ArticlePDF Available

The World Incidence and Prevalence of Autoimmune Diseases is Increasing

December 2015
International Journal of Celiac Disease 3(4):151-155

DOI:10.12691/ijcd-3-4-8

Authors:

Aaron Lerner

. Chaim Sheba Medical Center, the Zabludowicz Center for Autoimmune Diseases, Tel-Hashomer, Israel

Wusterhausen Patricia

Torsten Matthias

Epidemiological data provide evidence of a steady rise in autoimmune disease throughout Westernized societies over the last decades. Multiple publications exist, describing past or actual incidences/prevalence of individual autoimmune diseases, however, long term studies on selected populations are scarce. Aims: to calculate the % increases per year of autoimmune diseases frequencies worldwide, analyze the differential increases per country and disease, and identify geoepidemiological trends. Methods: A systematic review was performed to identify incidence and prevalence of autoimmune diseases. 30 Studies from the last 30 years were identified using Medline, Google, and Cochrane Library databases. Only long-term regional or national follow-ups are reported. Results: The means ± s.d. of the net % increased /year incidence and prevalence of autoimmune diseases worldwide were 19.1±43.1 and 12.5±7.9, respectively. Rheumatic, endocrinological, gastrointestinal and neurological autoimmune diseases revealed the following annual % increases per year: 7.1, 6.3, 6.2, and 3.7, respectively. In all of these, differences between old vs new frequencies were highly significant (p < 0.0001). Comparing various autoimmune diseases, celiac disease increased the most and the highest increase in incidence, comparing old to new surveys is allocated to myasthenia gravis. Despite considerable variations between the countries, celiac, type 1 diabetes and myasthenia gravis frequencies increased the most in Canada, Israel and Denmark, respectively. Frequencies of the autoimmune diseases increased significantly in the West and North when compared to East and South, respectively. Conclusions: Despite multiple reports on autoimmune diseases frequencies, long-term longitudinal follow-ups are scarce. Incidences and prevalences have increased significantly over the last 30 years. Rheumatic, endocrinological and gastrointestinal autoimmune diseases in Israel, Netherlands, USA and Sweden increased the most. These observations point to a stronger influence of environmental factors as opposed to genetic factors on autoimmune disease development.

The net % increase/year of the incidence and prevalence of autoimmune diseases worldwide

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(A) The net %/year increases of diseases' categories. (B) The table below is detailing the different diseases and countries surveyed The net increase/year of various diseases in specific countries and old vs. new surveys of incidence/prevalence of various autoimmune diseases, are shown in Figure 3A and 3B, respectively. Figure 3A shows the total net increase of Old vs. New surveys of incidence/prevalence of various autoimmune diseases, (mean time interval RA 14.5, AT 13.5, Chron`s 11.5, IBD 11.0, IDDM 17.8, Celiac 16.8 and MG 27 years, respectively), During the reported time interval. CD increased the most (26.3/year %) and the higher increase in incidence, comparing old to new surveys is allocated to MG (432%)

…

The geoepidemiology of the net increase %/year of autoimmune diseases

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International Journal of Celiac Disease, 2015, Vol. 3, No. 4, 151-155

Available online at http://pubs.sciepub.com/ijcd/3/4/8

DOI:10.12691/ijcd-3-4-8

The World Incidence and Prevalence of Autoimmune

Diseases is Increasing

Aaron Lerner1,*, Patricia Jeremias2, Torsten Matthias2

1B. Rappaport School of Medicine, Technion-Israel Institute of Technology, Haifa, Israel

2AESKU.KIPP Institute, Wendelsheim, Germany

*Corresponding author: aaronlerner1948@gmail.com

Received September 27, 2015; Revised October 29, 2015; Accepted November 11, 2015

Abstract Epidemiological data provide evidence of a steady rise in autoimmune disease throughout Westernized

societies over the last decades. Multiple publications exist, describing past or actual incidences/prevalence of

individual autoimmune diseases, however, long term studies on selected populations are scarce. Aims: to calculate

the % increases per year of autoimmune diseases frequencies worldwide, analyze the differential increases per

country and disease, and identify geoepidemiological trends. Methods: A systematic review was performed to

identify incidence and prevalence of autoimmune diseases. 30 Studies from the last 30 years were identified using

Medline, Google, and Cochrane Library databases. Only long-term regional or national follow-ups are reported.

Results: The means ± s.d. of the net % increased /year incidence and prevalence of autoimmune diseases worldwide

were 19.1±43.1 and 12.5±7.9, respectively. Rheumatic, endocrinological, gastrointestinal and neurological

autoimmune diseases revealed the following annual % increases per year: 7.1, 6.3, 6.2, and 3.7, respectively. In all of

these, differences between old vs new frequencies were highly significant (p< 0.0001). Comparing various

autoimmune diseases, celiac disease increased the most and the highest increase in incidence, comparing old to new

surveys is allocated to myasthenia gravis. Despite considerable variations between the countries, celiac, type 1

diabetes and myasthenia gravis frequencies increased the most in Canada, Israel and Denmark, respectively.

Frequencies of the autoimmune diseases increased significantly in the West and North when compared to East and

South, respectively. Conclusions: Despite multiple reports on autoimmune diseases frequencies, long-term

longitudinal follow-ups are scarce. Incidences and prevalences have increased significantly over the last 30 years.

Rheumatic, endocrinological and gastrointestinal autoimmune diseases in Israel, Netherlands, USA and Sweden

increased the most. These observations point to a stronger influence of environmental factors as opposed to genetic

factors on autoimmune disease development.

Keywords: autoimmune disease, incidence, prevalence, surge, geoepidemiology

Cite This Article: Aaron Lerner, Patricia Jeremias, and Torsten Matthias, “The World Incidence and

Prevalence of Autoimmune Diseases is Increasing.” International Journal of Celiac Disease, vol. 3, no. 4 (2015):

151-155. doi: 10.12691/ijcd-3-4-8.

1. Introduction

Increasing evidence is accumulating for a steady rise in

the frequency of autoimmune diseases (AD), in the last

decades [1]. In fact, the rise in ADs parallels the surge in

allergic and cancer conditions while infections are less

frequent in the Western societies, creating the basis for the

hygiene hypothesis [2]. Multiple sclerosis (MS), type 1

diabetes (IDDM), inflammatory bowel diseases (mainly

Crohn’s disease) (IBD), systemic lupus erythematosus

(SLE), primary biliary cirrhosis, myasthenia gravis (MS),

autoimmune thyroiditis (AT), hepatitis and rheumatic

diseases (RA), bullous pemphigoid, and celiac disease

(CD) are several examples [3,4]. Their relationship to

socioeconomic status, their rapid increase in developed

countries and observations in selected migrant populations,

indicate some form of environmental impact, rather than

long-term genetic influences which are driving these

recent evolutionary processes [1,2,3,4,5]. Among many

others, three major environmental factors, strongly related

to socioeconomical status are suspected to drive these

phenomena: infections, ecology and nutrition. The

purpose of the present review is to calculate the surge per

year of AD frequencies worldwide and analyze the

differential increases of AD per country and disease

identifying geoepidemiological trends. There is a plethora

of publications on the incidences/prevalences of ADs in

medical literature, most of them describe past or actual

frequencies of individual ADs, however, long term

comparative follow-up studies on selected populations, in

individual countries are scarce.

2. Methods

A Medline search was performed using the following

search words: autoimmune disease or syndrome, incidence,

prevalence or frequency, spanning the period 1985-2015.

152 International Journal of Celiac Disease

Special emphasis was given to the identification of

increase/surge or decrease in incidence/prevalence

worldwide. Suitable publications were identified by

periodical scans of PubMed but also Google, and the

Cochrane Library databases, were screened. Original

papers, in the English language, especially those on

epidemiology of autoimmune diseases commonly

encountered, were identified. Foreign language papers

with English abstracts were also identified. Only long-

term regional or national longitudinal follow-ups are

reported. Hospital archived data, specific high-risk groups

or case reports, were excluded. Entities were validated and

used when directly stating at least one of the

abovementioned epidemiological indices. Chi-square test

or Fisher`s exact test were used for categorical data and p-

values less than 0.05 were considered as statistically

significant. Statistical analyses were performed using the

statistics software MedCalc version 15.6.1.

3. Results

30 studies were identified. The means ± s.d. of the

net % increased /year incidence and prevalence of ADs

worldwide were 19.1±43.1 and 12.5±7.9, respectively

(Figure 1). Of interest, grouping the different ADs to

disease categories, the highest net % increase per year was

noted in the rheumatologic (7.1), followed by endocrine

(6.3), gastrointestinal (6.2) and neurological diseases (3.7).

In all of these, differences between old vs new frequencies

were highly significant (p< 0.0001) (Figure 2). The table

inserted in Figure 2 details the diseases and the countries

included in the 4 disease categories.

Figure 1. The net % increase/year of the incidence and prevalence of

autoimmune diseases worldwide

Figure 2. (A) The net %/year increases of diseases’ categories. (B) The table below is detailing the different diseases and countries surveyed

The net increase/year of various diseases in specific

countries and old vs. new surveys of incidence/prevalence

of various autoimmune diseases, are shown in Figure 3A

and 3B, respectively. Figure 3A shows the total net

increase of Old vs. New surveys of incidence/prevalence

of various autoimmune diseases, (mean time interval RA

14.5, AT 13.5, Chron`s 11.5, IBD 11.0, IDDM 17.8,

Celiac 16.8 and MG 27 years, respectively), During the

reported time interval. CD increased the most

(26.3/year %) and the higher increase in incidence,

comparing old to new surveys is allocated to MG (432%)

(Figure 3A and Figure 3B). Geoepidemiologically, the

following countries had high to low % increases /year of

AD frequencies: Israel, Netherlands, USA, Sweden, UK,

Finland, Canada, and Denmark with 12.9, 10.0, 8.8, 8.4,

7.8, 7.6, 7.3 and 6.3 %, respectively. There was no

statistically significant difference between children and

adults in the increase of AD incidence/ prevalence

(p=0.8036). Figure 4 shows, as an example, two frequent

ADs like CD and IDDM and one, less frequent one like

MG surveys in various countries. A considerable variation

is noticed between the countries. CD, IDDM and MG

International Journal of Celiac Disease 153

frequencies increased the most in Canada, Israel and Denmark, respectively.

Figure 3. (A) Old vs. New surveys of incidence/prevalence of various autoimmune diseases. (B) The list of various diseases in specific countries and

the years’ ranges

Figure 4. The net increase %/year of 3 autoimmune diseases in the surveyed countries

154 International Journal of Celiac Disease

The geoepidemiologic trend of the net increase %/year

of the various ADs is described in Figure 5. Frequencies of the ADs increased significantly in the West and North

when compared to East and South, respectively.

Figure 5. The geoepidemiology of the net increase %/year of autoimmune diseases

4. Discussion

Population-based estimates of the incidence/prevalence

of ADs in different countries are crucial for investigating

possible etiologies or influencing environmental factors or

underlining risk factors.

Quantification of the likely healthcare burden and the

planning of future strategies to face the ongoing epidemic

of ADs is of no less importance. More so, the beneficial

aspects of early recognition of ADs are well known.

Multiple AD related complications can be prevented or

treated when the disease is diagnosed early enough. The

increased awareness responsible for the surge in

diagnosed patients, needs to continue together with a

lower threshold for screening high risk populations using

a cheap, non-invasive and reliable antibody biomarker to

prevent delays in diagnosing such a common but

preventable disease [6,7,8].

The net increased incidences/prevalences of ADs in the

Northern and Western countries, compared to the Southern

and Eastern ones follows the global geoepidemiological

trends of autoimmune diseases [9,10]. By reviewing

available literature, it can be deduced that frequency of

ADs have increased significantly over the last 30 years.

The recent outbreak of autoimmune diseases in

industrialized countries has brought into question the

factors contributing to this increased incidence. Given the

constancy of genetics, growing attention has focused on

environmental factors, and in particular, the western

lifestyle [3,4,11]. Indeed, over the last few decades

significant changes in western dietary habits,

environmental surroundings and pollution exposure,

infectious habitat and stress load, have led to a parallel

rise in autoimmune diseases. Thus, ADs occupies an

important place in this environmental mosaic of

autoimmunity, allergy and cancer surges [2].

The present study can serve as a platform for

geoepidemiological inquiries, concerning offending/

defending environmental changes. If CD is taken as an

example, how comes the surge in the disease frequency

was much higher in Canada, Israel and Netherlands,

compared to the low rates in Estonia and New Zealand?

Considering the diseases, what environmental forces

contributed to the higher surge of CD and MG, compared

to IBD and IDDM? Comparing the disease categories,

why are rheumatic disease surges higher than the

neurological ones? Is it the infectious or stress loads? The

intestinal disbiosis allocated to specific diseases? Driving

openers of the intestinal tight-junctions? Or is it the

increased public/professional awareness or the improved

diagnosis? A vast list of questions and so few answers.

The present study has multiple biases and drawbacks.

The follow up surveys were not done by the same team

nor by the same methodology, some of the relevant

studies might have escaped detection, the genetic makeup

and the environment are different in the screened countries,

the environmental forces are dynamic and most probably

changed during the last decades, the actual public and

professional awareness to autoimmunity and the

diagnostic bio-markers have evolved tremendously.

Despite those biases, the present study highlights the

significant surge in AD incidence and prevalence, detailing

the variations in disease entities and the corresponding

countries and substantiate the geoepidemiological trends.

The present literature survey is not aiming to investigate

etiologies or environmental factors affecting autoimmune

induction or progression. It is expected that an improved

knowledge of the worldwide distribution of autoimmune

disorders will help to understand the role of different

genetic factors and different environmental influences

involved in autoimmunogenesis. At a public level the

epidemiological studies are necessary to assess the social

and economic burdens impacting the health systems in the

different countries, and worldwide.

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Aliment Pharmacol Ther. 2007;26:1217-1225.

[2] Bach JF. The effect of infections on susceptibility to autoimmune

and allergic diseases. N Engl J Med 2002; 347: 911-920.

[3] Lerner A, Matthias T. Changes in intestinal tight junction

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rising incidence of autoimmune disease. Autoimmun Rev.

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[4] Lerner A, Matthias T. Possible association between celiac disease

and bacterial transglutaminase in food processing: a hypothesis.

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[5] Lerner A. The last two millennias eco-catastrophes are the driving

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[6] Ludvigsson JF, Rubio-Tapia A, van Dyke CT, et al. Increasing

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[7] Lerner A, Matthias T. Increased knowledge and awareness of

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Mar 2013
AM J GASTROENTEROL

Objectives: The prevalence of celiac disease (CD) varies greatly, potentially because of incomplete ascertainment of cases and small study samples with limited statistical power. Previous reports indicate that the incidence of CD is increasing. We examined the prevalence of CD in a well-defined US county. Methods: Population-based study in Olmsted County, Minnesota, USA. Using the infrastructure of the Rochester Epidemiology Project, medical, histopathology, and CD serology records were used to identify all new cases of CD in Olmsted County since 2000. Age- and sex-specific and adjusted (to the US white 2000 population) incidence rates for CD were estimated. Clinical presentation at diagnosis was also assessed. Results: Between 2000 and 2010, 249 individuals (157 female or 63%, median age 37.9 years) were diagnosed with CD in Olmsted County. The overall age- and sex-adjusted incidence of CD in the study period was 17.4 (95% confidence interval (CI)=15.2-19.6) per 100,000 person-years, increasing from 11.1 (95% CI=6.8-15.5) in 2000-2001 to 17.3 (95% CI=13.3-21.3) in 2008-2010. The temporal trend in incidence rates was modeled as a two-slope pattern, with the incidence leveling off after 2004. Based on the two classic CD symptoms of diarrhea and weight loss, the relative frequency of classical CD among incident cases decreased over time between 2000 and 2010 (P=0.044). Conclusions: The incidence of CD has continued to increase in the past decade in a North-American population.

Explosion of autoimmune diseases and the mosaic of old and novel factors

Article

Full-text available

Feb 2011
CELL MOL IMMUNOL

In recent decades, an enormous effort has been made to elucidate the pathogenesis of autoimmune and autoinflammatory diseases. Autoimmunity is a multifactorial process in which genetic, immunological, environmental and hormonal factors play in concert, together representing what was termed years ago the 'mosaic of autoimmunity'. To date, more than 80 systemic and organ-specific autoimmune diseases have been defined, and their cumulative burden is substantial, both medically and financially. Furthermore, the burden of autoimmune and autoinflammatory diseases is rising, making these diseases a ubiquitous global phenomenon that is predicted to further increase in the coming decades. In this issue of the journal, additional aspects of autoimmunity are detailed. Immune dysregulation and loss of self-tolerance are the cornerstones of autoimmunity.

Possible association between celiac disease and bacterial transglutaminase in food processing: a hypothesis

Article

Jan 2015

Google-driven search for big data in autoimmune geoepidemiology: Analysis of 394,827 patients with systemic autoimmune diseases

Article

Apr 2015

Systemic autoimmune diseases (SAD) are a significant cause of morbidity and mortality worldwide, although their epidemiological profile varies significantly country by country. We explored the potential of the Google search engine to collect and merge large series (>1,000 patients) of SAD reported in the Pubmed library, with the aim of obtaining a high-definition geoepidemiological picture of each disease. We collected data from 394,827 patients with SAD. Analysis showed a predominance of medical vs. administrative databases (74% vs. 26%), public health system vs. health insurance resources (88% vs. 12%) and patient-based vs. population-based designs (82% vs. 18%). The most unbalanced gender ratio was found in primary Sjögren syndrome (pSS), with nearly 10 females affected per 1 male, followed by systemic lupus erythematosus (SLE), systemic sclerosis (SSc) and antiphospholipid syndrome (APS) (ratio of nearly 5:1). Each disease predominantly affects a specific age group: children (Kawasaki disease, primary immunodefficiencies and Schonlein-Henoch disease), young people (SLE Behçet disease and sarcoidosis), middle-aged people (SSc, vasculitis and pSS) and the elderly (amyloidosis, polymyalgia rheumatica, and giant cell arteritis). We found significant differences in the geographical distribution of studies for each disease, and a higher frequency of the three SAD with available data (SLE, inflammatory myopathies and Kawasaki disease) in African-American patients. Using a "big data" approach enabled hitherto unseen connections in SAD to emerge. Copyright © 2015 Elsevier B.V. All rights reserved.

Role of “Western Diet” in Inflammatory Autoimmune Diseases

Article

Dec 2014
CURR ALLERGY ASTHM R

Developed societies, although having successfully reduced the burden of infectious disease, constitute an environment where metabolic, cardiovascular, and autoimmune diseases thrive. Living in westernized countries has not fundamentally changed the genetic basis on which these diseases emerge, but has strong impact on lifestyle and pathogen exposure. In particular, nutritional patterns collectively termed the "Western diet", including high-fat and cholesterol, high-protein, high-sugar, and excess salt intake, as well as frequent consumption of processed and 'fast foods', promote obesity, metabolic syndrome, and cardiovascular disease. These factors have also gained high interest as possible promoters of autoimmune diseases. Underlying metabolic and immunologic mechanisms are currently being intensively explored. This review discusses the current knowledge relative to the association of "Western diet" with autoimmunity, and highlights the role of T cells as central players linking dietary influences to autoimmune pathology.

The last two millennias echo-catastrophes are the driving forces for the potential genetic advantage mechanisms in celiac disease

Article

Aug 2011

Aaron Lerner

Many human genes have adapted to the constant threat of exposure to changing environmental conditions. Balancing selection is the result of an initial stage of positive selection that favors the spread in a population of a new allele until selection opposes its fixation and balanced situation is established. It is suggested that the disadvantageous celiac patients survived the last two millennias echo-catastrophes by adapting to the extreme temperature changes and their consequences in Europe. Genetic selective diversity induced by changing environment, enabled the celiac population to survive. Such a genetic positive selection is represented by the HEF C282Y mutation of hemochromatosis, SH2B3 loci and the HLA celiac disease-associated repertoire, enabling the celiac to overcome iron deficiency anemia and micro pathogen richness, respectively. The increased incidence of those evolutionary events in the celiac patients is a recent phenomenon that occurred in the latest era of the modern human history. The present hypothesis can shed light on additional selective genetic adaptations, echo catastrophe-driven that are at the basis of autoimmune disease-affected population survival and current expansion.