Celiac Disease: Clinical Perspective Dig Dis 2015;33:137–140 DOI: 10.1159/000370204
Clinical Manifestations of Celiac Disease Peter H.R. Green Suneeta Krishnareddy Benjamin Lebwohl
Key Words Clinical presentation · Diarrhea · Anemia · Screening
Abstract Celiac disease (CD) is an immune-based condition affecting multiple organ systems. Clinical manifestations are manifold in form and number due to the multisystem nature of CD. There has been a progressive change in the clinical manifestations over the recent decades with fewer patients, both adults and children, presenting with a diarrheal, classical form. This, in children, is seen in only the youngest, while growth issues, screening at-risk groups and recurrent abdominal pain are the most common modes of presentation among children. Among adults, diarrhea is the most common presentation followed by anemia. Screening at-risk groups, metabolic bone disease and incidental recognition at endoscopy performed for reflux are the other main modes of presentation. The bulk of those with CD remain undiagnosed. The symptoms are often common, and increased medical education should lead to greater awareness in the medical community and an increased rate of diagnosis. © 2015 S. Karger AG, Basel
Introduction
The clinical manifestations of celiac disease (CD) are many [1]. Although CD was first characterized as a pediatric diarrheal illness with a prominent malabsorption syndrome, it is now considered a disease of any age with adults predominating. There is a vast array of symptoms originating in any organ system (table 1). As well as shift© 2015 S. Karger AG, Basel 0257–2753/15/0332–0137$39.50/0 E-Mail [email protected] www.karger.com/ddi
ing to adults, there has been a shift in the mode of clinical presentation. Recently, there have been attempts to define the nomenclature of the types or clinical presentations of CD [2]. The major classifications are classical and nonclassical CD. Regarding classical CD, these patients present with diarrhea, malabsorption, or a malnutrition syndrome. As for nonclassical CD, these patients do not have signs or symptoms of malabsorption or diarrhea. This group includes: asymptomatic CD – this category refers to patients who have no symptoms on presentation; subclinical CD – patients in this category have symptoms that fall below the threshold of clinical detection that would warrant testing for CD in routine clinical practice; potential CD – this category refers to patients with positive CD-related serologies but normal small intestinal biopsy; a subset of these patients may develop CD in the future. Some of these patients may have a temporary celiac or gluten autoimmunity, which is seen in both adults and children, though this is most well documented in the latter [3, 4]. We are not aware why some patients present with diarrhea and others do not. The classical presentation does not correlate with the degree of villous atrophy [5], or length of bowel involvement as assessed by video capsule imaging [6]. Neurohormonal mechanisms may be an important cause of symptoms as abnormalities in serotonin metabolism have been described in some patients [7]. While in the United States analysis of the NHANES data revealed that the prevalence of CD was 0.71% (95% CI 0.58–0.86%), the majority, 83%, were not diagnosed [8]. Among those diagnosed, women predominate (2:1), and the peak age at diagnosis is between 30 and 60 years of age [9]. Peter H.R. Green, MD The Celiac Disease Center at Columbia University 180 Fort Washington Avenue, Suite 936 New York, NY 10032 (USA) E-Mail Pg11 @ columbia.edu
Downloaded by: NYU Medical Center Library 128.122.253.228 - 5/13/2015 10:03:49 PM
The Celiac Disease Center at Columbia University, New York, N.Y., USA
Table 1. Clinical manifestations of CD
Symptoms directly related to CD
Constitutional
Fatigue Weight loss
Cardiovascular
Gastrointestinal
Hematologic
Respiratory Endocrine
Diarrhea Abdominal pain Bloating Dyspepsia Reflux Iron deficiency Folate deficiency Copper deficiency Dyspnea due to anemia
Musculoskeletal Neurologic
Osteoporosis Infertility Myalgias, arthralgias ‘Brain fog’
Cutaneous
Dermatitis herpetiformis
There has been a progressive decrease in the percentage of patients presenting with a diarrheal syndrome. This trend is attributed to a changing nature of CD, greater knowledge of the nonclassical manifestations among physicians and the advent of serological testing [10, 11]. Among adults seen in our Celiac Disease Center at Columbia University in New York, the major mode of presentation was diarrhea; however, it occurred in only 36% of patients. Other presentations included: anemia (13%); screening high-risk groups (8%), namely those with a family history, associated autoimmune diseases or Down syndrome; metabolic bone disease (5%), or incidental at endoscopy performed typically for esophageal reflux disease (4%). Twenty percent were classified as ‘other’ modes of presentation. This group included those with dermatitis herpetiformis (DH), abnormal liver function tests, low ferritin without anemia, abdominal pain, low cholesterol as well as a variety of mineral or vitamin deficiencies (fig. 1). Patients with DH have a similar degree of deficiencies irrespective of whether they present predominantly with DH or predominantly CD and coexistent DH as a minor concern [12]. 138
Dig Dis 2015;33:137–140 DOI: 10.1159/000370204
Symptoms due to conditions associated with CD
Dyspnea/edema (cardiomyopathy) Angina (ischemic heart disease) Palpitations (atrial fibrillation) Dysphagia/reflux (eosinophilic esophagitis) Bloating (small intestinal bacterial overgrowth) Diarrhea (pancreatic insufficiency)
Thrombocytopenia (idiopathic thrombocytopenia purpura) Pneumonia, influenza, tuberculosis Pulmonary hemosiderosis Fatigue, cold intolerance (hypothyroidism) Arthritis (rheumatoid arthritis) Gluten ataxia Migraine Peripheral neuropathy Psoriasis Urticaria Acne
Among the pediatric population seen at our Center, recurrent abdominal pain, growth issues (short stature and failure to thrive) and screening were the most common modes of presentation, each accounting for about 25%. Diarrheal presentations only accounted for 12 years of age, and growth issues occurred in all age groups [14]. Overweight and obese adults and children may present with CD [13, 15]. Among adults seen in our center, 17.3% were underweight, 60.7% normal, 15.2% overweight, and 6.8% obese. Factors associated with low BMI were female sex, Marsh IIIb/c histology, and presentation with diarrhea. On a gluten-free diet, those who were underweight gained weight, whereas 54% of overweight and 47% of obese patients lost weight; this was associated with being followed by our dietitian [15]. Similarly, overweight children lost weight on the diet [13]. Anemia was the second most frequent presentation in our series and the most common hematologic manifestation of CD [16]. The anemia in CD is multifactorial in Green/Krishnareddy/Lebwohl
Downloaded by: NYU Medical Center Library 128.122.253.228 - 5/13/2015 10:03:49 PM
System
Anemia (13%)
Bone disease (5%)
Screening (8%)
Incidental at EGD (4%)
Fig. 1. Presentation of CD in adults (n = 1,499), Columbia Univer-
sity Medical Center. EGD = Esophagogastroduodenoscopy.
etiology with both iron deficiency and anemia of chronic disease predominating [17]. While patients may have folate or vitamin B12 deficiency, macrocytic anemia is uncommon. There is no scoring system or disease activity index for CD like there is for Crohn’s disease. However, our recent study of patients who presented with diarrhea compared to those who presented with anemia suggested that those with anemia had more severe disease. The anemia group had higher ESR, serum tissue transglutaminase levels, more severe degrees of villous atrophy and worse bone disease [18]. At presentation, patients with CD typically have low total cholesterol and HDL levels that improve after treatment with a gluten-free diet [19]. We have utilized the patients’ HDL levels to predict the presence of CD among those with iron deficiency anemia. We found that screening for CD should at least be done for iron deficiency anemia patients who present with HDL levels
Clinical Manifestations of Celiac Disease Peter H.R. Green Suneeta Krishnareddy Benjamin Lebwohl
Key Words Clinical presentation · Diarrhea · Anemia · Screening
Abstract Celiac disease (CD) is an immune-based condition affecting multiple organ systems. Clinical manifestations are manifold in form and number due to the multisystem nature of CD. There has been a progressive change in the clinical manifestations over the recent decades with fewer patients, both adults and children, presenting with a diarrheal, classical form. This, in children, is seen in only the youngest, while growth issues, screening at-risk groups and recurrent abdominal pain are the most common modes of presentation among children. Among adults, diarrhea is the most common presentation followed by anemia. Screening at-risk groups, metabolic bone disease and incidental recognition at endoscopy performed for reflux are the other main modes of presentation. The bulk of those with CD remain undiagnosed. The symptoms are often common, and increased medical education should lead to greater awareness in the medical community and an increased rate of diagnosis. © 2015 S. Karger AG, Basel
Introduction
The clinical manifestations of celiac disease (CD) are many [1]. Although CD was first characterized as a pediatric diarrheal illness with a prominent malabsorption syndrome, it is now considered a disease of any age with adults predominating. There is a vast array of symptoms originating in any organ system (table 1). As well as shift© 2015 S. Karger AG, Basel 0257–2753/15/0332–0137$39.50/0 E-Mail [email protected] www.karger.com/ddi
ing to adults, there has been a shift in the mode of clinical presentation. Recently, there have been attempts to define the nomenclature of the types or clinical presentations of CD [2]. The major classifications are classical and nonclassical CD. Regarding classical CD, these patients present with diarrhea, malabsorption, or a malnutrition syndrome. As for nonclassical CD, these patients do not have signs or symptoms of malabsorption or diarrhea. This group includes: asymptomatic CD – this category refers to patients who have no symptoms on presentation; subclinical CD – patients in this category have symptoms that fall below the threshold of clinical detection that would warrant testing for CD in routine clinical practice; potential CD – this category refers to patients with positive CD-related serologies but normal small intestinal biopsy; a subset of these patients may develop CD in the future. Some of these patients may have a temporary celiac or gluten autoimmunity, which is seen in both adults and children, though this is most well documented in the latter [3, 4]. We are not aware why some patients present with diarrhea and others do not. The classical presentation does not correlate with the degree of villous atrophy [5], or length of bowel involvement as assessed by video capsule imaging [6]. Neurohormonal mechanisms may be an important cause of symptoms as abnormalities in serotonin metabolism have been described in some patients [7]. While in the United States analysis of the NHANES data revealed that the prevalence of CD was 0.71% (95% CI 0.58–0.86%), the majority, 83%, were not diagnosed [8]. Among those diagnosed, women predominate (2:1), and the peak age at diagnosis is between 30 and 60 years of age [9]. Peter H.R. Green, MD The Celiac Disease Center at Columbia University 180 Fort Washington Avenue, Suite 936 New York, NY 10032 (USA) E-Mail Pg11 @ columbia.edu
Downloaded by: NYU Medical Center Library 128.122.253.228 - 5/13/2015 10:03:49 PM
The Celiac Disease Center at Columbia University, New York, N.Y., USA
Table 1. Clinical manifestations of CD
Symptoms directly related to CD
Constitutional
Fatigue Weight loss
Cardiovascular
Gastrointestinal
Hematologic
Respiratory Endocrine
Diarrhea Abdominal pain Bloating Dyspepsia Reflux Iron deficiency Folate deficiency Copper deficiency Dyspnea due to anemia
Musculoskeletal Neurologic
Osteoporosis Infertility Myalgias, arthralgias ‘Brain fog’
Cutaneous
Dermatitis herpetiformis
There has been a progressive decrease in the percentage of patients presenting with a diarrheal syndrome. This trend is attributed to a changing nature of CD, greater knowledge of the nonclassical manifestations among physicians and the advent of serological testing [10, 11]. Among adults seen in our Celiac Disease Center at Columbia University in New York, the major mode of presentation was diarrhea; however, it occurred in only 36% of patients. Other presentations included: anemia (13%); screening high-risk groups (8%), namely those with a family history, associated autoimmune diseases or Down syndrome; metabolic bone disease (5%), or incidental at endoscopy performed typically for esophageal reflux disease (4%). Twenty percent were classified as ‘other’ modes of presentation. This group included those with dermatitis herpetiformis (DH), abnormal liver function tests, low ferritin without anemia, abdominal pain, low cholesterol as well as a variety of mineral or vitamin deficiencies (fig. 1). Patients with DH have a similar degree of deficiencies irrespective of whether they present predominantly with DH or predominantly CD and coexistent DH as a minor concern [12]. 138
Dig Dis 2015;33:137–140 DOI: 10.1159/000370204
Symptoms due to conditions associated with CD
Dyspnea/edema (cardiomyopathy) Angina (ischemic heart disease) Palpitations (atrial fibrillation) Dysphagia/reflux (eosinophilic esophagitis) Bloating (small intestinal bacterial overgrowth) Diarrhea (pancreatic insufficiency)
Thrombocytopenia (idiopathic thrombocytopenia purpura) Pneumonia, influenza, tuberculosis Pulmonary hemosiderosis Fatigue, cold intolerance (hypothyroidism) Arthritis (rheumatoid arthritis) Gluten ataxia Migraine Peripheral neuropathy Psoriasis Urticaria Acne
Among the pediatric population seen at our Center, recurrent abdominal pain, growth issues (short stature and failure to thrive) and screening were the most common modes of presentation, each accounting for about 25%. Diarrheal presentations only accounted for 12 years of age, and growth issues occurred in all age groups [14]. Overweight and obese adults and children may present with CD [13, 15]. Among adults seen in our center, 17.3% were underweight, 60.7% normal, 15.2% overweight, and 6.8% obese. Factors associated with low BMI were female sex, Marsh IIIb/c histology, and presentation with diarrhea. On a gluten-free diet, those who were underweight gained weight, whereas 54% of overweight and 47% of obese patients lost weight; this was associated with being followed by our dietitian [15]. Similarly, overweight children lost weight on the diet [13]. Anemia was the second most frequent presentation in our series and the most common hematologic manifestation of CD [16]. The anemia in CD is multifactorial in Green/Krishnareddy/Lebwohl
Downloaded by: NYU Medical Center Library 128.122.253.228 - 5/13/2015 10:03:49 PM
System
Anemia (13%)
Bone disease (5%)
Screening (8%)
Incidental at EGD (4%)
Fig. 1. Presentation of CD in adults (n = 1,499), Columbia Univer-
sity Medical Center. EGD = Esophagogastroduodenoscopy.
etiology with both iron deficiency and anemia of chronic disease predominating [17]. While patients may have folate or vitamin B12 deficiency, macrocytic anemia is uncommon. There is no scoring system or disease activity index for CD like there is for Crohn’s disease. However, our recent study of patients who presented with diarrhea compared to those who presented with anemia suggested that those with anemia had more severe disease. The anemia group had higher ESR, serum tissue transglutaminase levels, more severe degrees of villous atrophy and worse bone disease [18]. At presentation, patients with CD typically have low total cholesterol and HDL levels that improve after treatment with a gluten-free diet [19]. We have utilized the patients’ HDL levels to predict the presence of CD among those with iron deficiency anemia. We found that screening for CD should at least be done for iron deficiency anemia patients who present with HDL levels
