Zusammenfassung
Die Anämie ist eine der häufigsten extraartikulären Organmanifestationen bei der rheumatoiden Arthritis (RA), verursacht zum Teil ausgeprägte Symptome und besitzt auch wegen der Beeinflussung von anderen extraartikulären Manifestationen (z. B. Arteriosklerose) eine erhebliche Bedeutung bei der RA. Die Ursachen einer Anämie von RA-Patienten können sehr vielschichtig sein, am häufigsten sind die Anämie bei chronischer Entzündung und die Eisenmangelanämie. Diese beiden Anämieformen können auch kombiniert vorkommen. Die Störungen des Eisenstoffwechsels, welche die wichtigste pathophysiologische Grundlage der Anämie bei RA darstellen, werden durch die veränderte Synthese und Funktion von Hepcidin, einem von Leber und immunkompetenten Zellen synthetisierten Peptid, sowie dem Eisentransporter Ferroportin vermittelt. Die charakteristischen Veränderungen von Eisenstoffwechsel und Hepcidin-Synthese bei chronischen Entzündungen werden entscheidend durch proinflammatorische Zytokine, insbesondere Interleukin-6 beeinflusst. Daher hat die funktionelle Antagonisierung von Zytokinen im Rahmen der Therapie einer RA auch therapeutische Effekte hinsichtlich der extraartikulären Manifestation Anämie.
Abstract
One of the most frequent extra-articular organ manifestations in rheumatoid arthritis (RA) is anemia. As anemia in RA patients may result in severe symptoms and aggravation of other disease manifestations (e.g. arteriosclerosis), the influence on the course of RA is profound. However, the importance of anemia in RA patients is frequently underestimated. The etiology of anemia in RA is complex. Anemia of inflammation (AI) and iron deficiency anemia, alone or in combination are the most frequent forms of anemia in RA. Changes in iron metabolism are the leading causes of anemia in RA patients and mainly induced by the altered synthesis and function of hepcidin and ferroportin. Hepcidin, a peptide produced in the liver and immunocompetent cells, impairs the expression of ferroportin on iron-secreting cells, thus reducing iron bioavailability. The typical changes of iron metabolism and hepcidin synthesis in RA are induced by proinflammatory cytokines, primarily interleukin-6. Hence, the treatment of RA with cytokine antagonists has significant therapeutic implications on anemia in the context of inflammation and impaired iron metabolism.
Literatur
Aalto K, Honkanen V, Lahdenne P (2011) Iron status during anti-TNF therapy in children with juvenile idiopathic arthritis. Clin Rheumatol 30:115–119
Arndt U, Kaltwasser JP, Gottschalk R et al (2005) Correction of iron-deficient erythropoiesis in the treatment of anemia of chronic disease with recombinant human erythropoietin. Ann Hematol 84:159–166
Baker JF, Ghio AJ (2009) Iron homoeostasis in rheumatic disease. Rheumatology (Oxford) 48:1339–1344
Cook JD (2005) Diagnosis and management of iron-deficiency anaemia. Best Pract Res Clin Haematol 18:319–332
Dabbagh AJ, Trenam CW, Morris CJ et al (1993) Iron in joint inflammation. Ann Rheum Dis 52:67–73
Demirag MD, Haznedaroglu S, Sancak B et al (2009) Circulating hepcidin in the crossroads of anemia and inflammation associated with rheumatoid arthritis. Intern Med 48:421–426
Doyle MK, Rahman MU, Han C et al (2009) Treatment with infliximab plus methotrexate improves anemia in patients with rheumatoid arthritis independent of improvement in other clinical outcome measures-a pooled analysis from three large, multicenter, double-blind, randomized clinical trials. Semin Arthritis Rheum 39:123–131
Finkelstein RA, Sciortino CV, Mcintosh MA (1983) Role of iron in microbe-host interactions. Rev Infect Dis 5(Suppl 4):759–777
Fleming RE, Ponka P (2012) Iron overload in human disease. N Engl J Med 366:348–359
Ganz T (2006) Molecular pathogenesis of anemia of chronic disease. Pediatr Blood Cancer 46:554–557
Ganz T, Nemeth E (2009) Iron sequestration and anemia of inflammation. Semin Hematol 46:387–393
Hastka J, Lasserre JJ, Schwarzbeck A et al (1993) Zinc protoporphyrin in anemia of chronic disorders. Blood 81:1200–1204
Kaltwasser JP, Kessler U, Gottschalk R et al (2001) Effect of recombinant human erythropoietin and intravenous iron on anemia and disease activity in rheumatoid arthritis. J Rheumatol 28:2430–2436
Macdougall IC, Cooper AC (2002) Erythropoietin resistance: the role of inflammation and pro-inflammatory cytokines. Nephrol Dial Transplant 17(Suppl 11):39–43
Munoz M, Villar I, Garcia-Erce JA (2009) An update on iron physiology. World J Gastroenterol 15:4617–4626
Nemeth E, Rivera S, Gabayan V et al (2004) IL-6 mediates hypoferremia of inflammation by inducing the synthesis of the iron regulatory hormone hepcidin. J Clin Invest 113:1271–1276
Nemeth E, Tuttle MS, Powelson J et al (2004) Hepcidin regulates cellular iron efflux by binding to ferroportin and inducing its internalization. Science 306:2090–2093
Park CH, Valore EV, Waring AJ et al (2001) Hepcidin, a urinary antimicrobial peptide synthesized in the liver. J Biol Chem 276:7806–7810
Peeters HR, Jongen-Lavrencic M, Raja AN et al (1996) Course and characteristics of anaemia in patients with rheumatoid arthritis of recent onset. Ann Rheum Dis 55:162–168
Peyssonnaux C, Zinkernagel AS, Datta V et al (2006) TLR4-dependent hepcidin expression by myeloid cells in response to bacterial pathogens. Blood 107:3727–3732
Pinto JP, Dias V, Zoller H et al (2010) Hepcidin messenger RNA expression in human lymphocytes. Immunology 130:217–230
Punnonen K, Irjala K, Rajamaki A (1997) Serum transferrin receptor and its ratio to serum ferritin in the diagnosis of iron deficiency. Blood 89:1052–1057
Raj DS (2009) Role of interleukin-6 in the anemia of chronic disease. Semin Arthritis Rheum 38:382–388
Smolen JS, Beaulieu A, Rubbert-Roth A et al (2008) Effect of interleukin-6 receptor inhibition with tocilizumab in patients with rheumatoid arthritis (OPTION study): a double-blind, placebo-controlled, randomised trial. Lancet 371:987–997
Sow FB, Alvarez GR, Gross RP et al (2009) Role of STAT1, NF-kappaB, and C/EBPbeta in the macrophage transcriptional regulation of hepcidin by mycobacterial infection and IFN-gamma. J Leukoc Biol 86:1247–1258
Van Santen S, Van Dongen-Lases EC, De Vegt F et al (2011) Hepcidin and hemoglobin content parameters in the diagnosis of iron deficiency in rheumatoid arthritis patients with anemia. Arthritis Rheum 63:3672–3680
Weiss G, Goodnough LT (2005) Anemia of chronic disease. N Engl J Med 352:1011–1023
Wilson A, Yu HT, Goodnough LT et al (2004) Prevalence and outcomes of anemia in rheumatoid arthritis: a systematic review of the literature. Am J Med 116(Suppl 7A):50–57
Interessenkonflikt
Der korrespondierende Autor gibt an, dass kein Interessenkonflikt besteht.
Author information
Authors and Affiliations
Corresponding author
Rights and permissions
About this article
Cite this article
Wahle, M. Anämie bei Patienten mit rheumatoider Arthritis. Z. Rheumatol. 71, 864–868 (2012). https://doi.org/10.1007/s00393-011-0925-0
Published:
Issue Date:
DOI: https://doi.org/10.1007/s00393-011-0925-0