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Keywords:

  • Arthropathy;
  • Granulocyte and monocyte adsorption apheresis;
  • Mac-1;
  • Multi-centered study;
  • Neutrophilic dermatosis

Abstract

  1. Top of page
  2. Abstract
  3. Patients and Methods
  4. Results
  5. Discussion
  6. Conclusion
  7. References

Granulocyte and monocyte adsorption apheresis (GMA), an extracorporeal apheresis instrument whose column contains cellulose acetate (CA) beads, is designed to remove activated granulocytes and monocytes. We previously demonstrated that GMA was useful for treating neutrophilic dermatoses and associated arthropathy as it adsorbs Mac-1 (CD11b/CD18)-expressing neutrophils to the CA beads by the binding of complement component (iC3b) and CD11b expressed on activated neutrophils. The objective of this study is to further assess the clinical effectiveness of GMA in the treatment of neutrophilic dermatoses and associated arthropathy. The effect of GMA for skin lesions and joint lesions was assessed in 44 and 23 patients, respectively. Mac-1 expression on peripheral neutrophils was measured by flow cytometry. Skin lesions and arthropathy improved in 39 of 44 patients (88.6%) and 22 of 23 (95.6%), respectively. Mac-1 (CD11b/CD18) expression on the peripheral neutrophils, 27.1 ± 6.66 MFI (mean fluorescence intensity) before treatment, was reduced to 17.9 ± 3.02 MFI by GMA (P < 0.05). Clinical effectiveness of GMA for the treatment of intractable neutrophilic dermatoses and associated arthropathy was further confirmed.

Granulocyte and monocyte adsorption apheresis (GMA) is an extracorporeal apheresis instrument designed to remove pathogenic granulocytes. It features a column containing cellulose acetate (CA) beads [1, 2]. Our previous clinical studies on the efficacy of GMA for treating various skin diseases and related arthropathy attributable to activated granulocytes yielded excellent results in patients with pyoderma gangrenosum (PG), pustular psoriasis (PP), psoriatic arthritis (PsA), Behçet's disease (BD), adult Still's disease, leg ulcers associated with rheumatoid arthritis, cutaneous allergic vasculitis (CAV), Reiter's disease (RD), and systemic lupus erythematosus (SLE) skin rash [3-12].

Activated granulocytes express Mac-1, a cell-surface adhesive molecule that belongs to the integrin family [13]. CD11b (integrin αM subunit) combines with CD18 (integrin β2 subunit) to form Mac-1 [14, 15], known as complement receptor 3 (CR3) [16, 17]. The CA beads in the GMA column activate and adsorb complement component iC3b, a ligand for Mac-1 [2, 18]. Based on these facts, we previously demonstrated that the column traps activated granulocytes by binding Mac-1 expressed on the granulocytes to iC3b on the beads [19].

In the present study, we assessed the efficacy of GMA in 44 patients with various skin diseases and 23 patients with arthropathy attributable to activated granulocytes.

Patients and Methods

  1. Top of page
  2. Abstract
  3. Patients and Methods
  4. Results
  5. Discussion
  6. Conclusion
  7. References

Patients

We enrolled 44 patients in this study. Of these patients, 18 had PP (four generalized and 14 palmoplantar form), five had PsA, one had psoriasis vulgaris (PV), nine had BD, and six had PG. The other five patients had RD, acrodermatitis continua of Hallopeau, CAV, Sweet's syndrome, and erythema nodosum (EN). Arthropathy was associated in 23 patients. Of 23 patients with arthropathy, 11 had PP (one generalized and 10 palmoplantar form), five had PsA, and four had BD. The other three patients had RD, CAV, and Sweet's syndrome (Table 1).

Table 1. Patients treated with granulocyte and monocyte adsorption apheresis therapy
Patient no.Age/SexDiagnosisSite of skin lesionsAffected jointsConcomitant medications and their duration prior to GMA
  1. Rt., right; Lt., left; (–), absence of lesions.

 159/FPustular psoriasisFace, trunk, arms, legsRt. shoulder joint, sternoclavicular joint, waist, rt. wrist joints, knee joints, toe jointsMethotrexate (2 mg) 2–1 cap/day 4 days, loxoprofen (60) 3 tab/day 1 week
 239/MPustular psoriasisTrunk, arms, legsnb- UVB, PUVA, CyA 150–100 mg/day, 9 months
 351/FPustular psoriasisArms, legs, buttocksPrednisolone pulse, prednisolone p.o, Etretinate, PUVA-bath, DDS, Colchicine
 437/FPustular psoriasisTrunk, arms, legsNone
 535/MPalmoplantar pustulosis + ArthropathyPalms, solesShoulder joints, sternoclavicular joint, waist, rt. IliumAcetaminophen (60 mg) 1tab, diclofenac sodium (25 mg) 1tab, single use
 677/FPalmoplantar pustulosisArms, legs, palms, solesNone
 738/FPalmoplantar pustulosis + ArthropathyPalms, solesSternoclavicular joint, hip joint, finger jointLoxsoprofen (60 mg) 1 tab, Single Use
 857/FPalmoplantar pustulosisPalms, solesPUVA, 3 months
 962/MPalmoplantar pustulosisSolesnb-UVB 2 years
1050/FPalmoplantar pustulosis + ArthropathyPalms, soleslt. shoulder joint, sternoclavicular joint, elbow joints, wrist jointsNone
1152/FPalmoplantar pustulosis + ArthropathyLt. soleShoulder joints, knee joints, wrist joints, ankle jointsCyA (100 mg) 3 years
1238/MPalmoplantar pustulosisPalms, solesNone
1358/MPalmoplantar pustulosis + ArthropathyPalms, solesSternoclavicular jointNone
1439/MPalmoplantar pustulosis + ArthropathyPalms, solesSternoclavicular joint, waistBiotin, PUVA, mynocycline, loxsoprofen (60 mg) 3 tab/day, 1 month
1558/FPalmoplantar pustulosis + ArthropathyLegs, palms, solesRt. ankle jointBiotin
1656/FPalmoplantar pustulosis + ArthropathyPalms, solesShoulder joints, sternoclavicular joint, waist, wrist joints, lt. finger joint, toe jointsMynocycline (100 mg), loxsoprofen (60 mg) 1tab, single use
1761/FPalmoplantar pustulosis + ArthropathyPalms, solesShoulder joints, sternoclavicular joint, wrist joints, finger joints, waist, hip joints, knee joints, ankle jointsPUVA, etretinate 30–10 mg/day, 6 months
1858/MPalmoplantar pustulosis + ArthropathyPalms, solesShoulder joints, elbow joints, waist, knee jointsLoxsoprofen (60 mg) 1 tab, acetaminophen (100 mg) 1 tab, single use
1967/MPsoriatic arthropathyTrunk, arms, legswrist joints, knee jointsNone
2024/MPsoriatic arthropathyArmsFinger joints, toe joint, lt. heelLoxoprofen (60 mg) 1 tab, single use
2126/MPsoriatic arthropathyLegsRt. shoulder joint, sternoclavicular joint, wrist joints, finger joints, ankle joints, toe jointsNone
2245/MPsoriatic arthropathyTrunk, arms, legs, buttocksKnee joints, toe joints, rt. finger jointsMeloxicam (10 mg) 1 cap, single use, loxoprofen (60 mg) 3-1tab/day, 4 years
2356/MPsoriatic arthropathyCubital fossa, palms, soles, handsNeck, knee joints, finger joints, toe joints, rt. heelLoxoprofen (60 mg) 3tab/day, 4 weeks
2451/MPsoriasis vulgarisTrunk, arms, legs, buttocksCyA, Etretinate, PUVA, nb-UVB
2536/FBehçet's diseaseLip, tongueMefenamic acid (250 mg) 1cap/day 5 months, loxoprofen (60 mg) 3tab/day 6 months,
2656/FBehçet's diseaseRt. labia minora, oral cavityLoxoprofen (60 mg) 1 tab, single use
2723/FBehçet's diseaseLt. labia majora, oral cavityLoxoprofen (60 mg) 3 tab/day 2 weeks
2836/FBehçet's diseaseRt. labia minora, oral cavityLt. knee jointColchicine (0.5 mg) 2 tab/day 1 year, loxoprofen (60 mg) 1 tab, single use
2918/FBehçet's diseaseOral cavity, back of hands, legsKnee joints, lt. elbow jointLoxoprofen (60 mg) 3–2 tab/day 9 months
3025/FBehçet's diseaseRt. labia majora, oral cavity, lipNone
3138/FBehçet's diseaseLip, oral cavityLt. knee joint, lt hip jointColchicine (0.5 mg) 2 tab/day 2 years
3239/FBehçet's diseaseLt. labia majoraLt. knee joint, lt. elbow jointPrednisolone 30–10 mg/day, 6 months, Colchicine (0.5 mg) 2 tab/day 6 months
3374/MBehçet's diseasePerianalLoxoprofen (60 mg) 1tab, single use
3437/MPyoderma gangrenosumBilateral axillae, back, buttocksNone
3537/MPyoderma gangrenosumaround artificial anusNone
3649/MPyoderma gangrenosumRt. lower legNone
3776/MPyoderma gangrenosumRt. lower legsNone
3821/MPyoderma gangrenosumNeck, face, trunkDapsone (25 mg) 3T/day, 1 month, PSL (5) 6T-3T/day, 6 months
3927/FPyoderma gangrenosumLower legsNone
4073/MReiter's diseasePenis, scrotum, rt. groin, rt. hand, rt. arm, rt. chestShoulder joints, elbow joints, waist, knee jointsDiclofenac (25 mg) suppository 1 tab, single use
4121/FAcrodermatitis continua of HallopeauPalms, fingersPUVA, CyA 250 mg/day, 7 days
4234/MCutaneous allergic vasculitisArms, legsAnkle jointsPrednisolone 20–10 mg/day, sporadically.
4365/MSweet's syndromeBack, lt. palm, lt. kneeLt. shoulder, waist, hip joints, lt. kneeLoxoprofen (60) 1tab, single use
4466/MErythema nodosumRt. leg, knees, rt. armCefotaxime

GMA

Granulocyte and monocyte adsorption apheresis is an extracorporeal-type apheresis unit that uses a column containing 3 × 104 pieces of 2 mm-diameter cellulose acetate beads. In the current series, GMA was performed 5 or 10 times at 5-day intervals. If the lesion showed amelioration but persisted at the completion of the 5th treatment, five more treatment sessions were added. In each session, 1800 mL of blood are drained from the cubital vein of one arm, passed at a flow rate of 30 mL/min through the GMA column, and returned to the cubital vein of the other arm. The GMA column, its circuit lines, and circuit system consisting of a regular dialysis circuit and a pump, were provided by Japan Immunoresearch Laboratories (Takasaki, Japan). GMA was performed without adding any other systemic remedy; in patients who already received medication, the dose was left unchanged. Concomitant medications and their duration prior to GMA are shown in Table 1. GMA was carried out after obtaining the prior written informed consent of all participants. All procedures conducted in GMA therapy were approved by the Human Investigation Committee of Kagoshima University Graduate School of Medical and Dental Sciences.

Clinical and laboratory evaluation

The severity of the patients' skin lesions was evaluated clinically based on overall lesional assessment (OLA) [20] and recorded on a 5-point scale where 0 = none, 1 = slight, 2 = mild, 3 = moderate, and 4 = severe. For OLA, we considered plaque elevation, erythema, and scaling for PV and PsA; pustules, erythema, and scaling for PP, Reiter's disease, and acrodermatitis continua; area and depth of ulcerations, granulation, and pain for pyoderma gangrenosum, Behçet's disease, and cutaneous allergic vasculitis (CAV); erythema, induration, and tenderness for Sweet's syndrome and erythema nodosum (EN). The response to treatment was rated as excellent in patients who improved by four grades (e.g. grade 4 to grade 0), as good when they improved by two or three grades, and as moderate when improvement was by a single grade; no change and exacerbation were also recorded. All clinical evaluations were made by three independent physicians; if their assessments differed, the median value of their judgment was recorded as the treatment outcome.

The degree of arthropathy, assessed by the patients based on joint pain, the number of affected joints, and the range of joint motion, was represented on a 10-cm visual analog scale (VAS). Treatment responses were recorded as excellent, good, and moderate when the VAS score was 20% or less, 50% or less, and 90% or less, respectively, of the baseline score, or as no change or exacerbation.

The white blood cell (WBC) count, neutrophil count, and C-reactive protein (CRP) were measured before starting GMA therapy and one day after the last treatment session.

Measurement of Mac-1 expression

Flow cytometric analysis of the expression of Mac-1 (integrin CD11b/CD18) on peripheral neutrophils from patients was performed using whole blood and mouse anti-human CD11b antibody (Immunotech, Marseille, France), which is not a blocking antibody, according to the manufacturer's instructions (Beckman Coulter, Fullerton, CA, USA). Briefly, after 30-min incubation of 50 μL of sodium citrate-anticoagulated whole blood with 10 μL of mouse anti-human CD11b antibody, 250 μL of lysis buffer (OptiLyse C; Beckman Coulter) were added. The mixture was incubated for 10 min, 250 μL phosphate-buffered saline (PBS) were added and this was followed by another 15-min incubation. Cells were pelleted by centrifugation at 400 × g for 5 min and analyzed for CD11b expression using an EPICS flow cytometer (Beckman Coulter). All incubations were at room temperature in the dark. Granulocytes were identified by gating on a biparametric histogram represented with side and forward scatter. Mac-1 expression was measured before starting GMA therapy and one day after the last treatment session.

Statistical analysis

For comparison of the WBC count, neutrophil count, CRP, and Mac-1 expression before and after treatment, Tukey–Kramer's method was used. The results are shown as the mean ± standard error (SE). A difference of P < 0.05 was considered significant.

Results

  1. Top of page
  2. Abstract
  3. Patients and Methods
  4. Results
  5. Discussion
  6. Conclusion
  7. References

Response of skin lesions to GMA therapy

We evaluated the skin lesions of 44 patients enrolled in this study. Excellent response was observed in 13 patients; five with PP, three with PG, two with PsA, two with BD, and one with CAV. Good and moderate responses were obtained in 17 and nine patients, respectively. The lesions in five patients (two with PP, two with BD, one with acrodermatitis continua of Hallopeau), were unchanged. In 39 of the 44 evaluated patients (88.6%), the skin lesions showed improvement by GMA therapy (Tables 2, 3).

Table 2. Treatment outcome in patients treated with granulocyte and monocyte adsorption apheresis therapy
Patient no.Age/SexDiagnosisTreatment sessionsVAS Before/AfterResponse of skin lesionsResponse of arthropathyMac-1 (MFI) Before/After
  1. After, one day after the last granulocyte and monocyte adsorption apheresis treatment session; Before, one day before the first granulocyte and monocyte adsorption apheresis treatment session; MFI, mean fluorescence intensity; n.a., not applicable because ofthe absence of lesions; n.d., not done; VAS, visual analog scale.

 159/FPustular psoriasis108/0ExcellentExcellent18.2/14.4
 239/MPustular psoriasis5n.a.Goodn.a.22.1/14.2
 351/FPustular psoriasis5n.a.Excellentn.a.71.7/25.2
 437/FPustular psoriasis5n.a.Excellentn.a.14.8/22.7
 535/MPalmoplantar pustulosis + Arthropathy108/4ModerateGood120.6/29.0
 677/FPalmoplantar pustulosis5n.a.Unchangedn.a.n.d.
 738/FPalmoplantar pustulosis + Arthropathy53/2ModerateModerate10.9/7.5
 857/FPalmoplantar pustulosis5n.a.Moderaten.a.38.0/8.0
 962/MPalmoplantar pustulosis5n.a.Goodn.a.18.5/11.9
1050/FPalmoplantar pustulosis + Arthropathy53/1ExcellentGood36.5/15.9
1152/FPalmoplantar pustulosis + Arthropathy53/1GoodGood55.9/41.9
1238/MPalmoplantar pustulosis5n.a.Goodn.a.8.3/8.4
1358/MPalmoplantar pustulosis + Arthropathy52/0GoodExcellent11.8/10.3
1439/MPalmoplantar pustulosis + Arthropathy59/6UnchangedModerate15.3/15.2
1558/FPalmoplantar pustulosis + Arthropathy54/1GoodGood35.3/37.2
1656/FPalmoplantar pustulosis + Arthropathy103/1GoodGood42.8/29.2
1761/FPalmoplantar pustulosis + Arthropathy106/1GoodGood42.4/23.6
1858/MPalmoplantar pustulosis + Arthropathy510/3ExcellentGood21.9/12.4
1967/MPsoriatic arthropathy107/5ModerateModerate19.9/3.0
2024/MPsoriatic arthropathy57/1ExcellentExcellent12.5/11.6
2126/MPsoriatic arthropathy54/0GoodExcellent97.0/30.6
2245/MPsoriatic arthropathy103/2ExcellentGood16.4/24.2
2356/MPsoriatic arthropathy58/6ModerateModerate52.4/11.1
2451/MPsoriasis vulgaris5n.a.Goodn.a.23.3/13.3
2536/FBehçet's disease10n.a.Moderaten.a.26.2/26.6
2656/FBehçet's disease5n.a.Goodn.a.15.8/18.3
2723/FBehçet's disease5n.a.Unchangedn.a.27.1/19.7
2836/FBehçet's disease54/0GoodExcellentn.d.
2918/FBehçet's disease56/3ModerateExcellentn.d.
3025/FBehçet's disease5n.a.Goodn.a.22.8/11.3
3138/FBehçet's disease56/1ExcellentExcellent9.1/13.5
3239/FBehçet's disease54/0ExcellentExcellent17.6/13.1
3374/MBehçet's disease5n.a.Unchangedn.a.20.0/12.0
3437/MPyoderma gangrenosum10n.a.Goodn.a.9.2/9.4
3537/MPyoderma gangrenosum10n.a.Excellentn.a.49.7/12.4
3649/MPyoderma gangrenosum10n.a.Excellentn.a.6.8/14.2
3776/MPyoderma gangrenosum5n.a.Moderaten.a.21.1/20.1
3821/MPyoderma gangrenosum5n.a.Moderaten.a.14.9/10.6
3927/FPyoderma gangrenosum10n.a.Excellentn.a.8.6/8.2
4073/MReiter's disease58/2GoodGood24.0/8.0
4121/FAcrodermatitis continua of Hallopeau5n.aUnchangedn.a.40.7/18.6
4234/MCutaneous allergic vasculitis55/0ExcellentExcellentn.d.
4365/MSweet' s syndrome510/9GoodUnchanged24.7/3.1
4466/MErythema nodosum5n.a.Goodn.a.26.9/24.2
Table 3. Response of skin lesions and arthropathy to granulocyte and monocyte adsorption apheresis therapy
 ExcellentGoodModerateUnchanged
Skin lesions    
Palmoplantar pustulosis (N = 14)2732
Behçet's disease (N = 9)2322
Pyoderma gangrenosum (N = 6)312 
Psoriatic arthropathy (N = 5)212 
Pustular psoriasis (N = 4)31  
Sweet's syndrome (N = 1) 1  
Psoriasis vulgaris (N = 1) 1  
Reiter's disease (N = 1) 1  
Erythema nodosum (N = 1) 1  
Cutaneous allergic vasculitis (N = 1)1   
Acrodermatitis continua of Hallopeau (N = 1)   1
Total (N = 44)131795
Arthropathy    
Palmoplantar pustulosis (N = 10)172 
Psoriatic arthropathy (N = 5)212 
Behçet's disease (N = 4)4   
Pustular psoriasis (N = 1)1   
Cutaneous allergic vasculitis (N = 1)1   
Reiter's disease (N = 1) 1  
Sweet's syndrome (N = 1)   1
Total (N = 23)9941

Representative patients are shown in Figure 1. Patient #4 with generalized PP had irregularly-shaped erythematous lesions with numerous pustules on her trunk and extremities. They had appeared 2 months prior to her visit to our department. The lesions showed dramatic improvement after the first treatment and completely disappeared after the fifth treatment (Fig. 1a). PG in patient #39, which manifested as multiple and painful ulcers on her lower legs, had become exacerbated 2 months before GMA therapy and subsided after 10 treatment sessions (Fig. 1b).

figure

Figure 1. Skin lesions before and after granulocyte and monocyte adsorption apheresis (GMA) treatment. (a) Patient # 4; pustular psoriasis (PP): Irregularly-shaped erythematous lesions with numerous pustules on her trunk and extremities showed dramatic improvement after the first treatment and completely disappeared after the 5th treatment session. (b) Patient #39; pyoderma gangrenosum (PG): Multiple ulcers on her legs had subsided after 10 treatment sessions.

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Response of arthropathy to GMA therapy

Arthropathy was evaluated in 23 patients. An excellent response was obtained in nine patients; four with BD, two with PP, two with PsA, and one with CAV. Good and moderate responses were observed in nine and four patients, respectively. The arthropathy of one patient with Sweet's syndrome remained unchanged. Overall, arthropathy improved in 22 of the 23 patients (95.6%) (Tables 2, 3).

Laboratory examinations

The mean values of the WBC and neutrophil count, CRP, and Mac-1 expression level before starting GMA therapy were 7664 ± 728/μL, 5110 ± 702/μL, 2.17 ± 1.26 mg/dL, and 27.1 ± 6.66 MFI (mean fluorescence intensity), respectively. They decreased to 6674 ± 632/μL, 4178 ± 494/μL, 1.14 ± 0.51 mg/dL, and 17.9 ± 3.0 MFI. The decrease in WBC- and neutrophil count and MAC-1 expression level was statistically significant (Table 4).

Table 4. Response of inflammatory indices to granulocyte and monocyte adsorption apheresis therapy
 BeforeAfter
  1. *Significantly different compared to the value before the granulocyte and monocyte adsorption apheresis treatment at P < 0.05. Before, 1 day before the first granulocyte and monocyte adsorption apheresis treatment; After, 1 day after the last granulocyte and monocyte adsorption apheresis treatment. CRP, C-reactive protein; MFI, mean fluorescence intensity; WBC, white blood cell count.

WBC (/μL)7664 ± 7286674 ± 632*
Neutrophils (/μL)5110 ± 7024178 ± 494*
CRP (mg/dL)2.17 ± 1.261.14 ± 0.51
Mac-1 (MFI)27.1 ± 6.6617.9 ± 3.02*

Adverse events

We encountered no adverse events in any of our GMA-treated patients.

Discussion

  1. Top of page
  2. Abstract
  3. Patients and Methods
  4. Results
  5. Discussion
  6. Conclusion
  7. References

The results of the present study, which is open-labeled and uncontrolled, further support our proposal that GMA therapy is effective and safe for the treatment of various skin diseases and associated arthropathy attributable to activated granulocytes. More than 88% of our patients benefited from GMA and no adverse effects were encountered. Inflammatory indices such as the WBC and neutrophil count decreased significantly in response to GMA therapy.

We previously showed that the expression of Mac-1, a heterodimer consisting of CD11b (integrin αM subunit) and CD18 (integrin β2 subunit), on the patients' peripheral neutrophils was increased compared to normal subjects and GMA adsorbs Mac-1 (CD11b/CD18)-expressing neutrophils selectively to the CA beads by the binding of complement component (iC3b) on CA beads and CD11b expressed on activated neutrophils [19]. In accordance with this mechanism, Mac-1 expression on the patients' peripheral neutrophils was significantly decreased in the present study. Our results clearly show that Mac-1 could be a useful biomarker for the neutrophilic diseases. As the results of the removal of activated neutrophils, effector cells of inflammation, serum levels of proinflammatory cytokines including interleukin-1 (IL-1), IL-6, IL-8, and tumor necrosis factor-α (TNF-α) were decreased and subsequently clinical manifestations are subsided by GMA therapy [21]. While the mean of Mac-1 expression level decreased significantly in response to GMA therapy, the decrease in MFI did not always correlate with the clinical response in each case. Our study to elucidate the factor responsible for sensitivity of each case is underway.

Based on our favorable clinical experience with GMA therapy and on the in vitro observations presented previously [19], a multi-centered, prospective, randomized trial of GMA for PP was performed. A total of 15 patients with moderate to severe PP were included. The severity was scored according to the practice guidelines for the treatment of pustular psoriasis, which is proposed by the Research Group for Rare and Intractable Dermatological Diseases funded by the Japanese Ministry of Health, Labour and Welfare. Eligible patients had to have >10% of their skin area to be covered by pustules. Oral etretinate, cyclosporine, methotrexate, prednisolone, and topical prednisolone/vitamin D3 could continue if it was started well in advance of entry. Patients were given five GMA treatment sessions at 6-day intervals. Efficacy was assessed by measuring the skin areas covered in pustules at baseline and 2 weeks after the last treatment session. In this study, one patient did not complete the first treatment session. Based on the PP severity scores relative to entry, the overall scores, the area of erythroderma, pustules, and edema were decreased significantly. Dermatology Life Quality Index (DLQI) was also improved significantly, reflecting better daily function, and quality of life. Good response was obtained in 12 patients (85.7%), and 10 patients maintained clinical response at 10 weeks after the last treatment session without any change in medication [22]. With this excellent outcome of the multi-centered study, GMA has been approved for the treatment of PP by the Japanese Ministry of Health, Labour and Welfare in October 2012.

Conclusion

  1. Top of page
  2. Abstract
  3. Patients and Methods
  4. Results
  5. Discussion
  6. Conclusion
  7. References

We propose that granulocyte and monocyte adsorption apheresis is a useful treatment modality for refractory skin diseases attributable to activated neutrophils as well as pustular psoriasis. We are currently engaged in the design of a multi-centered, prospective, randomized trial for other skin diseases of this sort.

References

  1. Top of page
  2. Abstract
  3. Patients and Methods
  4. Results
  5. Discussion
  6. Conclusion
  7. References