Immunologic Skin Disorders

Jacqueline Luna, MD, MBAH, FPDS

LPU-St. Cabrini Doctor of Medicine
Module in Dermatology
Level III
Outline

1. Psoriasis
2. Lupus Erythematosus
3. Pemphigus
PSORIASIS
 PSORIASIS
Prevalence ranges from 0.1% to 3% in various populations.
A chronic disorder with polygenic predisposition combined with
triggering environmental factors such as trauma, infection, or
medication.
Psoriasis is a common, immunologically mediated, inflammatory
disease characterized by skin inflammation, epidermal hyperplasia,
and increased risk of a painful and destructive arthritis as well as
cardiovascular morbidity and psychosocial challenges.
Erythematous scaly papules and plaques; pustular and
erythrodermic eruptions occur
Most common sites of involvement are the scalp, elbows,
knees, hands, feet, trunk, and nails
Psoriasis may begin at any age, but it is uncommon before the age
of 10 years.
It is most likely to appear between the ages of 15 and 30 years..
Clinical Features of Psoriasis

CUTANEOUS FINDINGS
PLAQUE TYPE PSORIASIS

The classic lesion of psoriasis is a well-demarcated,

raised, red plaque with a white scaly surface
Lesions can vary in size from pinpoint papules to
plaques that cover large areas of the body.
Psoriasis tends to be a symmetric eruption, and
symmetry is a helpful feature in establishing a
diagnosis.
PLAQUE TYPE PSORIASIS

Under the scale, the skin has a glossy

homogeneous erythema, and bleeding points
appear when the scale is removed, traumatizing
the dilated capillaries below (the Auspitz sign)
PLAQUE TYPE PSORIASIS

The Koebner phenomenon

Traumatic induction of psoriasis on nonlesional skin

The Koebner reaction usually occurs 7 to 14

days after injury
PLAQUE TYPE PSORIASIS

Psoriasis vulgaris is the most common form of psoriasis,

seen in approximately 90% of patients.
Red, scaly, symmetrically distributed plaques are
characteristically localized to the extensor aspects of the
extremities; particularly the elbows and knees, along with
scalp, lower lumbosacral, buttocks, and genital involvement
Other sites of predilection include the umbilicus and the
intergluteal cleft.
The extent of involvement varies widely from patient to
patient.
GUTTATE (ERUPTIVE) PSORIASIS

Characterized by eruption of small (0.5–1.5 cm in diameter)

papules over the upper trunk and proximal extremities

This form of psoriasis has the strongest association to

streptococcal throat infection frequently precedes or is
concomitant with the onset or flare of guttate psoriasis.
Antibiotic treatment has NOT been shown to be
beneficial or to shorten the disease course.
INVERSE PSORIASIS

Psoriasis lesions may be localized in the major

skin folds, such as the axillae, the genitocrural
region, and the neck.
Scaling is usually minimal or absent, and the
lesions show a glossy sharply demarcated
erythema, which is often localized to areas of
skin to skin contact
Sweating is impaired in affected areas
ERYTHRODERMIC PSORIASIS
Psoriatic erythroderma affects all body sites, including the
face, hands, feet, nails, trunk, and extremities
Although all the symptoms of psoriasis are present
Erythema is the most prominent feature, and scaling is
different compared with chronic stationary psoriasis.
Instead of thick, adherent, white scale, there is superficial
scaling.
Patients with erythrodermic psoriasis lose excessive heat
because of generalized vasodilatation, and this may cause
hypothermia.
Patients may shiver in an attempt to raise their body
temperature.
PUSTULAR PSORIASIS
Several clinical variants of pustular psoriasis
exist:
Generalized pustular psoriasis (von Zumbusch
type)
Annular pustular psoriasis
Impetigo herpetiformis
Two variants of localized pustular psoriasis—
pustulosis palmaris et plantaris and acrodermatitis
continua of Hallopeau
PUSTULAR PSORIASIS:
VON ZUMBUSCH

This is a distinctive acute variant of psoriasis

that is usually preceded by other forms of the
disease.
Attacks are characterized by fever that lasts
several days and a sudden generalized
eruption of sterile pustules 2 to 3 mm
in diameter
The pustules are disseminated over the trunk
and extremities, including the nail beds, palms,
and soles.
PUSTULAR PSORIASIS:
PUSTULOSIS PALMARIS ET PLANTARIS
Rare variant
localized to the palms and soles.
It may coexist with chronic plaque psoriasis
More common in females (about 78%)
Median age of onset of 47 years.
Psoriatic arthritis (PsA) can be seen with
pustulosis palmaris et plantaris, with a prevalence
of 13% to 25%.
Smoking is strongly associated with pustulosis
palmaris et plantaris, and about 80% of patients
are tobacco smokers at the time of presentation
NAIL CHANGES

Seen in up to 40% of patients

Nail involvement increases with age, with duration and extent of disease, and
with the presence of PsA.
Several distinct changes have been described and can be grouped according to
the portion of the nail that is affected
NAIL CHANGES
Nail pitting is one of the most
common features of psoriasis, involving
the fingers more often than the toes
Pits range from 0.5 to 2.0 mm in size
and can be single or multiple.
The proximal nail matrix forms the
dorsal (superficial) portion of the nail
plate, and psoriatic involvement of this
region results in pitting caused by
defective keratinization.
NAIL CHANGES
Oil spots and salmon patches
translucent, yellow-red discolorations
observed beneath the nail plate often
extending distally toward the hyponychium
caused by psoriasiform hyperplasia,
parakeratosis, microvascular changes, and
trapping of neutrophils in the nail bed.

Unlike pitting, which is also seen in

alopecia areata and other disorders, oil
spotting is considered to be nearly
specific for psoriasis.
NAIL CHANGES

Subungual hyperkeratosis
caused by hyperkeratosis of the nail
bed and is often accompanied by
onycholysis, which usually involves
the distal aspect of the nail.
COMPLICATIONS
 CARDIOVASCULAR
MORBIDITY

Risk of myocardial infarction is particularly

elevated in younger patients with severe
psoriasis, and vascular inflammation
COMPLICATIONS Metabolic syndrome was 2.9-fold more
frequent among patients with psoriasis, and the
most common diagnoses were
hypertension (35.6% in psoriasis vs 20.6% in
control participants)
hyperlipidemia (29.9% vs 17.1%)
 PSYCHOSOCIAL
RAMIFICATIONS
Emotional difficulties arise from concerns about
appearance, resulting in lowered self-esteem,
social rejection, guilt, embarrassment, emptiness,
sexual problems, and impairment of professional
COMPLICATIONS ability.

Psychological stress can also lead to depression

and anxiety. The prevalence of suicidal ideation
and depression in patients with psoriasis is higher
than that reported in people with other medical
conditions and the general population.
OTHER RISK FACTORS

Obesity
Obese individuals are more likely to present with severe psoriasis.
Obesity does not appear to have a role in defining the onset of psoriasis
Smoking
Heavy smoking (>20 cigarettes daily) has been associated with more than a twofold increased risk of severe
psoriasis
Infections
An association between streptococcal throat infection and guttate psoriasis has been repeatedly confirmed
Severe exacerbation of psoriasis can be a manifestation of HIV infection
Drugs
Medications that exacerbate psoriasis include antimalarials, blockers, lithium, nonsteroidal anti-inflammatory drugs
(NSAIDs), IFNs- and -, imiquimod, angiotensin-converting enzyme inhibitors, and gemfibrozil.
TOPICAL TREATMENTS:
CORTICOSTEROIDS

MOA: stabilizing and causing nuclear translocation of glucocorticoid

receptors, which are members of the nuclear hormone receptor
superfamily.
First-line therapy in mild to moderate psoriasis and in sites such as the
flexures and genitalia, where other topical treatments can induce
irritation.
Improvement is usually achieved within 2 to 4 weeks, with maintenance
treatment consisting of intermittent applications (often restricted to the
weekends).
TOPICAL TREATMENTS:
CORTICOSTEROIDS

Long-term topical corticosteroids may

cause skin atrophy, telangiectasia, striae,
and adrenal suppression.
Another concern is that when topical
steroids are discontinued, patients may
reflare, sometimes worse than it was
before treatment.
TOPICAL TREATMENTS:
VITAMIN D3 AND ANALOGUES

MOA: binds to the vitamin D receptor, another member of the nuclear hormone
receptor superfamily.
Vitamin D3
acts to regulate cell growth, differentiation, and immune function, as well as calcium and
phosphorus metabolism
shown to inhibit the proliferation of keratinocytes in culture and to modulate epidermal
differentiation
Inhibits production of several proinflammatory cytokines by psoriatic T-cell clones,
including IL-2 and IFN-
TOPICAL TREATMENTS:
VITAMIN D3 AND ANALOGUES

Vitamin D analogues
Calcipotriene
Calcipotriol
Tacalcitol
Maxacalcitol
TOPICAL TREATMENTS:
TOPICAL CALCINEURIN INHIBITORS

Tacrolimus (FK-506)
is a macrolide antibiotic, derived from the bacteria Streptomyces tsukubaensis, which, by
binding to immunophilin (FK506 binding protein), creates a complex that inhibits
calcineurin, thus blocking both T-lymphocyte signal transduction and IL-2 transcription.
Pimecrolimus
also a calcineurin inhibitor and works in a manner similar to tacrolimus.
Side Effects:
burning sensation at application site
TOPICAL TREATMENTS:
BLAND EMOLLIENTS

Between treatment periods, skin care with emollients should be performed to

avoid dryness.
Emollients reduce scaling, may limit painful fissuring, and can help control pruritus.
They are best applied immediately after bathing or showering.
The addition of urea (up to 10%) is helpful to improve hydration of the skin and
remove scaling of early lesions.
The use of liberal bland emollients over a thin layer of topical prescription
treatments improves hydration while minimizing treatment costs.
PHOTOTHERAPY

The mechanism of action of phototherapy appears to involve selective

depletion of T cells, predominantly those that reside in the epidermis.
Lupus Erythematosus
 Lupus erythematosus
• Is the root designation for a diverse array of clinical illnesses that
are linked together by the development of autoimmunity directed
predominantly at the molecular constituents of nucleosomes and
ribonucleoproteins.
• Some present with life-threatening manifestations of systemic LE
(SLE), whereas others, who are affected with what represents
the same basic underlying disease process, express little more than
isolated discoid LE (DLE) skin lesions throughout their illness.
• LE as clinical
spectrum
Overview of
 SLE

DOPAMINRASH
Outline of systemic manifestations of SLE
 Etiology and Pathogenesis
• NOT fully understood, although recent work has provided many new
insights.

• SLE is a disorder in which the interplay between host factors

(susceptibility genes, hormonal milieu, etc) and environmental factors
(UV, viruses, and drugs) leads to loss of self-tolerance, and induction
of autoimmunity.
 Acute Cutaneous Lupus Erythematosus
• Usual pattern of presentation: localized
to the face
– Still can assume a generalized distribution.
• Localized ACLE
– commonly been referred: classic butterfly rash
or malar rash of SLE
– confluent symmetric erythema and edema are
centered over the malar eminences and
bridges over the nose.
– The nasolabial folds are characteristically
spared
– Forehead, chin, and V area of the neck can be
involved, and severe facial swelling may occur.
ACLE
 ACLE
• ACLE is typically precipitated or exacerbated by
exposure to UV light.
• Postinflammatory pigmentary change is most
prominent in patients with heavily pigmented skin.
• Atrophic scarring does not occur in ACLE
– unless complicated by secondary bacterial infection.
 Subacute Cutaneous Lupus Erythematosus
• initially presents as
erythematous macules
and/or papules that evolve
into hyperkeratotic
papulosquamous or
annular/polycyclic plaques
– most patients have either
annular or papulosquamous
SCLE
– few develop elements of both
morphologic varieties
 SCLE
• SCLE lesions
– characteristically photosensitive
– occur in predominantly sun-exposed areas
– typically heal without scarring but can resolve
with long-lasting, if not permanent, vitiligo-like
leukoderma, and telangiectasias
 Chronic Cutaneous Lupus Erythematosus
• Classic Discoid Lupus
Erythematosus
– most common form of CCLE
– begin as red-purple macules,
papules, or small plaques and
rapidly develop a hyperkeratotic
surface.
– Early lesions typically evolve into
sharply demarcated, coin-shaped
(ie, discoid) erythematous
plaques covered by a
prominent, adherent scale that
extends into the orifices of
dilated hair follicles
 DLE
Discoid Lupus Erythematosus

– typically expand with

erythema and
hyperpigmentation at
the periphery, leaving
hallmark atrophic
central scarring,
telangiectasia, and
hypopigmentation.
 Management
• Initial management: should include an evaluation to rule out
underlying SLE disease activity at the time of diagnosis.
• All patients with CLE should receive instruction about
protection from sunlight and artificial sources of UV radiation,
and should be advised to avoid the use of potentially
photosensitizing drugs such as hydrochlorothiazide,
tetracycline, griseofulvin, and piroxicam.
• Local measures should be maximized and systemic agents
used if significant local disease activity persists or systemic
activity is superimposed.
 Sun Protection
• Advise patients to avoid direct sun exposure, wear tightly woven clothing
and broad-brimmed hats, and regularly use broad-spectrum, water-
resistant sunscreens (SPF [sun protection factor] ≥30
• UV-blocking films should be applied to home and automobile windows,
and acrylic diffusion shields should be placed over fluorescent lighting.
• Corrective camouflage cosmetics offer the dual benefit of being highly
effective physical sunscreens as well as aesthetically pleasing cosmetic
masking agents.
 Topical Glucocorticoids
• Superpotent topical class I agents, such as clobetasol
propionate 0.05% or betamethasone dipropionate
0.05%, produce the greatest benefit in CLE.
– Twice-daily application of the superpotent preparations to
lesional skin for 2 weeks followed by a 2-week rest period can
minimize the risk of local complications
– a topical calcineurin inhibitor can be used daily during the 2-
week rest period from topical corticosteroids.
– Ointments are more effective than creams for more
hyperkeratotic lesions such as hypertrophic DLE.
 Topical Glucocorticoids
• Occlusive therapy with glucocorticoid-impregnated tape or
glucocorticoids with plastic food wrap (eg, Saran or Glad
Press-N-Seal) can potentiate the beneficial effects of topical
glucocorticoids but also carries a higher risk of local side
effects.
• Class I or class II topical glucocorticoid solutions and gels are
best for treating the scalp.
 Topical Calcineurin Inhibitors
• Pimecrolimus 1% cream and tacrolimus 0.1% ointment
have demonstrated efficacy in the treatment of ACLE,
DLE, and SCLE
 Intralesional Glucocorticoids
• Intralesional glucocorticoids are more useful in the
management of DLE than SCLE.
• Intralesional glucocorticoids themselves can produce
cutaneous and subcutaneous atrophy (deep injections into
the subcutaneous tissue enhances this risk).
PEMPHIGUS
 PEMPHIGUS

• Group of autoimmune blistering diseases of skin and mucous

membranes
• Histology
• intraepidermal blisters due to acantholysis
• Immunopathology
• in vivo bound and circulating immunoglobulin directed against the cell
surface of keratinocytes
 MAJOR TYPES

1. Vulgaris (PV) – blister occurs in the deeper part of the

epidermis, just above the basal layer
2. Foliaceous (PF) - also called superficial pemphigus, the blister is
in the granular layer
3. Paraneoplastic
4. IgA Pemphigus
 PEMPHIGUS VULGARIS

• Skin lesions can be pruritic or painful.

• UV radiation exposure may exacerbate
disease.
• Primary lesion:
• Flaccid blister anywhere on the skin surface,
but typically NOT the palms and soles.
• Usually on normal- appearing skin, but may
develop on erythematous skin.
 PEMPHIGUS VULGARIS

• Fragile blisters & erosions (most common

skin lesions observed)
• Characteristic finding:
• erosions can be extended into visibly
normal skin by pulling the remnant of the
blister wall or rubbing at the periphery of
active lesions
• Temporary hair loss can be seen in
about 5% of patients and can rarely be a
presenting sign of disease
 PEMPHIGUS VULGARIS

• Nikolsky sign
• Lateral pressure is applied on the border of an intact blister resulting in dislodgement of the
normal epidermis and extension of blister
• Differentiate pemphigus from other blistering diseases of the skin such as pemphigoid
 PEMPHIGUS VULGARIS

• Mucous membranes most often affected:

oropharyngeal cavity and nasal mucosa.
• 87% of PV patients had ear, nose, or throat lesions,
with involvement of nasal mucosa (76%), pharynx
(66%), and larynx (55%)
• Laryngeal involvement was often asymptomatic.
• Intact blisters are rare.
• Oropharyngeal erosions: painful that the patient is
unable to eat or drink.
• may require inpatient hospitalization for disease control
and IV fluid and nutrient repletion
 PEMPHIGUS VULGARIS

• Ocular involvement (16%)

• some with erosions of the conjunctiva and corneal erosions
• Vulvar and cervicovaginal lesions (51% of women)
• May be asymptomatic
• Vulvar lesions are most common and may cause severe burning with
urination.
• Pap smears: acantholytic cells may be misinterpreted as indicative of
cervical dysplasia
 PATHOLOGY OF PEMPHIGUS VULGARIS

• Characteristic finding: suprabasal blister with

acantholysis
• Just above the basal cell layer, epidermal cells lose their
normal cell-to-cell contacts
• “row of tombstones”
• Basal cells stay attached to the BM, but may lose contact with
their neighbors.
• The upper epidermis remains intact, as these cells
maintain their cell adhesion
• Early PV lesions: eosinophilic spongiosis
 CLINICAL COURSE & PROGNOSIS

• Before glucocorticoid therapy

• PV was almost invariably fatal
• severe blistering
• malnutrition, dehydration, and sepsis
• PF was fatal in approximately 60% of patients
• PF was almost always fatal in elderly patients with concurrent medical
problems
 CORTICOSTEROIDS

• Mainstay treatment: glucocorticoids, usually prednisone

• Once controlled, tapering prednisone to as low a dose as possible is the goal

Full systemic dose 1.5 mg/kg/d of prednisone equivalent for 2-3 weeks

If with adjunctive immuno- suppresive 0.5- to 1.0-mg/kg/d single daily dose

therapy

Those who do not initially respond or Split the dose using a twice- or 3-times- daily schedule
worsen

Those with continued relapses with daily adjunctive immunosuppressive agents

prednisone >5-10 mg

Minimal therapy 5 to 10 mg daily of prednisone equivalent.

 CORTICOSTEROIDS

• Topical corticosteroids
• may be used as monotherapy in mild forms of disease, especially PF
• adjunctive therapy to help heal new lesions
• Patients with mucosal disease:
• glucocorticoid elixirs as a swish and spit for dental trays to help apply
class I corticosteroid gels or ointments to the gingiva
• Class I-IV help resolve new blisters, even in patients on systemic
glucocorticoids.
End