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.

Chiamaka L Okorie ¹, Krithika Nayudu ², Vinod E Nambudiri ^3 4

Exp Dermatol. 2024 Jan;33(1):e14934. doi: 10.1111/exd.14934. Epub 2023 Sep 19.

Deficiency of the interleukin-36 receptor antagonist (DITRA) is a rare autoinflammatory disorder caused by mutations in the IL36RN gene. This mutation leads to a lack of functional interleukin-36 receptor antagonists (IL-36Ra), which results in an overactive immune system and chronic inflammation. Despite its rarity, numerous case series and individual reports in the literature emphasize the importance of recognizing and managing DITRA. Early identification of the cutaneous signs of DITRA is crucial for accurate diagnosis and timely administration of appropriate treatment. This review article provides a comprehensive overview of the current understanding of the cutaneous, non-cutaneous and histopathological manifestations of DITRA, with a focus on reported treatments. The disease typically presents in early childhood, although the age of onset can vary. Patients with DITRA exhibit recurrent episodes of skin inflammation, often with a pustular or pustular psoriasis-like appearance. Additionally, non-cutaneous manifestations are common, with recurrent fevers and elevated acute-phase reactants being the most prevalent. The exact prevalence of DITRA is unknown. Some cases of loss-of-function mutations in the IL36RN gene, considered a hallmark for diagnosis, have been identified in patients with familial generalized pustular psoriasis (GPP). Biological therapies with inhibition of IL-12/23 and IL-17 are promising treatment options; paediatric patients with DITRA have shown complete response with mild relapses. New and emerging biologic therapeutics targeting the IL-36 pathway are also of interest in the management of this rare autoinflammatory disorder.

5.3 Granulocyte and monocyte apheresis (GMA) The use of GMA warrants further exploration.

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)

Yue Feng, Weihua Feng, Mei Xu, Chaoping Wu, Huanhuan Yang, Yu Wang, Huatian Gan, Rev Esp Enferm Dig 2023. doi:
10.17235/reed.2023.9808/2023.

Background: the association between sarcopenia and treatment outcomes in inflammatory bowel disease (IBD) is currently a subject of controversy.
Methods: a systematic search was performed of PubMed, Embase, Web of Science, and the Cochrane Library for studies published until April 2023. The quality assessment of each included study was performed using the Newcastle-Ottawa
Scale.
Results: seventeen studies were included with 2,895 IBD patients. Sarcopenia exhibited an increased risk of treatment failure (OR = 2.00, 95 % CI: 1.43-2.79) and notably increased the need for surgery (OR = 1.54, 95 % CI: 1.06-2.23) as opposed to a pharmacologic treatment plan change (OR = 1.19, 95 % CI: 0.71-2.01) among IBD patients. However, no significant association was found between sarcopenia and treatment failure in corticosteroid (OR = 1.21, 95 % CI: 0.55-2.64) or biologic agent (OR = 1.65, 95 % CI: 0.93-2.92) cohorts. Sarcopenia was also linked to elevated treatment failure risks in patients with Crohn’s disease (OR = 1.82, 95 % CI:1.15-2.90) and those diagnosed with ulcerative colitis (OR = 2.55, 95 % CI: 1.05-6.21), spanning both Asian (OR = 1.88, 95 % CI: 1.29-2.74) and non-Asian regions (OR = 2.17, 95 % CI: 1.48-3.18).
Conclusions: sarcopenia was considered as a novel marker for use in clinical practice to predict treatment failure, specifically, the need for surgery in IBD patients. This distinct cohort necessitates clinical attention and tailored care strategies.

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)

Arun K. Mankan, Paulina Czajka-Francuz, Maria Prendes, Sriram Ramanan, Marcin Koziej, Laura Vidal, Kamal S. Saini Front. Immunol., 2023, 14, doi.org=10.3389/fimmu.2023.1208137

As the first responders, neutrophils lead the innate immune response to infectious pathogens and inflammation inducing agents. The well-established pathogen neutralizing strategies employed by neutrophils are phagocytosis, the action of microbicide granules, the production of ROS, and the secretion of neutrophil extracellular traps (NETs). Only recently, the ability of neutrophils to sense and respond to pathogen-associated molecular patterns is being appreciated. This review brings together the current information about the intracellular recognition of DNA by neutrophils and proposes models of signal amplification in immune response. Finally, the clinical relevance of DNA sensing by neutrophils in infectious and non-infectious diseases including malignancy are also discussed.

Iago Rodríguez-Lago ¹, Leticia Abecia ², Iratxe Seoane ², Juan Anguita ³, José Luis Cabriada ⁴Gastroenterol Hepatol. 2023 Jul 6:S0210-5705(23)00370-9. doi: 10.1016/j.gastrohep.2023.07.001.[Article in English, Spanish]

Objective: Primary non-response and secondary loss of response to anti-TNF agents are common in inflammatory bowel disease. Increasing drug concentrations are correlated to better clinical response and remission rates. Combination of granulocyte-monocyte apheresis (GMA) with anti-tumor necrosis factor (TNF) agents could be an option in these patients. The objective of our study was to perform an in vitro assay to determine if the GMA device can lead to infliximab (IFX) adsorption.

Patients and methods: A blood sample was obtained from a healthy control. It was incubated with three concentrations of IFX (3, 6, and 9μg/ml) at room temperature for 10min. At that time, 1ml was collected to determine the IFX concentration. Then, 10ml of each drug concentration was incubated with 5ml of cellulose acetate (CA) beads from the GMA device at 200rpm for 1h at 37°C to simulate physiological human conditions. A second sample of each concentration was collected and IFX levels were determined.

Results: No statistically significant differences were observed in the IFX levels in the blood samples before and after incubation with the CA beads (p=0.41) and after repeated measurements (p=0.31). Mean change was 3.8μg/ml.

Conclusions: The in vitro combination of GMA and IFX did not change the circulating levels of IFX at the three concentrations tested, suggesting that there is no interaction between the drug and the apheresis device in vitro and that they might be safely combined with each other.

An in vitro analysis of the interaction between infliximab and granulocyte-monocyte apheresis – PubMed (nih.gov)

An in vitro analysis of the interaction between infliximab and granulocyte–monocyte apheresis – ScienceDirect

Matteo Megna 1, Elisa Camela 2, Angelo Ruggiero 1, Teresa Battista 1, Fabrizio Martora 1, Sara Cacciapuoti 1, Luca Potestio. Clin Cosmet Investig Dermatol. 2023 Jun 28:16:1677-1690. doi=10.2147/CCID.S407812

Generalized pustular psoriasis (GPP) is a severe and rare form of psoriasis, being a potentially life-threatening condition, characterized by recurring episodes or flares of widespread cutaneous erythema with macroscopic sterile pustules. An irregular innate immune response is linked to GPP, which is considered an auto-inflammatory disorder, while innate and adaptive immunopathogenic responses are involved in psoriasis pathogenesis. In consequence, different cytokine cascades have been suggested to be mainly involved in the pathogenesis of each different psoriasis form, with the interleukin (IL)23/IL17 axis implied in plaque psoriasis, and the IL36 pathway in the GPP. As regards GPP treatment, conventional systemic drugs available for plaque psoriasis are usually used as the first-line treatment option. However, contraindications and adverse events often limit the use of these therapies. In this scenario, biologic drugs may represent a promising treatment option. To date, even if 12 different biologics have been approved for plaque psoriasis, none of these is approved for GPP where they are employed off-label. Recently, spesolimab, an anti-IL36 receptor monoclonal antibody, has been recently approved for GPP. The purpose of this article is to assess the current literature about the use of biological therapies for the treatment of GPP to establish the basis for a shared GPP management algorithm.

Rie Shukuin ¹, Haruka Koizumi ¹, Aoi Ebata ¹, Satoko Imai ¹, Yuta Yamashita ¹, Mariko Ogawa-Momohara ¹, Takuya Takeichi ¹, Yoshinao Muro ¹, Norito Takami ², Masashi Akiyama ¹

J Dermatol. 2023 Jun;50(6):e181-e182.

Successful combination therapy of bimekizumab and granulocyte monocyte adsorption apheresis for generalized pustular psoriasis complicated with microscopic polyangiitis – PubMed (nih.gov)

Toshiyuki Yamamoto, Kenshi Yamasaki, Keiichi Yamanaka, Mayumi Komine, Tamihiro Kawakami, Osamu Yamamoto, Takuro Kanekura, Tetsuya Higuchi, Toshiya Takahashi, Yoshiaki Matsushima, Nobuyuki Kikuchi, Japanese Dermatological Association Pyoderma Gangrenosum Treatment Guidelines Drafting Committee Journal of Dermatology 50 (9) 2023, e253-e275 doi.org=10.1111/1346-8138.16845

Pyoderma gangrenosum (PG) is a rare, neutrophilic skin disease. For the purpose of accurate diagnosis and proper treatment of PG, the Japanese clinical practice guidance for PG developed by the Japanese Dermatological Association was published in 2022. In this guidance, clinical aspects, pathogenesis, current therapies, and clinical questions on PG are described from the viewpoints of current knowledge and evidence-based medicine. Here, the English version of the Japanese clinical practice guidelines for PG is presented and is intended to be widely referred to in the clinical examination and treatment of PG.