Context While therapy with immune checkpoint inhibitors such as nivolumab have substantially improved survival in several types of cancer, increased attention has been given to adverse immune events associated with their use, including the development of endocrine autoimmunity. Objectives First, to describe a patient with a two-year history of metastatic small cell lung cancer who had been treated with nivolumab a few months prior to presentation with the signs and symptoms of severe hypocalcemia and hypoparathyroidism. Second, to investigate the etiology of the patient’s hypoparathyroidism, including the presence of activating autoantibodies against the calcium-sensing receptor (CaSR), since humoral and cellular immune responses against the CaSR have been reported in patients with autoimmune hypoparathyroidism. Case and Results A 61-year-old female was admitted with persistent nausea, vomiting, epigastric pain, constipation, and generalized weakness. Laboratory analyses showed low total serum calcium, ionized calcium, and parathyroid hormone (PTH). The patient was diagnosed with severe hypocalcemia as a result of autoimmune hypoparathyroidism after testing positive for CaSR-activating autoantibodies. She was treated with intravenous calcium gluconate infusions followed by a transition to oral calcium carbonate plus calcitriol which normalized her serum calcium. Her serum PTH remained low0 during her hospitalization and initial outpatient follow-up despite adequate repletion of magnesium. Conclusions This case illustrates autoimmune hypoparathyroidism induced by immune checkpoint inhibitor-blockade. As immune checkpoint inhibitors are now used to treat many cancers, clinicians should be aware of the potential risk for hypocalcemia that may be associated with their use.

There is a considerable unmet demand for safe and efficacious medications in the realm of autoimmune and inflammatory diseases. The fate of the immune cells is precisely governed by control of various metabolic processes such as mitochondrial oxidative phosphorylation, glycolysis, fatty acid synthesis, beta-oxidation, amino acid metabolism, and several others including the pentose phosphate pathway, which is a unique source of metabolites for cell proliferation and maintenance of a reducing environment. These pathways are tightly regulated by the cytokines, growth factors, availability of the nutrients and host-microbe interaction. Exploring the immunometabolic pathways that govern the fate of cells of the innate and adaptive immune system, during various stages of activation, proliferation, differentiation and effector response, is crucial for new development of new treatment targets. Identifying the pathway connections and key enzymes will help us to target the dysregulated inflammation in autoimmune diseases. The mechanistic target of rapamycin (mTOR) pathway is increasingly recognized as one of the key drivers of proinflammatory responses in autoimmune diseases. In this review, we provide an update on the current understanding of the metabolic signatures noted within different immune cells of many different autoimmune diseases with a focus on selecting pathways and specific metabolites as targets for treatment.

Objective: The objective of this study is to investigate the clinical characteristics and treatment of patients with early‐onset gout.Methods: We retrospectively reviewed 327 adult patients with a first diagnosis of gout from 2008 to 2016 using the database of a multispecialty group practice in New England. Patients were classified into the following groups: age 30 years or younger at first diagnosis (group 1), age 31‐40 years (group 2), and age over 40 years (group 3). The clinical characteristics and treatment of gout were compared among the three groups.Results: We identified 87 patients in group 1 and 140 patients in group 2. Group 3 included 100 patients randomly chosen from the 7216 patients with a first diagnosis at age over 40 years. Patients within group 1 had significantly higher serum uric acid (sUA) levels at the time of diagnosis and a more prominent family history of gout. Younger patients (groups 1 and 2) had a significantly higher body mass index than patients over 40 years of age (group 3). A substantial number of younger patients also had hypertension or hyperlipidemia. The majority of younger patients met the 2012 American College of Rheumatology (ACR) guidelines for initiating urate‐lowering therapy (ULT) on the basis of frequency of gout attacks, whereas the majority of patients over 40 years of age met the guidelines for ULT on the basis of chronic kidney disease. Patients over 40 years of age were more likely to achieve an sUA level less than 6.0 mg/dl.Conclusion: Patients with a first diagnosis of gout at age 40 years or younger frequently had cardiovascular risk factors and were less likely to achieve an sUA level less than 6.0 mg/dl compared with patients over 40 years of age who were treated in routine clinical practice. Clinicians should be aware that patients with early‐onset gout may be an undertreated population with poor adherence to ULT and increased risk of recurrent gout and cardiovascular diseases.

SLE is increasingly recognized as an important risk factor for cardiovascular disease. Premature CAD and several other cardiac manifestations are resulting in significant morbidity and premature de...

Kikuchi–Fujimoto disease, which was originally described in young women, is a benign condition characterized by necrotizing lymphadenitis and fever. Even though the clinical course is usually self-limiting, it can be associated with recurrences and rarely can be associated with systemic lupus erythematosus or can be complicated with hemophagocytic lymphohistiocytosis. We report the case of a 17-year-old Sri Lankan Sinhalese schoolboy who presented with fever and cervical lymphadenopathy diagnosed as Kikuchi–Fujimoto disease and was complicated with hemophagocytic lymphohistiocytosis subsequently. Later he fulfilled the criteria for systemic lupus erythematosus. A 17-year-old previously healthy Sinhalese schoolboy presented with high-grade fever associated with chills and rigors associated with loss of appetite and loss of weight for more than 40 days. On examination, he had bilateral firm matted tender cervical lymphadenopathy and firm hepatomegaly. An excision biopsy of his right cervical lymph node revealed necrotizing lymphadenitis and immunohistochemistry of a lymph node biopsy favored Kikuchi disease. Initial antinuclear antibody and anti-double-stranded deoxyribonucleic acid tests were negative and his C3 and C4 levels were normal. An infections screening was negative. He was treated with steroids. While in hospital he developed hemophagocytic lymphohistiocytosis and renal impairment. Later his antinuclear antibody titer became positive in 1:160 and fulfilled the diagnostic criteria for systemic lupus erythematosus. He was managed with steroids and immune suppressive drugs and showed remarkable improvement. Although Kikuchi–Fujimoto disease is uncommon in male patients, it needs to be considered in patients with lymphadenopathy and fever. The disease can be complicated with hemophagocytic lymphohistiocytosis and the patients need continuous monitoring for the possible development of systemic lupus erythematosus later in the course.

Immune-related adverse events affecting parathyroid function are rarely reported with immune checkpoint inhibitors (ICPIs). Activating calcium-sensing receptor antibodies causing autoimmune hypoparathyroidism with nivolumab was recently reported. KEYNOTE-189 and CHECKMATE-067 trials reported a 21–29% hypocalcemia event rate, but the etiology of hypocalcemia was not reported. A chart review was performed to study patients receiving ICPI from 2015 to 2018 at multiple sites affiliated with Saint Vincent Hospital. The study population was divided into two groups based on the presence or absence of calcium altering conditions or medications. True hypocalcemia incidence was calculated after correcting calcium for albumin from the initiation of ICPI to their last follow-up. Group 1 (n = 83) includes patients with no calcium altering conditions or medications. Group 2 (n = 98) includes patients on calcium supplements (n = 17), vitamin D (n = 44), bisphosphonates (n = 24), >stage IIIB chronic kidney disease (CKD) (n = 5), and bone metastasis (n = 38). Hypocalcemia events in Group 1 vs. Group 2 were 8.4% and 19.3%, respectively. Our entire study demonstrated 26.8% vs. 1.1% of Grade I vs. II hypocalcemia events. However, after correcting the calcium for albumin, hypocalcemia incidence was 0.56% (n = 1). No further workup was done to investigate the etiology as that patient passed away. Our data suggest that the true hypocalcemia incidence after using albumin-corrected calcium values is very low in patients receiving IPCI, even in the presence of calcium altering factors. The percentage of patients with hypocalcemia is much higher and similar to the KEYNOTE-189 and CHECKMATE-067 trials when serum calcium values without albumin correction are used. Thus, the higher reported incidence of hypocalcemia in these trials is likely due to the reporting of serum calcium without albumin correction.