This presentation includes Investigations and basic as well recent advances in management of allergic rhinitis. Starting from antihistamines, steroid (systemic and topical), Immunotherapy. Hope its helpful for some Undergraduates and postgraduates

1. RECENT ADVANCES IN THE
MANAGEMENT OF ALLERGY
DR. MAYUR WARAD
ENT POST-GRADUATE

2.  Allergic rhinitis is characterized by inflammatory changes in the nasal mucosa caused by exposure to
inhaled allergens. It causes significant disability and is often poorly managed. There may be co morbidities
with other organs being involved, commonly the eyes causing allergic conjunctivitis and the lungs with
allergic asthma.
 DEFINITION- Rhinitis is defined clinically as having two or more symptoms of the following for during two
or more consecutive days for more than one hour on most days.
i. Anterior or Posterior rhinorrhoea,
ii. sneezing,
iii. nasal blockage and/or itching of the nose
Allergic rhinitis is diagnosed when these symptoms are caused by allergen exposure leading to an IgE mediated reaction.

3. PATHOPHYSIOLOGY-

4.  ALLERGIC RHINITIS - Seasonal/perennial/episodic or intermittent/persistent
 LOCAL ALLERGIC RHINITIS - Negative skin/radioallergosorbent testing but positive nasal allergen challenge
 NONALLERGIC RHINITIS Perennial (vasomotor): Constant symptoms of profuse, clear rhinorrhea and nasal
congestion without correlation to specific allergen exposure or signs of atopy
 Cold air–induced: Nasal congestion and rhinorrhea upon exposure to cold, windy weather; occurs in both
allergic and nonallergic individuals
 NONALLERGIC RHINITIS WITH EOSINOPHILIA SYNDROME - Most often seen in adults; characterized by
eosinophilia on nasal smears and with negative test results for specific allergens
 INFECTIOUS RHINITIS - Viral, bacterial, fungal
 GRANULOMATOUS RHINITIS - Sarcoidosis, granulomatosis with polyangiitis (Wegener granulomatosis).
 DRUG-INDUCED RHINITIS - Oral contraceptives, reserpine derivatives, hydralazine hydrochloride, topical
decongestants (rhinitis medicamentosa), β-blockers (eyedrops)

5.  RHINITIS FROM MECHANICAL OBSTRUCTION - Septal deviation, Foreign body, Choanal atresia or stenosis:
Adenoid hypertrophy: Common cause of nasal obstruction in children
 Others: Encephaloceles, lacrimal duct cysts, dermoids, nasal polyps
 NEOPLASTIC RHINITIS
 Benign: Juvenile angiofibroma, inverted papilloma Malignant: Adenocarcinoma, squamous cell carcinoma,
esthesioneuroblastoma, lymphoma, rhabdomyosarcoma

6. CLASSIFICATION

7. DIAGNOSIS-
 Allergy diagnosis includes an assessment of clinical presentations followed by in vivo and/or in vitro tests to
identify the culprit allergen responsible for the immunologic mechanism of immediate hypersensitivity.
 Demonstration of sensitization to a suspected allergen (i.e. the presence of allergen-specific IgE) is required
for the diagnosis.
 But not all sensitized individuals are clinically allergic. Therefore confirmation of allergy diagnosis requires
either a convincing relevant history or a reproducible allergic phenomenon by a ‘controlled challenge test’
(provocation test). Hence, ‘challenge test’ is accepted as the gold standard test in allergy diagnosis.

8. SKIN TESTING
 When specific allergens are introduced into the skin, cross-linking of the FcεRI occurs if allergen-specific IgEs
are present in sufficient quantities on the cutaneous mast cells.
 Transient wheal and flare responses develop as a result of mast cell activation and mediators release. These
represent the immediate phase of the allergic reaction.
 However, the size of the wheal does not directly correlate with the amount of histamine released.
 The two major methods of skin testing currently in use are the skin prick test (SPT) and the intra-dermal
test(IDT).
 SPT is the most appropriate initial test with overallpositive predictive value (PPV) of less than 50% forall
allergens but negative predictive value (NPV) is veryhigh (≥ 95%)

11. SKIN PRICK TEST
 After cleaning with a 70% alcohol solution, 1:10 or 1:20 weight/volume allergen extract solutions are placed
at least 2 cm apart on the volar surface of the forearm or upper back.
 lancet is used to prick through each droplet of allergen
 Histamine dichloride (10 mg/mL) and a negative control of diluent identical to that of the allergen extracts
(usually glycerinated saline) should always be included in the test.
 A wheal ≥ 3 mm with flare after 15 to 20 minutes is considered positive – the presence of sensitization

12. Serum-specific IgE measurement
 Allergen-specific IgE (sIgE) measurement is an in vitro test to
demonstrate sensitization
 Serum sIgE can be measured by sensitive immunoassays such as
radioimmunoassay, enzyme immunoassay or fluorescent
immunoassay.
 In these assays a serum is incubated with an allergen of interest
bound solid phase. IgEs with the specificity to the allergen of
interest will remain on the solid phase, which is then detected by a
labelled anti-IgE antibody
 SIgE measurement is indicated in the following situations:
i. High risk for anaphylaxis;
ii. Use of medications that can cause interference in SPT;
iii. Skin lesions unsuitable for SPT;
iv. Small children
 The level of sIgE is not directly correlated with the severity of

13.  Basophil activation test (BAT)
 The Basophil Activation Test (BAT) is an in vitro study of
peripheral basophils responses tostimuli.
 BAT can use whole blood and therefore is more
accessible than mast cells to study IgE mediated
responses in allergic reaction.
 The whole blood of the patient is incubated with the
allergen of interest. Basophils are stimulated due to the
 cross-linking of the specific IgE-FcεRI on basophil.
 Degranulation of basophils leads to the expression of
molecules (e.g. CD63) on the basophil cell surface.

14.  In an unstimulated phase these molecules are anchored on the membrane of intracellular
basophil granules, which
 contain histamine. CD63 expression closely correlates with histamine release in the
degranulation. These can be detected by the flow cytometry method.
 limitations in BAT.
 It is not well standardized (e.g. allergen concentration).
 It requires a fresh sample and highly skilled technicians.
 Interpretation of the test demands a highly trained immunologist/allergist

15. NASAL ALLERGEN CHALLENGE/NASAL PROVOCATION TEST
 Nasal allergen is introduced into nose and any reaction noted compared to placebo.
 It is a gold standard for allergy diagnosis
 It is used where a positive suggestive history is accompanied by negetive skin prick tests.
 Gradually increasing doses are used.
 Subjective symptoms - symptom score, visual analogue scale
 Objective symptoms nasal inspiratory peakflow sneeze count
rhinomanometry acoustic rhinometry spirometry

16.  TRETAEMENT
1. The prevention of allergic rhinitis
2. Methods of reducing allergen exposure
3. Pharmacological treatment of allergic rhinitis
4. Immunotherapy for allergic rhinitis
5. Surgical treatment
6. Complementary therapies

17.  REDUCING ALLERGEN EXPOSURE
 As the clinical effects of allergic rhinitis are caused by allergens it would seem logical that reduced
exposure would benefit symptoms.
 The major allergens to be found indoors are house dust mite, cat, dog and other furry animals, cockroach
and moulds.
 Outdoors the main allergens are airborne pollens which vary during the year and depend on local
conditions.

18. METHODS TO ACHIEVE ALLERGEN REDUCTION
 House dust mite allergen reduction aims to reduce the amount of mite allergens in the home:
 Wash bedding regularly (every 1–2 weeks) at 55–60 °C to kill mites (washing with cold water removes 90%
of mite allergens; washing at 55–60 °C kills mites)
 Wash pillows and duvets in hot water (55–60 °C) and encase pillows and mattresses with protective
coverings that have a pore size of 6 μm or less.
 Sufficient ventilation of dwellings to decrease humidity; aim to reduce indoor relative humidity to below
50% and avoid damp housing conditions.

19. ADDITIONAL STRATEGIES
 Use a good quality vacuum cleaner (if possible, one fitted with a HEPA filter)
 Use a damp duster when dusting and cleaning surfaces
 Replace wall to wall carpets with linoleum or wooden floors which can be wiped clean
 Remove/reduce curtains and soft furnishings in the bedroom
 Replace fabric-covered seating with leather or vinyl
 Remove soft toys from the bedroom; wash them at 55–60 °C or freeze them (in a kitchen deep-
freezer) to kill house dust mites
 Exposure of mattresses, rugs and carpets to direct strong sunlight (for more than 3 hours) kills mites
and can be used in appropriate regions.

21. PHARMACOLOGICAL TREATMENT OF ALLERGIC RHINITIS
 It should be stressed that these medications aim to achieve improved symptom control and are not a
cure for allergy. They generally need to be taken for as long as there is allergen exposure causing
symptoms.
 Symptom control is better for patients with intermittent allergic rhinitis if they start treatment prior
to exposure to the allergen to which they are sensitized. For example, patients with grass pollen
allergy should be advised to start treatment a month before the pollen season starts to try to avoid
the development of symptoms and nasal inflammation and to stop treatment at the end of the
season.

22. ANTIHISTAMINES
 The symptoms of running, sneezing and nasal and eye itching are histamine driven and antihistamines are the first-
line treatment for these symptoms in patients who have no problem with nasal obstruction.
 They have little effect on nasal blockage
 Second generation oral antihistamines such as loratadine and cetirizine are non-sedating safe for long-term use and
can be used for children. They have a rapid onset of action (usually less than an hour) and will give symptom
reduction on a once daily dosing.
 Antihistamines give better symptomatic control when
 used regularly rather than on an as required basis
 Topical antihistamines (for example azelastine) may be used intranasally to achieve rapid symptom control and can
be combined with a topical nasal steroid.
 It has the disadvantages of having a bitter taste that some patients
 Azelastine eyedrop may also be useful in reducing ocular symptoms.

23.  INTRANASAL GLUCOCORTICOSTEROIDS
 Glucocorticosteroids are the most effective treatment for allergic rhinoconjunctivitis, Topical use in the
form of a spray or drops is preferred to oral use to reduce side
 effects, although occasionally oral steroids may be useful, Intra-nasal application allows a high
concentration of the active drug to be delivered to the nasal mucosa with minimal
 systemic absorption.
 The drugs reduce all symptoms of allergic rhinitis and ocular symptoms and are the first line
 treatment of choice in patients who complain of nasal block.
 steroids have an effect on the production of pro-inflammatory mediators within the cell nucleus their
effect is slow to occur and long lasting. it can take two weeks for full benefit to be noticed. Patients
should be warned of this as some will give up on treatment if it does not work rapidly.

24. SYSTEMIC GLUCOCORTICOSTEROIDS
 Oral steroids may occasionally be useful in patients with
severe symptoms to allow reduction of mucosal swelling
and subsequent use of topical medication or to cover a
short period when symptom control is particularly bad.
 Prednisolone 20–40 mg/day is normally sufficient BUT oral
steroids may cause serious side effects so their use should
be considered carefully and length of treatment be kept as
short as possible.

25. LEUKOTRIENE RECEPTOR ANTAGONISTS (LTRAS)
 Cysteinyl leukotrienes are a family of eicosanoid inflammatory mediators (LTC4, LTD4 and LTE4) produced in
leukocytes, mast cells, eosinophils, basophils and macrophages by the oxidation of arachidonic acid by the
enzyme arachidonate 5–lipoxygenase.
 Their effects are to cause bronchoconstriction, increase vascular permeability and attract inflammatory cells
and as such are involved in the processes underlying asthma and allergic rhinitis. montelukast (a leukotriene
receptor antagonist) is licensed for the treatment of allergic rhinitis associated with asthma.
IPRATROPIUM
 Topical ipratropium bromide spray is effective at controlling watery rhinorrhoea and can be a useful addition
to a topical steroid if rhinorrhoea is not being well controlled.

26. DECONGESTANTS
 Topical (e.g. xylometazoline) and systemic decongestants
(e.g. pseudoepedrine) are available and have a place in
allergic rhinitis management.
 They reduce nasal obstruction and may allow access of a
topical steroid into an otherwise obstructed nose.
 The disadvantage is of rebound vasodilation when their use
is stopped leading to a worsening of symptoms and of
rhinitis medicamentosa with longer term use. A maximum
length of treatment of 7–10 days therefore is advised.

27. NASAL DOUCHING
 Saline nasal douches may help with symptom control and can physically remove an allergen from the nasal
mucosa. If pollen levels are high regular douching may be of benefit.

28. ALLERGIC RHINITIS MANAGEMENT (ALGORITHM OF THE
ARIA)

29. Immunotherapy
 Immunotherapy (sometimes called desensitization) is a method of inducing tolerance to an allergen and
therefore reducing unwanted symptoms. It can reduce the symptoms of allergic rhinitis, offer long-lasting
reduction of symptoms (even when treatment has stopped) and can prevent the progression of allergic
disease.
 It involves repeated exposure of the patient to the allergen usually,
 but not always, with a gradual increase in allergen dose. It can be given subcutaneously by injection (SCIT)
or sublingually in drops or tablets (SLIT).

30. SUBCUTANEOUS IMMUNOTHERAPY
 SCIT has been shown to be effective at decreasing rhinitis and rhinoconjunctivitis symptoms, improving
QOL, and reducing medication usage.
 Appropriate candidates for SCIT are patients who have failed pharmacotherapy or who desire a more
durable therapeutic benefit.
 Patients who are at high risk for development of asthma or new sensitizations may also benefit from AIT
CONTRAINDICATIONS-
1) Poorly controlled asthma,
2) Active autoimmune disorders
3) Malignancy
4) CV disease, partially controlled asthma, and autoimmune diseases in remission, as well as current use of
beta-blockers, are considered relative contraindications.
5) Pregnancy is a contraindication to initiating immunotherapy.

31.  SCIT is typically initiated at a dilute dose and escalated with weekly injections over a period
of weeks to months. Once main- tenance doses are achieved, injections are administered
less fre- quently, eventually on a monthly basis for the remainder of the planned treatment
protocol
 Duration of SCIT therapy is generally between 3 and 5 years. This is based on data from
studies in patients receiving SCIT with timothy grass extract. Patients receiving therapy for
3 or 4 years experienced remissions that persisted for at least 3 years in most patients.
 In polysensitized patients, there is some debate about single versus multiple allergen AIT.
European guidelines recommend dosing with the single most bothersome allergen,while
the US approach is generally to administer multiple offending allergen extracts in a
mixture. The available literature is not sufficiently robust to determine if one approach is
superior to another

32. SUBLINGUAL IMMUNOTHERAY
 whereby extracts are administered under the tongue, was controversial for many years but has gained
wide acceptance in Europe and continues to gain traction.
 Two large, double-blind, placebo-controlled randomized trials of timothy grass (Phleum pratense) AIT
tablets in North America were reported in 2011, one in children and adolescents and one in
adults.289,290 The subjects in both studies were randomized to receive either a once-daily grass tablet
treatment that contained 2,800 bioequivalent units (15 μg of Phl p 5) or placebo 16 weeks before the
2009 grass pollen season and during the whole season. In 345 children and adolescents, active treatment
improved daily symptom scores and daily medication use by 25% to 81%, respectively.289 Similar
improvements were noted in the adult study compared with placebo.
 The obvious advantage of this treatment over SCIT is ease of administration, usefulness in children who
dislike injections, and avoidance of the need to go to a doctor’s office to receive the treatment; this is
primarily related to the safety of SLIT and safety has been demonstrated in multiple studies in adults and
children.

33. INTRALYMPHATIC IMMUNOTHERAPY
 Intralymphatic immunotherapy (ILIT), whereby allergen is injected under ultrasound guidance into inguinal
lymph nodes, is being investigated with promising results.
 The hypothesis is that its efficacy is similar to that of SCIT in a much shorter time frame.
 A randomized, open trial in subjects with AR to grass pollen was done. In the trial, one group of subjects
received conventional SCIT that consisted of 54 injections over 3 years and the group taking ILIT received
three lymph node injections over 8 weeks with a much smaller dose than the SCIT group. Over the 3 years of
follow-up, ILIT induced tolerance to a nasal allergen challenge significantly faster than SCIT (4 months vs. 1
year), which resulted in significantly less rescue medication intake during the first pollen season than SCIT
and led to an identical reduction in nasal symptom scores during the first and third years of therapy
compared with SCIT.
 Finally, ILIT injections caused significantly fewer allergic adverse events than SCIT.

34. EPICUTANEOUS ALLERGEN-SPECIFIC IMMUNOTHERAPY
 Epicutaneous administration of allergen via a transdermal patch has recently been investigated as a
possible alternative to conventional AIT. The 4 published RCTs investigating epicutaneous AIT have
shown no difference in SPT endpoint or nasal provocation test compared to placebo.
 Improvement in symptom scores and medication usage was seen;
 however, the improvement does not appear to be robust.

35. REFERENCES-
 Scott-Brown’s Otorhinolaryngology Head and Neck Surgery 8TH EDITION
 Cummings Otorhinolaryngology Head and Neck Surgery 7TH EDITION
 https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7066682/

36. THANK YOU