DIAGNOSTIC DELAY IN ADULT CELIAC DISEASE A SINGLE CENTER [631211]

DIAGNOSTIC DELAY IN ADULT CELIAC DISEASE – A SINGLE CENTER
EXPERIENCE
Balaban Daniel Vasile1,2, Popp Alina1,3,4, Jurcuț Ciprian2, Dima Alina1, Jinga Mariana1,2
1 “Carol Davila” University of Medicine and Pharmacy, Bucharest, Romania
2 “Dr. Carol Davila” Ce ntral Military Emergency University Hospital, Bucharest, Romania
3 “Alessandrescu -Rusescu” National Institute for Mother and Child Health, Bucharest,
Romania
4 Tampere Center for Child Health Research, University of Tampere and Tampere
University Hospital, Finland

ABSTRACT
Introduction: Celiac disease (CD) is a common chronic digestive disease worldwide,
yet severely underdiagnosed. Moreover, in patients who finally get diagnosed, lengthy
delays are reported. Our aim was to assess the dia gnostic delay in Romanian adults
with CD.
Methods: Over a period of 5 years we recruited newly-diagnosed adult CD patients and
divided them into three groups , according to their clinical presentation – typical, atypical
or asymptomatic , screen -detect ed CD . Symptomatic p atients were questioned about the
onset of presenting symptoms (which was used to calculate the diagnostic delay) ,
previous medical appointments and the different medical specialties they had seen prior
to diagnosis.
Results: Altogether 34 newly -diagnosed adult CD patients were recruited. Of them , 6
were asymptomatic , screen -detected CD. For the remaining 28 symptomatic CD
patients , mean age 37 years , 75% female , the average diagnostic delay was 34 months
– longer in the atypical than typical forms (49 vs. 11 months ). Almost half (47.05%) of
the patients with atypical CD were referred to gastroenterology from other medical
specialties . Over one third of CD patients included had an earlier diagnosis of irritable
bowel sydrome. Four patients (t wo in each group ) had previous visits to a
gastroenterologist.
Conclusions: Our study showed a significant diagnostic delay in Romanian adults with
CD, of more than 2 years . A high index of suspicion regarding the various clinical
scenario s and targeted testing in high -risk groups is needed in order to minimise th is
diagnostic delay.
KEYWORDS : celiac disease; diagnostic; delay; awarness;

INTRODUCTION
With an estimated prevalence of 1%, celiac disease (CD) is one of the most
common chronic digestive conditions worldwide. Yet, CD is severely underdiagnosed
and in patients who finally get the diagnosis, lengthy delays are reported (1).
Along with an impaired quality of life (1), diagnostic delay exposes patients to
complication s of untr eated CD such as nutritional deficiencies, metabolic bone disease,
fertility disfunction or even malignancy. Unlike other conditions, where diagnostic tools
are not widely available leading to delay s in diagnosis , the diagnostic algorithm in CD
can be read ily performed in any Gastroenterology Department with access to
endoscopy and serology . Therefore, in the setting of a clearly defined diagnostic
approach and access to the necessary resources , other causes should be considered
for the diagnostic delay in CD, patient -related or doctor -related.
Diagnostic delays have been reported in Romanian cohorts for other chronic
digestive diseases such as inflammatory bowel disease (2), but data is missing for
Romanian adult s with CD. Our aim was to assess the diagn ostic delay in a cohort of
patients with newly -diagnosed CD and to detect also the barriers that led to a late
diagnosis.

METHODS
For this cross -sectional study, we included newly -diagnosed adult CD patients
over a period of 5 year s (2013-2017) at our center . CD diagnosis was made according
to 2013 ACG guideline ( 3). Data regarding medical history including previous medical
appointments were collected. Depending on the presentation, patients were divided into
three groups namely typical, atypical or asymptomatic screen -detected CD. P atients
were questioned about the onset of presenting symptoms, either digestive or extra –
digestive, which were used to calculate the diagnostic delay. We also recorded the
different medical specialties’ patients had previou sly seen before the diagnosis.
Statistical analysis was performed using SPSS 17 (SPSS Inc., Chicago, IL) and Epi Info

7.1.5 (CDC, Atlanta, GA). Approval from the local Ethics Committee was obtained for
this study.

RESULTS
Altogether 34 newly diagnosed adult CD patients were recruited for the study.
Among these, 6 were asymptomatic , screen -detected and were excluded for the final
analysis – Figure 1 ; it is to note that 3 out of the 6 were patients with dermatitis
herpetiformis referred to us by the dermat ologist.

Figure 1 Disease phenotype in our study cohort
The remaining 28 patients were the ones clinically symptomatic , with either
typical or atypical features . Mean age in this group was 37 ± 10 years , with 75% female
predominance. Mean diagnostic delay was 34 months, longer in the atypical when
compared to typical forms (49 vs. 11 months , p=0.16 ) – Figure 2 .

Figure 2 Mean diagnostic delay (months) in our study cohort

2/11 ( 18%) of the patien ts with typical CD were first evaluated in an infectious
disease s department, before seeing a gastroenterologist. Of the patients with atypical
CD, almost half ( 47.05%) were referred to gastroenterology from other medical
specialties like internal medicine (3), rheumatology (1), psychiatry (1), gynecology (1),
cardiology (1) or endocrinology (1). Recalling the diagnostic suspicion in these patients,
the clues which triggered testing were represented by unexplained anemia, type 1
diabetes mellitus, autoimmun e thyroid disease , and unexplained infertility. Also, o ver
one third (35.71%) of patients included had an earlier diagnosis of irritable bowel
sydrome (IBS).
Two patients in each group (atypical and typical CD) had been previously seen
by a gastroenterolog ist in the timeframe between the onset of presenting sign/symptom
and the final diagnosis ; moreover, two of them had also underwent upper digestive

endoscopy, without recording of endoscopic markers of villous atrophy and without
biopsy sampling from the d uodenum.

DISCUSSIONS
CD is nowadays well recognized as a clinical chameleon – its clinical
presentation can vary from the typical malabsorption syndrome to unexplained elevated
liver enzymes , depression or fertility problems (4), for which patie nts are reffered to
specialists other than gastroenterologists . These protean clinical presentations, along
with a lack of awareness among medical professionals (5), probably have a major
contribution in the diagnostic delay of CD.
In our study , there was a significant diagnostic delay of 2.8 years (34 months) ,
similar to results of recent studies , but lower than previous reported data – Table 1.
Table 1. Studies reporting diagnostic delay in CD
Study Year Mean diagnostic delay (months)
Croese J. e t al (6) 1979 73
Gregory C et al. ( 7) 1983 122
Favre G et al. ( 8) 2000 37.2
Sanders DS et al. ( 9) 2002 58.8
Norstrom F. et al ( 1) 2011 116.4
Aziz I et al. ( 10) 2012 156
Fuchs V et al ( 11) 2014 > 120 in 32% of participants
Vavricka SR et al. ( 12) 2016 87
Paez MA et al. ( 13) 2017 2.3/42 for gastrointestinal/non -gastrointestinal
symptoms group

One of the pitfalls before the correct diagnosis is that CD patients are frequently
mislabelled with IBS (14) and given symptomatic treatment, sometimes for long p eriods
of time – the case control study by Card TR et al. ( 14) showed that although many

patients were diagnosed as IBS in the last year prior to CD diagnosis, there was an
excess of IBS diagnoses even 10 years before. Others have reported significant doctor-
related diagnostic delays, particularly in wom en, but regardless of previous IBS
diagnosis (12). In our study population, a significant proportion of patients had been
previously diagnosed with IBS, setting a need for a n optimization of CD testing
indications in this large group of IBS patients .
As anticipated, typical presentation led to a earlier diagnosis than atypical forms
in our study cohort ; this is probably due to recognition of CD as a prototype of
malabsorbtion. However, the long diagnostic del ay in atypical CD (over 4 years)
suggests a lack of awarness of physicians regarding non -classic presentation of CD,
and this is of paramount importance as the adult CD is more often atypical (15). A
worrisome result in our study is the missed diagnosis in four patients that had been
previously seen by a gastroenterologist ; although gastroenterologists have the highest
diagnostic rate – 85% compared to 63% internists in the study by Dickey W . et al. ( 16),
our result suggests there is room for improvement in t he knowledge of gastroenterology
practitioners also.
Along with the need for increased awarness regarding the various clinical
manifestations of CD, especially the non -gastrointestinal ones, and the symptomatic
overlap with IBS , another important group tha t needs to be addressed is the at -risk
individuals, such as type 1 diabetes mellitus or autoimmune thyroid disease. The study
by Bakker et al. revealed a latency over 5 years before CD diagnosis in one third of type
1 diabetes mellitus patients who reporte d CD -related complaints (17).
Diagnostic delay is currently a concerning issue in CD epidemiology. Besides the
poor quality of life and poor outcomes, a long diagnostic delay also means a high
burden for health systems and waste of resources, both fina ncial and human.

CONCLUSIONS
There is a significant diagnostic delay in Romanian adult s with CD , of more than
2 years . Both gastroenterologists and physicians of other medical specialties need to

keep a high index of suspicion in order to minimise this diagnostic delay. Actions to
increase awareness of the wide clinical spectrum of this disease, along with improved
testing of high -risk groups, are warranted .

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