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Table of Contents
Year : 2022  |  Volume : 5  |  Issue : 3  |  Page : 154-158

Is there a link between mesh implantation and systematic autoimmune disease?

Department of General Surgery, Affiliated Zhongda Hospital, Southeast University, Nanjing, China

Date of Submission01-Jan-2022
Date of Decision18-Apr-2022
Date of Acceptance19-Apr-2022
Date of Web Publication28-Jun-2022

Correspondence Address:
Dr. Junsheng Li
Department of General Surgery, Affiliated Zhongda Hospital, Southeast University, Nanjing 210009
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Source of Support: None, Conflict of Interest: None

DOI: 10.4103/ijawhs.ijawhs_1_22

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Autoimmune/autoinflammatory syndrome induced by adjuvants (ASIA)/“Shoenfeld’s syndrome” corresponds to a spectrum of immune-mediated diseases triggered by exposure to various materials. Polypropylene (PP) mesh has become the standard for nearly all kinds of hernia repair. There are conflicting reports on the link between ASIA and PP mesh implantation for hernia repair. We reported a typical ASIA/“Shoenfeld’s syndrome” after inguinal hernia repair with PP mesh, and the patient's systematic syndrome was completely alleviated after mesh removal. The present case highlights that there is a link between ASIA/“Shoenfeld’s syndrome” and hernia repair with PP mesh, although not frequently. Both surgeons and patients should bear in mind this disease, and patients should be fully informed before surgery, and registry is an important and possible tool to evaluate and determine the frequency of ASIA after hernia repairs with PP meshes.

Keywords: Autoimmune/autoinflammatory syndrome induced by adjuvants (ASIA), complication, hernia repair, polypropylene mesh, Shoenfeld’s syndrome

How to cite this article:
Li J, Shao X, Cheng T, Ji Z. Is there a link between mesh implantation and systematic autoimmune disease?. Int J Abdom Wall Hernia Surg 2022;5:154-8

How to cite this URL:
Li J, Shao X, Cheng T, Ji Z. Is there a link between mesh implantation and systematic autoimmune disease?. Int J Abdom Wall Hernia Surg [serial online] 2022 [cited 2023 Feb 4];5:154-8. Available from: http://www.herniasurgeryjournal.org/text.asp?2022/5/3/154/349813

The autoimmune/inflammatory syndrome induced by adjuvants (ASIA)/“Shoenfeld’s syndrome” is a recently identified condition in which exposure to an adjuvant leads to an aberrant autoimmune response.[1],[2] This ASIA syndrome shares similar clinical manifestations, including myalgia, myositis, arthralgia, neurological manifestations, dry mouth, cognitive alterations, fever, and chronic fatigue syndrome (CFS).[3] Several foreign body materials have been reported to act as an adjuvant, including vaccines, silicons, mineral oils, and others.[2],[4]

Tension-free hernia repair with polypropylene (PP) mesh is a commonly used material. PP is the standard approach for most hernias, including inguinal hernias and ventral/incisional hernias. In addition, the transvaginal implantation of a PP meshes is also used to reinforce a weak pelvic floor for indications such as stress urinary incontinence (SUI) and pelvic organ prolapse (POP).[5] Theoretically, PP mesh may also act as a trigger for ASIA; however, the hernia mesh-induced ASIA was not well recognized, and conflicting evidence exists in the literature regarding the development of ASIA after hernia repair with PP mesh. Some reported that mesh-based hernia repair was not associated with the development of autoimmune diseases.[6],[7] On the contrary, Cohen postulated that PP mesh implants may increase the risk of developing (auto) immune diseases by acting as an adjuvant in both hernia repair and vaginal mesh implant.[8]

In this study, we reported a case of typical ASIA after right inguinal hernia repair with PP mesh, and all the systematic symptoms were resolved after mesh removal, which indeed highlights there is a link between ASIS and hernia repair with PP mesh. Both surgeons and patients should be aware of this issue.

  Case Presentation Top

A 37-year-old man presented with systematic complaints including myalgias, arthralgias, muscle weakness, dry eyes/dry mouth, chronic fatigue that could not be alleviated by rest or sleep, and sleep disturbances, but no pyrexia. He had been previously healthy; all these symptoms started 11 years ago after a right inguinal hernia repair with PP mesh. He recalled that he had no such symptoms before the right inguinal hernia surgery, and these symptoms appeared to manifest about 2 weeks after the hernia repair with a PP mesh, and the symptoms gradually began to be prominent. He also reported he had problems with concentration. Furthermore, he reported that he lost appetite, and became insensitive to food flavor. In addition, he had diarrhea frequently. He reported that his skin became insensitive to the changes in external temperature. His past medical history was unremarkable. After admission, the laboratory evaluation showed a normal complete blood count and blood chemistry, normal erythrocyte sedimentation rate, and the antinuclear antibodies (ANAs) were also negative. The findings of physical examination were normal, except for the previous scars in the inguinal area, with no tenderness.

He had been to several clinics for this problem, but the causes for this problem could not be identified, and the diagnosis of his complaints could not be established. Meanwhile, he underwent three times of colonoscopy due to irritable bowel syndrome in different hospitals, and the examinations were also quite normal. Finally, the patient came to us, and a diagnosis of ASIA was suspected, and the PP mesh implant was suspected because of a strong clinical suspicion based on the patient’s history. After a detailed discussion with the patient, he decided to remove the hernia mesh.

An elective operation was performed under general anesthesia, and the PP mesh, which contained a plug and patch, was completely removed. There were no signs of mesh infection, no mesh migration [Figure 1], and the spermatic cord was identified and preserved during the operation.
Figure 1: Polypropylene mesh was completely removed

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Surprisingly, 6 h right after the removal of the mesh, the patient reported that he felt the alleviation from those conditions, and he told us that he could smell the food flavor better than before, he could feel the slight changes in the external temperature which he could not before, and the next morning, he told us his sleep became better and refreshment, which he had not experienced for 10 years. After 5 days, the patient was discharged, and he told us he was completely satisfied with the rapid and systematic improvement of his condition, and during the 6-month follow-up, his previous syndrome did not occur.

The histological study showed a chronic inflammatory reaction. There was translucent blue amorphism in the fibrous adipose connective tissue, accompanied by multinucleated giant cell reaction and lymphocyte infiltration, suggesting the adjuvant disease [Figure 2]. The immunohistochemical study showed a positive stain of CD117 (+), CD 38 (+), CD138 (+), and CD163 (+).
Figure 2: Histological study showing a chronic inflammatory reaction, the translucent blue amorphism in the fibrous adipose connective tissue, accompanied by multinucleated giant cell reaction and lymphocyte infiltration

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  Discussion Top

Autoimmune/inflammatory syndrome induced by adjuvants (ASIA) encompasses conditions linked to previous exposure to an adjuvant substance.[1],[9] The syndrome is characterized by non-specific manifestations of autoimmune disease. The clinical picture is very heterogeneous, involving muscle, joint, and nervous system. A variety of adjuvants can induce ASIA. The well-known examples of adjuvants are aluminum hydroxide, squalene and silica, and silicones.[10],[11],[12]

Synthetic nonabsorbable PP mesh has become the dominant material in hernia surgeries and gynecologic surgeries.[13],[14],[15] However, there are conflicting opinions regarding whether the commonly used PP mesh could induce ASIA, and the evidence regarding this issue is limited. One study compared the incidence of the development of systematic/autoimmune disease between patients who underwent hernia repair with PP and patients who underwent colonoscopy. It was concluded that mesh-based hernia repair was not associated with the development of autoimmune disease, as the incidence of systematic/autoimmune disease was 1.6% in hernia group as compared with 1.7% in colonoscopy group (risk ratio [95%CI]: 0.93[0.79–1.09]).[16] However, recently, another study on the long-term mesh complication after laparoscopic mesh sacrohysteropexy reported that the development of newly diagnosed systemic autoimmune disorders was 5.8%.[17] Furthermore, in a study containing 40 patients referred to Autoimmunity Clinic with a history of mesh implantation, 18 patients had a hernia repair and 22 patients had a vaginal mesh implant. Thirty nine of the 40 patients presented with chronic fatigue, and 38 of the 40 patients had myalgia or muscle weakness. Remarkably, these symptoms started shortly after the operation in most patients, therefore, the diagnosis of ASIS was established in these patients. In 6 patients, the hernia mesh was completely removed, and partial recovery of the systemic disease in the 6 patients was observed.[8]

Our present case fulfilled the diagnostic criteria for autoinflammatory/autoimmunity syndrome induced by adjuvants (ASIA) [Table 1].[2] The patient reported that his systematic syndrome started shortly after the inguinal hernia repair and became prominent gradually. In the beginning, he could not correlate these syndromes with the hernia surgery, and he saw the doctors several times for the causes, and failed to be cured. Then he suspects that these complaints may be caused by the implanted mesh, as other possible causes, such as infection, trauma, and stress, were not present.
Table 1: Criteria for the diagnosis of autoimmune/inflammatory syndrome induced by adjuvants (ASIA)

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However, these symptoms are nonspecific and commonly occurred in the community; the causality between these symptoms and mesh was yet to be established. Therefore, with the patient’s full consent and thorough understanding, we aimed to remove the mesh, and the patient indeed feels the recovery from the systemic disease.

Virtually, all implanted materials can induce a foreign body giant cell reaction.[18] These effects are best studied in patients with silicone breast implants.[2],[11] Hwang et al.[19] demonstrated that primary polystyrene (PS) particles were potential immune stimulants that induced cytokine and chemokine production in a size-dependent and concentration-dependent manner. Immediately after implantation of a biomaterial, such as PP mesh, a layer of host proteins is deposited onto the biomaterial surface resulting in the attraction of phagocytes (predominantly macrophages of the pro-inflammatory M1 subtype).[18] Importantly, this process is critically dependent on the presence of activated mast cells and histamine.[20] Furthermore, biomaterials may act as an adjuvant resulting in the enhancement of the adaptive immune response to an autoantigen.[12] In addition, after implantation, a biofilm is formed[21],[22] and the microorganisms in this biofilm may also act as adjuvants. Meshes implement the formation of a persistent inflammation with an ambient fibrotic reaction, and in the inflammatory infiltrate several distinct cell types have been identified, but CD68+ macrophages are supposed to be the most important.[23] In a recent study, Klinge et al.[24] demonstrated the presence of various cell types and local cellular response to the foreign body with the use of five-marker multiplex immunofluorescence microscopy, and revealed the marked complexity of the biology within a foreign body granuloma (FBG). In their study, Klinge found that macrophages as well as lymphocytes and neutrophils played a key role in the chronic inflammation around these foreign bodies; however, the expression profiles of the cells within the FBG were more complex than expected with a high level of interference or coexpression. Klinge implied that although the clinical relevance of neutrophils and neutrophil extracellular traps (NETs) is obscure, the detection of extranuclear DAPI areas (EDA)s around the mesh fibers with abundant expression of histone, myeloperoxidase (MPO), and neutrophil elastase (NE) underlines the importance of the neutrophils and their formation of neutrophil extracellular traps, which may be responsible for the ongoing chronic inflammation and any possible autoimmune stress.

Therefore, it can be postulated that the systematic illness in prosthetic hernia repair patients is a variant of the autoimmunity/antoinflammatory syndrome induced by adjuvants (ASIA), as described by Shoenfeld and Agmon-Levin.[1]

In our case, the systematic symptoms started about 2 weeks after inguinal hernia repair with a PP mesh. It has been reported that most of the symptoms started shortly after the operation (61%), whereas others may develop several years later.[8] A genetic predisposition has also been implicated in the development of this immune-mediated disease and seems to be a prerequisite to the appearance of such autoimmune syndrome.[9],[25] In our present case, the laboratory examination is not specific; the auto-antibodies are normal. This is consistent with others’ reports, which found that these antibodies (i.e., antinuclear antibodies, ANCA) were only positive in 38% of patients.

Inguinal hernia repair is a common surgery. PP mesh has been safely used for decades in all kinds of hernia repair, and the local effects such as chronic pain have been extensively described; however, systemic effects are not yet well reported. The ASIA syndrome could be underreported because of unawareness and failure of attributing the syndrome to the previous surgery, or the patients who have the syndromes did not report them to doctors. Therefore, the registry is an important and possible tool to evaluate and determine the frequency of ASIA after hernia repairs with PP meshes.

Our present case demonstrated the link between PP mesh and the development of ASIA, and more importantly, the systemic syndromes were alleviated by mesh removal. Therefore, it is important for hernia surgeons to explicitly discuss these risks with patients to ensure together that they are making an informed decision.

Financial support and sponsorship

Not applicable.

Conflicts of interest

There are no conflicts of interest.

Ethical approval

All procedures performed in studies involving human participants were in accordance with the ethical standards of the institutional and/or national research committee and with the 1964 Helsinki declaration and its later amendments or comparable ethical standards. For this retrospective and case study, formal consent is not required.

Human and animal rights

This article does not contain any study with animals performed by any of the authors.

Informed consent

Informed consent was obtained from all individual participants included in the study.

  References Top

Shoenfeld Y, Agmon-Levin N. “ASIA”: Autoimmune/inflammatory syndrome induced by adjuvants. J Autoimmun 2011;36:4-8.  Back to cited text no. 1
Cohen Tervaert JW. Autoinflammatory/autoimmunity syndrome induced by adjuvants (ASIA; shoenfeld’s syndrome): A new flame. Autoimmun Rev 2018;17:1259-64.  Back to cited text no. 2
Watad A, Quaresma M, Brown S, Cohen Tervaert JW, Rodríguez-Pint I, Cervera R, et al. Autoimmune/inflammatory syndrome induced by adjuvants (shoenfeld’s syndrome): An update. Lupus 2017;26:675-81.  Back to cited text no. 3
Naviaux RK, Naviaux JC, Li K, Bright AT, Alaynick WA, Wang L, et al. Metabolic features of chronic fatigue syndrome. Proc Natl Acad Sci U S A 2016;113:E5472-80.  Back to cited text no. 4
Atherton MJ, Stanton SL. The tension-free vaginal tape reviewed: An evidence-based review from inception to current status. Bjog 2005;112:534-46.  Back to cited text no. 5
Clancy C, Jordan P, Ridgway PF. Polypropylene mesh and systemic side effects in inguinal hernia repair: Current evidence. Ir J Med Sci 2019;188:1349-56.  Back to cited text no. 6
Chughtai B, Sedrakyan A, Mao J, Eilber KS, Anger JT, Clemens JQ. Is vaginal mesh a stimulus of autoimmune disease? Am J Obstet Gynecol 2017;216:495.e1-7.  Back to cited text no. 7
Cohen Tervaert JW. Autoinflammatory/autoimmunity syndrome induced by adjuvants (shoenfeld’s syndrome) in patients after a polypropylene mesh implantation. Best Pract Res Clin Rheumatol 2018;32:511-20.  Back to cited text no. 8
Jara LJ, García-Collinot G, Medina G, Cruz-Dominguez MDP, Vera-Lastra O, Carranza-Muleiro RA, et al. Severe manifestations of autoimmune syndrome induced by adjuvants (shoenfeld’s syndrome). Immunol Res 2017;65:8-16.  Back to cited text no. 9
Ruiz JT, Luján L, Blank M, Shoenfeld Y. Adjuvants- and vaccines-induced autoimmunity: Animal models. Immunol Res 2017;65:55-65.  Back to cited text no. 10
Cohen Tervaert JW, Colaris MJ, van der Hulst RR. Silicone breast implants and autoimmune rheumatic diseases: Myth or reality. Curr Opin Rheumatol 2017;29:348-54.  Back to cited text no. 11
Babensee JE. Interaction of dendritic cells with biomaterials. Semin Immunol 2008;20:101-8.  Back to cited text no. 12
Fouda E, Thabet W, Elsaid M, Emile SH, Elbaz SA. A randomized clinical trial of mesh fixation with cyanoacrylate glue compared to sutures in inguinal hernia repair. Int J Abdom Wall Hernia Surg 2020;3:56-62.  Back to cited text no. 13
  [Full text]  
Li J, Bao P, Shao X, Cheng T. The management of indirect inguinal hernia sac in laparoscopic inguinal hernia repair: A systemic review of literature. Surg Laparosc Endosc Percutan Tech 2021;31:645-53.  Back to cited text no. 14
Sahin A, Ölcucuoglu E, Kulacoglu H. Crossing mesh tails in the lichtenstein repair method for medial (direct) inguinal hernia: Recurrence and chronic pain rates after five years. Hernia 2021;25:1231-8.  Back to cited text no. 15
Chughtai B, Thomas D, Mao J, Eilber K, Anger J, Clemens JQ, et al. Hernia repair with polypropylene mesh is not associated with an increased risk of autoimmune disease in adult men. Hernia 2017;21:637-42.  Back to cited text no. 16
Izett-Kay ML, Aldabeeb D, Kupelian AS, Cartwright R, Cutner AS, Jackson S, et al. Long-term mesh complications and reoperation after laparoscopic mesh sacrohysteropexy: A cross-sectional study. Int Urogynecol J 2020;31:2595-602.  Back to cited text no. 17
Major MR, Wong VW, Nelson ER, Longaker MT, Gurtner GC. The foreign body response: At the interface of surgery and bioengineering. Plast Reconstr Surg 2015;135:1489-98.  Back to cited text no. 18
Hwang J, Choi D, Han S, Jung SY, Choi J, Hong J. Potential toxicity of polystyrene microplastic particles. Sci Rep 2020;10:7391.  Back to cited text no. 19
Zdolsek J, Eaton JW, Tang L. Histamine release and fibrinogen adsorption mediate acute inflammatory responses to biomaterial implants in humans. J Transl Med 2007;5:31.  Back to cited text no. 20
Ajdic D, Zoghbi Y, Gerth D, Panthaki ZJ, Thaller S. The relationship of bacterial biofilms and capsular contracture in breast implants. Aesthet Surg J 2016;36:297-309.  Back to cited text no. 21
Langbach O, Kristoffersen AK, Abesha-Belay E, Enersen M, Røkke O, Olsen I. Oral, intestinal, and skin bacteria in ventral hernia mesh implants. J Oral Microbiol 2016;8:31854.  Back to cited text no. 22
Klinge U, Dievernich A, Tolba R, Klosterhalfen B, Davies L. CD68+ macrophages as crucial components of the foreign body reaction demonstrate an unconventional pattern of functional markers quantified by analysis with double fluorescence staining. J Biomed Mater Res B Appl Biomater 2020;108: 3134-46.  Back to cited text no. 23
Klinge U, Dievernich A, Stegmaier J. Quantitative characterization of macrophage, lymphocyte, and neutrophil subtypes within the foreign body granuloma of human mesh explants by 5-marker multiplex fluorescence microscopy. Front Med (Lausanne) 2022;9:777439.  Back to cited text no. 24
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  [Figure 1], [Figure 2]

  [Table 1]


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