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Published in: Arthritis Research & Therapy 1/2017

Open Access 01-12-2017 | Research article

Ultrasound verified inflammation and structural damage in patients with hereditary haemochromatosis-related arthropathy

Authors: Christian Dejaco, Andreas Stadlmayr, Christina Duftner, Viktoria Trimmel, Rusmir Husic, Elisabeth Krones, Shahin Zandieh, Emma Husar-Memmer, Gernot Zollner, Josef Hermann, Judith Gretler, Angelika Lackner, Anja Ficjan, Christian Datz, Roland Axman, Jochen Zwerina

Published in: Arthritis Research & Therapy | Issue 1/2017

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Abstract

Background

Chronic arthropathy occurs in approximately two thirds of patients with hereditary haemochromatosis (HH). The aim was to study inflammatory and structural lesions in patients with HH with (HH-A) and without arthropathy (HH-WA) using ultrasonography.

Methods

This was a cross-sectional study of 26 patients with HH-A, 24 with HH-WA and 37 with hand osteoarthritis (HOA). Clinical examination was performed in 68 joints, and we retrieved data on hand function, pain and global disease activity (all using a visual analogue scale (VAS)), morning stiffness and ferritin levels. Standard x-ray and ultrasound were conducted in 36 joints (hands, hips, knees and ankles), and we graded grey scale synovitis (GSS), power Doppler ultrasound (PD), osteophytes, erosions, tenosynovitis and cartilage damage semi-quantitatively in accordance with prior publications.

Results

Ultrasound revealed a high proportion of inflammatory changes in HH-A; GSS was found in 96.2% and PD signals in 80.8% of patients (median GSS score 9, PD score 2.5). The frequency of these findings was similar in HOA. Inflammation was also common in HH-WA, yielding GSS in 83.3% and PD signals in 50.0% of patients. Cartilage damage was most prominent in HH-A as compared to HH-WA and HOA (median scores 11.0, 2.5 and 2.0, respectively). The prevalence and extent of erosions and osteophytes were similar in all groups. None of the ultrasound scores was associated with pain or function; GSS, PD, osteophyte and cartilage scores correlated with x-ray-verified structural damage.

Conclusion

A high prevalence of ultrasound-verified inflammation and cartilage damage was found in HH-A, and to a lesser extent in HH-WA. These findings were associated with x-ray-verified damage but not with clinical scores of pain and function.
Literature
1.
go back to reference Datz C, Lalloz MR, Vogel W, Graziadei I, Hackl F, Vautier G, et al. Predominance of the HLA-H Cys282Tyr mutation in Austrian patients with genetic haemochromatosis. J Hepatol. 1997;27:773–9.CrossRefPubMed Datz C, Lalloz MR, Vogel W, Graziadei I, Hackl F, Vautier G, et al. Predominance of the HLA-H Cys282Tyr mutation in Austrian patients with genetic haemochromatosis. J Hepatol. 1997;27:773–9.CrossRefPubMed
2.
go back to reference Ludwiczek S, Theurl I, Bahram S, Schumann K, Weiss G. Regulatory networks for the control of body iron homeostasis and their dysregulation in HFE mediated hemochromatosis. J Cell Physiol. 2005;204:489–99.CrossRefPubMed Ludwiczek S, Theurl I, Bahram S, Schumann K, Weiss G. Regulatory networks for the control of body iron homeostasis and their dysregulation in HFE mediated hemochromatosis. J Cell Physiol. 2005;204:489–99.CrossRefPubMed
3.
go back to reference Siddique A, Kowdley KV. Review article: the iron overload syndromes. Aliment Pharmacol Ther. 2012;35:876–93.CrossRefPubMed Siddique A, Kowdley KV. Review article: the iron overload syndromes. Aliment Pharmacol Ther. 2012;35:876–93.CrossRefPubMed
4.
go back to reference Griffiths WJ. Review article: the genetic basis of haemochromatosis. Aliment Pharmacol Ther. 2007;26:331–42.CrossRefPubMed Griffiths WJ. Review article: the genetic basis of haemochromatosis. Aliment Pharmacol Ther. 2007;26:331–42.CrossRefPubMed
5.
go back to reference Schumacher HR, Straka PC, Krikker MA, Dudley AT. The arthropathy of hemochromatosis. Recent studies. Ann NY Acad Sci. 1988;526:224–33.CrossRefPubMed Schumacher HR, Straka PC, Krikker MA, Dudley AT. The arthropathy of hemochromatosis. Recent studies. Ann NY Acad Sci. 1988;526:224–33.CrossRefPubMed
6.
go back to reference Zwerina J, Dallos T. Osteoarthritis in hereditary metabolic diseases. Z Rheumatol. 2010;69:227–35. quiz 236.CrossRefPubMed Zwerina J, Dallos T. Osteoarthritis in hereditary metabolic diseases. Z Rheumatol. 2010;69:227–35. quiz 236.CrossRefPubMed
7.
go back to reference Atkins CJ, McIvor J, Smith PM, Hamilton E, Williams R. Chondrocalcinosis and arthropathy: studies in haemochromatosis and in idiopathic chondrocalcinosis. Q J Med. 1970;39:71–82.PubMed Atkins CJ, McIvor J, Smith PM, Hamilton E, Williams R. Chondrocalcinosis and arthropathy: studies in haemochromatosis and in idiopathic chondrocalcinosis. Q J Med. 1970;39:71–82.PubMed
8.
go back to reference Jager HJ, Mehring U, Gotz GF, Neise M, Erlemann R, Kapp HJ, et al. Radiological features of the visceral and skeletal involvement of hemochromatosis. Eur Radiol. 1997;7:1199–206.CrossRefPubMed Jager HJ, Mehring U, Gotz GF, Neise M, Erlemann R, Kapp HJ, et al. Radiological features of the visceral and skeletal involvement of hemochromatosis. Eur Radiol. 1997;7:1199–206.CrossRefPubMed
9.
go back to reference Dallos T, Sahinbegovic E, Aigner E, Axmann R, Schoniger-Hekele M, Karonitsch T, et al. Validation of a radiographic scoring system for haemochromatosis arthropathy. Ann Rheum Dis. 2010;69:2145–51.CrossRefPubMed Dallos T, Sahinbegovic E, Aigner E, Axmann R, Schoniger-Hekele M, Karonitsch T, et al. Validation of a radiographic scoring system for haemochromatosis arthropathy. Ann Rheum Dis. 2010;69:2145–51.CrossRefPubMed
10.
go back to reference Schmid H, Struppler C, Braun GS, Kellner W, Kellner H. Ankle and hindfoot arthropathy in hereditary hemochromatosis. J Rheumatol. 2003;30:196–9.PubMed Schmid H, Struppler C, Braun GS, Kellner W, Kellner H. Ankle and hindfoot arthropathy in hereditary hemochromatosis. J Rheumatol. 2003;30:196–9.PubMed
11.
go back to reference Karimi M, Jamalian N, Rasekhi A, Kashef S. Magnetic resonance imaging (MRI) findings of joints in young beta-thalassemia major patients: fluid surrounding the scaphoid bone: a novel finding, as the possible effect of secondary hemochromatosis. J Pediatr Hematol Oncol. 2007;29:393–8.CrossRefPubMed Karimi M, Jamalian N, Rasekhi A, Kashef S. Magnetic resonance imaging (MRI) findings of joints in young beta-thalassemia major patients: fluid surrounding the scaphoid bone: a novel finding, as the possible effect of secondary hemochromatosis. J Pediatr Hematol Oncol. 2007;29:393–8.CrossRefPubMed
12.
go back to reference Sahinbegovic E, Dallos T, Aigner E, Axmann R, Manger B, Englbrecht M, et al. Musculoskeletal disease burden of hereditary hemochromatosis. Arthritis Rheum. 2010;62:3792–8.CrossRefPubMed Sahinbegovic E, Dallos T, Aigner E, Axmann R, Manger B, Englbrecht M, et al. Musculoskeletal disease burden of hereditary hemochromatosis. Arthritis Rheum. 2010;62:3792–8.CrossRefPubMed
13.
go back to reference Altman R, Alarcon G, Appelrouth D, Bloch D, Borenstein D, Brandt K, et al. The American College of Rheumatology criteria for the classification and reporting of osteoarthritis of the hand. Arthritis Rheum. 1990;33:1601–10.CrossRefPubMed Altman R, Alarcon G, Appelrouth D, Bloch D, Borenstein D, Brandt K, et al. The American College of Rheumatology criteria for the classification and reporting of osteoarthritis of the hand. Arthritis Rheum. 1990;33:1601–10.CrossRefPubMed
14.
go back to reference Husic R, Gretler J, Felber A, Graninger WB, Duftner C, Hermann J, et al. Disparity between ultrasound and clinical findings in psoriatic arthritis. Ann Rheum Dis. 2014;73:1529–36.CrossRefPubMed Husic R, Gretler J, Felber A, Graninger WB, Duftner C, Hermann J, et al. Disparity between ultrasound and clinical findings in psoriatic arthritis. Ann Rheum Dis. 2014;73:1529–36.CrossRefPubMed
15.
go back to reference Backhaus M, Burmester GR, Gerber T, Grassi W, Machold KP, Swen WA, et al. Guidelines for musculoskeletal ultrasound in rheumatology. Ann Rheum Dis. 2001;60:641–9.CrossRefPubMedPubMedCentral Backhaus M, Burmester GR, Gerber T, Grassi W, Machold KP, Swen WA, et al. Guidelines for musculoskeletal ultrasound in rheumatology. Ann Rheum Dis. 2001;60:641–9.CrossRefPubMedPubMedCentral
16.
go back to reference Dejaco C, Duftner C, Wipfler-Freissmuth E, Weiss H, Graninger WB, Schirmer M. Ultrasound-defined remission and active disease in rheumatoid arthritis: association with clinical and serologic parameters. Semin Arthritis Rheum. 2012;41:761–7.CrossRefPubMed Dejaco C, Duftner C, Wipfler-Freissmuth E, Weiss H, Graninger WB, Schirmer M. Ultrasound-defined remission and active disease in rheumatoid arthritis: association with clinical and serologic parameters. Semin Arthritis Rheum. 2012;41:761–7.CrossRefPubMed
17.
go back to reference Hartung W, Kellner H, Strunk J, Sattler H, Schmidt WA, Ehrenstein B, et al. Development and evaluation of a novel ultrasound score for large joints in rheumatoid arthritis: one year of experience in daily clinical practice. Arthritis Care Res (Hoboken). 2012;64:675–82.CrossRef Hartung W, Kellner H, Strunk J, Sattler H, Schmidt WA, Ehrenstein B, et al. Development and evaluation of a novel ultrasound score for large joints in rheumatoid arthritis: one year of experience in daily clinical practice. Arthritis Care Res (Hoboken). 2012;64:675–82.CrossRef
18.
go back to reference Hammer HB, Bolton-King P, Bakkeheim V, Berg TH, Sundt E, Kongtorp AK, et al. Examination of intra and interrater reliability with a new ultrasonographic reference atlas for scoring of synovitis in patients with rheumatoid arthritis. Ann Rheum Dis. 2011;70:1995–8.CrossRefPubMed Hammer HB, Bolton-King P, Bakkeheim V, Berg TH, Sundt E, Kongtorp AK, et al. Examination of intra and interrater reliability with a new ultrasonographic reference atlas for scoring of synovitis in patients with rheumatoid arthritis. Ann Rheum Dis. 2011;70:1995–8.CrossRefPubMed
19.
go back to reference Ficjan A, Husic R, Gretler J, Lackner A, Graninger WB, Gutierrez M, et al. Ultrasound composite scores for the assessment of inflammatory and structural pathologies in psoriatic arthritis (PsASon-Score). Arthritis Res Ther. 2014;16:476.CrossRefPubMedPubMedCentral Ficjan A, Husic R, Gretler J, Lackner A, Graninger WB, Gutierrez M, et al. Ultrasound composite scores for the assessment of inflammatory and structural pathologies in psoriatic arthritis (PsASon-Score). Arthritis Res Ther. 2014;16:476.CrossRefPubMedPubMedCentral
20.
go back to reference Wakefield RJ, Balint PV, Szkudlarek M, Filippucci E, Backhaus M, D’Agostino MA, et al. Musculoskeletal ultrasound including definitions for ultrasonographic pathology. J Rheumatol. 2005;32:2485–7.PubMed Wakefield RJ, Balint PV, Szkudlarek M, Filippucci E, Backhaus M, D’Agostino MA, et al. Musculoskeletal ultrasound including definitions for ultrasonographic pathology. J Rheumatol. 2005;32:2485–7.PubMed
21.
go back to reference Finzel S, Englbrecht M, Engelke K, Stach C, Schett G. A comparative study of periarticular bone lesions in rheumatoid arthritis and psoriatic arthritis. Ann Rheum Dis. 2011;70:122–7.CrossRefPubMed Finzel S, Englbrecht M, Engelke K, Stach C, Schett G. A comparative study of periarticular bone lesions in rheumatoid arthritis and psoriatic arthritis. Ann Rheum Dis. 2011;70:122–7.CrossRefPubMed
22.
go back to reference Grassi W, Meenagh G, Pascual E, Filippucci E. “Crystal clear”-sonographic assessment of gout and calcium pyrophosphate deposition disease. Semin Arthritis Rheum. 2006;36:197–202.CrossRefPubMed Grassi W, Meenagh G, Pascual E, Filippucci E. “Crystal clear”-sonographic assessment of gout and calcium pyrophosphate deposition disease. Semin Arthritis Rheum. 2006;36:197–202.CrossRefPubMed
23.
go back to reference Sahinbegovic E, Dallos T, Aigner E, Axmann R, Engelbrecht M, Schoniger-Hekele M, et al. Hereditary hemochromatosis as a risk factor for joint replacement surgery. Am J Med. 2010;123:659–62.CrossRefPubMed Sahinbegovic E, Dallos T, Aigner E, Axmann R, Engelbrecht M, Schoniger-Hekele M, et al. Hereditary hemochromatosis as a risk factor for joint replacement surgery. Am J Med. 2010;123:659–62.CrossRefPubMed
24.
go back to reference Oke AR, Wong E, McCrae F, Young-Min S. Hereditary hemochromatosis arthropathy and Doppler ultrasound findings of synovitis. Rheumatology. 2017;56:1240–1.CrossRefPubMed Oke AR, Wong E, McCrae F, Young-Min S. Hereditary hemochromatosis arthropathy and Doppler ultrasound findings of synovitis. Rheumatology. 2017;56:1240–1.CrossRefPubMed
25.
go back to reference Frenzen K, Schäfer C, Keyßer G. Erosive and inflammatory joint changes in hereditary hemochromatosis arthropathy detected by low-field magnetic resonance imaging. Rheumatol Int. 2013;33:2061–7.CrossRefPubMed Frenzen K, Schäfer C, Keyßer G. Erosive and inflammatory joint changes in hereditary hemochromatosis arthropathy detected by low-field magnetic resonance imaging. Rheumatol Int. 2013;33:2061–7.CrossRefPubMed
26.
go back to reference Carroll GJ, Breidahl WH, Olynyk JK. Characteristics of the arthropathy described in hereditary hemochromatosis. Arthritis Care Res (Hoboken). 2012;64:9–14.CrossRef Carroll GJ, Breidahl WH, Olynyk JK. Characteristics of the arthropathy described in hereditary hemochromatosis. Arthritis Care Res (Hoboken). 2012;64:9–14.CrossRef
27.
go back to reference Husar-Memmer E, Stadlmayr A, Datz C, Zwerina J. HFE-related hemochromatosis: an update for the rheumatologist. Curr Rheumatol Rep. 2014;16:393.CrossRefPubMed Husar-Memmer E, Stadlmayr A, Datz C, Zwerina J. HFE-related hemochromatosis: an update for the rheumatologist. Curr Rheumatol Rep. 2014;16:393.CrossRefPubMed
28.
go back to reference Heiland GR, Aigner E, Dallos T, Sahinbegovic E, Krenn V, Thaler C, et al. Synovial immunopathology in haemochromatosis arthropathy. Ann Rheum Dis. 2010;69:1214–9.CrossRefPubMed Heiland GR, Aigner E, Dallos T, Sahinbegovic E, Krenn V, Thaler C, et al. Synovial immunopathology in haemochromatosis arthropathy. Ann Rheum Dis. 2010;69:1214–9.CrossRefPubMed
29.
go back to reference Smolen JS, van der Heijde DM, Keystone EC, van Vollenhoven RF, Goldring MB, Guérette B, et al. Association of joint space narrowing with impairment of physical function and work ability in patients with early rheumatoid arthritis: protection beyond disease control by adalimumab plus methotrexate. Ann Rheum Dis. 2013;72:1156–62.CrossRefPubMed Smolen JS, van der Heijde DM, Keystone EC, van Vollenhoven RF, Goldring MB, Guérette B, et al. Association of joint space narrowing with impairment of physical function and work ability in patients with early rheumatoid arthritis: protection beyond disease control by adalimumab plus methotrexate. Ann Rheum Dis. 2013;72:1156–62.CrossRefPubMed
30.
go back to reference Mandl P, Supp G, Baksa G, Radner H, Studenic P, Gyebnar J, et al. Relationship between radiographic joint space narrowing, sonographic cartilage thickness and anatomy in rheumatoid arthritis and control joints. Ann Rheum Dis. 2014;74:2022–7.CrossRefPubMed Mandl P, Supp G, Baksa G, Radner H, Studenic P, Gyebnar J, et al. Relationship between radiographic joint space narrowing, sonographic cartilage thickness and anatomy in rheumatoid arthritis and control joints. Ann Rheum Dis. 2014;74:2022–7.CrossRefPubMed
31.
go back to reference Mathiessen A, Slatkowsky-Christensen B, Kvien TK, Hammer HB, Haugen IK. Ultrasound-detected inflammation predicts radiographic progression in hand osteoarthritis after 5 years. Ann Rheum Dis. 2016;75:825–30.CrossRefPubMed Mathiessen A, Slatkowsky-Christensen B, Kvien TK, Hammer HB, Haugen IK. Ultrasound-detected inflammation predicts radiographic progression in hand osteoarthritis after 5 years. Ann Rheum Dis. 2016;75:825–30.CrossRefPubMed
32.
go back to reference Bajaj S, Lopez-Ben R, Oster R, Alarcon GS. Ultrasound detects rapid progression of erosive disease in early rheumatoid arthritis: a prospective longitudinal study. Skeletal Radiol. 2007;36:123–8.CrossRefPubMed Bajaj S, Lopez-Ben R, Oster R, Alarcon GS. Ultrasound detects rapid progression of erosive disease in early rheumatoid arthritis: a prospective longitudinal study. Skeletal Radiol. 2007;36:123–8.CrossRefPubMed
33.
go back to reference Mancarella L, Addimanda O, Cavallari C, Meliconi R. Synovial inflammation drives structural damage in hand osteoarthritis: a narrative literature review. Curr. Rheumatol. Rev. 2016 [Epub ahead of print]. Mancarella L, Addimanda O, Cavallari C, Meliconi R. Synovial inflammation drives structural damage in hand osteoarthritis: a narrative literature review. Curr. Rheumatol. Rev. 2016 [Epub ahead of print].
34.
go back to reference McBride A, Khan HI, Aitken D, Chou L, Ding C, Blizzard L, et al. Does cartilage volume measurement or radiographic osteoarthritis at baseline independently predict ten-year cartilage volume loss? BMC Musculoskelet Disord. 2016;17:54.CrossRefPubMedPubMedCentral McBride A, Khan HI, Aitken D, Chou L, Ding C, Blizzard L, et al. Does cartilage volume measurement or radiographic osteoarthritis at baseline independently predict ten-year cartilage volume loss? BMC Musculoskelet Disord. 2016;17:54.CrossRefPubMedPubMedCentral
35.
go back to reference Ottaviani S, Juge P-A, Aubrun A, Palazzo E, Dieude P. Sensitivity and reproducibility of ultrasonography in calcium pyrophosphate crystal deposition in knee cartilage: a cross-sectional study. J Rheumatol. 2015;42:1511–3.CrossRefPubMed Ottaviani S, Juge P-A, Aubrun A, Palazzo E, Dieude P. Sensitivity and reproducibility of ultrasonography in calcium pyrophosphate crystal deposition in knee cartilage: a cross-sectional study. J Rheumatol. 2015;42:1511–3.CrossRefPubMed
36.
go back to reference Wu Y, Chen K, Terkeltaub R. Systematic review and quality analysis of emerging diagnostic measures for calcium pyrophosphate crystal deposition disease. RMD Open. 2016;2:e000339.CrossRefPubMedPubMedCentral Wu Y, Chen K, Terkeltaub R. Systematic review and quality analysis of emerging diagnostic measures for calcium pyrophosphate crystal deposition disease. RMD Open. 2016;2:e000339.CrossRefPubMedPubMedCentral
37.
go back to reference Dallos T, Sahinbegovic E, Stamm T, Aigner E, Axmann R, Stadlmayr A, et al. Idiopathic hand osteoarthritis vs haemochromatosis arthropathy–a clinical, functional and radiographic study. Rheumatology. 2013;52:910–5.CrossRefPubMed Dallos T, Sahinbegovic E, Stamm T, Aigner E, Axmann R, Stadlmayr A, et al. Idiopathic hand osteoarthritis vs haemochromatosis arthropathy–a clinical, functional and radiographic study. Rheumatology. 2013;52:910–5.CrossRefPubMed
38.
go back to reference Carroll GJ, Breidahl WH, Bulsara MK, Olynyk JK. Hereditary hemochromatosis is characterized by a clinically definable arthropathy that correlates with iron load. Arthritis Rheum. 2011;63:286–94.CrossRefPubMed Carroll GJ, Breidahl WH, Bulsara MK, Olynyk JK. Hereditary hemochromatosis is characterized by a clinically definable arthropathy that correlates with iron load. Arthritis Rheum. 2011;63:286–94.CrossRefPubMed
39.
go back to reference Valenti L, Fracanzani AL, Rossi V, Rampini C, Pulixi E, Varenna M, et al. The hand arthropathy of hereditary hemochromatosis is strongly associated with iron overload. J Rheumatol. 2008;35:153–8.PubMed Valenti L, Fracanzani AL, Rossi V, Rampini C, Pulixi E, Varenna M, et al. The hand arthropathy of hereditary hemochromatosis is strongly associated with iron overload. J Rheumatol. 2008;35:153–8.PubMed
Metadata
Title
Ultrasound verified inflammation and structural damage in patients with hereditary haemochromatosis-related arthropathy
Authors
Christian Dejaco
Andreas Stadlmayr
Christina Duftner
Viktoria Trimmel
Rusmir Husic
Elisabeth Krones
Shahin Zandieh
Emma Husar-Memmer
Gernot Zollner
Josef Hermann
Judith Gretler
Angelika Lackner
Anja Ficjan
Christian Datz
Roland Axman
Jochen Zwerina
Publication date
01-12-2017
Publisher
BioMed Central
Published in
Arthritis Research & Therapy / Issue 1/2017
Electronic ISSN: 1478-6362
DOI
https://doi.org/10.1186/s13075-017-1448-0

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