Payal M Patel 1, Stephanie N Sanchez-Melendez 2 3, Vinod E Nambudiri Exp Dermatol. 2023 Aug;32(8):1227-1234. doi: 10.1111/exd.14787

Generalized pustular psoriasis (GPP) is a clinical entity distinct from psoriasis, associated with a poor clinical prognosis, often resulting in severe systemic complications and mortality. The relapsing nature of the disease with recurrent or intermittent flares imposes a significant burden on patients’ quality of life (QoL). Although inadequately studied, QoL data in GPP patients has been a recent point of investigation. We conducted a literature search on PubMed/MEDLINE using the following search terms: ‘generalized pustular psoriasis’ OR ‘pustular psoriasis’ AND ‘quality of life’. We identified 12 relevant articles that provide insight into the large impact of GPP on the QoL of patients, the burden of the disease and the treatment, and the success of new treatment options in making a clinically important difference to QoL. This review illustrates a need for routine assessment of the QoL in interventional clinical trials for GPP and during physician encounters. This information can help guide clinicians on how to tailor the treatment approach from the patient’s perspective or illustrate whether new therapies offer meaningful benefits to patient care as we enter an era of exciting new treatments for this challenging condition.

Helena Rolandsdotter ^1 2, Michael Eberhardson ^1 3, Ulrika L Fagerberg ^4 5, Yigael Finkel ^1 2 , J Pediatr Gastroenterol Nutr 2018 Jan;66(1):84-89.

Objective: The aim of the study was to analyze the effect of granulocyte and monocyte apheresis (GMA) with mesalazine for induction of remission in pediatric patients with newly onset chronic inflammatory bowel disease (IBD) colitis. Methods: Thirteen pediatric patients with newly onset extensive IBD colitis were investigated per the ECCO/ESPGHAN IBD protocol. Of these 13, 12 received 10 treatments with Adacolumn (ADA) during a median of 6.25 weeks in combination with low-to-moderate doses of mesalazine, which was continued after apheresis. A control colonoscopy was performed 12 to 16 weeks after GMA treatment. Primary outcomes were mucosal healing (Mayo endoscopic score) and histopathologic grading of biopsies. A secondary outcome was disease activity as measured by the Pediatric Ulcerative Colitis Activity Index. Results: Twelve children (6 girls) with a median age of 14.6 years and a median duration of symptoms at diagnosis of 3.2 months received all planned 10 treatment sessions with ADA. Ten of 12 patients had pancolitis and 2 of 12 extensive colitis. A final diagnosis, however, indicated ulcerative colitis in 10 children and Crohn disease in 2 children. At control colonoscopy, 8 of 12 children were in clinical remission and the Mayo endoscopic score showed significant improvement in 9 of 12 patients (P = 0.006). Complete microscopic remission, according to the Geboes score, was observed in 2 patients. Conclusions: In this small study GMA for induction of remission of newly onset pediatric IBD colitis was effective in 8 of 12 patients. Further controlled studies are warranted to confirm the efficacy of this treatment model.

https://pubmed.ncbi.nlm.nih.gov/28604509/

Iago Rodríguez-Lago ¹, José Manuel Benítez ², Valle García-Sánchez ², Ana Gutiérrez ³, Laura Sempere ⁴, Daniel Ginard ⁵, Manuel Barreiro-de Acosta ⁶, José Luis Cabriada ⁷ , Gastroenterol Hepatol. Aug-Sep 2018;41(7):423-431.

Granulocyte and monocyte apheresis is well tolerated and accepted by patients with IBD. Although we found no significant differences according to type of IBD or apheresis regimen, patient perception was affected by clinical effectiveness.

https://pubmed.ncbi.nlm.nih.gov/29739692/

Premchand P, Ford L, Venkama DPWE-236 White cell aphaeresis (WCA) with adacolumn is effective in selected cases of chronic refractory colitis with high histological activityGut 2012;61:A394.

Introduction Treatment options for patients with chronic refractory colitis are limited. White cell aphaeresis (WCA) is effective in inducing clinical remission in chronic refractory colitis in patients with a strong inflammatory burden at baseline and histologically active disease. Previous multinational sham controlled trials have demonstrated significant improvement when patients with high histological activity (modified Rileys score) are selected for treatment. Methods A prospective study was conducted in 30 patients with severe steroid -dependent or steroid -refractory ulcerative colitis referred for WCA. Inclusion criteria were (i) High disease activity score (partial Mayo score ≥6) (ii) Intractable symptoms despite treatment with steroids and/or immunosuppressants (iii) Severe disease at endoscopy and histologically. The aim was to induce clinical and IBD-Q remission at 12 weeks. A Mayo score ≤3 defined clinical remission. The 32 item Inflammatory Bowel Disease questionnaire (IBD-Q) was used to assess quality of life prior to treatment and at 12 weeks. Results Patient Characteristics: Prior to treatment 28 patients (93.3%) were prescribed 5-ASA compounds. 12 patients (40%) were prescribed topical therapies (5-ASA enemas or suppositories/steroids enemas). 27 patients (90%) were steroid dependent (Prednisolone mean dose 21.1 mg, median 20 mg). Three patients (10%) were steroid refractory (no response to high dose oral steroids). 13 patients (43.3%) were prescribed Azathioprine of the remainder all had documented intolerance or a contraindication. One patient (3.3%) was prescribed six Mercaptopurine. Five patients had failed Infliximab (16.6%) and in one patient (3.3%) it was contraindicated. 1 patient (3.3%) had failed intramuscular Methotrexate. Outcomes: At week 12 clinical remission (Mayo score ≤3) was achieved in 22 patients (73.3%), 18 patients (60%) were no longer prescribed oral steroids. IBD-Q remission at week 12 was achieved in 19 patients (63.3%). Of the remainder, five patients (16.6%) achieved an IBD-Q response. Of eight patients (26.6%) who failed to achieve clinical remission at 12 weeks, one achieved delayed remission at 20 weeks. Of the remaining seven treatment failures, five underwent colectomy (16.6%). Conclusion WCA can be effective in inducing clinical remission and improving quality of life (IBD-Q) indices in chronic severe steroid refractory ulcerative colitis with highly active disease histologically. This data series suggests WCA should be considered before colectomy in this challenging patient group

https://gut.bmj.com/content/61/Suppl_2/A394.1.info

Takayuki Yamamoto, Satoru Umegae, Koichi Matsumoto February 2006 World Journal of Gastroenterology 12(4):520-5 DOI:10.3748/wjg.v12.i4.520

Active ulcerative colitis (UC) is frequently associated with infiltration of a large number of leukocytes into the bowel mucosa. Therefore, removal of activated circulating leukocytes by apheresis has the potential for improving UC. In Japan, since April 2000, leukocytapheresis using Adacolumn has been approved as the treatment for active UC by the Ministry of Health and Welfare. The Adacolumn is an extracorporeal leukocyte apheresis device filled with cellulose acetate beads, and selectively adsorbs granulocytes and monocytes / macrophages. To assess the safety and clinical efficacy of granulocyte and monocyte adsorptive apheresis (GMCAP) for UC, we reviewed 10 open trials of the use of GMCAP to treat UC. One apheresis session (session time, 60 min) per week for five consecutive weeks (a total of five apheresis sessions) has been a standard protocol. Several studies used modified protocols with two sessions per week, with 90-min session, or with a total of 10 apheresis sessions. Typical adverse reactions were dizziness, nausea, headache, flushing, and fever. No serious adverse effects were reported during and after GMCAP therapy, and almost all the patients could complete the treatment course. GMCAP is safe and well-tolerated. In the majority of patients, GMCAP therapy achieved clinical remission or improvement. GMCAP is a useful alternative therapy for patients with steroid-refractory or -dependent UC. GMCAP should have the potential to allow tapering the dose of steroids, and is useful for shortening the time to remission and avoiding re-administration of steroids at the time of relapse. Furthermore, GMCAP may have efficacy as the first-line therapy for steroid-naive patients or patients who have the first attack of UC. However, most of the previous studies were uncontrolled trials. To assess a definite efficacy of GMCAP, randomized, double blind, sham-controlled trials are necessary. A serious problem with GMCAP is cost; a single session costs ¥145 000 ($1 300). However, if this treatment prevents hospital admission, re-administration of steroids and surgery, and improves a quality of life of the patients, GMCAP may prove to be cost-effective.

https://www.researchgate.net/publication/7286897_Safety_and_clinical_efficacy_of_granulocyte_and_monocyte_adsorptive_apheresis_therapy_for_ulcerative_colitis

[Article in Korean ]Hyo Jong Kim ¹, Joo Sung Kim, Dong Soo Han, Suk-Kyun Yang, Ki Baik Hahm, Woo In Lee, Seog-Woon Kwon, Jai Hyun Choi, Won Ho Kim, Kyu Yong Choi, In Sung Song Korean J Gastroenterol  2005 Jan;45(1):34-44. PMID: 15665566

Background/aims: In chronic inflammatory conditions such as ulcerative colitis (UC), the migration of granulocytes and monocytes/macrophages from the circulation into the colonic mucosa is especially important in maintaining inflammation. The aim of this trial was to assess safety and efficacy of granulocyte and monocyte adsorption apheresis in patients with moderate-to-severe UC refractory to conventional drug therapies. Methods: Twenty-seven patients with moderate (55.6%) to severe (44.4%) active UC refractory to conventional drug therapies who had no changes in their conventional therapy regimen in the past two weeks before the recruitment were enrolled in an open-label trial. Concomitant medications were allowed, and steroids were tapered down according to the clinical activity during the course. We used an adsorptive type extracorporeal column (Adacolumn; JIMRO, Takasaki, Japan), which selectively adsorb granulocytes and monocytes. Patients took five apheresis sessions, each with 60 minutes duration for 5 consecutive weeks. The primary efficacy variables were clinical disease activity, short inflammatory bowel disease questionnaire (SIBDQ), C-reactive protein (CRP), and endoscopic scores. These variables were scored at regular intervals, and analyzed at week 7 on an intention-to-treat (ITT) principles. Results: At 7 weeks, 70.4% of patients showed overall improvement. Clinical disease activity (p < 0.0001), endoscopic score (p < 0.001), and the quality of life as assessed by SIBDQ (p < 0.0001) were significantly improved after the therapy. In 56.3% of concomitant steroid users, tapering down or discontinuation of steroids was possible. Treatment was well tolerated, and no severe adverse events were observed. Conclusions: Adacolumn was very efficacious in patients with moderate-to-severe active UC refractory to conventional drug therapy, but further assessment is needed.

https://pubmed.ncbi.nlm.nih.gov/15665566/

Takeshi Kusaka ¹, Ken Fukunaga, Kunio Ohnishi, Tadashi Kosaka, Toshihiko Tomita, Yoko Yokoyama, Koji Sawada, Yoshihiro Fukuda, Hiroto Miwa, Takayuki Matsumoto

J Clin Apher. 2004;19(4):168-73. doi: 10.1002/jca.20023.

Six patients with active Crohn’s disease (CD) unresponsive to conventional medications (CM) were treated with Monocyte-granulocytapheresis (M-GCAP). CD patients who scored 200-400 points in Crohn’s disease activity index (CDAI) in spite of receiving CM, including enteral nutrition, for at least 2 weeks were enrolled in our double series trial. Each series had 5 weekly M-GCAP and 2 follow-up weeks, and each M-GCAP treated 1,800 ml of patient’s peripheral blood. After the 1st series, patients who decreased more than 50 points on the CDAI were deemed responders and enrolled in the second series. Patients with a CDAI score less than 150 points were considered in remission. The patients’ quality of life was evaluated using an index (IBDQ) before and after the 1st series. The CDAI was significantly decreased comparing before and after the 1st series (258.2 +/- 36.2 vs. 166.5 +/- 16.6; P < 0.02). 50% of patients (3/6) responded to the therapy, and one case (16.7%) could be induced to remission. Significant removal was revealed only for white blood cells (25.6 +/- 16.9%; P < 0.05), especially granulocytes (29.5 +/- 22.5%; P < 0.05). A statistically significant improvement of IBDQ was revealed in the responders’ group (162.3 +/- 17.2 vs. 189.3 +/- 11.5; P < 0.03). M-GCAP could be an effective adjunctive therapy for active CD patients unresponsive to CM allowing them to maintain a high QOL. However, it might be difficult to improve patients who could not be induced to remission after the 1st series by applying another series.

https://pubmed.ncbi.nlm.nih.gov/15597346/

https://onlinelibrary.wiley.com/doi/10.1002/jca.20023

Takeshi Kusaka ¹, Ken Fukunaga, Kunio Ohnishi, Tadashi Kosaka, Toshihiko Tomita, Yoko Yokoyama, Koji Sawada, Yoshihiro Fukuda, Hiroto Miwa, Takayuki Matsumoto J Clin Apher. 2004;19(4):168-73. doi: 10.1002/jca.20023.

Six patients with active Crohn’s disease (CD) unresponsive to conventional medications (CM) were treated with Monocyte-granulocytapheresis (M-GCAP). CD patients who scored 200-400 points in Crohn’s disease activity index (CDAI) in spite of receiving CM, including enteral nutrition, for at least 2 weeks were enrolled in our double series trial. Each series had 5 weekly M-GCAP and 2 follow-up weeks, and each M-GCAP treated 1,800 ml of patient’s peripheral blood. After the 1st series, patients who decreased more than 50 points on the CDAI were deemed responders and enrolled in the second series. Patients with a CDAI score less than 150 points were considered in remission. The patients’ quality of life was evaluated using an index (IBDQ) before and after the 1st series. The CDAI was significantly decreased comparing before and after the 1st series (258.2 +/- 36.2 vs. 166.5 +/- 16.6; P < 0.02). 50% of patients (3/6) responded to the therapy, and one case (16.7%) could be induced to remission. Significant removal was revealed only for white blood cells (25.6 +/- 16.9%; P < 0.05), especially granulocytes (29.5 +/- 22.5%; P < 0.05). A statistically significant improvement of IBDQ was revealed in the responders’ group (162.3 +/- 17.2 vs. 189.3 +/- 11.5; P < 0.03). M-GCAP could be an effective adjunctive therapy for active CD patients unresponsive to CM allowing them to maintain a high QOL. However, it might be difficult to improve patients who could not be induced to remission after the 1st series by applying another series.

https://pubmed.ncbi.nlm.nih.gov/15597346/