Samah Hamdy El-Medany

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MUCOCUTANEOUS INVOLVEMENT IN Systemic Lupus
Erythematosus

• By
• Samah Hamdy El-Medany
• Ass. Lecturer in Rheumatology Physical medicine
  and Rehabilitation dep.

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INTRODUCTION

• Lupus Erythematosus (LE) is a difficult disease
  to classify in terms of skin findings because it
  can cause many different types of skin lesions,
  and the challenge is to determine how these
  lesions come about, how they fit together, and
  how best to treat them. By understanding the
  basis of these skin lesions, scientists can
  develop more effective therapies.

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INTRODUCTION
Gilliam (1977) initially proposed a
classification system for the skin lesions that
can be encountered in patients with LE and
divided the cutaneous manifestations of this
disease into those that are histologically
specific for LE (i.e., LE-specific skin disease)
and those that are not histologically specific
for this disease (i.e.,LE-non-specific skin
disease). In 2003, a modified classification
system of cutaneous LE (CLE) has been developed
including acute CLE, subacute CLE, chronic CLE,
and the intermittent subtype of CLE.
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Classification of Lupus ErythematosusAssociated
Skin Lesions
LE-Specific Skin Lesions LE-Specific Skin Lesions
Acute cutaneous LE Localized Generalized
Subacute cutaneous LE Annular Papulosquamous (psoriasiform)
Chronic cutaneous LE Classic DLE (Localized or Generalized)
Hypertrophic DLE
Lupus panniculitis (profundus)
Mucosal LE
Chilblain lupus
Intermittent cutaneous LE Lupus erythematosus tumidus
Modified from Sontheimer RD, Provost TT
Cutaneous Manifestations of Rheumatic Diseases.
Baltimore, Williams Wilkins, 1996.
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CLASSIFICATION OF LUPUS ERYTHEMATOSUSASSOCIATED
SKIN LESIONS
LE-Nonspecific Skin Lesions LE-Nonspecific Skin Lesions
Cutaneous vascular disease Vasculitis
Leukocytoclastic Palpable purpura, Urticarial vasculitis
Polyarteritis nodosalike
Papulonodular mucinosis
Livedo reticularis
Thrombophlebitis Raynaud's phenomenon, Erythromelalgia
LE-nonspecific bullous lesions Acquired epidermolysis bullosa
Dermatitis herpetiformislike bullous LE
Pemphigus erythematosus
Porphyria cutanea tarda
Alopecia (nonscarring) Lupus hair, Alopecia areata
Modified from Sontheimer RD, Provost TT
Cutaneous Manifestations of Rheumatic Diseases.
Baltimore, Williams Wilkins, 1996.
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Classification of Lupus ErythematosusAssociated
Skin Lesions
LE-Nonspecific Skin Lesions
Urticaria
Vasculopathy
Anetoderma/cutis laxa
Acanthosis nigricans (type B insulin resistance)
Periungal telangiectasia
Erythema multiforme
Leg ulcers
Sclerodactyly
Rheumatoid nodules
Calcinosis cutis
Modified from Sontheimer RD, Provost TT
Cutaneous Manifestations of Rheumatic Diseases.
Baltimore, Williams Wilkins, 1996.
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Photosensitivity
Photosensitivity refers to the development of a
rash after exposure to ultraviolet B (UVB)
radiation found in sunlight or fluorescent
lights. It occurs in 60 to 100 of patients with
SLE. The severity of cutaneous reaction depends
on the intensity of the UV source and the
duration of exposure.
This image displays the cheeks and nose of a
patient affected by systemic lupus that has been
aggravated by exposure to the sun.
The dull red patches of systemic lupus are
prominent in sun-exposed areas. When these
patches are seen on the cheeks, one can imagine
why the term butterfly rash is used.
This image displays how inflammation in systemic
lupus can be intense, causing very red skin
lesions.
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Pathophysiology of photosensitivity in LE
Lupus erythematosus (LE) represents an autoimmune
disease with great clinical variability in which
photosensitivity is a common feature for all
forms and subsets. Cutaneous LE lesions often
arise in sun-exposed areas and it is well
reported and recognized that sun exposure may
also exacerbate or induce systemic manifestations
of this disease.
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• Amplification cycle demonstrating UV-injury,
  apoptosis, necrosis, and chemokine production.
  Mediation of recruitment and activation of
  autoimmune T-cells and INF-alfa producing
  Plasmocytoid dendritic cells (PDCs). Release of
  more effector cytokines amplifying chemokine
  production and leukocyte recruitment leading to
  LE-lesion. (From Meller 2005).

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SPECIFIC CUTANEOUS MANIFESTATIONS OFLUPUS
ERYTHEMATOSUS
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Acute cutaneous lupus erythematosus

• Acute cutaneous lupus erythematosus (ACLE)
  usually occurs in association with systemic
  manifestations preceding by weeks or months the
  onset of a multisystem disease.
• Sun exposure is a common exogenous factor to
  precipitate ACLE. Furthermore, infections,
  especially with subtle types of viruses, or
  certain drugs, e.g. hydralazine, isoniazide, and
  procainamide, have also been found to induce or
  aggravate this disease.

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Acute cutaneous lupus erythematosus
Acute Cutaneous Malar Rash Note Sparing of
Nasolabial Folds

• There are localized and generalized
  manifestations of ACLE. The localized form
  commonly presents as the classic malar rash
  or butterfly rash on the central portion of
  the face and may only affect the skin
  transiently. Therefore, at the onset of disease,
  the patient may mistake this rash for sunburn. It
  usually begins with small, discrete erythematous
  macules and papules, occasionally associated with
  fine scales and gradually becomes confluent and
  hyperkeratotic. Facial swelling may be severe in
  some patients however, it mostly disappears
  without scarring and pigmentation.

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Acute cutaneous lupus erythematosus

• Similar lesions have also been found to occur on
  the forehead, the V-area of the neck, the upper
  limbs, and the trunk. In addition, patients may
  have diffused thinning or a receding frontal
  hairline with broken hair (lupus hair), and may
  further present with teleangiectasias and
  erythema of the proximal nail fold. Superficial
  ulcerations of the oral and/or nasal mucosa are
  also frequently accompanied with this subtype and
  may cause extreme discomfort in some patients.

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Acute cutaneous lupus erythematosus

• The generalized form of ACLE is a less common
  variety and may be located anywhere on the body
  although the preferred sites are above the
  waistline. The onset of this form usually with
  exacerbation of systemic manifestations
  developing a prolonged disease activity.
• The incidence of this generalized form is
  estimated to be approximately in 510 of
  patients with SLE.
• It is characterized by a symmetrically
  distributed maculopapular or exanthematous
  eruption with a pruritic component. The colour of
  the lesions is usually red or, less frequently,
  dull red or livid, and there have been reports
  of patients presenting with severe involvement of
  the oral mucosa or the palms and phalanges

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SUBACUTE CUTANEOUS LUPUSERYTHEMATOSUS
Subacute cutaneous lupus erythematosus (SCLE) is
not uniformly associated with SLE. About 50 of
affected patients have SLE, and about 10 of
patients with SLE have this type of skin lesion.
Patients with SCLE may present with annular or
psoriasiform skin lesions, and this is strongly
associated with anti-Ro (SS-A) and anti-La (SS-B)
antibodies. Patients with SCLE have a high
incidence of photosensitivity and rarely can
present with erythema multiformelike lesions
(Rowell's syndrome). Most patients with SCLE
have prominent cutaneous and musculoskeletal
complaints but generally do not develop a severe
systemic disease.
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• Subacute cutaneous lupus lesions. Typical
  features include symmetric, widespread,
  superficial, and non-scarring lesions.
  Involvement of the neck, shoulders, upper chest,
  upper back, and extensor surface of the hand is
  common. These lesions begin as small
  photosensitive, erythematous, scaly papules or
  plaques that evolve into a papulosquamous
  (psoriasiform) or annular polycyclic form as in
  this patient.

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• Subacute cutaneous lupus erythematosus (SCLE).
  Annular, polycyclic lesions with erythematous
  borders and central hypopigmentation on the back.

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• Another example of subacute cutaneous lupus
  erythematosus with annular lesions.

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Chronic cutaneous lupus erythematosus
1- Discoid lupus erythematosus

• Discoid lupus erythematosus (DLE) is the most
  common subtype of the chronic cutaneous variants
  of LE and may present as a localized or
  disseminated form.
• The localized form, characterized by limited
  cutaneous involvement of the head and scalp,
  usually accounts for 70 of patients with DLE,
  and the disseminated form, characterized by the
  extension to areas below the neck for 30 of
  patients with DLE.
• About 30 of patients with SLE may develop DLE
  lesions during the course of their disease and,
  in about 510 of patients, DLE lesions may
  already be present at the onset of the disease.

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Chronic cutaneous lupus erythematosus
Discoid lesions are characterized by discrete,
erythematous, slightly infiltrated plaques
covered by a well-formed adherent scale that
extends into dilated hair follicles (follicular
plugging). Discoid lesions are most often seen on
the sun-exposed parts, face, neck, scalp, ears
and infrequently on the upper torso. They tend to
expand slowly with active inflammation at the
periphery, and then to heal, leaving depressed
central scars, atrophy, telangiectasias, and
dyspigmentation (hyperpigmentation or
hypopigmentation).
Discoid LE
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Chronic CLE
Discoid LE

• Facial discoid lupus erythematosus lesions
  produce large areas of disfigurement on
  confluence. Note the erythema (indicating disease
  activity), keratin-plugged follicles, and dermal
  atrophy. The characteristic pattern of
  hyperpigmentation at the active border and
  hypopigmentation at the inactive center. Facial
  involvement of this sort can produce extreme
  psychosocial disability.

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(a)
(b)
(c)

• Discoid lupus erythematosus on the finger (a),
  palm (b), and beard area (c).

Discoid LE
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Discoid LE

• Examples of DLE of the scalp with characteristic
  plugging of follicles, and demonstrating marked
  scarring and pigment change. This situation is
  irreversible.

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Discoid LE
Chronic cutaneous lupus erythematosus

• About 2 of patients with DLE show a
  hyperkeratotic type of lesion consisting of dull,
  red, and indurated lesions.
• When the palms and soles are involved, the
  mobility can be difficult.
• Mucous membrane involvement can be found in 25
  of patients with DLE, but does not necessarily
  reflect systemic manifestation or high disease
  activity.
• The differential diagnosis of discoid lesions
  includes hypertrophic lichen planus, eczema, and
  actinic keratosis some early and scaly discoid
  lesions also must be differentiated from
  psoriasis.

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Chronic cutaneous lupus erythematosus
Discoid LE
Biopsy specimens of skin lesions from patients
with DLE contain immune complexes at the
dermal-epidermal junction. The basilar epithelium
in these areas is vacuolated and edematous, and
the dermis contains an inflammatory infiltrate.
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Chronic cutaneous lupus erythematosus
2- Chilblain lupus erythematosus (CCLE)

• The pathogenesis of this rare subtype is unknown,
  but microvascular injury secondary to exposure to
  cold and possible hyperviscosity from immunologic
  abnormalities may play a role.
• The risk of developing SLE is estimated to be
  approximately 20.
• The lesions of this type are clinically
  characterized by symmetrically distributed,
  circumscribed painful areas of livid and purple
  plaques.

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Chronic cutaneous lupus erythematosus
2- Chilblain lupus erythematosus

• Mostly, the dorsal and lateral parts of the
  hands, feet, ears, nose, elbows, knees, and
  calves are involved.

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Chronic cutaneous lupus erythematosus
3- Lupus erythematosus panniculitis (profundus)

• lupus profundus, presenting as a firm nodular
  lesion with or without an overlying cutaneous
  lesion. The nodules are often painful and consist
  of perivascular infiltrates of mononuclear cells
  plus panniculitis, manifested as hyaline fat
  necrosis with mononuclear cell infiltration and
  lymphocytic vasculitis. The nodules usually
  appear on the scalp, face, arms, chest, back,
  thighs, and buttocks ulcerations are uncommon,
  and they usually resolve leaving a depressed
  area. Some patients with lupus profundus show no
  other manifestations of SLE.

Multiple, erythematous nodules and indurated
plaques were present on the lower extremities. On
the right thigh and medial left knee there were
skin-colored, atrophic, scarred plaques.
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• An older lesion of lupus profundus, demonstrating
  depression of the skin surface due to marked
  atrophy of the underlying fat.

Lupus erythematosus panniculitis (profundus)
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INTERMITTENT CUTANEOUS LUPUS ERYTHEMATOSUS
Lupus erythematosus tumidus (LET)

• Tumid lupus, a rare variant, is characterized by
  photodistributed lesions with chronic
  pink-to-violaceous papules, nonscarring plaques,
  and nodules.
• Tumid lupus differs from other variants of CLE.
  Scarring which is the hallmark of DLE, does not
  occur in tumid lupus. Hypopigmentation,
  frequently evident in patients with SCLE with
  erythema and scaling, has never been detected in
  tumid lupus

A round erythematous edematous plaque on the
right malar region
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Single. erythematous, succulent, urticaria-like
plaques on the forehead
Intermittent cutaneous lupus erythematosus
LET
The prognosis in patients with LET is generally
more favorable than in those with other forms of
CLE
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Involvement of the mucous membranes occurs in 25
to 45 of patients with SLE. The most common
manifestations include irregularly shaped,
raised, white plaques areas of erythema silvery
white scarred lesions and ulcers with
surrounding erythema on the soft or hard palate
or buccal mucosa. The oral ulcers in SLE are
usually painless, and sometimes there is no
apparent association between their presence and
systemic disease activity. Oral lesions may be
the first signs of SLE.
Mucosal LE
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Characteristic discoid lesions with erythema,
atrophy, and depigmentation can occur on the
lips. Nasal ulcers have been noted in patients
with SLE. They usually are found in the lower
nasal septum, tend to be bilateral, and are
associated with active disease. Nasal septum
perforation has been reported in 4 of SLE
patients and is secondary to vasculitis.
Involvement of the upper airway mucosa also can
occur and cause hoarseness.
Mucosal LE
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NON - SPECIFIC CUTANEOUS MANIFESTATIONS OF LUPUS
ERYTHEMATOSUS
Alopecia (nonscarring)
Papulonodular mucinosis
Livedo reticularis
Vasculitic lesions
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Erythema multiforme
Dermatitis herpetiformis
Pemphigus erythematosus
Raynaud's phenomenon
Skin lesions which are seen not only in patients
with LE but are also found in association with
other conditions are defined as non-specific
cutaneous manifestations.
Non Specific CLE
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TYPES OF LUPUS ERYTHEMATOSUS AND THEIR
DIFFERENTIAL DIAGNOSIS
Pattern LE Typical lesion pattern Main differential diagnoses and comments
Discoid lupus erythematosus (DLE) Discoid lesions, typically facial Dermatitis, psoriasis, Bowen disease, telangiectatic actinic keratosis, reticulate erythematosus mucinosis , polymorphic light eruption (more variable than typical DLE), tinea faciei, lupus vulgaris. Jessner lymphocytic in?ltrate may be particularly dif?cult to distinguish. Scalp consider lichen planus, folliculitis decalvans.
Subacute cutaneous lupus erythematosus (SCLE) Lesions may be psoriasiform or annular photosensitivity is annular photosensitivity is also common Psoriasis, dermatitis (especially seborrheic on trunk), tinea corporis, mycosis fungoides or lymphomas, polymorphic light eruption, reticulate erythematosus mucinosis, dermatomyositis, drug-induced photosensitivity.
Acute cutaneous lupus erythematosus CLE Malar butterfly rash (for other lesions, the differential diagnosis is that of DLE or SCLE) Especially rosacea, seborrheic dermatitis. Also contact dermatitis, polymorphic light eruption and other photosensitivity.
Lupus profundus Inflammatory nodules affecting fat Other panniculitides can usually be excluded by the tendency for lupus profundus to affect the face, upper arm, or upper trunk (unusual in other panniculitis) plus patients often have known LE or positive antibody tests. In acute inflammatory stage, soft tissue injuries, infections, or neoplasia may be in the differential.
Chilblain LE DLE-like lesions of distal digits Dermatitis, perniosis.
LE tumidus Tumid facial lesions Polymorphic light eruption, Jessner lymphocytic in?ltrate, pseudolymphomas, mucinosis.
Mucosal LE Lip or buccal involvement Lip dermatitis, lichen planus. Buccal lichen planus, candidiasis, leukoplakia.
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If a skin rash is present, the doctor may take a
biopsy (a tissue sample) from the margin of a
skin lesion. A test known as a lupus band detects
antibodies known as immunoglobulin G (IgG), which
are located just below the outer layer of the
tissue sample. They are present in about 80 of
patients with active SLE and in between 30 - 40
of those with inactive disease. The biopsy will
not differentiate between systemic and discoid
lupus, but it can rule out other diseases.
Skin Tests
Microscopic image of direct immuno-fluorescence
using a fluorescent anti-IgG antibody on a skin
biopsy. The test shows a band-like accumulation
of IgG along the basement membrane ("lupus band
test positive)
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TREATMENT OF CUTANEOUS LUPUS ERYTHEMATOSUS

• Sunscreens are important therapeutically in all
  types of LE, especially SCLE and tumid LE.
• The usual treatment for discoid lesions is a
  potent topical corticosteroid.
• Intra-lesional steroid injections may be useful
  for refractory discoid lesions, or isolated areas
  of LE profundus.
• Antimalarials, usually hydroxychloroquine, are a
  useful therapy in many patients with SLE
  (especially if photosensitivity is prominent),
  and especially in SCLE.

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PRACTICE POINTS

• Always consider discoid lupus erythematosus (DLE)
  in any patient with scarring alopecia and
  evidence of inflammation (perifollicular erythema
  at the margin of scarred areas).  
• A butterfly rash without malaise or other
  systemic symptoms is unlikely to represent active
  systemic lupus erythematosus (SLE).     
• If you suspect SLE in a patient with
  photosensitivity and DLE-like lesions, but the
  ANA test is negative, check for anti-Ro
  antibodies the patient may have (SCLE).   
• Patients on antimalarials for lupus erythematosus
  must stop smoking to get good bene?t.

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Conclusions

• Cutaneous manifestations in patients with LE are
  very frequent, show a great variety and can occur
  at any stage of the disease.
• A classification system has been established
  dividing the skin lesions associated with LE in
  specific and non-specific manifestations.
• Patients who have a more generalized involvement
  of the skin tend to have more systemic symptoms
  than those with lesions localized to the face or
  neck.
• All cutaneous manifestations of LE can result in
  limited patient quality of life and disability

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REFERENCES

• Kelley's Textbook of Rheumatology, 8th ed. (2008)
• The Skin in Systemic Autoimmune Diseases (2006)
• http//www.lupus.org/webmodules/webarticlesnet/tem
  plates/new_aboutintroduction.aspx?articleid75zon
  eid9
• http//en.wikipedia.org/wiki/Systemic_lupus_erythe
  matosus
• http//www.lupusmalaysia.org/e/what-is-sle/
• http//www.cureresearch.com/l/lupus/stats-country.
  htm

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