Erythema

• It is redness of the skin that blanch under pressure of

a finger.

• It is due to an in blood within subpapillary plexus or

to an visibility due to changes in adjacent tissues.

• Diffuse erythematous eruptions due to drug

sensitivity, virus exanthems, streptococcal infection

or systemic dis., e.g. LE or lymphoma.

• Localized erythematous eruptions due to trauma,

heat, chemical irritants, light or cold, drug eruption.

Erythema

• With other skin diseases, e.g. eczema,

psoriasis, PRP, tinea and many geno-

dermatoses.

• Pregnancy & liver diseases.

• With systemic dis., e.g. SLE, Rhoid

arthritis.

• Idiopathic.

Palmar erythema

• An acute, self-limited, mucocutaneous syndrome with

marked tendency to recurrences.

• IF studies demonstrate IgM & C3 in the walls of

superficial dermal vessels, in lesions less than 24 hrs

old.

• Circulating immune complexes have been

demonstrated.

Erythema multiforme “EM”

What are target lesions?• The first zone consists of a dark or bliTarget lesions

typically consist of three zones.

• stered center (bull’s-eye) that is surrounded by a

second, pale zone.

• The third zone consists of a rim of erythema. Target

lesions classically are found on the palms of a patient

with erythema multiforme.

• Idiopathic: >50%.

• Drugs: e.g. sulphonamides, sulphones, contra-ceptive

pills.

• Infections:

Causes of erythema multiforme

Virus: H. simplex, vaccinia, AIDS, hepatitis B, Orf,

Milker’s nodes. Mycoplasma, histoplasmosis. Mycobacteria, e.g. TB, leprosy.

• Autoimmune & vascular diseases, e.g. LE, DM,

polyarteritis nodosa, Wegener’s granulomatosis.

• Malignancies, e.g. carcinoma, lymphoma, leukemia.

• Pregnancy, autoimmune progesterone dermatitis.

• X-ray therapy, sarcoidosis, contact reactions.

Causes of erythema multiforme (Cont’d)

Erythema multiforme (Cont’d)

Clinical features

1. EM minor (commoner)• An acute (about 7-10 days duration), bilateral &

symmetrical eruptions of multiforme lesions, i.e. macules, papules, urticarial & vesicular, with the characteristic iris or target lesions formed of erythematous maculopapules with cyanotic or purpuric center.

• The lesions appear in successive crops, each fades in 1-2 wks.

• The extremities & face are commonly affected.• Erosions of oral mucous membranes may occur

rarely.• Recurrent EM minor is usually associated with HS

preceding it by several days.

EM – clinical features (Cont’d)

2. EM major: it is the severe form known as “Stevens-

Johnson syndrome”• Most often occurs as a drug reaction.• High fever, malaise & arthralgia.• Generalized bullous & maculopapular lesions

occur with affection of oral mm in all cases in the form of extensive bullae formation followed by erosions.

• New crops of lesions develop over a period of 3-4 wks.

• Many organs may be affected: severe catarrhal or purulent conjunctivitis, genital mucosa, pneumonitis & renal affection.

• Death may occur in 5-15% of untreated cases.

• Skin &/or mm affection.

• Acute onset & self-limited episodic

course.

• Duration must be less than 6 ms “for

each episode”.

• Typical & fixed skin lesions >7 days.

• Target lesions.

Diagnostic criteria of EM

Erythema multiforme (Cont’d)

Treatment

• Treatment of the underlying cause.

• Systemic antibiotics.

• Minor cases require only symptomatic treatment.

• Major cases may require systemic steroids: 30-60 mg

prednisone daily.

Acyclovir may be used as a prophylactic measure

to prevent recurrence after herpes simplex.

Thalidomide is used to prevent relapses.

• A severe mucocutaneous & systemic reaction

which may represent the most severe end of

erythema multiforme major.

• It has been called Lyell’s syndrome which

includes also cases of SSS syndrome.

• TEN should be used only for non-

staphylococcus toxin-related disease.

Toxic epidermal necrolysis “TEN”

• The onset is often preceded by several hours to days

by skin tenderness, fever, malaise & arthralgias.

• Erythema, which may be morbilliform or diffuse,

occurs with +ve Nikolsky sign followed by large

flaccid bullae & detachment of large areas of necrotic

epidermis leaving large, raw, painful areas.

• Mucous membranes may be extensively involved.

Ocular conjunctiva is involved in 85% of pts.

• Complete healing takes place without scarring over 2

wks. Scarring of skin, mucosal surface as the conj. &

nails occurs with 2ry bacterial inf.

TEN (Cont’d)

• Drugs: the most common cause (80% of cases):

sulfonamides, phenytoin, phenylbutazone,

allopurinol, ampicillin, NSAIDs.

• GVHD.

• Infections, e.g. Herpes virus.

• Neoplasms, e.g. Hodgkin’s leukemia.

• SLE.

• Idiopathic.

Causes of TEN

• Symptomatic treatment.

• Local treatment:

TEN (Cont’d)Treatment

Extensive debridement of nonviable epidermis

followed by immediate wound cover with biological

dressings.

Hyperbaric oxygen.

• Systemic steroids.

• Plasmapheresis.

• High dose of IV immunoglobulins.

• Pentoxiphyllin IV.

• Asymptomatic, generalized eruption

affecting about 40% of the newborns.

• Onset is in the first 3 days of life in 90%

of the cases and is extremely rare at

birth.

• It resolves within 2-3 days without

pigmentation.

Erythema toxicum neonatorum

Urticaria

Urticaria

• Superficial swellings of dermis

wheals Itchy, pale in center pink

superficial plaques, resolve

over hours without a mark.

Surrounding flare is due to an

axon reflex.

Wheals “Hives”

Transient (24-48 hrs.)

> 48 hrs = Urticarial vasculitis

• Tender.

• Residual

hyperpigmentation.

Urticaria

• Deep swellings of dermis &

subcutaneous & submucosal tissues

Angioedema Painful, rather than pruritic

and take longer time to

resolve.• Wheals & angioedema often coexist,

but may occur alone.

I. Ordinary urticaria:

The spectrum of urticaria

• Acute• Chronic (recurrent 6 weeks):

- idiopathic (50%) - autoimmune (25-50%).

II. Physical urticaria (35%)• Adrenergic urt.• Aquagenic urt.• Cholinergic urt.• Cold urt.• Delayed pressure

urt.

• Dermographism (8.5%)• Exercise-induced

anaphylaxis • Localized heat urt.• Solar urt.• Vibratory angioedema

III.Contact urticaria: biologic, chemical.IV. Urticarial vasculitis (proved by skin biopsy)

V. Angioedema (without wheals)

1. Ordinary urticaria (72%)

- Acute

- Chronic (often idiopathic)

2. Immune-complex urticaria

Urticarial vasculitis (2.1%).

3. Physical & cholinergic (20%).

Classification

4. Contact urticaria

5. Angio-edema

- Hereditary “C1 esterase INH deficiency”

(0.5%)

- Acquired

- ACEI-induced

- Episodic angio-edema with eosinophilia

6. Diseases with urticaria as a component

Classification

Urticarias

• Pathophysiology

• Acute allergic urticarias: Type-I reaction.

Mast cell activation may be allergic or

non-allergic.

Histamine, PGD2, LTC4, LTD4, PAF &

Bradykinin ® VD, increased cap.

permeability ® fluids extravasation.

Urticarias

• Pathophysiology (Cont)

• Acute allergic urticarias: ® Substance P.

Drugs (Aspirin, NSAIDs, Polymyxin)

Radiocontrast media

Anaesthetic agents

Potential Provoking FactorsPotential Provoking Factors

1. Drugs: penicillin, aspirin, sulfonamides,

NSAIDs, ….

2. Foods (eggs, fish, strawberries, milk, …

etc.) & food additives (Azo dyes,

benzoates, penicillin).

Urticarias

Potential Provoking Factors (Cont.)Potential Provoking Factors (Cont.)3. Inhalants: e.g. pollen grains, house dust,

feathers.

4. Infections e.g. focal sepsis in tonsils,

teeth or sinuses, or urinary tract

infections.

Urticarias

Recently, Helicobacter pylori has been

suggested.

Potential Provoking Factors (Cont.)Potential Provoking Factors (Cont.)

5. Infestations: Intestinal worms.

6. Emotional stress especially in

cholinergic urticaria.

7. Systemic disease: SLE, lymphomas,

thyrotoxicosis.

Urticarias

• Heterogeneous group of disorders.• Sudden appearance of itchy red

transient wheals.

Urticarias

Episodes of wheals “wheal come & go” for duration

Less than 6 wks

Acute

More than 6 wks

Chronic

• Onset and duration of individual wheals

Diagnosis (mainly clinical)

Physical urticarias: appear within 10 min. of the

trigger stimulus and clear within an hr.

Contact urticaria: arises within 10-30 min. of

exposure to the contactant and settles over 2 hrs.

Ordinary urticaria: fades after 2-24 hrs (here today

& gone tomorrow).

Diagnosis (mainly clinical) (Cont’d)

Delayed pressure urticaria: arises several hours

after sustained pressure

and lasts at least a day

Urticarial vasculitis: last several days,

may bruise

& tend to burn rather than itch.

Urticarial drug reactions: last several days.

Size of individual wheals

• Reflect disease activity

and response to therapy.

General examination

of

associated systemic

disease

Autoimmune urticaria• 26-50% of patients with chronic urticaria have

functional autoantibodies that release histamine from

basophils.

• The autologous serum skin test (ASST):

• Decrease or absent peripheral blood basophils

“clinical marker”.

• Basophil histamine release assay is most specific.

• Clinically pts with and without autoantibodies are

similar!!

High sensitivity & high specificity. Reduced by oral antihistamines.

Physical urticarias

• Characterized by the predominant

physical stimulus that elicits them.

• Common for one form to overlap with

another, such as dermographism and

cholinergic urticaria.

Physical urticarias (Cont’d)

• Can also co-exist with ordinary

urticaria, e.g. 40% of pts with chronic

ordinary urticaria have delayed

pressure urticaria.

• They may present with wheals or

angioedema &, very rarely, anaphylaxis.

• Confirming the diagnosis with physical

challenge tests.

• A specific physical stimulus ® whealing.

• Cholinergic urticaria: micropapular

wheals in association with sweating

caused by heat, emotion or gus5tatory

stimuli.

Physical & Cholinergic urticarias

• Dermographism

Physical urticarias

- Immediate symptomatic- Red- Cholinergic- Delayed- With mastocytosis- White

I. Mechanical force Prevalence

++++-++++

+++-• Delayed pressure urticaria

• Vibratory angioedema

• Heat urticaria• Cholinergic urticaria

II. Heat Prevalence

+-+++

++++-

++

Physical urticarias (cont)

III. Cold

• Acquired• Due to cryoglobulins• Familial

IV. Solar

V. Aquagenic

VI. Contact urticaria

Symptomatic dermographism

• Red, itchy, linear wheal appearing within minutes of

light stroking of the skin.

• DD: Linear asymptomatic reddening commonly

seen in healthy people after scratching.

Blanching response seen in atopic eczema

white dermographism.

Cholinergic urticaria

• Multiple transient papular wheals 2-3

mm in diameter surrounded by a pink

flare.

• Caused by a rise in core temperature

due to exercise, overheating or stress.

Cholinergic urticaria (Cont’d)

• Angioedema is uncommon.

• Cholinergic sympathetic

innervation of sweat glands is

involved.

• Exercise-induced anaphylaxis may

resemble cholinergic urticaria in

some cases.

Delayed pressure urticaria

• The onset of urticaria is delayed from 2-

6 hrs after pressure is applied

perpendicularly to the skin.

• Mainly in palms, soles and lower back.

• The swellings tend to be deeper & more

painful than those of ordinary urticaria

& last 24 hrs or more.

Delayed pressure urticaria (Cont’d)

• Increased levels of IL-6.

• Poor response to antihistamines.

• Oral corticosteroids are often

necessary for disease control.

Cold urticaria

• The rapid onset of confluent or papular

wheals on the face, neck or hands after cold

exposure followed by rewarming of the skin.

• Angioedema or anaphylaxis may also occur

when it is severe.

• All acquired cold urticarias are idiopathic

(essential) & associated with short-lived

whealing.

Urticarial vasculitis

• Patients present with both urticaria &

arthritis

Normocomplementemic urticarial vasculitis is

usually idiopathic.

Hypocomplementemic urticarial vasculitis may

be associated with underlying SLE, Sjogren’s

syndrome or cryoglobulinemia closely linked

with hepatitis B or C virus.

• Treatment:

Urticarial vasculitis

- H1 + H2 bockers + NSAIDs

- Colchicine or dapsone

- Syst. Steroids

- Cytotoxic immunosuppressives

Investigations

• Blood tests are unnecessary.

• Blood eosinophilia should prompt stool examination

for parasitic infestations.

• ESR may be raised in urticarial vasculitis or

Schnitzler’s syndrome (recurrent urticaria, bone pain,

fever, high ESR and IgM paraprotenemia).

Investigations (Cont’d)

• Thyroid autoantibodies.

• Dietary exclusion.

• Oral challenge may reveal food

additives as a cause of chronic

urticaria.

• Skin biopsy is essential to confirm

urticarial vasculitis.

Management

of

Chronic Ordinary

Urticaria

Management of chronic ordinary urticaria

Remove identifiable cause

A) Non-drug therapy

1. General advice• Explanation and information.

• Cooling lotions, e.g. calamine or 1.0%

menthol in aqueous cream.

2. Avoidance of aggravating factors• Avoid aspirin, NSAIDs, codeine, morphine,

ACE inhibitors.

• Minimize stress, overeating, alcohol.

Management of chronic ordinary urticaria

A) Non-drug therapy (Cont’d)

3. Diet

• Exclusion diet: when indicated by history or

blinded placebo-controlled challenge, e.g. food

coloring and preservative avoidance.

• Low pseudoallergen diet: for 2-3 week trial in

drug non-responsive idiopathic urticaria.

Management of chronic ordinary urticaria

Remove identifiable cause

Pharmacological therapy

FIRST LINE

Fexofenadine (Telfast) 180

If little or no response

add sedating H1 antihistamine at

night

If little or no response

add H2 antagonist

All patients

Management of chronic ordinary urticaria

Pharmacological

therapySECOND LINE

Corticosteroids (for severe ordinary or delayed

pressure urticaria)

Short term use only

Epinephrine (severe throat angioedema or anaphylaxis

only)

Others (as determined by history & investigations)

Special indications

Management of chronic ordinary urticaria

Pharmacological

therapy

THIRD LINE

Immunotherapy

(severe refractory autoimmune

urticaria only)

Specialist use only