The immunoglobulin light-chain amyloidosis is a multisystemic disease which manifests by damage to the vital organs by light chain-derived amyloid fibril. Traditionally, the treatment has been directed to the underlying plasma cell clone with or without high dose chemotherapy followed by autologous stem cell transplantation using melphalan based conditioning. Now with the approval of highly tolerable anti-CD38 monoclonal antibody daratumumab based anti-plasma cell therapy in 2021, high rates of hematologic complete responses are possible even in patients who are otherwise deemed not a candidate for autologous stem cell transplantation. However, despite the progress, there remains a limitation in the strategies to improve symptoms particularly in patients with advanced cardiac involvement, those with nephrotic syndrome and autonomic dysfunction due to underlying systemic AL amyloidosis. The symptoms can be an ordeal for the patients and their caregivers and effective strategies are urgently needed to address them. The supportive care is aimed to counteract the symptoms of the disease and the effects of the treatment on involved organs’ function and preserve patients’ quality of life. Here we discuss multidisciplinary approach in a system-based fashion to address the symptom management in this dreadful disease. In addition to achieving excellent anti-plasma cell disease control, using treatment directed to remove amyloid from the vital organs can theoretically hasten recovery of the involved organs thereby improving symptoms at a faster pace. Ongoing phase III clinical trials of CAEL-101 and Birtamimab will address this question.

• Amyloidosis
• Hematology
• Light chain
• Multidisciplinary approach
• Supportive care

Amyloidosis, a heterogenous group of disorders, is characterized by the extracellular deposition of autologous, insoluble, fibrillar misfolded proteins. These extracellular proteins deposit in tissues aggregated in ß-pleated sheets arranged in an antiparallel fashion and cause distortion to the tissue architecture and function. In the current literature, about 60 heterogeneous amyloidogenic proteins have been identified, out of which 27 have been associated with human disease. Classified as a rare disease, amyloidosis is known to have a wide range of possible etiologies and clinical manifestations. The exact incidence and prevalence of the disease is currently unknown. In both systemic and localized amyloidosis, there is infiltration of the abnormal proteins in the layers of the gastrointestinal (GI) tract or the liver parenchyma. The gold standard test for establishing a diagnosis is tissue biopsy followed by Congo Red staining and apple-green birefringence of the Congo Red-stained deposits under polarized light. However, not all patients may have a positive tissue confirmation of the disease. In these cases additional workup and referral to a gastroenterologist may be warranted. Along with symptomatic management, the treatment for GI amyloidosis consists of observation or localized surgical excision in patients with localized disease, and treatment of the underlying pathology in cases of systemic amyloidosis. In this review of the literature, we describe the subtypes of amyloidosis, with a primary focus on the epidemiology, pathogenesis, clinical features, diagnosis and treatment strategies available for GI amyloidosis.

• Gastroenterology
• Hepatology
• Amyloidosis
• Dysmotility
• Endoscopy
• Therapeutics

• Cardiac amyloidosis
• Factor X deficiency
• Light chain amyloidosis
• Nephrotic syndrome
• Peripheral neuropathy
• Supportive care

• Amyloidosis/complications
• Amyloidosis/diagnosis
• Colic
• Colonic Diseases/diagnostic imaging
• Colonic Diseases/etiology
• Humans
• Intussusception/diagnostic imaging
• Intussusception/etiology

• AL amyloidosis
• Cardiac amyloidosis
• Nephrotic syndrome
• Supportive care
• Treatment

• Disease Management
• Humans
• Immunoglobulin Light-chain Amyloidosis/diagnosis
• Immunoglobulin Light-chain Amyloidosis/etiology
• Immunoglobulin Light-chain Amyloidosis/therapy
• Organ Specificity
• Palliative Care/methods

Gastrointestinal amyloidosis (GIA), a protein deposition disorder, represents a complex common pathway that encompasses multiple etiologies and presentations. It represents a significant diagnostic and treatment challenge. The disease results from the deposition of insoluble extracellular protein fragments that have been rendered resistant to digestion. GIA can be acquired or genetic, and most commonly results from chronic inflammatory disorders (AA amyloidosis), hematologic malignancy (AL amyloidosis), and end-stage renal disease (Beta-2 amyloidosis). The deposition of these abnormal proteins interferes with gastrointestinal tract (GI) organ structure and function, most notably in the liver and small bowel. Presentation from GI involvement includes cirrhotic sequelae, abdominal pain, malabsorption, and GI bleeding. Diagnosis hinges on pathologic examination of affected tissue, with classic green birefringence under polarized light. Abdominal fat pad and rectal mucosal biopsy have been described as sites of higher sensitivity for diagnosis. Serum amyloid P scintigraphy is near 90% sensitive for diagnosis of AA amyloidosis. Patients should be considered for further evaluation to rule out additional organ involvement, notably cardiac and renal. Treatment hinges on an adequate suppression of the predisposing inflammatory disorder, or malignancy, followed by supportive therapy. Prognosis varies depending on the etiology of the disease, with the AL subtype showing worse outcomes, as well as those with hepatic involvement. 

• amyloidosis
• gastrointestinal amyloidosis

• Abdominal Pain/etiology
• Aged
• Amyloidosis/complications
• Amyloidosis/etiology
• Anastomosis, Surgical
• Anemia/etiology
• Biopsy
• Bone Marrow/pathology
• Colon, Sigmoid/pathology
• Colon, Sigmoid/surgery
• Colonoscopy
• Diagnosis, Differential
• Female
• Gastrointestinal Hemorrhage/etiology
• Humans
• Immunoelectrophoresis
• Immunoglobulin lambda-Chains/analysis
• Intestinal Obstruction/diagnosis
• Intestinal Obstruction/etiology
• Intestinal Obstruction/immunology
• Multiple Myeloma/complications
• Multiple Myeloma/diagnosis
• Rectum/pathology
• Rectum/surgery

• Amyloid/metabolism
• Amyloidosis/complications
• Amyloidosis/diagnosis
• Amyloidosis/therapy
• Colitis, Collagenous/etiology
• Colitis, Collagenous/pathology
• Colitis, Collagenous/therapy
• Colitis, Ulcerative/etiology
• Colitis, Ulcerative/pathology
• Colitis, Ulcerative/therapy
• Female
• Gastroscopy
• Humans
• Middle Aged

• Amyloidosis/classification
• Amyloidosis/drug therapy
• Amyloidosis/therapy
• Antineoplastic Agents/therapeutic use
• Colchicine/therapeutic use
• Dimethyl Sulfoxide/therapeutic use
• Diuretics/therapeutic use
• Humans
• Hypertension/drug therapy
• Immunoglobulin Light Chains/analysis
• Organ Transplantation
• Peripheral Blood Stem Cell Transplantation
• Treatment Outcome