• Approaches to the development of clinical criteria for cases suspected of primary immunodeficiency (literature review)
en To content Full text of article

Approaches to the development of clinical criteria for cases suspected of primary immunodeficiency (literature review)

SOVREMENNAYA PEDIATRIYA.2018.8(96):92-98; doi 10.15574/SP.2018.96.92

Beglaryan S. A., Chernyshova L. I.
Shupyk National Medical Academy of Postgraduate Education, Kyiv, Ukraine

Topicality. For 2018, there are more than 350 nosologies of primary immunodeficiencies. Most cases of congenital immunodeficiencies remain undiagnosed due to the absence of pathognomonic symptoms with them and the low level of doctors' awareness of this pathology. Primary (congenital) immunodeficiencies are not fatal nowadays, as they can be treated. In case of the early diagnosing, children get a chance for a full life and, often, a complete recovery. So, development of criteria for identifying cases suspected of primary immunodeficiency is important.

Objective: Study of existing approaches to the development of clinical criteria for the detection of primary immunodeficiencies.

Material and methods. Collection and analysis of existing literature on clinical criteria related to manifestations of primary immunodeficiencies.

Results. We analyzed 13 works about development of criteria for primary immunodeficiencies diagnosis. Throughout the world, including Ukraine, a number of criteria have been developed, which may be clinical markers of suspected congenital immunodeficiency. There were different approaches for the development of clinical criteria for primary immunodeficiencies such as calculating the symptoms frequency, the χ2 fourfold table, regression analysis and making of an immunodeficiency4related score for assessing the hospitalized patients' diagnoses through the computer screening. One work shows separately developed criteria for children and adults.

Conclusions. The analysis of literature showed different methods for identifying patients with primary immunodeficiencies. Existing approaches can be a precondition for the further clinical criteria development for the early detection of primary immunodeficiencies.

Key words: paediatric immunology, primary immunodeficiencies, clinical criteria.


1. Bondarenko AV. (2016). Diagnosis and Medical, Social Support of Primary Immunodeficiencies in Children. DSc dissertation abstract. Кyiv: 46.

2. Volokha AP. (2009). Features of the Course of Primary Antibody Deficiencies in Children, Definition of Early Diagnostic Criteria and Justification of Differentiated Approaches to Treatment. DSc dissertation abstract. Кyiv: 40.

3. Kostiuchenko LV. (2012). Detection, Verification and Medical Support of Primary Combined Immunodeficiencies in Children. DSc dissertation abstract. Кyiv: 40.

4. Chernyshova LI, Bondarenko AV, Volokha AP. (2015). Criteria for a Suspicious Case of Primary Immunodeficiency in Children (Indications for Required Referral to Paediatric Immunologist). Informative letter on healthcare innovations N226. Кyiv: 4.

5. Chernyshova LI, Bondarenko AV, Kostiuchenko LV, Savvo OM, Volokha AP, Rabosh OV. (2015). Epidemiology of Primary Immunodeficiencies in Ukraine According to Patients' Registry. Child’s health. 7:16–23.

6. Arkwright PD, Gennery AR. (2011). Ten warning signs of primary immunodeficiency: a new paradigm is needed for the 21st century. Ann N Y Acad Sci. 1238: 7—14. https://doi.org/10.1111/j.1749-6632.2011.06206.x; PMid:22129048

7. Bousfiha AA, Jeddane L, Ailal F et al. (2013). Primary immunodeficiency diseases worldwide: more common than generally thought. J Clin Immunol. 33(1): 1—7. https://doi.org/10.1007/s10875-012-9751-7; PMid:22847546

8. Cunningham-Rundles C, Sidi P, Estrella L, Doucette J. (2004). Identifying undiagnosed primary immunodeficiency diseases in minority subjects by using computer sorting of diagnosis codes. J Allergy Clin Immunol. 113(4): 747—55. https://doi.org/10.1016/j.jaci.2004.01.761; PMid:15100683

9. Defining the term «malaria case». WHO update of malaria terminology. August 2015, Geneva, Switzerland. http://www.who.int/malaria/mpac/mpac-sept2015-terminology-annex1.pdf

10. Edgar JD, Buckland M, Guzman D et al. (2014). The United Kingdom Primary Immune Deficiency (UKPID) Registry: report of the first 4 years' activity 2008—2012. Clin Exp Immunol. 175(1): 68—78. https://doi.org/10.1111/cei.12172; PMid:23841717 PMCid:PMC3898556

11. Gathmann B, Binder N, Ehl S, Kindle G. (2012). The European internetbased patient and research database for primary immunodeficiencies: update 2011. Clin Exp Immunol. 167(3): 479—91. https://doi.org/10.1111/j.1365-2249.2011.04542.x; PMid:22288591 PMCid:PMC3374280

12. Hitzig WH. (2003). The discovery of agammaglobulinaemia in 1952. Eur J Pediatr. 162: 289—304. PMid:12692709

13. Lankisch P, Schiffner J, Ghosh S, Babor F, Borkhardt A, Laws HJ. (2015). The Duesseldorf warning signs for primary immunodeficiency: is it time to change the rules? J Clin Immunol. 35(3): 273—9. https://doi.org/10.1007/s10875-015-0149-1; PMid:25749910

14. Louis-Bar D. (1941). Sur un syndrome progressif comprenant des telangiecstasies capillaries cutanees et conjonctivales symetriques a dispositions naevoїde et de truobles cerebelleux. Conf Neurol (Basel). 4: 32—42. https://doi.org/10.1159/000106149

15. Marodi L, Casanova JL. (2009). Primary immunodeficiency diseases: the J Project. The Lancet. 373(9682): 2179—2181. https://doi.org/10.1016/S0140-6736(09)61171-5

16. Mellouli F, Mustapha IB, Khaled MB et al. (2015). Report of the Tunisian Registry of Primary Immunodeficiencies: 25-Years of Experience (1988—2012). J Clin Immunol. 35(8): 745—53. https://doi.org/10.1007/s10875-015-0206-9; PMid:26464197

17. Modell V, Gee B, Lewis DB et al. (2011). Global study of primary immunodeficiency diseases (PI) — diagnosis, treatment, and economic impact: an updated report from the Jeffrey Modell Foundation. Immunol Res. 51(1): 61—70. https://doi.org/10.1007/s12026-011-8241-y; PMid:21935653

18. Modell V, Orange JS, Quinn J, Modell F. (2018). Global report on primary immunodeficiencies: 2018 update from the Jeffrey Modell Centers Network on disease classification, regional trends, treatment modalities, and physician reported outcomes. Immunol Res. https://doi.org/10.1007/s12026-018-8996-5; PMid:29744770

19. Modell V, Quinn J, Orange J, Notarangelo LD, Modell F. (2016). Primary immunodeficiencies worldwide: an updated overview from the Jeffrey Modell Centers Global Network. Immunol Res. 64(3): 736—53. https://doi.org/10.1007/s12026-016-8784-z; PMid:26802037

20. Picard C, Bobby Gaspar H, Al-Herz W et al. (2018). International Union of Immunological Societies: 2017 Primary Immunodeficiency Diseases Committee Report on Inborn Errors of Immunity. Journal of Clinical Immunology. 38(1): 96—128. https://doi.org/10.1007/s10875-017-0464-9; PMid:29226302 PMCid:PMC5742601

21. Primary Immunodeficiency Diseases Report of an IUIS Scientific Committee (1999, Oct). Clinical and Experimental Immunology. 118(1): 1—28.

22. Primary immunodeficiency resource center. (2018, April). www.info4pi.org

23. Shillitoe B, Bangs C, Guzman D, et al. The United Kingdom Primary Immune Deficiency (UKPID) registry 2012 to 2017. (2018). Clin Exp Immunol. 192(3): 284—291. https://doi.org/10.1111/cei.13125

24. Shultz W. (1922). Ueber eigenartige Halserkraunkungen. (Apropos unusual diseases of the pharynx). Dtsch Med Wochenschr. 48: 1495—1497.

25. Subbarayan A, Colarusso G, Hughes SM et al. (2011). Clinical features that identify children with primary immunodeficiency diseases. Pediatrics. 127(5): 810—6. https://doi.org/10.1542/peds.2010-3680; PMid:21482601

26. Syllaba L, Henner K. (1926). Contribution a L'independence de l'athetose double idiopathique et congenital: atteinte familiale, syndrome distrophique, signe du reseau vasculaire conjonctival, integrite psychique. Rev Neurol (Paris). 1: 541—562.

27. WHO. (2013). Guidelines for measles and rubella outbreak investigation and response in the WHO European Region.. http://www.euro.who.int/__data/assets/pdf_file/0003/217164/OutbreakGuidelines-updated.pdf

28. WHO. (2018, April). Rabies vaccines: WHO position paper. Weekly epidemiological record. 16: 201—220. http://apps.who.int/iris/bitstream/handle/10665/272371/WER9316.pdf

29. Wiskott A. (1936). Familiarer, angeborener Morbus Werlhofii? Monatsschr Kinderheikld. 68: 212—216.

Article received: Jul 21, 2018. Accepted for publication: Dec 01, 2018.