Overview of Cutaneous Lupus Erythematosus

11/11/2019 Overview of cutaneous lupus erythematosus - UpToDate
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Overview of cutaneous lupus erythematosus

Author: Joseph F Merola, MD, MMSc, FAAD, FACR
Section Editors: David S Pisetsky, MD, PhD, Jeffrey Callen, MD, FACP, FAAD
Deputy Editors: Abena O Ofori, MD, Monica Ramirez Curtis, MD, MPH
All topics are updated as new evidence becomes available and our peer review process is complete.
Literature review current through: Oct 2019. | This topic last updated: Sep 19, 2019.
INTRODUCTION
Cutaneous lupus erythematosus (cutaneous LE) includes three subsets of LE-specific skin diseases: acute
cutaneous lupus erythematosus (ACLE), subacute cutaneous lupus erythematosus (SCLE), and chronic
cutaneous lupus erythematosus (CCLE) (table 1). CCLE encompasses discoid lupus erythematosus (DLE),
lupus erythematosus tumidus (LE tumidus), lupus profundus (also known as lupus panniculitis), chilblain lupus
erythematosus (chilblain LE), and lichenoid cutaneous lupus erythematosus-lichen planus overlap syndrome
(LE-LP overlap syndrome).
Cutaneous LE can occur as a manifestation of systemic lupus erythematosus (SLE) or independent of SLE. The
varying strengths of association between SLE and the individual subtypes of cutaneous LE are best illustrated in
a graphic (figure 1). Patients with SLE may also develop a variety of LE-nonspecific skin diseases, cutaneous
disorders that lack histologic features of LE, but occur with increased frequency in patients with SLE.
An overview of the various clinical manifestations of cutaneous LE and LE-nonspecific skin diseases is provided
here. In-depth discussions of SLE and the treatment of DLE and SCLE are provided separately. (See "Clinical
manifestations and diagnosis of systemic lupus erythematosus in adults" and "Initial management of discoid
lupus and subacute cutaneous lupus" and "Management of refractory discoid lupus and subacute cutaneous
lupus" and "Clinical manifestations and diagnosis of systemic lupus erythematosus in adults", section on
'Clinical manifestations'.)
CLASSIFICATION
The modified Gilliam grouping system for cutaneous manifestations of LE provides a helpful organizational
framework for the related but distinct clinical entities that comprise LE-specific and LE-nonspecific skin
diseases. The three subcategories under LE-specific skin disease and their major clinical variants include:
● Acute cutaneous lupus erythematosus (ACLE)
• Localized ACLE (ie, malar rash, butterfly rash)
• Generalized ACLE
• Toxic epidermal necrolysis-like ACLE
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● Subacute cutaneous lupus erythematosus (SCLE)
• Annular SCLE
• Papulosquamous SCLE
• Drug-induced SCLE
• Less common variants: erythrodermic, poikilodermatous, erythema multiforme-like (Rowell syndrome),

and vesiculobullous annular SCLE
● Chronic cutaneous lupus erythematosus (CCLE)
• Discoid lupus erythematosus (DLE)
- Localized DLE
- Generalized DLE
- Hypertrophic DLE
• Lupus erythematosus tumidus (LE tumidus)
• Lupus profundus (also known as lupus panniculitis)
• Chilblain lupus erythematosus (chilblain LE)
• Lichenoid cutaneous lupus erythematosus-lichen planus overlap syndrome (LE-LP overlap syndrome)
The key characteristic that unites the LE-specific skin diseases is histopathology. Common shared
histopathologic features include hyperkeratosis; epidermal atrophy; vacuolar interface dermatitis (liquefactive
degeneration of the basal layer of the epidermis); a superficial, perivascular, and perifollicular mononuclear cell
inflammatory infiltrate; thickening of the basement membrane; and pigment incontinence [1]. All of these
features are not necessarily present in all variants. In particular, interface dermatitis is a consistent
histopathologic feature of ACLE, SCLE, and discoid lupus erythematosus (the most common form of CCLE) but
is not a typical feature of LE tumidus or lupus profundus. Interface dermatitis may also be seen in non-LE
disorders, such as dermatomyositis.
In addition, most LE-specific skin diseases can occur in association with SLE, with the exception of LE tumidus,
for which associated SLE is rare (figure 1). LE-specific diseases may also occur in conjunction with other LE-
specific skin diseases and have a similar approach to treatment. (See 'Management' below.)
The designations "acute," "chronic," and "subacute" do not necessarily or strictly reflect the duration of activity of
the skin disease. The "acute" in ACLE reflects the often transient and recurrent course of ACLE and the
tendency for exacerbations of ACLE to occur during acute flares of SLE; in addition, the terminology was
originally coined in reference to a lack of residual long-term skin damage, dyspigmentation, or scarring. The
"chronic" in CCLE reflects both the often prolonged course of CCLE and the resulting chronic skin changes of
dyspigmentation and scarring that occur in DLE. SCLE may lead to longstanding skin dyspigmentation but
typically does not cause scarring.
Although ACLE, SCLE, and the variants of CCLE are described as distinct entities, patients may develop more
than one form of cutaneous LE. Many patients, up to 30 percent in some reports, may have overlap between
subsets of cutaneous LE, particularly SCLE and DLE [2].
ASSOCIATION WITH SLE
Cutaneous disease is common in systemic lupus erythematosus (SLE); approximately 80 percent of patients
develop skin disease at some point in their disease course. However, cutaneous LE frequently exists
independently of SLE and may be two to three times more prevalent than SLE [3-6].
The association with SLE varies among the subtypes of cutaneous LE and mainly has been estimated from
cross-sectional studies and retrospective studies [6-8]. Studies evaluating cross-sectional percent prevalence of
underlying SLE in patients with cutaneous LE have suggested the following levels of association with SLE
(these data do not reflect incident cohort data):
● ACLE – >90 percent [3]

● SCLE – 48 to 50 percent [9]
● Localized DLE – 5 to 10 percent [10]
● Generalized DLE – 15 to 28 percent [10]
● Lupus profundus/panniculitis – 5 to 10 percent [11]
● Lupus erythematosus tumidus – Rarely associated with SLE [12]
It is important to again note that these data represent the cross-sectional co-prevalence between cutaneous LE
and SLE, rather than a prospective incidence. A graphical representation of the associations between the
subtypes of cutaneous LE and SLE is provided (figure 1).
Patients who develop SLE after the onset of cutaneous LE often do so within the first few years after diagnosis
[13]. In a Danish nationwide cohort study that included 2380 patients with cutaneous LE (62 percent with DLE,
20 percent with SCLE, and the remainder with other or unspecified forms of cutaneous LE), patients who did not
have a diagnosis of SLE at the time of diagnosis had a 9 and 13 percent probability of a diagnosis of SLE 5 and
10 years after cutaneous LE, respectively [13]. The median time to diagnosis of SLE was two years. Women
and patients with SCLE had the greatest probability for a diagnosis of SLE.
LUPUS ERYTHEMATOSUS-SPECIFIC SKIN DISEASE
Acute cutaneous lupus erythematosus (ACLE), subacute cutaneous lupus erythematosus (SCLE), and chronic
cutaneous lupus erythematosus (CCLE) comprise LE-specific skin disease.
Acute cutaneous lupus erythematosus — ACLE is a manifestation of systemic lupus erythematosus (SLE)
that may present as a characteristic localized facial eruption, less commonly as a generalized eruption, and
rarely as a toxic epidermal necrolysis (TEN)-like presentation [14]. Localized ACLE appears in approximately
one-half of patients with SLE. Almost all patients with ACLE have SLE.
● Clinical manifestations – The facial eruption of localized ACLE (also known as "malar rash" or "butterfly
rash") is characterized by erythema in a malar distribution (cheeks and bridge of the nose) (picture 1A-B).
The nasolabial folds are spared.
Localized ACLE may precede other symptoms of SLE by months or even years or may be accompanied by
other symptoms and signs of acute SLE. The involved skin feels warm and appears slightly edematous.
The erythema may last for hours, days, or weeks and often recurs, particularly with sun exposure. In darker
skin types, postinflammatory hyperpigmentation or hypopigmentation may persist even after the acute
inflammatory stage has resolved.
Generalized ACLE presents as an erythematous maculopapular (morbilliform) eruption involving primarily

sun-exposed skin. The extensor surfaces of the arms and hands are common sites. Notably, the skin
overlying the knuckles often is spared, a feature that contrasts with dermatomyositis. Occasionally, the
inflammatory infiltrate is severe enough to produce vesicles or bullae. Severe cases can resemble TEN-like
ACLE [15-19]. (See "Clinical manifestations of dermatomyositis and polymyositis in adults" and "Stevens-
Johnson syndrome and toxic epidermal necrolysis: Pathogenesis, clinical manifestations, and diagnosis".)
● Histopathology – The classic histologic findings of localized and generalized ACLE are consistent with
interface dermatitis and include apoptotic keratinocytes, vacuolization of the basal cell layer of the
epidermis, a lymphohistiocytic infiltrate in the superficial dermis, and dermal mucin deposition [20]. The
findings can be subtle.
● Differential diagnosis – Localized ACLE should be distinguished from rosacea. Rosacea can present with
malar erythema and may be exacerbated by sun exposure (picture 2). Features that favor a diagnosis of
rosacea include involvement of the nasolabial fold, papules or pustules (papulopustular variant), and
exacerbation of erythema with typical rosacea triggers (spicy foods, caffeine, heat, etc). Although rarely
necessary, a skin biopsy can distinguish ACLE from rosacea [21]. (See 'Diagnosis' below and "Rosacea:
Pathogenesis, clinical features, and diagnosis".)
Other causes of facial erythema that may be confused with ACLE include sunburn, seborrheic dermatitis,
contact dermatitis, erysipelas, flushing (idiopathic or associated with carcinoid syndrome,
pheochromocytoma, or mastocytosis), and dermatomyositis. A skin biopsy can aid in distinguishing most of
these disorders from ACLE. An exception is dermatomyositis, which exhibits similar pathologic findings. A
helpful clinical feature of facial eruptions in dermatomyositis is the tendency to involve the nasolabial folds;
in ACLE, the nasolabial folds are spared (picture 3). (See "Approach to the patient with facial erythema"
and "Rosacea: Pathogenesis, clinical features, and diagnosis" and "Clinical manifestations of
dermatomyositis and polymyositis in adults".)
Subacute cutaneous lupus erythematosus — SCLE frequently is associated with SLE [22,23]. Approximately
50 percent of affected patients meet the 1997 American College of Rheumatology (ACR) classification criteria
for SLE, but subsequent studies have revealed that approximately 10 to 15 percent of patients presenting with
SCLE go on to develop severe clinical manifestations of SLE (eg, serious central nervous system or renal
disease) (table 2) [9]. SCLE can also occur as a result of drug exposure. (See "Clinical manifestations and
diagnosis of systemic lupus erythematosus in adults" and 'Drug-induced SCLE' below.)
The ACR classification criteria are known to have inherent limitations, which include classifying SLE too readily
in patients with SCLE. Based upon SCLE features alone, at least 3 or 4 of 11 criteria are often met (ie, SCLE
patients may have photosensitivity, positive antinuclear antibodies [SSA/Ro+], mild arthralgias, and/or oral
ulcers, which could suggest the diagnosis of SLE). However, these patients may have no other systemic end-
organ involvement or other SLE features. In 2012, the Systemic Lupus International Collaborating Clinics
(SLICC) proposed revised classification criteria that addressed some of these limitations regarding the
cutaneous disease manifestations (table 2). It should be noted that the ACR and SLICC criteria were developed
for study purposes and have limited use in clinical practice. (See "Clinical manifestations and diagnosis of
systemic lupus erythematosus in adults", section on 'Classification criteria'.)
There is a strong association between SCLE, human leukocyte antigen (HLA)-DR3, antibodies to Ro/SSA, and
polymorphisms in the tumor necrosis factor (TNF)-alpha promoter gene [24,25]. More than 80 percent of
patients with SCLE are positive for anti-Ro/SSA antibodies [26,27]. SCLE has also been associated with
homozygous deficiencies of the second component of complement [28,29]. (See "The anti-Ro/SSA and anti-
La/SSB antigen-antibody systems".)
● Clinical manifestations – SCLE begins as small, erythematous, slightly scaly papules that evolve into
either psoriasiform plaques (papulosquamous SCLE) or annular plaques (annular SCLE) (picture 4A-B).
The latter often coalesce to form polycyclic or figurative patterns. The plaques are typically erythematous
with variable amounts of overlying scale. The most common sites of involvement are somewhat
photodistributed and include the shoulders, forearms, neck, and upper torso. Despite a photoaggravated
nature of the condition, the face is often spared [23]. Dyspigmentation at sites of resolved SCLE is common
and may resemble vitiligo. Scarring usually does not occur. Less common variants include vesiculobullous
annular, poikilodermatous, erythrodermic, and erythema multiforme-like (Rowell syndrome) SCLE. Drug-
induced SCLE is reviewed separately. (See 'Drug-induced SCLE' below.)
Most patients with SCLE exhibit photosensitivity, with exacerbations of disease stimulated by sun exposure.
A case-control study of 76 patients with SCLE (including 48 who also fulfilled ACR criteria for SLE) and 24
patients with SLE without SCLE found photosensitivity nearly twice as prevalent in patients with SCLE than
in patients with SLE without SCLE (86 versus 46 percent, respectively) [30]. Associated arthralgias and oral
ulcers are reported; however, serious features such as cytopenias and serositis occur much less frequently.
● Histopathology – Compared with discoid lupus erythematosus (DLE), the histopathology of SCLE shows
less follicular plugging and hyperkeratosis, and the perivascular and appendageal lymphocytic infiltrates
tend to be more superficial. There is vacuolization of the basement membrane and mucin deposition in the
dermis. Basement membrane thickening is generally absent or minimal (picture 5A-B) [23,31]. (See 'Discoid
lupus erythematosus' below.)
● Differential diagnosis – The differential diagnosis of SCLE includes other disorders that may exhibit
erythematous papules or plaques such as psoriasis, tinea corporis, nummular eczema, dermatomyositis,
cutaneous T cell lymphoma, and drug eruptions [32]. If the diagnosis is uncertain, a biopsy can distinguish
SCLE. (See 'Diagnosis' below.)
Drug-induced SCLE — Many classes of drugs have been implicated in SCLE, including antihypertensive
drugs, lipid-lowering agents, proton pump inhibitors, antifungal agents, TNF-alpha inhibitors, and others (table 3)
[10,33-36]. A case-control study that included 234 patients with incident SCLE found that more than one-third of
cases appeared related to a drug exposure [33]. (See "Drug-induced lupus", section on 'Drug-induced
cutaneous lupus'.)
Drug-induced SCLE and idiopathic SCLE have similar clinical, histopathologic, and laboratory features and can
be indistinguishable in the absence of a helpful medication history. However, certain features may be more likely
to occur in each subtype. A retrospective study of 165 patients with idiopathic SCLE and 67 patients with drug-
induced SCLE found that, compared with patients with idiopathic SCLE, patients with drug-induced SCLE were
older (mean age 41 versus 53 years), reported more systemic symptoms (13 versus 48 percent), and were
more likely to have leukocytoclastic vasculitis on histopathology (none versus 11 percent) [37]. Findings that
were more common in idiopathic disease than in drug-induced disease included histopathology showing mucin
deposition (70 versus 36 percent) and direct immunofluorescence findings of both immunoglobulin M (IgM) and
C3c deposition at the dermoepidermal junction (52 versus 21 percent). Tissue eosinophilia does not help to
distinguish idiopathic from drug-induced SCLE [38].
Drug withdrawal often leads to improvement in drug-induced SCLE. In the retrospective study of 11 patients with
drug-induced SCLE and 79 patients with idiopathic SCLE, all cases of drug-induced disease resolved after drug
withdrawal. The mean time to resolution was seven weeks and Ro/SSA antibodies eventually disappeared in 8
of the 10 patients who previously tested positive for these antibodies [27]. Similarly, most patients in a
retrospective study of 15 patients with drug-induced SCLE experienced improvement in the clinical
manifestations of SCLE within eight weeks of drug withdrawal and a decrease in anti-Ro/SSA antibodies within
eight months following drug withdrawal [34].
Neonatal lupus — Neonatal lupus shares a variety of features with classic SCLE; therefore, some clinicians
consider the cutaneous manifestations of this entity a subtype of SCLE. Similarities with classic SCLE include
clinical features (arcuate erythematous plaques that resolve without scarring (picture 6)), histologic findings
(interface dermatitis), and an association with anti-Ro/SSA antibodies. (See 'Neonatal lupus' below and
"Neonatal lupus: Epidemiology, pathogenesis, clinical manifestations, and diagnosis".)
Chronic cutaneous lupus erythematosus — CCLE includes:
● Discoid lupus erythematosus (DLE)
● Lupus erythematosus tumidus (LE tumidus)
● Lupus profundus (lupus panniculitis)
● Chilblain lupus erythematosus (chilblain LE)
● Lichenoid cutaneous lupus erythematosus-lichen planus overlap syndrome (LE-LP overlap syndrome)
The most common type of CCLE is DLE, accounting for 73 to 85 percent of CCLE [7,39].
Discoid lupus erythematosus — It is estimated that 15 to 30 percent of patients with SLE develop DLE
[1,40,41]. Patients with localized or generalized DLE are estimated to have cross-sectional prevalences of
concurrent SLE between 5 and 28 percent. (See 'Association with SLE' above.)
The presence of DLE lesions among patients with SLE may modify the risk of specific SLE features. Compared
with SLE patients without DLE, those with DLE have increased risk for photosensitivity and leukopenia but
decreased risk for serositis and arthritis. There is no obvious change in risk of nephritis despite variable reports
of a "renal-protective effect" of the presence of discoid lesions among SLE patients [42,43].
Data on the risk for progression of DLE to SLE are limited to retrospective cohort studies, studies lacking power
to detect statistical significance of potential markers of progression, and studies that do not address DLE
specifically as a CLE subset. In these studies, progression to SLE has occurred in 0 to 28 percent of patients
initially presenting with DLE [7,13,41,44]. Progression to SLE often is delayed; in a Swedish-based population
cohort study, 10 percent of patients with DLE who subsequently developed SLE did so within the first year and
17 percent developed SLE within the first three years [8]. Two retrospective studies have suggested SLE
develops within five years in 50 percent of the DLE patients who indeed go on to develop SLE [10]. Risk factors
for progression include an increasing number of clinical and serologic features of SLE: more widespread DLE
lesions, arthralgias and arthritis, high antinuclear antibody (ANA) titers, leukopenia, and high erythrocyte
sedimentation rates [10,45,46].
It is worth noting that patients with DLE and other mucocutaneous manifestations of LE may meet ACR
classification criteria for SLE without having other end-organ disease [47]. Revised classification criteria (the
SLICC criteria) have been proposed to address some limitations of the ACR criteria. (See "Clinical
manifestations and diagnosis of systemic lupus erythematosus in adults", section on 'Classification criteria'.)
● Clinical manifestations – The classic findings of DLE are discrete, erythematous, somewhat indurated
plaques covered by a well-formed adherent scale that extends into dilated hair follicles (follicular plugging).
The plaques tend to expand slowly with active inflammation at the periphery and then heal, leaving
depressed central scars, atrophy, telangiectasias, and hyperpigmentation and/or hypopigmentation [45].
DLE most often involves the face, neck, and scalp but may also occur on the ears (particularly conchal
bowls) and, less frequently, on the upper torso (picture 7A-D). Localized DLE is limited to sites above the
neck. Generalized DLE refers to DLE occurring both above and below the neck.
Hypertrophic DLE is an uncommon clinical variant of DLE characterized by the development of

hyperkeratotic, verrucous plaques [48].
● Histopathology – Pathologic examination of DLE typically reveals hyperkeratosis, follicular plugging, basal
layer vacuolar changes, and a mononuclear cell infiltrate (predominantly T cells) near the dermal-epidermal
junction, dermal blood vessels, and appendages (picture 8) [31]. The basement membrane is usually
thickened, a change that is best appreciated with a periodic acid-Schiff (PAS) stain, and there is dermal
mucinosis. Although immunofluorescence microscopy may be positive in cutaneous LE, its use is limited by
false-positive results on sun-exposed skin and by negative results in longstanding chronic LE lesions. (See
'Direct immunofluorescence (lupus band test)' below.)
● Differential diagnosis – The cutaneous differential diagnosis of DLE includes:
• Tinea faciei
• Granuloma faciale (picture 9A-B)
• Sarcoidosis
• Lupus vulgaris (cutaneous tuberculosis)
• Lymphoproliferative disorders of skin (benign or malignant)
• Cutaneous leishmaniasis (eg, lupoid leishmaniasis, leishmaniasis recidivans)
• Tuberculoid leprosy
Verrucous/hypertrophic discoid lupus may be confused with hypertrophic lichen planus, keratoacanthoma,
squamous cell cancer, and prurigo nodularis. (See 'Diagnosis' below.)
● Risk for squamous cell carcinoma – Infrequently, squamous cell carcinoma develops in sites of DLE.
Squamous cell carcinoma in DLE is estimated to occur in 2 to 3 percent of DLE patients, is postulated to be
related to the presence of chronic inflammation, and is associated with increased risk for a poor prognosis
for squamous cell carcinoma [49].
Less common subtypes — LE tumidus, lupus profundus (lupus panniculitis), chilblain LE, and lupus
erythematosus-lichen planus (LE-LP) overlap syndrome are additional manifestations of CCLE.
Lupus erythematosus tumidus — Although often categorized as a form of LE-specific skin disease, the
rarity of association with concurrent SLE and the lack of interface dermatitis on pathology have raised debate
about where LE tumidus falls in the classification of cutaneous lupus disorders. In a series of 40 patients with LE
tumidus, only 10 percent were ANA-positive [50]. An increased incidence among smokers has been noted [51].
● Clinical manifestations – LE tumidus is characterized by photodistributed, chronic, pink to violaceous,

urticarial or edematous plaques or nodules [50,52,53]. Annular plaques may occur (picture 10A-B). Scale
and scarring are absent.
● Histopathology – There is a moderate to dense, superficial and deep, perivascular lymphocytic infiltrate,
consisting of predominately CD3+/CD4+ lymphocytes. In addition, there is mucin deposition in the papillary
and reticular dermis. Interface changes at the dermal-epidermal junction are absent in most cases. A
minority of patients exhibit focal interface changes [52].
● Differential diagnosis – The differential diagnosis of LE tumidus includes causes of erythematous to

violaceous plaques with absent surface change, such as benign lymphocytic infiltration of skin (Jessner's
disease), polymorphous light eruption, pseudolymphoma, B cell lymphoma, plaque mucinosis, and solar
urticaria. (See 'Diagnosis' below.)
Lupus profundus (lupus panniculitis) — Lupus profundus (also known as lupus panniculitis) is an
uncommon form of CCLE. Coexistent DLE occurs in at least one-third of patients with lupus profundus; SLE is
present in approximately 10 percent of patients [11,54].
● Clinical manifestations – Lupus profundus presents as indurated plaques or nodules with or without
overlying cutaneous changes [55]. The plaques or nodules may appear on the scalp, face, upper arms,
chest (particularly breasts), lower back, flank, upper thighs, or buttocks and are often tender or painful.
Infrequently, patients develop ulceration or calcifications at sites of involvement. Upon resolution, lupus
profundus may leave depressed areas of lipoatrophy (picture 11).
● Histopathology – Histopathologic examination reveals perivascular infiltrates of mononuclear cells plus

panniculitis, manifested as hyaline fat necrosis with mononuclear cell infiltration and lymphocytic vasculitis
(picture 12A-B). The presence of immune deposits in the dermal-epidermal junction on direct
immunofluorescence offers support for the diagnosis [56]. (See 'Diagnosis' below.)
● Differential diagnosis – Nodules of lupus profundus on the breast may raise concern for a breast
malignancy. The possibility of subcutaneous panniculitis-like T cell lymphoma, which often manifests with
subcutaneous nodules or plaques on the trunk or extremities, also should be considered [57]. A biopsy will
distinguish lupus profundus from these entities. (See 'Diagnosis' below.)
Chilblain lupus erythematosus — Chilblain LE is diagnosed in patients with clinical findings of pernio
(also known as chilblains) in conjunction with clinical or laboratory features of cutaneous or systemic LE.
Approximately 25 percent of patients who present with pernio meet classification criteria for SLE, and additional
patients (5 to 6 percent in one study) may fulfill SLE criteria subsequently [58]. (See "Pernio (chilblains)".)
Similar to idiopathic pernio, chilblain LE presents with tender, bright red to reddish-blue papules, nodules, or
plaques on the toes, fingers, nose, or ears precipitated by cold exposure (picture 13) [59]. Nodules on acral
areas may ulcerate. Chilblain LE is reviewed separately. (See "Pernio (chilblains)", section on 'Chilblain lupus
erythematosus'.)
Chilblain LE is distinct from lupus pernio, a subtype of sarcoidosis. (See "Cutaneous manifestations of
sarcoidosis", section on 'Lupus pernio'.)
Lupus erythematosus-lichen planus overlap syndrome — LE-LP overlap syndrome is a rare, chronic
disorder that has clinical, histopathologic, and immunofluorescence findings of both LE and lichen planus
[60,61].
● Clinical manifestations – The cutaneous findings of LE-LP overlap syndrome are usually persistent
atrophic blue-red to violaceous plaques or patches. The most common sites for involvement are the acral
portions of the extremities, particularly the palms and soles. The nails are commonly involved, and there
may be anonychia (absence of the nail). Photosensitivity and pruritus are generally absent.
● Histopathology – Histopathologic examination may reveal features of lichen planus (hyperkeratosis,

hypergranulosis, irregular acanthosis, pigment incontinence) and LE. Similarly, direct immunofluorescence
(DIF) microscopy may reveal features of lichen planus (cytoid bodies staining for IgM and fibrin in a fibrillar
pattern) and LE (immunoglobulin and complement deposition in a linear granular pattern along the dermal-
epidermal junction) [62]. (See "Lichen planus".)
Diagnosis — In general, cutaneous LE is largely a clinical diagnosis supported by contextual clinical features
(such as the presence of known underlying SLE). Confirmatory histopathologic examination is indicated when
diagnostic uncertainty remains (eg, atypical clinical presentation or clinical features that overlap with other
cutaneous diseases). For example, localized ACLE often can be diagnosed by recognition of erythema in the
classic malar distribution in a patient with known SLE, and clinical recognition of an eruption with the classic
morphology and distribution of DLE is acceptable for the diagnosis of DLE. In contrast, the skin lesions of lupus
profundus are often biopsied because of the nonspecific appearance of cutaneous nodules, and tumid lupus
erythematosus is often biopsied because of the nonspecific clinical features and absence of an association with
SLE. The overlap in the appearance of SCLE with other papulosquamous or annular skin disorders often
warrants a biopsy; however, in a patient who also exhibits photosensitivity and positive SSA/Ro antibodies,
diagnosis without a biopsy is reasonable.
Performance of direct immunofluorescence is of variable utility if the diagnosis remains uncertain after clinical
and histologic evaluation. (See 'Direct immunofluorescence (lupus band test)' below.)
Other than the strong association between Ro/SSA antibodies for SCLE, there are no antibodies that are
routinely predictive of variants of CLE. (See 'Subacute cutaneous lupus erythematosus' above.)
Given the association of cutaneous LE with SLE, patients with cutaneous LE should be evaluated for SLE.
While no clear guidelines exist for SLE screening or monitoring of the patient first presenting with cutaneous LE,
obtaining a clinical history with a particular focus on a rheumatologic review of systems is recommended. A
physical examination and select laboratory studies also should be performed. The evaluation for SLE is
reviewed in detail separately. (See "Clinical manifestations and diagnosis of systemic lupus erythematosus in
adults" and "Childhood-onset systemic lupus erythematosus (SLE): Clinical manifestations and diagnosis".)
If systemic features of SLE or laboratory abnormalities are present, referral to a rheumatologist is appropriate
for further evaluation and comanagement.
Direct immunofluorescence (lupus band test) — Direct immunofluorescence (DIF) evaluation of lesional
or nonlesional skin for deposition of a continuous band of immunoreactants along the dermal-epidermal junction
as part of the evaluation for cutaneous lupus or SLE is historically referred to as the "lupus band test." Use of
the terms "lesional lupus band test" and "nonlesional lupus band test" can help to clarify the source of the tissue
used for the test. Overall, DIF is of unclear value for the diagnosis of cutaneous LE. Therefore, we do not
routinely perform DIF.
Occasionally, demonstration of a continuous band of immunoreactants at the dermal-epidermal junction in tissue

taken from a site of cutaneous LE (ie, lesional lupus band test) is used to support a diagnosis of cutaneous LE
when histologic findings are nondiagnostic (picture 14) [63,64]. Although these findings are detected in lesional
skin from most patients with ACLE, the finding is not pathognomonic [65,66]. In particular, biopsies from sun-
exposed skin from individuals without cutaneous LE or SLE have demonstrated similar features, as shown in a
prospective study of 50 healthy young adults that found deposition of immunoglobulins at the dermal-epidermal
junction in 10 of 50 biopsy specimens (20 percent) taken from sun-exposed skin [66]. A subsequent study that
did not find immunoreactant deposition in sun-exposed skin from 41 healthy adults may have yielded different
results because of differences in protocol or other factors [67].
Management — The approach to the treatment of LE-specific skin disease is influenced by the subtype of
disease and the presence of underlying SLE. In all cases, photoprotection and use of appropriate broad-
spectrum sunscreens are recommended, given the known photoexacerbation of cutaneous LE. (See "Selection
of sunscreen and sun-protective measures" and "Initial management of discoid lupus and subacute cutaneous
lupus", section on 'Photoprotection'.)
Topical and intralesional corticosteroids, oral glucocorticoids, oral antimalarial drugs, and glucocorticoid-sparing
immunomodulatory agents have all been utilized depending on extent of disease and response to first- and
second-line therapies. The general approach to management of cutaneous LE is as follows:
First-line therapy typically involves:
● Photoprotection.
● Use of topical or intralesional corticosteroids, topical calcineurin inhibitors, and/or systemic glucocorticoids
depending on the extent of involvement and subset of disease.
● Systemic antimalarial agents (treatment with either hydroxychloroquine or chloroquine, or with the addition
of quinacrine to either of these agents) [68].
Second-line therapy typically involves glucocorticoid-sparing and immunomodulatory therapy and should take
into account underlying SLE end-organ manifestations, if present:
● Methotrexate (oral or subcutaneous): additional benefits may include treatment of SLE with inflammatory
arthritis component.
● Mycophenolate mofetil: may be of dual-benefit to patients with underlying lupus nephritis.
Other second- or third-line agents may include:
● Thalidomide, lenalidomide, systemic retinoids, oral dapsone, belimumab, or azathioprine.
Case reports exist for the use of ustekinumab [69-71], apremilast [72], clofazimine, intravenous immunoglobulin
(IVIG), cyclophosphamide, and other interventions. In addition, the findings of a prospective uncontrolled study
and retrospective study suggest that rituximab may be useful for some patients with refractory cutaneous LE
[73,74].
The treatment of DLE and SCLE is discussed in detail separately. (See "Initial management of discoid lupus and
subacute cutaneous lupus", section on 'Photoprotection' and "Management of refractory discoid lupus and
subacute cutaneous lupus".)
LUPUS NONSPECIFIC SKIN DISEASE
Cutaneous disorders that occur with increased frequency among patients with systemic lupus erythematosus
(SLE), but are not specific to SLE and lack histopathologic features of cutaneous LE comprise LE-nonspecific
skin disease (table 4). Of note, many of these lupus nonspecific skin diseases are reported to occur with flares
of underlying SLE.
Vascular abnormalities — Examples of cutaneous manifestations of vascular involvement in SLE include

periungual erythema, livedo reticularis, telangiectasia, Raynaud phenomenon, and vasculitis. Cutaneous
vascular abnormalities occur in approximately 50 percent of patients with SLE [75].
● Periungual erythema – Periungual erythema is due to dilated tortuous loops of capillaries and a prominent
subcapillary venous plexus along the base of the nail. Similar findings have been noted along the edges of
the upper eyelid.
● Livedo reticularis – Livedo reticularis refers to a reddish-cyanotic, reticular pattern on the skin of the arms,
legs, and torso, particularly with cold exposure (picture 15A-B). In SLE, livedo reticularis is induced by
vasospasm of the dermal ascending arterioles [76]. Vasospasm in these cutaneous vessels results in
decreased blood supply to the superficial horizontal vascular plexus, with a secondary increase in
circulation to the remaining patent vessels. Pathologic examination of involved blood vessels reveals
thickening of the walls of the dermal vessels with subsequent narrowing of the lumens and, in some cases,
intravascular thrombi.
● Raynaud phenomenon – Raynaud phenomenon in SLE is a vasospastic process that occurs in

approximately 15 to 30 percent of patients [77]. It is characterized by blanching of the nail beds, fingers,
and toes (and occasionally ears, nose, tongue, and nipples) with accompanying pain. Involvement of the
thumb or severe disease that leads to distal digital ulceration should raise suspicion for features of overlap
with systemic sclerosis. (See "Clinical manifestations and diagnosis of Raynaud phenomenon".)
● Vasculitis – Vasculitis develops in approximately 11 to 20 percent of patients with SLE [75,76,78]. The
most common form, occurring in 10 to 15 percent of cases, is urticarial vasculitis. In contrast to urticaria,
lesions of urticarial vasculitis may persist for more than 24 hours and frequently evolve into painful
petechiae or purpura that may heal with hyperpigmentation. (See "Urticarial vasculitis".)
Vasculitis may also affect small arteries, possibly resulting in microinfarcts of the tips of the fingers, the
toes, the cuticles of the nail folds (splinter hemorrhages), and the extensor surface of the forearm and shin
(picture 16). The palms of the hand, soles of the feet, and area around the ankle are less commonly
involved [79]. Ankle involvement may develop into painful punched-out ulcers and may heal slowly.
Periarteritis nodosa-like lesions may occur.
Nonscarring alopecia — Nonscarring (reversible) hair loss in patients with SLE may reflect telogen effluvium or
"lupus hair." Nonscarring hair loss usually responds well to treatment of SLE.
Telogen effluvium is characterized by a shift in follicular cycling that leads to premature shedding of hair. Telogen
effluvium can occur in the setting of serious illness or other significant physiologic stressors. (See "Telogen
effluvium".)
"Lupus hair" is generally seen during exacerbations of SLE. It is characterized by thin, unruly hair that easily
fractures [80]. Lupus hair usually occurs along the frontal hairline.
Other — Nail abnormalities, particularly pitting, ridging, and onycholysis, have been noted in 25 percent of
patients with SLE [81]. Approximately 20 percent of patients have redness of the lunula, a finding nearly always
associated with periungual erythema [82].
Papulonodular mucinosis is another LE-nonspecific skin disorder. This disorder typically presents as
asymptomatic, skin-colored papules or nodules on the trunk or proximal extremities and abundant mucin in the
papillary dermis and mid-dermis [83].
Multiple disseminated eruptive dermatofibromas have been reported in SLE, especially in immunosuppressed
patients [84].
Additional disorders included among LE-nonspecific skin disorders include [1]:
● Sclerodactyly
● Rheumatoid nodules
● Calcinosis cutis
● Nonspecific bullous eruptions (resulting from damage to the basal layer of the epidermis)
● Urticaria
● Cutis laxa/anetoderma
● Acanthosis nigricans
● Erythema multiforme
● Leg ulcers
● Palisaded neutrophilic and granulomatous dermatitis
OTHER MANIFESTATIONS OF LUPUS
Mucosal manifestations — Mucous membrane involvement can occur in the setting of cutaneous LE or
systemic lupus erythematosus (SLE). Mucosal involvement occurs in 12 to 45 percent of patients with SLE [85-
87].
Oral involvement may manifest as white plaques, areas of erythema, or punched-out erosions or ulcers with
surrounding erythema on the soft or hard palate or buccal mucosa (picture 17). The oral ulcers are usually
painless. Oral ulcers may be the first sign of SLE. There is no apparent association between the presence of
oral ulcers and systemic activity.
The oral manifestations of LE may demonstrate the typical histopathology of discoid lupus erythematosus
(DLE), including hyperkeratosis, atrophy of rete processes, and superficial and deep inflammatory infiltrates;
edema in the lamina propria, continuous or patchy periodic acid-Schiff (PAS)-positive deposits in the basement
membrane zone, deposition of intercellular mucin, and deposits of immunoglobulin and complement at the
dermal-epidermal junction are also seen [87,88]. Oral LE should be distinguished from lichen planus,
candidiasis, aphthous stomatitis, intraoral herpes, Behçet syndrome, bite marks, leukoplakia, and malignancy.
Nasal ulcers occur in some patients with SLE [89]. They are usually in the lower nasal septum and tend to be
bilateral. The appearance of nasal ulcers tends to parallel other features of active SLE. Nasal perforation,
possibly secondary to vasculitis, is infrequent, occurring in 4.6 percent of 885 patients with SLE who were
prospectively followed [90]. Involvement of the mucosa of the upper airway may also occur and may cause
hoarseness [79].
Oral mucous membrane lesions may respond to topical corticosteroids, tacrolimus 0.1% ointment, intralesional
corticosteroids, and systemic antimalarial drugs. The response to topical corticosteroids (usually Orabase mixed
with either triamcinolone 0.1% or clobetasol 0.05%) takes a few days to weeks, while the response to
hydroxychloroquine takes weeks to months. If the oral LE is refractory to these interventions and is causing
significant symptoms, more aggressive systemic therapies used for cutaneous LE may be tried. (See
"Management of refractory discoid lupus and subacute cutaneous lupus".)
Bullous cutaneous lupus erythematosus — Bullous cutaneous lupus erythematosus (bullous CLE) is a rare
and distinct complication of SLE characterized by the development of autoantibodies against type VII collagen
and subepidermal blistering [91,92]. Affected patients develop a vesicular or bullous eruption that may affect any
body site, including oral mucosa (picture 18A). There is a predilection for the upper trunk, upper extremities, and
neck. Bullae may arise on normal or erythematous skin. Pruritus is usually absent. Dyspigmentation may occur
in sites of resolved bullae. Scarring usually does not occur.
Typical biopsy findings in bullous CLE include subepidermal blistering and a neutrophil-predominant infiltrate in
the upper dermis and dermal edema (picture 18A-B). Vasculitis may be present. Direct immunofluorescence
studies demonstrate deposition of immunoglobulin (Ig)G, IgA, IgM, and/or complement at the basement
membrane zone [91].
Oral dapsone is the mainstay of treatment. Responses to dapsone are often rapid.
Neonatal lupus — Neonatal lupus is a rare syndrome that is associated with maternal antibodies to Ro/SSA, to
La/SSB, and, much less frequently, to U1RNP. Infants develop eruptions characterized by erythematous arcuate
patches or plaques with raised active margins shortly after birth (picture 6). Congenital heart block is the most
concerning complication of neonatal lupus. Following the birth of an infant with neonatal lupus, the risk for
congenital heart block is increased with subsequent pregnancies [93]. Of note, treatment with
hydroxychloroquine may decrease the risk of neonatal lupus (congenital heart block) in at-risk pregnancies [94].
Neonatal lupus erythematosus is reviewed separately. (See "Neonatal lupus: Epidemiology, pathogenesis,
clinical manifestations, and diagnosis".)
SOCIETY GUIDELINE LINKS
Links to society and government-sponsored guidelines from selected countries and regions around the world
are provided separately. (See "Society guideline links: Cutaneous lupus erythematosus".)
INFORMATION FOR PATIENTS
UpToDate offers two types of patient education materials, "The Basics" and "Beyond the Basics." The Basics
patient education pieces are written in plain language, at the 5th to 6th grade reading level, and they answer the
four or five key questions a patient might have about a given condition. These articles are best for patients who
want a general overview and who prefer short, easy-to-read materials. Beyond the Basics patient education
pieces are longer, more sophisticated, and more detailed. These articles are written at the 10th to 12th grade
reading level and are best for patients who want in-depth information and are comfortable with some medical
jargon.
Here are the patient education articles that are relevant to this topic. We encourage you to print or e-mail these
topics to your patients. (You can also locate patient education articles on a variety of subjects by searching on
"patient info" and the keyword(s) of interest.)
● Basics topic (see "Patient education: Discoid lupus (The Basics)")
SUMMARY AND RECOMMENDATIONS
● Cutaneous lupus erythematosus (cutaneous LE) may occur as an independent disorder or in association
with systemic lupus erythematosus (SLE). Cutaneous LE includes three subsets of LE-specific skin
disease: acute cutaneous lupus erythematosus (ACLE), subacute cutaneous lupus erythematosus (SCLE),
and chronic cutaneous lupus erythematosus (CCLE). A variety of non-LE cutaneous disorders may also
occur in patients with SLE (LE-nonspecific skin diseases). (See 'Classification' above.)
● The subtypes of LE-specific skin disease have varying strengths of association with SLE (figure 1).
Whereas ACLE almost always occurs in association with SLE, other types of lupus-specific skin disease
are less strongly associated with SLE. (See 'Association with SLE' above.)
● ACLE may occur as a localized, generalized, or toxic epidermal necrolysis-like eruption. The most common
manifestation is the localized facial eruption (malar rash, butterfly rash), which is characterized by the
development of erythema over the cheeks and bridge of the nose (picture 1A-B). ACLE may last for hours,
days, or weeks and often recurs. (See 'Acute cutaneous lupus erythematosus' above.)
● SCLE may occur as an idiopathic eruption, in association with SLE, or as a drug-induced disorder. SCLE
classically presents as psoriasiform or annular erythematous plaques on the shoulders, forearms, neck, or
upper torso (picture 4A-B). There is a strong association with Ro/SSA autoantibodies. The possibility of
drug-induced SCLE should always be reviewed, particularly when skin involvement is widespread or
severe. (See 'Subacute cutaneous lupus erythematosus' above.)
● Discoid lupus erythematosus (DLE) is the most common form of CCLE. Patients with DLE develop
erythematous, scaly plaques that may exhibit follicular plugging and heal with scarring (picture 7A-D).
Associated hypopigmentation and hyperpigmentation are common. Frequent sites for DLE are the face,
neck, scalp, and ears. Patients with the generalized variant of DLE also have involvement of the trunk or
extremities. A hypertrophic variant of DLE is characterized by hyperkeratotic, verrucous plaques. LE
tumidus, lupus profundus, chilblain LE, and lichenoid cutaneous lupus erythematosus-lichen planus overlap
syndrome are additional subtypes of CCLE. (See 'Chronic cutaneous lupus erythematosus' above.)
● Cutaneous LE is largely a clinical diagnosis supported by contextual clinical features (such as the presence
of known underlying SLE). Confirmatory histopathologic examination is indicated when diagnostic
uncertainty remains. Select patients with known SLE and/or classic clinical features of cutaneous LE may
not require a biopsy. (See 'Diagnosis' above.)
● The approach to the management of cutaneous LE is influenced by the extent of disease, subtype of
cutaneous LE, response to initial therapy, and the presence of underlying SLE. Photoprotection, topical
corticosteroids, topical calcineurin inhibitors, and oral antimalarials are common first-line treatments. (See
'Management' above.)
● LE may affect mucous membranes. Oral involvement may manifest as white plaques, erythema, erosions,
or ulcers. Oral LE should be distinguished from lichen planus, candidiasis, aphthous stomatitis, intraoral
herpes, Behçet syndrome, bite marks, leukoplakia, and malignancy. (See 'Mucosal manifestations' above.)
ACKNOWLEDGMENT
The editorial staff at UpToDate would like to acknowledge Samuel L Moschella, MD, FAAD, FACP, who
contributed to an earlier version of this topic review.
Use of UpToDate is subject to the Subscription and License Agreement.
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histopathological study of oral manifestations and immunohistochemical profile of epithelial maturation. J
Cutan Pathol 2006; 33:657.
88. Pennebaker JB, Gilliam JN, Ziff M. Immunoglobulin classes of DNA binding activity in serum and skin in
systemic lupus erythematosus. J Clin Invest 1977; 60:1331.
89. Rothfield N. Clinical features of systemic lupus erythematosus. In: Textbook of Rheumatology, Kelley WN,
Harris ED, Ruddy S, Sledge CB (Eds), WB Saunders, Philadelphia 1981.
90. Rahman P, Gladman DD, Urowitz MB. Nasal-septal perforation in systemic lupus erythematosus--time for
a closer look. J Rheumatol 1999; 26:1854.
91. Sebaratnam DF, Murrell DF. Bullous systemic lupus erythematosus. Dermatol Clin 2011; 29:649.
92. Contestable JJ, Edhegard KD, Meyerle JH. Bullous systemic lupus erythematosus: a review and update to
diagnosis and treatment. Am J Clin Dermatol 2014; 15:517.
93. Izmirly PM, Llanos C, Lee LA, et al. Cutaneous manifestations of neonatal lupus and risk of subsequent
congenital heart block. Arthritis Rheum 2010; 62:1153.
94. Izmirly PM, Costedoat-Chalumeau N, Pisoni CN, et al. Maternal use of hydroxychloroquine is associated
with a reduced risk of recurrent anti-SSA/Ro-antibody-associated cardiac manifestations of neonatal
lupus. Circulation 2012; 126:76.
Topic 4666 Version 28.0
GRAPHICS
Major categories of cutaneous lupus erythematosus
Acute cutaneous LE (ACLE)

Localized ACLE (malar rash, butterfly rash)
Generalized ACLE
Toxic epidermal necrolysis-like eruption
Subacute cutaneous LE (SCLE)

Annular SCLE
Papulosquamous SCLE
Chronic cutaneous LE (CCLE)

Localized DLE
Generalized DLE
Hypertrophic DLE/verrucous DLE
Mucosal DLE
Lupus panniculitis/lupus profundus
Lupus tumidus/tumid lupus*
Chilblains LE
Other clinical variants of cutaneous LE

Lupus-lichen planus overlap syndrome
Rowell syndrome (cutaneous lupus resembling erythema multiforme)
LE: lupus erythematosus; DLE: discoid lupus erythematosus.

* Some authors consider reticular erythematous mucinosis a form of tumid lupus.
References:
1. Sontheimer RD. The lexicon of cutaneous lupus erythematosus - a review and personal perspective on the nomenclature and
classification of the cutaneous manifestations of lupus erythematosus. Lupus 1997; 6:84.
2. Lee LA, Werth VP. Lupus erythematosus. In: Dermatology, 3rd ed, Bolognia JL, Jorizzo JL, Rapini RP, et al (Eds), Elsevier Limited,
2012. p.615.
Graphic 93804 Version 2.0
Coprevalent systemic lupus erythematosus by cutaneous lupus subtype
Circle size roughly reflects the relative prevalence of the subtypes of cutaneous lupus erythematosus.
SCLE: subacute cutaneous lupus erythematosus; ACLE: acute cutaneous lupus erythematosus; LE: lupus erythematosus; DLE: discoid lupus
erythematosus; SLE: systemic lupus erythematosus.
Data from:
1. Watanabe T, Tsuchida T. Classification of lupus erythematosus based upon cutaneous manifestations. Dermatological, systemic and
laboratory findings in 191 patients. Dermatology 1995; 190:277.
2. Sontheimer RD. Subacute cutaneous lupus erythematosus: 25-year evolution of a prototypic subset (subphenotype) of lupus
erythematosus defined by characteristic cutaneous, pathological, immunological, and genetic findings. Autoimmun Rev 2005; 4:253.
3. Chong BF, Song J, Olsen NJ. Determining risk factors for developing systemic lupus erythematosus in patients with discoid lupus
erythematosus. Br J Dermatol 2012; 166:29.
4. Watanabe T, Tsuchida T. Lupus erythematosus profundus: a cutaneous marker for a distinct clinical subset? Br J Dermatol 1996;
134:123.
5. Maize JC Jr, Costner M. Tumid lupus erythematosus: a form of lupus erythematosus. Arch Dermatol 2010; 146:451.
Adapted from: Grönhagen CM, Nyberg F. Cutaneous lupus erythematosus: An update. Indian Dermatol Online J 2014; 5:7.
Acute cutaneous lupus erythematosus
Malar erythema and subtle edema are present in this patient with systemic lupus
erythematosus.
Reproduced with permission from: www.visualdx.com. Copyright VisualDx. All rights reserved.
Acute cutaneous lupus erythematosus
An erythematous, edematous eruption is present on the malar area. Note the sparing of
the nasolabial folds.
Rosacea
Centrofacial redness with telangiectasias in rosacea.
Reproduced with permission from: www.visualdx.com. Copyright VisualDx. All rights

reserved.
Heliotrope eruption in dermatomyositis
Violaceous erythema on the upper lids in a patient with dermatomyositis. Mid-facial erythema that
does not spare the nasolabial folds is also present.
Courtesy of Jeffrey Callen, MD, FACP, FAAD.
Classification criteria for systemic lupus erythematosus
ACR criteria [1,2] SLICC criteria [3]
(4 of 11 criteria)* (4 of 17 criteria, including at least 1 clinical criterion and 1

immunologic criterion; ¶ OR biopsy-proven lupus nephritis Δ)
Criterion Definition Criterion Definition
Clinical criteria
Malar rash Fixed erythema, flat or raised, over the Acute cutaneous Lupus malar rash (do not count if malar
malar eminences, tending to spare the lupus discoid); bullous lupus; toxic epidermal
nasolabial folds necrolysis variant of SLE; maculopapular
lupus rash; photosensitive lupus rash (in the
absence of dermatomyositis); OR subacute
Photosensitivity Skin rash as a result of unusual reaction to cutaneous lupus (nonindurated psoriaform
sunlight, by patient history or clinician and/or annular polycyclic lesions that
observation resolve without scarring, although
occasionally with postinflammatory
dyspigmentation or telangiectasias)
Discoid rash Erythematosus raised patches with adherent Chronic cutaneous Classic discoid rash; localized (above the
keratotic scaling and follicular plugging; lupus neck); generalized (above and below the
atrophic scarring may occur in older lesions neck); hypertrophic (verrucous) lupus;
lupus panniculitis (profundus); mucosal
lupus; lupus erythematosus tumidus;
chilblains lupus; OR discoid lupus/lichen
planus overlap
Nonscarring Diffuse thinning or hair fragility with visible

alopecia broken hairs (in the absence of other
causes, such as alopecia areata, drugs, iron
deficiency, and androgenic alopecia)
Oral ulcers Oral or nasopharyngeal ulceration, usually Oral or nasal Palate, buccal, tongue, OR nasal ulcers (in
painless, observed by a clinician ulcers the absence of other causes, such as
vasculitis, Behçet syndrome, infection
[herpesvirus], inflammatory bowel disease,
reactive arthritis, and acidic foods)
Arthritis Nonerosive arthritis involving 2 or more Joint disease Synovitis involving 2 or more joints,
peripheral joints, characterized by characterized by swelling or effusion OR
tenderness, swelling, or effusion
Tenderness in 2 or more joints and at least
30 minutes of morning stiffness
Serositis Pleuritis – Convincing history of pleuritic Serositis Typical pleurisy for more than 1 day, pleural
pain or rubbing heard by a clinician or effusions, or pleural rub, OR
evidence of pleural effusion OR
Pericarditis – Documented by ECG, rub, or Typical pericardial pain (pain with

evidence of pericardial effusion recumbency improved by sitting forward) for
more than 1 day, pericardial effusion,
pericardial rub, or pericarditis by
electrocardiography in the absence of other
causes, such as infection, uremia, and
Dressler syndrome
Renal disorder Persistent proteinuria greater than 500 Renal Urine protein-to-creatinine ratio (or 24-hour
mg/24 hours or greater than 3+ if urine protein) representing 500 mg
quantitation not performed OR protein/24 hours, OR
Cellular casts – May be red cell, hemoglobin, Red blood cell casts
granular, tubular, or mixed
Neurologic Seizures OR psychosis – In the absence of Neurologic Seizures; psychosis; mononeuritis multiplex
disorder offending drugs or known metabolic (in the absence of other known causes, such
derangements (uremia, ketoacidosis, or as primary vasculitis); myelitis; peripheral
electrolyte imbalance) or cranial neuropathy (in the absence of
other known causes, such as primary
vasculitis, infection, and diabetes mellitus);
OR acute confusional state (in the absence
of other causes, including toxic/metabolic,
uremia, drugs)
Hematologic Hemolytic anemia – With reticulocytosis OR Hemolytic anemia Hemolytic anemia

disorder 3
Leukopenia – Less than 4000/mm total Leukopenia or Leukopenia (<4000/mm 3 at least once) (in
on 2 or more occasions OR lymphopenia the absence of other known causes, such as
3
Lymphopenia – Less than 1500/mm 3 on 2 Felty syndrome, drugs, and portal
or more occasions OR hypertension), OR
Thrombocytopenia – Less than Lymphopenia (<1000/mm 3 at least once)
100,000/mm 3 (in the absence of offending (in the absence of other known causes, such
drugs) as glucocorticoids, drugs, and infection)
Thrombocytopenia Thrombocytopenia (<100,000/mm 3) at

least once in the absence of other known
causes, such as drugs, portal hypertension,
and thrombotic thrombocytopenic purpura
Immunologic criteria
ANA An abnormal titer of ANA by ANA ANA level above laboratory reference range
immunofluorescence or an equivalent assay
at any point in time and in the absence of
drugs known to be associated with "drug-
induced lupus" syndrome
Immunologic Anti-DNA – Antibody to native DNA in Anti-dsDNA Anti-dsDNA antibody level above laboratory
disorders abnormal titer OR reference range (or >2-fold the reference
Anti-Sm – Presence of antibody to Sm range if tested by ELISA)
nuclear antigen OR
Positive antiphospholipid antibody on: Anti-Sm Presence of antibody to Sm nuclear antigen
1. An abnormal serum level of IgG or IgM

Antiphospholipid Antiphospholipid antibody positivity as
anticardiolipin antibodies OR
determined by any of the following: Positive
2. A positive test result for lupus test result for lupus anticoagulant; false-
anticoagulant using a standard positive test result for rapid plasma reagin;
method OR medium- or high-titer anticardiolipin
3. A false-positive serologic test for antibody level (IgA, IgG, or IgM); or positive
syphilis known to be positive for at test result for anti-beta 2-glycoprotein I
least 6 months and confirmed by (IgA, IgG, or IgM)
Treponema pallidum immobilization or
fluorescent treponemal antibody
absorption test
Low complement Low C3; low C4; OR low CH50
Direct Coombs Direct Coombs test in the absence of

test hemolytic anemia
ACR: American College of Rheumatology; SLICC: Systemic Lupus International Collaborating Clinics; SLE: systemic lupus erythematosus;
ECG: electrocardiogram; ANA: antinuclear antibodies; Anti-Sm: anti-Smith antibody; IgG: immunoglobulin G; IgM: immunoglobulin M;
Anti-dsDNA: anti-double-stranded DNA; ELISA: enzyme-linked immunosorbent assay; IgA: immunoglobulin A.
* For the ACR criteria, no distinction is made between clinical and immunologic criteria in determining whether the required number has
been met. The classification is based upon 11 criteria. For the purpose of identifying patients in clinical studies, a person is said to have SLE
if any 4 or more of the 11 criteria are present, serially or simultaneously, during any interval of observation.
¶ For the SLICC criteria, criteria are cumulative and need not be presently concurrently. A patient is classified as having SLE if he or she
satisfies 4 of the clinical and immunologic criteria used in the SLICC classification criteria, including at least 1 clinical criterion and 1
immunologic criterion.
Δ Alternatively, according to the SLICC criteria, a patient is classified as having SLE if he or she has biopsy-proven nephritis compatible with
SLE in the presence of ANAs or anti-dsDNA antibodies.
References:
1. Tan EM, Cohen AS, Fries JF, et al. The 1982 revised criteria for the classification of systemic lupus erythematosus. Arthritis Rheum
1982; 25:1271.
2. Hochberg MC. Updating the American College of Rheumatology revised criteria for the classification of systemic lupus erythematosus
(letter). Arthritis Rheum 1997; 40:1725.
3. Petri M, Orbai AM, Alarcón GS, et al. Derivation and validation of the Systemic Lupus International Collaborating Clinics classification
criteria for systemic lupus erythematosus. Arthritis Rheum 2012; 64:2677.
Subacute cutaneous lupus erythematosus
Erythematous, annular plaques with scale.

reserved.
Multiple erythematous, scaly papules are present on the upper back.

reserved.
Light micrograph demonstrating a vasculopathic interface dermatitis without

conspicuous follicular plugging. The infiltrate is largely confined to the superficial
half of the dermis.
Courtesy of Cynthia Magro, MD.
Light micrograph of skin biopsy demonstrating prominent suprabasilar

lymphocytosis accompanied by suprabasilar dyskeratosis in a patient with
subacute lupus erythematosus. These findings reflect antibody-dependent cell-
mediated injury of suprabasilar keratinocytes which manifest enhanced Ro
antigen expression due to UV exposure.
UV: ultraviolet.
Drugs implicated in the development of subacute cutaneous lupus
ACE inhibitors (captopril, cilazapril)
Antiarrhythmics (procainamide)
Anticonvulsants (phenytoin, lamotrigine)
Antifungals (griseofulvin, terbinafine)
Antihistamines (cinnarizine/thiethylperazine)
Antineoplastics (docetaxel, paclitaxel, anastrozole, gemcitabine, doxorubicin, tamoxifen, leuprorelin)
Beta blockers (acebutolol, oxprenolol)
Calcium channel blockers (diltiazem, nifedipine, nitrendipine, verapamil)
Diuretics (hydrochlorothiazide, spironolactone)
Immune modulators (leflunomide, interferon-alpha, interferon-beta)
Lipid-lowering agents (pravastatin, simvastatin)
NSAIDs (naproxen, piroxicam)
Proton pump inhibitors (omeprazole, lansoprazole, pantoprazole)
Sulfonylureas (glyburide)
TNF-alpha inhibitors (etanercept, infliximab, adalimumab, golimumab)
Others (D-penicillamine, bupropion, ticlopidine, ranitidine)
ACE: angiotensin-converting enzyme; NSAIDs: nonsteroidal anti-inflammatory drugs; TNF: tumor necrosis factor.
Data from:
1. Sontheimer RD, Henderson CL, Grau RH. Drug-induced subacute cutaneous lupus erythematosus: a paradigm for bedside-to-bench
patient-oriented translational clinical investigation. Arch Dermatol Res 2009; 301:65.
2. Vedove CD, Del Giglio M, Schena D, Girolomoni G. Drug-induced lupus erythematosus. Arch Dermatol Res 2009; 301:99.
3. Sheth N, Greenblatt D, Patel S, Acland K. Adalimumab-induced cutaneous lupus. Clin Exp Dermatol 2007; 32:593.
4. Adachi A, Horikawa T. Paclitaxel-induced cutaneous lupus erythematosus in patients with serum anti-SSA/Ro antibody. J Dermatol
2007; 34:473.
5. Trancart M, Cavailhes A, Balme B, Skowron F. Anastrozole-induced subacute cutaneous lupus erythematosus. Br J Dermatol 2008;
158:628.
6. Wiechert A, Tuting T, Bieber T, et al. Subacute cutaneous lupus erythematosus in a leuprorelin-treated patient with prostate
carcinoma. Br J Dermatol 2008; 159:231.
7. Funke AA, Kulp-Shorten CL, Callen JP. Subacute cutaneous lupus erythematosus exacerbated or induced by chemotherapy. Arch
Dermatol 2010; 146:1113.
8. Wiznia LE, Subtil A, Choi JN. Subacute cutaneous lupus erythematosus induced by chemotherapy: gemcitabine as a causative agent.
JAMA Dermatol 2013; 149:1071.
9. Grönhagen CM, Fored CM, Linder M, et al. Subacute cutaneous lupus erythematosus and its association with drugs: a population-
based matched case-control study of 234 patients in Sweden. Br J Dermatol 2012; 167:296.
Neonatal lupus erythematosus
Annular erythematous thin plaques are present on the head.
Discoid lupus erythematosus
A well-defined, erythematous plaque with scale, pigmentary alteration, and

scarring is present on this patient with discoid lupus erythematosus.

reserved.
Well-defined, erythematous plaques with scale are present on the cheek of this
patient with discoid lupus erythematosus.

reserved.
Follicular plugging is evident in this patient with discoid lupus erythematosus

involving the scalp.
Reproduced with permission from: Messenger A. Varieties of scarring alopecia.

Dermatology In Practice 2003; 11:20. Copyright © Hayward Medical
Communications.
Discoid lupus of the scalp
Discoid lupus erythematosus affecting the scalp and face. There are discoid plaques over
eyebrows, forehead, and scalp, with postinflammatory peripheral hyperpigmentation,
central depigmentation, scarring, and alopecia.
Copyright © 2017 American College of Rheumatology. Used with permission.
An attenuated epidermis is surmounted by an orthohyperkeratotic scale with

follicular plugging. An active vasculopathic interface dermatitis is present.
Granuloma faciale
A red-brown plaque is present on the face.

reserved.
Granuloma faciale
Red-brown plaque with prominent follicular orifices on the forehead.
Courtesy of Samuel Moschella, MD.
Lupus tumidus
Erythematous plaque without overlying scale on the face.
Lupus tumidus
Round, erythematous plaques on the upper arm.
Lupus panniculitis (lupus profundus)
Violaceous nodules (chest and abdomen) and lipoatrophy (upper arm) in lupus
panniculitis.
Copyright © Scott Crater, Dermatlas; http://www.dermatlas.org.
Lupus profundus
Biopsy of a patient with lupus profundus showing expansion of the interstices of

the fat lobule with disintegrating leukocytes and fibrin.
Lupus profundus
Histiocytes within the fat lobule contain engulfed nuclear debris producing cells
with a morphology reminiscent of a lupus erythematosus (LE) cell.
Chilblain lupus
Chilblain lupus characterized by reddish-blue nodules (in this case, on the

fingers) occurring in cold weather. The lesions improved after the administration
of nifedipine.
Direct immunofluorescence of skin in lupus erythematosus (lupus band

test)
Granular deposits of immunoglobulin G in the basement membrane zone on direct

immunofluorescence of lesional skin.
Reproduced with permission from: Winfield H, Jaworsky C. Connective tissue diseases. In: Lever's
Histopathology of the Skin, 10th ed, Elenitsas R, Johnson BL JR, Murphy GF, Xu X (Eds), Lippincott Williams
& Wilkins, Philadelphia 2008. Copyright © 2008 Lippincott Williams & Wilkins. www.lww.com.
Examples of cutaneous findings that can occur in SLE*
Cutaneous lupus erythematosus (ie, acute cutaneous lupus erythematosus, subacute cutaneous lupus erythematosus, chronic
cutaneous lupus erythematosus)
Bullous lupus erythematosus
Nonscarring alopecia
Lupus hair
Telogen effluvium
Vascular findings
Vasculitis
Cutaneous small vessel vasculitis (palpable purpura)
Urticarial vasculitis
Polyarteritis nodosa-like cutaneous lesions
Cutaneous findings associated with antiphospholipid antibodies

Livedo reticularis
Leg ulcers
Cutaneous necrosis
Thrombophlebitis
Digital infarcts
Acrocyanosis
Degos disease-like lesions
Livedoid vasculopathy
Periungual telangiectasia
Raynaud’s phenomenon
* Not an exhaustive list. Patients with features that overlap systemic lupus erythematous and another connective tissue disease may exhibit
cutaneous findings consistent with the latter disease (eg, sclerodactyly, rheumatoid nodules, heliotrope eruption). Other infrequent
associations have been reported (eg, erythromelalgia, sweet syndrome, papulonodular mucinosis, porphyria cutanea tarda, anetoderma,
etc).
References:
1. Sontheimer RD. The lexicon of cutaneous lupus erythematosus - a review and personal perspective on the nomenclature and
classification of the cutaneous manifestations of lupus erythematosus. Lupus 1997; 6:84.
2. Lee LA, Werth VP. Lupus erythematosus. In: Dermatology, 3rd ed, Bolognia JL, Jorizzo JL, Rapini RP, et al (Eds), Elsevier Limited,
2012. p.615.
Livedo reticularis
A red-blue, reticulated vascular network is present on the legs.

reserved.
Livedo reticularis
A reticulated vascular network is present on the lower leg.

reserved.
Lupus vasculitis
Palpable purpuric lesions on the shins in a patient with lupus and necrotizing
vasculitis of the skin, kidney, and brain.
Oral ulcers in lupus
Multiple white, hyperkeratotic lesions and erosive lesions are present on the
mucosa of the hard palate.
Bullous lupus
Multiple blisters in a young woman with bullous systemic lupus erythematosus.
Courtesy of Samuel L Moschella, MD.
Bullous systemic lupus erythematosus
Subepidermal blister with a predominantly neutrophilic dermal infiltrate.
Courtesy of Samuel L Moschella, MD.
Contributor Disclosures
Joseph F Merola, MD, MMSc, FAAD, FACR Grant/Research/Clinical Trial Support: Biogen [Cutaneous lupus
erythematosus]; Pfizer; Novartis [Psoriasis, psoriatic arthritis (Tofacitinib, secukinumab)]; Sanofi [Atopic dermatitis
(Dupilumab)]; Incyte; Aclaris Therapeutics [Alopecia]. Consultant/Advisory Boards: Biogen [Cutaneous lupus
erythematosus]; GlaxoSmithKline; Sanofi [Systemic lupus erythematosus]; AbbVie; Eli Lilly and Company; Novartis; Pfizer;
Janssen Pharmaceutica; Celgene; UCB [Psoriasis, psoriatic arthritis (Adalimumab, tofacitinib, secukinumab, ustekinumab,
apremilast, bimekizumab)]; Merck [Atopic dermatitis]; Samumed [Psoriasis]. Patent Holder: AbbVie [Psoriasis (Licensed
outcome measure)]. David S Pisetsky, MD, PhD Consultant/Advisory Boards: Celgene [Lupus (Phase 2 study of cereblon-
modulating agent)]; Lilly [Rheumatoid arthritis (Baricitinib)]; DILIsym [Drug-induced liver injury]; EMD Serono [SLE
(Evobrutinib)]. Jeffrey Callen, MD, FACP, FAAD Equity Ownership/Stock Ownership: Celgene; Pfizer; 3M; Johnson and
Johnson; Merck; Abbott Laboratories; AbbVie; Procter and Gamble; CVS; Walgreens [Various dermatologic conditions
(Thalidomide, apremilast, etanercept, adalimumab, tofacitinib)]. Equity Ownership/Stock Ownership (Spouse): Celgene;
Pfizer; 3M; Johnson and Johnson; Merck; Abbott Laboratories; AbbVie; Procter and Gamble; Amgen; CVS; Walgreens
[Various dermatologic conditions (Thalidomide, apremilast, etanercept, adalimumab, tofacitinib)]. Other Financial Interest:
Principia Biopharma [Safety monitoring board member (Developmental drug to treat pemphigus)]. Abena O Ofori,
MD Nothing to disclose Monica Ramirez Curtis, MD, MPH Nothing to disclose
Contributor disclosures are reviewed for conflicts of interest by the editorial group. When found, these are addressed by
vetting through a multi-level review process, and through requirements for references to be provided to support the content.
Appropriately referenced content is required of all authors and must conform to UpToDate standards of evidence.
Conflict of interest policy

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11/11/2019 Overview of cutaneous lupus erythematosus - UpToDate

Official reprint from UpToDate®

Overview of cutaneous lupus erythematosus

● Acute cutaneous lupus erythematosus (ACLE)

• Localized ACLE (ie, malar rash, butterfly rash)

• Toxic epidermal necrolysis-like ACLE

● Subacute cutaneous lupus erythematosus (SCLE)

• Less common variants: erythrodermic, poikilodermatous, erythema multiforme-like (Rowell syndrome),

● Chronic cutaneous lupus erythematosus (CCLE)

• Discoid lupus erythematosus (DLE)

• Lupus erythematosus tumidus (LE tumidus)

• Lupus profundus (also known as lupus panniculitis)

• Chilblain lupus erythematosus (chilblain LE)

ASSOCIATION WITH SLE

● ACLE – >90 percent [3]

LUPUS ERYTHEMATOSUS-SPECIFIC SKIN DISEASE

Generalized ACLE presents as an erythematous maculopapular (morbilliform) eruption involving primarily

Chronic cutaneous lupus erythematosus — CCLE includes:

● Discoid lupus erythematosus (DLE)

● Lupus erythematosus tumidus (LE tumidus)

● Lupus profundus (lupus panniculitis)

● Chilblain lupus erythematosus (chilblain LE)

Hypertrophic DLE is an uncommon clinical variant of DLE characterized by the development of

● Differential diagnosis – The cutaneous differential diagnosis of DLE includes:

• Granuloma faciale (picture 9A-B)

• Lupus vulgaris (cutaneous tuberculosis)

• Lymphoproliferative disorders of skin (benign or malignant)

• Cutaneous leishmaniasis (eg, lupoid leishmaniasis, leishmaniasis recidivans)

● Clinical manifestations – LE tumidus is characterized by photodistributed, chronic, pink to violaceous,

● Differential diagnosis – The differential diagnosis of LE tumidus includes causes of erythematous to

● Histopathology – Histopathologic examination reveals perivascular infiltrates of mononuclear cells plus

● Histopathology – Histopathologic examination may reveal features of lichen planus (hyperkeratosis,

Occasionally, demonstration of a continuous band of immunoreactants at the dermal-epidermal junction in tissue

First-line therapy typically involves:

● Mycophenolate mofetil: may be of dual-benefit to patients with underlying lupus nephritis.

Other second- or third-line agents may include:

● Thalidomide, lenalidomide, systemic retinoids, oral dapsone, belimumab, or azathioprine.

LUPUS NONSPECIFIC SKIN DISEASE

Vascular abnormalities — Examples of cutaneous manifestations of vascular involvement in SLE include

● Raynaud phenomenon – Raynaud phenomenon in SLE is a vasospastic process that occurs in

Additional disorders included among LE-nonspecific skin disorders include [1]:

● Palisaded neutrophilic and granulomatous dermatitis

OTHER MANIFESTATIONS OF LUPUS

SOCIETY GUIDELINE LINKS

INFORMATION FOR PATIENTS

● Basics topic (see "Patient education: Discoid lupus (The Basics)")

SUMMARY AND RECOMMENDATIONS

Use of UpToDate is subject to the Subscription and License Agreement.

3. Watanabe T, Tsuchida T. Classification of lupus erythematosus based upon cutaneous manifestations.

5. Vera-Recabarren MA, García-Carrasco M, Ramos-Casals M, Herrero C. Comparative analysis of

18. Paradela S, Martínez-Gómez W, Fernández-Jorge B, et al. Toxic epidermal necrolysis-like acute

Invest Dermatol 2000; 115:726.

(Baltimore) 2001; 80:180.

Topic 4666 Version 28.0

Major categories of cutaneous lupus erythematosus

Acute cutaneous LE (ACLE)

Toxic epidermal necrolysis-like eruption

Subacute cutaneous LE (SCLE)

Chronic cutaneous LE (CCLE)