Amyloidosis is defined as the extracellular deposition of non-branching fibrils composed of a variety of serum-protein precursors. Secondary amyloidosis is associated with several chronic inflammatory conditions, such as rheumatologic or intestinal diseases, familial Mediterranean fever, or chronic infectious diseases, such as tuberculosis. Although the association of amyloidosis with inflammatory bowel disease is known, amyloidosis secondary to ulcerative colitis (UC) is rare. A 36-year-old male patient with a 15-year history of UC presented with nausea, vomiting, and abdominal pain. He had been treated with infliximab for 6 years. At the time of admission, he had been undergoing treatment with mesalazine and adalimumab since the preceding 5 months. Esophagogastroduodenoscopy showed mucosal erythema, edema, and erosions with geographic ulcers at the 2nd and 3rd portions of the duodenum. Duodenal amyloidosis was diagnosed using polarized light microscopy and Congo red stain. Monoclonal gammopathy was not detected in serum and urine tests, while the serum free light chain assay result was not specific. An increase in plasma cells in the bone marrow was not found. Secondary amyloidosis due to UC was suspected. The symptoms were resolved after glucocorticoid therapy.
Secondary (AA) amyloidosis is caused by extracellular deposition of fibrils that are composed of serum amyloid A (SAA) protein, an acute phase reactant. It can occur in association with many chronic inflammatory conditions, including rheumatoid arthritis, ankylosing spondylitis, IBD, and periodic fever syndromes or with chronic infections such as tuberculosis and osteomyelitis.
A 36-year-old male patient with a 15-year history of UC presented with nausea, vomiting, and abdominal pain. When he was first diagnosed with UC 15 years ago, colonoscopy showed multiple ulcers, mucosal friability, and bleeding throughout the entire colon and rectum. The Mayo score was 9. After being diagnosed with UC, he was treated with mesalazine and intermittent steroid therapy for 9 years, until cyclosporine therapy was administered due to development of steroid-refractory UC 3 years later. As cyclosporine was not effective, he was then treated with infliximab for 6 years. Currently, he is being treated with mesalazine and adalimumab since 5 months. Clinical tests revealed mucosal friability and multiple erosions without ulcers and bleeding throughout the entire colon, while the Mayo score was 4. Upon physical examination, a normoactive bowel sound was heard, the abdomen was found to be flat, and tenderness was absent. No hepatomegaly or splenomegaly was noted. The laboratory results revealed leukocytosis (white blood cell count, 10,590/mm3), anemia (hemoglobin, 9.5 g/dL), and an elevated CRP level of 5.38 mg/dL. Esophagogastroduodenoscopy showed mucosal erythema, edema, and erosions with geographic ulcers at the 2nd and 3rd portions of the duodenum (
Amyloidosis is a general term used for disorders characterized by extracellular deposition of insoluble polymeric protein fibrils in tissues and organs. There are several types of amyloidosis, and the 2 major forms are AL (primary) and AA (secondary) types. AL amyloidosis is due to the deposition of protein derived from the Ig light chain and is most frequently caused by a clonal expansion of plasma cells. AA amyloidosis results from the deposition of fibrils that are composed of SAA protein, an acute phase reactant. AA amyloidosis may complicate several chronic inflammatory diseases, including IBD.
AA amyloidosis can affect a variety of organ systems, including the heart and kidneys. Kidneys are the most commonly affected organ system. Renal involvement often manifests as asymptomatic proteinuria, nephrotic syndrome, or renal failure.
To diagnose amyloidosis, tissue biopsy is essential to confirm the presence of amyloid protein. Polarized light microscopy using Congo red stain or electron microscopy can be used to confirm such amyloid deposits. Once amyloid is detected, the protein type should be determined by immunohistochemistry, immunoelectron microscopy, or mass spectrometry. Further testing to detect the presence of monoclonal Ig, as well as serum FLC assays, are recommended to distinguish between AL and AA amyloidosis. In the present case, AL amyloidosis was excluded by conducting serum and urine protein electrophoresis, immunofixation electrophoresis, and bone marrow biopsy.
The primary therapy for secondary amyloidosis involves treating the underlying inflammatory or infectious disease. The treatment of underlying diseases also decreases the SAA protein level. Colchicine can be used to treat and prevent secondary amyloidosis, particularly in familial Mediterranean fever.
The patient in the present case was previously treated with adalimumab, a tumor necrosis factor inhibitor, which is also used for the treatment of AA amyloidosis. However, the patient required additional therapy for amyloidosis, and glucocorticoids were administered to greatly reduce the severity of the underlying UC. Symptoms of nausea, vomiting, and abdominal pain were resolved, and the CRP level was normalized, within a few days after glucocorticoid treatment. Although glucocorticoid therapy is not an established treatment of gastrointestinal amyloidosis, in some cases, efficacy of steroids and octreotides for protein-losing enteropathy due to gastrointestinal amyloidosis has been reported.