Common Clinical Presentation caused by Dual Pathology; One Quite Rare and Other Exceedingly Common

May Kyi Oo, Lin Htet Thu, Min Zaw Oo

Summary

A 40-year-old woman presented to YGH with a 5-month history of chronic diarrhoea, abdominal pain, fever, and weight loss. Prior to admission, she underwent endoscopic tests at a private hospital, which revealed terminal ileitis and pancolitis with skip lesions. Biopsy of the terminal ileum showed amyloidosis. Following the diagnosis of gastrointestinal amyloidosis, she was managed conservatively; however, her symptoms remained unchanged. Her chest X-ray was normal, and there were no signs of tuberculosis on initial biopsy. At YGH, cervical lymphadenopathy was noted. Biopsy of the lymph node showed chronic granulomatous inflammation without Langhans giant cells and caseous necrosis. CT of the abdomen revealed multiple intra-abdominal lymph nodes and thickening of the terminal ileum wall. A repeat endoscopy and biopsy were performed again at YGH, and TB PCR from the caecum came back positive. She was started on anti-TB treatment, after which her fever subsided and the chronic diarrhoea resolved.

Background

Systemic amyloidosis is a disorder caused by the misfolding of proteins, resulting in the buildup of amyloid deposits in tissues and organs, which can impair their function. These amyloid deposits consist of tightly structured protein fibrils that are insoluble and resistant to breakdown. This resistance to degradation leads to the gradual accumulation of amyloid in affected tissues. So far, researchers have identified 36 proteins capable of forming amyloid, with at least 17 known to cause systemic forms of the disease. In systemic amyloidosis, the abnormal proteins are produced in one part of the body—such as the bone marrow or liver—but are deposited in distant organs like the heart or kidneys. Localized amyloidosis is characterized by the production of amyloidogenic precursor proteins at the same location as its deposition. It may commonly involve the respiratory tract, urinary bladder, breast, skin, or the GI tract¹.

In amyloidosis, gastrointestinal involvement can occur through infiltration of either the mucosal layer or the neuromuscular structures of the GI tract. Amyloid deposits are most commonly found in the stomach (42%), followed by the small intestine (26%) and the large intestine (24%) . In AL (light chain) amyloidosis, deposits typically accumulate in the muscularis mucosae, submucosa, and muscularis propria. This leads to the formation of polyp-like protrusions and thickening of the valvulae conniventes, often resulting in symptoms such as constipation, intestinal obstruction, or features of chronic intestinal pseudo-obstruction. Conversely, in AA (secondary) amyloidosis, amyloid primarily builds up in the mucosal layer, giving the mucosa a finely granular texture and making it prone to fragility and surface erosions. These changes commonly manifest as diarrhea and malabsorption³.

Case Presentation

A 40-year-old woman presented to YGH with a 5-month history of abdominal pain and loose stools. She had been previously in good health. Five months ago, she began experiencing cramping pain localized to the right side of her abdomen. The pain occurred 5 to 10 times daily, each episode lasting 5 to 10 minutes. It was not associated with meals and did not improve after bowel movements. The pain was non-radiating and also occurred during the night. She reported having loose stools 4 to 5 times per day, small to moderate in volume. The stools were watery, yellowish, and occasionally contained mucus, but there was no blood. She denied any pale, greasy, or black stools. The diarrhea also occurred at night and did not improve with fasting. There was no associated urgency. Other symptoms included nausea and vomiting, significant weight loss—approximately half of her body weight over three months—and high, intermittent fevers accompanied by night sweats. However, she did not report mouth ulcers, or difficulty swallowing.

On examination, the patient appeared thin and malnourished, with a BMI of 17. She had dry skin, bilateral pedal oedema, and pallor. There was no jaundice or finger clubbing. There was a 3×2 cm lymph node in the right cervical region. Her temperature was 101°F. Blood pressure was 100/70 mmHg, and heart rate was 90 beats per minute. Cardiovascular and respiratory examinations were unremarkable. Abdominal examination revealed a soft, non-tender abdomen with no hepatosplenomegaly.

Investigations

CXR – Normal

Colonoscopy – terminal ileitis and pancolitis with skip lesions

Biopsy – inflamed duodenal mucosa, terminal ileum and right colon, chronic inactive inflammation with focal areas of ? amyloid deposition ,Congo red positive- amyloidosis of terminal ileum

Fig 1. Histology of biopsy specimens

Bone Marrow Examination : Findings compatible with hypoplastic myelodysplastic marrow.

Right Cervical Lymph Node Biopsy : Showed chronic granulomatous inflammation. Caseous necrosis and Langhans giant cells were not seen.

CT Abdomen & Pelvis :

– Wall thickening of the terminal ileum
– Multiple enlarged mesenteric, para-aortic, pelvic side wall, and inguinal lymph nodes, some with necrotic centers
– Fatty liver

Second Colonoscopy (at our hospital) :

– Ulceration at the caecum and ascending colon
– Pancolitis (more prominent on the right than the left)
– Biopsy taken from the caecal ulcer for TB PCR

Caecum Biopsy Result : Severe chronic non-specific colitis

Tissue TB PCR (from caecal biopsy) : Positive for Mycobacterium tuberculosis complex. After tuberculosis was confirmed through caecal TB PCR, antiTB therapy was commenced. One week later, the patient became afebrile and her diarrhoea resolved.

Discussion

Gastrointestinal (GI) amyloidosis is defined by the presence of GI-related signs and symptoms confirmed by direct biopsy evidence of amyloid deposits in the gastrointestinal tract. In a study involving 2,334 patients with all types of amyloidosis, 3.2% had biopsy-proven amyloid involvement of the gastrointestinal tract, of which 21% had amyloidosis localized to the gastrointestinal tract without evidence of an associated plasma cell dyscrasia or involvement of other organs⁴ .

The most common clinical presentations include abdominal pain (41%), gastrointestinal bleeding (20%), weight loss (10%), and diarrhea (10%)². Laboratory investigations may reveal anemia, mild elevations in alkaline phosphatase (ALP) levels, increased acute phase reactants, and nutritional deficiencies due to malabsorption. Radiological findings in gastrointestinal amyloidosis are usually non-specific. Computed tomography (CT) may show diffuse or nodular thickening of the bowel wall, mesenteric thickening, or lymphadenopathy. The gold standard for diagnosing gastrointestinal amyloidosis is tissue biopsy, followed by Congo red staining and visualization under polarized light microscopy⁵ .

In AL amyloidosis, treatment focuses on suppressing the production of monoclonal immunoglobulin light chains by eliminating the malignant plasma cells. In AA amyloidosis, therapy is specifically aimed at controlling the underlying chronic inflammatory conditions—such as rheumatoid arthritis, inflammatory bowel disease, and psoriatic arthritis—as well as chronic infections like tuberculosis, bronchiectasis, and osteomyelitis. This helps reduce the acute phase response and the production of serum amyloid A protein⁵.

Most cases of localized gastrointestinal (GI) amyloidosis are of the AL type and the most common secondary causes of localized AA-type amyloidosis are not well described in the literature. Although amyloid typing was not performed in our patient, several findings suggest localized AA amyloidosis without systemic involvement: no plasma cell infiltration in the bone marrow, normal echocardiography, and normal renal function without proteinuria. Because the biopsy of the terminal ileum revealed amyloidosis without any histological features suggestive of inflammatory bowel disease or tuberculosis, the patient was managed with supportive care only at the previous hospital. At our hospital, TB PCR of the caecal biopsy returned positive, leading to the initiation of anti-TB drugs. The patient responded well to the treatment within a few days.

The sensitivity and specificity of TB PCR for gastrointestinal tuberculosis were 77.5% and 100%, respectively, while the sensitivity and specificity of histopathology were 20% and 100%, respectively⁶ . In endemic areas, intestinal tuberculosis should be considered as a potential cause of localized gastrointestinal amyloidosis, and TB PCR should be performed as a diagnostic test.

Learning points

• Gastrointestinal amyloidosis should be considered in the differential diagnosis of chronic diarrhea.
• In endemic areas, intestinal tuberculosis can be an underlying cause of localized GI amyloidosis.
• TB PCR offers higher sensitivity and comparable specificity to histopathology in the diagnosis of intestinal tuberculosis.

References

1. Muchtar E, Dispenzieri A, Magen H, Grogan M, Mauermann M, McPhail ED, et al. (2020) Systemic amyloidosis from A (AA) to T (ATTR): a review. Journal of Internal Medicine.;289(3):268–92.
2. Malone MAV, Castillo DAA, Santos HT, Kaur A, Elrafei T, Steinberg L, et al. (2024) A systematic review of the literature on localized gastrointestinal tract amyloidosis: Presentation, management and outcomes. European journal of haematology [Internet]. 113(4):400–15. Available from: https://pubmed.ncbi.nlm.nih.gov/39030954/
3. Tada S, Iida M, Yao T, K Kawakubo, Yao T, Okada M, et al. (1994) Endoscopic features in amyloidosis of the small intestine: Clinical and morphologic differences between chemical types of amyloid protein. Gastrointestinal Endoscopy. 1;40(1):45–50.
4. Cowan AJ, Skinner M, Seldin DC, Berk JL, Lichtenstein DR, O’Hara CJ, et al.(2012) Amyloidosis of the gastrointestinal tract: a 13-year, single-center, referral experience. Haematologica.;98(1):141–6.
5. Dahiya DS, Kichloo A, Singh J, Albosta M, Wani F. (2021) Gastrointestinal amyloidosis: A focused review. World Journal of Gastrointestinal Endoscopy. 16;13(1):1–12.
6. Sharma K, Sinha S, Sharma A, Nada R, Prasad K, Goyal K, et al. (2013) Multiplex PCR for rapid diagnosis of gastrointestinal tuberculosis. Journal of Global Infectious Diseases. 1;5(2):49–9.

Author Information

May Kyi Oo, Lin Htet Thu, Min Zaw Oo

1. Senior Consultant Physician, Department of Medicine, Yangon General Hospital, Yangon
2. 3rd-year postgraduate student (Internal Medicine)
3. Professor, Department of Medicine, Yangon General Hospital, Yangon