Review of Immune-Related Adverse Events (irAEs) in Non-Small-Cell Lung Cancer (NSCLC)-Their Incidence, Management, Multiorgan irAEs, and Rechallenge.

Immune checkpoint inhibitors (ICIs) have revolutionized the treatment of advanced malignancies, including non-small cell lung cancer (NSCLC). These agents have improved clinical outcomes and have become quite an attractive alternative alone or combined with other treatments. Although ICIs are tolerated better, they also lead to unique toxicities, termed immune-related adverse events (irAEs). A reconstituted immune system may lead to dysregulation in normal immune self-tolerance and cause inflammatory side effects (irAEs). Although any organ system can be affected, immune-related adverse events most commonly involve the gastrointestinal tract, endocrine glands, skin, and liver. They can occur anytime during the treatment course and rarely even after completion. Owen and colleagues showed that approximately 30% of patients with NSCLC treated with ICIs develop irAEs. Kichenadasse et al. conducted a thorough evaluation of multiorgan irAEs, which is of particular interest because information regarding these types of irAEs is currently sparse. It is important to delineate between infectious etiologies and symptom progression during the management of irAEs. Close consultation with disease-specific subspecialties is encouraged. Corticosteroids are the mainstay of treatment of most irAEs. Early intervention with corticosteroids is crucial in the general management of immune-mediated toxicity. Grade 1-2 irAEs can be closely monitored; hypothyroidism and other endocrine irAEs may be treated with hormone supplementation without the need for corticosteroid therapy. Moderate- to high-dose steroids and other additional immunosuppressants such as tocilizumab and cyclophosphamide might be required in severe, grade 3-4 cases. Recently, increasing research on irAEs after immunotherapy rechallenge has garnered much attention. Dolladille and colleagues assessed the safety in patients with cancer who resumed therapy with the same ICIs and found that rechallenge was associated with about 25-30% of the same irAEs experienced previously (4). However, such data should be carefully considered. Further pooled analyses may be required before we conclude about ICIs' safety in rechallenge.

Ischemic Stroke in a Patient With Polyneuropathy, Organomegaly, Endocrinopathy, Monoclonal Protein, and Skin Changes Syndrome Treated With Lenalidomide.

Polyneuropathy, organomegaly, endocrinopathy, monoclonal protein, and skin changes (POEMS) syndrome is an uncommon multisystemic disease associated with plasma cell dyscrasia. Due to the disease's rarity and an even rarer presentation of stroke in afflicted patients, a direct association between POEMS syndrome and stroke remains ambiguous. Thrombocytosis, hyperfibrinogenemia, and increased levels of inflammatory cytokines occur in this disease, which can predispose patients to thromboembolic events. Immunomodulators can also enhance thrombosis, the chances of which increase when they are combined with dexamethasone. We present a case of a 28-year-old patient with an ischemic stroke, which may have been triggered by the combination of POEMS syndrome-associated vasculitis and the thrombogenic nature of lenalidomide-dexamethasone therapy.

Checkpoint Inhibitor in a Melanoma Patient With Polyendocrinopathy and Gangrenous Gallbladder With a Mass.

Checkpoint inhibitors are introduced as a therapy for clinical use for various cancers, and clinicians are documenting new adverse effects. This is the first case report to the best of our knowledge of a patient on checkpoint inhibitor presenting with both polyendocrinopathy and gangrenous gallbladder disease with a mass negative for malignancy.71-year-old man presented four years after his initial diagnosis of stage IV, unresectable, non-ulcerated, acryl, lentiginous malignant melanoma. On presentation, he had gangrenous cholecystitis and was treated with laparoscopic cholecystectomy. Incidentally, the patient was diagnosed two years ago with hypothyroidism, hypophysitis, secondary adrenal insufficiency, and pneumonitis, each suspected to be secondary to treatment with pembrolizumab (Keytruda), a monoclonal anti-programmed cell death-1 antibody. He presented to the emergency department for a gallbladder attack and underwent successful laparoscopic cholecystectomy. The intra-operative finding on opening the specimen was an unusual looking exophytic mass but was negative for malignancy on pathology report and reported as gangrenous cholecystitis. His clinical condition before and after surgery was complicated by worsening comorbidities thought to be secondary to pembrolizumab therapy, which required acute care hospitalizations in the weeks before and after his presentation with cholecystitis. The patient had a few admissions from other co-morbidities post-surgery and was doing better. Immunotherapy with pembrolizumab may have secondary and tertiary effects with unusual presentations that are difficult to interpret for the primary oncology team and even tougher to do for community physicians who may subsequently encounter these patients. The relationship of this patient's comorbidities with immune-related adverse events was not apparent until record requests were conducted after surgery and are still not entirely clear after a literature review. More data is needed to guide decision algorithms and to predict which patients may experience these effects.

IgG4-Related Diseases-Continues To Be a Cancer Mimicker.

Immunoglobulin G4-related disease (IgG4-RD) is a chronic multisystem immune-mediated disease. Histologically, it presents as infiltration with IgG4-secreting plasma cells affecting many organs such as the pancreas, lacrimal glands, salivary glands, kidneys, and arteries, resulting in chronic fibrosis and scarring within the tissue which over time forms into a mass. It is a slow-growing process that usually remains indolent until it causes a mass effect or tissue infiltration. Our patient was found to have a pancreatic mass on imaging concerning pancreatic neoplastic lesions. He subsequently underwent biopsy for histology/pathology and IgG4 levels, which led to our diagnosis of IgG4-RD. Imaging, blood tests, and, most importantly, histopathological features of the involved organ are important in determining the diagnosis. This is important as a treatment plan will be based on the given diagnosis, and patients with IgG4-RD respond very well to systemic steroid therapy.

Rare case of bilateral wrist and foot drop from SLE-related vasculitic polyneuropathy.

Systemic lupus erythematosus (SLE) is a heterogeneous, chronic, inflammatory, autoimmune disease characterised by multiorgan involvement and the production of multiple autoantibodies. Neurological manifestations in SLE patients are frequently reported-the prevalence is 37%-90%. We present a unique case where the patient presented with bilateral wrist and foot drop for 4 days, which later led to the diagnosis of SLE-related vasculitic polyneuropathy. During the course of treatment, the patient received prednisone, rituximab and hydroxychloroquine. At 6-month follow-up, patient had reported significant improvement in her weakness with increased mobility in upper and lower extremities. Prompt diagnosis and treatment are necessary in these cases to prevent disease progression and morbidity.

Cerebral Venous Sinus Thrombosis with Bilateral Abducens Palsy in a Patient with Heterozygous Prothrombin G20210A Mutation.

We present a rare case of cerebral venous thrombosis in a patient with heterozygous mutation of the prothrombin G20210A gene. A 24-year-old Caucasian male complained of sudden onset diplopia due to bilateral abducens palsy and throbbing headache with pulsatile tinnitus. Computed tomography revealed extensive thrombus in the right sigmoid sinus, right transverse sinus, and the superior sagittal sinus. Except for the prothrombin mutation, no other predisposing risk factors were found. The patient was treated with heparin, later transitioned to enoxaparin and warfarin, and subsequently, the symptoms improved on follow-up. This case reveals the rare occurrence of cerebral venous thrombosis in a patient having prothrombin gene G20210A mutation alone. Early diagnosis and treatment can lead to a good prognosis.

A Rare Case of Adult-onset Still's Disease with Anti-Ro Antibody Positive.

Adult-onset Still's disease (AOSD) is a rare systemic inflammatory disorder. The exact pathogenesis is unknown but believed to have multiple etiologies. The Yamaguchi criteria are used to aid in the diagnosis of AOSD. Typical characteristics are spiking fevers, febrile rash, arthritis, and the absence of other serologic markers of rheumatic diseases. We present a case of a 31-year-old Hispanic female who presented with fevers, arthritis, febrile rash, high ferritin levels, and cervical and axillary lymphadenopathies. The unique feature of our case is that the patient was positive for antinuclear antibody (ANA) titers of greater than 1:640 and anti-Ro antibody. She responded with the pulse dose steroids and later prescribed methotrexate and tapered off prednisone with improvement in her symptoms.