Allergic disease

1. Internal Medicine
Allergic Diseases
By
Prof. Dr. Zainalabideen A. Al-Abdulla,
MRCPI, DTM&H., Ph.D., FRCPath. (U.K.)

2. Allergic Diseases
Learning Objectives
1. To discuss the most important allergic
diseases, and their clinical features,
investigation, diagnosis and management.
2. To elaborate on anaphylaxis as a medical
emergency.
3. To show you some important images for
the above mentioned conditions.

3. Allergic Diseases (A.D.)
Allergyis a medical term which means that the patient
develops symptoms upon contact with allergens to which
the patient is sensitized.
Atopy(= Placelessness, unclassifiable) is inappropriate
(exaggerated) IgEantibody production to harmless
environmental substances (allergens) in a genetically
predisposed individual, but not necessarily develops
symptoms (silent).

4. Cont./…Allergic Diseases (A.D.)
So,
Atopy is a condition for the development of
allergy but is not itself allergy (i.e. you need to
be atopic to become allergic, but not all atopic
people develop allergy).

5. Prevalence of Allergic Diseases
Allergic diseases affect about 15-20% of the
population worldwide.
• A child whose parents do not suffer from allergy
has a 15% chance of becoming allergic.
• If the mother is allergic the risk increases to 60% .
• If both parents are allergic the risk is 80% (i.e.
sometimes allergies can jump a generation).

6. Pseudo-allergy/Anaphylactoid reactions
•These conditions are with similar symptoms to
allergy but are not caused by IgE and occur
commonly in non-atopic people.
• They are caused by the release of histamine and
result in a spectrum of symptoms vary from rash to
anaphylaxis. They are usually caused by aspirin,
NSAIDs (e.g. Ibuprofen), opiates, and I.V. radio-
contrast media, and others.

7. Pathology & predisposition to A.D. “Hygiene
hypothesis” may explain the susceptibility to
development of allergy.
• Infections in early life may protect from
development of allergy (i.e. good sanitation and
health care may lead to a penalty of development of
allergy).
• Genetic predisposition, mechanisms of IgE
exaggerated production, and the ability of epithelial
barrier to protect against entrance of allergic
agents. Cont./…

8. Cont./…Pathology & predisposition to A.D.
• Environmental factors such pollution and
cigarette smoke.
- All of the above mentioned factors are
contributory elements to the development of
allergic diseases.

9. Common allergic diseases
1. Urticaria and angioedema
2. Atopic dermatitis
3. Allergic conjunctivitis
4. Allergic rhinitis (hay fever)
5. Allergic asthma
6. Food allergy
7. Drug allergy
8. Allergy to insect venom
9. Anaphylaxis/ Anaphylactoid

10. General clinical assessment
1. Assess nature of symptoms and specific triggers of
allergy. Potential allergens at home and workplace
should be identified.
2. The time lag between exposure to a potential
allergen and onset of symptoms (allergic reaction
occurs within minutes after exposure to allergens).
3. Enquiry about other concomitant allergic
conditions (past or present) cont./…

11. Cont./…General clinical assessment
4. Family history of allergic diseases should
be carefully assessed.
5. Drug history should be taken including
compliance, side effects, & complementary
therapies:
Differentiate drug allergy from side effects, overdose
and intolerance to the drugs.

12. Urticaria (nettle rash, hives)
• Urticaria is an area of focal dermal edema
secondary to transient increase in capillary
permeability when it lasts < 24 hours .
- This is vs when it lasts for > 24 hours in urticarial
vasculitis due to hepatitis B, SLE or idiopathic).
- This can be clarified by drawing a circle around a
wheal with a pen and examining the patient 24
hours later.
Cont./…

13. Cont./…Urticaria (nettle rash, hives)
• When present for a period of <6 weeks it is an
acute urticaria (may be associated with angioedema
of lips, face or throat), and when is present for >6
weeks it is a chronic urticaria.
• Urticaria is characterized by itching.

14. Urticaria (Nettle Rash, Hives)

15. Urticaria (nettle rash, hives)
Urticaria
(nettle
rash,
hives)

16. Management urticaria
1. Non-sedative antihistamine (e.g. loratidine,
fexofenadine or cetirizine).
2. H2-blockers such as cimetidine or ranitidine are not
recommended any more for allergy therapy due to their
link with malignancy development and also increasing
the need for allergy medications.
3. Mast cell stabilizers (e.g. cromoglycate (CRG),
omalizumab, or Beta 2-adrenergic agonists) or
leukotriene inhibitors (montelukast 10 mg tablet once
daily, or Zafirlukast 20-40 mg once daily) may also be
used and better than CRG.
4. Systemic corticosteroids are widely used, but are of
little benefit.

17. Angioedema
Angioedema is the episodic, localized, non-pitting
swelling of submucous or subcutaneous tissues. It
affects most commonly the face, extremities and
genitalia. When involves the larynx/ tongue or
intestine, it may cause life-threatening respiratory
obstruction or abdominal pain & distension
respectively. Angioedema is characterized by pain
without itching.

18. Angioedema
Angioedema
Angioedema

19. Types of angioedema
1. Allergic reaction to specific triggers; treated with
anti-histamine
2. Idiopathic angioedema; treated with anti-
histamine
3. Hereditary angioedema; treated with modified
androgen derivative (danazol), pure C1INH infusion,
or fresh frozen plasma
4. ACE-inhibitor (ACEI) associated angioedema ; stop
the medication

20. Anaphylaxis
• Anaphylaxis is a potentially life - threatening,
systemic allergic reaction caused by degranulation of
mast cells and release of vasoactive amines.
• Death may occur if the patient has
a preexisting asthma or adrenaline (epinephrine)
administration is delayed.

21. Clinical assessment
• The severity, time between exposure to allergens
and onset of the symptoms, potential triggers and
route of exposure (e.g. drugs, foods, latex, insect
venom...etc) should be assessed since clinical
features depend on these factors:
• If an allergen is inhaled the major symptom is
frequently wheezing. Venom or drug exposure
should be differentiated from their direct toxic
effects.

22. Clinical manifestations of anaphylaxis
• Anaphylaxis starts in few minutes up to one hour.
• Symptoms : Impending doom (death), loss of
consciousness, shortness of breath, generalized skin
rash with itching mainly of the palms, soles and
genitalia, and abdominal pain /diarrhea.
cont./…

23. cont./…Clinical manifestations of anaphylaxis
On examination
Laryngeal obstruction, stridor, tachypnoea,
angioedema of lips, eyes and mucous membranes,
flushing and sweating, and urticaria with discrete
erythematous wheals with raised margins,
hypotension, wheeze, and tachycardia or cardiac
arrhythmias.

25. Management of Anaphylaxis
Anaphylaxis is an acute medical emergency, and
should be handled immediately:
1. Prevent further contact with allergen (e.g. removal of bee
sting if any).
2. Ensure airway (may need endo-tracheal intubation).
3. Administration of I.M. adrenaline immediately: 0.3 – 1.0
ml of 1:1000 solution, repeat at 5-10 min. intervals if
response is inadequate.
4. Administration of antihistamine: e.g. chlorpheniramine 10
mg I.M. or slow I.V. injection.
cont./…

26. cont./…Management of Anaphylaxis
5. Administration of corticosteroids: e.g. hydrocortisone 200
mg I.V. (prevents rebound symptoms)
6. Supportive treatments including:
A. Nebulized beta 2-agonist to decrease
bronchoconstriction, e.g. salbutamol (Ventolin),
terbutaline (bricanyl)- both are short-acting.
B. I.V. fluid to restore or maintain B.P.
C. Oxygen
D. Keep the patient in an Intensive Care Unit (ICU)
for 12 hours.
cont./…

27. Cont./…Management of anaphylaxis
7. Recovered patients should be referred for specialist
assessment. The aim is to identify the trigger factor, educate
the patient for avoidance, and possible immunotherapy.
8. Self- injectable adrenaline (EpiPen) should be prescribed
for patients suffered from previous anaphylaxis and their
families should be instructed on its use. MedicAlert (or card)
bracelet carried by the patient may also be useful.

28. General investigations for A.D.
Skin Prick Test (SPT)
It is the “gold standard’’ of allergy testing. Droplets
of diluted common allergens with a negative control
are placed on the forearm or back, and are
punctured through with a sterile lancet or a special
SPT device ID.
After 15 min local wheal and flare are seen
Antihistamine drugs should be discontinued 4 days
before testing.
Cont./…

29. General Medicine

30. Cont./…General investigations for A.D.
Specific IgE tests
These tests can be done by ELISA, or very rarely
nowadays by RIA (RAST).
Total serum IgE and eosinophilia
Raised or normal IgE level may present in allergy.
Eosinophilia is common in atopic individuals, but
>20% may be due to non-atopic causes.
Cont./…

31. Cont./… General investigations for allergic diseases
Challenge test
It is a supervised exposure to allergens and usually
performed special centers. It is useful in the
investigation of occupational asthma or food allergy.
Mast cell tryptase
The peak of serum level is after 1-2 hours of
exposure, and remains elevated for 24 hours
afterwards. It is measured at the time of the reaction
(0), and 3 and 24 hours afterwards.

32. General management of allergy
1. Avoidance in the main step in the management.
2. Antihistamine (block H1 receptors) in particular the
long acting, non-sedating preparations are used for
treatment and prophylaxis.
3. Corticosteroids decrease pro-inflammatory
cytokines. They can also be used topically to minimize
side effects.
4. Sodium cromoglicate (mast cells membrane
stabilizers); used only for prophylaxis against asthma
(“Intal” inhaler), allergic rhinitis (“Rynacrom” nasal
spray), and allergic conjunctivitis (“Opticrom” eye
drops).
cont./…

33. Cont./… General management of allergy
5. Antigen-specific immunotherapy (hypo-
sensitization/ de-sensitization) is carried out by
subcutaneous injection of increasing amount of the
sensitizing allergen. It is used for the treatment of
allergic rhinitis, allergic asthma and stinging
hypersensitivity, but not for food allergy, or chronic
urticaria/angioedema.
6. Omalizumab (Xolair) is humanized monoclonal
antibody (IgG1) that inhibits the binding of IgE to
mast cells and basophils.

34. USEFUL
INFORMATION
(just for your own information)
Videos:
https://www.youtube.com/watch?v=ljYuV_7LKn0
https://www.youtube.com/watch?v=1A2rr-5FpeU
https://www.youtube.com/watch?v=wtFLg8WZ9u4

35. The degranulation process in a Mast cell:
1 = antigen; 2 = IgE; 3 = FcεRI; 4 = preformed mediators
(histamine, proteases, chemokines, heparin); 5 =
granules; 6 = Mast cell; 7 = newly formed mediators
(prostaglandins, leukotrienes, thromboxanes, platelet-
activating factor)

36. eNitric Oxide Test for Asthma
An exhaled nitric oxide (eNO) test is one of several
tests that can be used to check for asthma. It
involves breathing into a mouthpiece attached to a
machine that measures the level of nitric oxide gas in
the breath. Nitric oxide is produced by the body
normally, but high levels in the breath can mean that
the airways are inflamed =
a sign of asthma (NR eNO = 20 - 30 PPB)
# PPB = Parts Per Billion

37. eNitric
Oxide Test
for Asthma