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LUPUS ERYTHEMATOSUS

Name of the Doctor :-Dr. Manisha Nijhawan

SPECTRUM OF LE

MODIFIED GILLIAM CLASSIFICATION

LE SPECIFIC LESIONS

� Chronic cutaneous LE

� Subacute cutaneous LE

� Acute cutaneous LE

LE NON SPECIFIC LE LESIONS

A. Cutaneous vascular disease

� Vasculitis

� Leukocytoclastic vasculitis

� Palpable purpura

� Urticarial vascultis

� Periarteritis nodosa like lesions

� Vasculopathy

� Secondary Atrophie blanche(milan’s atrophy)

� Periungual telangiectasia

� Livedo reticularis (collagen vascular disease / erythema ab

igne)

� Thrombophlebitis

� Raynaud’s phenomena

� Erythromelalgia

B. Non scarring alopecia

� Lupus hair

� Telogen effluvium

� Alopecia areata

C. Sclerodactly

D. Rheumatoid nodules

E. Calcinosis cutis

F. LE-Non specific bullous lesions

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G. Urticaria

H. Papulonodular mucinosis

I. Cutis laxa / Anetoderma

J. Acanthosis nigricans

K. Erythema multiforme

L. Leg ulcers

M. Lichen planus

CHRONIC CUTANEOUS LE

� Classic discoid LE

� Localized DLE

� Generalized DLE

� Hypertrophic/verrucous DLE

� Lupus profundus/lupus panniculitis

� Mucosal DLE

� Oral DLE

� Conjunctival DLE

� LE tumidus (papulomucinous LE)

� Lichenoid DLE (LE/lichen planus overlap)

� Rosaceous LE

� Pigmented macular type

� Acneform type

� LE telangiectaticus

� Rowell syndrome

� Chilblain LE

Age

� Onset in the fourth decade in females and slightly later in

males

Genetics

� Positive associations with HLA‐B7, ‐B8, ‐Cw7, ‐DR2, ‐DR3

and ‐DQw1

Sex

� F > M (2 : 1)

Ethnicity

� Common in Asians, African Americans, Afro‐Caribbeans.

Associated diseases

� Porphyria ,pemphigus, myasthenia gravis and thymoma

PREDISPOSING FACTORS

� Trauma (11%) (X‐rays and diathermy)

� Stress (12%)

� Ultraviolet exposure (5%) (psoralen with UVA and laser light)

� Infection (3%) (herpes zoster)

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� Drugs: Isoniazid, penicillamine, griseofulvin and dapsone

� Seasonal exacerbation both in winter (10%) and summer

(50%)

� Cold exposure (2%)

Types

� Localized:- head and scalp, usually accounts for 70% of DLE.

� Generalized form:- characterized by the extension to more

than the head-body area - 30% of DLE

C/F

� Well-defined, disk-shaped erythematous plaque (few

millimeters to 15cm)

� Grayish hyperkeratosis that is extremely adherent to the skin

and involves dilated pilosebaceous follicles whose removal is

difficult

� Resolution with atrophy and scarring

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LOCALIZED DISEASE[70%]

� Face is most commonly affected and the scalp, ears, nose,

arms, legs and trunk to a lesser extent

� Scalp is involved in 60 % of cases and 1/3 rd of patients

develop scarring alopecia

� Photosensitivity in about 70%

� Circumscribed or discoid type is frequent and involves

cheeks, bridge of the nose, ears, side of the neck and scalp

� Thin white scarred area, slightly raised, red border or zone

of hyperpigmentation

� Adherent scale present, when removed undersurface shows

horny plugs which have occupied dilated Pilosebaceous

Canals - ‘Tin-tack’ sign

� On treatment over the course of some months, lesions flatten

and may clear completely without much scarring

� If hyperkeratosis is marked, a warty lesion with a red,

slightly raised edge (sites - Nose, Temples, Ears and Scalp)

� Non-itching hyperkeratotic papulonodular lesions on the

Arms and Hands, resembling keratoacanthoma, hypertrophic

lichen planus or nodular prurigo

� Localized cribriform scarring occurs on Face

� Wide follicular pits,

sometimes containing

scale or blackheads, occur

mainly in the concha or

triangular fossa of the ear

( SHUSTER’S SIGN)

DISSEMINATED DLE (DDLE)

� DLE occur in a widespread pattern on the Trunk and limbs,

or may be localized to other body sites

� Occurs mainly in Women (cigarette smokers)

� Lesions are persistent, resistant to therapy and associated

with severe psychological upset

� Non‐‐‐‐itchy, hyperkeratotic,papulonodular lesions on the

arms and hands

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HYPERTROPHIC OR VERRUCOUS LUPUS

ERYTHEMATOSUS

� Commonly affect the extensor

surface of the arms and legs,

the upper back and the face

� Dull, red and indurated

lesions that are covered by

keratotic multilayered horny

white or yellow scales with a

central crateriform atrophy

DLE OF LIPS AND ORAL MUCOSA

� Involved in approximately 9 to 35% of

patients.

� Lower lip – common site in indian

population

� Present as discrete scaly papules ,

plaques or diffuse cheiltis

� Lesions in buccal mucosa and palate

can present as chronic plaques , LP

like lesions or leucoplakia

CHILBLAIN LUPUS

� LE characterized by cold-induced

lesions localized in acral areas

C/F :-

� Located on fingers, toes, calves, heels,

knees, elbows, nose and ears

� Papuloerythematous Purplish,

sometimes Infiltrated, Pruriginous or

Painful elements and may ulcerate

� Heterogenous mutation TREX1 or

SAMHD1 in familial form

AICARDI- GOUTIERES SYNDROME

Recurrent sterile

fever

Developmental

delay

Chilblains

AR

ADAR1, IFIH1,

TREX1 gene

mutation

LUPUS ERYTHEMATOSUS PROFUNDUS

� Firm depressed NODULES

� Involvment of the lower dermis and

subcutaneous tissue

C/F:-

� Frequently in women (20 to 60 y)

� F:M :: 2:1

� Predilection for the face, proximal

extremities, buttocks, breasts and

trunk

� Complications includes ulceration ,

calcification and secondary infection

� Lobular panniculitis

� Nodular aggregates

lymphocyte

� Hyaline necrosis of fat

lobules

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LE TUMIDUS

� One of MOST PHOTOSENSITIVE variant

� Presents as erythematous , urticarial or annular plaques with minimal surface change

� Sites – Zygomatic area of face, extensor aspects of arms, upper trunk, V area of neck

ROSACEOUS LE

� Presents with Nodular lesion

on the nose, cheeks, forehead

� Associated erythema and

flushing

LE TELANGIECTATICUS

� Characterized by persistent ,

blotchy reticulate

telangiectasia

� Sites – cheeks , neck ,ears ,

extensor knees and heels

DLE OF NASAL , OCULAR AND GENITAL

MUCOSA

� NASAL – lesions on nasal

septum present as persistent

erythematous plaques ,

crusting , scarring of

affected area

� OCULAR – can present as

u/l or b/l erythematous

plaques of the eyelid margin ,

usually lower eyelid

� Long standing case can lead

to Tarsal conjunctival

scarring, loss of eyelashes

LE and EM

� First described by rowell and co-workers , occurrence of EM

in association with LE

� CRITERIA by Zeitouni ( 3 major , 3 minor )

MAJOR MINOR

1.Presence of LE 1. Chilblains

2.EM like lesions 2. Positive RA factor

3.Speckled pattern of ANA 3. Anti RO or LA ab

Histopathology

� ORTHOHYPERKERATOSIS

� Follicular plugging

� Atrophy of stratum malphigi

� Hydropic degeneration of basal cells

� Colloid bodies

� Thick basement membrane

� Lymphocytic infiltration at DEJ and in a periadnexal and

perivascular distribution

� Interstitial mucin deposition

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IMMUNOPATHOLOGY

� Immunohistology shows the presence of immunoglobulins

IgG, IgA, IgM and complement at the dermal– epidermal

junction

� In approximately 80% of patients.

� Immunohistology shows the presence of immunoglobulins

IgG, IgA, IgM and complement at the dermal– epidermal

junction

� In approximately 80% of patients.

LUPUS BAND TEST ( LBT)

� Deposition of immunoglobulins and complement components in the skin , demonstrable as a linear band at the BMZ by DIF.

� Considered positive when one or more immunoreactants ( Ig G, A, M, C3 ) are found.

� Lesional LBT and nonlesional LBT are used to denote biopsy from involved and uninvolved skin.

� Lesional – skin lesion

� Non lesional - (A) UV exposed, uninvolved – forearm

(B) UV protected uninvolved- buttocks

� Homogeneous, Granular or Thready patterns occur

� Deposition is usually homogeneous in older lesions

� More frequent on the face and in untreated lesions, rarely on

trunk, and decrease after treatment with topical

corticosteroids

USES:-

1) It is a very sensitive and specific test for LE

� 90-95% have positive LBT in involved skin

� Sensitivity is higher than that of other laboratory variables

2) Immunoglobulin and complement at DEJ in

� SLE - Involved and uninvolved skin

� DLE -Involved skin

3) Making a diagnosis of SLE without cutaneous lesions :-

A Positive band test in clinically normal skin from covered

area provides early confirmation of SLE

4) Diagnosis of SLE from other ANA positive diseases like

drug induced LE, rheumatoid arthritis, scleroderma,

dermatomyositis and mixed connective tissue diseases

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5) Prognostic significance–

� Positive LBT from sun protected normal skin indicates

decreased long term survival

� It helps in assessing the severity of the disease and correlates

positively with risk of developing nephritis

INVESTIGATIONS

� CBC

� ESR

� LFT / RFT

� URINE ANALYSIS

� ANA level

� ANTI ds DNA level

� C3, C4 level

� Dermascopy

� Whitish halo

� Follicular plugging

� Telangiectasia

LABORATORY ABNORMALITIES IN DLE

AUTOANTIBODIES

ANA

� Positive in 20-30%

� Homogeneous type of antinuclear factor being twice as frequent as

the ‘speckled’ type

� They are more common in 1. Older patients

2. Long duration of disease

3. Extensive skin involvement

4. Chilblains

5. Raynaud’s phenomenon

6. Joint pains

Others:-

� Anti-DNA antibodies - 1% to 27%

� Antibodies to single-stranded DNA (IgM in 20% ) occur in

nearly one-fifth and may indicate widespread and

progressive disease

� Ro antibodies are found in 10% of patients

� Anti-La [SS-B] is associated with ‘speckled’ antinuclear

factor

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� Rheumatoid factor in those patients with DLE and erythema

multiforme (rowell syndrome)

� Soluble IL-2 receptors

� A high incidence of antithyroid antibodies has been found

in DLE, particularly in females, and gastric parietal cell

cytoplasmic antibodies occur in 13% of patients

PROGNOSIS

� Risk of developing SLE is 5% in localised and 22 % in

disseminated type

� Females developing DLE before the age of 40 years with

HLA-B8, have an increased risk of ‘converting’ to SLE

� Squamous cell and less commonly, basal cell carcinomas

occasionally occur in the scars of DLE, particularly on the

scalp, ears, lips and nose (incidence - 3.3%)

RISK FACTORS FOR THE DEVELOPMENT OF

SLE IN DLE PATIENTS

� Disseminated DLE -22%

� Generalised lymphadenopathy

� SCLE/ ACLE skin lesions

� LE non specific lesions – vasculitis, Diffuse non scarring

alopecia, Periungual capillary nail fold telangectasia,

� Unexplained anemia, marked leukopenia

� False positive test for syphilis

� Persistantly positive high ANA titres

� Anti single stranded DNA antibody

� Hypergammaglobulinemia

� High ESR

� Positive non lesional LBT

� High levels of elevated IL 2 receptor levels

GENERAL MEASURES

PHOTOPROTECTION

� Avoidance of sun exposure

� Physical protection

� Broad spectrum sunscreen

� Cessation of smoking

� Elimination of photosensitizing drugs

LOCAL THERAPY

� Potent or ultrapotent topical steroids

� Calcineurin inhibitors - Pimecrolimus cream or Tacrolimus ointment

� Intralesional corticosteroid into small lesions resistant to topical therapy

� Topical retinoids, calcipotriol and imiquimod have also been reported to be

helpful in a few patients

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SYSTEMIC THERAPY

� Antimalarials especially hydroxychloroquine

� Systemic corticosteroids

� Immune modulators such as Methotrexate, Mycophenolate,

Dapsone, Ciclosporin , Azathioprine

� Retinoids, acitretin, isotretinoin

� If sun protection is strict, vitamin D supplementation

Severe disease may require more aggressive treatment:-

� Cyclophosphamide

� Thalidomide

� Intravenous immunoglobulin

Physical T/T

� LASER THERAPY

� CRYO

� EXCISION

� DERMABRASION

Oral agents useful in the management of

DLE

SCLE

� Recurrent nonscarring, Non indurated lesions occuring in

a Photodisributed pattern with characterstic

immunological feature of RO/LA AUTOANTIBODY

PRODUCTION

� Single nucleotide polymorphism in TNF ALPHA

PROMOTOR REGION

� Usually occurs in Young and Middle aged women

� Drug induced form may be seen in either sex and at older

age of onset

� SCLE may be induced by

� Thiazides

� Griseofulvin ,Terbinafine

� Antiepileptics

� NSAIDS

� ACE inhibitors , Ca channel blockers

� Anti TNF alpha

� SCLE has been reported with malignancies of breast, lung

and hodgkin’s lymphoma

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� Lesions occur on PHOTOEXPOSED areas , centrofacial area may

be spared

� Two characterstic lesion present

A. Papulosquamous

B. Annular

Other Rare morphological varients are

� Pityriasiform

� Exanthematous

� Erythrodermic

� TEN like lesions

� LE gyratum rapens

� Pts with SCLE can develop DLE or lesions of ACLE or LE non

specific lesions like

� Raynaud’s phenomenon

� Livido reticlaris

� Cutaneous vaculitis

� ANA positivity – 70 %

� Majority of pts have anti RO autoab > anti LA

� Good prognosis

H/P

� Histological changes differ in degree from those in DLE and

are more intense at DEJ

� Hydropic degenration is severe (subepidermal cleft)

� Edema of dermis is more

� Focal extravasation of RBC and dermal fibrinoid deposits

Management

� Avoid UV exposure

First line-

� Sunscreens

� topical or intralesional corticosteroids or the topical macrolides

� pimicrolimus and tacrolimus

Second line-

� Hydroxychloroquine

� Chloroquine (sulphate or phosphate)

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Third line

� oral corticosteroids (methylprednisolone)

� Acitretin, Isotretinoin

� Dapsone

� Oral, intravenous and subcutaneous methotrexate

� Thalidomide

� UVA , long‐term

� cefuroxime acetyl

� Mycophenolate mofetil

� Intravenous immunoglobulin

� Etanercept