IGM is a rare chronic inflammatory benign disease of the breast with a different clinical presentation and controversial optimal treatment modality. Recently observed more in Middle Estern breastfeeding women.[21] The main etiologies of this disease are unknown. Autoimmunity to proteins and some microorganisms, or breastfeeding reactions are suspected etiologies [12, 22].
Surgery had an elevated full remission rate along with a relatively low recurrence rate but avoided as much as is feasible for cases concerning surgical scarring and immunosuppressive agents are preferred in the treatment of IGM. However, the systemic corticosteroids have several side effects[23], [24], [25]
In our center, oral steroids are mainly used when patients develop systemic symptoms. Furthermore, immunosuppressive treatment with methotrexate is used when the disease progresses during oral steroid treatment alone. Based on the lengthy course and high dose of oral steroid therapy, side effects are unavoidable and have become a serious challenge in ensuring treatment adherence.
Recent investigations suggest topical or local injection steroids for better cosmetic outcomes and also if patients intend rapid remission. [13, 26, 27]
To the best of our knowledge and review of literature, few studies suggest local injection as an alternative treatment of surgery or systemic steroids and MTX therapy.[14, 18]
In the present study, we tried to compare the effectiveness of local steroid injection, combined systemic immunosuppressive administration and intralesional corticosteroid injection and systemic immunosuppressive administration alone.
In our study, We show that local steroid injection are as effective as systemic immunosuppressive administration.
Recently, one study [13] suggests that intralesional steroid injection was an effective treatment for IGM compared with systemic steroid treatment, active observation and surgical resection. These treatment modalities are amongst the commonly reported treatment options for IGM.
Surgery has unfortunate cosmetic outcomes, tardy scar healing, and high relapse rates. For this reason, systemic steroid treatment has been the common treatment in IGM[12, 26, 28, 29].
Systemic steroid therapy has longterm disease control but patients experience various side effects such as weight gain, hirsutism, diabetes mellitus, and Cushing’s syndrome lead to limitations in treatment.[30]
Recentely, some studies suggest the use of topical treatment and local steroid injection in IGM.
In a randomized study by Cetin et al [26], the efficiency of the topical and systemic steroid treatment was similar in IGM. Although cases responded later to topical treatment, with a mean recovery period of 22 weeks with topical treatment compared to 11.7 weeks on systemic therapy. In the same study, The lack of systemic side effects in topical treatment (2.4% vs. 38.2%) increased the compliance of the patients with the topical therapy. They demonstrated that systemic, topical, and combined therapies had no superiority, and topical therapy was among first-line treatment because it had fewer side effects and more compliance than systemic therapy.
In a study by Altintoprak et al.[12] clinical improvement in 28 IGM patients occurred in an average of 8.3 weeks without topical steroid-related side effects, mean follow up of 37.2 months showed success rate of over 90% in long-term.
There is no reported randomized prospective clinical trial study that compared systemic therapy with local injection for IGM treatment. To the best of our knowledge, our study is the first prospective randomized trial to assess the efficacy of local corticosteroid injection and systemic use. Four studies suggested an injection of steroids into the breast cavity; all studies showed good clinical and radiological response without complications. [13, 15, 17, 18]
In Kim et al.’s study [16], they compared intralesional triamcinolone (2–4 cc, 40mg/ml) injected once every 1 or 2 weeks with or without oral steroid (10 mg/daily) administration, and this was repeated until the resolution of symptoms and ultrasonography findings considered as treatment goal and treatment stopped afterwards. Intralesional Triamcinolone injection was an effective treatment modality for IGM. The recurrence rate was zero in the above-mentioned study.
In a retrospective non-randomised study by Toktas et al[18], the combination of steroid injection and topical steroid therapy in IGM showed same results as first line therapy which is systemic steroid therapy in patients with non-complicated IGM. Local steroid injection may even be more effective than systemic treatment in term of pooled analysis of complete and partial reponse rate, respectively (93.5% vs 71.9%).
In our study, the excellent and good response rate in the local injection group (90.3%) and combined therapy group (89.4%) were more than the systemic group (80%).
The Mean size of the largest mass in the combined therapy group was larger than other groups, significantly. Breastfeeding reactions is one of the suspected etiology of IGM. The mean breast feeding time in combined therapy group patients was more than two other groups. These two issues may affect response rate to the treatment in this group.
A low recurrence rate is an important treatment goal. The relapse rate during treatment of the injection alone group was zero, relapse in combined and systemic therapy groups was 2 (5.2%) and 4 (13.3%) during the first 5 month period which considered as poor control.
To date, surgery is one of the best treatment options with a low recurrence rate and high complete remission (CR) rate. [24, 31] The meta-analysis of the CR and recurrence rate revealed overall estimates of 94.5% (95% CI 88.9%, 98.3%) and 4.0% (95% CI 1.5%, 8.4%), respectively.[24]
The CR rates and recurrence rate of IGM cases treated with oral steroids ranged from 30.8%[32] to 100.0%[33, 34] and from 0.0%[34] to 46.2%[35], respectively. The pooled estimates for CR rate and recurrent rate of steroids were 71.8% (95% CI 67.1%, 76.3%) and 20.9% (95% CI 9.2%, 16.1%), respectively.[24]
In our study, CR rate and recurrence rate of systemic therapy patients were 56.6% and 3.3%, respectively.
Two studies [12, 36] reported a CR rate of 100% for IGM patients treated with topical steroids. The recurrent rates were 10.7% and 18.2%, respectively. The pooled estimate for CR rate and recurrence rate of topical steroids were 98.8% (95% CI 93.3%, 99.8%) and 14.3% (95% CI 5.4%, 26.6%).[24]
In our study, CR rate of combined therapy and local injection group were 63.1% and 64.5%, respectively. The recurrence rate of combined therapy and local injection groups were
13.2% and 16.4% respectively.
The results of our clinical study indicated that local steroid injection alone and in combination with systemic therapy could quickly control the symptoms and be effective as systemic therapy alone to treat IGM.
The efficacy of local injection steroid therapy was validated for breasr limited IGM of the breast in our study. The optimal steroid, dosage, and injection site remain unclear. Different steroids should be injected in future studies to find the optimal steroid dosage. Although young women have dense mammary glands, administering CS into the gland tissue is difficult, but we suggest intralesional injection in the palpable mass and normal breast tissue in patients with IGM under sonography giude.
We selected the intralesional and also four spaces around the mastitis lesion as the injection site because steroids in this site could be absorbed by the breast tissue and would thereby have a rapid effect. In this study, the effectiveness of local betamethasone injection was verified.
In addition to high efficiency and low recurrence rates, the side effects of local corticosteroid therapy should be considered. Although the exact amount of systemic absorption and the side-effects associated with local injections remain unclear, the effects associated with oral CS use could also occur with local CS injection [37]. To minimize possible side-effects, we used up to four injections (28 mg of betamethasone, comparable to 233 mg of prednisone and equivalent to a 1-week oral dose of prednisone for a 70-kg patient) during the whole therapeutic cycle and used injection steroids as a follow-up treatment. Since a vast majority of IGM patients were healthy young women and a low dosage was used in our study, the risk of systemic side-effects was significantly reduced.
In the limitation section of this super selective study that might result in treatment allocation bias,short patient follow-up times was one of the pitfalls. short term follow up might have an impact on the recurrence rates.
A trials with a larger sample size and alternative steroid administration can provide a comprehensive understanding of the efficacy and treatment-related side effects of local steroid injections in limited breast IGM.