Cristina Suárez Ferrer 1, Eduardo Martin-Arranz 2, María Dolores Martín-Arranz, Gastroenterol Hepatol 2024 Jan 12:S0210-5705(24)00018-9. doi: 10.1016/j.gastrohep.2024.01.002. Online ahead of print.
Aim: Granulocyte and monocyte apheresis (GMA) is a potential therapeutic option when combined with various drugs for treatment of ulcerative colitis (UC). In this study, we analyze the efficacy and safety of GMA combined with vedolizumab (VDZ) during induction in patients with moderate-severe UC and incomplete response to steroids.

Patients and methods: Single-center retrospective review of patients receiving GMA+VDZ. Data on the disease and previous treatments were collected. Clinical response was classified as no response, response without remission, and remission. Available data on biochemical and endoscopic response were included. Adverse events (AEs) were recorded.

Results: The study population comprised 6 patients with UC who had received GMA+VDZ during induction after failure of an anti-TNF agent. The median number of GMA sessions was 5 (IQR 4-5; 3-10). All the patients received VDZ 300mg iv at 0, 2, and 6 weeks, and 5 (83%) received an additional dose at week 10. During maintenance, all the patients continued VDZ iv every 8 weeks. The median follow-up was 57.6 months (IQR: 39-74). Four of the 6 patients achieved clinical remission after GMA+VDZ and continued in deep remission until the end of follow-up. A median, non-significant decrease of 1378μg/g (IQR: 924-5778μg/g) was observed for calprotectin and 42.2mg/l (IQR: 15.3-113.5) for CRP vs. baseline. No patient underwent colectomy. No treatment-related AEs were observed.

Conclusions: GMA+VDZ during induction can be effective and safe in selected patients with moderate-severe UC and partial response to steroids.

Muhammad Hassan Shakir 1 2, Salman A Basit 1, Syed Muhammad Hussain Zaidi 1, Sarasija Natarajan 1, Omar Z Syed 1, Mohammad Asim Amjad 1, Douglas Klamp, Cureus. 2023 Nov 6;15(11):e48399. doi: 10.7759/cureus.48399. eCollection 2023

Sweet syndrome (SS) is an acute febrile neutrophilic dermatosis. Although perceived to be rare, the disease may well have been underreported due to lack of exposure in low-volume clinical settings and due to the use of rather strict clinical criteria for diagnosis. It presents as cutaneous papules, plaques, or nodules in an asymmetric distribution that follows fever and flu-like symptoms. Data on the disease is ever-expanding. Several associations have been identified, including drugs, infections, malignancies, and autoimmune diseases. Different disease patterns and histological variants have been identified. Pathophysiology is complex and multifactorial but appears to involve mechanisms that negatively influence neutrophil apoptosis and facilitate neutrophil recruitment. The existing diagnostic criteria exclude cases with vasculitis; over time, cases of neutrophilic dermatoses with vasculitis have been reported as SS as long as other criteria were met. Newer diagnostic models have been proposed, some arguing against the exclusion of vasculitis. Steroids continue to be the mainstay of treatment, and steroid responsiveness continues to be a part of the diagnostic criteria, although newer treatment modalities have been used and have shown promise. No established guidelines exist for management. We present a case of Idiopathic SS with vasculitis along with a brief review of the existing literature. We agree to the inclusion of vasculitis as proposed by the newer diagnostic criteria.

AM Varghese1, PK Uppala2, RK Keelu1, SV Sai Krishna3, NV Kandra1, U Uttaravalli4, VS Somarouthu5 and M K Balijepalli
SA Pharmaceutical Journal 90, 51, 2023

Sweet syndrome (SS) is an uncommon auto-inflammatory disorder presenting with acute pyrexia, leucocytosis and erythematous skin lesions with dense neutrophilic dermal infiltration. SS is seen as adverse reaction to some drugs, microbes and is associated with certain myeloproliferative or haematological neoplasms and is also seen with autoimmune diseases like inflammatory bowel disease, systemic lupus erythematosus, rheumatoid arthritis, etc. A female aged 43 years, came to the hospital with high fever and erythematous, pus-filled plaques and nodules on her face, neck, shoulders and extremities, after taking cotrimoxazole (antibacterial agent) in tablet form 480 mg twice daily for five days for urinary tract infection. The diagnosis of SS was arrived upon from the biopsy reports showing predominant neutrophilic infiltrate, and relevant laboratory tests. Treatment included oral prednisone (corticosteroid) and the symptoms resolved in two months.

Shuzo Kaneko ¹, Tsuyoshi Zen ¹, Susumu Banjoya ², Toshiaki Nuki ³, Ainori Hoshimoto ¹, Makiko Harano ¹, Sou Hagiwara ¹, Eri Imai ¹, Yusuke Tsukamoto ¹ Intern Med. 2023 Sep 1;62(17):2565-2569. doi: 10.2169/internalmedicine.1728-23.

Multisystem inflammatory syndrome in adults (MIS-A) is a life-threatening disease that can develop weeks after coronavirus disease 2019 (COVID-19). MIS-A symptoms include multiorgan involvement, especially gastrointestinal tract and heart involvement, and Kawasaki disease-like symptoms. We herein report a 44-year-old Japanese man with MIS-A who had contracted COVID-19 five weeks ago and went into shock after acute gastroenteritis, acute kidney injury, and Kawasaki disease-like symptoms. Methylprednisone pulse and high-dose intravenous immunoglobulin resulted in recovery of shock and his renal function, but diffuse ST-segment elevation on electrocardiography and pericardial effusion with a fever emerged after therapy. Additional granulocyte-monocyte adsorptive apheresis successfully ameliorated the cardiac involvement.

Successful Use of Granulocyte and Monocyte Adsorptive Apheresis in a Patient with Post-COVID-19 Multisystem Inflammatory Syndrome in Adults – PubMed (nih.gov)

Successful Use of Granulocyte and Monocyte Adsorptive Apheresis in a Patient with Post-COVID-19 Multisystem Inflammatory Syndrome in Adults – PMC (nih.gov)

Nobuhiro Ueno Seisuke Saito Masahiro Sato Yuya Sugiyama doi: 10.21203/rs.3.rs-3037827/v1

Background: A remission induction therapy of granulocyte and monocyte adsorptive apheresis (GMA) with Adacolumn was given to patients with active Crohn’s disease (CD). However, establishing an appropriate treatment strategy for GMA in patients with active CD remains unclear. Methods: This multicenter retrospective cohort study encompassed patients with CD who underwent GMA in seven independent institutions in Japan from January 2010 to March 2023. All clinical data were obtained from medical records. This study aimed to evaluate the clinical efficacy, safety, and subsequent clinical progression after GMA in patients with CD. Result: This study enrolled 173 patients with active inflammatory bowel disease who underwent GMA with Adacolumn, and among them, 16 patients with CD with mild to moderate disease activity were analyzed. Concomitant medication, including steroids, immunomodulators, and biologics, was used in 93.7% of all cases. The overall remission and response rates were 25.0% and 68.8%, respectively. The response rate between groups concerning the frequency and total GMA sessions revealed no significant difference. Six (37.5%) patients experienced adverse events (AEs). All AEs were related to the trouble in blood access and recovered soon without any sequelae. Regarding the factors associated with response to GMA, the responder group had a significantly longer disease duration (336 vs 44 months, p = 0.036) and exhibited a relatively lower rate of intestinal strictures and a median score of a simple endoscopic score for CD (SES-CD) (9.1 vs 60 %, p = 0.063 and 10 vs 21.5, p = 0.091, respectively). Further, all patients responding to GMA received biologics that were continuously used before and after GMA. Furthermore, 36.4% of patients remained on the same biologics 52 weeks after GMA. Notably, all patients who continued the same biologics had previously experienced a loss of response to anti-tumor necrosis factor-α agent. Conclusion: Therefore, GMA may exhibit heightened effectiveness in patients with moderately active CD without severe endoscopic activity. Moreover, it represents a potential novel therapeutic option for refractory CD, particularly with insufficient response to biologics.

(PDF) The clinical efficacy and safety of granulocyte and monocyte adsorptive apheresis in patients with Crohn’s disease: A multicenter retrospective cohort study (researchgate.net)

Rish K Pai ¹, Douglas J Hartman ², Claudia Ramos Rivers ³, Miguel Regueiro ⁴, Marc Schwartz ³, David G Binion ³, Reetesh K Pai Clin Gastroenterol Hepatol 2020 Oct;18(11):2510-2517.e5. doi: 10.1016/j.cgh.2019.12.011. Epub 2019 Dec 14.

Background & aims: We investigated correlations between histologic features of the colonic mucosa in patients with ulcerative colitis (UC) and clinical outcomes during a 3-year follow-up period. Methods: We obtained baseline biopsies from all colorectal segments (n = 889) from 281 patients with UC enrolled in a prospective study at a single center from 2009 through 2013. Biopsies were assessed in a blinded manner using validated histologic scoring systems (the Geboes score, Nancy histopathologic index, and Robarts histopathologic index). Clinical, endoscopic, and histologic data were collected and tested for correlations with systemic corticosteroid use, hospitalization, and colectomy within 3 years of the index colonoscopy. Results: We found histologic evidence of UC activity (Geboes score ≥ 2B.1) in biopsies from 182 patients (65%) and endoscopic evidence of UC activity in 149 patients (53%) (substantial agreement, κ = 0.60). Histologic features of UC activity were associated with increased rates of systemic corticosteroid use, colectomy, and hospitalization in the entire cohort (P < .05 for all) and associated with increased rates of systemic corticosteroid use in an analysis limited to patients in endoscopic remission (P < .001). In patients in endoscopic remission, only histologic activity was independently associated with use of systemic corticosteroids (multivariate odds ratio, 6.34; 95% CI, 2.20-18.28; P = .001). Similar results were seen when the entire cohort was analyzed. Compared with patients without histologic evidence of UC activity, patients with only a small number of mucosal neutrophils still had higher rates of systemic corticosteroid use (P < .001). Conclusions: Histologic evidence of UC activity, including small numbers of neutrophils in the colonic mucosa, is the only factor independently associated with use of systemic corticosteroids. Complete resolution of neutrophil-associated inflammation should be a target for treatment of UC.

https://pubmed.ncbi.nlm.nih.gov/31843598/

https://www.cghjournal.org/article/S1542-3565(19)31438-7/fulltext

Munenori Kawai, Chiharu Kawanami, Akihisa Fukuda & Hiroshi Seno

Clin J Gastroenterol. 2021 Oct;14(5):1561-1566. doi: 10.1007/s12328-021-01460-0. Epub 2021 Jun 8.

An 18-year-old woman was admitted to our hospital with fever, diarrhea and painful skin ulcers in both pretibial areas starting 19 days earlier. The skin lesions appeared deep necrotic ulcers with violaceous undermined borders. She had been diagnosed as ulcerative colitis and primary sclerosing cholangitis (PSC) 6 and 5 years before, respectively, and had stopped having regular check-up and refused medication for years. Her clinical history and skin lesions led us to suspect of pyoderma gangrenosum (PG). The skin biopsy showed aseptic abscess formation with neutrophils infiltration in the dermis without bacteria. Thus, she was diagnosed with PG. 1 mg/kg/day of prednisolone was administered and ten sessions of granulocyte and monocyte adsorption apheresis (GMA) were started. Magnetic resonance cholangiography showed multifocal bile duct strictures due to PSC. Total colonoscopy revealed ulcerative pancolitis with spared normal mucosa in the rectum. After the treatments, her symptoms and the skin lesion improved dramatically. She was discharged on the 45th day with 25 mg/day of prednisolone. In conclusion, this is the first reported case of PG with PSC-associated colitis that showed dramatic response to the concomitant GMA therapy with corticosteroids. Together with previous reports, concomitant GMA therapy with corticosteroids may be an effective treatment for PG.

https://pubmed.ncbi.nlm.nih.gov/34101129/

Maki Miyakawa, Hiroki Tanaka, Tomoyoshi Shibuya,Taro Osada, Eiji Hosoi Gastroenterol. 2019 156 (6) Suppl.S-666–S-667

Background: Few studies have assessed the safety of granulocyte and monocyte adsorptive apheresis (GMA) in patients with inflammatory bowel disease (IBD) undergoing concomitant treatment with multiple immunosuppressant medications. To address this research gap, we investigated adverse effects associated with GMA in patients with IBD treated with multiple immunosuppressants  who  participated  in  the  “Post-marketing  surveillance  study  on  the safety and response of GMA treatment in patients with Crohn’s disease or ulcerative colitis with at least one special situation who received Adacolumn® (PARTICULAR).” Methods: The PARTICULAR study was a retrospective, multicenter cohort study of patients with ulcerative colitis (UC) or Crohn’s disease (CD) who received GMA between November 2013 and March 2017. Patients meeting at least one of the following special situation were enrolled: elderly (<=65 years) or pediatric/adolescent (>=18 years) patients, patients with anemia, or patients undergoing concomitant treatment with multiple immunosuppressants. GMA was performed using Adacolumn® (JIMRO, Takasaki, Japan). Each patient received up to 11 GMA sessions, and all adverse events (AEs) during the study period were recorded. The incidence of AEs was investigated relative to the number and type of immunosuppressants using univariate and multivariate logistic regression analyses. Results: A total of 437 patients (368 UC, 69 CD) from 93 institutions were included. Of these, 140, 169, 101, and 27 patients received none, 1, 2, and >=3 immunosuppressants, respectively. In total, 125 patients received multiple immunosuppressants. Concomitant prednisolone, immunomodulators, anti-tumor necrosis factor agents, and calcineurin inhibitors were administered in 189, 151, 89, and 24 patients, respectively. The incidence of AEs was 11% in all 437 patients and 8%, 12%, 12%, and 26% in patients receiving none, 1, 2, and >=3 immunosuppressants, respectively. In multivariate logistic regression analysis, anemia and concomitant immunosuppressants were independently associated with the incidence of AEs. Particularly, a higher number of concomitant immunosuppressants showed an increasing trend with odds ratios related to AEs. In contrast, concomitant corticosteroids were associated with a reduced risk of AEs. Nausea/vomiting and headache were the most common AEs in patients on multiple immunosuppressant medications (5.6% and 3.2%, respectively). Conclusions: Concomitant treatment with immunosuppressants was independently associated with the incidence of AEs such as nausea/vomiting and headache in patients with IBD receiving GMA. As the number of concomitant immunosuppressants increased, the incidence of AEs also increased. However, our data also suggest that GMA is safe in patients with IBD receiving prednisolone.

https://www.gastrojournal.org/action/doSearch?text1=granulocyte+and+monocyte+apheresis+&field1=AllField&AfterYear=2018&BeforeYear=2021&pageSize=50&startPage=&SeriesKey=ygast

Masashi Ohno ¹, Shigeki Koyama, Mariko Ohara, Kazumi Shimamoto, Yu Kobayashi, Fumiyasu Nakamura, Kazuki Mitsuru, Akira Andoh

Intern Med.  2016;55(1):25-30. doi: 10.2169/internalmedicine.55.5422. Epub 2016 Jan 1.

A 36-year-old woman was admitted to our hospital due to swelling and redness of the left lateral malleolus and dorsum of the left foot with severe pain, with a flare-up of ulcerative colitis (UC). A pathologic examination by skin biopsy led to a diagnosis of pyoderma gangrenosum (PG). She was treated with the intravenous administration of prednisolone (60 mg/day), and granulocyte and monocyte adsorption apheresis (GMA) was performed twice-a-week for 5 weeks. This treatment dramatically improved both the skin and colonic mucosal lesions. These results suggest that a combination of GMA and corticosteroids might be recommendable to induce the remission of serious PG complicated with UC.

https://pubmed.ncbi.nlm.nih.gov/26726081/

https://www.jstage.jst.go.jp/article/internalmedicine/55/1/55_55.5422/_article

Keiichi Tominaga ¹, Masakazu Nakano, Mina Hoshino, Kazunari Kanke, Hideyuki Hiraishi

BMC Gastroenterol. 2013 Mar 1;13:41. doi: 10.1186/1471-230X-13-41.

Background: Patients with ulcerative colitis (UC) are treated with prednisolone (PSL), which causes adverse side effects. Extracorporeal granulocyte/monocyte adsorption (GMA) with an Adacolumn depletes elevated/activated myeloid lineage leucocytes as sources of inflammatory cytokines. We were interested to evaluate the efficacy, safety and the treatment cost for PSL and GMA. Methods: Forty-one patients with active UC had achieved remission with GMA, at 1 or 2 sessions/week, up to 10 sessions (n=24) or with orally administered PSL (1mg/kg bodyweight, n=17). Clinical activity index (CAI) ≤4 was considered clinical remission. Following remission, patients received 5-aminosalicylic acid (2250-3000mg/day) or sulphasalazine (4000-6000mg/day) as maintenance therapy and were followed for 600 days. The total treatment cost was assessed based on 1€=150JPY. Results: PSL was tapered after two weeks, and discontinued when a patient achieved remission. The average time to the disappearance of at least one major UC symptom (haematochezia, diarrhoea, or abdominal discomfort) was 15.3 days in the GMA group and 12.7 days in the PSL group, while time to remission was 27.9 days in the GMA group and 27.6 days in the PSL group, CAI 0.8 and 2.0, respectively. The Kaplan-Meier plots showed similar remission maintenance rates over the 600 days follow-up period. The average medical cost was 12739.4€/patient in the GMA group and 8751.3€ in the PSL group (P<0.05). In the GMA group, 5 transient adverse events were observed vs 10 steroid related adverse events in the PSL group (P<0.001). Conclusions: In appropriately selected patients, GMA has significant efficacy with no safety concern. The higher cost of GMA vs PSL should be compromised by good safety profile of this non-pharmacological treatment intervention.

https://pubmed.ncbi.nlm.nih.gov/23452668/

https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3599731/