Idiopathic granulomatous mastitis (IGM) is a chronic inflammatory disease of the breast, the etiology of which, has still not been elucidated. There have been several mechanisms proposed to explain the pathogenesis. Since the first description of the disease, it has proved itself to be a great diagnostic and therapeutic challenge. It is very often misdiagnosed as cancer, resulting in myriad workup by the physician and great distress to the patient. Clear guidelines as to the management have still not been described. Here, we describe two patients who presented with IGM and have been successfully treated. The first patient was treated with a combination of steroids and antibiotics. The second patient achieved remission of the disease with antibiotics alone. We also propose an algorithm for the management of IGM.

Background: Patients with pre-existing autoimmune disease (AD) have been largely excluded from clinical trials of immune checkpoint inhibitors (ICI), so data on safety of ICIs among patients with pre-existing AD are relatively limited. There is a need for deeper understanding of the type and management of complications from ICI in patients with pre-existing AD. We sought to investigate the safety of ICIs in patients with pre-existing ADs as well as factors associated with AD flare.Methods: Consecutive patients with pre-existing AD who received monotherapy as well as combination of ICI therapies at our institution from September 2015 through September 1 st , 2018 were identified.Clinical information was abstracted via manual chart review. Clinical factors associated with AD flare were determined using multivariable logistic regression.Results: A total of 42 patients were identified of whom 12 developed AD flare. All flares were treated with oral or topical corticosteroids, while a patient with flare of rheumatoid arthritis was treated with tofacitinib and another patient with Crohn's flare was treated with infliximab. Female sex, smoking status, higher age at the start of ICI therapy, cancer type, such as melanoma and lung cancer as compared to other cancers, were not significantly associated with AD flare, however, patients with underlying rheumatologic AD were noted to have a five times greater likelihood of flare as compared to other non-rheumatologic AD. Nine patients developed new immune related adverse events (IRAEs) unrelated to underlying AD, such as inflammatory poly-arthropathy, neuropathy, hypothyroidism, diarrhea, lichenoid drug eruptions, which were managed with oral and/or topical corticosteroids. ICI was stopped in six patients due to AD flare, in four patients due to IRAE flare (out of which one resumed ICI after resolution of IRAE). Conclusions:In patients with pre-existing AD treated with ICI, AD flare occurred in 28% of patients and were managed successfully with corticosteroids alone or with additional disease-modifying therapies. ICI could be considered in patients with AD, but with very close monitoring and preemptive multidisciplinary collaboration.

Immune checkpoint inhibitors have ushered in a new era in cancer management. Nivolumab is a human immunoglobulin G4 (IgG4) monoclonal antibody that selectively inhibits programmed cell death-1 (PD-1) activity by binding to the PD-1 receptor. This inhibits suppression of the T-cell activity, which can in turn cause increased killing of cancer cells. This alteration in the activity of the T cells can cause them to lose their ability to identify host cells and leads to immune-related adverse effects (irAE). Nivolumab-induced hepatotoxicity is rare and accounts for 3–6% of all irAE. We present a case of nivolumab-induced hepatitis. A woman who was treated for recurrent renal cell carcinoma presented with hepatitis. Workup for other causes was negative and the hepatitis was attributed to the administration of nivolumab. She was started on oral steroids followed which she initially improved. However, she later presented with massive upper gastrointestinal bleeding secondary to gastroduodenal ulcers and subsequently developed acute tubular necrosis and passed from the complications. Immune checkpoint inhibitors have proven to be a promising approach in the management of a wide array of neoplasms by immunomodulation. As these agents are becoming standard of therapy in the management of cancers, a heightened vigilance in the diagnosis of irAE is warranted. With heightened vigilance, early recognition can lead to decreased mortality and morbidity.

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