Reaching multidisciplinary consensus on classification of anaphylaxis for the eleventh revision of the World Health Organization's (WHO) International Classification of Diseases (ICD-11)
© The Author(s). 2017
Received: 5 September 2016
Accepted: 5 March 2017
Published: 16 March 2017
Although currently misclassified in the International Classification of Diseases (ICD) and still not officially listed as a rare disease, anaphylaxis is a well-known clinical emergency. Anaphylaxis is now one of the principal headings in the “Allergic and hypersensitivity conditions” section recently compiled for the forthcoming 11th Revision of ICD (ICD-11). We here report the building process used for the pioneering “Anaphylaxis” subsection of ICD-11 in which we aimed for transparency as recommended in the ICD-11 revision guidelines.
During an online intensive scientific and technical discussions with ICD-11 Topic Advisory Groups and Expert Working Groups, we drafted a total of 35 proposals for the classification of anaphylaxis. From all the 35 proposals, 77% were implemented, 20% remain to be implemented, and the others being partially implemented (1.5%) or rejected (1.5%).
For the first time, anaphylaxis is now properly classified and has attained greater visibility within ICD. In addition to all the benefits expected from the actions we have undertaken in updating the terminology, definitions and classification of allergic and hypersensitivity conditions for ICD-11, we strongly believe that anaphylaxis should be a public health priority and that it should therefore be formally added into the list of rare diseases in order to support awareness and quality clinical management of patients.
KeywordsAnaphylaxis Classification International Classification of Diseases World Health Organization
Anaphylaxis as a rare disease: definitions, epidemiology and unmet needs
Regional epidemiological data cite anaphylaxis incidence rates ranging from 1.5 to 7.9 per 100 000 person-years in European countries  and estimated in at 5.1% (95% CI, 3.4 to 6.8%) in the United States . Based on these statistics, anaphylaxis would fit well the definition of a rare disease, although it is not currently listed in rare diseases registries . The epidemiological criteria for designating a condition a “rare disease” vary depending on the reference in consideration but, conceptually, rare diseases can be defined as life-threatening or chronic debilitating disorders which are of low prevalence and typically require combined efforts to address them. The global epidemiological morbidity  and mortality  data for anaphylaxis remain unclear due to the lack of standardized tools for capturing harmonized and accurate data, particularly in the International Classification of Diseases, Injuries and Cause of Death (ICD). This fact has a direct impact on the awareness it receives for healthcare planning and resource allocation, quality patient management and public health policy.
Anaphylaxis in the International Classification of Diseases
The ICD is a global standard diagnostic classification for mortality and morbidity statistics maintained by the World Health organization (WHO). Currently the majority of countries use the tenth revision of ICD (ICD-10) or adaptations thereof . ICD-10 has inherited a structure from previous versions of ICD in which topographic distribution frequently takes precedence over underlying mechanisms, triggers or any of the concepts currently used for allergic and hypersensitivity conditions. As a result, only two terms in ICD-10 for anaphylaxis are hidden within section T78 of Other and unspecified effects of external causes under the unsatisfactory title Adverse effects, not elsewhere classified . The inadequacy of this classification is a major reason for the under-notification of anaphylaxis in vital statistics .
From this Foundation may be extracted any number of traditional tabular lists, which differ from the Foundation in that a single entity may appear in only one location (as in ICD-10 and, as in the latter’s proposed replacement, the ICD-11 for Mortality and Morbidity Statistics (ICD-11 MMS)). This will also permit the construction of a range of specialist classifications in which the detail contained in the Foundation is retained but which can link to ICD-11 MMS.
To further inform the allergy community and to ensure that the revision process is transparent as advised in the ICD-11 revision agenda, we report the building process we used for the pioneering “Anaphylaxis” subsection of ICD-11.
Building the “Anaphylaxis” subsection of ICD-11
The ICD-11 beta draft platform  can be considered a WHO web-observatory in which the representatives of RSG and TAGs can monitor the proposal submissions and comments. Based on these, the RSG members can approve, partially approve or reject a proposal. Each proposal is then scrutinized by WHO and, if accepted, can then be implemented and incorporated into the current version of ICD-11, following which the change will be visible in the Browser. A proposal may be rejected in part or in full with the reasons for the decision provided by commentaries to the proposal. Alternatively further clarification may be sought from the proposer.
In order to document the construction process fully, we analyzed all of the above actions in order to describe the historic and current status of the Anaphylaxis sub-section and analyze the reasons for the principal changes. For this evaluation we considered actions related exclusively to this sub-section and proposals related to the patient’s background (e.g. personal history of anaphylaxis). Some proposals related to the topic were submitted during the revision process in order to adjust the higher ICD-11 hierarchy in general (e.g. removal of all anaphylaxis and allergic or hypersensitivity conditions from the parent Adverse effects, not elsewhere classified after the construction of the new section). We did not include proposals not directly related to the patient, such as Family history of anaphylaxis.
The “Anaphylaxis” sub-section of ICD-11
As a result of all the previous actions, 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.
Allergic and hypersensitivity disorders are managed not only by allergists but also by specialists from a range of different disciplines. As a consequence, intensive scientific and technical discussions with TAGs and EWGs were essential for achieving consensus for the new classification, which will for the first time enable anaphylaxis to be properly represented within ICD.
Since anaphylaxis has never been addressed by a single section in the ICD, it was to be expected that most of the proposals were for content enhancement and complex hierarchical change. These kinds of proposals, in general, support the building processes of new structures. The only partially implemented proposal appeared as such because the incorrect proposal type (deletion of entity) was inadvertently selected for removal of the link to a second parent, which is a hierarchical change. As explained above, the polyhierarchical structure of the ICD-11 Foundation enables any given entity to be linked to more than one parent (Fig. 2).
The only rejected proposal concerned the addition of “Anaphylaxis classified by clinical severity” as a new entity. The reason for the rejection was that ICD-11 enables diagnoses to be linked to a range of parameters by the addition of one or more “extensions” in a process termed post-coordination. WHO has been promoting this classification strategy in which a stem entity (e.g. Anaphylaxis) can be more fully defined by linking it to a range of different value sets including severity, anatomical location and causal agent . All the proposals that have yet to be implemented are related to “personal history of” or to instances where the use of post-coordination would enable the intended meaning to be captured, such as severity grade or allergens and triggers.
Some limitations of the current study may have to be considered. Since the online ICD-11 beta draft is not final and is updated regularly, the current results may not be reproduced if reanalyzed in the future with the same methodology. Although this manuscript presents some technical aspects of classification and new ICD-11 concepts, its aim is also to serve as an introduction to ICD-11 for ICD end-users in the allergy community using anaphylaxis as an example.
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. 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 decision-making and public health measures to reduce the morbidity and mortality attributable to allergy. Examples are the availability of adrenaline auto-injectors 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.
The Orphanet, lead by the French National Institution of Health and Medical Research (INSERM) and the French Ministry of Health, is responsible for developing an inventory of rare diseases and a classification system which could serve as a template to update International terminologies. When the WHO launched the revision process of the ICD, a rare diseases TAG was established. So far 5,400 rare diseases listed in the Orphanet database have an endorsed representation in the foundation layer of ICD-11 , but anaphylaxis is not yet into the list.
For the first time, anaphylaxis is now properly classified and has attained greater visibility within ICD. Additionally to all the benefits expected by the actions to update terminology, definitions and classification of allergic and hypersensitivity conditions through the ICD-11 revision, we strongly believe that anaphylaxis is a public health priority and that in order to support awareness and quality clinical management of patients it should therefore be formally added to the list of rare diseases.
International Classification of Diseases
Revision Steering Group
Topic Advisory Group
World Health Assembly
World Health Organization
We are extremely grateful to all the representatives of the ICD-11 Revision Project with whom we have been carrying on fruitful discussions, helping us to refine the classification presented here: Robert Jakob, Linda Best, Nenad Kostanjsek, Robert J G Chalmers, Jeffrey Linzer, Linda Edwards, Ségolène Ayme, Bertrand Bellet, Rodney Franklin, Matthew Helbert, August Colenbrander, Satoshi Kashii, Paulo E. C. Dantas, Christine Graham, Ashley Behrens, Julie Rust, Megan Cumerlato, Tsutomu Suzuki, Mitsuko Kondo, Hajime Takizawa, Nobuoki Kohno, Soichiro Miura, Nan Tajima and Toshio Ogawa.
Joint Allergy Academies: American Academy of Allergy Asthma and Immunology (AAAAI), European Academy of Allergy and Clinical Immunology (EAACI), World Allergy Organization (WAO), American College of Allergy Asthma and Immunology (ACAAI), Asia Pacific Association of Allergy, Asthma and Clinical Immunology (APAAACI), Latin American Society of Allergy, Asthma and Immunology (SLAAI).
Availability of data and materials
Data sharing not applicable to this article as no datasets were generated or analyzed during the current study. The ICD-11 beta draft platform is open to the public.
LKT and PD contributed to the construction of the document (designed the study, analyzed and interpreted the data, and wrote the manuscript). RJGC, SA and MAC contributed to tuning the document and revision of the manuscript. All authors read and approved the final manuscript.
The authors declare that they do not have any conflict of interests related to the contents of this article.
Consent for publication
Pascal Demoly and Luciana Kase Tanno received an unrestricted AstraZeneca ERS-16-11927 grant through CHRUM administration.
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