Atypical Familial Mediterranean Fever Complicated with Gastrointestinal Amyloidosis Diagnosed due to Paroxysmal Arthralgia and Intractable Diarrhea, Successfully Treated with Tocilizumab

Aikawa, Erika; Shimizu, Toshimasa; Koga, Tomohiro; Endo, Yuichi; Umeda, Masataka; Hori, Tomoko; Irie, Junji; Kuroda, Kishio; Eguchi, M; Okamoto, Momoko; Tsuji, Sosuke; Takatani, Ayuko; Isobe, Takashi; Sumiyoshi, Remi; Kawashiri, Shin‐ya; Iwamoto, Naoki; Ichinose, Kunihiro; Tamai, Mami; Nakamura, Hideki; Origuchi, Tomoki; Kawakami, Atsushi

doi:10.2169/internalmedicine.2277-18

Cited by 6 publications

(10 citation statements)

References 17 publications

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“…Tey also have a higher incidence of complications, such as gastrointestinal (GI) amyloidosis. Amyloidosis is the extracellular deposition of misfolded fbrillar proteins in tissues, disrupting tissue anatomy and function [4,[7][8][9]. GI amyloidosis often presents as recurrent abdominal pain, nausea, vomiting, weight loss, diarrhea, constipation, bleeding, fecal incontinence, dysphasia [7,10,11], or hepatomegaly [12].…”

Section: Discussionmentioning

confidence: 99%

“…The production of inflammatory markers, such as IL-1 and IL-18, results in serositis [ 1 ]. Recurrent FMF attacks lead to continued tissue deposition of serum amyloid A (SAA) protein, an acute-phase reactant [ 4 , 5 ]. SAA protein deposition in the gut causes gastrointestinal (GI) amyloidosis, a rare yet severe complication that often presents as chronic diarrhea and recurrent abdominal pain [ 4 , 6 ].…”

Section: Introductionmentioning

confidence: 99%

“…Recurrent FMF attacks lead to continued tissue deposition of serum amyloid A (SAA) protein, an acute-phase reactant [ 4 , 5 ]. SAA protein deposition in the gut causes gastrointestinal (GI) amyloidosis, a rare yet severe complication that often presents as chronic diarrhea and recurrent abdominal pain [ 4 , 6 ]. Herein, we report a rare case of gastric and colorectal amyloidosis as a unique cause of intractable diarrhea in a patient with a suspected history of adult-onset FMF.…”

Section: Introductionmentioning

confidence: 99%

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Gastric, Colonic, and Rectal Amyloidosis in the Setting of Familial Mediterranean Fever: A Unique Cause of Intractable Diarrhea

Bathobakae,

Ansari,

Mahmoud

et al. 2024

Case Reports in Gastrointestinal Medicine

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Familial Mediterranean fever (FMF) is a hereditary disorder characterized by episodes of fever, polyserositis, or cutaneous inflammation. The FMF attacks last 1–3 days and have no apparent triggers. Recurrent deposition of the serum amyloid A (SAA) protein in the gut can cause intractable diarrhea, dysmotility, and recurrent abdominal pain. Gastrointestinal amyloidosis is a rare, but serious, complication of FMF. In this case report, we describe a rare case of chronic diarrhea and recurrent abdominal pain due to FMF-induced gastrointestinal amyloidosis.

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Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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Gastric, Colonic, and Rectal Amyloidosis in the Setting of Familial Mediterranean Fever: A Unique Cause of Intractable Diarrhea

Bathobakae,

Ansari,

Mahmoud

et al. 2024

Case Reports in Gastrointestinal Medicine

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“…Tocilizumab has been successful in controlling disease activity in the majority of patients with crFMF reported as single cases, with good control of secondary amyloidosis in some of them (120)(121)(122)(123)(124)(125). Tocilizumab effects over proteinuria in FMF-associated amyloidosis has been analyzed in two series of 11 and 12 patients resistant to colchicine, anti-IL-1, or anti-TNF agents, in whom the previous colchicine therapy was maintained (126,127).…”

Section: Tocilizumab In Autoinflammatory Diseases Familial Mediterranmentioning

confidence: 99%

Current Therapeutic Options for the Main Monogenic Autoinflammatory Diseases and PFAPA Syndrome: Evidence-Based Approach and Proposal of a Practical Guide

Soriano

Espinosa

et al. 2020

Front. Immunol.

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recommendation based on the EULAR standardized operating procedures for EULAR-endorsed recommendations (11, 12). Category Evidence from LEVELS OF EVIDENCE 1A Meta-analysis of randomized controlled trials 1B At least one randomized controlled trial 2A At least one controlled study without randomization 2B At least one type of quasi-experimental study 3 Descriptive studies, such as comparative studies, correlation studies, or case-control studies 4 Expert committee reports or opinions and/or clinical experience of respected authorities Grade Directly based on STRENGTH OF RECOMMENDATION A Category 1 evidence B Category 2 evidence or extrapolated recommendation from category 2 evidence C Category 3 evidence or extrapolated recommendation from category 1 or 2 evidence D Category 4 evidence or extrapolated recommendation from category 2 or 3 evidence the number of attacks (20). Since then, colchicine has become the basis of FMF treatment, and later on, several clinical trials definitively established its efficacy in preventing attacks and developing amyloidosis (21-23). Colchicine was officially approved in 2009 by the US Food and Drug Administration (FDA) for the acute flares of gout and FMF, as a single-ingredient oral formulation (Colcrys R) (24). Nowadays, according to 2016 EULAR recommendations for the management of FMF, colchicine represents the first-line treatment in FMF, with a level of evidence 1B and grade of recommendation A (13). Among other biological functions, colchicine has antiinflammatory properties based on the inhibition of leukocyte chemotaxis, which is caused by its interaction with tubulin and the resulting dysfunction of microtubules. Microtubules, composed by α-and β-tubulin heterodimers, are involved in cell division, signal transduction, migration, secretion, and regulation of gene expression (25). Colchicine has the ability to bind in a poorly reversible manner to soluble non-polymerized tubulin in the cells, with the formation of a tubulin-colchicine complex (26, 27), and the subsequent movement inhibition of intracellular granules (28). The predominant effect of colchicine on leukocytes, and more specific on granulocytes, has been correlated with the high concentrations of the drug in neutrophils compared to lymphocytes and monocytes. In this regard, defects in the efflux pumps with low activity of the P-glycoprotein 1 (PGY-1) efflux pump of granulocytes might explain the accumulation of colchicine in their cytoplasm (29, 30). Other anti-inflammatory effects of colchicine include the reduction of TNF-α production by macrophages and TNF-α

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“…After 5 years with ongoing tocilizumab and colchicine he remained well, with normal CRP and amyloid levels.Nikiphorou et al [114]An 18-year-old man had multiple admissions for meningoencephalitis, pyrexia, and anemia. Genetic testing revealed heterozygosity for the MEFV gene.Sirolimus was unsuccessful in controlling symptoms, leading to a trial of tocilizumab which resulted in suppression of CRP and amyloid to normal levels and enabled steroid withdrawal.Aikawa et al [115]A 53-year-old man with recurrent episodes of large joint pain and a low-grade fever at irregular intervals for 16 years developed right knee and ankle arthralgia, watery diarrhea, and abdominal pain. Following an ileum and colon biopsy, he was diagnosed with gastrointestinal amyloidosis.…”

Section: Main Textmentioning

confidence: 99%

Update on the management of colchicine resistant Familial Mediterranean Fever (FMF)

Hasbani

Jawad

Uthman

2019

Orphanet J Rare Dis

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Background Familial Mediterranean Fever (FMF), an autoinflammatory disease, is characterized by self-limited inflammatory attacks of fever and polyserositis along with high acute phase response. Although colchicine remains the mainstay in treatment, intolerance and resistance in a certain portion of patients have been posing a problem for physicians. Main body Like many autoimmune and autoinflammatory diseases, many colchicine-resistant or intolerant FMF cases have been successfully treated with biologics. In addition, many studies have tested the efficacy of biologics in treating FMF manifestations. Conclusion Since carriers of FMF show significantly elevated levels of serum TNF alpha, IL-1, and IL-6, FMF patients who failed colchicine were successfully treated with anti IL-1, anti IL-6, or TNF inhibitors drugs. It is best to use colchicine in combination with biologics.

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Atypical Familial Mediterranean Fever Complicated with Gastrointestinal Amyloidosis Diagnosed due to Paroxysmal Arthralgia and Intractable Diarrhea, Successfully Treated with Tocilizumab

Cited by 6 publications

References 17 publications

Gastric, Colonic, and Rectal Amyloidosis in the Setting of Familial Mediterranean Fever: A Unique Cause of Intractable Diarrhea

Gastric, Colonic, and Rectal Amyloidosis in the Setting of Familial Mediterranean Fever: A Unique Cause of Intractable Diarrhea

Current Therapeutic Options for the Main Monogenic Autoinflammatory Diseases and PFAPA Syndrome: Evidence-Based Approach and Proposal of a Practical Guide

Update on the management of colchicine resistant Familial Mediterranean Fever (FMF)

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