When leukocytoclastic vasculitis (LCV) presents in patients with SLE, other causes of LCV, such as medications and infections, should be excluded before a diagnosis of primary lupus-associated LCV is assigned. Cutaneous vasculitis in a patient with SLE may predict the development of lupus nephritis.53
Urticarial vasculitis is not uncommon in SLE patients and presents as tender urticarial papules and plaques, often over bony prominences, which last longer than 24 hours. It often involves nondependent areas of skin.59
Involvement of medium and/or large vessels in the skin, may present as purpuric plaques with stellate or retiform borders with or without cutaneous necrosis and ulceration, or subcutaneous nodules, and can be a marker for associated mononeuritis multiplex and/or visceral vasculitis.60
LE-nonspecific vasculitis must be distinguished from vasculopathy due to thromboembolism because it may present with similar clinical findings. LE-nonspecific vasculopathy is most commonly the result of antiphospholipid antibodies. Digital skin lesions in SLE patients are frequently falsely attributed to vasculitis61
Livedo reticularis should be considered as a separate LE-nonspecific cutaneous vascular reaction, although it has clear overlap with vasculopathy. It manifests as net-like, blanchable, complete or incomplete, red-purple rings on the extremities and is the result of impeded flow of blood through vessels. Macular erythema over the thenar- and hypothenar eminences of the palms has been reported in lupus patients. Reticulated palmar erythema can also be a sign of vasculopathy associated with antiphospholipid antibodies. Dilated capillaries of the nail folds have been found in LE patients but less frequently than in patients with dermatomyositis (including clinically amyopathic dermatomyositis) or systemic sclerosis. Erythromelalgia (erythermalgia) is characterized by intense burning pain in the feet and hands, accompanied by local macular erythema and warmth. It differs from Raynaud's phenomenon in that it worsens with exposure to heat instead of cold. It may be seen as an isolated clinical entity or in association with several different underlying illnesses, including SLE. Telangiectasia and erythema of the proximal nail fold were found in 76% of patients who had both DLE and SLE, but none in patients with DLE in the absence of SLE, suggesting that it, too, is a rather sensitive indicator for systemic disease activity.57
Other Lupus Erythematosus-Nonspecific Skin Lesions
Urticaria is sometimes associated with LE and is thought to be a manifestation of the immune dysregulation of the disease process. One study found chronic urticaria in 44% of 73 SLE patients, sometimes occurring as the presenting disease manifestation.54
SLE patients may present with LE-nonspecific cutaneous mucinosis. Such patients may develop indurated erythematous papules, nodules, or plaques, typically on the trunk and/or arms. Histopathologic examination of these lesions reveals diffuse dermal mucin deposits. A number of nail changes have been noted in LE patients, including leukonychia, nail pitting or ridging, onycholysis, onychomadesis, and red lunula.62–64
Other conditions seen more commonly in the setting of LE that are on the list of LE-nonspecific skin lesions include lichen planus, acanthosis nigricans, cutis laxa, anetoderma, multiple dermatofibroma, acquired ichthyosis, and interstitial granulomatous dermatitis.65–70