Delta Journal of Ophthalmology

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


Basem M Ibrahim1, Randa S Abdel-Latif2,  
1 Department of Ophthalmology, Zagazig University, Zagazig, Egypt
2 Department of Medical Microbiology & Immunology, Zagazig University, Zagazig, Egypt

Correspondence Address:
Basem M Ibrahim
Department of Ophthalmology, Faculty of Medicine, Zagazig University, Zagazig 44519
Egypt

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.



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 Jun 19 ];19:1-8
Available from: http://www.djo.eg.net/text.asp?2018/19/1/1/224570


Full Text

 Introduction



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



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

Diagnostic procedures

Ophthalmic history

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

Full ophthalmological examination

With a special focus in conjunctival examination for the presence of conjunctival hyperemia, papillae, giant tarsal papillae, limbal infiltrates, corneal epithelial plaques, and ulcer.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



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}

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}{Table 3}

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}{Table 5}

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}{Figure 1}

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}{Figure 2}

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}{Figure 3}

 Discussion



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



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.

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