Granulomatous mastitis has several etiologies. In general, the etiology of this disorder can be divided into two major groups including infectious and non-infectious causes. Infectious causes are the main cause of granuloma formation in the human body [
5] and granulomatosis can be caused by mycobacterial, fungal and bacterial infections. Non-infectious causes of granulomatosis mastitis are sarcoidosis, Wegener granulomatosis, and the reaction of a breast to a foreign body [
6]. Erythema nodosum is usually idiopathic. However, there are other possibilities which may result in this non-specific cutaneous manifestation including beta-hemolytic streptococcal infections, mycobacterial infections, sarcoidosis, inflammatory bowel disease (Crohn's disease and ulcerative colitis) and carcinoma (mainly lymphoma or leukemia) [
7].
As mentioned above, the specimen cultures of bacterial, fungal and mycobacterial infections were negative; the results of the AFB stain and Mantoux test were negative as well. In addition, the solid response to treatment with prednisolone points towards a non-infectious etiology. There was no evidence of any form of malignancy in the pathological examination. Since ANCA was normal, Wegener granulomatosis disease was excluded. The patient did not have any gastrointestinal complaints and inflammatory bowel disease is not a usual cause of granulomatous mastitis.
The cutaneous manifestation of sarcoidosis is divided into two different types: specific and non-specific [
8]. As granulomas are seen on biopsy, the sarcoid skin manifestation will be entitled specific cutaneous sarcoid lesions [
8]. In our case, granulomas were detected on breast biopsy. So, the breast abscess of our patient is a specific kind of sarcoid lesion. However, erythema nodosum is recognized as the most common non-specific skin manifestation of sarcoidosis [
8]. Hence, it can be said that our case had both specific and non-specific cutaneous sarcoid lesions. To the best of our knowledge, only seven patients with sarcoidosis following IFN-β therapy have been reported in the literature. The initial report by Abdi
et al. in 1987 reported the case of a 57-year-old woman with renal cell carcinoma who developed pulmonary sarcoidosis following treatment with IFN-β and vinblastine [
9]. Subsequent reports include a case report by Bobbio-Pallavicini
et al. in 1995 which discusses a woman diagnosed with multiple myeloma who developed sarcoidosis involving different organs, including liver, bone, and lungs following treatment with IFN-β [
10]. Mehta
et al., in 1998, reported the case of a 57-year-old man with MS who developed cutaneous sarcoidosis after being treated with IFN-β for 2 years and 2 months [
11]. More recently, in 2005, O'Reilly
et al. reported the case of another patient with pulmonary sarcoidosis following weekly treatment with IFN-β [
12]. Since that time, three other patients have been reported, all published in 2012. Of these three patients, one was a 39-year-old woman with skin and pulmonary involvement after 3 years of IFN-β treatment, the second one was a 35-year-old man who developed pulmonary sarcoidosis after 6 years of IFN-β treatment, and the third one was a 30-year-old woman with a 5-month history of IFN-β treatment who also had only pulmonary sarcoidosis [
13‐
15]. The present patient was a 33-year-old Caucasian woman with MS who was treated with IFN-β for 2.5 years and developed both pulmonary and cutaneous sarcoidosis. From a clinical standpoint, in all seven reported patients, IFN-β was discontinued after the discovery of the adverse developments. The first patient was not treated [
9]. However, the second patient was treated with corticosteroids, and the third patient recovered following treatment with a combination of hydroxychloroquine, psoralen, and ultraviolet A [
10,
11]. One patient improved without any treatment and one was treated with prednisone, hydroxychloroquine, and methotrexate [
8,
9]. The final two reported patients were treated with prednisolone and hydroxychloroquine due to the continuity of the signs and complaints, and prednisolone, respectively. In the last patient, prednisolone resulted in complete resolution [
12,
13]. Treatment of our patient with a combination of indomethacin and prednisolone caused a significant decrease in the signs and symptoms. A total of eight patients, including the current presented patient, have been reported to have sarcoidosis following treatment with IFN-β, six of which were patients with MS. The average duration of treatment with IFN-β was 28.1 months. In a considerable presentation, the rate of pulmonary and skin involvement in these eight patients was 87.5% and 37.5%, respectively. While IFN-β-induced sarcoidosis may appear to be a separate entity, further research should be conducted to determine factors involved in the occurrence of sarcoidosis following IFN-β treatment. The development of sarcoidosis following treatment with IFN-β seems evident; however, the event may be attributed to its immunomodulatory properties or its effect on the activation of proinflammatory mediators, which can result in the formation of granuloma [
13]. The diagnosis of IFN-induced sarcoidosis (IIS) in a patient with MS may be questionable since it is difficult to establish a clear-cut causal relationship. It is well known that sarcoidosis is a great imitator of MS [
16]. Therefore, views that the patients presented in this report had from the beginning only sarcoidosis and not MS should be taken into consideration. However, it should be stressed that the available data on the ratio of involved organs in the patients with IIS are different from natural sarcoidosis [
4], so it is most probable that IFN-β, similar to IFN-α, can cause sarcoidosis in patients with MS due to its immunomodulatory properties. Further, it should be noted that the immunopathology of MS may actually contribute to the induction of sarcoidosis in patients undergoing IFN-β treatment. In general, this phenomenon is a form “biologics-induced autoimmune disease”, which has been recently described by Perez-Alvarez
et al. and includes diverse autoimmune diseases caused by different biological drugs [
17].