Yuko Higashi ^1 2, Atsuko Ibusuki ¹, Tomoko Fukushige ¹, Ryoko Sagara ¹, Risako Yonezawa ¹, Natsumi Terada ¹, Hisao Kawahira ¹, Kimiko Kazumura ³, Takuro Kanekura ¹

Ther Apher Dial. 2025 Aug;29(4):702-706. doi: 10.1111/1744-9987.70043. Epub 2025 May 25.

Introduction: Activated neutrophils play a crucial role in the development of neutrophilic dermatoses, including pustular psoriasis. Adsorptive granulocyte and monocyte apheresis (GMA) is an effective treatment for skin disorders. Although previous basic research has demonstrated neutrophil activation, no efficient method exists to assess it in clinical settings.

Methods: We measured neutrophil activity in patients with GPP who underwent GMA therapy using the FLP-H4200, a newly developed neutrophil activity evaluation system. Blood samples were collected before the first and after the fifth GMA session.

Results: In Case 1, which responded to GMA, the neutrophil activation value decreased from 118 603 to 26 234, reaching the normal range. In Case 2, the response to GMA was poor, and the neutrophil activation value decreased from 140 623 to 76 780, which remained significantly above the normal level.

Conclusion: These results suggest that the neutrophil activity evaluation system may be useful for assessing disease severity and therapeutic efficacy.

Ludovica Franceschin ¹, Alessia Guidotti ¹, Roberto Mazzetto ¹, Jacopo Tartaglia ¹, Christian Ciolfi ¹, Mauro Alaibac ¹, Alvise Sernicola ¹

Biomolecules. 2024 Nov 27;14(12):1515. doi: 10.3390/biom14121515.

Neutrophil-mediated inflammation is a key feature of immune-mediated chronic skin disorders, but the mechanistic understanding of neutrophil involvement in these conditions remains incomplete. Dapsone, colchicine, and tetracyclines are established drugs within the dermatologist’s therapeutic armamentarium that are credited with potent anti-neutrophilic effects. Anti-neutrophilic drugs have established themselves as versatile agents in the treatment of a wide range of dermatological conditions. Some of these agents are approved for the management of specific dermatologic conditions, but most of their current uses are off-label and only supported by isolated reports or case series. Their anti-inflammatory and immunomodulatory properties make them particularly valuable in managing auto-immune bullous diseases, neutrophilic dermatoses, eosinophilic dermatoses, interface dermatitis, and granulomatous diseases that are the focus of this review. By inhibiting inflammatory pathways, reducing cytokine production, and modulating immune responses, they contribute significantly to the treatment and management of these complex skin conditions. Their use continues to evolve as our understanding of these diseases deepens, and they remain a cornerstone of dermatological therapy.

GMA is a promising alternative in patients who have failed conventional therapies for generalized pustular psoriasis, pyoderma gangrenosum, Behçet’s disease, and hidradenitis suppurativa. The strengths of GMA lie in its favorable tolerability and peculiar mode of action that is able to deplete inflammation without causing immunodeficiency.

Lluís Puig ¹, Hideki Fujita ², Diamant Thaçi ³, Min Zheng ⁴, Ana Cristina Hernandez Daly ⁵, Craig Leonardi ⁶, Mark G Lebwohl ⁷, Jonathan Barker ⁸

Dermatol Ther (Heidelb). 2024 Sep;14(9):2331-2378. doi: 10.1007/s13555-024-01230-z. Epub 2024 Aug 1.

Generalized pustular psoriasis (GPP) is a rare, chronic and potentially life-threatening autoinflammatory skin disease characterized by widespread eruption of sterile pustules, with or without systemic inflammation. GPP can significantly reduce patients’ quality of life (QoL). Several therapeutic approaches have been described in the literature, but there is no consensus on optimal treatment. In this review, we summarize published literature on efficacy, safety and QoL outcomes associated with current treatment of GPP with both approved and non-approved products. Embase and MEDLINE databases were searched (1980-September 2023). A search protocol was designed in accordance with the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines and registered on the PROSPERO database (CRD42021215437). Details on publication, population, intervention, efficacy, safety and QoL were captured and checked by independent reviewers. In total, 118 publications were included, with only 19% of publications reporting on the results of clinical trials. Treatment modalities reported for GPP included non-biologic systemic therapies such as retinoids, cyclosporine and methotrexate, topical agents, biologics and small molecules, among others. Results were highly heterogeneous and methodological quality was very low, with only the interleukin-36R inhibitor spesolimab reporting results from placebo-controlled randomized trials; based on this, spesolimab is now approved for GPP treatment in regions including the USA, Japan, China, the EU and several other countries. Some other biologics are approved exclusively in Japan and Taiwan for the treatment of GPP based on open-label studies with small patient numbers in lieu of double-blind studies. Non-standardization of clinical outcomes across studies remains a major hurdle in reaching a consensus on optimal treatment. However, recently trials have been conducted using well-defined, disease-specific endpoints to evaluate GPP-targeted treatments, which will hopefully advance patient care. In conclusion, this review highlights the need for prospective randomized studies with GPP-specific endpoints to determine the optimal treatment strategy.

GMA was approved for the treatment of GPP in Japan in 2012 

Grisell Starita-Fajardo 1, David Lucena-López 1, María Asunción Ballester-Martínez 2, Montserrat Fernández-Guarino 2, Andrés González-García Int J Mol Sci. 2023 Oct 26;24(21):15622. doi: 10.3390/ijms242115622

Neutrophilic dermatoses (NDs) are a group of noninfectious disorders characterized by the presence of a sterile neutrophilic infiltrate without vasculitis histopathology. Their physiopathology is not fully understood. The association between neutrophilic dermatoses and autoinflammatory diseases has led some authors to propose that both are part of the same spectrum of diseases. The classification of NDs depends on clinical and histopathological features. This review focuses on the recent developments of treatments in these pathologies.

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.

Koji Kamiya ¹, Yumi Aoyama ², Mariko Kawata ², Tetsuya Takiguchi ³, Seiko Mitsui ², Yoshiki Tokura ⁴, Keiji Iwatsuki ² , Eur J Dermatol. 2015 Apr;25(2):189-90.

https://pubmed.ncbi.nlm.nih.gov/26075324/

Tomomi Fujisawa ¹, Kana Murase, Yoko Okumura, Hiroyuki Kanoh, Tomoaki Doi, Shouzo Yoshida, Shinji Ogura, Mariko Seishima

Ther Apher Dial 2011 Aug;15(4):374-8. doi: 10.1111/j.1744-9987.2011.00961.x. Epub 2011 Jun 7.

Generalized pustular psoriasis (GPP) is one of the neutrophilic dermatoses mainly caused by activated neutrophils and monocytes. Granulocyte and monocyte adsorption apheresis (GCAP) is a useful extracorporeal circulation therapy for removal of activated granulocytes and monocytes. In this study, GCAP was used to treat three patients with different types of GPP; the diagnoses indicated patient 1 had GPP, patient 2 had GPP developed from psoriasis vulgaris and patient 3 had GPP based on psoriatic erythroderma. We performed GCAP on each of these patients once a week, for a total of five times. We found that the patients’ pustules and edema disappeared and their erythema was reduced by GCAP therapy. Moreover, no adverse effects were observed. Thus, we conclude GCAP could be effective for treating various types of GPP.

https://pubmed.ncbi.nlm.nih.gov/21884472/

Takuro Kanekura ¹, Katsuya Hiraishi, Koichi Kawahara, Ikuro Maruyama, Tamotsu Kanzaki

Ther Apher Dial 2006 Jun;10(3):247-56. doi: 10.1111/j.1744-9987.2006.00369.x.

In the present study, we have shown that granulocyte and monocyte adsorption apheresis (GCAP), an extracorporeal apheresis instrument whose column contains cellulose acetate (CA) beads, is useful for skin diseases attributable to activated granulocytes and psoriatic arthritis (PsA). We assessed the clinical effectiveness of GCAP and investigated the mechanisms underlying the adsorption of pathogenic granulocytes. The effect of GCAP was assessed in 14 patients with neutrophilic dermatoses and 16 with PsA. The mechanisms by which the instrument adsorbs activated granulocytes were investigated using an in vitro mini-column system that mimics the GCAP. Skin lesions and arthropathy improved in 22 of 29 patients (75.9%) and 14 of 18 (77.8%), respectively. Mac-1 (CD11b/CD18) expression on the peripheral neutrophils, increased compared with normal subjects, was reduced by GCAP. In the mini-column system, CA beads adsorbed 50% neutrophils; and adsorption was inhibited significantly by treating plasma with EDTA and blood cells with antihuman CD11b monoclonal antibody. GCAP was useful for treating neutrophilic dermatoses and PsA. GCAP adsorbs Mac-1-expressing neutrophils to the CA beads by the binding of complement component (iC3b) on CA beads and CD11b expressed on activated neutrophils.

https://pubmed.ncbi.nlm.nih.gov/16817789/