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Granulocyte and monocyte adsorption apheresis for leg ulcers in a patient with rheumatoid arthritis

2005; Elsevier BV; Volume: 52; Issue: 6 Linguagem: Inglês

10.1016/j.jaad.2005.01.105

1097-6787

Takuro Kanekura, Yuji Mochitomi, Shizuyo Fujimoto, Koichi Kawahara, Ikuro Maruyama, Tamotsu Kanzaki,

Blood disorders and treatments

To the Editor: Rheumatoid arthritis (RA) is a refractory disease characterized by chronic, systemic, and progressive arthritis. RA patients often have leg ulcers caused by rheumatoid vasculitis. Cytokines including interleukin (IL)-1, IL-2, IL-6, tumor necrosis factor–α, interferon-γ, and granulocyte-macrophage colony stimulating factor are produced by granulocytes of RA patients.1Lipsky P.E. Rheumatoid arthritis.in: Wilson J.D. Braunwald E. Isselbacher K.J. Harrison's Principles of Internal Medicine. 12th ed. McGraw-Hill, New York1991: 1437-1443Google Scholar Granulocyte and monocyte adsorption apheresis (GCAP), first employed to treat ulcerative colitis,2Kanekura T. Maruyama I. Kanzaki T. Granulocyte and monocyte adsorption apheresis for pyoderma gangrenosum.J Am Acad Dermatol. 2002; 47: 320-321Abstract Full Text Full Text PDF PubMed Scopus (44) Google Scholar uses a column containing cellulose acetate beads to remove pathogenic granulocytes and monocytes extracorporeally. We describe a RA patient whose arthralgia and leg ulcers improved dramatically following GCAP. A 56-year-old woman with a 10-year history of RA with typical multiple arthritis, had leg ulcers for 5 years that recurred despite treatment with systemic corticosteroids and cyclosporin. She used a wheelchair because of difficulty in walking and arthralgia of her hip, knee, and ankle joints. She had multiple round ulcers 0.5 cm to 4 cm in diameter on her lower legs (Fig 1, A) with sharp margins and a necrotic base. We discontinued cyclosporin and performed GCAP therapy 10 times at 5-day intervals without altering the corticosteroid dose (20 mg daily). After the second session, granulation tissue appeared, the discharge decreased, and her pain improved. The ulcers were almost completely covered by regenerated skin after the seventh session and cleared at the completion of therapy (Fig 1, B). Her arthralgia, assessed by a visual analog scale, was scored as 8 in the bilateral hip, knee, and ankle joints before GCAP treatment. It was 6 in her right hip joint and 0 in the other joints after GCAP therapy. Her white blood cell count, her neutrophil count, and her C-reactive protein were decreased in response to GCAP treatment (Table I). No adverse effects, including thromboembolic phenomena, occurred in the course of therapy. Cellulose acetate beads in the column activate and absorb complement components that are ligands for adhesive molecule integrin Mac-1 (CD11b/CD18) expressed on activated granulocytes.3Kanekura T. Gushi A. Iwata M. Fukumaru S. Sakamoto R. Kawahara K. et al.Treatment of Behçet's disease with granulocyte and monocyte adsorption apheresis.J Am Acad Dermatol. 2004; 51: S83-S87Abstract Full Text Full Text PDF PubMed Scopus (27) Google Scholar Hypothesizing that the column traps activated granulocytes by these mechanisms, we examined Mac-1 expression on neutrophils and found it to be increased prior to and reduced following GCAP therapy (Table I).Table IResults of GCAP therapy for rheumatoid arthritis with leg ulcersBeforeAfterWBC (/μl)71006200Neutrophils (/μl)54004800CRP (mg/dl)1.330.28Mac-1 (MFI)∗The mean MFI ± SD of neutrophils from 4 normal subjects was 10.5 ± 1.2 (range 9.0-12.0).39.722.0VAS Right hip joint86 Left hip joint80 Bilateral knee joints80 Bilateral ankle joints80After, One day after the last (10th) GCAP treatment; before, one day before the first GCAP treatment; CRP, C-reactive protein; GCAP, granulocyte and monocyte adsorption apheresis; MFI, mean fluorescence intensity; VAS, visual analog scale of joint pain; WBC, white blood cell count.∗ The mean MFI ± SD of neutrophils from 4 normal subjects was 10.5 ± 1.2 (range 9.0-12.0). Open table in a new tab After, One day after the last (10th) GCAP treatment; before, one day before the first GCAP treatment; CRP, C-reactive protein; GCAP, granulocyte and monocyte adsorption apheresis; MFI, mean fluorescence intensity; VAS, visual analog scale of joint pain; WBC, white blood cell count. In RA patients, serum matrix metalloproteinases were elevated.4Tchetverikov I. Ronday H.K. Van El B. Kiers G.H. Verzijl N. TeKoppele J.M. et al.MMP profile in paired serum and synovial fluid samples of patients with rheumatoid arthritis.Ann Rheum Dis. 2004; 63: 881-883Crossref PubMed Scopus (140) Google Scholar Increased cytokines and matrix metalloproteinases may result in delayed resolution of leg ulcers. Adjunctive therapies for RA leg ulcers (eg, topical agents, prostaglandins, and plasmapheresis) are only partly successful. Our case suggests that GCAP therapy is a useful treatment option for RA leg ulcers and possibly intractable skin disorders associated with activated granulocytes.2Kanekura T. Maruyama I. Kanzaki T. Granulocyte and monocyte adsorption apheresis for pyoderma gangrenosum.J Am Acad Dermatol. 2002; 47: 320-321Abstract Full Text Full Text PDF PubMed Scopus (44) Google Scholar, 3Kanekura T. Gushi A. Iwata M. Fukumaru S. Sakamoto R. Kawahara K. et al.Treatment of Behçet's disease with granulocyte and monocyte adsorption apheresis.J Am Acad Dermatol. 2004; 51: S83-S87Abstract Full Text Full Text PDF PubMed Scopus (27) Google Scholar, 5Kanekura T. Yoshii N. Yonezawa T. Kawabata H. Saruwatari H. Kanzaki T. Treatment of pustular psoriasis with granulocyte and monocyte adsorption apheresis.J Am Acad Dermatol. 2003; 49: 329-332Abstract Full Text Full Text PDF PubMed Scopus (39) Google Scholar However, it may be contraindicated in patients with infectious diseases or leukopenia.