This is the first study to report a case management model applied for GM patients. Although GM is a benign disease, its recurrence, one of the main challenges in the management of patients with the disease, has been reported to occur in 5%-50% of patients [10,11,12]. In our study, the recurrence rate of 11.2% is low in this range. Seventeen patients experienced recurrence, including ten with new lesions in the ipsilateral breast and seven with new lesions in the contralateral breast.
In recent years, the prevalence of granulomatous mastitis has been rapidly increasing, and the most affected patients are women of childbearing age [39]. In two studies, Freeman et al. reported that up to 86% of GM patients had a history of pregnancy in the past 5 years [38]. Prasad et al. reported that 73 patients with GM had a mean age of approximately 33 years and a history of childbirth 4.6 years before mastitis on average [40]. In our study, which had similar characteristics to previously reported studies, the median age of the patients was 32 years (range 22–48), 119 patients had a history of childbirth within the last 5 years, 15 patients had concurrent pregnancy, and 4 patients were currently breastfeeding. These findings indicated that hormones play an important role and may be related to the secretion theory, which has an important place in the pathophysiology of GM [12]. It has been postulated that GM results from a localized autoimmune response to the retained or extra vacated fat- or protein-rich secretions in the breast ducts in women of childbearing age due to previous hyperprolactinemia [41]. Therefore, the breast care for women of childbearing age deserves our attention.
GM patients mostly have mass and pain symptoms, and skin lesions and abscesses can be observed in mass localization. Findings such as fistula, erythema nodosum, and nipple or skin retraction can also be observed [1, 2, 35]. In many studies, the most common reported complaint at the time of the initial visit was a unilateral painful breast mass [35, 42]. Similarly, 98.7% of the patients had mass and pain complaints, and 92.1% of the patients presented with a unilaterally affected breast. The case managers made initial judgments and provided tentative guidance based on clinical presentations. At the initial visit, there were mass (74, 48.7%), abscess (66, 43.4%), and refractory types (12, 7.9%), which were not associated with recurrence in the later stages (P = 0.2). As the disease progressed, 10 mass type cases were actually abscess type cases, and 4 abscess type cases were actually refractory type cases. An important consideration for case managers is the care of the affected breast (shown in Fig. 2 and Fig. 3). Wound care should consist of managing drainage from fistulae with gauze and other nonadherent dressings. Tape should be avoided due to further abrasion and irritation of the skin [43]. Meanwhile, if a patient has a superficial abscess, a case manager should percutaneously perform puncture aspiration, and determine how deep the abscess is, while a mammographer, assisted by ultrasound guidance, performs puncture drainage, to create a path for the drainage of secretions and reduction of pressure in the inflamed area due to the accumulation of inflammatory fluid.
The effect of medical and surgical treatment in the case management. The underlined part of the figure shows the scope of the lesion located by ultrasound. a Before the treatment. b After the steroids treatment for 4 months and before surgical treatment. c Before stopping the steroids treatment and after right breast lesion excision for 1.5 months
The effect of medical treatment in the case management. a Before the medical treatment and wound care. b After the tubercle bacillus drug and wound care for 14 months
Comparing the most recent publications on GM to older studies, there is no new information on this benign breast disease. Therefore, the best management of this disease is still unclear [11, 12]. The usual treatment for GM is close observation, medical treatment, surgical management, or a combination of medication and surgery [3, 15, 44]. In the present study, only 1 (0.7%) patient recovered under observation, 82 (53.9%) recovered with medication and surgery (as shown in Fig. 2), and 69 (45.4%) recovered with medication alone (as shown in Fig. 3). Multivariate analysis revealed that medication and surgery was significantly associated with recurrence (RR = 4.128, 95% CI [1.026–16.610], P = 0.0046) (Table 6). Regarding the cause of recurrence, previous studies have ascribed the incompleteness of excision to the failure of surgical treatment, or inconsistent follow-up times. In this study, case managers assessed changes in the size of the breast mass and the proportion of the mass to the breast size and considered whether the patients could undergo surgical excision with minimal impact on the aesthetics of the breast. Breast lesion excision by minimally invasive surgery or open surgery was applied, which may have a risk of incomplete surgical excision. Akcan et al. and Yabanoğlu et al. reported that complete excision of the breast lesion or wide excision with or without medication achieved low recurrence rates [38, 45]; however, it is possible to cause damage to the breast due to the excessive removal of tissues. Therefore, the biggest problem with surgical treatment is the contradiction between the surgical effect and the postoperative aesthetic effect. Whether the surgical procedure that is chosen which increases the recurrence rate of GM requires further investigation.
Our study demonstrated that medical treatment is the most prevalent treatment, regardless of whether it is coupled with surgical treatment. Drug therapies have numerous side effects, such as Cushion’s syndrome, skin rash, abnormal liver enzymes and abnormal uric acid and [46]. In our study, 8 (5.3%) patients suffered from skin rash, 11 (7.2%) had abnormal liver enzymes, 3 (2.0%) had abnormal uric acid, and 1 (0.7%) had edema on the lips and face (as shown in Table 3). In this stage, case managers served as a treatment team by linking physicians, pharmacists, dermatologists, obstetricians, and general practitioners. They immediately communicated with the multidisciplinary team, and then guided patients regarding their medications, and finally, most of the side effects disappeared within 1 week.
To the best of our knowledge, there are no studies investigating medication adherence in GM patients. In our study, it shown that the MMAS-8 was completed by 154 patients, with 39% who had high adherence, 46.4% who had medium adherence, and 14.6% who had low adherence. As a result of case manager guidance, the “low” medication adherence rate of GM patients was much lower than that of 30% and 50% of reported for adults with chronic disease [47, 48]. Furthermore, “high” medication adherence (RR = 0.428, 95% CI 0.224–0.867, P = 0.015) at 2 months after initial medication use was significantly associated with a lower rate of recurrence in multivariate analysis. At the initial stage, the case managers paid more attention to the changes in the patients’ breast symptoms than to patient medication adherence, and the guidance and supervision of medical staff to patient medication need improvement. Currently, several reports have demonstrated the importance of regular visits to a physician, adequate patient contact time in clinical practice, and patient education to improve medication adherence to treatment [49, 50].
Recent evidence indicates that the occurrence and recurrence of GM is associated with the Corynebacterium species, especially Corynebacterium kroppenstedtii [39, 51]. In our study, samples of C. kroppenstedtii were obtained by ultrasound guidance for the puncture or biopsy of breast abscesses or hypoechoic masses. Breast pus or tissues were used for bacterial culture, and the positive rate of C. kroppenstedti was only 23.69% (36/152). In different studies, the positive rate of C. kroppenstedtii varies considerably, mainly due to the detection techniques. Li et al. [52] reported that nanopore sequencing showed accurate C. kroppenstedti detection over the culture method in GM patients. Therefore, the need to improve detection techniques for the Corynebacterium species will facilitate the study of the relationship between GM and bacteria.
In this study, the results showed that 22 (14.47%) patients had excitant food before the onset of GM. The recent literature reports that bacterial interactions have been confirmed between the breast and gut [53, 54]. Li et al. hypothesized that imbalances among the external environment, host, and microbiota lead to the occurrence of GM as follows: External factors disturb the balance between the immune microenvironment and breast flora and induce the release of inflammatory factors and milk secretion, resulting in damage to the mammary epithelium. The positive feedback between the immune and inflammatory reactions eventually induces GM [13]. The consumption of stimulating foods may disrupt the intestinal flora and induce inflammation. Therefore, patients with GM should be given information regarding disease considerations related to diet, sleep, behaviors, etc., as shown in Table 1.
Our study has several limitations. First, it cannot be confirmed whether interesting factors such as dietary and lifestyle habits are related to the occurrence and recurrence of GM. Second, the effects of this case management model cannot be assessed by this study. Therefore, there are several directions for our next work, including developing targeted strategies based on the case management model and exploring the effectiveness of this model in GM patients.
In conclusion, this study identified some factors associated with the recurrence of the disease under a case management model. “Low” medication adherence was a significant risk factor for the recurrence of granulomatous mastitis. The patients treated with medication and surgery did not have a reduced recurrence rate compared to those treated with medication alone.