Since Kessler and Wolloch defined IGM in 1972, despite time and developing technology and treatment modalities, uncertainty in the physiopathology of IGM and debates on its treatment continue [2, 3]. Although autoimmunity is the cause most supported by the literature, various etiological factors such as various hormonal disorders (hyperprolactinemia, etc.), oral contraceptive use, autoimmune factors, microorganisms, smoking, and alpha 1-antitrypsin deficiency have been blamed [8–10]. The fact that the physiopathology of IGM is not well known has hampered effective treatment. [11]. In addition to surgical and non-surgical treatment modalities, the use of local steroids has recently been discussed in the literature. In this study, we aimed to discuss cases with IGM treated with local and systemic steroids in light of current literature.
The rate of smoking and oral contraceptive use, which are etiological factors, was 0-23.7% and 15.3%-52.6%, respectively [3, 12–15]. In our study, while smoking was 12.3% in the LC group, it was 20.4% in the OC group. There was no history of oral contraceptive use in either group of our patients. In this context, the effects of smoking and oral contraceptive use on the pathophysiology of the disease are questionable.
Although most patients receive antibiotic treatment before the definitive diagnosis because of diagnostic uncertainty, routine antibiotic use is not recommended given thats IGM is a sterile condition [3, 16]. Oral steroid and antibiotic use rates were very high in the OC group. The lack of high treatment responses has led to the reuse of these medications. High doses and long-term use of these medications cause some complications and increase the cost of treatment. The fact that these were lower in the LC group (steroid use;10.5%, antibiotic use;75.4%) indicates the effectiveness of the local steroid treatment and a more effective professional approach to the disease. Similarly, the tru-cut biopsy rates are high in the LC group.
Although one of the most used methods in the treatment of IGM is steroid therapy and surgery, there are many options such as follow-up, antibiotics, non-steroidal anti-inflammatory drugs, colchicine, methotrexate, azathioprine, imuran, and mycophenolate mofetil. And there is a current study about local steroid use [3, 11–13, 15, 17, 18]. There are opinions that wide local excision is the most ideal treatment. However, surgical excision may have a high recurrence rate, poor wound healing, fistulization, and cosmetic problems [19]. In recent years, medical treatments have been more preferred in the treatment of IGM [15]. Corticosteroids have been defined as first-line therapy because of their positive results [12]. On the other hand, steroids are known to cause side effects that affect all systems such as blood sugar irregularity (steroid-induced diabetes mellitus), weight gain, Cushing's syndrome, and body weight gain, and as a result they require a change in treatment algorithm [11, 15, 20–22]. Topical corticosteroids are used in the treatment of many skin diseases, especially atopic dermatitis, due to their anti-inflammatory, vasoconstrictive, antiproliferative and immunosuppressive effects. While steroids can be easily absorbed through normal skin, their absorption at the site of inflammation is increased [18, 23].
Topical steroid use was first described in an IGM case by Altintoprak et al. in 2011. They saw a significant improvement in the patient's clinic after 5 weeks of treatment [18]. In their next studies, they treated 28 patients with only topical steroid for an average of 8.2 weeks (range 4–12 weeks) and noted that the long-term efficacy of treatment was more than 90% [11]. After that Munot et al. applied local steroids to the breast lesion in 4 patients and noted clinical and radiological improvement in all patients [24]. In our previous study, in which we treated patients with uncomplicated IGM with local steroids, we showed that there was 93.5% improvement in the lesion in the first month after the first dose. The rate of patients with complete response after the third dose was 93.4% [3].
When we look at the treatment durations of different studies in the literature; Lai et al. [25] found that the duration of treatment in the observation treatment group was 14.5 months. Cetinkaya et al. [15] in their study, found that the duration of improvement in the observation group was 5.6 months (1.3-13.8) and 3.9 months (0.8-9.8) in the systemic steroid treatment group. Azizi et al. [12] described the recovery period of the observation group as 9 months in their study. By 15 months of treatment with MTX, 75% achieved disease remission, and 13-15 (range 1-30) months were median duration of treatment [13]. In a study by Montazer et al. [26] improvement was seen after 12 months in 93.3% of patients in the group treated with high-dose steroids (50 mg daily), while 53.3% of patients in the low-dose steroid group were able to improve after 6 months [27]. In their study in which they performed steroid injection, Alper et al. showed that 89.3% of the patients had complete recovery in their mean follow-up of 11.8 (5-20) months. In our study, 98.2% (56 patients) in the LC group and 87.0% (47 patients) in the OC group were complete responders after three months (p=0.001). When comparing our study with the literature, we see that the treatment time in the the LC group was significantly shorter. In other words, we see that we can reach a high cure rate in a shorter time.
Equally as difficult as treatment in patients with IGM is the recurrence of the disease. Although it varies according to the type of treatment in the literature, the recurrence rate in IGM is reported to be between 5-50%. The recurrence rate in this study was 24.8% [12]. Montazer et al. [26] found no significant difference in the recurrence rate between the conservative and surgical treatment groups. Cetinkaya et al. [15] found that recurrence rates were 14.3% in the observation group, 42.9% in the systemic corticosteroid group, and 21.4% in the antibiotic group. Postolova et al. [13] found that recurrence rate was 50% after surgery. They found that 15.8% of patients had recurrence during their treatment with MTX. In our study, while 7% (4 patients) of the patients in the LC group had recurrence, 37% (20 patients) in the OC group had recurrence (p=0.001). The literature indicates that the recurrence rate was significantly lower according to the use of systemic.
The greatest restriction on the use of the steroid is undoubtedly its side effects. Cetinkaya et al. [15] reported in their study that the treatment was not successful in more than half of the patients they treated with steroids and that the patients had problems due to various side effects. In another study involving treatment with MTX, side effects were reported in 15.7% of patients [13]. Yin et al. [2] stated in their article that the side effects of topical, systemic, and combined steroid treatments were 2.4%, 38.2% and 30.3%, respectively. Munot et al. [24] reported they had no side effects in any of the 4 patients they treated with steroid injection [27]. In a study in which they used local steroids, Alper et al. found that none of the 28 patients with IGM observed steroid-related side effects. In our previous study, which was multicentric, the rate of steroid-related side effects was 2.2% in the local steroid group, while it was 9.4% in the systemic steroid group [3]. In our study, there were no steroid-related side effects in the LC group and 11.1% (6 patients) in the OC group.
Wide surgical excision may be required to prevent recurrence; however, it causes large defects in the breast, resulting in negative cosmetic outcomes and psychological burden [2]. Chirappapa et al. [28] reported in their cohort study that surgical resection offered no advantage over steroids in terms of healing time, and even 52% (13/25) of patients had wound complications. Shin et al. [29] reported that surgical resection may result in significant breast deformity, extensive scarring, and other complications. In our study, the patients' need for surgery was 3.5% in the LC group and 59.3% in the OC group (p=0.001).