Allergic diseases. Anaphylactic shock. Quincke’s edema.
Oral manifestation of allergic lesions (erythema multiforme,
reccurent aphtous stomatitis).
Hypersensitivity
Hypersensitivity refers to excessive,
undesirable (damaging, discomfort-producing and sometimes fatal) reactions
produced by the normal immune system. Hypersensitivity reactions require a
pre-sensitized (immune) state of the host. Hypersensitivity reactions can be
divided into four types: type I, type II, type III and type IV, based on the mechanisms
involved and time taken for the reaction. Frequently, a particular clinical
condition (disease) may involve more than one type of reaction.
TYPE I
HYPERSENSITIVITY
Type I hypersensitivity is also known as
immediate or anaphylactic hypersensitivity. The reaction may involve skin (urticariaand eczema), eyes (conjunctivitis), nasopharynx (rhinorrhea, rhinitis), bronchopulmonary tissues (asthma) and
gastrointestinal tract (gastroenteritis). The reaction may cause a range of
symptoms from minor inconvenience to death. The reaction usually takes 15 - 30
minutes from the time of exposure to the antigen, although sometimes it may
have a delayed onset (10 - 12 hours).
Immediate
hypersensitivity is mediated by IgE. The primary cellular
component in this hypersensitivity is the mast cell or basophil. The reaction
is amplified and/or modified by platelets, neutrophils and eosinophils. A
biopsy of the reaction site demonstrates mainly mast
cells and eosinophils.
The
mechanism of reaction involves preferential production of IgE, in response to
certain antigens (often called allergens). The
precise mechanism as to why some individuals are more prone to type-I
hypersensitivity is not clear. However, it has been shown that such individuals
preferentially produce more of TH2 cells that secrete IL-4, IL-5 and IL-13
which in turn favor IgE class switch. IgE has very high affinity for its
receptor (Fcε; CD23) on mast cells and basophils.
A
subsequent exposure to the same allergen cross links the cell-bound IgE and triggers
the release of various pharmacologically active substances (figure 1).
Cross-linking of IgE Fc-receptor is important in mast cell triggering. Mast
cell degranulation is preceded by increased Ca++ influx, which is a crucial process; ionophores which increase cytoplasmic Ca++also
promote degranulation, whereas, agents which deplete cytoplasmic Ca++ suppress degranulation.
The
agents released from mast cells and their effects are listed in Table 1. Mast
cells may be triggered by other stimuli such as exercise, emotional stress,
chemicals (e.g., photographic developing medium, calcium ionophores, codeine, etc.),anaphylotoxins (e.g., C4a, C3a, C5a, etc.). These reactions, mediated by
agents without IgE-allergen interaction, are not hypersensitivity reactions,
although they produce the same symptoms.
|
Table 1. Pharmacologic Mediators of Immediate Hypersensitivity |
|
|
MEDIATOR |
|
|
Preformed mediators in granules |
|
|
histamine |
bronchoconstriction,
mucus secretion, vasodilatation, vascular permeability |
|
tryptase |
proteolysis |
|
kininogenase |
kinins and vasodilatation, vascular permeability,
edema |
|
ECF-A |
attract eosinophil and neutrophils |
|
Newly formed mediators |
|
|
leukotriene
B4 |
basophil
attractant |
|
leukotriene
C4, D4 |
same as
histamine but 1000x more potent |
|
prostaglandins
D2 |
edema and
pain |
|
PAF |
platelet
aggregation and heparin release: microthrombi |
The reaction is amplified by PAF (platelet activation factor)
which causes platelet aggregation and release of histamine, heparin and
vasoactive amines. Eosinophil chemotactic factor of anaphylaxis (ECF-A) and
neutrophil chemotactic factors attract eosinophils and neutrophils,
respectively, which release various hydrolytic enzymes that cause necrosis.
Eosinophils may also control the local reaction by releasing arylsulphatase, histaminase, phospholipase-D and prostaglandin-E, although this role of eosinophils is now in question.
Cyclic nucleotides appear to play a significant role in
the modulation of immediate hypersensitivity reaction, although their exact
function is ill understood. Substances which alter cAMP and cGMP levels
significantly alter the allergic symptoms. Thus, substances that increase
intracellular cAMP seem to relieve allergic symptoms, particularly
broncho-pulmonary ones, and are used therapeutically (Table 2). Conversely,
agents which decrease cAMP or stimulate cGMP aggravate
these allergic conditions.
|
Table 2 - Relationship
between allergic symptoms and cyclic-nucleotides |
|
|
Lowering of cyclic-AMP |
elevation of cyclic-AMP |
|
stimulation of α-adrenergic
receptor or blocking
of β-adrenergic receptor |
stimulation of β-adrenergic
receptor blocking of α-adrenergic
receptor inhibition of phosphodiesterase binding of
histamine-2 or PGE to their receptors |
|
elevation of cyclic-GMP |
|
|
stimulation
of γ-cholinergic receptor |
|
|
WORSENING OF SYMPTOMS |
IMPROVEMENT OF SYMPTOMS |
Diagnostic
tests for immediate hypersensitivity include skin (prick and intradermal) tests
(fig. 1A), measurement of total IgE and specific IgE antibodies against the
suspected allergens. Total IgE and specific IgE antibodies are measured by a
modification of enzyme immunoassay (ELISA). Increased IgE levels are indicative
of an atopic condition, although IgE may be elevated in
some non-atopic diseases (e.g., myelomas, helminthic infection, etc.).
There
appears to be a genetic predisposition for atopic
diseases and there is evidence for HLA (A2) association.
Figure 1A close-up view of intradermal skin test with
multiple positive allergen responses
Symptomatic treatment is achieved with
anti-histamines which block histamine receptors. Chromolyn sodium inhibits mast
cell degranulation, probably, by inhibiting Ca++ influx. Late onset allergic symptoms,
particularly bronchoconstriction which is mediated by leukotrienes, are treated with leukotriene receptor blockers
(Singulair, Accolate) or inhibitors of thecyclooxygenase pathway (Zileutoin). Symptomatic, although short
term, relief from bronchoconstriction is provided by bronchodilators
(inhalants) such as isoproterenol derivatives (Terbutaline, Albuterol). Thophylline
elevates cAMP by inhibiting cAMP-phosphodiesterase and inhibits intracellular
Ca++ release is also
used to relieve bronchopulmonary symptoms.
The use of IgG antibodies against the Fc
portions of IgE that binds to mast cells has been approved for treatment of
certain allergies, as it can block mast cell sensitization.
Hyposensitization (immunotherapy or
desensitization) is another treatment modality which is successful in a number
of allergies, particularly to insect venoms and, to some extent, pollens. The
mechanism is not clear, but there is a correlation between appearance of IgG
(blocking) antibodies and relief from symptoms. Suppressor T cells that
specifically inhibit IgE antibodies may play a role.
TYPE II
HYPERSENSITIVITY
Type II hypersensitivity is also known as
cytotoxic hypersensitivity and may affect a variety of organs and tissues. The
antigens are normally endogenous, although exogenous chemicals (haptens) which can attach to cell membranes can also lead to
type II hypersensitivity. Drug-induced hemolytic anemia, granulocytopenia and thrombocytopenia are such examples. The reaction time is minutes to
hours. Type II hypersensitivity is primarily mediated by antibodies of the IgM
or IgG classes and complement (Figure 2). Phagocytes and K cells may also play
a role.
Figure 2. Type II cytotoxicity mechanism
The lesion contains antibody, complement
and neutrophils. Diagnostic tests include detection of circulating antibody
against the tissues involved and the presence of antibody and complement in the
lesion (biopsy) by immunofluorescence. The staining pattern is normally smooth
and linear, such as that seen in Goodpasture's nephritis (renal and lung basement membrane) (figure
3A) and pemphigus (skin intercellular protein, desmosome) (figure 3B).
Figure 3A Immunofluorescent stain of
immunoglobulin G (IgG) showing linear pattern in Goodpasture's syndrome
Figure 3B Pemphigus vulgaris - immunofluorescence
Treatment involves anti-inflammatory and
immunosuppressive agents.
TYPE III
HYPERSENSITIVITY
Type III hypersensitivity is also known as
immune complex hypersensitivity. The reaction may be general (e.g.,
serum sickness) or may involve individual organs including skin (e.g.,
systemic lupus erythematosus, Arthus reaction), kidneys (e.g., lupus
nephritis), lungs (e.g., aspergillosis), blood vessels (e.g., polyarteritis), joints (e.g., rheumatoid arthritis) or
other organs. This reaction may be the pathogenic mechanism of diseases caused
by many microorganisms.
The reaction may take 3 - 10 hours after
exposure to the antigen (as in Arthus
reaction). It is mediated by soluble
immune complexes. They are mostly of the IgG class, although IgM may also be
involved. The antigen may be exogenous (chronic bacterial, viral or parasitic
infections), or endogenous (non-organ specific autoimmunity: e.g., systemic lupus
erythematosus, SLE). The antigen is soluble and not attached to the organ
involved. Primary components are soluble immune complexes and complement (C3a,
4a and 5a). The damage is caused by platelets and neutrophils (Figure 4). The
lesion contains primarily neutrophils and deposits of immune complexes and
complement. Macrophages infiltrating in later stages may be involved in the
healing process.
Figure 4. Mechanism of damage in immune complex
hypersensitivity
The affinity of antibody and size of immune complexes are
important in production of disease and determining the tissue involved.
Diagnosis involves examination of tissue biopsies for deposits of
immunoglobulin and complement by immunofluorescence microscopy. The
immunofluorescent staining in type III hypersensitivity is granular (as opposed
to linear in type II such as seen in
Goodpasture's syndrome). The presence of immune complexes in serum and
depletion in the level of complement are also diagnostic. Polyethylene
glycol-mediated turbidity (nephelometry)
binding of C1q and Raji cell
test are utilized to detect
immune complexes. Treatment includes
anti-inflammatory agents.
TYPE IV
HYPERSENSITIVITY
Type IV hypersensitivity is also known as
cell mediated or delayed type hypersensitivity. The classical example of this
hypersensitivity is tuberculin (Montoux) reaction (figure 5)
Figure 5
Mantoux intradermal tuberculin skin test for
tuberculosis
which peaks 48 hours after the injection of
antigen (PPD or old tuberculin). The lesion is characterized by induration and erythema.
|
Table 3
- Delayed hypersensitivity reactions |
||||
|
Type |
Reaction time |
Clinical appearance |
Histology |
Antigen and site |
|
contact |
48-72 hr |
eczema |
lymphocytes,
followed by macrophages; edema of epidermis |
epidermal
(organic chemicals, poison ivy, heavy metals, etc.) |
|
tuberculin |
48-72 hr |
local
induration |
lymphocytes,
monocytes, macrophages |
intradermal
(tuberculin, lepromin, etc.) |
|
granuloma |
21-28 days |
hardening |
macrophages,
epitheloid and giant cells, fibrosis |
persistent
antigen or foreign body presence (tuberculosis, leprosy, etc.) |
Type IV
hypersensitivity is involved in the pathogenesis of many autoimmune and
infectious diseases (tuberculosis, leprosy, blastomycosis, histoplasmosis,
toxoplasmosis, leishmaniasis, etc.)
and granulomas due to infections and foreign antigens. Another form
of delayed hypersensitivity is contact dermatitis (poison ivy (figure 6),
chemicals, heavy metals, etc.)
in which the lesions are more papular. Type IV hypersensitivity can be classified into
three categories depending on the time of onset and clinical and histological
presentation (Table 3).
Figure 6 Poison Ivy
Mechanisms of damage in delayed
hypersensitivity include T lymphocytes and monocytes and/or macrophages.
Cytotoxic T cells (Tc) cause direct damage whereas helper T (TH1) cells secrete
cytokines which activate cytotoxic T cells and recruit and activate monocytes
and macrophages, which cause the bulk of the damage (figure 4). The delayed
hypersensitivity lesions mainly contain monocytes and a few T cells.
Major lymphokines involved in delayed hypersensitivity
reaction include monocyte chemotactic factor, interleukin-2, interferon-gamma,
TNF alpha/beta, etc.
Diagnostic tests in vivo include delayed cutaneous reaction (e.g. Montoux test (figure 5)) and patch
test (for contact dermatitis). In vitro tests for delayed hypersensitivity
include mitogenic response, lympho-cytotoxicity and IL-2 production.
Corticosteroids and other immunosuppressive
agents are used in treatment.
|
Table 5 - Comparison of
Different Types of hypersensitivity |
||||
|
characteristics |
type-I |
type-II |
type-III |
type-IV |
|
antibody |
IgE |
IgG, IgM |
IgG, IgM |
None |
|
antigen |
exogenous |
cell
surface |
soluble |
tissues
& organs |
|
response
time |
15-30
minutes |
minutes-hours |
3-8 hours |
48-72
hours |
|
appearance |
weal &
flare |
lysis and
necrosis |
erythema
and edema, necrosis |
erythema
and induration |
|
histology |
basophils
and eosinophil |
antibody
and complement |
complement
and neutrophils |
monocytes
and lymphocytes |
|
transferred
with |
antibody |
antibody |
antibody |
T-cells |
|
examples |
allergic
asthma, hay fever |
erythroblastosis fetalis,
Goodpasture's nephritis |
SLE, farmer's lung disease |
tuberculin
test, poison ivy, granuloma |
Anaphylaxis.
Introduction
Anaphylaxis is a sudden onset (or
rapidly progressive) severe systemic allergic reaction, affecting multiple
organs. Its onset may be heralded by skin and/or mucosal changes (flushing,
urticaria, angio-oedema)
and progress to include life-threatening airway, lung and/or circulation
problems.
However, it is important in outlining guidelines to emphasise the importance of
prompt administration of adrenaline (epinephrine)
and resuscitation measures. Antihistamine use is included in the guidelines but
there is a lack of evidence either to support or refute their value in the
treatment of anaphylaxis. They are certainly very much secondary in importance
and useful to treat cutaneous manifestations of anaphylaxis but without
relieving airway symptoms or hypotension. Administration of antihistamines
should certainly never delay administration of adrenaline (epinephrine). There
is a similar lack of evidence for use of steroids, although they may have value
in preventing a biphasic reaction.
Incidence
The number
of people who suffer severe systemic allergic reactions is increasing. The
incidence is about 1-3 reactions per 10,000 population per annum, although
anaphylaxis is not always recognised, so certain UK studies may underestimate
the incidence.
Aetiology
An anaphylactic reaction occurs when an allergen
reacts with specific IgE antibodies on mast cells and basophils (type 1
hypersensitivity reaction), triggering the rapid release of stored histamine
and the rapid synthesis of newly formed mediators. These cause capillary
leakage, mucosal oedema and ultimately shock and asphyxia. Anaphylactic
reactions can vary in severity and rate of progression - they may progress
rapidly (over a few minutes) or occasionally in a biphasic manner. Rarely,
manifestations may be delayed by a few hours (adding to diagnostic difficulty),
or persist for more than 24 hours. Anaphylactoid reactions are not IgE-mediated
but cause similar mast cell activation.
A significant number of cases of anaphylaxis are idiopathic.
The most common triggers of anaphylaxis:
·
Foods:
o
Peanuts.
o
Pulses .
o
Tree nuts (e.g. brazil nut, almond,
hazelnut).
o
Fish and shellfish.
o
Eggs.
o
Milk.
o
Sesame.
·
Venom, for example:
o
Bee stings.
o
Wasp stings.
·
Drugs, including:
o
Antibiotics.
o
Opioids.
o
Non-steroidal anti-inflammatory
drugs (NSAIDs).
o
Intravenous (IV) contrast media.
o
Muscle relaxants.
o Other anaesthetic drugs.
Presentation
There is
often (but not always) a history of previous sensitivity to an allergen, or
recent history of exposure to a new drug (e.g. vaccination). Initially,
patients usually develop skin symptoms, including generalised itching,
urticaria and erythema, rhinitis, conjunctivitis and angio-oedema.
Signs that the airway is becoming involved include itching of the palate or
external auditory meatus, dyspnoea, laryngeal oedema (stridor)
and wheezing (bronchospasm). General symptoms include
palpitations and tachycardia (as opposed to bradycardia in simple
vasovagal episode at immunisation time), nausea, vomiting and abdominal pain,
feeling faint - with a sense of impending doom; and, ultimately, collapse and
loss of consciousness.
Airway swelling, stridor, breathing difficulty, wheeze, cyanosis, hypotension,
tachycardia and reduced capillary filling suggest impending severe reaction.
If no history is available in a collapsed patient, use an ABCDE advanced
life-support approach (see box, below) to recognise and treat an anaphylactic
reaction. Treat life-threatening problems as you find them. The basic
principles of treatment are the same for all age groups.
Differential diagnosis
Life-threatening
conditions:
·
Sometimes an anaphylactic reaction
can present with symptoms and signs that are very similar to
life-threatening asthma - this is
most common in children.
·
A low blood pressure (BP) - or
normal in children - with a petechial or purpuric rash can be a sign of septic
shock.
·
Seek help early if there are any
doubts about the diagnosis and treatment.
Non-life-threatening
conditions - these usually respond to simple
measures:
·
Faint (vasovagal episode).
·
Panic attack.
·
Breath-holding episode in a child.
·
Idiopathic (non-allergic) urticaria
or angio-oedema.
Emergency
treatment
Treatment in an emergency means
following without delay a systematic assessment and treatment plan.
|
Quick reference anaphylaxis algorithm · Rapid assessment: o Airway: look for
and relieve airway obstruction; call for help early if there are signs of
obstruction. Remove any traces of allergen remaining (e.g. nut fragments
caught in teeth, with a mouthwash; bee stings without compressing any
attached venom sacs). o Breathing: look
for and treat bronchospasm and signs of respiratory distress. o Circulation:
colour, pulse and BP. o Disability:
assess whether responding or unconscious. o
Exposure: assess skin with adequate exposure, but avoid excess heat loss. · Consider anaphylaxis when there is compatible history of rapid-onset
severe allergic-type reaction with respiratory difficulty and/or hypotension,
especially if there are skin changes present. · Give high-flow oxygen - using a mask with an oxygen reservoir (greater than 10 litres
min-1 to prevent reservoir collapse). · Lie the patient flat: o
Raise the legs (care, as this may
worsen any breathing problems). o In pregnant patients, use a left lateral tilt of at least 15° (to avoid
caval compression). · Adrenaline (epinephrine) intramuscularly (IM) in the anterolateral aspect of the middle
third of the thigh (safe, easy, effective): o
Adult IM dose 0.5 mg IM (= 500
micrograms = 0.5 mL of 1:1000) adrenaline (epinephrine). o
Child IM dose (the equivalent
volume of 1:1000 adrenaline (epinephrine) is shown in brackets): § >12 years: 500 micrograms IM (0.5 mL), i.e. the same as the adult
dose. § >6-12 years: 300 micrograms IM (0.3 mL). § <6 years: 150 micrograms IM (0.15 mL). o Note: half doses of
adrenaline (epinephrine) may be safer for patients on amitriptyline,
imipramine, monoamine oxidase inhibitor (MAOI) or beta-blocker. · When skills and equipment are available: o
Establish airway (in anaphylaxis,
airway obstruction from tissue swelling is difficult to overcome and early
expert intubation is often needed). o
IV fluid challenge: § Insert one or more large-bore IV cannulae (enable the highest flow). § Use intraosseous access (if trained to do so) in children when IV access
is difficult. § Give a rapid fluid challenge: § Adults - 500 mL of warmed crystalloid solution (e.g., Hartmann's or 0.9%
saline) in 5-10 minutes if the patient is normotensive or one litre if the
patient is hypotensive. § Use smaller volumes (e.g. 250 mL) for adult patients with known cardiac
failure and use closer monitoring (listen to the chest for crepitations after
each bolus). § The use of invasive monitoring, e.g., central venous pressure (CVP), can help to assess fluid resuscitation. §
For children - give 20 mL/kg of
warmed crystalloid. o
Chlorphenamine (after initial resuscitation). Dose depends on age: § >12 years and adults: 10 mg IM or IV slowly. § >6-12 years: 5 mg IM or IV slowly. § >6 months-6 years: 2.5 mg IM or IV slowly. §
<6 months: 250 micrograms/kg IM
or IV slowly. o
Hydrocortisone (after initial resuscitation). Dose depends on age: § >12 years and adults: 200 mg IM or IV slowly. § >6-12 years: 100 mg IM or IV slowly. § >6 months-6 years: 50 mg IM or IV slowly. § <6 months: 25 mg IM or IV slowly. o Monitor: § ECG § BP |
Monitoring
·
All critically ill patients should
be given oxygen.
·
Maintain the PaO2 as
close to normal as possible (approximately 13 kPa or 100 mm Hg).
·
When/if a pulse oximeter is
available:
o Titrate the oxygen to maintain an oxygen saturation of 94-98%.
o In the sickest patients this is not always possible so you may have to
accept a lower value, i.e., above 8 kPa (60 mm Hg), or 90-92% oxygen saturation
on a pulse oximeter.
·
A normal SpO2 on
oxygen does not necessarily mean ventilation is adequate (because the pulse
oximeter detects oxygenation and not hypercapnia). The patient may be breathing
inadequately (with a high PaCO2).
·
Use bag-mask ventilation while
calling urgently for expert help. In an anaphylactic reaction, upper airway
obstruction or bronchospasm can make bag mask ventilation difficult or
impossible.
· Consider early tracheal intubation (if equipment and expertise are
available). If the patient is intubated, give high-concentration oxygen with a
self-inflating bag.
Blood
pressure - reassess the pulse rate and BP regularly (every 5 minutes).
Aim for:
·
In adults, normal BP (or a systolic
BP greater than 100 mm Hg).
·
In children:
o 0 to1 month: minimum 50-60 mm Hg.
o >1 to12 months: minimum 70 mm Hg.
o >1 to 10 years 70+ (age in years x 2) mm Hg.
o >10 years: minimum 90 mm Hg.
·
If the patient does not improve,
repeat the fluid challenge.
·
If there are symptoms and signs of
cardiac failure (shortness of breath, increased heart rate, raised JVP, a third
heart sound, and inspiratory crackles in the lungs on auscultation):
o Decrease or stop the fluid infusion.
o Seek expert help (inotropes or vasopressors may be needed).
Follow-up
When time
allows:
·
Immediate:
o
Take a full history from the patient (relatives,
friends, and other staff).
o
Review the patient's notes and charts. Study both
absolute and trends of values relating to vital signs.
o
Check that important routine medications are prescribed
and being given.
o
Review the results of laboratory or radiological
investigations.
o
Consider what level of care is required by the
patient, e.g., transport to hospital if in the community.
o
In the patient's notes, make complete entries of your
findings, assessment and treatment. Record the patient's response to therapy.
o
Consider definitive treatment of the patient's
underlying condition.
·
In the long term:
o
Refer to an allergist or allergy clinic to try to
identify the allergen, so that it can be avoided in future.
o
Organise self-use of pre-loaded pen injections for
future attacks (e.g. EpiPen®; containing 0.3 mL of 1 in 1000 strength (that is,
300 micrograms) for adults; and for children 0.3 mL of 1 in 2000 (150
micrograms)). This again may be best done in allergy clinics.
o
Give a written self-management plan and arrange to
teach the patient and relatives how to use syringes
Angioedema
Angioedema or Quincke's
edema is the rapid swelling (edema) of the dermis, subcutaneous
tissue,mucosa and submucosal tissues.
Symptoms:
•
The skin of the face,
normally around the mouth, and the mucosa of the mouth and/or throat, as well
as the tongue, swell up over the period of minutes to several hours.
•
The swelling can also
occur elsewhere, typically in the hands. The swelling can be itchy or
painful.
•
There may also be
slightly decreased sensation in the affected areas due to compression of the
nerves.
•
Urticaria(hives) may
develop simultaneously.
•
In severe
cases, stridor
of the airway occurs, with gasping or wheezy inspiratory
breath sounds and decreasing oxygen levels.
Causative factors:
•
Food related products
for Quincke's edema associated with urticaria.
•
Drugs like
penicillin, aspirin, phenytoin and others,
•
Infection- bacterial
and viral
•
Venoms, medication and
food can induce anaphylaxis in sensitized individuals.
•
•
Hereditary
angio-oedema is an autosomal-dominant disorder associated with recurrent
episodes of edema of the subcutaneous tissue without.
•
•
Onset is usually
in early childhoodbut may be delayed even into late adult life.
Treatment
•
Angioneurotic odema is
a medical emergency, it always better to seek the medical help immediately
•
To give airway support
in case of medical support
•
Antihistamines
•
Corticosteroids
•
Adrenaline in acute
condition
•
C1 esterase inhibitors
in case of hereditary angioneurotic edema
Erythema multiforme
Erythema multiforme (EM) is an acute, self-limited, and
sometimes recurring skin condition that is considered to be a type IV
hypersensitivity reaction associated with certain infections, medications, and
other various triggers.
Symptoms:
•
Fever
•
General ill feeling
•
Itching of the
skin
•
Joint aches
•
Multiple skin
lesions:
– Start quickly and may return
– May spread
– May appear as a nodule, papule,
or macule and may look like hives
– Central sore surrounded by pale red rings, also called a
"target", "iris", or "bulls-eye"
– May have vesicles and blisters of various sizes
(bullae)
– Located on the upper body, legs, arms, palms, hands, or feet
– May involve the face or lips
– Usually even on both sides (symmetrical)
History:
•
In EM, there may be no
prodrome or a mild upper respiratory tract infection.
•
The rash starts
abruptly, usually within 3 days. It starts on the extremities, being
symmetrical and spreading centrally.
•
Half of children with
the rash have recent herpes labialis.
•
It usually precedes
the erythema multiforme by 3 to 14 days but it can sometimes be present at the
onset.
Examination:
•
The iris or target
lesion is the classical feature of the disease.
•
Initially there is a
dull red flat spot or wheal that enlarges slightly up to 2 cm over 24 to 48
hours.
•
In the middle, a small
bump, vesicle, or bulla develops, flattens, and then may clear. The
intermediate ring forms and becomes raised, pale, and swollen. The periphery
slowly becomes purple and forms a concentric lesion, resembling a target. Some
lesions are atypical targets with only 2 concentric rings.
•
The Koebner phenomenon
may occur. This is where a lesion occurs along the line of trauma and it is typical
of psoriasis and lichen planus.
•
Lesions appear first
on the extensor surfaces of the periphery and extend centrally. The palms, neck
and face are often involved but the soles and flexures of the extremities less
often.
•
There may be mucosal
involvement in 70% of patients but it tends to be mild and limited to just one
mucosal surface (for example mouth or vulva).
•
Oral lesions are most
common with lips, palate and gingiva affected. There may be red conjunctivae
and tearing, but eye involvement tends to be mild.
•
Genital involvement
can produce painful hemorrhagic bullae and erosions.
Investigations:
No specific investigations are indicated.
•
Nikolsky's sign is positive
•
A punch biopsy may be
required to confirm diagnosis.
Management:
In recurrent disease due to HSV, antiviral therapy is helpful.
•
Symptomatic treatment
may include analgesics, mouth wash and local skin care.
•
Steroid creams may be
used. If the mouth is very sore, attention may have to be given to hydration
and nutrition.
•
Lubricating drops for
eyes may be required.
Skin Tests
Scratch test (also known as a
puncture or prick test). This test is
done by placing a drop of a solution containing a possible allergen on the
skin, and a series of scratches or needle pricks allows the solution to enter
the skin. If the skin develops a red, raised itchy area (called a wheal), it
usually means that the person is allergic to that allergen. This is called a
positive reaction.
Intradermal test.
Intradermal test. After examining and cleaning the skin, a small amount
of the allergen is injected just under the skin, similar to
a tuberculosis test.
•
During this
test, a small amount of the allergen solution is injected into the skin.
•
An
intradermal allergy test may be done when a substance does not cause
a reaction in the skin prick test but is still suspected as an allergen for
that person.
•
The intradermal test is more sensitive than the skin prick
test but is more often positive in people who do not have symptoms to that
allergen (false-positive test results).
Patch test.
For a skin patch test, the allergen solution is placed
on a pad that is taped to the skin for 24 to 72 hours. This test is used to
detect a skin allergy called contact dermatitis.
Allergy blood tests
•
Allergy blood tests look for substances
in the blood called antibodies. Blood tests are not as sensitive as skin tests
but are often used for people who are not able to have skin tests.
•
The most common type of blood test used
is the enzyme-linked immunosorbent assay (ELISA, EIA). It measures the blood
level of a type of antibody (called immunoglobulin E, or IgE) that the body may
make in response to certain allergens. IgE levels are often higher in people
who have allergies or asthma.
•
Other lab testing methods, such as radioallergosorbent
testing (RAST) or an immunoassay capture test (ImmunoCAP, UniCAP, or Pharmacia
CAP), may be used to provide more information.
References:
1. Danilevskiy M.F. et al. “ Diseases
of the mucous membrane of the mouth.” - K.: "Medytsyna", 2010.
2. Bruch J.M. Clinical oral medicine and pathology/ J.M. Bruch,
N.S. Treister// London.:Humana Press, 2010
3. Cawson R. E. Cawson’s essentials of oral pathology and oral
medicine. Seventh edition/ Cawson R. E. et. al.
//Elsevier science limited, 2002.
4. Slootweg P. Dental pathology – a practical introduction/ P.J.
Slootweg// Berlin.: Springer, 2007.
5. Da Silva J.D. Oxford American Handbook of Clinical Dentistry
(Oxford American Handbooks in Medicine) / J.D. Da Silva et al.//
Oxford University Press, 2007.
6. http://en.wikipedia.org/wiki/Anaphylaxis
7. http://pathmicro.med.sc.edu/mobile/m.immuno-17.htm
8. http://www.patient.co.uk/doctor/anaphylaxis-and-its-treatment
9. http://en.wikipedia.org/wiki/Angioedema
10. http://en.wikipedia.org/wiki/Erythema_multiforme
Information was prepared by Sukhovolets I.O.