Methotrexate‐based regimen as initial treatment of patients with idiopathic granulomatous mastitis

Mahbubeh Haddad MD1 | Fereshte Sheybani MD1,2 | Mahnaz Arian MD1 | Masoumeh Gharib MD3

Lobular granulomatous mastitis (LGM) or idiopathic granulomatous mastitis (IGM) is an idiopathic breast inflammation that affects young or middle‐aged women throughout the world. It is an important di- agnostic and therapeutic challenge, as most patients were initially misdiagnosed by the physicians, leading to diagnostic confusion and heightened anxiety.1 About the management of patients with IGM different therapeu- tic strategies have been proposed; however, the efficacy of none of them was evaluated in randomized placebo control trials.2 A recent systematic review regarding treatment for IGM showed that surgical managements with or without corticosteroids are associated with high complete resolution rate and relatively low recurrence rate.3 However, not all patients prefer or are candidate for surgical inter- vention and some patients require a corticosteroid‐sparing medical treatment. There are a few reports of IGM patients who treated with corticosteroid‐sparing anti‐inflammatory drugs including colchicine, methotrexate (MTX), azathioprine, or hydroxychloroquine in the lit- erature.4-6 Methotrexate as an immunosuppressive agent has been used in combination with corticosteroids for treatment of IGM. However, MTX monotherapy or in combination with low doses of corticosteroid has been rarely used.5

In the present retrospective cohort, we reviewed the clinical out- come of our patients with IGM who referred to infectious disease clinic of Mashhad University of Medical Sciences, Mashhad, Iran and were treated with MTX‐based regimen. Patients who referred to our clinic with granulomatous mastitis were evaluated and treated ac- cording to the diagnostic and therapeutic protocol that is provided in Figure 1. Patients were followed up clinically and their recurrences recorded. Overall, 21 patients with granulomatous mastitis were referred to our clinic. Among those with granulomatous mastitis, 18 were diagnosed as IGM and 3 tuberculous mastitis. Of 18 patients with IGM, 17 cases could be followed up and included in the study. All patients were female with a mean age of 36 ± 6.8 years. They were all married except for one with previous history of prolactinoma who developed her symptoms several months after removal of hypoph- yseal adenoma while receiving prolactin‐lowering agents. Summary of findings is showed in Table 1. Two patients developed IGM during pregnancy. One of them who developed severe breast inflammation with bilateral ankle ar- thritis and multiple erythema nodosum in the second trimester did not receive any medications despite severity of symptoms and signs because of her unwillingness to take pills during pregnancy and lac- tation. She followed up until 6 months after delivery when the in- flammation gradually subsided and draining sinuses healed with scar formation. Another patient who developed symptoms during the third trimester presented during her lactational period and received low doses of prednisone. She responded well to treatment with no relapse during the follow‐up period.

Among patients who developed adverse drug effects, only one case who reported hair loss stopped treatment and in others the adverse effects were mild (eg, nausea, mild headache, decreased in appetite, and mild increase in liver function tests). The patients who experienced significant hair loss completed 3 months of treatment with MTX plus low dose of prednisone when we finally decided to stop her treatment. At that time her symptoms and signs were resolved, and she received no other treatment without relapse of symptoms during more than 1‐year follow‐up period. Overall, three patients experienced relapse of symptoms during follow‐up period. In all of them, the severity of symptoms and signs were mild to moderate and they were all responded well to retreat- ment with low dose methotrexate. Our results demonstrate a favorable result of MTX‐based medi- cal treatment for IGM patients and the rate of relapse or recurrence during their follow‐up period. About seventy‐four percent of our pa- tients with IGM received MTX‐based regimen. All patients showed complete remission and 17.6% experienced relapse of disease after treatment tapering that responded well to low dose MTX treat- ment. The adverse drug reactions were mild except for one patient who experienced continuing hair loss during the treatment period. Accordingly, for those patients with IGM who are not candidate for surgical intervention or require corticosteroid‐sparing medical treat- ment, as well as those whose symptoms recur after tapering of their initial treatment, MTX‐based treatment could be an attractive alter- native therapeutic option with favorable outcome and less frequent side effects. To our knowledge, this is the first study on MTX‐based initial treatment of IGM. The majority of available literature on IGM re- ported treatment with surgical management or high doses of cor- ticosteroids 3 that is associated with considerable adverse drug.

MTX had been initiated at different stages or their treatment was changed to MTX because of a lack of response to corticosteroid treatment, recurrence or corticosteroid‐induced adverse reactions, while in others MTX in combination with corticosteroid was the ini- tial treatment. Most of the reports on MTX in the management of IGM used it in combination with high doses of corticosteroid or after recurrence of symptoms during or after tapering of corticosteroids 2,7‐9; however, MTX monotherapy or in combination with low doses of corticosteroids were rarely reported.5 Despite the findings associated to the therapeutic protocol in our study, we found another important feature regarding IGM that was a clinical anergic response to purified protein derivative of tu- berculin (PPD) among patients with IGM in this study and also in our previous report of 22 patients with IGM 1 that could raise the possi- bility of similar pathogenicity of IGM and sarcoidosis.10


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