https://orcid.org/0000-0003-4117-6603
Idiopathic granulomatous mastitis (IGM) is a rare benign inflammatory breast entity characterized by lobulocentric granulomas. In recent years, the knowledge on this disease, which is not as rare as it was supposed in the past, has considerably grown. Currently, it has been estimated that IGM can be ruled out in 0.44 and 1.6% of all breast biopsy specimens, following accepted pathological criteria [Citation1].
The etiology of IGM remains controversial and several contributing factors, such as use of contraceptive pill, high level of prolactin [Citation2], smoking and alpha-1 antitrypsin deficiency [Citation3], have been emerged in the last decades. Overall, an autoimmune reaction related to presence of milk proteins in the interstitial breast tissues, as consequence of micro-trauma secondary to infection, trauma or chemical irritation, seems to be the most accredited hypothesis for explaining the genesis of IGM [Citation4]. This assumption is strongly supported not only by the clinical response to steroid treatment of women with IGM, but also by the immunohistochemical demonstration of T-lymphocyte dominance in biopsy specimens. In particular, T-cell mediated inflammation could be responsible for ductal damage and consequent formation of noncaseating granulomas [Citation5].
Given this background, we would highlight an original study about IGM recently published in Journal of Investigative Surgery. Notably, this case series focuses on the serum levels of interleukin (IL)-17 and IL-22 in women affected by IGM [Citation6]. Thanks to the discovery that levels of these cytokines are higher in patients with IGM compared to patients without this diagnosis, the authors of the study have strongly supported the hypothesis that autoimmune mechanisms may have a not negligible role in IGM. In the current literature, several immune regulatory functions have been described for IL-17 and IL-22: specifically, while IL-17 is commonly associated with induction of allergic responses, IL-22 may contribute to synthesis of innate antimicrobials (i.e. defensins). Interestingly, IL-17 seems to act with IL-22 to induce expression of antimicrobial peptide by keratinocytes [Citation7]. It has been previously reported that aberrations of expression and function of both cytokines may have a critical role in genesis and establishment of some autoimmune diseases such as human rheumatoid arthritis or multiple sclerosis [Citation8].
Even if an autoimmune trigger could be likely involved in IGM pathogenesis, the mechanism underlying the development of this disease still remains not so well identified. We deem that ascertaining the precise cause behind the IGM could certainly lead to an improvement in the clinical management of patients affected. In near future, new studies could be carried out to find out if IGM is associated to organ-specific and systemic autoimmune diseases. Moreover, the fact that some patients with specific autoimmune disease may have a higher risk of developing IGM can lead to the organization of follow-up in centers with adequate expertise and this may subsequently decrease the time necessary to diagnose the IGM.
Currently there is no consensus regarding the treatment of patients affected by IGM: an algorithm differentiating treatments (expectant management, use of steroid and/or methotrexate, surgical excision) according to extension and severity of the disease has been proposed [Citation9]; however, at the moment, the therapeutic management of patients with IGM is still different in each center.
The discovery of increased levels of IL-17 in the serum of IGM patients could open the door to new targeted therapies, such as biological drugs. In recent years specific IL-17 inhibitors (i.e. secukinumab) have been marketed and are used in patients affected by psoriasis or psoriatic arthritis [Citation10].
Obviously, we have to underscore that this study is limited by a small sample size and by the fact that only a single center is involved in patients’ recruitment and data analysis; this does give high level of evidence to the results obtained. However, these data seem to support the autoimmune pathogenesis at the basis of the IGM. Future studies based on larger patients’ population will certainly increase the current knowledge about this disease.
Disclosure statement
The authors declare that they have no competing interests.
References
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- Bani-Hani KE, Yaghan RJ, Matalka II, et al. Idiopathic granulomatous mastitis: time to avoid unnecessary mastectomies. Breast J. 2004;10(4):318–322. doi:10.1111/j.1075-122X.2004.21336.x.
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- First in the world regulatory approval of Novartis’ Cosentyx(TM) in Japan for both psoriasis and psoriatic arthritis. Novartis AG. 2014. 12–26. Available at: https://www.novartis.com.cn/xin-wen-zhong-xin/xin-wen-fa-bu/Cosentyx-in-Japan. Retrieved 2015-03-12.