Yukari Okubo ¹, Ryuhei Okuyama ², Shinichi Imafuku ³, Yayoi Tada ⁴, Keiichi Yamanaka ⁵, Kazumitsu Sugiura ⁶, Yukie Yamaguchi ⁷, Masahito Yasuda ⁸, Wataru Sakamoto ⁹, Morihisa Saitoh ⁹, Akimichi Morita ¹⁰; Study Investigators

Dermatol Ther (Heidelb). . 2025 Jul;15(7):1883-1899. doi: 10.1007/s13555-025-01429-8. Epub 2025 May 19.

Introduction: Generalized pustular psoriasis (GPP) is a rare, severe, and chronic inflammatory skin disease characterized by widespread pustules that leads to unpredictable and potentially serious disease flares. Information regarding treatment status for GPP and treatment patterns for flares is important but limited as a result of the rarity of the condition. We conducted a 10-year, retrospective, longitudinal chart review of treatment patterns at GPP referral hospitals in Japan.

Methods: Eligible patients with GPP had at least 6 months of continuous observation data within 10 years after the date of protocol approval. Data were collected from patient records and annual patient reports. Patient characteristics and treatment details, including in relation to flare occurrence, were analyzed.

Results: The median age of patients (N = 205) was 53 years; 48.3% were female and most had mild or moderate GPP (66.8%). Patients commonly received nonbiologic systemic therapy (86.3%) and a similar proportion received biologics (79.5%); 95.1% received topical treatment and 22.4% received systemic adrenal corticosteroids. Use of nonbiologic systemic therapy decreased, and use of biologics increased, over the study period. During the observation period, the proportion of patients receiving biologic therapy increased after a flare (from 41.4% receiving biologics when flares occurred to 62.9% initiating a new biologic post flare).

Conclusion: In Japanese clinical practice, the evolution of treatment practices for GPP has seen an increased use of biologic therapies over time. Biologic use was common after flares; however, some flares occurred during biologic therapy, indicating a need for improved treatment options to maintain stable disease and prevent flares.

Chisato Tawada ¹, Yoko Ueda ², Yoko Mizutani ¹, Xiaoyu Zang ¹, Kayoko Tanaka ¹, Hiroaki Iwata ¹

Exp Dermatol. 2025 Mar;34(3):e70076. doi: 10.1111/exd.70076.

Reactive oxygen species (ROS) are involved in the pathogenesis of generalised pustular psoriasis (GPP), but this involvement has not been fully elucidated. We performed the diacron-reactive oxygen metabolite (d-ROM) test and the biological antioxidant potential (BAP) test on sera from nine patients with active GPP who were hospitalised and treated at our hospital, (6/9 with GMA) including three patients with pustular psoriasis of pregnancy (PPP). The serum d-ROM and BAP levels were evaluated before treatment and at 1 month of treatment. We also performed immunostaining of 4-hydroxy-2-nonenal (4-HNE) in skin tissues. In the GPP patients, the average d-ROM levels were significantly reduced at 1 month of treatment (reduced to 343.0 ± 82.1 U.Carr from 423.2 ± 95.0 U.Carr, p = 0.005). The Generalised Pustular Psoriasis Area and Severity Index (GPPASI) score correlated with d-ROM levels (r = 0.57, p = 0.10), suggesting that those levels reflect the disease severity. In normal pregnancy, d-ROM values are known to increase from mid-term to late-term. The d-ROM values increased when GPP worsened in the case of PPP. Immunohistochemical staining of 4-HNE was positive for subcorneal pustules, neutrophils, and for the cytoplasm of epidermal keratinocytes, especially in upper epidermal layers. Our findings indicate that 4-HNE may play an important role in GPP and PPP.

Sneha Annie Sebastian ¹, Oroshay Kaiwan ², Edzel L Co ³, Meghana Mehendale ⁴, Babu P Mohan

Spartan Med Res J. 2024 Sep 9;9(3):123397. doi: 10.51894/001c.123397. eCollection 2024.

Introduction: Ulcerative colitis (UC) is a chronic inflammatory bowel disorder (IBD) with periods of relapse and remission. Current advancements in clinical research have led to the development of more refined and effective medical therapy for UC.

Summary of the evidence: Traditional therapeutic agents such as 5-aminosalicylates (5-ASAs), sulfasalazine (SASP), corticosteroids, and immunomodulatory drugs have remained the gold standard for decades. However, their novel formulations and dosage regimens have changed their sequences in the medical management of UC. Several other novel drugs are in the final phases of clinical development or have recently received regulatory approval designed to target specific mechanisms involved in the inflammatory cascade for UC.

GMA has shown its efficacy in mild to moderate UC and refractory UC (steroid-dependent UC or biologic/immunologic resistant UC or lost their response to biologics) for remission induction.

Conclusions: This narrative review sought to provide a comprehensive knowledge of the potential benefits of standard and emerging therapies, including novel formulations, new chemical entities, and novel therapeutic approaches in managing UC. Keywords: Ulcerative colitis, 5- Aminosalicylic acid, sulfasalazine, corticosteroids, biologics, immunomodulators, novel formulations.

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.

E Papathanasiou , P Markopoulos , M Tzouvala , A Ioannou , E Tsironi , E Zacharopoulou , M Tzakri , E Pantelakis , G Leonidakis , G Bamias , S Michopoulos , E Zampeli

Journal of Crohn’s and Colitis, Volume 18, Issue Supplement_1, January 2024, Pages i1356–i1357, https://doi.org/10.1093/ecco-jcc/jjad212.0857

Background: Selective depletion of myeloid lineage leucocytes by adsorptive granulocyte and monocyte apheresis (GMA) with Adacolumn ^® was introduced as a nonpharmacologic treatment for ulcerative colitis (UC) in 2000. It has been reported that GMA may be effective in combination with immunosuppressive treatment in a subset of patients. Τhe purpose of our study is the evaluation of the effectiveness and safety of GMA as a complementary treatment in patients with refractory ulcerative colitis.

Methods: Prospective data collection of a patient cohort with refractory UC receiving Adacolumn ^® as an adjunct to their medical treatment. The therapeutic protocol has 2 phases: The induction phase entails two sessions per week for at least 3 weeks. The maintenance includes one weekly session for one month, one session every 15 days for one the next month, and monthly sessions thereafter. The patients’ medical treatment was maintained during the sessions. As a failure to GMA was considered the need for colectomy, the switch to a different treatment and inability to discontinue steroids. Response was evaluated after completion of at least 6 sessions of GMA.

Results: Ten patients with refractory UC were offered Adacolumn^® between February 2021 and September 2023. Mean age was 39.6 years (22-61years). All patients had failed at least one biologic treatment and two-thirds two biologics. Their treatment which was maintained during GMA was: tofacitinib 10mg bid for 4 patients, ustekinumab 90mg sc every 8 weeks for 3, vedolizumab 300 mg every 8 weeks for 2, and corticosteroids 16mg for one. The median duration of treatment was 5.1 months (2-13 months), while the median number of sessions was 16 (6-45). Clinical and endoscopic remission was achieved in two cases (20%), after 13 sessions for both (in brackets in the Table) whereas two patients (20%) responded clinically according to partial Mayo score. Treatment failure was documented for 6 patients (60%) after 6-45 sessions. Patient number 4 performed 45 sessions in different hospitals because he was reluctant to be operated. Three underwent colectomy and three discontinued due to non-response. No adverse effects were observed. The initial median of partial Mayo score was 6 (5-9) while at the end of the evaluation was 4.5 (0-9). Table 1 summarizes the results of our study.

Conclusion

1) GMA may be beneficial as an adjunct to biologics in refractory to medical treatment UC patients.

2) Interestingly, all patients on tofacitinib showed a favorable response after the addition of GMA.

This observation may help define a subset of UC patients who may benefit the most.

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)

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)

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