The effect of Citrus/Cydonia comp.® on hay fever

Considering the high prevalence of allergic rhinitis and the fact that a
significant number of sufferers with severe symptoms are resistant to treatment
with usual pharmacotherapy (antihistamines and topical nasal corticosteroids)
(Wilson et al., 2005), there still is a space and need for the development of
new treatment concepts.
Citrus/Cydonia comp. is an anthroposophic medicine, which contains lemon juice
(Citrus limon, succus) and a aqueous extract from quince (Cydonia oblonga,
fructus rec., 1:2.1). For over eighty years now, Citrus/Cydonia comp. is being
prescribed as a subcutaneous injection or as a nasal spray for patients who
suffer from seasonal allergic rhinitis. In several European countries,
Citrus/Cydonia comp. is commercially available under the trade name *Gencydo®*
for the prophylaxis and treatment of allergic diseases, specifically those
affecting the respiratory tract such as hay fever.
A survey on clinical experiences, carried out among a group of 39 general
practitioners in the Netherlands, indicates that the subcutaneous treatment
with Citrus/Cydonia comp. ampoules is profoundly effective (Bruin et al.,
2001). Firstly, a permanent effect from the treatment with Citrus/Cydonia comp.
tends to be experienced, which indicates that the patients in question are
claiming to lastingly suffer less from hay fever or even that they are free
from complaints. Secondly, the effect is occurring within a period of two
weeks, up to three months, after the actual treatment. Thirdly, the effect is
optimal after a treatment of several years. In a therapeutic causality report,
positive effects with Citrus/Cydonia comp. were observed in a group of 13
patients suffering from grass pollen mediated hay fever (Baars et al., 2005).
In most patients, Citrus/Cydonia comp. injections were given before the onset
of and during the grass pollen season and symptom severity did not increase
during the pollen season. Furthermore, 69% of the patients reported an
improvement of symptoms. In addition, a prospective, observational study on the
effect of Citrus/Cydonia comp. nasal spray on hay fever symptoms reported
positive results without side effects in 140 patients (Rother and Oexle, 2008).
Recently, the immunological pathways underlying the positive effects of
Citrus/Cydonia comp. in patients with seasonal allergic rhinitis were studied
(Baars and Savelkoul, 2008). Therefore, peripheral blood mononuclear cells
(PMBCs) were isolated from a healthy and an allergic donor and the effect of
Citrus/Cydonia comp. on differentiation capacity and Th1 (e.g. IFN-*) and Th2
(e.g. IL-5) cells was examined. Citrus/Cydonia comp. showed a selective effect
on the differentiation of T-cells by producing relatively more IL-10 than
IL-12. Furthermore, it also had an effect on the induction of regulatory (IL-10
producing) T-cell subsets. It was therefore concluded that Citrus/Cydonia comp.
can potentially restore the disturbed immune state of allergic rhinitis
patients by modulation of the Th1-Th2 balance. This immunotherapeutic potency
and the positive results from the observed clinical cases, form the rational to
further evaluate the effects of Citrus/Cydonia comp. in seasonal allergic
rhinitis.
The tolerability and safety of Gencydo nasal spray was investigated in a
prospective observational study with 140 patients (Rother and Oexle, 2008).
Furthermore, between January 1997 and December 2005, 3.1 million single doses
of injection preparations were sold. Between April 1997 and July 2006, only 2
adverse drug reactions were reported.
Based on the considerations laid down above, Citrus/Cydonia comp. may be an
effective and safe treatment for seasonal allergic rhinitis. Due to its
selective effect on immunological pathways, Citrus/Cydonia comp. might restore
the disturbed immune state of rhinitis patients by modulation of the Th1-Th2
balance.

Several observational studies have shown that Citrus/Cydonia comp. might be an
effective treatment option for patients suffering from seasonal allergic
rhinitis. In these studies Citrus/Cydonia comp. was either administered
subcutaneously or given as a nasal spray. In the present SuNa Hay Fever Pilot
Study we will compare the efficacy and safety of subcutaneous versus nasal
spray administration of Citrus/Cydonia comp. in patients with seasonal allergic
rhinitis by specifically investigating which route of administration is more
effective in the differentiation and inductions of (regulatory) T-cells. The
primary outcome variables are changes in immunological parameters such as
IL-10, IL-12 and IL-5 at week 6, as studied in PMBCs isolated from the blood of
the patients, respectively. Further objectives are to investigate the influence
of Citrus/Cydonia comp. subcutaneous injections versus nasal spray on the
change in clinical symptoms by means of nasal and non-nasal symptom scores. The
safety and tolerability of Citrus/Cydonia comp. injections and nasal spray will
be investigated by determining adverse events surveillance.

A randomised, comparative clinical trial with two parallel groups

After a 2-week run in period the patients will be randomised to a 6 weeks
treatment period.
Treatment group A:
Subcutaneous injections:
twice a week, 1% Citrus/Cydonia comp.
Treatment group B:
Nasal spray:
1-2 sprays of Citrus/Cydonia comp. in each nostril, 4 times a day

- All patients will have to complete 2 times a day a questionnaire and will
have taken two blood samples.
- The patients that participate in the research group will receive 2 times a
week Citrus/ Cydonia comp. injections subcutaneous administrated or 4 times a
day Gencydo nasal spray.
- In the 2 weeks before onset of the study, participants cannot use regular hay
fever medication which will result in an increase of hay fever symptoms.

The risks are the common small risks of subcutaneous administration and venous
blood samples.

There are no known side effects of the subcutaneous administration of Citrus/
Cydonia comp. other than local and small pain symptoms that last for only a
short amount of time. Also known to mild adverse events have been reported for
Gencydo nasal spray (dry and irritated nasal mucosa).