Brief Article Open Access
Copyright ©2011 Baishideng Publishing Group Co., Limited. All rights reserved.
World J Gastroenterol. Dec 7, 2011; 17(45): 4971-4978
Published online Dec 7, 2011. doi: 10.3748/wjg.v17.i45.4971
Burden of celiac disease in the Mediterranean area
Luigi Greco, Laura Timpone, Abdelhak Abkari, Mona Abu-Zekry, Thomas Attard, Faouzi Bouguerrà, Paskal Cullufi, Aydan Kansu, Dusanka Micetic-Turk, Zrinjka Mišak, Eleftheria Roma, Raanan Shamir, Selma Terzic
Luigi Greco, Laura Timpone, European Laboratory for Food Induced Diseases, Federico II University of Naples, 80131 Naples, Italy
Abdelhak Abkari, Hopital des Enfant Ibn Rochd de Casablanca, 20100 Casablanca, Morocco
Mona Abu-Zekry, Children’s Hospital, Gastrointestinal Unit, Cairo University, 12611 Giza, Egypt
Thomas Attard, University of Malta, Medical School, Guardamangia MSD 06, Malta
Faouzi Bouguerrà, Hopital des Enfants de Tunis, 1006 Tunis, Tunisia
Paskal Cullufi, Department of Gastroenterology and Hepatology, University Hospital Center “Mother Teresa”, nr 371 Tirana, Albania
Aydan Kansu, Department of Pediatric Gastroenterology, Ankara University, Dikimevi/Mamak, Ankara 06100, Turkey
Dusanka Micetic-Turk, University Medical Centre, Paediatric Department, Ljubljanska, 2000 Maribor, Slovenia
Zrinjka Mišak, Children’s Hospital Zagreb, 10000 Zagreb, Croatia
Eleftheria Roma, Athens University, Aghia Sophia Children’s Hospital, Goudi, 11527 Athene, Greece
Raanan Shamir, Schneider Children’s Medical Center of Israel, Tel-Aviv University, Petach-Tikva 49202, Israel
Selma Terzic, University Clinical Center Tuzla, Children's Hospital, 75000 Tuzla, Bosnia Herzegovina
Author contributions: Greco L, Timpone L, Abkari A, Abu-Zekry M, Attard T, Bouguerrà F, Cullufi P, Kansu A, Micetic-Turk D, Mišak Z, Roma E, Shamir R and Terzic S directly participated in the study, including substantial contributions to conception and design of the study and acquisition of data; Greco L, Timpone L and Shamir R analyzed the data, wrote the manuscript and provided statistical analysis of data.
Supported by European Laboratory for Food Induced Diseases, Federico II University of Naples
Correspondence to: Luigi Greco, Professor of Medicine, Chief, European Laboratory for Food Induced Diseases, Federico II University of Naples, 80131 Naples, Italy. ydongre@unina.it
Telephone: +39-081-7463275 Fax: +39-081-7462375
Received: March 19, 2011
Revised: June 15, 2011
Accepted: June 22, 2011
Published online: December 7, 2011

Abstract

AIM: To estimate the burden of undiagnosed celiac disease (CD) in the Mediterranean area in terms of morbidity, mortality and health cost.

METHODS: For statistics regarding the population of each country in the Mediterranean area, we accessed authoritative international sources (World Bank, World Health Organization and United Nations). The prevalence of CD was obtained for most countries from published reports. An overall prevalence rate of 1% cases/total population was finally estimated to represent the frequency of the disease in the area, since none of the available confidence intervals of the reported rates significantly excluded this rate. The distribution of symptoms and complications was obtained from reliable reports in the same cohort. A standardized mortality rate of 1.8 was obtained from recent reports. Crude health cost was estimated for the years between symptoms and diagnosis for adults and children, and was standardized for purchasing power parity to account for the different economic profiles amongst Mediterranean countries.

RESULTS: In the next 10 years, the Mediterranean area will have about half a billion inhabitants, of which 120 million will be children. The projected number of CD diagnoses in 2020 is 5 million cases (1 million celiac children), with a relative increase of 11% compared to 2010. Based on the 2010 rate, there will be about 550 000 symptomatic adults and about 240 000 sick children: 85% of the symptomatic patients will suffer from gastrointestinal complaints, 40% are likely to have anemia, 30% will likely have osteopenia, 20% of children will have short stature, and 10% will have abnormal liver enzymes. The estimated standardized medical costs for symptomatic celiac patients during the delay between symptom onset and diagnosis (mean 6 years for adults, 2 years for children) will be about €4 billion (€387 million for children) over the next 10 years. A delay in diagnosis is expected to increase mortality: about 600 000 celiac patients will die in the next 10 years, with an excess of 44.4% vs age- and sex-matched controls.

CONCLUSION: In the near future, the burden of CD will increase tremendously. Few Mediterranean countries are able to face this expanding epidemic alone.

Key Words: Pediatric, Celiac disease, Short stature, Anemia, Osteopenia, Purchasing power parity, Standardized mortality rate, Mediterranean area



INTRODUCTION

Recent epidemiological studies show that the prevalence of celiac disease (CD) is underestimated not only in Europe, but also among the populations of Mediterranean regions such as the Middle East and North Africa[1-3], where its prevalence is similar to that recently observed in Western countries[4]. Indeed, in these two regions, a very high prevalence of CD has recently been reported both in the general population and in at-risk groups[2]. These high frequencies are associated with the widespread consumption of wheat and barley[1,5] and the high frequency of the DR3-DQ2 CD-predisposing haplotypes in these populations[6,7]. But these factors alone do not satisfactorily account for the spread of the CD epidemic in recent years[8,9]. The prevalence of CD among the general population varies from 0.14% to 1.17%[10-20]: 1%-1.3% in Turkey[10-12], 0.6%-0.96% in Iran[13,14], 0.5% in Egypt[15], 0.6% in Tunisia and Israel[16-19], and < 0.5% in Jordan, Lebanon and Kuwait[5,20]. Among high-risk groups [including patients with a positive family history, insulin-dependent diabetes mellitus (IDDM), thyroiditis] the prevalence of CD ranges from 2.4% to 44%, assessed by serological markers and biopsy[21-24].

Egypt, and indeed all North African countries, were significant producers of wheat, and largely used barley for beer brewing; they were considered the “granary”of Romans for over 4 centuries. Bread, mostly made of wheat flour and called “the survival” in some local languages[1], has been a staple food for thousands of years. Similarly, the widespread use of couscous [from grossly milled durum wheat (Triticum durum)] dates back over 2000 years. But the use of wheat and other gluten-containing cereals is also increasing in the countries where it has been a staple for centuries[25,26].

The diffusion of pasta across all the Mediterranean countries is relatively recent and stems from the industrial development of grain processing. Unfortunately, a side effect of this positive dispersal may be the enormous increase in gluten intolerance, which is at a truly epidemic level. CD is now a widespread public health problem that also involves the populations of developing countries, as well as China and India[27,28]. However, this epidemic is not fully recognized since a sizeable number of cases are neither diagnosed nor cared for. In many Mediterranean countries, few cases are diagnosed because of the low level of awareness, knowledge and skill to deal with the problem, the lack of diagnostic resources and the attribution of CD symptoms to other, similar, illnesses[5,20]. The low awareness of CD often leads to a delay in diagnosis, which contributes to an excess of medical costs (CD includes growth failure, infant malnutrition, gastrointestinal diseases, anemia and more than 20 associated symptoms and conditions) and mortality.

All partners taking part in this study agreed that, to date, the best available estimation of CD-associated medical cost was that reported by Long et al[29], and supported by Hershcovici et al[31]. The annual medical cost in the year preceding the diagnosis of CD, excluding diagnostic costs, was estimated to be $5023/patient, $1764 more than the cost of the same patients in the year after diagnosis[29]. In the four years preceding the diagnosis of symptomatic CD, the direct medical cost was estimated to be $11 037/patient. For a symptom- and age-matched control individual, not affected by CD, the cost after 4 years was estimated at $7073, with a difference of $3964 (about $1000/patient per year). This difference is due to increased in-patients admissions, out-patient cost, laboratory tests, radiology, and office visits[29]. The diagnosis of CD resulted in a 30% reduction in direct medical expenditure. A similar 30% reduction in direct medical costs after diagnosis of CD was reported by Green et al[30]; the mean medical expenditure decreased from $8502 per capita to $7133 for the 2 years after diagnosis of CD.

The CD epidemic is the largest epidemic of food-induced permanent disease in the Euro-Mediterranean region. Very few countries of this region are able to face this expanding problem. The aim of this study was to estimate what the burden of CD will be in the near future, and how the CD epidemic will affect morbidity, mortality and health costs. We aim to provide stakeholders with a reliable prediction of the incoming picture of CD in the Mediterranean area, and so enable them to take action to face this epidemic.

MATERIALS AND METHODS
Population statistics

For statistics regarding each country in the Mediterranean area, we accessed authoritative international sources (World Bank, World Health Organization and United Nations). Population size, median age, number of children (0-14 years), population growth rate, birth rate, death rate, infant mortality rate and literacy were retrieved and validated across multiple sources. The projected population from 2010 to 2020 was computed by adopting the 2008 growth rate as a constant over the following decade because the predicted rate of change of the growth rate would have not significantly affected our estimate. The number of children was incremented yearly by the birth rate and corrected for the infant mortality rate although mortality from 1 to 14 years is minimal in all the countries included in this evaluation.

Celiac disease

The prevalence of CD among the populations of Mediterranean countries, such as the Middle East and North Africa[1-3], is similar to that recently observed in Western countries[4]. The prevalence of CD among the general population varies from 0.14% to 1.17%[10-20]: 1%-1.3% in Turkey[10-12], 0.6%-0.96% in Iran[13,14], 0.5% in Egypt[15], 0.6% in Tunisia and Israel[16-19], and < 0.5% in Jordan, Lebanon and Kuwait[5,20]. An overall prevalence rate of 1% cases/total population was finally estimated to better represent the frequency of the disease in the area, since none of the available confidence intervals of the reported rates significantly excluded this 1% rate. The rate of symptomatic vs asymptomatic patients was obtained from several reliable reports from the area[3,9,10,17]. In summary, 85% of symptomatic patients are likely to suffer from gastrointestinal symptoms, which include diarrhea, abdominal pain, vomiting, irritable bowel, and gastritis[5,13,20,32-37]. Among the non-gastrointestinal complaints, the available estimates suggest 20% of children are affected by short stature[5,20,33-35,37], 40% of all cases are affected by anemia[5,20,32,36,37], 30% are afflicted by osteopenia[32,33,35,37], and 10% by abnormal liver enzymes[37,38].

Mortality has been reported in excess of 1.8 compared to age- and sex-matched controls[31,39,40]. The risk of cancer in undiagnosed adults is significantly increased and the mortality is almost doubled in the total cohort of affected persons compared with the general population[41,44].

Crude medical costs

Crude health costs were estimated for the years between symptoms and diagnosis only for symptomatic adults and children, and were standardized for purchasing power parity (PPP) to account for the different economic profile among Mediterranean countries. Since gross national product is different across countries, the PPP is based on the law of one price; in the absence of transaction costs, identical goods will have the same price in different markets. The PPP equalizes the purchasing power of different currencies for a given basket of goods, thereby providing a standardized estimate of cost across countries.

We assume that the cohort of CD without symptoms does not increase the average medical cost compared to non CD individuals (but this should also be revised, since a significant number of patients identified by screening had a posteriori clinical symptoms). Therefore, medical costs are estimated only for 1:7 adults and 1:5 children with CD symptoms.

For each individual adult we assigned (on the basis of the reports cited and the clinical experience of the study partners), a minimal period of 6 years of delay between symptom onset and diagnosis of the disease[45,46], while this delay was two years for each assigned child with CD[9,20]. During that period an adult with CD required, in excess of age- and sex-matched controls, at least: 2 in-patient admissions, 1 out-patient admission, 3 primary medical consultations, 2 specialized consultations, and 4 laboratory tests. Similarly, children needed at least: 1 in-patient admission and 1 out-patient admission, 3 medical consultations, 1 specialized consultation and 2 laboratory tests (Table 1).

Table 1 Excess need of health resources before the diagnosis of celiac disease.
nAdult cost (€)nChild cost (€)
In-patient admission2981812254
Out-patient admission18791586
Medical consultations31003150
Specialist consultations2150150
Lab test44462297
Total per patient11 3933337
Estimated medical costs

The costs of health services were estimated based on the 2007 costs of the Italian National Health Service (NHS) which is similar to that of several European countries. We summed the total costs of the medical services required for each child or adult patient to obtain a standardized cost/per patient before the diagnosis of CD was made (Table 1). In this way, we obtained an estimation of the financial load (only for medical expenses) of symptomatic patients. The estimated cost according to the Italian NHS was then standardized for each country according to its PPP index. The total load of medical expenses for each country was calculated by multiplying the individual cost by the number of symptomatic patients estimated (adults and children).

Summary of reference data

(1) CD prevalence = 1%; incidence: new cases/year estimated at 1% of the live births, corrected for infant mortality rate; (2) symptomatic adults: 1 of every 7 cases, children 1:5 cases; (3) mortality of the total CD cohort: standardized mortality rate 1.8 compared to age- and sex-matched population; (4) delay between symptoms and diagnosis: adults 6 years, children 2 years; (5) associated conditions: 10%-15% of the total cohort - autoimmune disorders 30% (Turkey 1.9%, Iran 33%) and IDDM 10% (6.7%-18.5%); (6) complications: 16% of symptomatic CD patients; and (7) non gastrointestinal symptoms: short stature 20% (only children), anemia 40% (20%-80%), osteopenia 30% (30%-50%), abnormal liver function 10% (Turkey 38%, Iran 25%)

RESULTS

Table 2 shows the population growth, number of children aged 0-14 years and the predicted figures for the year 2020, calculated based on a constant growth rate. The Mediterranean area will have about half a billion individuals by the year 2020, more than 100 million of which will be children aged 0-14 years. This estimate is likely to be in the low range, since some countries with a large population are likely to grow at a higher rate than this estimate before the year 2010.

Table 2 Populations now and after 10 years.
PopulationChildren 0-14Median age (yr)Population growth rate (%)Children 0-14 in 10 yrTotal population in 10 yr
Albania3 619 778853 88329.90.5901 6673 822 345
Algeria33 769 6698 878 66526.61.29 999 56638 032 972
Bosnia4 590 310673 77039.80.3696 9624 748 317
Cyprus792 604154 44535.51.7182 623937 214
Croatia4 491 543708 68341-0.1705 0064 468 242
Egypt81 713 51725 983 67224.8231 776 57599 931 053
France64 057 79011 894 69839.40.512 564 08867 662 729
Greece10 722 8161 531 60641.80.11 551 16910 859 777
Israel7 112 3591 989 31229.11.72 347 8698 394 303
Italy58 126 2127 870 22643.307 833 31457 853 596
Lebanon3 971 9411 032 88829.31.11 153 0964 434 197
Libya6 173 5792 048 54823.92.22 539 5997 653 427
Malta403 53266 11239.50.468 805419 967
Morocco34 343 21910 473 478251.111 683 1388 309 775
Syria19 747 5867 146 56921.728 716 75424 086 361
Slovenia2 007 711273 46441.50273 6552 009 117
Spain40 525 0025 864 41941.10.15 906 78040 817 729
Tunisia10 383 5772 413 48429.212 660 71311 447 236
Turkey71 892 80717 545 89027.71.319 965 02581 805 009
Mediter458 445 552107 403 81233.20.9121 526 405507 693 365

Table 3 shows the prevalence of CD in each country in 2010 and the predicted prevalence in 2020. Within 10 years, the Mediterranean area will have to face more than 5 million cases of CD, one million of which will be in children. The large majority will not have clear symptoms and their diagnosis and care will be significantly delayed. Among the adult CD population, about 550 000 will present symptoms, while only 240 000 out of the 1 million estimated celiac children will be symptomatic. Table 4 shows the estimated number of clinical complaints associated with the CD epidemic. It is likely that more than 48 000 children will be affected by growth failure, there will be 317 000 cases of anemia and 238 000 individuals will be afflicted with osteopenia. Table 5 shows the estimated financial burden of the CD epidemic. There is no scope for a detailed calculation of costs, which will be related more to the availability of and access to medical services than to the actual cost of the service, but these figures help to understand the financial burden of the undiagnosed disease. European countries may not be impressed by these estimates but, for several other Mediterranean countries, these predicted costs might be a consistent load to the gross national product. More than €4 billion is a prudent estimate; only crude medical costs are included, not individual or social cost.

Table 3 Prevalence of celiac disease in the next 10 years1.
Estimated celiacs todayEstimated celiac children today at 1%Projected prevalence of CD in next 10 yrProjected celiac children in next 10 yr
Albania36 198853938 2239017
Algeria337 69788 787380 33099 996
Bosnia45 903673847 4836970
Cyprus7926154493721826
Croatia44 915708744 6827050
Egypt817 135259 837999 311317 766
France640 578118 947676 627125 641
Greece107 22815 316108 59815 512
Israel71 12419 89383 94323 479
Italy581 26278 702578 53678 333
Lebanon39 71910 32944 34211 531
Libya61 73620 48576 53425 396
Malta40356614200688
Morocco343 432104 735383 098116 831
Syria197 47671 466240 86487 168
Slovenia20 077273520 0912737
Spain405 25058 644408 17759 068
Tunisia103 83624 135114 47226 607
Turkey718 928175 459818 050199 650
Mediter4 584 4561 074 0385 076 9341 215 264
Table 4 Symptoms and diseases associated with symptomatic cases.
Symptomatic adults next 10 yr 1:7Symptomatic children next 10 yr 1:5Gastrointestinal symptomsAnaemiaOsteopeniaAbnormal liverChildren with short stature
Albania41721803507923901793598361
Algeria40 04819 99951 04024 01918 01460054000
Bosnia57881394610428732154718279
Cyprus1078365122757743314473
Croatia53761410576827142036679282
Egypt97 36463 553136 77964 36748 27516 09212 711
France78 71225 12888 26441 53631 15210 3845026
Greece13 298310213 940656049201640620
Israel8638469611 333533340001333939
Italy71 45815 66774 05634 85026 13787123133
Lebanon46872306594427972098699461
Libya7305507910 5274954371512381016
Malta5021385432561926428
Morocco38 03823 36652 19424 56218 42161404673
Syria21 95717 43433 48215 75611 81739393487
Slovenia247954725731211908303109
Spain49 87311 81452 43324 67518 50661692363
Tunisia12 552532115 1937149536217871064
Turkey88 34339 930109 03251 30938 48212 8277986
Mediter551 667243 053675 512317 888238 41679 47248 611
Table 5 Excess cost of undiagnosed symptomatic celiac patients.
Purchasing power parityStandardized cost for an adult in 6 yr of delay, €Standardized cost for a child in 2 yr of delay, €Total cost for adults in the next 10 yr, €Total cost for children in the next 10 yr, €Total cost of symptomatic in the next 10 yr, €
Albania7.164280482111 698 5751 481 02013 179 595
Algeria6.8692688787107 662 16415 748 296123 410 460
Bosnia7.361288184416 673 6541 176 26517 849 919
Cyprus17.7692820297 468 819741 2468 210 065
Croatia28.5411 171327260 057 8664 613 88664 671 751
Egypt6.1232396702233 320 21444 609 799277 930 013
France33.6813 18138611 037 513 56397 017 2771 134 530 840
Greece29.8811 6953426155 520 66410 627 416166 148 080
Israel28.3911 112325595 985 20215 284 247111 269 450
Italy29.1111 3933337814 080 08652 279 538866 359 625
Lebanon14.235568163126 097 3363 761 03329 858 369
Libya14.335608164340 966 1788 342 75749 308 935
Malta23.58923027044 630 407372 0445 002 450
Morocco4.604180252868 540 19412 332 57580 872 769
Syria4.7183953940 388 1869 393 15649 781 342
Slovenia29.6911 619340328 807 4111 862 76730 670 178
Spain33.713 1893863657 786 97645 639 366703 426 342
Tunisia8.254323094640 548 5415 035 25545 583 796
Turkey12.4848831430431 358 58257 108 945488 467 527
Mediter17.92701220543 879 104 619387 426 8874 266 531 506

Table 6 shows the estimated number of deaths in the celiac disease cohort and the excess of deaths compared to age- and sex-matched controls. At the present rate, there will be more than 250 000 CD-related deaths in the Mediterranean area in 2020.

Table 6 Excess mortality in undiagnosed cases2.
Projected prevalence of CD in the next 10 yrDeath rate, deaths/1000 individualsPopulation expected deaths (next 10 yr)Celiac deaths in next 10 yrExcess celiac deaths in next 10 yr
Albania38 2235.1193 79334881550
Algeria380 3304.61 764 73031 76514 118
Bosnia47 4838.6409 78073763278
Cyprus93726.459 9821080480
Croatia44 68211.8525 01894504200
Egypt999 3114.94 876 63587 77939 013
France676 6278.65 791 930104 25546 335
Greece108 59810.51 141 36320 5459131
Israel83 9435.4455 81182053646
Italy578 53610.76 201 905111 63449 615
Lebanon44 3426267 38248132139
Libya76 5343.4260 98246982088
Malta42008.435 193633282
Morocco383 0984.71 815 88332 68614 527
Syria240 8643.7896 01316 1287168
Slovenia20 0919.2184 83933271479
Spain408 177104 077 69173 39832 622
Tunisia114 4725.2595 25610 7154762
Turkey818 05064 908 30188 34939 266
Mediter5 076 934734 462 486620 325275 700
DISCUSSION

Celiac disease is a very common chronic disease that affects adults and children in all wheat-consuming countries. It has also recently been reported in countries where its prevalence was previously unknown, such as China[27]. For more than two decades, we have been discussing the difference in the prevalence of CD among countries in Europe, North America and South America, and the conclusion is that there is no country where CD prevalence is significantly different from the overall prevalence of about 1%. Interestingly, the prevalence, at a global level, is not related either to the amount of wheat consumed by each country or to the prevalence of the human leukocyte antigen (HLA) DR3-DQ2 and DR4-DQ8 haplotype worldwide[47].

An excess prevalence of CD has been reported in an isolated population in North Africa and in a large population in Sweden, but again it is plausible that this excess prevalence reflects a bias related to the cohort rather than a true excess. The prevalence of CD is increasing worldwide, including in Europe[4], China[27] and India[28]. The only region where it has not yet been described is Central Africa, and this may be explained by the absence in this region of HLA predisposing haplotypes, and of polymorphisms of the major non-HLA genes, namely SH2B3, IL12A, SCHIP, IL18RAP, and IL1RL1, among others[47,48]. Recently, Barada et al[2] from Lebanon produced a comprehensive report of the situation in the countries that face the Mediterranean Sea, thereby increasing the awareness of CD in the area.

The EUROMED program supports several health-promoting activities across the Mediterranean, such as the surveillance of infectious diseases program and the Program for Transplants and Oncology EuroMed (Cancer Registries Network, Cancer screening and early diagnosis program, Mediterranean Transplant Network). Italy has requested that the CD epidemic be included in these programs (http://www.eeas.europa.eu/euromed/index_en.htm). The first step in facing this epidemic is to estimate the burden of CD in the area. Here we provide a reliable and simple picture of the present situation and a prediction of the development of the CD epidemic in the next 10 years, up to 2021.

The prediction obtained by simple straightforward calculations is impressive. Mediterranean countries will have to be prepared to deal with a considerable number of CD patients in the near future. There will be more than 5 million cases, one million of which will be children. But, more than the overall figures, each country will be especially concerned about the national figures. Our estimates are conservative figures, since we estimated a constant population growth over the next ten years, whereas the faster growing countries may have a more rapid growth rate than slower growing countries. Data on symptoms and common clinical problems are available only for symptomatic individuals, while a considerable percentage of so-called “asymptomatic” subjects notoriously report significant complaints a posteriori[49]. A limitation of this study is related to the uncertainties inherent in any prediction given the wide confidence intervals of rates. However, the starting 1% prevalence rate is not only very robust, because of innumerable replications, but it also probably underestimates rather than overestimates the problem[4,28,50]. The rate of symptomatic versus asymptomatic individuals is also fairly conservative.

The financial burden estimate is not aimed to acquire more precision; we provide a gross figure for the spectrum of resources needed in each country for the services required by symptomatic patients. The priority issue is the availability of services; in many African countries, services are mostly only available in large cities and specialized health institutions. In the rural areas, the availability of services can be far less than that required. Hence, the cost of these services should, sadly, be subtracted from the total financial burden. This impending cohort of CD patients does require, and moreover will require, access to health services as inpatients or outpatients, for medical consultations, laboratory tests and, after diagnosis, financial support for a lifelong gluten-free diet. There is universal concern and many countries demand the expertise and support for dissemination of know how and capacity building for the management of CD.

The EuroMed - MEDICEL project (http://www.medicel.unina.it) offers a platform to analyze the problem and develop strategies, but active national plans are required to face the burgeoning epidemic, and the heavy burden that it will place on the health and the finances of the population.

ACKNOWLEDGMENTS

This project was supported by Italian Ministry of Health, Direction of International Affairs, Project MEDICEL.

COMMENTS
Background

The incidence of celiac disease (CD) (i.e., permanent gluten intolerance), is increasing in all countries in which there is awareness of this intolerance. In all Western countries, including the United States and South America, the observed prevalence of the disease went from 1:1000 individuals to more than 1:100 individuals in two decades. However, large series of cases have recently been reported from “new” countries like India, China, North Africa and the Middle East. Celiac disease is expanding over and above any predicted trend, and has taken on the semblance of a real epidemic.

Research frontiers

This expanding “epidemic” raises a series of unanswered research questions related to the following hot topics: (1) the weight of environmental factors in the increase of CD; (2) the genetic profile associated with predisposition to CD; (3) population differences in terms of genetic and environmental factors; and (4) the development of “sensitivity” to gluten.

Innovations and breakthroughs

In next 10 years, the Mediterranean area will have about half a billion inhabitants, 120 million of whom will be children. The projected number of CD cases in 2020 will be 5 million cases (1 million celiac children), with a relative increase of 11% compared to 2010. At a 2010 constant rate, there will be about 550 000 symptomatic adults and 240 000 sick children: 85% of patients will suffer from gastrointestinal complaints, 40% are likely to have anemia, 30% will be afflicted with osteopenia, 20% of children will have short stature and 10% will have abnormal liver enzymes. The estimated standardized medical costs for symptomatic celiac disease during the years of delay between onset of symptoms and diagnosis (mean: 6 years for adults, 2 years for children) will be about €4 billion (€387 million for the children) over the next 10 years. A delay in diagnosis is expected to increase mortality; about 600 000 deaths will occur among individuals affected by CD in the next 10 years, with an excess of 44.4% compared to age- and sex-matched controls.

Applications

The data produced in this study provide a picture of the cohort of patients affected by CD that will develop over the next 10 years in each country of the Mediterranean Basin. Stakeholders and health professionals in each country now have the figures with which it is possible to base adequate plans to face this epidemic. The diagnostic protocol must be simplified and made available not only in specialized centers, usually in large cities, but it should be especially important in rural districts.

Terminology

CD: Celiac disease is a permanent intolerance to gluten based on a genetic predisposition; Projected prevalence: The number of celiac cases that are expected to be present over the next 10 years; Excess mortality: Undiagnosed celiac cases have twice the risk of death compared to age- and sex-matched controls. If the expected cases are not diagnosed, there will be more than 200 000 excess deaths in the Mediterranean area; Growth failure: 20% of children (about 50 000) with undiagnosed CD are affected by weight loss and short stature, due to a growth failure.

Peer review

The paper is well written and deals with an important problem people are continuously facing.

Footnotes

Peer reviewer: Ron Shaoul, MD, Director, Pediatric Gastroenterology and Nutrition Unit, Meyer Children’s Hospital, Rambam Medical Center, PO Box 9602, Haifa 31096, Israel

S- Editor Sun H L- Editor Rutherford A E- Editor Li JY

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