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.

Miho Takahashi*, Hitoshi Tsuchihashi and Rei Watanabe

J. Cutan. Immunol. Allergy, 13 March 2025 Volume 8 – 2025 | https://doi.org/10.3389/jcia.2025.14441

A 41-year-old woman had been diagnosed with generalized pustular psoriasis (GPP) for 4 years. Her symptoms had been stabilized with cyclosporine (2 mg/kg/day). Despite increasing the cyclosporine dosage to 3 mg/kg/day, the skin lesions did not improve and the patient developed a fever.  A CT scan revealed a mass lesion measuring 2.5 cm × 4 cm in the right breast and axillary lymphadenopathy. Based on the CT findings, the patient was suspected of having left breast cancer. To manage GPP, granulocyte and monocyte adsorption (GMA) was initiated to minimize the possible adverse effects on the suspected cancer. During the five courses of GMA, the patient’s body temperature returned to a normal degree and the pustules and erythema gradually improved. However, the erythema on her trunk remained. GMA was selected as the initial treatment because the therapeutic strategy for the breast cancer had not yet been determined. Meanwhile, etretinate, corticosteroids, biologics, and their combination are also strong candidates for acute exacerbated GPP. Subsequently, subcutaneous brodalumab administration was introduced; brodalumab allowed the patient to concurrently undergo chemotherapy for breast cancer. The patient underwent a left breast mastectomy and was diagnosed with right breast cancer with right axillary lymph node metastasis. The patient started hormonal therapy, and tumor markers showed a decreasing trend. However, she gradually developed skin metastases, which grew despite treatment. The patient died of breast cancer 4 years after diagnosis. Brodalumab was continued for 4 years, during which no recurrence of GPP was observed.

In conclusion, due to the rarity of the disease, selecting an appropriate therapy for GPP is often challenging especially considering the management of complications. Further accumulation of the treatment experience would be desirable.

Elizabeth M. Staley MD, PhD, Huy P. Pham MD, MPH

Transfusion Medicine and Hemostasis (Fourth Edition), Elsevier, 2025, chapter 87, Pages 399-401, ISBN 9780323960144, https://doi.org/10.1016/B978-0-323-96014-4.00049-5.

Leukocytaphersis (or leukapheresis) is a therapeutic procedure in which white blood cells (WBCs) are selectively removed from the patient’s circulation. The procedure is performed for the treatment of hyperleukocytosis most commonly in the setting of leukemia. Adsorptive cytapheresis utilizes apheresis in association with a medical device to selectively extract leukocyte subsets (activated monocytes and granulocytes) from the patient’s circulation. Adsorptive cytapheresis has been utilized for the treatment of multiple inflammatory conditions including inflammatory bowel disease, systemic lupus erythematosus, psoriasis, Behçet’s disease, and rheumatoid arthritis.

Johannes Hasskamp ¹, Christian Meinhardt ², Petrease H Patton ³, Antje Timmer ¹

Cochrane Database Syst Rev.2025 Feb 27;2(2):CD000478. doi: 10.1002/14651858.CD000478.pub5.

Background: Maintenance of remission is essential in inflammatory bowel disease (IBD) in terms of disease course and long-term prognosis. The thiopurines azathioprine and 6-mercaptopurine have longstanding merit in ulcerative colitis, but more therapeutic options have been developed. This review is an update and extension of a review last published in 2016.

Objectives: To assess the effectiveness and safety of azathioprine and 6-mercaptopurine in monotherapy or combined therapy regimens compared to placebo or active controls for the maintenance of remission in ulcerative colitis.

Search methods: We searched Cochrane Central Register of Controlled Trials (until May 2023), ClinicalTrials.gov (until May 2023), Embase (until August 2022), MEDLINE (until May 2023), and WHO ICTRP (until May 2023). We checked reference lists of the included studies and, if needed, contacted the authors to request more data or information.

Main results: We included 10 studies in the review, including 468 adult participants with ulcerative colitis. The risk of bias across these was low for most outcomes, but we considered some outcomes to have some concerns or high risk of bias due to insufficient information on concealment of allocation and outcome measurement. Based on five placebo-controlled studies, azathioprine or 6-mercaptopurine may reduce the risk of failing to maintain remission. In the thiopurine group, 45% (64/143) of participants failed to maintain remission compared to 67% (96/143) of participants receiving placebo (RR 0.66, 95% confidence interval (CI) 0.54 to 0.82; 5 studies, 286 participants; low-certainty evidence). Three studies reported withdrawals due to adverse events. Among participants on azathioprine, 4% (3/80) withdrew due to adverse events compared to 0% (0/82) of placebo participants (RD 0.04, 95% CI -0.02 to 0.09; 3 studies, 162 participants; low-certainty evidence). The evidence is of low certainty when comparing 6-mercaptopurine to 5-aminosalicylate. Based on one three-armed trial, 27% (3/11) of 6-mercaptopurine participants failed to maintain remission compared to 100% (2/2) of 5-aminosalicylate participants (RR 0.35, 95% CI 0.13 to 0.97; 1 study, 13 participants; low-certainty evidence). This trial also involved an induction phase; we only included the results for participants in remission. The single trial comparing 6-mercaptopurine to 5-aminosalicylate did not report separate data on adverse events and withdrawals due to adverse events for the subgroup with successful induction of remission, so we could not analyze these outcomes for this comparison.

Authors’ conclusions: Low-certainty evidence suggests that azathioprine or 6-mercaptopurine therapy may be more effective than placebo for the maintenance of remission in ulcerative colitis. More research is needed to evaluate the value of therapeutic drug monitoring and the effects of various treatment modalities on long-term safety.

Namiko Abe ¹, Yuko Higashi ², Chiharu Tateishi ³, Takuro Kanekura ², Daisuke Tsuruta ³, Tomoko Kobayashi ¹, Yukari Okubo ¹

J Dermatol. 2025 Apr;52(4):642-650. doi: 10.1111/1346-8138.17667. Epub 2025 Feb 12.

Granulocyte and monocyte adsorptive apheresis (GMA) selectively removes activated granulocytes and monocytes from the peripheral blood. In 2012, GMA was approved in Japan as a treatment for generalized pustular psoriasis and localized pustular psoriasis or palmoplantar pustulosis (PPP). Limited evidence from case reports and monocentric studies suggested that GMA is an effective treatment for skin and joint symptoms of PPP with pustulotic arthro-osteitis (PAO). The present, prospective, observational study was performed at three dermatology departments in Japan to evaluate the efficacy and safety of GMA in patients with PPP with PAO. Between April 2017 and December 2020, two male and 12 female patients with PPP and PAO were enrolled. Their mean age, mean duration of skin manifestations, and mean duration of PAO symptoms was 52.8 years, 51.2 months, and 44.9 months, respectively. GMA was applied weekly over five sessions. The skin and joint symptoms were assessed at baseline, post-GMA, and at the 3-month follow-up. A total of 12 patients completed five GMA sessions, and two patients discontinued the treatment because of adverse events. Thus, 12 patients were finally assessed post-GMA, and 10 patients were assessed at the 3-month follow-up. The assessment of GMA efficacy demonstrated that the skin symptoms had remarkably improved and improved in 33.3% (4/12) and 70% (7/10) of the patients post-GMA and at the 3-month follow-up, respectively. Furthermore, the joint symptoms had remarkably improved in 66.7% (8/12) and 60% (6/10) of the patients post-GMA and at the 3-month follow-up, respectively. These results suggest that GMA is effective in treating the skin and joint symptoms of PPP with PAO.

Mary Grace Hash¹, Guang Orestes², Camile Delva³, Bailey Patrick⁴, Donna Pham⁵, Olivia Biddle⁶, Teonna Sharpe⁷, Kaitlyn Miner⁸, Kelly Frasier^9,*

Dermis. 5(1):28.

Psoriasis treatment demonstrates significant racial disparities, with Black patients and other individuals with skin of color experiencing higher disease severity yet receiving less access to advanced therapies compared to White patients. This review examines existing literature on differences in prescription patterns, treatment modalities, and clinical outcomes for psoriasis in White versus Black populations. Focus is placed on biologics, systemic non-biologic therapies, phototherapy, and topical treatments, highlighting inequities in treatment access, clinician decision-making, and infrastructure availability. Black patients are consistently underprescribed advanced therapies, such as IL-17 and IL-23 inhibitors, despite evidence supporting their efficacy in severe plaque-dominant phenotypes. Instead, systemic corticosteroids and methotrexate are disproportionately prescribed, even though they are associated with suboptimal outcomes and higher side-effect profiles. Phototherapy, while effective for darker skin types, is less frequently recommended due to barriers including access and clinician unfamiliarity with tailoring treatment for skin of color. Emerging data suggests that the specialty of the prescribing clinician plays a role in these disparities, with non-dermatologists being less likely to initiate biologic therapies and more likely to prescribe older systemic treatments. Additionally, structural barriers, including limited access to dermatologists and phototherapy centers equipped for darker skin tones, exacerbate inequities. This review identifies key gaps in understanding, including the impact of implicit bias on treatment decisions, differences in adherence and patient-reported outcomes by race, and the role of systemic factors such as insurance coverage and geographic access to care. Strategies to address these disparities include expanding education for non-dermatologist providers, improving infrastructure for phototherapy, and incorporating culturally sensitive approaches into patient education and clinician training.

Tomotaka Tanaka ¹, Daiki Hirano ¹, Syohei Ishimaru ¹, Keiko Arataki ¹

Cureus 2025 Jan 18;17(1):e77641. doi: 10.7759/cureus.77641. eCollection 2025 Jan.

We report the case of a 37-year-old male patient diagnosed with moderate left-sided ulcerative colitis (UC). Initial therapy with 5-aminosalicylic acid (5-ASA) was terminated within days due to exacerbation of symptoms, leading to a diagnosis of 5-ASA intolerance. Although induction of remission was achieved with prednisolone, the patient developed steroid dependency. Treatment with vedolizumab and ustekinumab subsequently failed to achieve clinical or endoscopic improvement. Intensive granulocyte and monocyte apheresis (GMA) was introduced, successfully inducing remission. However, during maintenance therapy with GMA, the patient experienced a relapse. Initiation of golimumab yielded suboptimal results, necessitating a combination therapy involving prednisolone and reintensified intensive GMA. This multimodal approach successfully achieved remission induction and maintenance. This case highlights the potential utility of intensive GMA in combination with golimumab and prednisolone for the management of refractory UC, particularly in patients with 5-ASA intolerance and failure of multiple biologic agents. A brief review of the relevant literature is included.

M Hupé , G Bouguen , A Buisson , C Landman , M Uzzan , S Nancey , C Guillaume , G Cyrielle , M Charkaoui , M Serrero , A Wampach , M Collins , R Altwegg , F Cholet , A Amiot

Journal of Crohn’s and Colitis, Volume 19, Issue Supplement_1, January 2025, Page i1338, https://doi.org/10.1093/ecco-jcc/jjae190.0858

Background: Granulocyte and monocyte adsorptive apheresis (GMA) with ADACOLUMN® (JIMRO Takasaki Japan) is an effective and safe therapeutic option for patients with mild to moderate inflammatory bowel disease (IBD) refractory to pharmacological therapy, especially ulcerative colitis (UC). The aim of this study was to report effectiveness of GMA in patients with IBD.

Methods: All consecutive active, non-operated UC patients and Crohn’s disease (CD) patients treated with GMA in 15 French tertiary-care centres from 2007 to september 2024 were assessed. Patients received 4 to 8 weekly sessions of GMA alone or in combination with previously failing advanced therapy. Patients were assessed for effectiveness at week 14 and at week 54 for those continuing GMA as maintenance therapy and at every visit for safety. Clinical remission, steroid-free clinical remission, clinical response, colectomy as well as safety were ascertained.

Results: One hundred and twenty-nine patients with IBD (75 males, median age: 40.9 IQR[29.3-58.1] years, 102 with UC, IBD duration: 7.0 [2.9-13.1] years) were included. One hundred patients (77.5%) were previously treated with immunosuppressants and 97 (72.2%) with at least one anti-TNF. In patients with UC, baseline median total Mayo score was 7 [6-12] and mean CRP level was 23.3 ± 86.0 mg/L. In patients with CD, baseline median Harvey-Bradshaw index was 9 [7.25-10.75] and mean CRP level was 21.9 ± 27.3 mg/L. In patients with UC, week 14 clinical remission, steroid-free clinical remission and response rates were 33.3%, 27.5% and 52.0%, respectively. In patients with CD, week 14 clinical remission, steroid-free clinical remission and response rates were 33.3%, 29.6% and 66.7%, respectively. At week 14, nine patients with UC and 3 patients with CD required emergent surgery. At week 14, adverse events were reported in 26 (20.2%) and were mainly related to flare of IBD in 16 (12.4%). Other adverse events which were never classified as serious included headache in 3, arthromyalgia in 3 and abdominal pain, diarrhea, grade-1 increase in liver enzymes and mild hypotension in one. At week 54, 48 patients were still treated with maintenance GMA therapy including 13 with CD and 35 with UC. At week 54, steroid-free clinical remission rates were 38.5% (5/13) in patients with CD and 60% (21/35) in patients with UC.

Conclusion: In this real world cohort of patients with refractory IBD, GMA induced steroid-free clinical remission in one third of patients with CD and UC at W14. In patients continuing GMA maintenance therapy, steroid-free clinical remission was observed in one third of patients with CD and two thirds of patients with UC. Safety profile was favourable mostly related to relapse of IBD.

Yoshifumi Hamasaki ¹, Ryo Matsuura ², Takahide Shinagawa ³, Soichiro Ishihara ³, Sozaburo Ihara ⁴, Mitsuhiro Fujishiro ⁴, Kent Doi ⁵, Masaomi Nangaku ^1 2

J Clin Med Res. 2024 Dec;16(12):625-634. doi: 10.14740/jocmr6071. Epub 2024 Dec 20.

Background: Granulocyte and monocyte adsorption apheresis (GMA) is a therapeutic option for remission induction in the active ulcerative colitis (UC) patients. Effects of high processed blood volume of GMA as remission induction therapy on the long-term prognosis of UC patients have remained unclear. For this study, we investigated the relation between re-exacerbation of UC and the processed blood volume of GMA performed as induction therapy.

Methods: Data from UC patients treated using a total of 10 GMA sessions as remission induction therapy during 2012 – 2022 were retrospectively collected and analyzed. The relation between the GMA dose, processed blood volume of GMA divided by body weight, and UC re-exacerbation requiring inpatient treatment within 1 year was evaluated.

Results: This study examined data of 72 active UC patients, with median age of 44.4 years (65% male) and median GMA dose of 34.2 mL/kg/session. Kaplan-Meier analysis showed the 1-year exacerbation-free rate was significantly higher in the higher GMA dose group than in the lower GMA dose group (P = 0.008). Cox proportional hazards regression analyses revealed a higher GMA dose as inversely associated with the re-exacerbation of UC within 1 year (hazard ratio: 0.36, 95% confidence interval: 0.17 – 0.78). Extended treatment time of GMA session beyond 60 min contributed to achieving the higher GMA dose and did not increase unexpected treatment termination because of clotting.

Conclusion: Greater processed blood volume of GMA per patient body weight may be associated with a lower 1-year exacerbation rate in UC patients.

Masashi Akiyama ¹

J Dermatol. 2025 Mar;52(3):400-407. doi: 10.1111/1346-8138.17585. Epub 2024 Dec 19.

Generalized pustular psoriasis (GPP) is a severe autoinflammatory keratinization disease (AiKD) characterized by acute flares of widespread sterile pustules and high fever. GPP is potentially life-threatening. Recently clarified genetic predisposing factors for GPP suggest that the excessive activation of innate immune pathways in the skin, including of interleukin (IL)-1 and IL-36 signaling, plays a significant role in the GPP pathogenesis. IL36RN, CARD14, AP1S3, MPO, SERPINA3, BTN3A3, and MEFV have been identified as GPP-related genes. The pathogenesis of GPP provoked by variants in these seven genes is tightly associated with the excessive activation of innate immune pathways and the resulting autoinflammation in the skin. Various biologics, including inhibitors for the tumor necrosis factor, IL-17, and IL-23 pathways, are used as treatments for GPP. The new understanding of the genetic background of GPP, mentioned above, indicates that the genetic predisposing factors are predominantly related to the excessive activation of innate immunity and autoinflammation. In this context, inhibitors of inflammatory signaling, including of the IL-1 and IL-36 pathways, have been used in clinical practice and investigated as potential future therapies.