Reactive erythemas and vasculitis

Urticaria
• Definitions:

- It is a common reaction pattern in which pink, itchy or burning

swelling (wheal) can occur anywhere in the body.

- Lesions are evanescent (individual lesions do not last for longer

than 24h) – a rash that comes and goes-
Distribution: Generalized
Type of lesion: Wheals

- Divided into : according to duration of eruption

1- Acute ( if the duration < 6 week)
2- Chronic ( if the duration > 6 week)
• Chemicals (Aspirin)
• Type 1 hypersensitivity (IgE mediated)
• Autoimmune (Antibodies directed at IgE receptors
on Mast cells)
• Trauma
• Spontaneous (Chronic Urticaria)

Mast cell degranulation

Releasing of chemicals like:
1- Histamine
2- Heparin
3- Protease
4- 5-hydroxytryptamine
5- Inflammatory mediators (PG, IL, neutrophils & eosinophils)

These chemicals will lead to increase in the capillary

permeability >> Transient leakage of fluid >> Developing
wheal
1- Physical urticaria:
a- Cold urticaria:
Patient develop wheal in the area exposed to cold (face).

b- Solar urticaria:
Wheal occur within minutes of sun exposure (direct contact is not necessary).
Some patient may have erythropoietic protoporphyria (Autosomal dominant
condition caused by mutation in ferrochelatase gene), and most of the patients
have IgE mediated urticarial reaction to sun light.

c- Heat urticaria:
Wheal arises in the area that was in contact with a hot object.
d- Cholinergic urticaria:
It is response to anxiety ,heat, sexual excitement or strenuous exercise. Here the vessels
over-react to acetylcholine released from sympathetic nerves in the skin. It is a transient
2-5 mm follicular macule or papule that resemble a blush or viral exanthem. On neck, chest,
and back.

e- Dermographism:
Scratching the skin by a tunk depressor, few minutes later wheals will develop and this can
be normal in 5%.
The most common type of physical urticaria; here the skin mast cells release extra-
histamine after excessive rubbing or scratching, leaving a linear wheal.
Here it’s red Dermographism, white Dermographism is seen in atopic eczema.

f- Delayed pressure urticaria:

Sustained pressure causes edema of the underlying skin and subcutaneous tissue 3-6 hr
later. And the swelling lasts up to 48 hr. Kinins and PG mediated (Not histamine).
Common site for this type: feet after walking, hands after clapping, and buttocks after
sitting.
The word dermographism scratched on
the forearm of a patient.
2- Hypersensitivity urticaria:
- The commonest type of urticaria.
- Caused by IgE mediated (type 1) hypersensitivity.
- The ten I’s of antigen encounter in hypersensitivity urticaria:
1- Ingestion
2- Inhalation
3- Instillation
4- Injection
5- Insertion
6- Insect bite
7- Infection
8- Infusion
9- Infestation
10- Inunctions (contact)
3- Autoimmune urticaria:
Patient with chronic urticaria has autoimmune disease of IgG
antibodies that bind to to IgE or to Fc IgE receptors on mast
cells leading to mast cell degranulation.
4- Pharmacological urticaria:
Drugs cause the mast cell to release histamine in a non-allergic
manner.
-Ex.: Aspirin, NSAIDs, ACEI, morphine.
So drug history is important in urticaria.
5- Contact urticaria:
This is may be IgE mediated or caused by
a pharmacological effect.

- Wheals occur most often around the

mouth.
- Food and food additives are the most
common culprits.
- Latex allergy
❖Angioedema
- Variant of urticaria
- Primarily affects SC tissues, so
> Less demarcated
> Less red
- Most commonly occurs at junctions between skin and
mucous membranes (peri-orbital, peri-oral and genital
areas)
- May be associated with swelling of the tongue and
laryngeal mucosa .
- Sometimes accompanies chronic urticaria.
• Complication of urticaria :

- Normally it is an uncomplicated condition but the itch

may lead to sleep disturbances, decreased activity and
depression.
- some can present with an anaphylactic shock
(angioedema) if it affected the laryngeal mucosa it can
lead to asphyxiation.
• DDx of urticaria :

1. Infestations and insect bites but those have a central punctum and may
last more than 24 hrs
2. Erythema multiform
3. Urticarial vasculitis but here the lesions last more than 24hrs
4. Bullous disease they start as urticarial lesions but then the
bullae makes the diagnosis obvious
5. Hereditary angioedema
- Some endogenous cause of - Some exogenous cause of urticaria:
urticaria :
1- Drugs
1- Infection 2- Food
2- Intestinal parasite 3- Bites
3- Connective tissue disorder 4- Pollens
4- Hyper-eosinophilic syndrome 5- Insect
5- Hyperthyroidism 6-Animal
6- Cancer, lymphoma
• Treatment :

• Identify the causing agent (If suspected) and avoid it

• We can use anti histamines (mainstay)
• New Second generation (anti-h1 blockers) cause no sedative effect
• cetirizine, levocetirizine, desloratadine, loratadine, and fexofenadine.
• Should be taken daily even if the patient does not have any wheals.
• After 1 month wheal-free period we stop it.
• If not responding the dose can be increased up to 4 times.
• If still not responding we grade up the treatment
• Montelukast: leukotriene antagonist
• Ciclosporin
• Biological agents: Omalizumab monoclonal antibody that binds to free IgE
• In sever cases epinephrine or psudoepinephrine can be used, but causes
sedation
Erythema multiforme
Erythema multiforme

• An acute, self-limiting but often relapsing,

mucocutaneous inflammatory condition.
• Hypersensitivity response induced by a variety of causes;
infections, drugs (the type is complex)…
• Characterized clinically by target lesions.
• In many cases the etiology is not identified.
Possible triggers

• Idiopathic cause
• Recent infection:
❖Herpes simplex virus
❖Mycoplasma pneumoniae
❖Hepatitis A, B and C
o Drugs: antimalarials, anticonvulsants, lidocaine injections, sulfa-based medications, and
NSAIDs
o Pregnancy
o Malignancy
o Recent vaccination
Presentation

• Preceded by a possible trigger

• ACROFACIAL distribution
• Type of lesion: targetoid lesion
• Presents with multiple types of lesions—macules, papules, vesicles, typical target lesions; annular
erythematous rings with an outer erythematous zone and central blistering and atypical targetoid
papules with no central blistering.
• The lesions have a rapid onset and usually increase in number over 4 to 7 days. They can cause
general discomfort but are not itchy until they start to heal.
• Typically presents in a symmetrical distribution of lesions over the dorsal surfaces of the
extensor extremities with minimal mucous membrane involvement.
• The lesions heal within 1-2 without scarring.
Differential diagnosis

• Annular variant of urticaria

• While urticaria may recur, resolution of lesions in 24 hours is the norm
• central blistering and target lesions will be absent
• Other bullous disorders
• EN
• Vasculitis
 Investigations & Complications

• Most cases of EM can be diagnosed by history and clinical examination alone, and
no further investigations are needed. If uncertain biopsy can be carried out though
not routine.
• Other Investigations are directed at identifying a cause
• CBC; abnormal white cell count
• For HSV : Tzanck smears (multinucleated giant cells), culture and chest x-rays
• For Mycoplasma pneumoniae: serology tests , and chest x-ray

• Complications:
• With EM there are usually no complications though secondary bacterial infection may develop
 Management

• EM is self-limiting, with management based on the following strategies:

• Supportive care to maintain hydration and prevent erosions from developing secondary bacterial
infection
• Treatment of suspected precipitating infections
• Suppression therapy with antivirals if recurrent disease is caused by herpes simplex virus (HSV)
• Topical or systemic corticosteroids to reduce inflammation.
Erythema Nodosum
• Definition:

- Inflammation to the subcutaneous fat. (Panniculitis)

- It is an immunological reaction caused by bacteria , viral or fungal

infection & drugs or systemic disease.
- In general the most common cause is idiopathic, but if there was
a cause the most common one is recent infection (URTI)
• Presentation:
- The lesion is tender, red nodules develop alone or in groups
on shins (most common site)& forearms.
- Some patient have painful joint & fever.
- Individual Lesions last up to 2 weeks, the whole condition
(disease/erruption) usually resolves in 6-8 week.
• Complication:

1- Walking difficulty.
2- Erythema nodosum leprosum occur when lepromatous leprosy patient
establish cell-mediated immunity to mycobacterium leprae ( sever fever .
malaise, lethargy). Not a complication but rather a different entity/variant.
►Differential diagnosis:

-Trauma.
-Infection (Cellulitis).
-Phlebitis.
-Polyartritis nodosa.
-alpha1-antitrypsin deficiency. Causes Panniculitis.
- Systemic lupus erythromatous. Causes Panniculitis.
- Urticaria
- EM
- Vasculitis
Causes
• The most common cause is idiopathic.
• If we have a cause the most common one is infection whether
bacterial or viral.
• TB (ask about travel history, respiratory symptoms)
• Pregnancy
• Oral contraceptives
• Drugs (penicillin, iodide)
• IBD
• Sarcoidosis (ask about respiratory symptoms)
• Connective tissue disease: Lupus
• Malignancy
• Investigation:

- History & PE.

- Chest x-ray. (TB & Sarcoidosis)
- Throat culture for streptococcus.
- Interferon-gamma-release assay (TB) & ASO titer (for strep
infection).
• Treatment:

- Identify& eliminate the cause.

- Antibiotics. Usually we don’t use it unless we have strept infection.
- Bed rest
- Leg elevation
- Lesions are painful so NSAIDs.
- Potassium iodide.
Vasculitis
• inflammation around superficial or deep blood vessels.

• showing inflammation within the vessel wall, with endothelial cell

swelling, necrosis or fibrinoid change.

• The clinical manifestations depend upon the size of the blood vessel
affected
• Types:
1. Leucocytoclastic vasculitis (small blood vessel vasculitis)
2. Polyartiritis nodosa (medium blood vessels vasculitis)
3. Wegners granulomatosis (small - medium blood vessels vasculitis)
1. Leucocytoclastic (small vessel) vasculitis
(allergic or hypersensitivity vasculitis, anaphylactoid purpura)

• Pathogenesis
Immune complexes may lodge in the walls of blood
vessels, activate complement and attract
polymorphonuclear leucocyte.
Enzymes released from these can degrade the vessel
wall.
Type 3 hypersensitivity reaction.
 Presentation
The most common presentation of vasculitis is
painful palpable purpura.
Lesions arise in dependent areas (the forearms
and legs) in ambulatory patients, or on the
buttocks and flanks in bedridden one.
Some have a small, livid or black center, caused by
necrosis of the tissue overlying the affected blood
vessel.

6/20/2021
• Henoch–Schönlein purpura is an IgA mediated small vessel
vasculitis
associated with palpable purpura, arthritis and abdominal
pain, often preceded by an upper respiratory tract infection.
Children are most commonly, but not exclusively affected.
• Henoch-Schönlein purpura.
Palpable purpuric lesions are most common on dependent areas the
lower extremities and buttocks but can appear on the arms, face, and
ears, the trunk is usually spared.
 Investigation
• Urine analysis ,checking for proteinuria and
haematuria(RBC cast)
• kidney function test
-skin biopsy(confirmatory test )
How to diagnose Henoch–Schönlein
purpura ?
• HX ,PE
Differential diagnosis
1. Clotting system disorders
2. Sepsis. (mainly mengiococcemia can present with petechia and
purpura)
3. Reactive erythemas

Treatment:
• Children: supportive, if recurrent /severe ==>steroid
• Adult :steroid ,cyclophosphamide
• So anti-inflammatory agents to control the inflammation, and to prevent
disease progression.
Urticarial vasculitis
• Urticarial vasculitis
a small vessel vasculitis characterized by urticaria-like lesions
which last for longer than 24 h, leaving bruising and then
pigmentation (haemosiderin) at the site of previous lesions.
There may be foci of purpura in the wheals and other skin signs
include angioedema.
General features include malaise and arthralgia.
Urticarial vasculitis causes :
SLE
RA
DRUGS
CANCER
INFECRION
SYSTEMIC VASCULITIS SYNDROM

Differential diagnosis
1-clotting system disorders
2-sepsis.
3-Urticaria.
Vasculitic purpuras are raised (palpable).

Complications:
According to the underlying cause(SLE/RA: systemic, drugs: mostly cutaneous)
-Vasculitis may simply be cutaneous.
-systemic 🡺 other organs will be damaged, including the kidney, central nervous system, gastrointestinal tract
and lungs.

THE MOST SERIOUS COMPLICATION IS KIDNEY INVOLVEMENT, that’s why urine analysis and KFT are a must for
any patient presenting with vasculitis.
• Investigations:

1- Identify the cause and detect internal involvement.

2- Chest x-ray, ESR.
3- the most important test is urine analysis ,checking for
proteinuria and haematuria.
4-Skin biopsy
5- Finding of circulating immune complexes.
6- Decrease total complement or decrease C4.( lupus, RA)
7- Test for hepatitis, RF, ANA, cryoglobulins.
8- Direct immunoflurescence.
9- HSP vasculitis is confirmed by IgA deposit in the blood vessels.
• Treatment:

1- Identify cause & eliminate it.

2- Bed rest & antihistamine.
3- Cholchicine & dapsone.
4- Systemic corticosteroid or immunosuppressant agent
(cyclophosohamide) for those whose vasculitis is damaging the
kidneys or other internal organs.