Combined immune checkpoint inhibitor therapy with nivolumab and ipilimumab causing acute-onset type 1 diabetes mellitus following a single administration: two case reports.

BACKGROUND: The use of immune checkpoint inhibitor (ICI) therapy is becoming a standard of care for several cancers. Monoclonal antibodies targeting cytotoxic T-lymphocyte antigen-4 (CTLA-4) and programmed cell death protein 1 (PD-1) or its ligand (PD-L1) cause a broad spectrum of autoimmune adverse events. ICI-induced type 1 diabetes mellitus (T1DM) is extremely rare (< 1%) but potentially life-threatening. It appears to be more common with PD-1 blockade (or combination immunotherapy) than with anti-CTLA-4 therapy, often during the first three to six months of therapy. CASES PRESENTATION: We report an acute onset T1DM with severe inaugural diabetic ketoacidosis (DKA) and remarkably elevated Glutamic Acid Decarboxylase antibody (GADA) titres following a single administration of combined ICI therapy with nivolumab (anti-PD-1) and ipilimumab (anti-CTLA-4) in two adult patients with advanced metastatic melanoma. In these cases, the time to diabetes onset was remarkably short (two and five weeks), and one presented with fulminous T1DM in a previous long-standing type 2 diabetes mellitus. CONCLUSIONS: Oncological patients treated with combination therapy of anti-PD-1 and anti-CTLA-4 can develop a particular pattern of T1DM, with very rapid onset within a few weeks after starting ICI therapy, even in the presence of an existing type 2 diabetes. ICI-induced T1DM is a medical emergency in presence of severe inaugural DKA and requires a collaboration between specialists and primary care physicians, as well as patient education, for early diagnosis and supportive care.

Madurella mycetomatis infection of the buttock in an Eritrean refugee in Switzerland: a case report.

BACKGROUND: Mycetoma is a neglected infectious disease caused by a fungus (eumycetoma) or bacteria (actinomycetoma); it is characterized by chronic local inflammation with sinus formation and purulent discharge. Its course can be quite devastating because of the difficulty in diagnosing the infection and in eliminating the causative agent. Although endemic in many countries in the tropics and subtropics, the migration of Africans to Europe may increase the presence of this neglected disease in European countries. We present a case of an Eritrean patient living in a non-endemic country who was diagnosed as having an infection of Madurella mycetomatis in an atypical location in his body. CASE PRESENTATION: We report the case of a 35-year-old African male refugee from Eritrea, living in Switzerland since 2015, who presented with a 1-year history of a painful soft tissue swelling associated with dark nodules in his right buttock. He mentioned having several previous surgeries after 2001 while he was in Eritrea due to recurrent abscess formation on this body area. In the previous months, the swelling had become more significant and nodules started draining a purulent fluid. An initial diagnostic hypothesis of buttock abscess was made and he was referred to a dermatologist for diagnostic confirmation and further specialist care due to the size and atypical presentation. After a punch biopsy, the diagnosis of eumycetoma was confirmed and cultures developed Madurella mycetomatis. The initial treatment approach consisted of oral treatment by itraconazole; however, a surgical resection of the lesions was finally needed. CONCLUSIONS: Although rare, mycetoma should be diagnosed as early as possible to avoid long-lasting complications. Primary care physicians in European countries are frequently in the first line of care of migrant patients and therefore should be aware of the common and uncommon clinical presentations of mycetoma.