Hypoalbuminemia as an Unusual Presentation of Undiagnosed Atypical Celiac Disease in an 84-Year-Old Woman
Article information
Abstract
Celiac disease is a chronic, immune-mediated enteropathy that is precipitated by dietary gluten in genetically predisposed individuals. Gastrointestinal symptoms and signs of malabsorption characterize a classical form of the disease, while patients with nonclassical celiac disease lack significant gastrointestinal symptoms. We report an uncommon case of celiac disease in an 84-year-old oligosymptomatic female with a recently treated colon tumor, diagnosed during the investigation of profound hypoproteinemia and hypoalbuminemia. In this case, two factors could have been misleading about the cause of hypoalbuminemia: malignant tumor and advanced age. Since the oncological disease was in remission, and the albumin concentration in the healthy elderly people in the community usually exceeds 38 g/L until after the age of 90, we pursued an alternative cause, leading to the diagnosis of celiac disease. Even in the absence of intestinal symptoms, advanced age, or other diagnoses, celiac disease should be considered a potential differential diagnosis in every patient presenting with hypoalbuminemia.
INTRODUCTION
Celiac disease is a chronic, immune-mediated enteropathy precipitated by dietary gluten in genetically predisposed individuals.1) Although previously considered a pediatric disease, the number of cases diagnosed in adults has increased nowadays.2) The estimated global prevalence of celiac disease based on serologic studies is approximately 1%, with female predominance.3) Given the vastly variable clinical presentation, it is estimated that for each clinically diagnosed patient with celiac disease, five to ten seropositive individuals remain unrecognized.4) The clinical form of celiac disease can be subclinical (asymptomatic), classical, and nonclassical (extraintestinal). Classical form of the disease is characterized by gastrointestinal symptoms and signs of malabsorption (e.g., diarrhea, weight loss, abdominal discomfort, flatulence, and other signs of nutrient or vitamin deficiency). Patients with nonclassical celiac disease lack significant gastrointestinal symptoms and usually have selected nutrient deficiencies with extraintestinal manifestations (e.g., anemia, osteoporosis, arthritis, increased aminotransferases, neurological symptoms, and several associated autoimmune diseases).5) Considering the present increase in the incidence of nonclassical forms of celiac disease, clinicians should maintain a high level of awareness of its extraintestinal manifestations.6) Here, we report an uncommon case of celiac disease, diagnosed in an 84-year-old oligosymptomatic female during the investigation of profound hypoproteinemia and hypoalbuminemia.
CASE DESCRIPTION
The patient is an 84-year-old Caucasian female with arterial hypertension, osteoporosis, and a transient ischemic attack in her past medical history. She was hospitalized for intermittent pain in the right upper abdomen. Laboratory findings at the time showed microcytic anemia, mildly elevated liver transaminases, and hypoalbuminemia (26 g/L). A multi-slice computed tomography of the abdomen raised suspicion of a transverse colon neoplasm. Given these findings, a colonoscopy was performed, revealing a circular tumor in the aboral part of the transverse colon that was not passable for the endoscope. Values of carcinoembryonic antigen were within the normal range (0.54 µg/L) and radiological assessment did not detect any secondary lesions. A surgical procedure was performed, resulting in the resection of the transverse colon with the formation of a colo-colonic anastomosis. Pathohistological examination of the sampled tissue confirmed the presence of colon adenocarcinoma. The patient was examined by an oncologist who, considering her age, comorbidities, and poor general condition, did not recommend systemic antineoplastic treatment. A follow-up examination revealed no suspicion of neoplastic disease recurrence 1 year later. There were slightly elevated liver transaminases (aspartate aminotransferase of 37 IU/L, alanine aminotransferase of 44 IU/L) and elevated lactate dehydrogenase of 256 IU/L in laboratory results. No potential oncological lesions were found on the abdominal ultrasonography. The following year, at the age of 86, a further follow-up was conducted as the patient continued to experience weakness and fatigue. Laboratory findings at that time showed mildly elevated liver enzymes (aspartate aminotransferase of 43 IU/L, alanine aminotransferase of 53 IU/L), folate deficiency (6.92 nmol/L), hypoproteinemia (63 g/L), and hypoalbuminemia (37 g/L). Given the normal liver function, hypoproteinemia was considered a result of malabsorption, and the serology tests for celiac disease were done. Antibodies against tissue transglutaminase IgA class were significantly elevated (>128 U/mL). An esophagogastroduodenoscopy showed scalloping and flattening of duodenal folds, fissuring over the folds, and a mosaic pattern of the mucosa (Figs. 1, 2). Biopsies of the duodenal mucosa confirmed intraepithelial lymphocytosis with severe villous atrophy and crypt hyperplasia, consistent with Marsh type 3c lesions, confirming celiac disease (Figs. 3, 4). The patient was introduced to a strict gluten-free diet. A diagnostic re-evaluation was performed after five months, showing a drop of antibodies against tissue transglutaminase (21 U/mL), normal liver enzymes (aspartate aminotransferase of 26 IU/L, alanine aminotransferase of 34 IU/L), normal folate levels of 19.48 nmol/L, normal serum protein of 70 g/L, and normal serum albumin of 43 g/L with an improvement of general condition, performance status and disappearance of weakness and fatigue.
Duodenoscopy showing scalloping and flattening of duodenal folds with fissures (arrows).
Duodenoscopy showing a mosaic pattern of the mucosa (arrow).
Photomicrograph of a duodenal biopsy confirming intraepithelial lymphocytosis immunohistochemically (arrow) with positive staining for CD3 monoclonal antibody (immunohistochemistry, 100×).
Photomicrograph of a duodenal biopsy reveals flattened mucosa with marked villous atrophy (left arrow), crypt hyperplasia (right arrow) and increased intraepithelial lymphocytes (H&E stain, 100×).
Written informed consent has been obtained from the patient to publish this paper.
DISCUSSION
The time to establish the diagnosis of celiac disease is often longer than 10 years in symptomatic patients. In contrast, patients with atypical or no symptoms may never be diagnosed.3,7)
Epidemiological research on celiac disease in older populations is limited and yields highly variable findings.8) This variability is likely a consequence of differing diagnostic criteria employed across studies. Celiac disease diagnosis is ultimately comprised of positive serologic tests verified by the characteristic histopathologic findings of an intestinal biopsy.9) In the studies with the above-mentioned inclusion diagnostic criteria, celiac disease was rarely detected in people over 65 years of age, while the rate in people over 80 years of age was significantly lower.8)
However, this case’s specificity, maybe even uniqueness, is not the patient old age but the atypical presentation of the disease. In patients with celiac disease, hypoalbuminemia is the result of increased plasma protein leakage from the affected intestine along with malabsorption occurring due to loss of villi.10) The consequences of malabsorption are diarrhea, steatorrhea, bloating, abdominal cramps, and weight loss. In contrast, in this case, the patient exhibited malabsorption without any accompanying gastrointestinal symptoms, with hypoalbuminemia being the sole manifestation of the disease. This atypical presentation posed significant challenges to the diagnostic process.
Hypoalbuminemia is not a regular laboratory finding in the atypical form of celiac disease, as observed in our case. In this case, two factors could have been misleading about the cause of hypoalbuminemia. In patients with malignant tumors, the serum albumin level could decrease because of malnutrition, systemic inflammatory responses, and increased loss through the bowel.11) It must be emphasized that the overall risk of colorectal cancer in patients with celiac disease is comparable to that of the general population.9,12)
Another potential factor complicating diagnostic treatment is the patient’s age as the aging process is associated with decreased levels of serum albumin.13) Given the remission of the oncological disease, thus eliminating cachexia-induced hypoalbuminemia, and considering that the albumin concentration in healthy elderly people in the community typically exceeds 38 g/L until after the age of 90, we sought another potential cause.14) Suspected celiac disease was verified by serological testing in combination with pathohistological analysis of duodenal mucosa. In several scientific papers, the connection between hypoalbuminemia and increased mortality in the elderly has been confirmed, which further emphasizes the importance of this finding.15) The symptoms improved after establishing a gluten-free diet, and the relevant laboratory findings were normalized.
Despite the absence of intestinal symptoms, advanced age, or other diagnoses, celiac disease should be considered as a differential diagnosis in every patient with hypoalbuminemia. A timely diagnosis of celiac disease and the introduction of a gluten-free diet leads to rapid withdrawal of symptoms, improved quality of life, and prevention of unnecessary diagnostic work-up.
Notes
We thank Gabrijela Stanić, MD, PhD, for the photomicrographs.
CONFLICT OF INTEREST
The researchers claim no conflicts of interest.
FUNDING
None.
AUTHOR CONTRIBUTIONS
Conceptualization, EF; Investigation EF, VM, VAM; Methodology, EF, LK; Supervision, EF, SF, LK; Writing–original draft EF, VM, VAM; Writing–review & editing, EF, SF, MM.