How can the World Health Organization’s International Classification of Diseases (ICD)-11 change the clinical management of anaphylaxis?

KEYWORDS:

• Anaphylaxis
• epidemiology
• epinephrine
• International Classification of Diseases (ICD)
• management

Anaphylaxis is currently recognized as a severe, life-threatening systemic hypersensitivity reaction characterized by rapid onset and the potential to endanger life. Since anaphylaxis is characterized by rapidly developing life-threatening airway and/or breathing and/or circulation problems, the need of rapid management of this condition is well-known. Epinephrine (adrenaline), injected by the intramuscular route, is the medication of choice for the first-aid treatment of anaphylaxis [1–3].

Regional epidemiological data cite anaphylaxis incidence rates ranging from 1.5 to 7.9 per 100 000 person-years in European countries [4] and estimated in at 5.1% (95% CI, 3.4% to 6.8%) in the United States [5]. In all countries, epidemiological and health services research can serve as a baseline for quality improvement, prioritization of anaphylaxis programs, and eventual reduction in morbidity and mortality. However, the global epidemiological morbidity [6] and mortality [7] data for anaphylaxis remain unclear due to the lack of standardized tools for capturing harmonized and accurate data, particularly in the International Classification of Disease (ICD) (Table 1). As an example, we confirmed in 2012, the under notification of anaphylaxis deaths due to difficult coding under the ICD-10 [7] and documented previously [8,9].

Table 1. Anaphylaxis classification and coding in ICD-10 and in ICD-11.

ANAPHYLAXIS ICD-10 CODES (2016 version)			ANAPHYLAXIS ICD-11 CODES (November 2016 version)
Chapter XIX Injury, poisoning and certain other consequences of external causes (S00-T98)			Chapter 04 Disorders of the immune system
	Other and unspecified effects of external causes (T66-T78)		Section Allergic and hypersensitivity conditions
T78	Adverse effects, not elsewhere classified		Subsection Anaphylaxis
	Note:		4B50 Anaphylaxis due to allergic reaction to food
	This category is to be used as the primary code to identify the effects, not elsewhere classifiable, of unknown, undetermined or ill-defined causes. For multiple coding purposes this category may be used as an additional code to identify the effects of conditions classified elsewhere.		4B51 Drug-induced anaphylaxis
	T78.0 Anaphylactic shock due to adverse food reaction		4B52 Anaphylaxis due to insect venom
	T78.1 Other adverse food reactions, not elsewhere classified		4B53 Anaphylaxis provoked by physical factors
	T78.2 Anaphylactic shock, unspecified		4B53.1 Exercise-induced anaphylaxis
	Allergic shock	NOS		4B53.2 Cold-induced anaphylaxis
	Anaphylactic reaction			4B53.Y Anaphylaxis provoked by other specified physical factors
	Anaphylaxis			4B53.Z Anaphylaxis provoked by unspecified physical factors
	T78.3 Angioneurotic oedema		4B54 Anaphylaxis due to inhaled allergens
	Giant urticaria		4B55 Anaphylaxis due to contact with allergens
	Quincke oedema		4B56 Anaphylaxis secondary to mast cell disorder
	T78.4 Allergy, unspecified		4B5Y Other specified anaphylaxis
	Allergic reaction NOS		4B5Z Anaphylaxis, unspecified
	Hypersensitivity NOS
	Idiosyncracy NOS
	T78.8 Other adverse effects, not elsewhere classified
	T78.9 Adverse effect, unspecified

The ICD is an international standard diagnostic classification for mortality and morbidity statistics (MMS) maintained by the World Health organization (WHO). Uses include monitoring of the incidence and prevalence of diseases, observing reimbursements and resource allocation trends, and keeping track of safety and quality guidelines. In use by more than 100 countries, the ICD also includes the counting of deaths as well as diseases, injuries, symptoms, reasons for encounter, factors that influence health status, and external causes of disease [10]. The weak identity of disorders in the ICD contributes to the lack of ascertainment and recognition of their importance for health care planning and resource allocation, and prevents clinical research from being performed. Regarding mortality statistics, unless the data have been compiled using the same methods and according to the same standards, comparisons potentially yield misleading results. For these reasons, the WHO issued international instructions on data collection, coding and classification, and statistical presentation of causes of death. In most countries, mortality statistics are routinely compiled according to regulations and recommendations adopted by the World Health Assembly [10]. The international mortality coding instructions presuppose that data have been collected with a death certificate conforming to the International form of medical certificate of cause of death. On current death certificates, a limited number of ICD codes are valid as underlying causes of death, and death certificates do not include the word anaphylaxis per se [7].

Anaphylaxis resides in ICD-10 under the nonspecific ‘Chapter XIX Injury, poisoning and certain other consequences of external causes’ which the main references are ‘Anaphylactic shock due to adverse food reaction’ (T78.0) and ‘Anaphylactic shock, unspecified’ (T78.2) (Table 1). Moreover, the term ‘shock’, which means the drop of blood pressure, is one of the anaphylaxis manifestations, however, should not be taken as synonymous or always together. It suggests the need of implementing a severity degree classification for anaphylaxis into the ICD [6], currently implemented for ICD-11.

Understanding the specifications of more accurate anaphylaxis morbidity and mortality statistics can support the identification of patients at highest risk, facilitating the implementation of prevention measures. In theory, such data could be used to support national and international public health strategies such as mapping emerging triggers, assessing the safety of marketed products, and establishing the mandatory declaration of most relevant allergens. Besides, these data can support decision-making actions and advocate for a better management of anaphylaxis through the global affordable availability of auto-injectable adrenaline (AAI), as first-line medications in the treatment of this condition.

The WHO lists adrenaline as an essential medication for the treatment of anaphylaxis [9]. However, it is not readily available in the form of auto-injectors in more than 65% of world countries [11] in which best management of patients with anaphylaxis is therefore impossible. The key issues leading to the lack of availability of AAI include cost but also national regulations, lack of regional evidence about the value of epinephrine and the limited accurate data about the epidemiology of anaphylaxis morbidity and mortality data. For these reasons, regional and international allergy academies support the initiatives to narrow these gaps. Our WHO Collaborating Center is deeply involved in this process and our first key goal is to ensure the availability of essential medications for patients, therefore the AAI in low and middle-income countries and to promote better management and education in high-income countries, with the support of the WHO-Family of International Classifications, academic, and scientific networks, the Joint Allergy Academies, stakeholders and patients’ organizations. The WHO Collaborating Center leadership is working in an education program in order to support the transition for the ICD-11.

With the aim of having a better representation of allergic and hypersensitivity conditions, including anaphylaxis, in international classification systems and taking the window of opportunity presented by the ICD-11 revision, the documented anaphylaxis deaths under-notification data [7] triggered a cascade of strategic international actions acknowledged by a Joint Allergy Academies’ consortium composed by six international regional allergy academies, the ICD WHO governance [6,7,12–20] in order to update the classifications of allergic and hypersensitivity conditions for the new ICD edition. The design of the anaphylaxis subsection was based on the Allergic and hypersensitivity diseases proposal, which had been validated by crowd-sourcing [13] and simplified [15] according to ICD Revision Steering Group (RSG) guidance. The construction of the new Allergic and hypersensitivity conditions section of the ICD-11 resulted by intensive scientific, academic and technical discussions to ensure comparability and consistency. The development of the ‘Anaphylaxis’ sub-section involved strong academic input and extensive consultation and agreement from the relevant Topic Advisory Groups and Expert Working Groups (Figure 1). The intensive exchange of e-mails and teleconference/videoconferences started in February 2014 and was the basis for the submission of proposals into the online ICD-11 beta draft platform [21]. All the actions of the Allergy Working Group have so far been undertaken with RSG guidance. All the terms of the ICD-11 count with definitions.

Figure 1. Framework of groups in charge of the international classification of diseases (ICD)-11 revision process.

These efforts have resulted in the construction of the pioneer ‘Allergic and hypersensitivity conditions’ section under the ‘Disorders of the Immune system’ chapter of the online ICD-11 Beta draft [21,22]. In the new ‘Allergic and hypersensitivity conditions’ section of ICD-11, it was possible to build a sub-section specifically addressed to anaphylaxis. For the first time, anaphylaxis is elected as individualized conditions into the ICD-11 frame, receiving a sub-section addressed to this condition. The new ‘Anaphylaxis’ sub-section was constructed, with 11 entities classified under 7 main headings: Anaphylaxis due to allergic reaction to food, Drug-induced anaphylaxis, Anaphylaxis due to insect venom, Anaphylaxis provoked by physical factors, Anaphylaxis due to inhaled allergens, Anaphylaxis due to contact with allergens and Anaphylaxis secondary to mast cell disorders (Table 1), and followed a multi-hierarchical framework. As an example, ‘anaphylaxis due to contrast media’ is multi-parented by ‘drug or pharmaceutical agent hypersensitivity’, ‘adverse cutaneous effects of diagnostic procedures’, ‘miscellaneous urticarial disorders’ and ‘drug-induced anaphylaxis’ (Figure 2). The construction of the new section dealing with anaphylaxis means that the latter will now be recognized as a clinical condition requiring specific documentation and management.

Figure 2. Taking the example from ‘anaphylaxis due to radiocontrast media’ to demonstrate the multi-hierarchical framework of ICD-11.

From the public health perspective, by allowing all the relevant diagnostic terms for anaphylaxis to be included in the ICD-11 MMS, WHO has recognized their importance not only to clinicians but also to epidemiologists, statisticians, health-care planners, and other stakeholders. Importantly the new classification will enable the collection of more accurate epidemiological data to support quality management of patients with allergies, better health care planning and gathering public health measures to reduce the morbidity and mortality attributable to allergy. Examples are the availability of AAI in all countries for patients at risk, the provision of resuscitation kits in public places and the implementation of prevention campaigns in surgical and radiology departments.

Overall, the WHO indicates that the ICD is currently responsible for allocating about 70% of the world’s health expenditures, meaning by USD 2.3 trillion in 2013 and USD 2.6 trillion in 2014 according to the National Center for Health Statistics [10,22]. Therefore, every modification into the ICD framework may have a potential impact in health finance and economy. Greater specificity regarding clinical conditions and services delivered will provide payers, policy makers, and providers with better information to make major refinements to payment and reimbursement systems, including the design and implementation of pay-for-performance program [22].

Increasing the specification of conditions will help clarify the connection between a provider’s performance and the patient’s condition. Accurate and updated diagnostic, and procedure codes will improve data on the outcomes, efficacy, and costs of new medical technology and facilitate fair reimbursement policies for the use of this system. It will help payers and providers more easily identify patients in need of disease management and more effectively tailor disease management programs [22].

Although the WHO’s ICD-11 is still some time away to be officially implemented in diverse health systems for final use, the new classification will enable the collection of more accurate epidemiological data to support quality management of patients with allergies, and better facilitate health-care planning and decision-making and public health measures to prevent and reduce the morbidity and mortality attributable to allergic diseases. The improved logic and standardized definitions through the ICD-11 will also facilitate international comparisons of quality care and the sharing of best practice globally.

Declaration of interest

Pascal Demoly and Luciana Kase Tanno received an unrestricted Novartis and MEDA/Mylan Pharma grants through CHRUM administration. The authors have no other relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript apart from those disclosed.

Reviewer disclosures

Peer reviewers on this manuscript have no relevant financial or other relationships to disclose

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This paper is not funded.