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.

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.

Rolf Bambauer¹*, Ralf Schiel², Octavio J Salgado³and Richard Straube (2024) Adv Res Dermatol Cosmetics 3: 1017

Severe and/or refractory dermatological diseases with immunologic origin to conventional therapy have a bad
prognosis. Autoimmune blistering diseases have a high morbidity and mortality. Therapeutic apheresis is an essential supportive treatment for severe and refractory dermatological diseases with an immunologic origin, particularly autoimmune blistering diseases. This approach has been shown to significantly improve the prognosis of these diseases.
Therapeutic apheresis, combined with immunosuppressive therapy and/or human monoclonal antibodies, has treated successfully autoimmune blistering skin disorders. These diseases are caused by the immune system’s targeting of structural proteins in the skin and/or mucous membranes. Improved diagnostic methods have allowed to determine that the incidence and prevalence of these disorders have doubled in the last 15 years to 25 new cases per million people per year owing to an aging population. Over the last 45 years, therapeutic apheresis, in combination with immunosuppression and/or human monoclonal antibodies, has significantly increased survival rates. Therapeutic apheresis using hollow fiber modules is safe and highly effective in eliminating autoantibodies and other toxins from the bloodstream, leading to rapid clinical improvement in dermatological conditions. The guidelines of the for American Application Committee of the American Society for Apheresis are cited dermatologic disorders, which could be treated with therapeutic apheresis

Tom Macleod, Charles Bridgewood, Dennis McGonagle, The Lancet Rheumatology Volume 5, Issue 1, January 2023, Pages e47-e57

Neutrophilic inflammation is a pervasive characteristic common to spondyloarthropathies and related disorders. This inflammation manifests as Munro’s microabscesses of the skin and osteoarticular neutrophilic inflammation in patients with psoriatic arthritis, intestinal crypt abscesses in patients with inflammatory bowel disease, ocular hypopyon in anterior uveitis, and neutrophilic macroscopic and microscopic inflammation in patients with Behçet’s disease. Strong MHC class I associations are seen in these diseases, which represent so-called MHC-I-opathies, and these associations indicate an involvement of CD8 T-cell immunopathology that is not yet well understood. In this Personal View, we highlight emerging data suggesting that the T-cell-neutrophil axis involves both a T-cell-mediated and interleukin (IL)-17-mediated (type 17) recruitment and activation of neutrophils, and also a sequestration of activated neutrophils at disease sites that might directly amplify type 17 T-cell responses. This amplification likely involves neutrophilic production of IL-23 and proteases as well as other feedback mechanisms that could be regulated by local microbiota, pathogens, or tissue damage. This crosstalk between innate and adaptive immunity offers a novel explanation for how bacterial and fungal microbes at barrier sites could innately control type 17 T-cell development, with the aim of restoring tissue homoeostasis, and could potentially explain features of clinical disease and treatment response, such as the fast-onset action of the IL-23 pathway blockade in certain patients. This axis could be crucial to understanding non-response to IL-23 inhibitors among patients with ankylosing spondylitis, as the axial skeleton is a site rich in neutrophils and a site of haematopoiesis with myelopoiesis in adults.

Role of neutrophil interleukin-23 in spondyloarthropathy spectrum disorders – ScienceDirect

Role of neutrophil interleukin-23 in spondyloarthropathy spectrum disorders – The Lancet Rheumatology

Laura Gnesotto ¹, Guido Mioso ¹, Mauro Alaibac ¹

Exp Ther Med 2022 Jun 24;24(2):536. doi: 10.3892/etm.2022.11463. eCollection 2022 Aug. DOI: 10.3892/etm.2022.11463

Adsorptive granulocyte and monocyte apheresis (GMA) is an extracorporeal treatment that selectively removes activated myeloid lineage leukocytes from peripheral blood. This technique consists of a column with cellulose acetate beads as absorptive leukocytapheresis carriers, and was initially used to treat ulcerative colitis. A literature search was conducted to extract recently published studies about the clinical efficacy of GMA in patients with different skin disorders, reporting information on demographics, clinical symptoms, treatment and clinical course. Dermatological diseases, in which GMA has been performed, include generalized pustular psoriasis, pyoderma gangrenosum, palmoplantar pustular psoriasis, Behcet’s disease, Sweet’s syndrome, adult-onset Still’s disease, impetigo herpetiformis, reactive arthritis, acne and hidradenitis suppurativa syndrome, cutaneous allergic vasculitis and systemic lupus erythematosus. In most patients, GMA was started after the failure of conventional therapeutic options and it was helpful in the majority of cases. Based on the information summarized, GMA could be considered a valid non-pharmacological treatment option for patients with several dermatological conditions, which are difficult to treat with other pharmacological preparations.

 PASH syndrome; cutaneous allergic vasculitis; granulocyte and monocyte apheresis; neutrophilic dermatoses; reactive arthritis; systemic lupus erythematosus.

https://pubmed.ncbi.nlm.nih.gov/35837066/

https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9257973/

Nina Worel ¹, Behrouz Mansouri Taleghani ², Erwin Strasser ³ Transfus Med Hemother 2019 Dec;46(6):394-406. doi: 10.1159/000503937. Epub 2019 Nov 6.

The section “Preparative and Therapeutic Hemapheresis” of the German Society for Transfusion Medicine and Immunohematology (DGTI) has reviewed the actual literature and updated techniques and indications for evidence-based use of therapeutic apheresis in human disease. The recommendations are mostly in line with the “Guidelines on the Use of Therapeutic Apheresis in Clinical Practice” published by the Writing Committee of the American Society for Apheresis (ASFA) and have been conducted by experts from the DACH (Germany, Austria, Switzerland) region.

https://pubmed.ncbi.nlm.nih.gov/31933569/

https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6944925/

M Hachiya, T Sakurai, Y Nagata, A Hidaka, Y Akita, H Miyashita, Y Maruyama, R Miyazaki, M Noguchi, R Sawada, J Mitobe, M Mitsunaga, T Yamasaki, T Kato, M Saruta, Journal of Crohn’s and Colitis, Volume 12, Issue supplement_1, February 2018,

Approximately 30% of all cases and 50% of severe cases that had received biologics were not able to avoid surgery. In severe cases, it is important to evaluate early treatment efficacy and prognostic factors because the median time of administration of biologics was only 9 weeks. However, no independent prognostic factor was found in this study.

https://academic.oup.com/ecco-jcc/article/12/supplement_1/S173/4808214

Yong Eun Park ¹, Jae Hee Cheon ^1 2 , Korean J Intern Med. 2018 Jan;33(1):1-19.

Recently, there has been a line of evidence suggesting that biologics such as infliximab and adalimumab are effective in treating intestinal BD. Moreover, new biologics targeting proteins other than tumor necrosis factor α are emerging and are under active investigation. Therefore, in this paper, we review the current therapeutic strategies and new clinical data for the treatment of intestinal BD.

https://pubmed.ncbi.nlm.nih.gov/29207867/

Yuko Higashi ¹, Mitsuyoshi Shimokawa, Kazuhiro Kawai, Takuro Kanekura, J Dermatol. 2013 Dec;40(12):1042-4.

We present a 39-year-old pregnant woman with Behçet’s disease who was treated successfully with granulocyte and monocyte adsorption apheresis (GMA). There were no complications or adverse effects during her pregnancy and delivery. The neonate manifested no abnormalities.

https://pubmed.ncbi.nlm.nih.gov/24303809/

J. Muñoz, M. Clavo, O. Garcia, D. Reina, A. Vidaller, R. Lafuente & L. I. Massuet

ISBT Science Series (2007) 2, 96–101

There is a strong basis to support the modulators properties of innate immunity of GCAP, although there is a lack of data that explains deeply the interactions between the mechanisms involved. GMA may represent a new therapy that offers not a single pathway effect but a global modulation of the most important pathways involved in innate immune response. Future investigations should elucidate the intimate mechanism of action.

https://www.researchgate.net/publication/239319651_Adsorptive_monocyte_and_granulocyte_apheresis_in_the_chronic_inflammatory_illness_ulcerous_colitis_Crohn’s_disease_rheumatoid_arthritis_and_Behcet_syndrome