- Email: [email protected]
Treatment of psoriatic arthritis with granulocyte and monocyte adsorption apheresis
Treatment of psoriatic arthritis with granulocyte and monocyte adsorption apheresis Takuro Kanekura, MD, PhD,a Hisashi Kawabata, MD, PhD,a Ikuro Maruyama, MD, PhD,b and Tamotsu Kanzaki, MD, PhDa Kagoshima, Japan Granulocyte and monocyte adsorption apheresis (GCAP) is a new extracorporeal apheresis treatment modality that removes pathogenic granulocytes. Recently, we found that GCAP is useful for treating pyoderma gangrenosum and pustular psoriasis. We thought that this treatment may also be effective for treating other disorders attributable to activated granulocytes and studied the efficacy of GCAP in 4 patients with psoriatic arthritis. Treatment with GCAP resulted in remarkable clearing of joint pain, suggesting that GCAP is valuable for treating arthritis as well as skin disorders. We present a detailed description of these patients and this novel therapy. (J Am Acad Dermatol 2004;50:242-6.)
P
soriatic arthritis is an inflammatory disorder of the systemic joints characterized by its association with psoriasis.1 Arthralgia is the major complaint of patients with this disorder, and various systemic treatments, including the administration of retinoids, cyclosporin, nonsteroidal anti-inflammatory drugs (NSAIDs), methotrexate, and corticosteroids, are only partially successful. Granulocyte and monocyte adsorption apheresis (GCAP) has been used to treat ulcerative colitis2 which is often associated with pyoderma gangrenosum.3 We previously reported that GCAP was remarkably effective in patients with pyoderma gangrenosum.4 Therefore, we speculated that it may also be useful for treating other disorders with prominent granulocytic infiltration and demonstrated that pustular psoriasis was improved after GCAP treatment.5 We now report 4 patients with psoriatic arthritis whose severe arthritis responded well to GCAP.
From the Department of Dermatologya and the Laboratory of Molecular Medicine,b Kagoshima University Faculty of Medicine. The GCAP columns used in this study were provided by Japan Immunoresearch Laboratories, Takasaki, Japan. Conflict of interest: None identified. Reprint requests: Takuro Kanekura, MD, PhD, Department of Dermatology, Kagoshima University Faculty of Medicine, 8-35-1 Sakuragaoka, Kagoshima 890-8520, Japan. E-mail: [email protected]. 0190-9622/$30.00 Copyright © 2004 by the American Academy of Dermatology, Inc. doi:10.1016/S0190-9622(03)02474-5
242
PATIENTS AND METHODS Patients Four patients with psoriatic arthritis, diagnosed according to the criteria of Bennet,6 were enrolled in this study. Patient 1. A 52-year-old man with polyarthropathy had a 13-year history of psoriasis vulgaris and psoriatic arthritis. Prior to his referral to our department he had been treated elsewhere with topical corticosteroids and tacalcitol and with systemic therapy using corticosteroids, retinoid, or cyclosporin. The systemic treatments were effective for his psoriasis; however, his arthropathy showed little improvement. On physical examination, there were a few small erythematous plaques on his navel and lower extremities. A biopsy taken from the lesion on his navel revealed hyperkeratosis, acanthosis with elongation of rete ridges, and lymphocytic infiltration in the vicinity of the capillaries in the papillary dermis. These findings were compatible with a diagnosis of psoriasis vulgaris. He suffered from severe arthralgia in his shoulder, elbow, wrist, hip, knee, and ankle joints and was unable to raise his arms; his gait was also disturbed. Patient 2. A 57-year-old woman had a 20-month history of palmoplantar pustular psoriasis and arthritis. On her palms, we noted irregularly shaped patches of erythema containing a number of pustules 1-2 mm in diameter. A biopsy specimen obtained from her left palm revealed that the intraepidermal unilocular pustule contained numerous neutrophils. Based on clinical and histopathological findings, her skin lesion was diagnosed as palmoplantar pustular psoriasis. She was unable to flex her right wrist and knee joints, raise her arms, and turn
Kanekura et al 243
J AM ACAD DERMATOL VOLUME 50, NUMBER 2
Table I. Results of GCAP therapy for psoriatic arthritis Patient No./ Age (y)/Sex
1/52/M 2/57/F 3/38/M 4/62/M
WBC (/l)
VAS
Neutrophils (%)
Neutrophils (/L)
CRP (mg/dL)
Before
After
Before
After
Before
After
Before
After
Before
After
8 10 9 8
1 1 2 2
9100 9100 7300 16100
7600 8400 6100 9800
72 63 76 80
62 54 67 78
6550 5730 5550 12800
4710 4540 4090 7640
0.52 0.74 0.87 18.0
0.20 0.36 0.21 9.20
After, 1 day after the fifth GCAP treatment; before, 1 day before the first GCAP treatment; VAS, visual analog scale of joint pain.
her head because of severe arthralgia. She also felt pain in her sternoclavicular joint. Patient 3. A 38-year-old man visited our department complaining of skin lesions on his trunk and limbs and multiple arthralgia. He had first noticed the skin lesions 15 years earlier and had suffered from joint pain for 5 months. On physical examination, irregularly-shaped erythematous scaly plaques, varying between 2 and 4 cm, were noted on his trunk and extremities. A biopsy specimen obtained from a lesion on the lower portion of his left leg showed hyperparakeratosis, the absence of a granular layer, elongation of rete ridges, and inflammatory infiltrates in the papillary dermis and the vicinity of the capillaries. Based on clinical and histopathological findings, a diagnosis of psoriasis vulgaris was made. He had arthralgia in his right elbow, right ankle, right fifth finger, and left thumb joints. Because of the joint pain, he had difficulty walking and writing. Patient 4. A 62-year-old man was referred to our department with skin lesions over his entire body and arthralgia in his ankles and finger joints. He had a 14-year history of psoriasis. Five years earlier, he developed pustular psoriasis and arthritis. He was treated with psoralen plus ultraviolet A (PUVA) therapy and systemic therapy with corticosteroids or methotrexate which produced only transient effects. Physical examination revealed numerous pustules, 1-2 mm in diameter, on irregularly-shaped erythematous patches on his trunk and limbs. He had arthralgia in his finger joints and ankles. On his first visit, he limped and could not hold a pen because of his arthralgia. GCAP therapy GCAP (from the Japan Immunoresearch Laboratories, Takasaki, Japan) is an extracorporeal-type granulocyte and monocyte apheresis unit that employs a column designed to remove pathogenic granulocytes. The column contains 220 g (3 ⫻ 104) of 2 mm-diameter cellulose acetate beads. GCAP was performed 5 times at 5-day intervals without
systemic therapy. At each treatment session, blood was drained from the cubital vein of one arm, circulated through the column, and returned to the cubital vein of the other arm. The flow rate was 30 ml/min and the duration of each circulation was 60 min. GCAP was carried out after written, informed consent was obtained; all procedures were approved by the Kagoshima University Faculty of Medicine Human Investigation Committee. The cost of GCAP treatment is approximately $1000 per session. Clinical evaluation The degree of arthralgia was assessed on a visual analog scale (VAS). Arthritis was evaluated by Tc99m bone scintigraphy. The white blood cell (WBC) count and C-reactive protein (CRP) were measured before and after GCAP therapy.
RESULTS Evaluation by VAS All 4 patients showed remarkable improvement of their arthralgia and the degree of their pain, assessed by VAS, decreased by at least 6 points (Table I). Evaluation by Tc-99m bone scintigraphy Pre-treatment bone scintigraphy showed enhanced accumulations of the radiotracer in multiple joints of patient 1 (Fig 1, A) and in the right wrist, right knee, and sternoclavicular joints of patient 2 (Fig 2, B). GCAP therapy produced a decrease in the accumulated radiotracer in the shoulder, elbow, knee, and ankle joints of patient 1 (Fig 1, B) and the right wrist and knee joints of patient 2 (Fig 2, B). In patient 4, a moderate decrease of the radiotracer in his ankle joints was observed post-treatment. Patient 3, on the other hand, manifested no significant changes; however, his arthralgia was improved remarkably. Evaluation by laboratory examinations As shown in Table I, GCAP therapy produced a decrease in the WBC, the number of neutrophils, and the level of CRP in all 4 patients.
244 Kanekura et al
J AM ACAD DERMATOL FEBRUARY 2004
Fig 1. A, Case 1. Tc-99m bone scintigraphy shows enhanced accumulations of the radiotracer in multiple joints. B, Case 1. In response to GCAP, the accumulation of the radiotracer in the shoulder, elbow, knee, and ankle joints is decreased.
Fig 2. A, Case 2. Tc-99m bone scintigraphy shows enhanced accumulations of the radiotracer in the right wrist, right knee, and sternoclavicular joints. B, Case 2. In response to GCAP, the accumulation of the radiotracer in the right wrist and knee joints is decreased.
Response of skin lesions The psoriasis vulgaris of patients 1 and 3 showed little response to GCAP therapy. On the other hand, the pustular psoriasis of patients 2 and 4 was im-
proved. The erythema and pustules of patient 2 disappeared completely. Patient 4 continued to manifest slight erythematous patches; however, his pustules disappeared after the 5th session of treatment.
J AM ACAD DERMATOL VOLUME 50, NUMBER 2
DISCUSSION GCAP is an extracorporeal-type granulocyte and monocyte apheresis unit. The GCAP column traps activated granulocytes and monocytes, effector cells of inflammation that modulate inflammation by releasing a variety of cytokines including interleukin-1 (IL-1), IL-6, IL-8, and tumor necrosis factor-␣ (TNF␣).7 Cellulose acetate beads activate and adsorb complement components and alter the expression of adhesion molecules on granulocytes.8,9 Passage through the GCAP column increases the expression of integrin Mac-1 (CD11b/CD13), a complement ligand, and decreases the expression of L-selectin.9 This altered expression of adhesion molecules is thought to result in the adhesion of granulocytes and monocytes to the activated complement components on the beads.10,11 GCAP has been used to treat ulcerative colitis2 which is often associated with pyoderma gangrenosum. We already demonstrated the beneficial effects of GCAP in patients with pyoderma gangrenosum and pustular psoriasis and suggested that GCAP may be useful for treating disorders with prominent granulocyte infiltration.4,5 Our current study demonstrated that GCAP was effective in our 4 patients with psoriatic arthritis; all manifested remarkable improvement of their arthralgia. Patient 1 was dramatically improved after the third treatment and was able to walk without difficulty, climb stairs, and raise his arms easily. This patient’s NSAID (diflofenac, 75 mg/day) was stopped after GCAP treatment. Patient 2 experienced improvement in her arthralgia after the second session of treatment. After the fifth treatment, her joint pain disappeared and she was able to turn her head, raise her arms, and sit on the floor easily. Patient 3 first felt improvement in his joint pain after the second session. After the fifth, his arthralgia improved, his gait became normal, and he was able to write again. Similarly, patient 4 showed improvement of his arthralgia and following treatment, he could walk and write without difficulty. Prior to GCAP therapy, patient 1 was treated with corticosteroids, retinoid, and cyclosporin; patient 4 with corticosteroids and methotrexate. Although these systemic treatments were ineffective, GCAP was beneficial for treating their arthritis. This observation suggests that in some patients, GCAP may be more useful for treating arthritis than conventional systemic therapies. The efficacy of another extracorporeal treatment, extracorporeal photochemotherapy (ECPC), in patients with psoriatic arthritis has been evaluated.12-15 While it produced some measurable effects, its efficacy was not dramatic and simultaneous adjuvant therapy with methotrexate, retinoid, and corticoste-
Kanekura et al 245
roids was required.12-14 In addition, the ECPC procedure was complex and time-consuming. ECPC was carried out on 2 consecutive days at 4-week intervals and in most patients, 6 or more procedures (20 weeks) were required for benefit manifestation.13,14 On the other hand, we noticed dramatic improvement in our patients’ arthritis within 25 days, and no systemic treatments were necessary. These results indicate the advantage of GCAP over ECPC. In contrast to the dramatic improvement of arthritis, the skin lesions of our 4 patients responded differently to GCAP. Psoriasis vulgaris in patients 1 and 3 did not respond to GCAP, whereas pustular psoriasis in patients 2 and 4 did. This is consistent with our earlier observation in 2 patients with pustular psoriasis.5 These results can be explained by the histopathological features of these lesions. In pustular psoriasis, pustules containing neutrophils may be the major pathological lesion. In psoriasis vulgaris, on the other hand, the presence of fewer, if any, neutrophils makes it unlikely that they played a major pathogenic role. We employed Tc-99m bone scintigraphy to assess the effect of GCAP on our patients’ arthritis. Although arthralgia was improved by GCAP in all 4 patients, only 3 manifested a decrease in the accumulated radiotracer. While Tc-99m bone scintigraphy shows the effect of inflammatory processes on bone metabolism, it may not disclose the degree of neutrophil infiltration. Further evaluation is required to determine whether Tc-99m bone scintigraphy is appropriate for assessing the effect of GCAP. Based on the treatment outcomes presented here, we suggest that GCAP, a useful treatment modality in patients with pyoderma gangrenosum4 and pustular psoriasis,5 may also benefit patients with psoriatic arthritis and other skin disorders. We thank Mitsuhiro Sekiyama, MD, Chiaki Baba, MD, Hiroshi Saruwatari, MD, Noriko Yoshii, MD, and Yuko Higashi, MD, PhD, for performing the GCAP treatments. REFERENCES 1. Camp RDR. Psoriatic arthritis. In: Champion RH, Burton JL, Ebling FJG, editors. Textbook of Dermatology. 6th ed. Cambridge: Blackwell Science; 1998. p. 1643-9. 2. Sawada K, Ohnishi K, Kosaka T, Fukui S, Yamamura M, Amano K, et al. Leukocytapheresis therapy with leukocyte removal filter for inflammatory bowel disease. J Gastroenterol 1995;30:124-7. 3. Callen JP. Pyoderma gangrenosum. Lancet 1998;351:581-5. 4. Kanekura T, Maruyama I, Kanzaki T. Granulocyte and monocyte adsorption apheresis for pyoderma gangrenosum. J Am Acad Dermatol 2002;47:320-1. 5. Kanekura 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: 329-32.
246 Kanekura et al
6. Bennet RM. Psoriatic arthritis. In: McCarty DJ, editor. Arthritis and Allied Conditions. Philadelphia: Lea & Febiger; 1979. p. 64255. 7. Nagashima M, Yoshino S, Tanaka H, Yoshida N, Kashiwagi N, Saniabadi AR. Granulocyte and monocyte apheresis suppresses symptoms of rheumatoid arthritis: a pilot study. Rheumatol Int 1998;18:113-8. 8. Lee J, Hakim RM, Fearon DT. Increased expression of the C3b receptor by neutrophils and complement activation during haemodialysis. Clin Exp Immunol 1984;56:205-14. 9. Watanabe S, Ohara M, Takase Y, Ishida H, Kasukawa R. Modulation of adhesion molecules and carbohydrate antigens on granulocytes of patients with rheumatoid arthritis treated with granulo-monocytapheresis. Jpn J Rheumatol 1996;6:253-64. 10. Ishida H, Ohara M, Watanabe S, Takase Y, Kasukawa R. Treatment of rheumatoid arthritis by granulo-monocytapheresis. Jpn J Rheumatol 1996;6:113-24.
J AM ACAD DERMATOL FEBRUARY 2004
11. Sawada K, Ohnishi K, Kosaka T, Chikano S, Yokota Y, Egashira A, et al. Leukocytapheresis with leukocyte removal filter as new therapy for ulcerative colitis. Ther Apher 1997;1:207-11. 12. Wilfert H, Honigsmann H, Steiner G, Smolen J, Wolff K. Treatment of psoriatic arthritis by extracorporeal photochemotherapy. Br J Dermatol 1990;122:225-32. 13. de Misa RF, Azana JM, Harto A, Ledo A. Extracorporeal photochemotherapy in the treatment of severe psoriatic arthropathy. Br J Dermatol 1992;127:448. 14. de Misa RF, Azana JM, Harto A, Boixeda P, Moreno R, Ledo A. Psoriatic arthritis: one year of treatment with extracorporeal photochemotherapy. J Am Acad Dermatol 1994;30:1037-8. 15. Vahlquist C, Larsson M, Ernerudh J, Berlin G, Skogh T, Vahlquist A. Treatment of psoriatic arthritis with extracorporeal photochemotherapy and conventional psoralen-ultraviolet A irradiation. Arthritis Rheum 1996;39:1519-23.
P
soriatic arthritis is an inflammatory disorder of the systemic joints characterized by its association with psoriasis.1 Arthralgia is the major complaint of patients with this disorder, and various systemic treatments, including the administration of retinoids, cyclosporin, nonsteroidal anti-inflammatory drugs (NSAIDs), methotrexate, and corticosteroids, are only partially successful. Granulocyte and monocyte adsorption apheresis (GCAP) has been used to treat ulcerative colitis2 which is often associated with pyoderma gangrenosum.3 We previously reported that GCAP was remarkably effective in patients with pyoderma gangrenosum.4 Therefore, we speculated that it may also be useful for treating other disorders with prominent granulocytic infiltration and demonstrated that pustular psoriasis was improved after GCAP treatment.5 We now report 4 patients with psoriatic arthritis whose severe arthritis responded well to GCAP.
From the Department of Dermatologya and the Laboratory of Molecular Medicine,b Kagoshima University Faculty of Medicine. The GCAP columns used in this study were provided by Japan Immunoresearch Laboratories, Takasaki, Japan. Conflict of interest: None identified. Reprint requests: Takuro Kanekura, MD, PhD, Department of Dermatology, Kagoshima University Faculty of Medicine, 8-35-1 Sakuragaoka, Kagoshima 890-8520, Japan. E-mail: [email protected]. 0190-9622/$30.00 Copyright © 2004 by the American Academy of Dermatology, Inc. doi:10.1016/S0190-9622(03)02474-5
242
PATIENTS AND METHODS Patients Four patients with psoriatic arthritis, diagnosed according to the criteria of Bennet,6 were enrolled in this study. Patient 1. A 52-year-old man with polyarthropathy had a 13-year history of psoriasis vulgaris and psoriatic arthritis. Prior to his referral to our department he had been treated elsewhere with topical corticosteroids and tacalcitol and with systemic therapy using corticosteroids, retinoid, or cyclosporin. The systemic treatments were effective for his psoriasis; however, his arthropathy showed little improvement. On physical examination, there were a few small erythematous plaques on his navel and lower extremities. A biopsy taken from the lesion on his navel revealed hyperkeratosis, acanthosis with elongation of rete ridges, and lymphocytic infiltration in the vicinity of the capillaries in the papillary dermis. These findings were compatible with a diagnosis of psoriasis vulgaris. He suffered from severe arthralgia in his shoulder, elbow, wrist, hip, knee, and ankle joints and was unable to raise his arms; his gait was also disturbed. Patient 2. A 57-year-old woman had a 20-month history of palmoplantar pustular psoriasis and arthritis. On her palms, we noted irregularly shaped patches of erythema containing a number of pustules 1-2 mm in diameter. A biopsy specimen obtained from her left palm revealed that the intraepidermal unilocular pustule contained numerous neutrophils. Based on clinical and histopathological findings, her skin lesion was diagnosed as palmoplantar pustular psoriasis. She was unable to flex her right wrist and knee joints, raise her arms, and turn
Kanekura et al 243
J AM ACAD DERMATOL VOLUME 50, NUMBER 2
Table I. Results of GCAP therapy for psoriatic arthritis Patient No./ Age (y)/Sex
1/52/M 2/57/F 3/38/M 4/62/M
WBC (/l)
VAS
Neutrophils (%)
Neutrophils (/L)
CRP (mg/dL)
Before
After
Before
After
Before
After
Before
After
Before
After
8 10 9 8
1 1 2 2
9100 9100 7300 16100
7600 8400 6100 9800
72 63 76 80
62 54 67 78
6550 5730 5550 12800
4710 4540 4090 7640
0.52 0.74 0.87 18.0
0.20 0.36 0.21 9.20
After, 1 day after the fifth GCAP treatment; before, 1 day before the first GCAP treatment; VAS, visual analog scale of joint pain.
her head because of severe arthralgia. She also felt pain in her sternoclavicular joint. Patient 3. A 38-year-old man visited our department complaining of skin lesions on his trunk and limbs and multiple arthralgia. He had first noticed the skin lesions 15 years earlier and had suffered from joint pain for 5 months. On physical examination, irregularly-shaped erythematous scaly plaques, varying between 2 and 4 cm, were noted on his trunk and extremities. A biopsy specimen obtained from a lesion on the lower portion of his left leg showed hyperparakeratosis, the absence of a granular layer, elongation of rete ridges, and inflammatory infiltrates in the papillary dermis and the vicinity of the capillaries. Based on clinical and histopathological findings, a diagnosis of psoriasis vulgaris was made. He had arthralgia in his right elbow, right ankle, right fifth finger, and left thumb joints. Because of the joint pain, he had difficulty walking and writing. Patient 4. A 62-year-old man was referred to our department with skin lesions over his entire body and arthralgia in his ankles and finger joints. He had a 14-year history of psoriasis. Five years earlier, he developed pustular psoriasis and arthritis. He was treated with psoralen plus ultraviolet A (PUVA) therapy and systemic therapy with corticosteroids or methotrexate which produced only transient effects. Physical examination revealed numerous pustules, 1-2 mm in diameter, on irregularly-shaped erythematous patches on his trunk and limbs. He had arthralgia in his finger joints and ankles. On his first visit, he limped and could not hold a pen because of his arthralgia. GCAP therapy GCAP (from the Japan Immunoresearch Laboratories, Takasaki, Japan) is an extracorporeal-type granulocyte and monocyte apheresis unit that employs a column designed to remove pathogenic granulocytes. The column contains 220 g (3 ⫻ 104) of 2 mm-diameter cellulose acetate beads. GCAP was performed 5 times at 5-day intervals without
systemic therapy. At each treatment session, blood was drained from the cubital vein of one arm, circulated through the column, and returned to the cubital vein of the other arm. The flow rate was 30 ml/min and the duration of each circulation was 60 min. GCAP was carried out after written, informed consent was obtained; all procedures were approved by the Kagoshima University Faculty of Medicine Human Investigation Committee. The cost of GCAP treatment is approximately $1000 per session. Clinical evaluation The degree of arthralgia was assessed on a visual analog scale (VAS). Arthritis was evaluated by Tc99m bone scintigraphy. The white blood cell (WBC) count and C-reactive protein (CRP) were measured before and after GCAP therapy.
RESULTS Evaluation by VAS All 4 patients showed remarkable improvement of their arthralgia and the degree of their pain, assessed by VAS, decreased by at least 6 points (Table I). Evaluation by Tc-99m bone scintigraphy Pre-treatment bone scintigraphy showed enhanced accumulations of the radiotracer in multiple joints of patient 1 (Fig 1, A) and in the right wrist, right knee, and sternoclavicular joints of patient 2 (Fig 2, B). GCAP therapy produced a decrease in the accumulated radiotracer in the shoulder, elbow, knee, and ankle joints of patient 1 (Fig 1, B) and the right wrist and knee joints of patient 2 (Fig 2, B). In patient 4, a moderate decrease of the radiotracer in his ankle joints was observed post-treatment. Patient 3, on the other hand, manifested no significant changes; however, his arthralgia was improved remarkably. Evaluation by laboratory examinations As shown in Table I, GCAP therapy produced a decrease in the WBC, the number of neutrophils, and the level of CRP in all 4 patients.
244 Kanekura et al
J AM ACAD DERMATOL FEBRUARY 2004
Fig 1. A, Case 1. Tc-99m bone scintigraphy shows enhanced accumulations of the radiotracer in multiple joints. B, Case 1. In response to GCAP, the accumulation of the radiotracer in the shoulder, elbow, knee, and ankle joints is decreased.
Fig 2. A, Case 2. Tc-99m bone scintigraphy shows enhanced accumulations of the radiotracer in the right wrist, right knee, and sternoclavicular joints. B, Case 2. In response to GCAP, the accumulation of the radiotracer in the right wrist and knee joints is decreased.
Response of skin lesions The psoriasis vulgaris of patients 1 and 3 showed little response to GCAP therapy. On the other hand, the pustular psoriasis of patients 2 and 4 was im-
proved. The erythema and pustules of patient 2 disappeared completely. Patient 4 continued to manifest slight erythematous patches; however, his pustules disappeared after the 5th session of treatment.
J AM ACAD DERMATOL VOLUME 50, NUMBER 2
DISCUSSION GCAP is an extracorporeal-type granulocyte and monocyte apheresis unit. The GCAP column traps activated granulocytes and monocytes, effector cells of inflammation that modulate inflammation by releasing a variety of cytokines including interleukin-1 (IL-1), IL-6, IL-8, and tumor necrosis factor-␣ (TNF␣).7 Cellulose acetate beads activate and adsorb complement components and alter the expression of adhesion molecules on granulocytes.8,9 Passage through the GCAP column increases the expression of integrin Mac-1 (CD11b/CD13), a complement ligand, and decreases the expression of L-selectin.9 This altered expression of adhesion molecules is thought to result in the adhesion of granulocytes and monocytes to the activated complement components on the beads.10,11 GCAP has been used to treat ulcerative colitis2 which is often associated with pyoderma gangrenosum. We already demonstrated the beneficial effects of GCAP in patients with pyoderma gangrenosum and pustular psoriasis and suggested that GCAP may be useful for treating disorders with prominent granulocyte infiltration.4,5 Our current study demonstrated that GCAP was effective in our 4 patients with psoriatic arthritis; all manifested remarkable improvement of their arthralgia. Patient 1 was dramatically improved after the third treatment and was able to walk without difficulty, climb stairs, and raise his arms easily. This patient’s NSAID (diflofenac, 75 mg/day) was stopped after GCAP treatment. Patient 2 experienced improvement in her arthralgia after the second session of treatment. After the fifth treatment, her joint pain disappeared and she was able to turn her head, raise her arms, and sit on the floor easily. Patient 3 first felt improvement in his joint pain after the second session. After the fifth, his arthralgia improved, his gait became normal, and he was able to write again. Similarly, patient 4 showed improvement of his arthralgia and following treatment, he could walk and write without difficulty. Prior to GCAP therapy, patient 1 was treated with corticosteroids, retinoid, and cyclosporin; patient 4 with corticosteroids and methotrexate. Although these systemic treatments were ineffective, GCAP was beneficial for treating their arthritis. This observation suggests that in some patients, GCAP may be more useful for treating arthritis than conventional systemic therapies. The efficacy of another extracorporeal treatment, extracorporeal photochemotherapy (ECPC), in patients with psoriatic arthritis has been evaluated.12-15 While it produced some measurable effects, its efficacy was not dramatic and simultaneous adjuvant therapy with methotrexate, retinoid, and corticoste-
Kanekura et al 245
roids was required.12-14 In addition, the ECPC procedure was complex and time-consuming. ECPC was carried out on 2 consecutive days at 4-week intervals and in most patients, 6 or more procedures (20 weeks) were required for benefit manifestation.13,14 On the other hand, we noticed dramatic improvement in our patients’ arthritis within 25 days, and no systemic treatments were necessary. These results indicate the advantage of GCAP over ECPC. In contrast to the dramatic improvement of arthritis, the skin lesions of our 4 patients responded differently to GCAP. Psoriasis vulgaris in patients 1 and 3 did not respond to GCAP, whereas pustular psoriasis in patients 2 and 4 did. This is consistent with our earlier observation in 2 patients with pustular psoriasis.5 These results can be explained by the histopathological features of these lesions. In pustular psoriasis, pustules containing neutrophils may be the major pathological lesion. In psoriasis vulgaris, on the other hand, the presence of fewer, if any, neutrophils makes it unlikely that they played a major pathogenic role. We employed Tc-99m bone scintigraphy to assess the effect of GCAP on our patients’ arthritis. Although arthralgia was improved by GCAP in all 4 patients, only 3 manifested a decrease in the accumulated radiotracer. While Tc-99m bone scintigraphy shows the effect of inflammatory processes on bone metabolism, it may not disclose the degree of neutrophil infiltration. Further evaluation is required to determine whether Tc-99m bone scintigraphy is appropriate for assessing the effect of GCAP. Based on the treatment outcomes presented here, we suggest that GCAP, a useful treatment modality in patients with pyoderma gangrenosum4 and pustular psoriasis,5 may also benefit patients with psoriatic arthritis and other skin disorders. We thank Mitsuhiro Sekiyama, MD, Chiaki Baba, MD, Hiroshi Saruwatari, MD, Noriko Yoshii, MD, and Yuko Higashi, MD, PhD, for performing the GCAP treatments. REFERENCES 1. Camp RDR. Psoriatic arthritis. In: Champion RH, Burton JL, Ebling FJG, editors. Textbook of Dermatology. 6th ed. Cambridge: Blackwell Science; 1998. p. 1643-9. 2. Sawada K, Ohnishi K, Kosaka T, Fukui S, Yamamura M, Amano K, et al. Leukocytapheresis therapy with leukocyte removal filter for inflammatory bowel disease. J Gastroenterol 1995;30:124-7. 3. Callen JP. Pyoderma gangrenosum. Lancet 1998;351:581-5. 4. Kanekura T, Maruyama I, Kanzaki T. Granulocyte and monocyte adsorption apheresis for pyoderma gangrenosum. J Am Acad Dermatol 2002;47:320-1. 5. Kanekura 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: 329-32.
246 Kanekura et al
6. Bennet RM. Psoriatic arthritis. In: McCarty DJ, editor. Arthritis and Allied Conditions. Philadelphia: Lea & Febiger; 1979. p. 64255. 7. Nagashima M, Yoshino S, Tanaka H, Yoshida N, Kashiwagi N, Saniabadi AR. Granulocyte and monocyte apheresis suppresses symptoms of rheumatoid arthritis: a pilot study. Rheumatol Int 1998;18:113-8. 8. Lee J, Hakim RM, Fearon DT. Increased expression of the C3b receptor by neutrophils and complement activation during haemodialysis. Clin Exp Immunol 1984;56:205-14. 9. Watanabe S, Ohara M, Takase Y, Ishida H, Kasukawa R. Modulation of adhesion molecules and carbohydrate antigens on granulocytes of patients with rheumatoid arthritis treated with granulo-monocytapheresis. Jpn J Rheumatol 1996;6:253-64. 10. Ishida H, Ohara M, Watanabe S, Takase Y, Kasukawa R. Treatment of rheumatoid arthritis by granulo-monocytapheresis. Jpn J Rheumatol 1996;6:113-24.
J AM ACAD DERMATOL FEBRUARY 2004
11. Sawada K, Ohnishi K, Kosaka T, Chikano S, Yokota Y, Egashira A, et al. Leukocytapheresis with leukocyte removal filter as new therapy for ulcerative colitis. Ther Apher 1997;1:207-11. 12. Wilfert H, Honigsmann H, Steiner G, Smolen J, Wolff K. Treatment of psoriatic arthritis by extracorporeal photochemotherapy. Br J Dermatol 1990;122:225-32. 13. de Misa RF, Azana JM, Harto A, Ledo A. Extracorporeal photochemotherapy in the treatment of severe psoriatic arthropathy. Br J Dermatol 1992;127:448. 14. de Misa RF, Azana JM, Harto A, Boixeda P, Moreno R, Ledo A. Psoriatic arthritis: one year of treatment with extracorporeal photochemotherapy. J Am Acad Dermatol 1994;30:1037-8. 15. Vahlquist C, Larsson M, Ernerudh J, Berlin G, Skogh T, Vahlquist A. Treatment of psoriatic arthritis with extracorporeal photochemotherapy and conventional psoralen-ultraviolet A irradiation. Arthritis Rheum 1996;39:1519-23.