Primary intestinal lymphangiectasia as a component of autoimmune polyglandular syndrome type I: A report of 2 cases.

Primary intestinal lymphangiectasia as a component of autoimmune polyglandular syndrome type I: A report of 2 cases.

Indian J Gastroenterol. 2007 Nov-Dec

Makharia GK, Tandon N, Stephen Nde J, Gupta SD, Tandon RK.
Department of Gastroenterology and Human Nutrition, All India Institute of Medical Sciences, New Delhi 110 029, India. govindmakharia@gmail.com.

Correspondence Address: Makharia Govind KDepartment of Gastroenterology and Human Nutrition, All India Institute of Medical Sciences, New Delhi 110 029 India

Abstract

Chronic diarrhea and steatorrhea occur frequently in patients with autoimmune polyglandular syndrome (APS) type I. Intestinal lymphangiectasia has been reported earlier as a cause of steatorrhea in a young girl with APS Type I. We describe 2 patients with APS Type I who were found to have intestinal lymphangiectasia, one of whom had symptomatic protein-losing enteropathy.

Chronic diarrhea and steatorrhea occur in 18-24% of patients with autoimmune polyglandular syndrome (APS) type I. Intestinal lymphangiectasia has been described earlier as a cause of steatorrhea in a young girl with APS Type I. We describe 2 patients with APS Type I who were found to have intestinal lymphangiectasia.

Case 1

A 38-year-old woman had been having generalized tonic clonic seizures since the age of 20 years. At the age of 32 years, she underwent surgery for premature subcapsular cataract. In 1999, she was diagnosed to have hypothyroidism and started on L-thyroxine. Since 2000, she developed generalized anasarca with ascites and pleural effusion. She did not have diarrhea or steatorrhea. She also developed multiple patches of vitiligo. She reported to our hospital emergency room in 2001 with complaints of easy fatigability, day-time somnolence, cold intolerance, secondary amenorrhea, fever and altered sensorium. She was stable hemodynamically but had hypothermia.

Investigations: Hemoglobin 10.8 g/dL, macrocytosis, normal bilirubin and transaminases, alkaline phosphatase 75 IU/L, serum total protein 47 g/L (albumin 18), serum calcium 1.57 mmol/L (normal 2.2-2.6; ionized calcium 0.72 mmol/L), serum phosphate 2.7 mmol/L (normal 1.0-1.4), serum folate 10.7 ng/mL (normal 3.5-16.1), serum B12 101.8 pmol/L (normal 148-443), serum iron 13.4 mmo1/L (normal 9-27) and total iron binding capacity was 69.2mmo1/L (normal 45-66). D-xylose excretion in urine was 0.49 g over 5 hours following a 5 g load (normal >1 g/5g/5h). Twenty-four hour fecal fat excretion was 0.93 g. Upper gastro-intestinal endoscopy showed thickened duodenal folds with multiple whitish spots and white tipped villi. Duodenal mucosal biopsy showed a normal crypt:villous ratio and dilated lacteals in the lamina propria suggestive of lymphangiectasia. 99mTechenitium human serum albumin scans showed evidence of protein-losing enteropathy. Secondary causes of intestinal lymphangiectasia were excluded by a normal transit of radiotracer on 99mTechenitium HSA lymphoscintigraphy, a normal barium meal follow through and absence of any peripheral, mediastinal or abdominal lymphadenopathy.

Thyroid function tests revealed free T4 of 16 pmol/L (normal 13-23), thyroid-stimulating hormone 13.57 mU/mL (normal 0.27-4.2) while the patient was receiving 100 mg of L-thyroxine daily. Serum leutinizing hormone was 2.6 IU/L (normal 0.5-15.0), serum follicle stimulating hormone 5.4 IU/L (normal 0.2-10), serum prolactin 25 ng/mL (normal 0-18.8). Serum cortisol measured at 1800 h was 380 nmol/L (normal for evening level 70-345).

She had manifestations of hypoparathyroidism, hypothyroidism, pernicious anemia and secondary amenorrhea. In addition she had protein-losing enteropathy due to intestinal lymphangiectasia. She was treated with thyroxine, calcium, vitamin D, and vitamin B12 supplementation, human albumin, and medium chain triglyceride-based diet. Her anasarca improved on human albumin supplementation and medium chain triglyceride diet. After follow up of a period of about 18 months, she died because of overwhelming sepsis.

Case 2

A 33-year-old man had swelling of face and extremities, recurrent syncope and constipation since childhood. He was diagnosed as hypothyroidism and treated with thyroxine. He had features of myxedema, postural hypotension, anemia, hyperpigmentation of the buccal mucosa, dystrophic and dry skin, enamel hypoplasia and short stature.

Investigations: Hemoglobin 6.6 g/dL, and mean corpuscular volume 114 fl, serum bilirubin 1.3 mg/dL, ALT 10 IU/L, AST 52 IU/L, alkaline phosphatase 84 IU/L. Serum total protein 62 g/L (albumin 33 g/L), serum calcium 1.7 mmol/L, serum phosphate 1.7mmol/L. The anti-parietal cell antibody was positive; antinuclear antibody, anti-smooth muscle antibody, anti-liver-kidney-microsomal antibody, and anti-thyroid peroxidase antibody were negative. TSH 46 mU/mL, serum free T3 3.5 pmol/L, serum free T4 12.2 pmol/L. Basal morning cortisol at 8 AM was 690 nmol/L (normal 140-690), which rose to 772 nmol/L after 250 mg of adrenocorticotrophic hormone stimulation. Serum parathyroid hormone (PTH) level was 59.2 pg/mL (normal 16-46) with serum calcium 1.7 mmol/L. Serum follicle stimulating hormone was 13.5 IU/L, serum leutinizing hormone 13.5 IU/L, serum prolactin 27.1 mg/L and serum testosterone was 6 ng/mL (normal 3-10).UGI endoscopy revealed atrophic gastritis, esophageal candidiasis (smears showed fungal hyphae), thickened duodenal folds and multiple whitish nodular lesions with white tops in between and over the mucosal folds suggestive of intestinal lymphangiectasia. The jejunal biopsy showed dilation of lymphatic channels in the lamina propria and mild increase in the chronic inflammatory cells. The secondary causes of intestinal lymphangiectasia were excluded.

In summary, he had primary hypothyroidism, hypo-parathyroidism, macrocytic anemia, esophageal candidiasis and ectodermal dystrophy which suggested a diagnosis of APS type I. In addition, he had primary intestinal lymphangiectasia. He was treated with thyroxine, hydrocortisone, calcium, parenteral B12. His symptoms improved and hemoglobin rose to 9 g. He lost to follow up after 9 months.

Autoimmune polyglandular syndrome (APS) type I is comprised of a broad spectrum of diseases including chronic muco-cutaneous candidiasis, hypoparathyroidism hypothyroidism and type 1 diabetes mellitus. Patients with this syndrome and their families may have other non-endocrine manifestations, including ectodermal dystrophy, pernicious anemia, chronic atrophic gastritis, autoimmune hepatitis, vitiligo, alopecia, asplenia, cholelithiasis and keratoconjunctivitis.

Intestinal lymphangiectasia by virtue of loss of lymphocytes, immunoglobulins and albumin in the intestine may complicate the natural history of APS type I. Primary intestinal lymphangiectasia is mostly congenital and may be associated with lymphatic ductal abnormalities at other sites and organs. Secondary intestinal lymphangiectasia on the other hand occurs mostly due to inflammatory diseases of the small bowel, mesenteric tuberculosis, lymphoma, Whipple's disease, Crohn's disease, retroperitoneal fibrosis, and constrictive pericarditis.It has also been reported in systemic autoimmune diseases such as systemic lupus erythematosus and progressive systemic sclerosis. Although the exact pathogenesis of intestinal lymphangiectasia in SLE and PSS is not known, immunological injury has been suggested.Acquired hypospenism, enamel hypoplasia and nail dystrophy which are seen in patients with APS type I, have also been reported in patients with primary intestinal lymphangiectasia.

It is therefore, conceivable that these APS and intestinal lymphangiectasia share a similar etiology and/or pathogenetic mechanism; intestinal lymphangiectasia may be responsible for gastrointestinal manifestations in patients with APS type I.

Indian Journal of Gastroenterology