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 Table of Contents  
CASE REPORT
Year : 2017  |  Volume : 37  |  Issue : 3  |  Page : 117-119

Gastrointestinal amyloidosis in a patient with systemic sclerosis


1 Department of Medicine, Division of Rheumatology, Immunology and Allergy, Tri-Service General Hospital, National Defense Medical Center, Taipei, Taiwan, Republic of China
2 Department of Internal Medicine, Division of Gastroenterology, Tri-Service General Hospital, National Defense Medical Center, Taipei, Taiwan, Republic of China
3 Department of Pathology, Tri-Service General Hospital, National Defense Medical Center, Taipei, Taiwan, Republic of China

Date of Web Publication19-Jun-2017

Correspondence Address:
Tsung-Yun Hou
No. 325, Sec. 2, Cheng.Gong Road, Neihu 114, Taipei, Republic of China. Tel: +886. 2. 87923311#12609; Fax: +886. 2. 87927209
Republic of China
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Source of Support: None, Conflict of Interest: None


DOI: 10.4103/jmedsci.jmedsci_64_16

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  Abstract 

There were more than 90% of systemic sclerosis (SSc) patients developing gastrointestinal tract involvement with affecting esophagus mostly. However, a typical gastrointestinal manifestation may be not the only result of SSc. We described a 70-year-old female with SSc presented poor appetite, intermittent heartburn sensation, nausea, frequent sensation of abdominal fullness, and intermittent dull pain for 2 months. The esophagogastroduodenoscopy showed gastrointestinal as gastroesophageal reflux disease. The biopsy revealed amorphous material deposited in the vascular walls and apple-green birefringence in a polarization examination with Congo red staining which proved amyloidosis. The SSc patient with gastrointestinal involvement suggests to receive esophagogastroduodenoscopy, and a biopsy may be helpful to these patients to examine the possibility of secondary amyloidosis. These patients need more aggressively disease activity control.

Keywords: Amyloidosis, gastroesophageal reflux disease, systemic sclerosis


How to cite this article:
Chiu YH, Chen PJ, Chang YM, Hou TY. Gastrointestinal amyloidosis in a patient with systemic sclerosis. J Med Sci 2017;37:117-9

How to cite this URL:
Chiu YH, Chen PJ, Chang YM, Hou TY. Gastrointestinal amyloidosis in a patient with systemic sclerosis. J Med Sci [serial online] 2017 [cited 2018 Aug 18];37:117-9. Available from: http://www.jmedscindmc.com/text.asp?2017/37/3/117/208468


  Introduction Top


Systemic sclerosis (SSc) is an autoimmune disease characterized by antibody production, small vessel vasculopathy, and increased fibroblast deposition of extracellular matrix. The clinical presentation involves skin thickening and variable internal organ involvement.[1] More than 90% of SSc patients have gastrointestinal tract involvement, which mostly affects the esophagus followed by the small bowel and the anorectal region.[2] The gastrointestinal manifestations from vascular damage, neurogenic impairment, and finally progress to myogenic dysfunction by smooth muscle collagenous fibrosis and atrophy.[3] However, a typical manifestation of gastrointestinal as gastroesophageal reflux disease (GERD) and abdominal discomfort may not the only result of SSc.


  Case Report Top


A 70-year-old female had been diagnosed with SSc 2 years previously. She presented with body weight loss, symmetric tightening, and induration of the skin on her fingers, polyarthralgia, Raynaud's phenomenon, dry eyes, and mouth. Serology showed an antinuclear antibody titer of more than 1:1280 with a centromere pattern and circulating anticentromere level of 304 U/ml but was negative for anti-topoisomerase I (anti-SLC-70), antineutrophil cytoplasmic antibodies (anti-MPO and anti-PR3), anti-Mi-2, anti-RO, anti-LA, anti-Smith, anti-RNP, anti-double-stranded DNA (anti-dsDNA), antihistone antibodies, and anti-ribosomalP protein autoantibodies. She was regularly followed up at our rheumatology clinic and prescription with methylprednisolone 4 mg/day and hydroxychloroquine 200 mg twice per day in November 2014, which was tapered to hydroxychloroquine 200 mg twice per day in February 2015. Due to progressive weakness and stiffness of her fingers, she was prescribed with hydroxychloroquine 200 mg twice per day, azathioprine 50 mg/day, and mycophenolate mofetil 250 mg twice per day in June 2015.

She had a poor appetite, intermittent heartburn sensation, nausea, and frequent abdominal fullness for 2 months. She received esophagogastroduodenoscopy which revealed GERD Los Angeles Grade B in September 2015. She then received pantoprazole 40 mg/day and mosapride 5 mg 3 times per day. However, her gastrointestinal upset persisted. For persisted polyarthralgia and gastrointestinal upset, she received rituximab 1000 mg in November 2015 and maintained therapy with hydroxychloroquine 200 mg twice per day, azathioprine 50 mg per day, and mycophenolate mofetil 250 mg twice per day.

The patient came to our emergency department for a poor appetite and vomiting with coffee ground material for 2 days. The esophagogastroduodenoscopy showed GERD Los Angeles Grade B and superficial gastritis in December 2015. A biopsy of the esophagogastric junction was also performed during esophagogastroduodenoscopy. The pathology of her biopsy showed eosinophilic amorphous material deposited in the vascular walls and aggregation of submucosa and focal lymphocytes. The amorphous material showed apple-green birefringence in a polarization examination with Congo red staining [Figure 1].
Figure 1: A biopsy of esophageal tissue at the esophagogastric junction. The section showed a picture of eosinophilic amorphous material deposited in the vascular walls and submucosa. (a) The amorphous material showed apple-green birefringence in Congo red staining in a polarization examination (b)

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She was admitted for the evaluation of amyloidosis in January 2016. Serum protein electrophoresis showed albumin 54.5%, alpha-1 globulin 5.2%, alpha-2 globulin 12%, beta globulin 13.2%, and gamma globulin 15.1%. Immunoglobulin (Ig) monoclonality was not noted in her serum, with IgG 1120 mg/dL, IgM 77 mg/dL, IgA 81 mg/dL, IgD <48 U/mL, and IgE <5 IU/dL. Serum-free light chain analysis showed kappa 6.88 mg/L and lambda 10.3 mg/L with a free light chain ratio of 0.67. There was a trace of protein in her urine analysis, and daily protein loss was 96 mg. The 24 h creatinine clearance was 95.56 mL/min. Pathology of an abdominal wall fat pad biopsy revealed a picture of a relatively normal epidermis with focally increased dermal collagen bundles and decreased periadnexal fatty tissue of the skin. She received esophagogastroduodenoscopy and random biopsies of the esophagus, stomach, and duodenum. No vessels were noted on the esophagus and stomach samples. However, the duodenum biopsy showed a picture of amorphous pink material deposition over the perivascular area of the duodenal tissue. This material was focally positive in Congo red and thioflavin-S staining [Figure 2]. The patient reported that her gastrointestinal upset had more partially improved at her follow-up visit in February 2016.
Figure 2: A duodenum biopsy showed amorphous pink material deposited over the perivascular area. (a) When stained with thioflavin S, the material presented with an apple-green color under a fluorescence microscope (b)

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  Discussion Top


There are around 70%–90% of patients with SSc experience involvement of the esophagus, with the distal two-thirds being mostly affected by GERD, esophagitis, stricture, dysmotility, or Barrett's esophagus.[2] The histological lesions are similar to those in other organs affected by SSc, which are fibrotic in nature.[4] Our patient presented with the symptoms of GERD, and she was suspected of having SSc with gastrointestinal involvement initially.

Systemic amyloidosis is a syndrome of amyloid fibril extracellular deposition, which is a combination of more than thirty precursor proteins with a core structure of β strands and various nonfibrillary constituents including glycosaminoglycans and serum amyloid P (SAP).[5] The SAP component binds to all types of amyloid fibrils, and this combination of fibrils is resistant to proteolytic and phagocytosis.[6] The gold standard to identify amyloid deposition is Congo red staining with apple-green birefringence under cross-polarized light. Thioflavin T, thioflavin S, and other conformation-specific probes also stain amyloid proteins.[7] Amyloid light chain amyloidosis is a result of plasma cell dyscrasia-related monoclonal Ig light chain deposition and accounts for 68% of cases of amyloidosis, whereas amyloid A (AA) amyloidosis is secondary to inflammatory disorders and accounts for 12% of cases of amyloidosis.[5] The inflammatory properties and expression of cytokines, especially interleukin-6, induce the overproduction of serum AA in the liver.[8] Other types of amyloidosis including hereditary (amyloid transthyretin, fibrinogen A α-chain, apolipoprotein A1 amyloid, lysozyme amyloid, and gelsolin amyloid), long-term dialysis-related β2-microglobulin amyloid, and leukocyte cell-derived chemotaxin 2 amyloid.[5] According to the disease course, our patient is most likely had AA amyloidosis resulted from chronic inflammation of SSc.

The treatment goal of AA amyloidosis is to control the underlying inflammatory disease. Several clinical trials have focused on SAP or SAA antibodies inducing macrophages to destroy the deposits.[9] Secondary amyloidosis patients require more aggressive treatment of the underlying inflammatory disease to achieve an SAA level of <4 mg/L.[5] We are currently unable to test for SAA, SAP, or perform SAP scintigraphy in our clinic. It is difficult to confirm the relationship between two diseases or is it just coincidence. We reviewed the reports of secondary amyloidosis in a patient with SSc [Table 1]. The SSc patient with gastrointestinal involvement suggests to receive esophagogastroduodenoscopy, and a biopsy may be helpful to these patients to examine the possibility of secondary amyloidosis. These patients need more aggressively disease activity control.
Table 1: Published case reports of amyloidosis with systemic sclerosis

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Declaration of patient consent

The authors certify that they have obtained all appropriate patient consent forms. In the form the patient(s) has/have given his/her/their consent for his/her/their images and other clinical information to be reported in the journal. The patients understand that their names and initials will not be published and due efforts will be made to conceal their identity, but anonymity cannot be guaranteed.

 
  References Top

1.
van den Hoogen F, Khanna D, Fransen J, Johnson SR, Baron M, Tyndall A, et al. 2013 classification criteria for systemic sclerosis: An American college of rheumatology/European league against rheumatism collaborative initiative. Arthritis Rheum 2013;65:2737-47.  Back to cited text no. 1
    
2.
Gyger G, Baron M. Systemic sclerosis: Gastrointestinal disease and its management. Rheum Dis Clin North Am 2015;41:459-73.  Back to cited text no. 2
    
3.
Sjogren RW. Gastrointestinal motility disorders in scleroderma. Arthritis Rheum 1994;37:1265-82.  Back to cited text no. 3
    
4.
Denton CP, Black CM, Abraham DJ. Mechanisms and consequences of fibrosis in systemic sclerosis. Nat Clin Pract Rheumatol 2006;2:134-44.  Back to cited text no. 4
    
5.
Wechalekar AD, Gillmore JD, Hawkins PN. Systemic amyloidosis. Lancet 2016;387:2641-54.  Back to cited text no. 5
    
6.
Tennent GA, Lovat LB, Pepys MB. Serum amyloid P component prevents proteolysis of the amyloid fibrils of Alzheimer disease and systemic amyloidosis. Proc Natl Acad Sci U S A 1995;92:4299-303.  Back to cited text no. 6
    
7.
Reinke AA, Gestwicki JE. Insight into amyloid structure using chemical probes. Chem Biol Drug Des 2011;77:399-411.  Back to cited text no. 7
    
8.
Westermark GT, Fändrich M, Westermark P. AA amyloidosis: Pathogenesis and targeted therapy. Annu Rev Pathol 2015;10:321-44.  Back to cited text no. 8
    
9.
Richards DB, Cookson LM, Berges AC, Barton SV, Lane T, Ritter JM, et al. Therapeutic clearance of amyloid by antibodies to serum amyloidPcomponent. N Engl J Med 2015;373:1106-14.  Back to cited text no. 9
    


    Figures

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    Tables

  [Table 1]



 

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