Mrs. J.P. is a 50-year-old woman with a long-standing history of reflux disease, emphysema, chronic iron deficiency anemia and hypothyroidism. She was referred for ongoing symptoms of fatigue, mild hepatic dysfunction and ongoing leg swelling.
She’s been experiencing symptoms of intermittent epigastric pain and tiredness over the past few years. These symptoms were already investigated once in the past. She underwent gastroscopies and colonoscopies, and was diagnosed with reflux disease. She also had various abdominal ultrasounds and CT scans of the abdomen over the years and all were unremarkable save for fatty liver. There was no history of jaundice or hepatitis but she recalled receiving a a blood transfusion in 1995. She’s also had ongoing ankle swelling for the past few years.
She denies symptoms of heartburn, reflux, nausea or vomiting. She has occasional diarrhea but no bleeding per rectum or melena. She denies symptoms of abdominal cramps or tenesmus. Her appetite has been fair and there’s been no weight loss. She reports no fever, chills or night sweats. She denies history of kidney disease or heart disease, and has no symptoms of chest pain, shortness of breath, orthopnea or paroxysmal nocturnal dyspnea. She’s fairly active and works as a manager of a motel. She had a previous hysterectomy and hernia repair.
Her medications include levothyroxine 0.175 mg a day, esomeprazole 40 mg a day, intermittent iron supplementations (for years) and B12 once a month. She quit cigarettes in 2000 after smoking for 25 years. She drinks socially in moderation.
Physical examination is essentially unremarkable for a woman of stated age and average build. She weighs 54 kilos at a height of 160 cm. Blood pressure is 112/69 mm Hg with regular rhythm. Heart sounds are normal and lungs clear. Jugular venous pressure is normal. Abdomen is soft and benign without masses or hepatomegaly. There is 1+ pitting pedal edema.
Pertinent laboratory data shows slightly elevated AST of 70 (14-36 U/L), ALT of 87 (9-52 U/L), normal GGT of 22 (8-78 U/L), slightly elevated ALP of 140 (38-126 U/L) and low albumin of 25. Hemoglobin is low normal at 124 g/L and urinalysis (twice) is negative for blood and protein. Hepatitis B serology and anti-HCV are negative. Anti-nuclear antibody and anti-mitochondrial antibodies are also negative. Anti-smooth muscle is weakly positive. Ceruloplasmin and immunoglobulin levels are normal. Serum ferritin is between 5 and 15 for the past 6 months. She had a liver biopsy because of mild, persistent elevation of transaminases and GGT and low serum albumin, but the biopsy was unremarkable.
What’s the cause of her ongoing leg swelling?
An otherwise healthy 50-year-old woman presents with leg and ankle swelling. Turn to page 11 for details of her case.
Ankle swelling is often secondary to cardiac, kidney or chronic liver disease, and accordingly our patient Mrs. J.P. underwent evaluation to assess these possibilities. But there was no history, symptoms or signs of heart disease, and urinalysis — checked twice — failed to show proteinuria. The possibility of chronic liver disease was high on the differential diagnosis because of mild elevation of hepatic enzymes, low serum albumin and fatty liver on imaging studies, but a liver biopsy (adequate specimen) showed normal hepatic parenchyma.
Although she had undergone multiple investigations in the past, in view of the history of chronic intermittent diarrhea, long-term iron deficiency and persistent hypoalbuminemia, the possibility of celiac disease was reconsidered. The tissue transglutaminase, endomysial and gliadin antibodies were requested. The endomysial antibody was negative, tissue transglutaminase IgA was > 100 units [normal < 20] and both gliadin antibodies IgA and IgG were strongly positive with titre of > 100 units [normal < 20]. A small bowel biopsy confirmed the diagnosis of celiac disease. She has since begun an appropriate dietary therapy.
This woman’s pedal edema was caused by hypoalbuminemia resulting from chronic malabsorption secondary to celiac disease.
Celiac disease is characterized by a lifelong intolerance to the gluten present in wheat, rye or barley. It’s relatively common in the western world, with prevalence at 1% in the general population, and higher in patients with type 1 diabetes, autoimmune disease, iron deficiency or family history [3-6%]. The prevalence is especially high [10-15%] in patients with symptomatic iron deficiency anemia.
It’s often under-diagnosed because of atypical presentation and, in the past, reluctance to perform duodenal biopsy, long the gold standard for diagnosis. But newer, non-invasive blood tests have greatly simplified screening and diagnosis. The tissue transglutaminase antibody test, which has a sensitivity of 95% and specificity approaching 100%, is now commonly used to screen and diagnose patients. The optimal treatment remains unchanged — strict adherence to a gluten-free diet that restores biochemical and nutritional parameters, improves quality of life and prevents complications.
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