Nobuhiro Ueno ^1 2, Yu Kobayashi ³, Aki Sakatani ², Tatsuya Dokoshi ³, Keitaro Takahashi ³, Katsuyoshi Ando ³, Shin Kashima ³, Kentaro Moriichi ³, Hiroki Tanabe ³, Yuki Kamikokura ⁴, Mishie Tanino ⁴, Mikihiro Fujiya ² 

J Clin Apher. 2025 Jun;40(3):e70030. doi: 10.1002/jca.70030.

Ulcerative colitis (UC) is a chronic inflammatory condition requiring lifelong management, with anti-tumor necrosis factor α (anti-TNF-α) agents often used for refractory cases. However, secondary loss of response (LOR) to these agents, due to anti-drug antibodies, poses a significant therapeutic challenge. This report describes a case where granulocyte and monocyte adsorptive apheresis (GMA) maintenance therapy successfully restored the efficacy of an anti-TNF-α agent in a 26-year-old male with active UC experiencing LOR to infliximab. Following GMA induction therapy and continued infliximab administration, clinical symptoms improved, fecal calprotectin levels decreased, and clinical remission was achieved. Long-term maintenance with GMA enabled sustained clinical remission, with mucosal healing observed one year post-therapy. This case suggests that GMA maintenance therapy may serve as a novel therapeutic approach for patients with active UC experiencing LOR to anti-TNF-α agents. However, further studies are warranted to elucidate the underlying mechanisms and validate its efficacy.

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.

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.

Maki Setake ¹, Ryosaku Tomiyama ¹, Tomoya Kuda ², Kanetaka Maeshiro ³, Akira Hokama ⁴

Rev Esp Enferm Dig. 2024 Oct 4. doi: 10.17235/reed.2024.10795/2024. 

A 17-year-old man with ulcerative colitis (UC) presented to our hospital with neck pain and fever after vomiting. On examination, a snowflake sensation was noted in the neck. A chest radiograph showed extensive subcutaneous emphysema in the chest. CT scans showed extensive subcutaneous emphysema in the neck, shoulders and axilla, as well as pneumomediastinum and pneumothorax. A diagnosis of pneumomediastinum with exacerbation of UC was made, and he was fasted and treated with antibiotics. Intensive granulocyte and monocyte adsorption apheresis (GMA) was started for exacerbation of UC. His symptoms and the radiological findings of pneumomediastinum improved. He remained in remission on azathioprine. UC is a chronic inflammatory bowel disease (IBD) associated with extraintestinal manifestations (EIM). Very few cases have been complicated by pneumomediastinum. The increase in alveolar pressure due to vomiting and systemic inflammation-related pleural or esophageal damage may cause pneumomediastinum in this case. Prevention of progression to mediastinitis and treatment of exacerbated UC are contradictory. GMA was successful because it was not an immunosuppressive therapy. Our case highlights that rare EIM may complicate exacerbation of UC.

Marion Thomas ¹, Olivier Fogel ¹, Omar Al Tabaa ¹, Alice Combier ¹, Sandrine Ninino ², Patricia Detre ², Yannick Allanore ¹, Jérôme Avouac ³

Joint Bone Spine. 2024 Dec;91(6):105781. doi: 10.1016/j.jbspin.2024.105781. Epub 2024 Sep 24.

Mingdan Zhao, Fujun Huang, Lei Tang, Xun Zhou,Miao Zhang, Mengxue Liao,Lirong Liu,Mengya Huang, Front. Immunol. 2024, 15,doi.org=10.3389/fimmu.2024.1354578

Acute generalized pustular psoriasis (GPP) is a serious illness. Despite various treatment methods, there is still lack of effective treatment plans for refractory cases with multiple comorbidities. This case report presents a 67-year-old woman with acute GPP, stage 4 chronic kidney disease (CKD), type 2 diabetes, and cardiovascular disease, in whom skin symptom disappearance and kidney function improvement were observed after the use of oral tacrolimus as the sole therapy. This is the first report on the application of tacrolimus in the treatment of acute GPP, especially refractory acute GPP. The successful treatment indicates that there are shared immune pathways between acute GPP and CKD, and the pathways can be interdicted by tacrolimus. Further studies are needed to optimize the therapy to maximize efficacy and minimize toxicity.

Satoshi Tanida 1 2, Ryoji Kubo 3, Shoichiro Yoshii 3, Takuya Takahama 2, Shun Sasoh 2, Yoshimasa Kubota 2, Tesshin Ban 2, Tomoaki Ando 2, Makoto Nakamura 2, Takashi Joh 2 Case Reports J Clin Med Res . 2023 Dec;15(10-11):446-455. doi: 10.14740/jocmr5005. Epub 2023 Nov 3.

A 44-year-old woman who had been diagnosed with ulcerative colitis (UC) at 22 years old was diagnosed with severe flare-up of UC based on endoscopic findings associated with new-onset active pyoderma gangrenosum (PG) on both lower legs after she decided to discontinue UC treatment. Systemic treatment with intravenous prednisolone at 30 mg/day had achieved insufficient response to UC and PG, resulting in a diagnosis of corticosteroid-refractory UC and PG. Combination therapy with upadacitinib at 45 mg/day plus intensive granulocyte and monocyte adsorptive apheresis (GMA) was started to achieve clinical remission of UC. Ten weeks after starting this combination therapy, clinical improvement of UC was achieved with PG ulcer healing on both lower legs. A combination of upadacitinib plus intensive GMA may offer an effective therapeutic option for patients with active PG in addition to UC but has yet to be approved for induction or maintenance treatment of PG worldwide. PG is a dermatological involvement in UC patients that requires attention.

Mauro Mastronardi, Elisabetta Cavalcanti, Nunzia Labarile, Raffaele Armentano, Francesco Gabriele, Margherita Curlo, Therapeutic Advances in Chronic Disease. 2023;14. doi:10.1177/20406223231194190

Extraintestinal manifestations occur rather frequently in ulcerative colitis (UC) and Crohn’s disease patients and are usually related to an exacerbation of the underlying intestinal bowel disease but sometimes may run a course independent of the inflammatory bowel diseases (IBD). About one-third of patients with IBD develop extraintestinal manifestations, such as pyoderma gangrenosum (PG). PG is an uncommon inflammatory skin disorder of unknown pathogenesis. There are no specific serological or histological markers, and diagnosis is predominantly clinical. Topical and systemic therapies are both vital aspects of treatment and immune modulators have been used with increasing success in recent years, although immunosuppressive drugs raise some concerns due to an increased risk of serious and opportunistic infections and cancer, particularly in elderly and comorbid patients, underlining the unmet need for safer alternative therapies. Thus, in this case report, we highlighted an adsorptive granulocyte/monocyte apheresis (GMA) as a new therapeutic possibility in IBD patients with extraintestinal manifestations. We report a case of a 60-year woman with a history of UC with a Mayo grade 3 score which was associated with a PG. Given that the patients maintained clinical remission with vedolizumab, we preferred not to perform a combined treatment with other antitumor necrosis factor-alpha or ciclosporin, thus avoiding an increased risk of serious infections in the patient. Therefore, we performed the extracorporeal leukocyte apheresis. The patient progressed favorably, with progressive improvement of skin and bowel disease. Therefore, adsorptive GMA has a very favorable safety profile and has been confirmed in numerous studies. In this study, we underlined that an intensive regimen of GMA paves the way to an ideal option for patients with severe and refractory PG complicated with UC.

Mauro Mastronardi 1, Elisabetta Cavalcanti 2, Nunzia Labarile 1, Raffaele Armentano 3, Francesco Gabriele 4, Margherita Curlo 1 Ther Adv Chronic Dis. 2023 Nov 3:14:20406223231194190. doi: 10.1177/20406223231194190.

Extraintestinal manifestations occur rather frequently in ulcerative colitis (UC) and Crohn’s disease patients and are usually related to an exacerbation of the underlying intestinal bowel disease but sometimes may run a course independent of the inflammatory bowel diseases (IBD). About one-third of patients with IBD develop extraintestinal manifestations, such as pyoderma gangrenosum (PG). PG is an uncommon inflammatory skin disorder of unknown pathogenesis. There are no specific serological or histological markers, and diagnosis is predominantly clinical. Topical and systemic therapies are both vital aspects of treatment and immune modulators have been used with increasing success in recent years, although immunosuppressive drugs raise some concerns due to an increased risk of serious and opportunistic infections and cancer, particularly in elderly and comorbid patients, underlining the unmet need for safer alternative therapies. Thus, in this case report, we highlighted an adsorptive granulocyte/monocyte apheresis (GMA) as a new therapeutic possibility in IBD patients with extraintestinal manifestations. We report a case of a 60-year woman with a history of UC with a Mayo grade 3 score which was associated with a PG. Given that the patients maintained clinical remission with vedolizumab, we preferred not to perform a combined treatment with other antitumor necrosis factor-alpha or ciclosporin, thus avoiding an increased risk of serious infections in the patient. Therefore, we performed the extracorporeal leukocyte apheresis. The patient progressed favorably, with progressive improvement of skin and bowel disease. Therefore, adsorptive GMA has a very favorable safety profile and has been confirmed in numerous studies. In this study, we underlined that an intensive regimen of GMA paves the way to an ideal option for patients with severe and refractory PG complicated with UC.

Yoshitaka Furuto ¹, Rikimaru Sawada ², Akio Namikawa ¹, Nobuyuki Matsuhashi ², Yuko Shibuya ¹ Cureus. 2023 Aug 16;15(8):e43599. doi: 10.7759/cureus.43599.

Granulocyte/monocyte adsorptive apheresis (GMA) therapy is a treatment method for ulcerative colitis (UC). Twice-weekly GMA regimens are usually administered to treat severe UC. Although GMA efficacy is considered frequency-dependent, there is no uniformly accepted optimal GMA regimen, and there is insufficient evidence regarding optimal GMA therapy frequency for acute fulminant UC. Case 1 was of a 33-year-old man, and case 2 was of a 20-year-old woman. They were diagnosed with acute fulminant UC and treated with steroid therapy, but exhibited exacerbated UC, and their conditions worsened. We, therefore, initiated intensive frequent GMA therapy (conducted 10-11 times during a 13-day period). In both cases, remission was achieved within two weeks of therapy induction. Herein, we describe two consecutive cases in which rapid remission of acute fulminant UC was achieved without adverse events using intensive frequent GMA therapy. These cases suggest that intensive frequent GMA therapy might induce rapid remission in acute fulminant UC cases and may be more effective than twice-weekly GMA regimens.

Intensive Frequent Granulocyte Adsorptive Apheresis Therapy for Acute Fulminant Ulcerative Colitis: Two Consecutive Case Reports – PubMed (nih.gov)

Intensive Frequent Granulocyte Adsorptive Apheresis Therapy for Acute Fulminant Ulcerative Colitis: Two Consecutive Case Reports – PMC (nih.gov)