• Users Online: 112
  • Home
  • Print this page
  • Email this page
Home About us Editorial board Ahead of print Current issue Search Archives Submit article Instructions Subscribe Contacts Login 


 
 Table of Contents  
ORIGINAL ARTICLE
Year : 2018  |  Volume : 19  |  Issue : 1  |  Page : 1-8

Comparison between sublingual immunotherapy and subcutaneous immunotherapy in the treatment of pollen-induced vernal keratoconjunctivitis in children


1 Department of Ophthalmology, Zagazig University, Zagazig, Egypt
2 Department of Medical Microbiology & Immunology, Zagazig University, Zagazig, Egypt

Date of Submission10-Aug-2017
Date of Acceptance17-Nov-2017
Date of Web Publication1-Feb-2018

Correspondence Address:
Basem M Ibrahim
Department of Ophthalmology, Faculty of Medicine, Zagazig University, Zagazig 44519
Egypt
Login to access the Email id

Source of Support: None, Conflict of Interest: None


DOI: 10.4103/DJO.DJO_50_17

Rights and Permissions
  Abstract 

Purpose
The aim of this study was to compare between sublingual immunotherapy (SLIT) and subcutaneous immunotherapy (SCIT) in the treatment of pollen-induced vernal keratoconjunctivitis (VKC) in children.
Patients and methods
This was a prospective randomized case series. Forty-six patients with grass pollen-induced VKC were enrolled in this study. The cases were divided randomly into two groups: group A included 23 children treated by SLIT and group B included 23 children treated by SCIT. All cases were assessed for improvement by measurement of the level of specific immunoglobulin E (IgE)/6 months and by clinical scoring system/3 months. This system comprises the total subjective symptom scores (TSSS) and the total ocular sign score (TOSS). Data were collected, compared, and analyzed.
Results
Both routes, SLIT and SCIT, led to a statistically significant effect (P˂0.001) in the improvement of these cases of pollen-induced VKC, and this was evident from all of the follow-up variables including specific IgE test, TSSS, and TOSS. There was no statistically significant difference between the two routes of administration of immunotherapy in the specific IgE test, TSSS, and TOSS at all the follow-up visits (P<0.05).
Conclusion
SLIT had the same efficacy as SCIT in the treatment of children with grass pollen-induced VKC, but with less pain and a shorter and a more convenient schedule compared with that of SCIT.

Keywords: children, pollen, subcutaneous immunotherapy, sublingual immunotherapy, vernal keratoconjunctivitis


How to cite this article:
Ibrahim BM, Abdel-Latif RS. Comparison between sublingual immunotherapy and subcutaneous immunotherapy in the treatment of pollen-induced vernal keratoconjunctivitis in children. Delta J Ophthalmol 2018;19:1-8

How to cite this URL:
Ibrahim BM, Abdel-Latif RS. Comparison between sublingual immunotherapy and subcutaneous immunotherapy in the treatment of pollen-induced vernal keratoconjunctivitis in children. Delta J Ophthalmol [serial online] 2018 [cited 2018 May 26];19:1-8. Available from: http://www.djo.eg.net/text.asp?2018/19/1/1/224570


  Introduction Top


Vernal keratoconjunctivitis (VKC) is a severe chronic ocular disease frequently affecting adolescents and children younger than 10 years of age [1].

About 50% of cases of VKC have corneal manifestations such as corneal erosion, superficial punctate keratopathy, corneal ulcers, persistent corneal epithelial defects, and corneal plaque [2],[3]. Vision is usually markedly impaired [4]. Topical steroids are frequently used to control exacerbations of VKC, which may have led to severe side-effects such as cataract, glaucoma, and ocular infections. Steroid-induced glaucoma is not infrequent and could result in blindness [5].

Allergen immunotherapy (desensitization), sometimes recognized as allergy shots, consists of administration of allergen extracts in gradually increasing doses for a relatively long period (years). Forms of immunotherapy include subcutaneous injection, sublingual drops, tablets, or sprays [6]. The concept of immunotherapy involves pushing the body to develop a normal immune response to the allergen, rather than the intense reaction that it develops when exposed to this allergen, which includes redness, watery eyes, burning sensation, and severe itching [7].

Allergen immunotherapy can result in long-lasting relief of symptoms of allergy even after stoppage of treatment as it reduces sensitivity to allergens [8]. The main advantage of immunotherapy over eye drops or other allergy medications is that immunotherapy leads to no major ocular complications, although it may take a long time (several months or even years) to produce adequate results [7].

Noon [9] was the first author who described the use of allergen-specific immunotherapy in the treatment of allergic diseases in 1911. Werfel [10] considered subcutaneous allergen-specific immunotherapy as one of the safest methods for desensitization. However, other authors promoted the use of sublingual immunotherapy (SLIT) in the treatment of allergic diseases [11],[12].

The present study aimed to compare SLIT with subcutaneous immunotherapy (SCIT) in the treatment of children with pollen-induced VKC.


  Patients and methods Top


This is a prospective randomized study that was carried out between October 2014 and September 2016. The study was approved by the Local Ethical Committee of Zagazig University. Written informed consent was obtained from the patients’ guardians for participation in the study.

This study included 46 patients with grass pollen-induced VKC as proved by a specific immunoglobulin E (IgE) test. All the cases were resistant to medical treatment such as topical steroids, sodium chromoglycate, topical, and systemic antihistamines for at least 1 month of treatment.

Exclusion criteria were as follows:
  1. Allergy to allergens other than pollen.
  2. Other ocular diseases such as corneal ulcer, iridocyclitis, glaucoma, and ocular infection.
  3. Presence of systemic diseases other than allergy.
  4. History of previous desensitization therapy.
  5. Presence of environmental instability (patients frequently varying their environmental conditions.


Diagnostic procedures

Ophthalmic history

  1. Age, sex, occupation, and possible predisposing allergens such as heat, dust and pollens.
  2. History of the allergic conjunctivitis in terms of onset, course, duration, and previous medications.
  3. History of allergic manifestations such as itching, eye redness, lacrimation, photophobia, and ropy discharge.


Full ophthalmological examination

  1. With a special focus in conjunctival examination for the presence of conjunctival hyperemia, papillae, giant tarsal papillae, limbal infiltrates, corneal epithelial plaques, and ulcer.
  2. Intraocular tension was determined using the applanation tonometer.


Clinical scoring system

There are two scoring systems for follow-up of cases of VKC; one is subjective depending on the patient’s complaints, called the total subjective symptom scores (TSSS), and the other is objective depending on the observed ocular signs, called the total ocular sign score (TOSS), which were graded as suggested by Bonini et al. [13]. These scores were utilized for comparison of patients within the groups and also among the groups.

TSSS were recorded by the patient once monthly (itching, photophobia, tearing, foreign body sensation, and burning sensation) [14].

Each variable was graded as follows: 0=absent, 1=mild, 2=moderate, or 3=severe.

These scores were summed and averaged to yield the total score/3 months. The maximal value of TSSS was 15.

TOSS was recorded every 3 months. These scores comprised hyperemia of bulbar and palpebral conjunctiva, papillae, giant papillae, and limbal infiltrates. Grading of any sign was performed as follows: 0=nothing, 1=mild, 2=moderate, and 3=severe.

The details of this scoring are as follows:

The numbers and sizes of the papillae are graded as follows: 0=no papillae, 1=little papillae≤0.2 mm, 2=papillae size 0.3: 1 mm, and 3=papillae size>1: 3 mm all over the tarsal conjunctiva.

The numbers and sizes of the giant cobblestone-like papillae (>3 mm) of the superior tarsal conjunctiva are graded as follows: 0=no papillae, 1=little giant papillae 3: 4 mm, 2=the papillae are 3: 4 mm all over the tarsal conjunctiva, or some papillae 4: 6 mm in size, and 3=the papillae are 4: 6 mm all over the tarsal conjunctiva.

The numbers and sizes of the limbal papillae were graded as follows: 0=no papillae, 1=little papillae 0.1: 1 mm, 2=papillae size 0.1: 1 mm or few papillae 2: 3 mm in size, and 3=papillae size 2: 3 mm or more.

Objective ocular signs at each visit were summed (TOSS). The maximal value of TOSS was 15. These scores were used for comparison within and between the groups.

The cases were divided randomly into two groups according to the route of administration of immunotherapy:

Group A: included children treated by SLIT.
Group B: included children treated by SCIT.

Measurement of serum-specific immunoglobulin E

A venous blood sample (5 ml) was collected before treatment, at 6, and 12 months, and serum was separated from the sample. Quantitative estimation of specific IgE in serum was performed by an immune blot assay against circulating aeroallergen with Allergy Screen Panel 2A EGY (Mediwiss Analytic GmbH, Hanover, Germany). Rapid Reader (Improvio; Mediwiss Analytic GmbH) was used to analyze Serum s-IgE levels with a limit of detection of 0.35 kAU/l. All the steps were performed according to the manufacturer’s instructions.

Treatment protocol

Subcutaneous immunotherapy

SCIT involved two stages: the preliminary build-up stage, when the dose and concentration of the allergen were increased, and the maintenance stage, where a fixed therapeutic dose of the allergen was administrated over a period of time.

SCIT during the build-up stage involved two injections every week. The extracts were available as aqueous solution bottles (Omega Laboratories Ltd, Montreal, Quebec, Canada). During the build-up stage, there was a 10-fold increase in the concentration between each bottle (1/1000, 1/100, 1/10), together with an increase in the volume injected (0.2, 0.4, 0.6, 0.8 and 1 ml of each vial) for 3 months.

SCIT during the maintenance stage consisted of the injection of 1 ml of concentration number 3 weekly as a maintenance dose [15].

Sublingual immunotherapy

The build-up stage of SLIT was only 2 months. During both the build-up and the maintenance stage, the dose of SLIT was once a day.

The fourth build-up vial (highest concentration 1 : 25) was prepared by diluting the available grass pollen concentrate (10 000 BAU/ml; Jubilant HollisterStier LLC, Chicago, Illinois, USA) by adding 0.2 ml of this concentrate to 4.8 ml of 50% glycerin. The protocol used five-fold dilutions to prepare the subsequent vial (third build-up vial) by adding 1 ml of vial 4–4 ml of 50% glycerin to yield 5 ml of vial 3; the same steps were repeated to prepare vial 2 and vial 1.

The daily dose of each build-up vial began with one drop for 1 week, two drops for 1 week, and then three drops for 1 week, starting with vial 1, vial 2, and vial 3 until the maintenance dose (three drops of the fourth vial) was reached. All subsequent maintenance vials continued daily during the follow-up period [16],[17].


  Results Top


Forty-six patients with VKC were enrolled in this study. These cases were proven to have allergy to grass pollen by a specific IgE test.

The male-to-female ratio in group A was 1.3 (57% males and 43% females), whereas in group B, it was 1.88 (65% males and 35% females). The mean age was 10.4±3.1 years (range: 6.4–14.5 years) in group A and 9.5±2.5 years (range: 5.5–13.45 years) in group B. There was no statistically significant difference in the age distribution, sex distribution, type, and duration of VKC between the two groups ([Table 1]).
Table 1: Demographic and clinical characteristics of the studied groups

Click here to view


There was a statistically significant improvement in VKC cases treated with SLIT (group A) as proved by specific IgE ([Table 2]) and TSSS and TOSS ([Table 3]).
Table 2: Specific immunoglobulin E after sublingual treatment (group A)

Click here to view
Table 3: Total subjective symptom scores and total ocular sign score after sublingual treatment (group A)

Click here to view


Similarly, there was a statistically significant improvement in VKC cases treated with SCIT (group B) as proved by specific IgE as shown in [Table 4] and TSSS and TOSS as shown in [Table 5].
Table 4: Specific immunoglobulin E after subcutaneous treatment (group B)

Click here to view
Table 5: Total subjective symptom scores and total ocular sign score after subcutaneous treatment (group B)

Click here to view


There was no statistically significant difference between sublingual treatment (group A) and subcutaneous treatment (group B) in specific IgE levels either before or after immunotherapy ([Table 6] and [Figure 1]).
Table 6: Difference between sublingual treatment (group A) and subcutaneous treatment (group B) in terms of specific immunoglobulin E

Click here to view
Figure 1: Comparison between sublingual treatment (group A) and subcutaneous treatment (group B) in terms of specific immunoglobulin E (IgE).

Click here to view


Similarly, there was no statistically significant difference between sublingual treatment (group A) and subcutaneous treatment (group B) in the TSSS either before or after immunotherapy ([Table 7] and [Figure 2]).
Table 7: Difference between sublingual treatment (group A) and subcutaneous treatment (group B) in terms of total subjective symptom scores

Click here to view
Figure 2: Comparison between sublingual treatment (group A) and subcutaneous treatment (group B) in terms of total subjective symptom scores (TSSS).

Click here to view


In addition, there was no statistically significant difference between sublingual treatment (group A) and subcutaneous treatment (group B) in the TOSS as shown in [Table 8] and [Figure 3].
Table 8: Difference between sublingual treatment (group A) and subcutaneous treatment (group B) in terms of total ocular sign score

Click here to view
Figure 3: Comparison between sublingual treatment (group A) and subcutaneous treatment (group B) in terms of total ocular sign score (TOSS).

Click here to view



  Discussion Top


The traditional treatment of exacerbations of VKC usually involves the use of topical steroids, which carry the risk of many ocular complications [5]. VKC may be treated alternatively by immunotherapy against the causative allergens and consequently the use of steroids can be entirely avoided [7].

Modifying immune responses by SCIT is a possibly curative approach [18]. The first study of treatment of grass pollen allergy by modifying immune responses of patients with grass pollen extract was available a hundred years ago [9]. Since then, numerous researches have shown that SCIT is a valuable treatment for VKC [19],[20]. In addition, SCIT can reduce the risk of bronchial asthma in children with VKC [21]. Prevention of the development of new sensitizations is another advantage of SCIT [22],[23].

Numerous studies have attempted to find alternative routes to SCIT so that injections can be avoided. SLIT is well tolerated and seems to be an attractive alternative to SCIT, especially in children. It has a better compliance, with no risk of severe allergic reactions as in SCIT [23],[24].

In this study, SLIT was compared with SCIT in the treatment of children with grass pollen VKC who were either resistant to medical treatment or showed major ocular side effects of medications. Most studies found an excellent correlation between VKC and grass pollen allergy [25].

In the current study, quantitative specific IgE level, TSSS, and TOSS were used for evaluation, follow-up, and comparison between the groups.

Several studies reported a marked change in both symptoms and sign scores after SLIT, particularly for seasonal allergens such as grass pollen [25],[26],[27],[28],[29],[30]. This was in agreement with the present study, where there was a statistically highly significant difference between the results of specific IgE (before sublingual treatment, and at 6 and 12 months of treatment) and the results of TSSS and TOSS(before sublingual treatment, at 3, 6, 9, and 12 months of treatment). However, some studies showed no significant change in both symptoms and sign scores after SLIT [31],[32], which could be attributed to the small sample size in these studies and the use of different allergens (Parietaria, Molive pollen, and Dermatophagoides pteronyssinus).

SCIT was the only way to alter the abnormal immune response that caused the allergic disease a century ago. It is one of the most important treatments available to allergic patients [33]. Radtke and Grammer [34] found that SCIT led to a decrease in nearly 60–75% of symptoms, and this improvement after SCIT was also evident in the studies by Kovesi et al. [31], Yukselen et al. [32], and Mahdy et al. [35]. This was in agreement with the present study, where there was a statistically highly significant difference between the results of specific IgE (before SCIT, and at 6 and 12 months of treatment) and the results of TSSS and TOSS (before SCIT, and at 3, 6, 9, and 12 months of treatment).

SLIT was used introduced to treat allergy only 15 years ago, but it is an extension to SCIT [28]. The early studies were directed mainly at confirming the efficacy of SCIT [36].

Many studies have compared SLIT and SCIT. Mauro et al. [37] reported that there was no statistically significant difference between them in reducing the symptom scores (SLIT 4.67 vs. SCIT 3.93) after 1 year of treatment of allergic patients. Similarly, Antúnez et al. [38] found that there was similar improvement in clinical scoring in children with respiratory allergic diseases treated with either SLIT or SCIT. This was in agreement with the current study data, which indicated that there was no statistically significant difference between SLIT and SCIT in the results of specific IgE before treatment, and at 6 and 12 months of treatment. The present study also showed that there was no statistically significant difference between SLIT and SCIT into the results of TSSS before treatment, at 3, 6, 9, and 12 months of treatment and TOSS before treatment, at 3, 6, 9, and 12 months of treatment. However, some studies showed different results such as Tahamiler et al. [39], who showed that SCIT yielded superior results compared with the SLIT in patients with allergic rhinitis.

Norman [40], described a number of essential indications for immunotherapy such as poor response to medical treatment, requirement to decrease or avoid long-term medical treatment, concomitant allergic rhinitis or bronchial asthma, undesirable complications of medications, and the cost of pharmacotherapy.

Zuidmeer et al. [41] reported that SCIT with some food allergen may be used for allergies to peaches and fish, but it may be complicated by anaphylactic shock. Moreover, SCIT is not suitable for patients receiving beta blockers or those with severe or unstable bronchial asthma. Therefore, SLIT can be considered a practical substitute for SCIT.


  Conclusion Top


SLIT had the same efficacy as SCIT in the treatment of children with grass pollen-induced VKC, but with less pain and a shorter and a more convenient schedule compared with that of SCIT.

Financial support and sponsorship

Nil.

Conflicts of interest

There are no conflicts of interest.

 
  References Top

1.
Panadda L, Orathai J, Nualanong V, Panida K, Phimramphai S, Pakit V. A double-masked comparison of 0.1% tacrolimus ointment and 2% cyclosporine eye drops in the treatment of vernal keratoconjunctivitis in children. Asian Pac J Allergy Immunol 2012; 30:177–184.  Back to cited text no. 1
    
2.
Cameron JA. Shield ulcers and plaques of the cornea in vernal keratoconjunctivitis. Ophthalmology 1995; 102:985–993.  Back to cited text no. 2
    
3.
Kumagai N. Epidemiology of allergic conjunctival diseases. J Jpn Ophthalmol Assoc 1988; 69:905–909.  Back to cited text no. 3
    
4.
Kumagai N, Fukuda K, Fujitsu Y, Yamamoto K, Nishida T. Role of structural cells of the cornea and conjunctiva in the pathogenesis of vernal keratoconjunctivitis. Prog Retin Eye Res 2006; 25:165–187.  Back to cited text no. 4
    
5.
Tabbara KF. Ocular complications of vernal keratoconjunctivitis. Can J Ophthalmol 1999; 34:88–92.  Back to cited text no. 5
    
6.
Bousquet J, Walter G, Cox L, Pawankar R, Baena-Cagnani E, Blaiss M et al. Sub-lingual immunotherapy − World Allergy Organisation Position Paper 2009. World Allergy Organ J 2009; 11:233–281.  Back to cited text no. 6
    
7.
Mahdy R, Nada W, Shahien E, Boghdadi G, Marei A. Hyposensitization in the treatment of resistant cases of vernal keratoconjunctivitis. Cutan Ocul Toxicol 2010; 29:198–202.  Back to cited text no. 7
    
8.
Akdis M, Akdis CA. Mechanisms of allergen-specific immunotherapy. J Allergy Clin Immunol 2007; 119:780–789.  Back to cited text no. 8
    
9.
Noon L. Prophylactic inoculation against hay fever. Lancet 1911; 1:1572–1573.  Back to cited text no. 9
    
10.
Werfel T. Epicutaneous allergen administration: a novel approach for allergen-specific immunotherapy? J Allergy Clin Immunol 2009; 124:1003–1004.  Back to cited text no. 10
    
11.
Burastero S, Mistrello G, Paolucci C, Breda D, Roncarolo D, Zanotta S, Falagiani P. Clinical and immunological correlates of pre-co-seasonal sublingual immunotherapy with birch monomeric allergoid in patients with allergic rhinoconjunctivitis. Int J Immunopathol Pharmacol 2009; 22:343–352.  Back to cited text no. 11
    
12.
Malling H, Montagut A, Melac M, Patriarca G, Panzner P, Seberova E, Didier A. Efficacy and safety of 5-grass pollen sublingual immunotherapy tablets in patients with different clinical profiles of allergic rhinoconjunctivitis. Clin Exp Allergy 2009; 39:387–393.  Back to cited text no. 12
    
13.
Bonini S, Bonini S, Lambiase A, Marchi S, Pasqualetti P, Zuccaro O et al. Vernal keratoconjunctivitis revisited: a case series of 195 patients with long-term follow up. Ophthalmology 2000; 107:1157–1163.  Back to cited text no. 13
    
14.
Bleik JH, Tabbara KF. Topical cyclosporine in vernal keratoconjunctivitis. Ophthalmology 1991; 98:1679–1684.  Back to cited text no. 14
    
15.
Cox L, Nelson H, Lockey R, Calabria C, Chacko T, Finegold I et al. Allergen immunotherapy: a practice parameter third update. J Allergy Clin Immunol 2011; 127:S1–S55.  Back to cited text no. 15
    
16.
The American Academy of Otolaryngic Allergy (AAOA). Consensus sublingual immunotherapy dosing protocol; 2006.  Back to cited text no. 16
    
17.
Diego S. Sublingual immunotherapy: a useful tool for the allergist in private practice. Biomed Res Int 2016; 93:23–26.  Back to cited text no. 17
    
18.
Malling H. Immunotherapy as an effective tool in allergy treatment. Allergy 1998; 53:461–472.  Back to cited text no. 18
    
19.
Bousquet J, Lockey R, Malling H, the WHO Panel Members. Allergen immunotherapy: therapeutic vaccines for allergic diseases. A WHO Position Paper. J Allergy Clin Immunol 1998; 102:558–562.  Back to cited text no. 19
    
20.
Joint Task Force. Practice parameters for allergen immunotherapy. J Allergy Clin Immunol 1996; 98:1001–1011.  Back to cited text no. 20
    
21.
Moller C, Dreborg S, Ferdousi H, Halken S, Host A, Jacobsen L. Pollen immunotherapy reduces the development of asthma in children with seasonal rhinoconjunctivitis (the PATStudy). J Allergy Clin Immunol 2002; 109:251–256.  Back to cited text no. 21
    
22.
Pajno G, Barbiero G, de Luca F, Morabito L, Parmiani S. Prevention of new sensitizations in asthmatic children monosensitized to house dust mite by specific immunotherapy. A six-year follow-up study. Clin Exp Allergy 2001; 31:1392–1397.  Back to cited text no. 22
    
23.
Canonica G, Passalacqua G. Non-injection routes for immunotherapy. J Allergy Clin Immunol 2003; 111:437–448.  Back to cited text no. 23
    
24.
Wilson D, Torres Lima M, Durham S. Sublingual immunotherapy for allergic rhinitis. Cochrane Database Syst Rev 2003; 2:CD002893.  Back to cited text no. 24
    
25.
Volkmar M, Kopp J, Armin G, Carl-Peter B. Prospective, randomized, double-blind, placebo-controlled multi-centre study on the efficacy and safety of sublingual immunotherapy. Allergy 2004; 59:1285–1293.  Back to cited text no. 25
    
26.
Hordijk G, Antvelink J, Luwema R. Sublingual immunotherapy with a standardised grass pollen extract; a double-blind placebo-controlled study. Allergol Immunopathol (Madr) 1998; 26:234–240.  Back to cited text no. 26
    
27.
Pradalier A, Basset D, Claudel A, Couturier P, Wessel F, Galvain S et al. Sublingual-swallow immunotherapy (SLIT) with a standardized five-grasspollen extract (drops and sublingual tablets) versus placebo in seasonal rhinitis. Allergy 1999; 54:819–828.  Back to cited text no. 27
    
28.
Lima M, Wilson D, Pitkin L, Roberts A, Nouri-Aria K, Jacobson M et al. Grass pollen sublingual immunotherapy for seasonal rhinoconjunctivitis: a randomized controlled trial. Clin Exp Allergy 2002; 32:507–514.  Back to cited text no. 28
    
29.
Feliziani V, Lattuada G, Parmiani S, Dall Aglio P. Safety and efficacy of sublingual rush immunotherapy with grass allergen extracts. A double-blind study. Allergol Immunopathol (Madr) 1995; 23:224–230.  Back to cited text no. 29
    
30.
Quirino T, Lemoli E, Siciliani E, Parmiani S, Milazzo F. Sublingual versus injective immunotherapy in grass pollen allergic patients: a double blind (double dummy) study. Clin Exp Allergy 1996; 26:1253–1261.  Back to cited text no. 30
    
31.
Kovesi T, Schuh S, Spier S, Bérubé D, Carr S, Watson W. Achieving control of asthma in preschoolers. CMAJ 2010; 182:172–183.  Back to cited text no. 31
    
32.
Yukselen A, Kendirli S, Yilmaz M, Altintas D, Karakoc G. Effect of one-year subcutaneous and sublingual immunotherapy on clinical and laboratory parameters in children with rhinitis and asthma: a randomized, placebo-controlled, double-blind, double-dummy study. Int Arch Allergy Immunol 2012; 157:288–298.  Back to cited text no. 32
    
33.
Nelson HS. Subcutaneous injection immunotherapy for optimal effectiveness. Immunol Allergy Clin North Am 2011; 31:211–226.  Back to cited text no. 33
    
34.
Radtke M, Grammer L. Subcutaneous administration of allergen vaccines. Clin Allergy Immunol 2008; 21:321–332.  Back to cited text no. 34
    
35.
Mahdy RA, Nada WM, Marei AA. Subcutaneous allergen-specific immunotherapy versus topical treatment in vernal keratoconjunctivitis. Cornea 2012; 31:525–528.  Back to cited text no. 35
    
36.
Bousquet J, Van Cauwenberge P. Allergic rhinits and its impact on asthma. J Allergy Clin Immunol 2001; 108:240–245.  Back to cited text no. 36
    
37.
Mauro M, Russello M, Incorvaia C, Gazzola G, Frati F, Moingeon P et al. Birch-apple syndrome treated with birch pollen immunotherapy. Int Arch Allergy Immunol 2011; 156:416–422.  Back to cited text no. 37
    
38.
Antúnez C, Mayorga C, Corzo JL, Jurado A, Torres MJ. Two-year follow-up of immunological response in mite-allergic children treated with sublingual immunotherapy. Comparison with subcutaneous administration. Pediatr Allergy Immunol 2008; 19:210–218.  Back to cited text no. 38
    
39.
Tahamiler R, Saritzali G, Canakcioglu S, Ozcora E, Dirican A. Comparison of the long-term efficacy of subcutaneous and sublingual immunotherapies in perennial rhinitis. ORL J Otorhinolaryngol Relat Spec 2008; 70:144–150.  Back to cited text no. 39
    
40.
Norman PS. Immunotherapy: 1999–2004. J Allergy Clin Immunol 2004; 113:1013.  Back to cited text no. 40
    
41.
Zuidmeer-Jongejan L, Fernandez-Rivas M, Poulsen LK, Neubauer A, Asturias J, Blom L et al. FAST: Towards safe and effective subcutaneous immunotherapy of persistent life-threatening food allergies. Clin Transl Allergy 2012; 2:5.  Back to cited text no. 41
    


    Figures

  [Figure 1], [Figure 2], [Figure 3]
 
 
    Tables

  [Table 1], [Table 2], [Table 3], [Table 4], [Table 5], [Table 6], [Table 7], [Table 8]



 

Top
 
 
  Search
 
Similar in PUBMED
   Search Pubmed for
   Search in Google Scholar for
 Related articles
Access Statistics
Email Alert *
Add to My List *
* Registration required (free)

 
  In this article
Abstract
Introduction
Patients and methods
Results
Discussion
Conclusion
References
Article Figures
Article Tables

 Article Access Statistics
    Viewed511    
    Printed70    
    Emailed0    
    PDF Downloaded81    
    Comments [Add]    

Recommend this journal


[TAG2]
[TAG3]
[TAG4]