UNIVERSITY OF GRONINGEN / FACULTY OF MEDICAL SCIENCES

Development of a clinical decision support system for diagnosis and

management of allergy patients in primary care

E.M. Roerdink

Student number: 1852566

01-02-2013 until 01-07-2013

Supervisor: Prof. dr. A.E.J. Dubois (facultair begeleider)

Dr. B.M.J. Flokstra- de Blok

Drs. T.M. Brakel

University Medical Center Groningen: department of pediatrics, allergy

1

Abstract

Aim. To support General Practioners (GPs) in diagnosis and management of allergy

patients, the University Medical Center Groningen (UMCG), in collaboration with

Labnoord, developed a clinical decisison support system for allergy patients. The aim of

this study was to develop a classification of allergic diseases, as well as a list with allergy

medication. Also, to develop a diagnostic decision tool, answers on the diagnostic

questionnaire and IgE-results should be matched to an allergic diagnosis. Finally, the aim

was to determine the agreement between a golden standard and a diagnosis made by the

diagnostic decision tool.

Methods. The diagnostic questionnaire was tested for patients visiting the clinic of the

(pediatric) allergology and dermatology departments of the UMCG. The questionnaire

was checked for missing or redundant questions. A classification of allergic diseases was

formulated, based on NHG (“Nederlands Huisartsen Genootschap”) clinical practice

guidelines and expert opinion. Using the “Pharmacotherapeutic Compass”

(“Farmacotherapeutisch Kompas”) the allergy medication was classified. An allergy

specialist matched the answers on the questionnaire to allergic diagnoses, which together

with the IgE-results resulted in a diagnostic tool with decision rules. Two allergy

specialists and two dermatology specialists made a diagnosis (the golden standard) using

information available in “Poliplus”. Two researchers made a diagnosis using the decision

tool. Agreement between the golden standard and the diagnosis based on the decision

tool was calculated by defining the true-positive and false-negative diagnoses. The inter-

rater reliability between the two allergy specialists, the two dermatology specialists, and

the two researchers was calculated using Cohen’s kappa.

Results. The allergic diseases were classified and the decision tool with decision rules

was constructed. A list with indicated and contra-indicated allergy medication was

formulated. In 69.2% of the cases there was agreement between the golden standard and

the diagnosis based on the decision tool. Three questions on the questionnaire were

redundant and one question was missing. There was moderate agreement found between

the allergy specialists and moderate agreement between the dermatologists. Only

regarding treatment of eczema of the body, poor agreement was found. Between the two

researchers very good agreement was found.

Conclusion. The agreement between the golden standard and the diagnostic tool IDEAL

was fairly good and the inter-rater reliability was varying. The questionnaire and the

decision tool have to be adjusted based on the findings of this pre-testing. Next, the

questionnaire has to be validated and the IDEAl system has to be tested in a pilot study

for effectiveness.

2

Samenvatting

Doel. Om huisartsen te ondersteunen bij het diagnosticeren en behandelen van

allergiepatienten heeft het Universitair Medisch Centrum Groningen, in samenwerking

met Labnoord een beleidsondersteuningssysteem ontwikkeld. Het doel van dit onderzoek

was om zowel de allergische aandoeningen te classificeren als ook de allergiemedicatie.

Om een diagnostische beslissingsysteem te ontwikkelen, moeten antwoorden op de

vragenlijst en de IgE-resultaten worden gekoppeld aan een allergische diagnose. Tot slot

was het doel van dit onderzoek om de overeenstemming tussen een gouden standard en

een diagnose gebaseerd op het diagnostische beslissingssysteem te bepalen.

Methode. De vragenlijst is getest bij patienten die de kliniek van de (kinder)allergologie

en dermatologie afdeling van het UMCG bezochten. De vragenlijst werd gecontroleerd

voor ontbrekende of overbodige vragen. Allergische aandoeningen werden

geclassificeerd, gebaseerd op NHG standaarden en de mening van een expert. Met

behulp van het farmacotherapeutisch kompas werd de allergie medicatie geclassificeerd.

Een allergoloog heeft de antwoorden op de vragenlijst gekoppeld aan allergische

diagnoses, die samen met de IgE-resultaten restuleert in een diagnostisch

beslissingssysteem met beslissingsregels. Twee allergologen en twee dermatologen

stellen een diagnose (de gouden standaard) met behulp van informatie uit Poliplus. Twee

onderzoekers stelden de diagnose met behulp van het beslissingsysteem.

Overeenstemming tussen de gouden standard en de diagnose gebaseerd op het

beslissingsysteem werd berekend aan de hand van de terecht-positieve en fout-negatieve

diagnoses. De inter-beoordelaar betrouwbaarheid tussen de twee allergologen, de twee

dermatologen en de twee onderzoekers werd berekend met Cohen’s kappa.

Resultaten. De allergische aandoeningen zijn geclassificeerd en het beslissingssysteem

met de beslisregels zijn ontwikkeld. Een lijst met geindiceerd en contra-geindiceerde

medicatie is opgesteld. In 69.2% van de gevallen was er overeenstemming tussen de

gouden standaard en de diagnose gemaakt door het beslissingsysteem. Drie vragen waren

overbodig en 1 vraag ontbrak. Er was gemiddelde overeenstemming tussen de

allergologen en ook gemiddelde overeenstemming tussen de dermatologen. Alleen met

betrekkeing tot de behandeling van eczeem van het lichaam, werd slechte overeenkomst

gevonden. Tussen de twee onderzoekers werd uitstekende overeenkomst gevonden.

Conclusie. De overeenstemming tussen de gouden standaard en het beslissingssysteem

IDEAL was redelijk goed en de inter-beoordelaar betrouwbaarheid was wisselend. De

vragenlijst en het belissingssysteem moeten worden aangepast op basis van de resultaten

van dit vooronderzoek. Daarna zal de vragenlijst gevalideerd moeten worden en moet het

IDEAL systeem voor effectiviteit getest worden in een pilot studie.

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Contents

1. Introduction ............................................................................................................................... 4 1.1 Pathophysiology of allergy ................................................................................................... 4

1.1.1 Allergic rhinitis .............................................................................................................. 5 1.1.2 Food allergy ................................................................................................................... 6 1.1.3 Atopic Dermatitis ........................................................................................................... 6 1.1.4 Asthma ........................................................................................................................... 6

1.2 Prevalence of allergy & allergy management in primary care............................................. 7 1.3 Problems concerning care of allergy patients in primary care ............................................ 7 1.4 Clinical decision support system: IDEAL ............................................................................. 8 1.5 Aim of the study & research questions ................................................................................ 10

1.5.1 Research questions ....................................................................................................... 10

2. Methods .................................................................................................................................... 11 2.1 Questionnaire testing .......................................................................................................... 11 2.2 Development of the IDEAL system ...................................................................................... 11 2.3 Testing of the IDEAL system ............................................................................................... 14

2.3.1 Agreement between golden standard and IDEAL ....................................................... 14 2.3.2 Inter-rater reliability ..................................................................................................... 15

3. Results....................................................................................................................................... 17 3.1 Development IDEAL system ................................................................................................ 17 3.2 Descriptive statistics ........................................................................................................... 17 3.3 Agreement between golden standard and IDEAL ............................................................... 18 3.4 Inter-rater agreement .......................................................................................................... 20

4. Discussion ................................................................................................................................. 21 4.1 Limitations .......................................................................................................................... 22 4.2 Conclusions ......................................................................................................................... 23

5. References ................................................................................................................................ 24

Appendix 1: CARAT vragenlijst ................................................................................................ 28

Appendix 2: IDEAL vragenlijst ................................................................................................ 28

Appendix 2: IDEAL vragenlijst ................................................................................................. 29

Appendix 3: begeleidende brief kinderallergologie .................................................................. 31

Appendix 4: toestemmingsverklaring ........................................................................................ 32

Appendix 5: folder ....................................................................................................................... 33

Appendix 6: classificatielijst ....................................................................................................... 33

Appendix 6: classificatielijst ....................................................................................................... 34

Appendix 7: voorbeelden beslissingssysteem ............................................................................ 41

Appendix 8: medicatielijst .......................................................................................................... 48

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1. Introduction

1.1 Pathophysiology of allergy

Allergy can be described as an immunological hypersensitivity reaction of the body.

Normally, the immune system of a healthy individual does not react to harmless

antigens, however in allergic individuals it does react to these antigens, referred to as

allergens. Allergic reactions occur immediately after exposure to the allergen, or later.

During an immediate reaction T-helper cells (Th2-cells), immunoglobuline E (IgE), mast

cells and eosinophil granulocytes are involved.1 The allergen induces CD4+ Th2-cells,

which in combination with B-lymphocytes produce IgE specific to this antigen and this

binds to the Fc-receptor of the mast cells and basophilic granulocytes. After cross-linking

of IgE with the allergen, the cells are activated and mediators are released

(e.g.histamine). This process of IgE binding to the mast cells is called sensitization. The

mediators released from the mast cells cause increased vascular permeability,

vasodilatation and bronchial and visceral smooth muscle contraction. After this

immediate reaction, a late reaction can follow. In late allergic reactions, neutrophilic

granulocytes, eosinophilic granulocytes, macrophages and CD4+ Th2-cells are involved.

This late reaction is induced by cytokines, which are released from the Th2-cells and

mast cells. IgE is primarily found on mast cells, activated eosinophils and circulating

basophils.2 The late reaction starts at 4-6 hours and takes 8-12 hours to develop. Late

reactions mainly occur in the lungs (causing symptoms of asthma) and the skin (causing

eczematous reactions).2

Histamine causes an increased blood flow in the surrounding area and an increase in

vascular permeability. Enzymes, such as mast-cell chymase, tryptase, and serine

esterases are also released and cause tissue destruction. Released TNF-alpha (tumor

necrosis factor alpha) activates endothelial cells, which causes an increase of expressed

adhesion molecules. This in turn attracts leukocytes and lymphocytes. Besides the

released histamine, enzymes and TNF-alpha, also chemokines and lipid mediators are

released. These mediators are responsible for the acute and chronic inflammatory

response. The lipid mediators are important for the late response. They cause smooth

muscle contraction, increased vascular permeability, mucus secretion and activation of

leukocytes. Also arachidonic acid is produced, which leads to the formation of

prostaglandins, thromboxanes, and leukotrienes.2 Eosinophil granulocytes, also produced

in an allergic reaction, are mainly found in tissues and have probably a function in the

defense against infection. Activated eosinophils release toxic granule proteins and free

radicals, which can kill micro-organisms, especially parasites. However, in allergic

disease, these toxins and free radicals cause tissue damage. A second effect of

eosoniphils is synthesis of mediators such as prostaglandins, leukotrienes, and cytokines.

These maintain the inflammatory response. Basophils are also produced in allergic

reactions and together with eosinophils, basophils also cause tissue damage in allergic

reactions.

5

Total IgE and specific IgE to a certain allergen can be measured. IgE-levels will be

increased in atopic individuals.3 Atopic individuals are genetically predisposed to

produce IgE to certain allergens. As mentioned before, sensitization implies allergens

specific IgE production, however not every sensitized person develops allergic

symptoms. Total IgE is not specific to allergic disease and is less informative than

specific IgE for diagnosing allergy.4 The most severe allergic reaction is an anaphylactic

reaction.2 This reaction is caused by widespread mast-cell activation. A decrease of

vascular permeability can cause hypotension and airway obstruction. Anaphylactic shock

can be life threatening. Atopic disease can occur at different ages, symptoms can appear

and disappear and be replaced by other symptoms. Atopy is caused by a combination of

genetic and environmental factors.5 Environmental factors related to atopy include

allergen exposure, cigarette smoke, low birth weight, and infections.5,6

Examples of

atopic diseases are allergic rhinitis, atopic dermatitis (AD), food allergy, and asthma.

Atopic dermatitis typically manifests in infancy, in contrast to asthma and allergic

rhinoconjunctivitis, which manifest later in childhood. The transition of atopic dermatitis

via asthma to rhinitis is called the atopic march.7 The main allergen causing problems

during the first year of life is cow’s milk. Later in life inhalation of allergens commonly

causes allergic disease.8 Children with AD, are at risk for developing asthma

9, children

with allergic rhinoconjunctivitis for developing asthma, and children with asthma for

developing allergic rhinoconjunctivitis.10,11

Allergic diseases such as rhinitis, asthma,

AD, or food allergy can result in a reduction of quality of life.11,12,13,14

1.1.1 Allergic rhinitis

Allergic rhinitis is a disorder characterized by symptoms of nasal congestion, rhinorrhea,

sneezing, and itching.15

When the nasal symptoms are accompanied by ocular symptoms,

the disorder is called rhinoconjunctivitis. Allergic rhinitis is an IgE-mediated allergy.

After binding of the allergen to IgE, histamine is released. This results in an increase in

vascular permeability of the nose and the nerve endings are stimulated, which leads to

sneezing and itching. This is the early phase reaction of rhinitis. The late reaction occurs

6-12 hours later and is characterized by hyperreactivity and priming. Priming means that

very small amounts of allergen(s) that would normally not induce an allergic reaction can

cause symptoms. Allergic rhinitis is caused by inhalation of aero-allergens, such as grass,

tree pollens, or house dust mites. Intranasal or ocular corticosteroids, local and oral

antihistamines together with allergen avoidance measures are treatment options for

allergic rhinoconjunctivitis. Immunotherapy is also a treatment option for allergic

rhinitis. Application of immunotherapy in primary care will be discussed later in this

introduction.15

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1.1.2 Food allergy

Adverse reactions to foods can be caused by non-allergic diseases (such as lactose-

intolerance) and allergic disease.16

Food allergy can be further divided in IgE-mediated

food allergy and non-IgE mediated food allergy. In IgE-mediated food allergy a raised

specific IgE test result or a positive skin test can be found. The golden standard to

diagnose food allergy is the double-blind placebo-controlled food challenge. During this

test, the patient receives the suspected food allergen on the verum day, and a placebo on

the placebo day. The food is masked in a matrix. Both patient and physician are unaware

which day is the verum day and which day the placebo day. An alternative test is an open

challenge, however, more false-positive test results can occur.17

Symptoms related to

food allergy are varying, from skin symptoms such as urticaria, to gastro-intestinal

symptoms (diarrhea, vomiting), or respiratory symptoms (rhinitis, coughing).16

Anaphylactic symptoms can also occur with food allergy. Specific symptoms such as

urticaria or asthma can be treated. After the diagnosis is set, the food should be

eliminated from the diet. Also, in case of (an increased risk of) anaphylactic reactions, an

epinephrine auto-injector (EAI) should be prescribed.14

As described before, anaphylaxis

can result in an anaphylactic shock that can be life-threatening. Administration of

epinephrine can prevent this.

1.1.3 Atopic Dermatitis

AD is a condition characterized by erythema, vesicles, crusting, scaling of the skin,

papules, lichenification, and itching.18

This form of eczema occurs in atopic children, in

other words children also susceptible for developing asthma, allergic rhinitis/

conjunctivitis, and/or food allergy. In a cohort study, children with AD developed asthma

in about 30% and allergic rhinitis in 15%.19

This type of eczema is often IgE-mediated.

However, for diagnosing AD, IgE-testing is not recommended because it does not add to

the diagnosis of AD. Treatment of AD consists of emollients in mild AD and local

applied corticosteroids for more severe forms of AD. Relatively new in the treatment of

AD are immunomodulators, such as tacrolimus or pimecrolimus, but they are not part of

standard treatment yet.18

1.1.4 Asthma

Patients with asthma have airway hyperreactivity, resulting in repeated periods of

bronchus constriction.20

Hyperreactivity can result from allergic stimuli or other stimuli

such as physical strain, smoke, dust, fog, cold air, or viral infections. About 80% of

children with persisting asthma are allergic. From the age of 6 years, children can be

diagnosed with asthma, based on history, physical examination, and spirometry. Before

the age of 6 the symptoms are described as wheezing with or without coughing.

Symptoms of asthma can be prevented by avoiding causative stimuli (such as house dust

7

mite).

Treatment of asthma exists of bronchodilators and/or inhalation

corticosteroids.20,21

1.2 Prevalence of allergy & allergy management in primary care

In the Netherlands, the prevalence of allergic and non-allergic rhinitis is 25 per 1000 men

and 31 per 1000 women.15

AD occurs in 16 per 1000 patients, in primary care. Mostly

children are affected with AD. In children under the age of 1, the prevalence is 220

(boys) and 140 (girls) per 1000 patients.18

The prevalence of self-perceived food allergy

or food intolerance is more than 10% of the population. Yet, food allergy only affects 1-

4% of children and adults.16

The most common food allergy in newborns is cow’s milk

allergy. The prevalence is 1-3% and decreases in toddlers. Asthma occurs in 5-10% of

the population. The prevalence of asthma is higher in boys until puberty, after puberty

the prevalence of asthma is higher in girls.20

In adults, the prevalence of asthma in

primary care is 28 per 1000 patients.21

See Table 1 for prevalences of allergic disease in

the Netherlands.

Table 1: Prevalences of allergic disease in the Netherlands

Atopic Dermatitis 16 *

Rhinoconjunctivitis 25-31*

Food allergy 1-4% **

Asthma 5-10%**

* Per 1000 patients, in primary care

** Of all children and adults

The prevalence of allergic disease worldwide is increasing.22,23

This increase of allergic

disease is not fully understood but can be explained by genetic and environmental factors

and life style changes. Allergic disease is associated with three factors: westernization,

urbanization, and affluence.23

A study performed in Greece by Priftis et al. shows the

effect of urbanization on the prevalence of allergy.24

In this longitudinal cohort study, an

association between urban environment and a higher prevalence of allergic rhinitis was

found. Rural living and the risk of atopy during childhood were negatively associated.

1.3 Problems concerning care of allergy patients in primary care

Medical care of allergy patients mainly takes place in primary care. This, together with

the increasing number of allergy patients, results in an increased workload for GPs.25

The

General Practice Research database from the UK shows that about 50% of patients aged

<18 years visits the GP with an allergic complaint at least once. Approximately 1 in 3

children are diagnosed with AD, 1 in 5 with asthma, and 1 in 10 with rhinitis.26

A large

8

National Allergy Societies Survey was performed to asses the most important allergies

diagnosed and managed in primary care, and the criteria for referral to secondary care.25

Sixteen countries participated in this survey. The most frequent allergic diseases

managed in primary care were allergic rhinitis, atopic dermatitis, asthma, and food

allergy. Other allergies, such as drug allergy and anaphylaxis are referred to secondary

care. Also, this survey showed that there is a need for education about recognition of

allergic disease and the diagnostic workup for GPs.25

Diagnostic testing by GPs for allergy patients can be beneficial in several ways, for

instance it can result in better allergen avoidance, disease monitoring, and specific allergy

treatment.27

A diagnostic test available in primary care to test for sensitization is the IgE-

test, such as the CAP-FEIA (ImmonoCAP).28

However, there is no consensus about when

to use IgE-testing. Guidelines indicate that patients with severe, persisting and/or

recurrent allergic symptoms should undergo allergy testing.26

This is dependent on the

prevalence of allergy in different countries.25

Since patients with allergy symptoms

initially come to the GP, the challenge for the GP is to know when to use which

diagnostic tool for a patient. Performing skin prick testing is only recommended for

physicians with specific allergy training.25

IgE-testing in combination with the clinical

history of the allergy patients can be used by the GP to diagnose the patient correctly.

Diagnostic testing by primary care physicians leads to more appropriate referrals to

specialists and therefore more effective utilization of health care.25

In the Netherlands the

number of IgE-tests requested by GPs has increased.30

Simultaneously, there is a lack of

knowledge about interpretation of this test by GPs. Therefore, the interpretation of IgE-

results has proven to be difficult for GPs.30

For these reasons, it would be beneficial to

provide the GP additional information together with the IgE test results, to make the

interpretation of the results more useful.

Aside from problems with allergy diagnostics, it appears that GPs also struggle with

appropriate prescription of EAIs. In a study performed in Dutch high school children,

93% of children who should have been prescribed an EAI, had not been prescribed one.31

This indicates that there is an underprescription of EAIs and suggests that GPs may

underprescribe this device. Use of immunotherapy (IT) in primary care and referral for

IT can also improve in primary care. The National Allergy Societies Survey showed that

most patients in primary care had access to IT for aeroallergens, bee/wasp, or sublingual

IT.25

However, referrals to allergy specialists for initiating the IT was more problematic;

in only 43% of cases referral for IT occurred.

In a study performed by Goossens et al, the knowledge of GPs concerning food allergy

in the Netherlands was studied.32

It was found that GPs did not feel confident to diagnose

a patient with food allergy and to manage this patient. Also, recognizing anaphylactic

reactions by the GP was problematic.

1.4 Clinical decision support system: IDEAL

Because of the increasing prevalence of allergy and the problems for GPs concerning

diagnosis and management of allergy patients outlined above, a clinical support system is

being developed at the University Medical Center Groningen (UMCG), in collaboration

9

with LabNoord. This clinical decision support system for allergy patients is called

IDEAL (“In vitro Diagnostiek en Eerstelijns Allergie Leidraad”). Since 2010 a

diagnostic allergy questionnaire has been developed. This questionnaire is partly based

on the CARAT questionnaire (Appendix 1). This is a diagnostic questionnaire for asthma

and rhinoconjunctivitits. Since August 2011 the diagnostic questionnaire has been tested

in allergy patients. A variant of the questionnaire for children and for adults was

formulated. Later, it was decided that a single questionnaire was more convenient. One

of the reasons is that for children under the age of 15 the questionnaire is completed by

the parent(s), so the need for a separate questionnaire for children is minimal.

In the proposed clinical decision support system, an advice for GPs about diagnosis and

treatment of allergy patients will be formulated, based on the diagnostic questionnaire

and specific IgE test results. The advice is based on the NHG clinical practice guidelines,

and knowledge and experience of allergy specialists. The GP can refer to the system

when needed. The advice for the GP will be free of obligations, i.e., GPs can decide to

comply with the advice or not. The system will be automatized in the future. The system

aims at improving the interpretation of laboratory results for allergy patients. The system

will improve expertise of GPs about allergy, and this consequently leads to a more

efficient diagnosis and treatment for the patient. It will also lead to more accurate

referrals to the allergy specialist. A recent study in the UK showed that only 43% of

patients referred to secondary care by their GP, was actually diagnosed with an allergy.

This indicates that a large proportion of patients seen by specialists, are patients without

an allergy.33

No comparable data is available for the Netherlands, however, personal

communication with two allergology specialists from the UMCG confirm that also in the

Netherlands many unnecessary referrals are made by GPs.34,35

A consult in primary care

costs €28 and in secondary care €72.36

Hence, more accurate referral of allergy patients

by GPs, can result in a saving of costs. Patients with manageable and uncomplicated

allergies should be seen in primary care and only patients with special indications should

be referred to specialists. The system will also provide information about laboratory tests

for allergy. Less unnecessary testing will also contribute to the saving of costs. At

LabNoord, a test for total IgE costs € 36,45. In 2010, 6191 IgE-tests were ordered at this

laboratory, and in the first half of 2011 3873 tests were ordered. This counts up to a total

of € 224.980 for 2010 and € 140.745 for the first half of 2011. Annually this can result in

a saving of € 200.000.(LabNoord: personal communication.)

The IDEAL system was developed according to the asthma-COPD service for primary

care.37

This service has also been developed by the UMCG in collaboration with

LabNoord.38

Analogous to the IDEAL system, the asthma-COPD service aims at

supporting the GP with diagnoses, management, and follow-up of the patient. The

spirometry results together with a questionnaire are sent to the pulmonologist in the

UMCG. An advice about the diagnosis and management of the patient is sent to the GP.

This system has proven to be successful. The system has led to less asthma/ COPD

exacerbations, less complaints, more control of the disease, and less referrals to

secondary care.38

It is expected that the IDEAL clinical decision support system will

achieve the same: better control of allergy patients and their complaints, more efficient

referral to secondary care, and also more adequate diagnostic testing.

10

To summarize, a clinical decision support system was developed to support GPs with

diagnosing and treating allergy patients. This system should lead to more efficient

referrals, better treatment of allergy patients, and a cost reduction by more accurate

diagnostic testing.

1.5 Aim of the study & research questions

The aim of this study was to develop a classification of allergic diseases and also for the

allergic medication. To develop a decision tool, the possible answers to the questions of

the diagnostic questionnaire should be matched to the allergic diagnoses. Also, the

agreement between a golden standard and the diagnosis made using the decision tool has

to be determined. Finally, the inter-rater reliability between the two allergy specialists,

two dermatology specialists and the two researchers will be determined.

1.5.1 Research questions

1. How can allergic diseases be classified, based on severity and therapy?

2. Which answers on the diagnostic questionnaire correspond to which diagnosis?

3. What medication is indicated or contra-indicated for the different allergic

disease? What are the generic and brand names of these drugs? Which dose and

frequency of these drugs are indicated for the different allergic diseases?

4. Can the diagnosis made by the specialist during the real-life encounter with the

patient also be made based on the diagnostic questionnaire alone? What is the

concordance between the gold-standard-based diagnosis (by specialists based on

real-life encounter) and the system-based diagnosis (by researchers based on

diagnostic questionnaire and diagnostic decision tool) ?

5. What is the inter-rater reliability between two allergy specialists, or between two

dermatology specialists, when making a diagnosis using the reporting of the real-

life encounter with the patient?

6. What is the inter-rater reliability between two medical researchers when making a

diagnosis using the diagnostic questionnaire?

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2. Methods

2.1 Questionnaire testing

The existing diagnostic questionnaire was tested in patients to improve the questionnaire.

Improvements included completeness of the questionnaire (to check whether questions

about all allergic disease were included), redundancy of questions, and phrasing of

questions. The questionnaire was tested in patients of the allergology, pediatric

allergology, and dermatology department, as well as primary care. The allergology,

pediatric allergology and dermatology department of the UMCG were closely involved

in the development of the clinical support system. GPs which had already participated in

a previous part of testing the clinical supporty system, were also participating in this

study. In the dermatology department, only patients with eczema were asked to

participate. Patients visiting the clinic were asked to complete the questionnaire. Every

patient received an envelope with a questionnaire, an informed consent form, an

information letter and a flyer (see Appendix 2-5). Patients were supposed to complete the

questionnaire before seeing the physician. However, in some departments the

questionnaires were sent to the patient’s home. Patients wrote the date of completion on

the questionnaire. Parents were asked to complete the questionnaire for their children

under the age of 15. The study was approved by the local medical ethics committee

(METc 2011/273).

2.2 Development of the IDEAL system

The IDEAL system consists of several components, which will be described next. A

diagrammatical representation of the IDEAL components and their relations is presented

in Figure 1.

Classification of allergic diseases. A classification of allergic diseases was formulated,

based on NHG clinical practice guidelines and expert opinion (two allergy and two

dermatology specialists involved in this project). The allergic diseases were subdivided

with respect to severity and therapeutic consequences. For instance, rhinoconjunctivitis

can be subdivided in mild, moderate or severe rhinoconjunctivitis; with respect to

therapeutic consquences it can be subdivided into adequate treatment, over-treatment,

under-treatment, etc.

Classification of allergy medication. In order to be able to match allergic diagnosis with

a treatment, a list of allergy medication was formulated. Using the

‘Farmacotherapeutisch Kompas’ the allergy medication was matched to the allergic

diseases, and contra-indicated medication was identified. Also, the dose and frequency of

12

the drugs for the different allergic disease was categorized. The result was checked by an

allergy specialist.

13

Figure 1. Description of the IDEAL system, consisting of system development, system

diagnosis, and system testing.

14

Decision tool. An allergy specialist matched the possible answers on the diagnostic

questionnaire and specific IgE results to a diagnosis within the previously formulated

classification (see Classification of allergic diseases above). This results in a diagnostic

decision tool with decision rules. A completed questionnaire by a patient is used as input

for the decision tool, which determines the corresponding diagnosis based on decision

rules as previously determined by the expert.

2.3 Testing of the IDEAL system

Descriptive statistics of the patients will be given: percentage of male/female, mean age,

percentage of IgE-results, mean time interval between consult in the clinic and

completion of the questionnaire, percentage of specialists who assessed their own

patients (after seeing the patients in the clinic).

Inclusion criteria

Patients were included if they were referred to the dermatology, allergology, and

pediatric allergology department and had already been seen in the clinic. All

questionnaires returned in the time period of this study (10-05-2013- 01-07-2013) were

used in this study.

2.3.1 Agreement between golden standard and IDEAL

A golden standard was defined as the diagnosis based on the real-life encounter (e.g., the

consult in the clinic). Two allergy specialists received a list of UMCG-numbers of the

patients who completed the diagnostic questionnaire and a short description of the main

complaint of the patient. They had not seen the questionnaire, but made a diagnosis using

information of the real-life encounter in the clinic. This information was found in the

patient information system ‘Poliplus’. The diagnosis had to be one from the classified

allergic diseases. Also, two dermatology specialists were asked to do the same for the

eczema patients. This diagnosis was defined as the ‘golden standard’.

The testing phase consisted of determining the agreement between the golden standard

and the diagnosis made by IDEAL. This was done in the following way.

The qualitative degree of agreement was divided in the following categories:

*No agreement: different diagnosis

(e.g. asthma vs. no asthma).

*Partial agreement: same allergic disease, with more then 1 severity score

difference

(e.g. seisonal rhinioconjunctivitis vs. perennial

rhinoconjunctivitis, or mild asthma vs. severe asthma)

*Substantial agreement: same allergic disease, only 1 severity score difference

(e.g. mild asthma vs. moderate asthma)

*Total agreement: exact same diagnosis and severity score.

15

For all allergy and dermatology specialists, percentages of no agreement, partial-,

substantial- and total agreement were compared to those of the researchers.

In order to define a quantitative degree of agreement in a statistical sense it was

necessary to reduce the categories of allergic diseases in the classification list. Therefore

the categories of allergic disease were reduced to the main categories:

rhinoconjunctivitis, asthma, bee/wasp allergy, eczema, anaphylaxis, food allergy, latex

allergy, work or hobby related allergies, drug allergies, and urticaria/angio-oedema. Only

when there was agreement between the two (allergy or dermatology) specialists and also

between the two researchers, then the true-positive (TP) and false-negative (FN)

diagnoses were determined. The percentage of correct diagnoses resulting from IDEAL

were calculated (TP/ TP+FN) *100%. Also, the confidence interval was calculated with

the following formula:

where p equals TP/TP+FN and n is the total number of diagnoses.

2.3.2 Inter-rater reliability

To test for inter-rater reliability, Cohen’s kappa and corresponding confidence interval

were calculated for the three groups, i.e., the allergy specialists, the dermatology

specialists, and the medical researchers.

In the case of the allergy specialists, the following categories were defined:

rhinoconjunctivitis not allergic, rhinoconjunctivitis allergic seasonal, rhinoconjunctivitis

allergic perennial, asthma allergic, asthma not allergic, anaphylaxis, food allergy low

risk, food allergy high risk, food allergy unlikely, drug allergy, urticaria/ angio-oedema,

and bee/wasp allergy.

In the case of the dermatology specialists, the agreement concerning the severity of

eczema and the agreement concerning the therapy of eczema were defined. Therefore,

the following categories were defined.

For the severity of eczema:

1. Facial eczema: no eczema, mild eczema, moderate eczema and severe eczema.

2. Eczema of the body: no eczema, mild eczema, moderate eczema and severe

eczema.

For the treatment of eczema:

1. Eczema not under control/ possible under-treatment of the eczema.

2. Well controlled eczema/ adequate treatment of the eczema.

3. Possible over-treatment

In the case of the medical researchers using the IDEAL system, the following categories

were defined: rhinoconjunctivitis, food allergy likely, food allergy unlikely, asthma,

16

anaphylaxis, drug allergy, urticaria/ angio-oedema, bee/wasp allergy, work related/

hobby related allergy, eczema.

According to Peat et al.39

a kappa value of 0.5 or above represents moderate agreement, a

value above 0.7 represents good agreement, and a kappa above 0.8 represents very good

agreement. The confidence interval for kappa was calculated by the formula: kappa +/-

1.96*SE (kappa and standard error SE given by SPSS).

SPSS statistics 20 was used to analyze the data.

17

3. Results

3.1 Development IDEAL system

Since 10-05-2013, 94 completed questionnaires were returned. From the dermatology

department, 11 questionnaires were returned, from the allergology department 33

questionnaires, from the pediatric allergology department 12 questionnaires, and from

primary care 37 questionnaires were returned. (See Appendix 2 for the most recent

version of the questionnaire.)

The allergic diseases were classified by the expert, see the classification in Appendix 6.

This classification was approved by the second allergy specialist. Indicated and contra-

indicated medication for allergy patients (rhinoconjunctivitis, atopic dermatitis, asthma,

urticaria, anaphylaxis etc.) were formulated. Generic and brand names of the drugs and

the dose and frequency of these drugs were collected. See appendix 8 for these lists. The

decision tool was constructed, resulting in a set of decision rules. See Appendix 7 for

three examples of decision rules. In a similar manner, the decision rules for the other

allergic diseases were formulated.

The following questions were redundant for making any diagnosis, see Appendix 2:

question 2.11 (How often, in the worst period of the year, did you have to use extra

medication because of nose and/or asthma symptoms?), question 2.12 (Outside this worst

period, are your complaints: the same, less serious, considerably less serious, or absent?)

and question 3 (Which of the following is present in your home? Cat, dog, bird, rodent,

mold/fungus, carpeting in the bedroom). These questions did not occur in any of the

decision rules for making the allergic diagnoses.

3.2 Descriptive statistics

Of the 94 returned questionnaires, 42 concerned patients from the dermatology and the

(pediatric) allergology departments. These patients had already been seen in the clinic

and were therefore included in this study. The 37 questionnaires from primary care could

not be used in this study, because these patients were not seen in the clinic and therefore

no golden standard could be set. From the 42 questionnaires, 11 were from the

dermatology department, 20 from the allergology department and 11 from the pediatric

department. (See table 2)

Table 2: Departments of returned questionnaires

Number of returned

questionnaires Percentage

Dermatology 11 26.2%

Allergology (adult) 20 47.6%

Pediatric Allergology 11 26.2%

Total 42 100%

18

In 18 patients total IgE’s were measured, with a mean value of 557 kU/ml, range: 25

kU/ml - 4230 kU/ml. Also for 18 patients the specific IgE’s were measured. The values

of the IgE-results were used to differentiate between allergic and non-allergic asthma,

and between allergic and non-allergic rhinoconjunctivitis. In 14 cases, the relevant IgE-

results were missing, while the decision rules required these results.

Table 3: Characteristics of patients (n=42)

Gender, male/female 38.1%, 61.9%

Mean age, min/max age 26.2 years 2 months, 68 years

Date of filling in questionnaire Min: 05-04-2012 Max: 22-05-2013

Mean, SD interval* 7.92 days 11.0 days

*Interval between date of consult and of completing questionnaire.

Patients were seen in the allergology clinic by 5 different specialists, in the dermatology

clinic by 7 different specialists and in the pediatric clinic by only one specialist. The two

allergology specialists assessed 7 and 11 of their own patients (seen in the clinic),

respectively. The dermatology specialist assessed 1 own patient. For the other specialist

it was unknown.

Patients completed their questionnaire on the same day of the consult in 31.0% of the

cases. In 7,1% of cases the questionnaire was filled in 1 or 2 days after their consult in

the clinic. In 14.3% the questionnaire was filled in not later than a week before the

consult. And 33,3% of patients completed their questionnaire more than a week before

their consult. In 14.3% of the cases the date of completing the questionnaire was missing.

The mean interval between the date of the consult and completing the questionnaire was

7.92 days before the consult in the clinic, with a standard deviation of 11.0 days. For

patients with eczema this mean interval was 18.3 days (before the consult in the

hospital), with a standard deviation of 11.7 days.

3.3 Agreement between golden standard and IDEAL

In Table 4, the frequencies of agreement between the allergy and dermatology specialists

compared to the medical researchers are presented. Especially for the allergy diagnoses

other than eczema, there was often no agreement between the specialists (golden

standard) and medical researchers using the decision tool. Total agreement was not often

present. Therefore, more detailed analyses of the comparison between the golden

standard and diagnoses based on IDEAL will be given.

Of all diagnoses with agreement between the allergy specialists, between de dermatology

specialists and between medical researchers 1 and 2, 18 diagnoses were true-positive

diagnoses and 8 were false-negative. This results in a percentage of correct diagnoses by

IDEAL of 69.2%, with 95% confidence interval (CI) [67.18 ; 71.22 ].

19

Table 4: agreement between specialists and researchers

Total

agreement

Substantial

agreement

Partial

agreement

No

agreement

Total

diagnoses*

A/ E 6 (15.4%) 9 (23.1%) 6 (15.4%) 18 (46.2%) 39 (100%)

A/ F 7 (17.9%) 8 (20.5%) 7 (17.9%) 17 (43.6%) 39 (100%)

B/ E 10 (27.0%) 7 (18.9%) 6 (16.2%) 14 (37.8%) 37 (100%)

B/ F 8 (21.6%) 6 (16.2%) 11 (29.7%) 12 (32.4%) 37 (100%)

C/ E 2 (11.8%) 1 (5.9%) 10 (58.8%) 4 (23.5%) 17 (100%)

C/ F 3 (17.6%) 5 (29.4%) 2 (11.8%) 7 (41.2%) 17 (100%)

D/ E 4 (30.8%) 4 (30.8%) 2 (15.4%) 3 (13.3%) 13 (100%)

D/ F 5 (38.5%) 2 (15.4%) 1 (7.7%) 5 (38.5%) 13 (100%)

Total 45 42 45 80

A= allergy specialist 1

B= allergy specialist 2

C= dermatology specialist 1

D= dermatology specialist 2

E= researcher 1

F= researcher 2

*More than 1 diagnosis per patient is possible.

In cases where the two allergy specialists were mutually agreeing about the diagnosis

and also the two medical researchers had mutual agreement, the agreement between the

allergy specialists and the medical researchers is shown in Table 5.

Table 5: Agreement between 2 allergy specialists and 2 medical researchers

Agreement: Yes Agreement: No

Rhinoconjunctivitis 8 0

Food allergy 2 2

Bee/wasp allergy 1 0

Urticaria/ angio-oedema 0 7

Asthma 1 0

For rhinoconjunctivitis, in 8 cases IDEAL was able to diagnose rhinoconjunctivitis

correctly. However, for urticaria/angio-oedema, IDEAL was not able to make this

diagnosis at all. For food allergy, in 2 cases there was agreement and in 2 cases there was

disagreement. In the first case of disagreement, the patient had a suspected cow’s milk

allergy. For the answers on the questions: “Are other dairy products tolerated?” and

“After what dose do the symptoms start? (traces, daily portion etc.)” conflicting

20

information was documented in “Poliplus’’. This resulted in disagreement between the

diagnosis based on the IDEAL system and the diagnosis made by the specialists using

Poliplus. These questions are important for differentiating between a likely food allergy

and an unlikely food allergy. In the other case, the diagnosis resulting from the consult in

the hospital was oral allergy syndrome. This syndrome was missing in the decision rules

and therefore was not diagnosed by the questionnaire.

For the dermatology patients, in 6 cases there was agreement between the dermatology

specialists about eczema of the body and eczema of the face. In all 6 cases, the IDEAL

system was able to make the correct diagnosis eczema.

3.4 Inter-rater agreement

For the 11 patients with eczema, 10 were seen in the clinic. In 7 cases there was

agreement among the dermatologists about the severity of the eczema of the body.

Cohen’s kappa showed a moderate agreement (k= 0.526, p=0.000, 95%CI [0.14 ; 0.914

]). For the severity of the facial eczema, there was also moderate agreement (k= 0.617,

p=0.003, 95%CI [0.22;1.02]) Also, agreement about the treatment of the patients with

eczema was defined. Regarding treatment of the eczema of the body, poor agreement

was found (k= 0.182, p=0.229, 95%CI [-0.08 ; 0.44]). Regarding treatment of the facial

eczema, moderate agreement was found (k= 0,660, p=0,002, 95%CI [0.29; 1.03]).

For the 31 allergy patients, 42 diagnoses were made. Using Cohen’s kappa, a moderate

agreement was found (k= 0.545, p=0,000, 95%CI [0.367; 0.723]) for the two allergists.

For medical researchers 1 and 2, very good agreement was found (k= 0.975, p=0.000,

95%CI [0.939; 1.010]).

21

4. Discussion

Allergy patients are primarily managed in primary care. Because of the increasing

prevalence of allergic disease, GPs have to manage increasingly more allergy patients.

The interpretation of IgE-results can be difficult for GPs. Also, treatment of allergy

patients is suboptimal, for instance concerning referral for immunotherapy and

prescription of epinephrine-auto-injectors. To support GPs in diagnosis and

management of allergy patients, a clinical support system IDEAL was developed. A

diagnostic questionnaire was developed. Classifications of allergic diseases and

medication were developed. A diagnostic decision tool was developed based on decision

rules determined by an allergy specialist. The agreement between the golden standard

and the IDEAL system was determined, and also the inter-rater reliability between the

two (allergy and dermatology) specialists and between the two researchers was

determined.

The diagnostic questionnaire was tested on patients referred to the UMCG by their GP.

The response was good, 94 questionnaires were returned. Exact agreement between the

golden standard and the diagnosis based on IDEAL only occurred in 15.4%-38.5% of the

cases. When using the less strict classification of allergic disease, the agreement was

69.2%. There were large differences in agreement for the different types of allergic

disease. Rhinoconjunctivitis was correctly diagnosed by the IDEAL system in 100% of

the cases. In contrast, urticaria/angio-oedema was not diagnosed at all by IDEAL,

because urticaria/ angio-oedema was not integrated into the decision tool. This is because

a specific question for urticaria/angio-oedema was missing in the questionnaire.

Although question 7.1 does concern urticaria/angio-oedema, many patients with

urticaria/ angio-oedema left this question blank. It is plausible that such patients do not

recognize their symptoms in the question, or they do not know the cause of the

symptoms and therefore leave the question blank. It could also be due to bad phrasing of

the question. For food allergy, there was 50% agreement between the golden standard

and IDEAL. In the first case of disagreement this was caused by conflicting information

between the questionnaire and ‘Poliplus’. In the second case, oral allergy syndrome was

missing in the decision rules. Consequently, this diagnosis should be integrated in a

future version of the decision tool.

Three questions were redundant for making the diagnoses using the decision tool. Since

these questions do give addional information that can support the diagnosis, but are not

strictly required, it can be argued that these questions can be removed from the

questionnaire. However, in the present study the questionnaire and the decison tool were

pre-tested. When these questions are also proven to be redundant in a future pilot study,

these questions can be permanently removed from the questionnaire.

Between the dermatology specialists, moderate agreement was found for both severity of

eczema of the body and face. Agreement about the treatment of the eczema patients was

poor (body) and moderate (face). There were only 11 eczema patients, and 1 patient had

22

not been seen yet. This limits the meaning of the kappa value. Between the allergy

specialists, moderate agreement was found. However, the confidence interval was wide,

which could be explained by the small sample size of 31 patients. The agreement

between the two researchers was very good. This indicates that the decision tool is quite

consistent in interpretation.

4.1 Limitations

This study has some limitations. First, observer bias may have occurred. Some of the

specialists had already seen patients in their clinic before assessing these patients for this

study. Possibly, they made the assessment based on the consult with the patient, in

contrast to the other specialist who made the diagnosis merely based on the information

in Poliplus. Besides observer bias, spectrum bias also occurred. This study was

performed with a questionnaire of patients seen in secondary care. However, the

questionnaire was developed for patients in primary care. The prevalence and severity of

patients referred to secondary care may differ from the average population in primary

care.

Normally, for determining the validity (construct validity) of a questionnaire, the

sensitivity and specificity are calculated, using a 2x2 table. Based on one golden standard

and one diagnosis made by the measurement instrument that is being validated, the true-

positive, true-negative, false-positive and false-positive diagnoses should be determined.

In this study, the golden standard was based on the consult of the patient in the clinic.

Only one (or sometimes two) allergic conditions were handled during a consult.

However, based on the questionnaire, several allergic diagnoses can be made. Therefore

it is not possible to compare one diagnosis with one other diagnosis and to determine the

sensitivity and specificity in this study.

Another limitation involves the classification of allergic diseases. The classification used

in this study was very detailed. Therefore small differences in the assessment of the

specialists and researchers were often present. This was resolved by formulating less

detailed categories before testing for agreement.

A reason for the differences in agreement found, relates to the lack of IgE-results in 14

patients. Therefore an exact diagnosis could not be made by the researchers. Another

reason for the differences in diagnosis could be due to the time interval between the

consult in the clinic and the completing of the questionnaire by the patient. The mean

interval was 7.92 days. In this time there might have occurred changes in presentation of

the patient. This is especially true for patients with eczema, which is a fluctuating

disease. For the patients with eczema, the mean interval was even higher: 18.3 days.

Three patients completed their questionnaire after the consult in the hospital; this could

also result in bias.

Exact agreement being rare in this study does imply that the IDEAL system still needs to

improve. For instance, the diagnosis urticaria/angio-oedema was never made based on

the questionnaire. This emphasizes the need for an improved question about urticaria and

angio-oedema.

23

4.2 Conclusions

Regardless of the limitations discussed above, the most important aim of the study could

be achieved: to determine the agreement between the golden standard and the diagnostic

tool IDEAL, as well as the inter-rater reliability. This study aims to make the first steps

towards an automatized clinical support system. With the clinical support system

IDEAL, GPs will be supported in diagnosing and managing their allergy patients. After

pre-testing the questionnaire in this study, the next step is to improve the questionnaire,

the classification and the decision rules, based on the findings described above. The

medication advice for the GP has to include non-medicinal advice for the different

allergies (avoidance and allergen reduction measures, good skin care measures, etc.).

Subsequently the questionnaire has to be validated and a pilot study has to be performed

in primary care to evaluate the effectiveness of the IDEAL system.

24

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28

Appendix 1: CARAT vragenlijst

29

Appendix 2: IDEAL vragenlijst

30

Appendix 3: begeleidende brief kinderallergologie

Beste ouder,

In het UMCG zijn we bezig een systeem te ontwikkelen dat de diagnostiek en behandeling van

allergiepatiënten makkelijker maakt voor huisartsen. Om dit te kunnen ontwikkelen is het nodig

dat zoveel mogelijk ouders, waarvan de kinderen naar de allergiepoli komen, de

allergievragenlijst voor ons invullen. Wij vragen u ons te helpen door het volgende te doen:

Vul de vragenlijst in of laat uw kind dat ouder is dan 15 jaar het zelf invullen.

Wilt u erop letten dat alle gegevens bovenaan de vragenlijst volledig ingevuld zijn?

(Datum invullen vragenlijst, naam huisarts etc.).

Vul de toestemmingsverklaring in.

Stuur de vragenlijst en de toestemmingsverklaring in de retourenvelop naar ons óf lever

beiden in bij het eerste polibezoek.

Voor meer informatie kunt u de bijgeleverde folder lezen of uw vragen stellen aan:

Thecla Brakel

Telefoon: (050) 3638 671

E-mail: t.m.brakel@rug.nl

Wij willen u alvast hartelijk bedanken voor uw medewerking!

Met vriendelijke groeten,

Ewoud Dubois (Allergoloog)

Emmy Roerdink (Stagiaire)

Thecla Brakel (Wetenschappelijk onderzoeker)

31

32

Appendix 4: toestemmingsverklaring

Geachte meneer, mevrouw,

Uw kind gaat binnenkort vanwege allergische klachten naar de kinderallergologie-poli. Wij

hopen dat u de vragenlijst wilt invullen en gratis naar ons wilt sturen in de bijgeleverde

enveloppe. Wij vragen uw toestemming om gebruik te maken van de ingevulde gegevens. Deze

gegevens kunnen we goed gebruiken om een allergiedienst te ontwikkelen waarmee we de zorg

voor allergische patiënten nog verder willen verbeteren. De gegevens zullen in een

geanonimiseerd bestand opgeslagen worden en zullen niet tot u of uw kind te herleiden zijn.

Meer informatie over de allergiedienst kunt u vinden in de bijgevoegde folder. Mocht u nog

vragen hebben of meer informatie willen, dan kunt u contact opnemen met Thecla Brakel,

coördinator van de allergiedienst telefoonnummer: 050-3638671 of e-mail: t.m.brakel@rug.nl

Toestemmingsverklaring

Voor het gebruiken van de ingevulde gegevens in de vragenlijst.

Ik geef toestemming:

Voorletters en achternaam

:…………………………………………………….

Burgerservicenummer

(BSN)

:…………………………………………………….

Handtekening

:…………………………………………………….

Datum

:…………………………………………………….

Alvast hartelijk dank voor het invullen van de vragenlijst en uw toestemming.

Prof. dr. A. E. J. Dubois E.M. Roerdink

Drs. T. M. Brakel

33

Appendix 5: folder

34

Appendix 6: classificatielijst

Classsificatie rhinoconjunctivitis

1.1. Geen rhinoconjuntivitis

Niet allergische rhinoconjunctivitis

1.2. Milde rhinoconjunctivitis, niet behandeld

1.3. Milde rhinoconjunctivitis, niet afdoende behandeld

1.4. Matige rhinoconjunctivitis, niet behandeld

1.5. Matige rhinoconjunctivitis, niet afdoende behandeld

1.6. Ernstige rhinoconjunctivitis, niet behandeld

1.7. Ernstige rhinoconjunctivitis, niet afdoende behandeld

1.8. Moeilijk behandelbare rhinoconjunctivitis

1.9. Afdoende behandelde rhinoconjunctivitis

1.10 Overbehandelde rhinoconjunctivitis

Allergische rhinoconjunctivitis perenniaal

1.11. Milde rhinoconjunctivitis, niet behandeld

1.12. Milde rhinoconjunctivitis, niet afdoende behandeld

1.13. Matige rhinoconjunctivitis, niet behandeld

1.14. Matige rhinoconjunctivitis, niet afdoende behandeld

1.15. Ernstige rhinoconjunctivitis, niet behandeld

1.16. Ernstige rhinoconjunctivitis, niet afdoende behandeld

1.17. Moeilijk behandelbare rhinoconjunctivitis

1.18. Afdoende behandelde rhinoconjunctivitis

1.19 Overbehandelde rhinoconjunctivitis

Allergische rhinoconjunctivitis seizonaal

1.20. Milde rhinoconjunctivitis, niet behandeld

1.21. Milde rhinoconjunctivitis, niet afdoende behandeld

1.22. Matige rhinoconjunctivitis, niet behandeld

1.23. Matige rhinoconjunctivitis, niet afdoende behandeld

1.24. Ernstige rhinoconjunctivitis, niet behandeld

1.25. Ernstige rhinoconjunctivitis, niet afdoende behandeld

1.26. Moeilijk behandelbare rhinoconjunctivitis

1.27. Afdoende behandelde rhinoconjunctivitis

1.28 Overbehandelde rhinoconjunctivitis

Overig

1.29 Rinitis medicamentosa

35

Classificatie astma

2. 1 Geen astma

Niet-allergisch astma (RAST neg)

2.2 Milde astma, niet behandeld/niet erkend

2.3 Milde astma, niet afdoende behandeld

2.4 Matig astma, niet behandeld

2.5 Matig astma, niet afdoende behandeld

2.6 Ernstig astma, niet behandeld

2.7 Ernstig astma, niet afdoende behandeld

2.8 Moeilijk behandelbaar astma

2.9 Afdoende behandeld astma

2.10 Overbehandeld astma/Behandeling ongeschikt

Allergisch astma (RAST pos)

2.11 Milde astma, niet behandeld/niet erkend

2.12 Milde astma, niet afdoende behandeld

2.13 Matig astma, niet behandeld

2.14 Matig astma, niet afdoende behandeld

2.15 Ernstig astma, niet behandeld

2.16 Ernstig astma, niet afdoende behandeld

2.17 Moeilijk behandelbaar astma

2.18 Afdoende behandeld astma

2.19 Overbehandeld astma/Behandeling ongeschikt

Overig astma

2.20 Beroepsgebonden astma

36

Bij- en wesp classificatie

3.1 Geen reactie

3.2 Locale reacties: vermijdingsadviezen evt. Verwijzing als de large locals heel groot en

frequent zijn.

3.3 Dermale reactie:

a. < 15 jaar: behandeling niet noodzakelijk; geruststelling

b. > 15 jaar: EAI, verwijzen voor VIT

3.4 Meer dan dermale reactie, niet levensbedreigend*:

c. < 10 jaar behandeling niet noodzakelijk; geruststelling

d. > 10 jaar EAI, verwijzen voor VIT

3.5.Levensbedreigende reactie/ ernstige co morbiditeit

Ongeacht leeftijd EAI + verwijzen voor VIT.

N.b. er is zelden een indicatie voor behandeling onder de 5 jaar

* Tot aan de liprand

Vit= Venom immunotherapy

37

Classificatie eczeem

Lichaam

4.1 Geen actief eczeem

4.2 Geen actief eczeem, goed onder controle

4.3 Geen actief eczeem, mogelijk overbehandeld

4.4 Mild eczeem, mogelijk onderbehandeld

4.5 Mild eczeem, adequaat behandeld

4.6 Mild eczeem, mogelijk overbehandeld

4.7 Matig eczeem, mogelijk onderbehandeld

4.8 Matig eczeem, adequaat behandeld

4.9 Matig eczeem, mogelijk overbehandeld

4.10 Ernstig eczeem, wellicht onderbehandeld

4.11 Ernstig eczeem, niet onder controle

4.12 Zeer ernstig eczeem, wellicht onderbehandeld

4.13 Zeer ernstig eczeem, niet onder controle

Gezicht

4.14 Geen actief eczeem

4.15 Geen actief eczeem, goed onder controle

4.16 Geen actief eczeem, mogelijk overbehandeld

4.17 Mild eczeem, mogelijk onderbehandeld

4.18 Mild eczeem, adequaat behandeld

4.19 Mild eczeem, mogelijk overbehandeld

4.20 Matig eczeem, mogelijk onderbehandeld

4.21 Matig eczeem, adequaat behandeld

4.22 Matig eczeem, mogelijk overbehandeld

4.23 Ernstig eczeem, wellicht onderbehandeld

4.24 Ernstig eczeem, niet onder controle

4.25 Zeer ernstig eczeem, wellicht onderbehandeld

4.26 Zeer ernstig eczeem, niet onder controle

38

Classificatie Anafylactie

5.1 Geen anafylactie

5.2 Anafylactie waarbij 1 tractus betrokken is.

5.3 Anafylactie waarbij meer dan 1 tractus betrokken is.

39

Classificatie voedselallergie

6.1 Geen voedselallergie

6.2 Zeer onwaarschijnlijk voedselallergie

6.3 Voedsel OAS:

6.4 Voedsel niet levensbedreigende reactie, wel systemisch, meer dan alleen OAS: laag

risico voedselallergie

6.5 Als 4 maar met minimaal 2 risicofactoren: hoog risico voedselallergie*

6.6 Voedsel geeft astmatische klachten: hoog risico voedselallergie

6.7 Voedsel levert levensbedreigende reactie: hoog risico voedselallergie

6.8 Voedselallergie met ernstig/slecht te behandelen astma: hoog risico voedselallergie.

6.9 Globus hystericus: als dit vast staat is het geen voedselallergie

*

voortschrijdend inzicht: wij zijn destijds begonnen met voedselallergie + 2

risicofactoren (van 1. leeftijd>12, 2. pinda of notenallergie 3. coexistent astma en

4. systemische reacties op sporen of indirect contact) = hoog risico voedselallergie

hier hebben wij aan toegevoegd:

i. ad 2. ook als pinda of noten nooit gehad, sesam, pijnboompitten, vis en

schaaldieren

ii. ad 3 astmatische reacties op het voedingsmiddel

wij hebben een astmatische reactie gehad op ei bij een jongetje van 3 die

potentieel levensbedreigend was op de VPU; in de nieuwe EAACI Guidelinres

staat dat ernstig/ontregeld/moeilijk behandelbaar astma samen met een

voedselallergie altijd hoog risico is – dit standpunt wil ik overnemen

samenvattend betekend dit dat voedselallergie laag risico is (4 hierboven) tenzij:

i. er reeds een levensbedreigende reactie is geweest, of

ii. er ook ernstig/ontregeld/moeilijk te behandelen astma is, of

iii. er een astmatisch reactie op het voedingsmiddel is geweest, of

iv. er 2 of meer van de volgende aan de orde zijn:

1. leeftijd >12

2. coexistent astma

3. pinda of noten of sesam of schaaldieren of vis verdacht of nooit

gehad

4. systemische reacties op sporen of indirect contact

40

Classificatie overige allergie

Latex

7.1 Latex/rubber allergie:

Beroepsgebonden/hobby

7.2 Beroeps- of hobby gebonden allergie:

Geneesmiddelen allergie

7.3 Milde geneesmiddelenallergie + geen vitale indicatie; wel alternatieven mogelijk:

7.4 Milde geneesmiddelenallergie + vitale indicatie en/of geen alternatieven

7.5 Ernstige geneesmiddelenallergie:

Urticaria/ angio-oedeem

7.6 Urticaria/ angio-oedeem voldoende behandeld:

7.7 Urticaria/ angio-oedeem onder behandeld:

7.8 Urticaria/ angio-oedeem moeilijk te behandelen:

Overig

7.9 Twijfel: oproepen op spreekuur huisarts, anamnese verder uitvragen, allergie beoordelen

Medicatie

7.10 Ongepaste farmacotherapie:

7.11. Juiste medicatie:

7.12. Risicovolle/ toxische medicatie:

7.13 Anders nl:

41

Appendix 7: voorbeelden beslissingssysteem

X= at least one should be checked

O= cannot be checked

Empty box= not relevant for this diagnosis

For seizonal rhinitis, one of the seasons summer, spring or autumn should be checked and at least

one pollen (tree or grass) corresponding with the season. Spring corresponds with tree pollen and

summer with grass pollen.

For perennial rhinitis, one indoor/ aeroallergen should be checked.

42

43

44

45

46

47

48

Appendix 8: medicatielijst

GENERIEKE NAAM MERKNAMEN DOSERING

ECZEEM

MEDICAMEN

TEUS

Neutrale vette

zalven

Koelzalf

Lanettecreme of zalf

Vaseline

Zinkoxide

Cetomacrogolcrème

Licht/ matig

potente

corticosteroiden

Hydrocortisonacetaat

1% (HCA)

2 dd

(Klasse I-II) Triamcinolonacetaat

0.1% (TAC)

Triamcinolon creme of zalf 1-3 dd, afbouwen 1 dd en 2-3x/week max

30-60g per week

Clobetason-17-butyraat 0.05%

Emovate 2 dd max 30-60 g per week

Hydrocortison-17-

butyraat 0.1%

Locoid 1-3 dd, afbouwen 1 dd en 2-3x/week max

30-60g per week

Fluticason 0.05% en

0.0005%

Cutivate 2 dd

Hydrocortison creme/zalf

2 dd afbouwen 1 dd en 2-3x/week max. 30-60 g per week

Flumetason Locacorten 2 dd afbouwen 1 dd en 2-3x/week

Elidel

Tacrolimus

Sterk potente

corticosteroiden

Betamethason-17-

valeraat 0.1%

Betnelan 2 dd na verbetering 1 dd max 30-60 g per

week

(Klasse III-IV) Diflucortolonvaleraat 0.1%

Nerisona 2 dd, na enkele dagen 1 dd. Na verbetering 2-3 x/week. Max 30-60 g per week.

Momethason 0.1% Elocon, Mometason zalf 1 dd max 60 g per week

Desoxymethason 0.25% Ibaril, Topicorte 1-3 dd (creme) 1-4 dd (emulsie) max. 30-

60 g per week

Betamethasondiproprion

aat 0.05%

Diprosone 2 dd max 30-60 g per week

Clobetasol-17-proprionaat 0.05%

Dermovate, Clarelux, Clobex Creme/zalf: 2 dd Shampoo: 1 dd Schuim: 2 dd. Max 50 g per week

Betamethasondiproprion

aat 0.05%

Diprolene 2 dd max 30-60 g per week

NIET-

MEDICAMEN

TEUS

Krappakje

Badolie

ANTI-

HISTAMINIC

A (H1-

RECEPTORA

NTAGONIST

EN)

Zie kopje Anti-

Histaminica

(H1-receptorantago

nisten)

TEGEN JEUK

49

RHINOCONJ

UNCITIVITIS

NEUSDRUPP

ELS/SPRAY

Anti-

histaminicum nasaal

Azelastine Allergodil neusspray 1 mg/ml Volwassenen en kinderen> 6 jaar: 2 dd 1

verstuiving

Otrivin neusallergie neusspray

1 mg/ml

Levocabastine Livocab neusspray 0,5 mg/ml Volwassenen en kinderen: 2 tot 3-4 dd 2

verstuivingen per neusgat

Nasaal

corticosteroid

Beclometason Beclometason neusspray 50

mg/dosis

2 dd 2 verstuivingen per neusgat verminderen naar 2 dd 1

Budesonide Budesonide neusspray 50

mg/dosis of 100 mg/dosis

Alle merknamen: volwassenen en

kinderen> 6 jaar 1 dd 128 µg of 200 µg

(ieder neusgat)

Rhinocort neusspray 32

mg/dosis of 64 mg/dosis

Fluticason Avamys nuesspray 27,5 mg/dosis

Flixonase neusdruppel;s 1

mg/ml of nuesspray 50 mg/dosis

Fluticason nuesspray 50

mg/dosis

Mometason Nasonex neusspray 50

mg/verstuiving

Volwassenen en kinderen> 12 jaar: 1 dd 2

verstuivingen per neusgat daarna 1 dd 1

(max 1 dd 4)

Kinderen 6-11 jaar: 1 dd 1 verstuiving per

neusgat

Triamcinolon Nasacort neusspray 55 mg/dosis

Volwassenen en kinderen> 12 jaar: 1 dd 2 verstuivingen per neusgat daarna 1 dd 1

Kinderen 6-12 jaar: 1 dd 1 (max 2 per

verstuivingen per neusgat per dag)

Sympathicomimethicum

Oxymetazoline Nasivin spray of druppels 0,5 mg/ml

Alle merknamen: !! Max 5-7 dagen!!

Vicks Sinex neusspray 0,5

mg/ml

Nasivin: Volwassenen en kinderen> 6 jaar:

1-3 dd 2-3 druppels of 1 verstuiving per neusgat (max 4-6 dd)

Kinderen 1-6 jaar: nuessprat 0,25 µg/ml 2-3

dd 1 verstuiving elk neusgat

Baby's en kinderen < 1 jaar: druppels 0m1

µg/ml 2-3 dd 1 druppel per neusgat (max 3 dd)

Vicks Sinex: volwassenen en kinderen> 10

jaar 2-3 dd 1-2 verstuivingen elk neusgat (spray) en 4-6 dd 1-2 verstuivingen

(knijpfles)

Kinderen 6-10 jaar: neusspray 2-3 dd 1 verstuiving (neusspray) 4-6 dd 1

verstuiving (knijpfles)

Xylometazoline Otrivin neusspray/ neusdruppels 0,1% of 0,05%

1mg/ml

Alle merknamen: !! Max 5-7 dagen !!

Otrivin Menthol neusspray 0,1% 1 mg/ml

Volwassenen en kinderen> 6 jaar: 4-6 dd 2-3 druppels of 1 spray 0,1%

Xylometazoline neusdruppels

0,05% 0,5 mg/ml 0,1% 1 mg/ml 0,05% 0,5 mg/ml of

Kinderen 2-6 jaar: 1-3 dd 1-2 druppels of 1

spray 0,05%

50

0,1% 1 mg/ml

Xylometazoline neusdruppels

0,025% 0,25 mg/ml of spray 0,025% 0,25 mg/ml

Kinderen 3 maand-2 jaar: 1-3 dd 1-2

druppels 0,025%

Xylometazoline/ipatropi

um

Otrivin Duo neusspray 70 mg

xylometazoline 84 mg ipratropium per verstuiving

Volwassenen: tot 3 dd 1 verstuiving.

Max 7 dagen!!

Overige neussprays

Cromoglicinezuur Allergo- COMOD neusspray 20 mg/ml

Alle merknamen: 4-6 dd 1 verstuiving per neusgat (20 µg/ml)

Cromoglicinezuur nuesspray

20 mg/ml

3-4 dd 1 verstuiving per nuesgat (40 µg/ml)

Lomusol neusspray 20 mg/ml

of 40 mg/ml

Prevalin 20 mg/ml of 40 mg/ml

Natriumchloride Natriumchloride neusdruppels 8 mg/ml

4 dd 2/3 neusdruppels per neusgat

Niet-sederend

antihistaminicu

m

Azelastine Allergodil oogdruppels 0.05%

0,5 mg/ml

Alle merknamen:

Azelastin-POS oogdruppels

0,05% 0,5 mg/m;

Seizoensgebonden allergische

conjunctivitis: Volwassenen en kinderen

vanaf 4 jaar: 1 druppel in ieder oog 2×/dag.

Emedastine Emadine oogdruppels 0,05%

0,5 mg/ml

Volwassenen en kinderen > 3 j.: 1 druppel

2×/dag in het aangedane oog.

Levocabastine Livocab 0,05% 0,5 mg/ml 3-4 dd 1 druppel ieder oog

Olopatadine Opatonol oogdruppels 0,1%

1mg/ml

Volwassenen en kinderen ≥ 3 j.: 1 druppel

2×/dag (om de 8 uur) in de conjunctivale zak.

Sederend

antihistaminicu

m

Ketotifen Zaditen oogdruppels

0,025%0,25 mg/ml of unidose

0,25 mg/ml

Volwassenen en kinderen ≥ 3 jaar: 1

druppel 2×/dag in de conjunctivale zak.

Altriabak oogdruppels 0,025%

0,25 mg/ml

Overige

(voorkomt vrijkomen

histamine)

Cromoglicinezuur Allerg-Abak oogdruppels 2%

20 mg/ml

Alle merknamen: 2-6 dd 1-2 druppels per

oog

Allergo-COMOD oogdruppels 2% 20 mg/ml

Cromoglicinezuru oogdruppels

2% 20 mg/ml

Opticrom oogdruppels 2% 20

mg/ml

Prevalin oogdruppels 2% 20

mg/ml

Nedocromil Tilavist oogdruppels 2% 20

mg/ml

Volwassenen en kinderen vanaf 6 jaar:

Seizoengebonden allergische

conjunctivitis: 1 druppel tweemaal per dag

in ieder oog, zo nodig viermaal per dag.

Niet-seizoengebonden allergische

conjunctivitis: 1 druppel viermaal per dag

in ieder oog.

OOGDRUPPE

LS

Sympathicomi

meticum

Fenylefrine Visadron oogdruppels 0,125%

1,25 mg/ml

3 dd 1-2 druppels in conjunctivaalzak

Anti-histaminicum

Azelastine Allergodil oogdruppels 0.05% 0,5 mg/ml

Seizoengebonden allergische conjunctivitis: Volwassenen en kinderen

vanaf 4 jaar: 1 druppel in ieder oog

Azelastin-POS 0,05% 0,5 2×/dag, zonodig verhogen tot max. 4×/dag.

51

mg/ml

Niet-seizoensgebonden ('perennial')

allergische conjunctivitis: Volwassenen en kinderen > 12 j:

1 druppel in ieder oog 2×/dag, zonodig

verhogen tot max. 4×/dag.

Emedastine Emadine oogdruppels 0,05%

0,5 mg/ml

Volwassenen en kinderen> 3 j: 2 dd 1

druppel aangedane oog

Ketotifen Zaditen oogdruppels 0,025%

0,25 mg/ml

Volwassenen en kinderen ≥ 3 jaar: 1

druppel 2×/dag in de conjunctivale zak.

Altriabak oogdruppels 0,025%

0,25 mg/ml

Levocabastine Livocab oogdruppels 0,05% 0,5 mg/ml

2 dd (3-4) 1 druppel ieder oog

Olopatadine Opatanol oogdruppels 0,1% 1

mg/ml

Volwassenen en kinderen ≥ 3 j.: 2 dd 1

druppel in conjunctivale zak.

Cromonen Cromoglicinezuur Allerg-Abak oogdruppels 2%

20 mg/ml

2-6 dd 1-2 druppels ieder oog

Allergo-COMOD oogdruppels 2% 20 mg/ml

Cromoglicinezuur oogdruppels

2% 20 mg/ml

Opticrom oogdruppels 2% 20

mg/ml

Prevalin oogdruppels 2% 20 mg/ml

Nedocromil Tilavist oogdruppels 2% 20

mg/ml

Volwassenen en kinderen vanaf 6

jaar:Seizoengebonden allergische conjunctivitis: 2 dd 1 druppel per oog

Zo nodig 4 dd. Niet-seizoengebonden

allergische conjunctivitis: 4 dd 1 druppel per oog

Orale steroiden Betamethason Celestone 0,5 mg Oraal: begindosering: 0,25–8 mg per dag; kinderen:

Oraal: begindosering: 17,5–250 microg/m²

lichaamsoppervlak per dag.

Dexamethason Dexamethason Capsule 10-40

mg

4 dd 0,25-2 mg

Prednisolon Prednisolon caspule, 10-75 mg drank 1 mg/ml of 5 mg/ml en

tablet 5, 20 of 30 mg

4 dd 2,5-5 mg

Prednison Lodotra tablet 1 mg, 2 mg of 5

mg

Alle merknamen:begindosering per dag:

0,5-1 mg/kg lichaamsgewicht in 2-4 doses

Prednison tablet 5 mg

Triamcinolon Triamcinolon tablet 4 mg Oraal: Lichaamsgewicht boven 35 kg:

begindosering 8-16 mg per dag ineens of in 3-4 doses, soms tot 48 mg per dag.

Onder 35 kg: 4-12 mg ineens of in

verdeelde doses. Verminderen met 2 mg iedere 2-3 dagen.

ANTI- Zie kopje Anti-

52

HISTAMINIC

A (H1-

RECEPTORA

NTAGONIST

EN)

Histaminica (H1-

receptorantago

nisten)

ANAFYLAXI

E/

VOEDSELAL

LERGIE

Sympathicomi

meticum

Auto-injector: volwassenen 0,3 of 0,5 mg

i.m. zo nodig na 5-15 min tweede injectie

Epinefrine (adrenaline) Anapen 150, 300 of 500 Kinderen: 15-30 kg, 0,15 mg i.m. eventueel

na 5-15 min herhalen

I.m. Epipen 0,5 mg/ml 0,3 ml (junior) of 0m1 mg/ml 0,3 ml

Jext 0,15 ml of 0,3 ml (1

mg/ml)

ASTMA

Sympathicomi

metica

Efedrine Efedrine injecties 50 µg/ml Bronchospasmen: 12,5-25 µg s.c.,

eventueel i.m.

Formoterol Atimos dosisaerosol 12 µg/dosis

Alle merknamen: onderhoudsbehandeling astma volwassenen 1-2 dd 6-12 µg of 2 dd

4 µg, bij acute aanvallen 6-12 µg

tot 36 µg per keer en 72 µg per dag. Kinderen ≥ 6j: 1-2 dd 12 µg (max 24 µg

per dag) 6-12 µg extra bij acute aanval

Foradil dosisaerosol 12 µg/dosis of inhalatiepoeder

capsule 12 µg

Profylaxe inspannings- of allergeengeïnduceerd astma: Volwassenen:

12 µg 15 min voor inspanning of inhaleren

koude lucht.

Formoterol inhalatiepoedere

capsule 12 µg, cyclocaps 12

µg, easyhaler 12 µg/dosis

ernstig astma kan 24 µg nodig zijn.

Kinderen ≥6 j: 6-12 µg 15 min voor

inspanning of blootstelling koude lucht

of Novolizer 6 µg/dosis of 12

µg/dosis

Oxis inhalatiepoeder Turbuhaler 6 of 12 µg/dosis

Indacaterol Onbrez inhalatiepoeder

Breezhaler 150 µg

Volwassenen: 150 microg 1×/dag,

maximaal 300 microg 1×/dag.

Salbutamol Airomir dosisaerosol 100

µg/dosis

Alle merknamen: volwassenen cyclocaps

200-400 µg max 1600 µg per dag. Diskus 200 µg max 800 µg

Salbutamol dosisaerosol 100µg

/dosis, novolizer 100 µg/dosis, cyclocaps 200 µg

Novolizer 100 µg max 800 µg per dag,

dosisaerosol 100-200 µg max 800 µg per dag.

of inhalatievloeistof 5 mg/ml,

steri-Neb 1 of 2 mg/ml

Kinderen: cyclocaps 100-200 µg,

dosisaerosol of inhalatiepoeder novolizer 100 µg max 4 dd.

Ventolin inhalatie dosisaerosol

100 µg/dosis, inhalator babyhaler of volumatic.

Profylaxe inspannings-of allergeen-

geinduceerd astma: volwassenen cyclocaps, diskus 400 µg, dosisaerosol of novolizer

200 µg

of diskus 200 µg/dosis, inhalatievloeistof nebvules 1 of

2 of 5 mg/ml

Kinderen: cyclocaps 200µg dosisaerosol of novolizer 100 µg

Salbutamol oraal Salbutamol tablet 2 mg of 4 mg Volwassenen: zo nodig 1-4 dd 4 mg Kinderen: 1-4 dd 1-2 mg (2-6jaar) 2 mg (6-

12 jaar) en 2-4 mg (12>)

Ventolin drank oraal 0,4 mg/ml

Salmeterol Serevent dosisaerosol 25

µg/dosis, volumatic 25 µg/dosis of diskus 50 µg/dosis

Astma: Volwassenen en kinderen ≥ 12 j.:

50 microg 2×/dag; ernstige luchtwegobstructie100 microg 2×/dag.

Kinderen 4–12 j.: 50 microg 2×/dag.

53

Profylaxe van inspanningsastma:

Volwassenen en kinderen ≥ 4 j.: 50 microg

30–60 minuten voorafgaand aan de

inspanning.

Terbutaline Bricanyl inhalatiepoeder 250 of

500 µg/dosis

Volwassenen: 0,25–0,5 mg, zo nodig elke 6

uur, in ernstige gevallen max. 1 mg, max. 4

mg per 24 uur.

Xanthinederivaten

Theofylline Theofylline Klysma 10 30 50 mg/ml

Alle merknamen:Acute astma-aanval: Volwassenen en kinderen vanaf 6

maanden: Rectaal (klysma) 5 mg/kg

lichaamsgewicht eenmalig

Theolair tablet retard 175 mg,

250 mg of 350 mg

Onderhoud: Oraal: begindosering 200–350

mg iedere 12 uur. Na 3 dagen verhogen of

verlagen. (gewoonlijk 10–15 mg/kg lichaamsgewicht )

Kinderen tot 17 jaar: Oraal: begindosering

13–16 mg/kg lichaamsgewicht per dag daarna verhogen tot

1–9 jaar: max. 24 mg/kg per dag; 9–12 jaar:

max 20 mg/kg per dag; 12–16 jaar: max. 18 mg/kg per dag, als 2 retardtabletten.

Parasympathcol

ytica

Ipratropium Atrovent 20 µg/dosis inhalatievloeistof 125 of 250

µg/ml

Alle merknamen: Onderhoudsbehandeling astma en COPD: Volwassenen en kinderen

≥ 6 j.:

Ipratropium Inhalatiepoeder

cyclocaps 40 µg

Dosisaerosol/inhalatiepoeder: 40 microg 3–

4×/dag.

Ipraxa Volwassenen en kinderen > 12 j.: Inhalatievloeistof: 250–500 microg 3–

4×/dag. Voor de behandeling van acuut

bronchospasme: 500 microg. Kinderen van 6–12 j.: Inhalatievloeistof: 250 microg per

keer, zo nodig herhalen

Acute astma-aanval zo nodig in combinatie

met een kortwerkend β2-

sympathicomimeticum):

Volwassenen en kinderen > 12 j.: Inhalatievloeistof: 500 microg per keer,

Kinderen van 6–12 j.: Inhalatievloeistof:

250 microg per keer

Kinderen van 0–6 jaar Inhalatievloeistof:

alleen acuut astma: 125–250 microg tot

maximaal 1 mg/dag.

Inhalatiecorticosteroiden

Beclometason Beclodin dosisaerosol 100 µg/dosis

Alle merknamen: dosisaerosol volwassenen 100-200 microg/dag zo nodig 800

microg/dag (licht astma).

Beclometason dosisaerosol 50 100 of 250 µg/dosis of

cyclocaps 100 µg

matig/ernstig 800-1600 microg/dag zo nodig 2000 microg/dag. Onderhoud: 200-

800 microg 2x dag.

Qvar dosisaerosol 50 of 100 µg/dosis (inhalator of

aerochamber)

Kinderen < 12 j.: 50–100 microg 2–4×/dag, max. 500 microg per dag.

Dosisaerosol extrafijn: Volwassenen: Dosisaerosol extrafijn: 50–200 microg

2×/dag; max. 800 microg per dag.

Kinderen > 5 j.: 50–100 microg 2×/dag, max. 100 microg 2×/dag.

Inhalatiepoeder Volwassenen: : 100–200

microg 2×/dag, bij onvoldoende effect 200–400 microg 2×/dag

Kinderen: 100–200 microg 2×/dag.

54

Budesonide Budesonide dosisaerosol 200

µg inhalatiepoeder 200 of 400 µg, vernevelvloeistof 0m,125

0,25 of 0,5 mg/ml

Alle merknamen: Astma: Volwassenen:

Dosisaerosol: 200–1600 microg /dag ofwel 1–2 inhalaties 2–4×/dag

Larbex Steri-Neb vernevelvloeistof 0,25 mg/ml

matig persisterend astma 200–800 microg/dag, ernstig 800–1600 microg per

dag

Pulmicort dosisaerosol 100 of 200 µg/dosis, inhalatiepoeder

100, 200 of 400 µg/dosis

Inhalatiepoeder: begindosering 200–400 microg 1–2×/dag ('Novolizer') of 2–4×/dag

('Turbuhaler'); ernstig astma:

of vernevelvloeistof 125, 250 of 500 µg/ml

1600 microg/dag. Vernevelvloeistof: individueel; begin- en onderhoudsdosering

Pulmicort 500–1000 microg in

Ribuspir dosisaerosol 200 µg/dosis

2 doses. max. 1500–2000 microg per dag

Kinderen 0,5–12 j.: Vernevelsuspensie:

Budesonide vernevelvloeistof/Larbex Steri-Neb: 250-1000 microg/dag;

Pulmicort 250–500 microg /dag. Kinderen

2-6 j.: Dosisaerosol: 100 microg 2-4×/dag.

Kinderen > 7 j.: Dosisaerosol: 200 microg

2-4×/dag. 'Turbuhaler'/'Cyclocaps':

begindosering 100–200 microg 2–4×/

dag. max. 400 microg per dag.

Ciclesonide Alvesco dosisaerosol 80 of 160 µg/dosis.

Volwassenen en kinderen > 12 j.: 160 microg 1×/dag

Fluticason Flixotide dosisaerosol 50 125

of 250 µg/dosis of inhalatiepoeder diskus of

nebules

Onderhoudsbehandeling van astma:

Volwassenen en kinderen > 16 j.: Dosis-aerosol/inhalatiepoeder: begindosering

(100, 250, 500 of 100 µg/ml) 100 microg 2×/dag; onderhoudsdosering afhankelijk van de ernst van astma 100–

500 microg 2×/dag; bij ernstig

astma of oraal corticosteroïdgebruik max. 2 mg per dag. Kinderen 4–16 j.: Dosis-

aerosol/inhalatiepoeder:

begindosering 50 microg 2×/dag; onderhoudsdosering afhankelijk van de

ernst van astma 50–200 microg 2×/dag.

Kinderen 1–4 j.: Dosis-aerosol: 100 microg 2×/dag;

Ernstig astma Inhalatievloeistof:

Volwassenen en kinderen > 16 jaar: 500–2000 microg 2×/dag.

Kinderen 4–16 j.: 500–1000 microg

2×/dag.

Acute exacerbaties Volwassenen en

kinderen >16 j.: Inhalatievloeistof: 2000

microg 2×/dag

Kinderen 4–16 j.: 1000 microg 2×/dag

Anti-leukotrienen

Montelukast Singulair tablet 4 mg, 5 mg of 10 mg

Als adjuvans bij onderhoudsbehandeling van astma en profylaxe inspanningsastma:

Volwassenen en kinderen

≥ 15 j.: 10 mg per dag vóór het slapen gaan. Kinderen 6–14 j.: 5 mg per dag vóór

het slapen gaan. Kinderen ½–5 j.:

Volwassenen en kinderen > 12 j.: 160

microg 1×/dag

Immunomodula

ntia

Omalizumab Xolair 150 mg/ml Volwassenen, adolescenten en kinderen (≥

6 j.): Onderhoudsdosering: 75–600 mg s.c. per keer in 1 tot

4 injecties elke 2 of 4 weken; maximaal

150 mg per injectieplaats en 600 mg omalizumab iedere twee weken.

55

Combinatieprep

araten

Formoterol/beclometaso

n

Foster dosisaerosol 100/6 Volwassenen: 1–2 inhalaties ('100/6' )

tweemaal per dag, maximaal 4 inhalaties

per dag.

Fenoterol/ipratropium Berodual dosisaerosol 20/50 Acute astma-aanval: Volwassenen en kinderen > 6 j.: 2 inhalaties, zo nodig na 5

min herhalen; max. 8 inhalaties per dag.

Intermitterend en langdurig gebruik bij astma en COPD: Volwassenen en kinderen

> 6 j.: 1–2 inhalaties per keer

max. 8 inhalaties per dag; gemiddeld 1–2 inhalaties 3×/dag.

Formoterol/ budesonide Symbicort inhalatiepoeder

100/6, 200/6 of 400/12

Onderhoudsbehandeling van astma:

Volwassenen en kinderen > 12 jaar: 1–2 inhalaties ('100/6' of '200/6') of

1 inhalatie '400/12' 2×/dag, bij volwassenen

tot max. 4 inhalaties '200/6' 2×/dag. Volwassenen: 'Zo nodig'

Totaal 6 inhalaties per keer en 8 per dag

(uitzondering 12) Kinderen 6–11 jaar:: 2 inhalaties '100/6' 2×/dag.

Formoterol/ fluticason Flutiform 50/5, 125/5, 250/10 Onderhoudsbehandeling bij astma:

Volwassenen en kinderen > 12 jaar: 2 inhalaties '50/5' 2×/dag

('s morgens en 's avonds), bij onvoldoende

controle van de astma 2 inhalaties '125/5' 2×/dag.

Bij aanhoudend onvoldoende controle kan

alléén bij volwassenen de dosering worden verhoogd tot 2 inhalaties '250/10' 2×/dag.

Salbutamol/ ipratropium Combivent inhalatievloeistof

2,5 mg

Volwassenen en kinderen vanaf 12 jaar: 1

ampul/flacon inhalatievloeistof voor eenmalig gebruik drie- à viermaal

Ipramol inhalatievloeistof 2,5

mg

per dag òf 5–10 ml inhalatievloeistof

'0,1/1' FNA òf 2–4 ml inhalatievloeistof '0,25/2,5' FNA.

Ipratropium/ salbutamol

vernevelvloeistof 2,5 mg

Ipratropium/ salbutamol

vernevelvloeistof 0,1/1 of

0,25/2,5

Salbutamol/ fluticason Seretide dosisaerosol 25/50,

25/125, 25/250

Volwassenen en kinderen ≥ 12 j.: Astma:

Eén inhalatie van het inhalatiepoeder of 2

inhalaties met de dosisaerosol 2×/dag

of inhalatiepoeder 50/100,

50/250, 50/500

Begindosering: Eén inhalatie '50/100'

2×/dag

Kinderen 4–12 j.: Eén inhalatie van het inhalatiepoeder '50/100' of 2 inhalaties met

de dosisaerosol '25/50' 2×/dag;

max. 200 microg fluticason per dag.

URTICARIA

ANTI-

HISTAMINIC

A (H1-

RECEPTORA

NTAGONIST

EN)

Zie kopje Anti-

Histaminica

(H1-receptorantago

nisten)

ANTI- Zie kopje Anti-

56

HISTAMINIC

A (H2-

RECEPTORA

NTAGONIST

EN)

Histaminica (H2-

receptorantago

nisten)

Volwassenen en kinderen ≥ 15 j.: 10 mg

per dag vóór het slapen gaan.

Selectieve

leukotrieenanta

gonist

Montelukast Singulair tablet 10 mg of

granulaat 4 mg of kauwtablet 4

of 5 mg

Kinderen 6–14 j.: 5 mg per dag vóór het

slapen gaan. Kinderen ½–5 j.: 4 mg vóór

het slapen gaan.

(Staat niet voor

indicatie

urticaria FTK!)

Volwassenen, adolescenten en kinderen (≥

6 j.): Onderhoudsdosering: 75–600 mg s.c.

per keer in 1 tot 4 injecties elke 2 of 4 weken

Monoklonaal

anti-lichaam

Omalizumab Xolair injectie 150 mg/ml 0,5

of 1 ml

maximaal 150 mg per injectieplaats en 600

mg omalizumab iedere twee weken. Dosis afhankelijk IgE en lichaamsgewicht.

ANTI-

HISTAMINIC

A (H1-

RECEPTORA

NTAGONIST

EN)

*ECZEEM,

RHINITIS,

URTICARIA,

ANAFYLAXIE

Volwassenen/kinderen >12j: 3 dd 1

Alle merknamen: Volwassenen/kinderen

>12j: 1 dd 1

Niet-sederende H1-

receptorantagon

isten

Acrivastine Semprex 8mg Kinderen 6-12 jaar: 2 dd 1/2 tablet of 5 ml

Cetirizine Cetirizine tablet 10 mg of

drank 1mg/ml

Kinderen 2-6 jaar: 2 dd 2,5 ml

Prevalin Allerstop tablet 10 mg

Reactine tablet 10 mg

Zyrtec tablet 10 mg of drank

1mg/ml

Alle merknamen: Volwassenen en

kinderen> 12 jaar: 1 dd 1

Kinderen 6-12 jaar: 1 dd 1/2

Desloratadine Aerius drank/stroop 0,5 mg/ml of tablet 5 mg

Kinderen 1-6 jaar: 1 dd 2,5 ml

Dasselta 5 mg

Desloratadine drank/tablet 0,5

mg/ml of 5 mg

Alle merknamen: Allergische rhinitis:

volwassenen en kinderen> 12 jaar: 1 dd 1

of 1 dd 2

Neoclarityn 5 mg Urticaria volwassenen: 1 dd 1

Ebastine Ebastine 10 mg Alle merknamen: Allergische rhinitis:

volwassenen en kinderen≥ 12 jaar: 1 dd 1

Kestine 10 mg Urticaria volwassenen en kinderen≥ 12

jaar: 1 dd 1

Fexofenadine Fexofenadine 120 mg, 180 mg

STP-free 120 mg Alle merknamen: kinderen 2-6 jaar 2dd 2.5

ml drank

Telfast 180 mg of junior 30 mg Volwassenen en kinderen≥ 6 jaar: 1 dd 1

Levocetirizine Levocetirizine 5 mg Niet onder 2 jaar!

Xyzal 5 mg of drank 0m5

mg/ml

Alle merknamen: volwassenen en

kinderen> 12 jaar 1 dd 1

Kinderen 2-12 jaar/ lichaamsgewicht 30 kg of minder: 1 dd 5 mg

57

Loratadine Allerfre 10 mg Lichaamsgewicht meer dan 30 kg: 1 dd 10

mg

Claritine 10 mg of stroop 1

mg/ml

Volwassenen en kinderen > 12 jaar: 1 dd 1

Loratadine stroop 1 mg/ml of

tablet 10 mg

Volwassenen en kinderen ≥ 12 jaar: 1 dd 1

Mizolastine Mizollen 10 mg Kinderen 6-12 jaar en ≥ 25 kg: 1 dd 1/2 (of 5 ml drank)

Rupatadine Rupafin 10 mg of drank

1mg/ml

Volwassenen: 5-40 mg per dag

Kinderen: 0.75-1 mg/kg lichaamsgewicht

per dag

Sederende H1-receptorantagon

isten

Alimemazine Nedeltran 5mg 1-2 jaar: 2,5-10 mg/dag

2-5 jaar: 10-20 mg/dag

5-10 jaar: 20-30 mg/dag

Volwassenen en kinderen >12 jaar: 2 dd 1

(allergische aandoeningen), indien

anafylaxie 2 mg eventueel na 15 min herhalen

Volwassenen: 3 dd 1 m, max 32 mg per

dag

Clemastine Tavegyl 1 mg Kinderen 2-6 jaar: 3 dd 1/2 tablet

Cyproheptadine Periactin 4 mg Kinderen 7-14 jaar: 3 dd 1 max. 16 mg per

dag

Volwassenen en kinderen> 12 jaar: 3-4 dd 1 max 12 mg per dag

Kinderen 6-12 jaar: 3-4 dd 1/2 max 6 mg

per dag

Dexchloorfeniramine Polaramine 2 mg Volwassenen: 3 dd 20-40 druppels

Kinderen 1-3 jaar: 3 dd 10-15 druppels

Dimetindeen Fenistil 1 mg/ml druppels Kinderen> 3 jaar: 3 dd 15-20 druppels

Jeuk: volwassenen 3-4 dd 25 mg

Kinderen vanaf 12 maand: 1 mg/kg

lichaamsgewicht per dag max 2 mg/kg/dag

Hydroxyzine Hydroxyzine tablet 10 mg, 25 mg

Alle merknamen: volwassenen en kinderen vanaf 6 jaar 2 dd 1 (of 2 dd 2)

Kinderen 6 maand t/m 5 jaar: 1 dd 1/2 (max

tot 3 jaar 1 mg, max 3-5 jaar 2 mg per dag)

Ketotifen Ketotifen stroop 0,2 mg/ml of

tablet 1 mg

Allergische aandoeningen: volwassenen 2

dd 1 kindeern 2 dd 1 mg/kg

lichaamsgewicht.

Zaditen 1 mg (lichaamsgewicht van 10–20 kg een halve

tablet 2×/dag en van 20–40 kg 1 tablet

2×/dag)

Oxatomide Tinset 30 mg Astma: volwassenen 2 dd 2, kinderen 2 dd

1 mg/kg lichaamsgewicht

(lichaamsgewicht van 10–20 kg een halve tablet 2×/dag en van 20–40 kg 1 tablet

2×/dag)

Volwassenen: 15-150 mg per dag

Kinderen> 2 jaar: 2-4 dd 0,2 mg/kg

lichaamsgewicht

Promethazine Promethazine 25 mg of stroop

1mg/ml

400 of 800 mg

ANTI-

HISTAMINIC

UM (H2-

RECEPTORA

NTAGONIST)

Cimetidine Cimetidine tablet 200 mg, 400 mg of 800 mg

1 dd 40 mg of 1 dd 20 mg

58

*URTICARIA

(STAAN NIET

VOOR DEZE

INDICATIE

IN FTK!)

Famotidine Famotidine tablet 20 mg of 40

mg

300 of 2 x 150 mg per dag

Nizatidine Axid capsule 150 mg Alle merknamen: 2x 150 mg per dag of 300

mg

Ranitidine Ranitidine tablet 150 mg, 300

mg

Ranitidine tablet 75 mg

Zantac tablet 150 mg of 300

mg

Zantac tablet 75 mg

IMMUNOTHE

RAPIE

Allergeenextrac

t gras

Grazax Grazax: Volwassenen en

kinderen > 5 j: 75.000 SQ-T

1×/dag

Oralair Oralair: Volwassenen < 45 j.

en kinderen > 5 j.:

Startbehandeling: dag 1: 100 IR; dag 2: 200 IR.

Onderhoud: 1 tablet van 300 IR

Allergeenextrac

t gras-,

boompollen parenteraal

Alutard Alutard: Instelfase: injectie 1:

20 SQ–E, injectie 2: 40 SQ–E,

injectie 3: 80 SQ–E

Pollinex boom-of

graspollen

, injectie 4: 200 SQ–E, injectie

5: 400 SQ–E, injectie 6: 800 SQ–E, injectie 7: 2000 SQ–E,

injectie 8: 4000 SQ–E, injectie

9: 8000 SQ–E, injectie 10: 10.000 SQ-E, injectie 11:

20.000 SQ-E,

injectie 12: 40.000 SQ-E, injectie 13: 60.000 SQ-E,

injectie 14 80.000 SQ-E,

injectie 15 100.000 SQ-E langzaam subcutaan toedienen

in de strekzijde van de

bovenarm.

Het doseringsinterval is 7

dagen.

Pollinex: Volwassenen en

kinderen > 12 j.: Instelfase:

injectie 1: 300 SU, injectie 2: 800 SU,

injectie 3: 2000 SU, langzaam

subcutaan toedienen in de strekzijde van de bovenarm.

Allergeenextrac

t graspollen parenteraal

Allergovit pollen Allergovit: Instelfase: injectie

1: 100 TE, injectie 2: 200 TE, injectie 3: 400 TE, injectie 4:

800 TE,

Alutard SQ timotheegras

injectie 5: 1500 TE, injectie 6: 3000 TE, injectie 7: 6000 TE;

Purethal pollen Alutard: Instelfase: injectie 1:

20 SQ–E, injectie 2: 40 SQ–E, injectie 3: 80 SQ–E,

injectie 4: 200 SQ–E, injectie

5: 400 SQ–E, injectie 6: 800 SQ–E, injectie 7: 2000 SQ–E,

injectie 8: 4000 SQ–E, injectie

9: 8000 SQ–E, injectie 10: 10.000 SQ-E, injectie 11:

20.000 SQ-E,

59

injectie 12: 40.000 SQ-E,

injectie 13: 60.000 SQ-E,

injectie 14: 80.000 SQ-E,

injectie 15: 100.000 SQ-E

Purethal: Instelfase: injectie 1:

0,05 ml, injectie 2: 0,1 ml, injectie 3: 0,2 ml, injectie 4:

0,3 ml,

injectie 5: 0,4 ml, injectie 6: 0,5 ml, injectie 7: 0,5 ml,

injectie 8: 0,5 ml,

Allergeenextract huisstofmijt

parenteraal

Artuvac mijten Alutard: Instelfase: injectie 1: 20 SQ–E, injectie 2: 40 SQ–E,

injectie 3: 80 SQ–E, injectie 4:

200 SQ–E,

Alutard SQ

huisstofmijten

injectie 5: 400 SQ–E, injectie

6: 800 SQ–E, injectie 7: 2000

SQ–E, injectie 8: 4000 SQ–E,

Depothal huisstofmijten injectie 9: 8000 SQ–E, injectie

10: 10.000 SQ-E, injectie 11:

20.000 SQ-E, injectie 12: 40.000 SQ-E,

injectie 13: 60.000 SQ-E,

injectie 14: 80.000 SQ-E, injectie 15: 100.000 SQ-E

Artuvac: Instelfase: injectie 1:

0,1 BE, injectie 2: 0,3 BE, injectie 3: 0,6 BE, injectie 4:

1,4 BE,

injectie 5: 2,8 BE, injectie 6: 5,6 BE, injectie 7: 14 BE,

injectie 8: 28 BE, injectie 9: 56

BE,

injectie 10: 140 BE, injectie

11: 280 BE, injectie 12: 560

BE, injectie 13: 700 BE,

Depothal: Instelfase: injectie 1:

2 AU, injectie 2: 4 AU, injectie

3: 8 AU, injectie 4: 20 AU, injectie 5: 40 AU,

injectie 6: 80 AU, injectie 7: 200 AU, injectie 8: 400 AU,

injectie 9: 800 AU, injectie 10:

2000 AU,

injectie 11: 4000 AU, injectie

12: 6000 AU, injectie 13: 8000

AU, injectie 14: 10.000 AU;

Allergeenextrac

t insectengif

parenteraal

Alutard giffen Alutard: Instelfase: injectie 1:

20 SQ–E, injectie 2: 40 SQ–E,

injectie 3: 80 SQ–E,

Pharmalgen injectie 4: 200 SQ–E, injectie

5: 400 SQ–E, injectie 6: 800

SQ–E, injectie 7: 2000 SQ–E,

injectie 8: 4000 SQ–E, injectie

9: 8000 SQ–E, injectie 10:

10.000 SQ-E, injectie 11:

20.000 SQ-E,

injectie 12: 40.000 SQ-E,

injectie 13: 60.000 SQ-E, injectie 14: 80.000 SQ-E,

injectie 15: 100.000 SQ-E

Pharmalgen: Instelfase: conventioneel schema: injectie

1: 0,01 microg, injectie 2: 0,1

microg,

injectie 3: 1 microg, injectie 4:

5 microg, injectie 5: 10 micrg

injectie 6: 20 microg, injectie 7: 30 microg,

60

injectie 8: 40 microg, injectie

9: 50 microg, injectie 10: 60

microg, injectie 11: 80 microg,

injectie 12: 80 microg

Allergeenextrac

t kattenepitheel

parenteraal

Alutard SQ Epithelia Alutard: Instelfase: injectie 1:

20 SQ–E, injectie 2: 40 SQ–E,

injectie 3: 80 SQ–E,

injectie 4: 200 SQ–E, injectie

5: 400 SQ–E, injectie 6: 800

SQ–E, injectie 7: 2000 SQ–E,

injectie 8: 4000 SQ–E, injectie

9: 8000 SQ–E, injectie 10:

10.000 SQ-E, injectie 11: 20.000 SQ-E,

injectie 12: 40.000 SQ-E,

injectie 13: 60.000 SQ-E, injectie 14: 80.000 SQ-E,

injectie 15: 100.000 SQ-E