This is a comprehensive analysis of a large cohort of patients with immune checkpoint inhibitor-associated myopathy. Shelly et al. highlight its unique features of ocular involvement and normal creatine kinase levels in some patients, mimicking myasthenia gravis. Multifocal clusters of necrotic fibers are characteristics and occur in even patients without hyperCKemia. Immune checkpoint inhibitors have revolutionized the landscape of cancer treatment. Alongside their many advantages, they elicit immune-related adverse events, including myopathy, which potentially result in substantial morbidity if not recognized and treated promptly. Current knowledge of immune checkpoint inhibitor-associated myopathy is limited. We conducted 5-year retrospective study of patients with immune checkpoint inhibitor-associated myopathy. Clinical features, survival and ancillary test findings were analyzed and compared with those of immune-mediated necrotizing myopathy patients without immune checkpoint inhibitor exposure seen during the same time period. We identified 24 patients with immune checkpoint inhibitor-associated myopathy (median age 69 years; range: 28-86) and 38 patients with immune-mediated necrotizing myopathy. Ocular involvement occurred in 9/24 patients with immune checkpoint inhibitor exposure, without electrodiagnostic evidence of neuromuscular transmission defect, and in none of immune-mediated necrotizing myopathy patients (P < 0.001). Myocarditis occurred in eight immune checkpoint inhibitor-associated myopathy patients and in none of immune-mediated necrotizing myopathy patients (P < 0.001). Median creatine kinase was 686 IU/L in immune checkpoint inhibitor cohort (seven with normal creatine kinase) compared to 6456 IU/L in immune-mediated necrotizing myopathy cohort (P < 0.001). Lymphopenia was observed in 18 and seven patients with and without immune checkpoint inhibitor exposure, respectively (P < 0.001). Myopathological findings were similar between patients with and without immune checkpoint inhibitor exposure, consisting of necrotic fibers with no or subtle inflammation. Necrotic fibers however arranged in clusters in 10/11 immune checkpoint inhibitor-associated myopathy patients but in none of immune checkpoint inhibitor-naïve patients (P < 0.001). Despite the lower creatine kinase levels in immune checkpoint inhibitor-exposed patients, the number of necrotic fibers was similar in both groups. Immune checkpoint inhibitor-associated myopathy patients had higher frequency of mitochondrial abnormalities and less number of regenerating fibers than immune-mediated necrotizing myopathy patients (P < 0.001). Anti-HMGCR (Hydroxy-3-Methylglutaryl-CoA Reductase) or signal recognition particle antibodies were absent in patients with immune checkpoint inhibitor exposure but positive in two-thirds of immune checkpoint inhibitor-naïve patients. Most patients with immune checkpoint inhibitor-associated myopathy responded favorably to immunomodulatory treatments, but four died from myopathy-related complications and one from myocarditis. Intubated patients had significantly shorter survival compared to non-intubated patients (median survival of 22 days; P = 0.004). In summary, immune checkpoint inhibitor-associated myopathy is a distinct, treatable immune-mediated myopathy with common ocular involvement, frequent lymphopenia, and necrotizing histopathology, which contrary to immune-mediated necrotizing myopathy, is featured by clusters of necrotic fibers and not accompanied by anti-HMGCR or signal recognition particle antibodies. Normal or mildly elevated creatine kinase level does not exclude the diagnosis.

No abstract

Posterior reversible encephalopathy syndrome (PRES) may present with diverse clinical symptoms including visual disturbance, headache, seizures and impaired consciousness. MRI shows oedema, usually involving the posterior subcortical regions. Triggering factors include hypertension, pre-eclampsia/eclampsia, renal failure, cytotoxic agents and autoimmune conditions. The mechanism underlying PRES is not certain, but endothelial dysfunction is implicated. Treatment is supportive and involves correcting the underlying cause and managing associated complications, such as seizures. Although most patients recover, PRES is not always reversible and may be associated with considerable morbidity and even mortality.

Background: Fingolimod is used to reduce relapse rates in relapsing-remitting multiple sclerosis (MS). It is a sphingosine 1-phosphate (S1P) analogue having antagonistic effects on S1P receptors. Its immunosuppressive effect is due to reduced circulating lymphocyte numbers, and it may also be associated with impaired intrinsic cancer surveillance. Fingolimod side effects include increased rates and severity of viral infections particularly varicella zoster. Methods: We present five cases of chronic and treatment refractory warts associated with fingolimod therapy. Results: Each of the five cases presenting with chronic warts while receiving fingolimod therapy had prolonged periods of lymphopenia and improvements were seen following dose reduction or cessation of fingolimod. Conclusion: Cutaneous warts are associated with human papilloma virus (HPV) infection, suggesting an increased risk of other HPV-driven conditions such as cervical cancer following fingolimod administration. HPV viruses are responsible for approximately 90% of cervical cancers as well as a significant portion of anogenital cancers and have a high prevalence in sexually active adults. Given the reduced immune response to viral infections and potential impaired cancer surveillance in those receiving fingolimod, HPV vaccination and frequent assessment for the development of HPV-associated malignancies are recommended.

No abstract

No abstract

The triad of central nervous system symptoms, visual disturbance and hearing impairment is an oft-encountered clinical scenario. A number of immune-mediated diseases should be considered among the differential diagnoses including: Susac syndrome, Cogan syndrome or Vogt-Koyanagi-Harada disease; demyelinating conditions such as multiple sclerosis or neuromyelitis optica spectrum disorder; systemic diseases such as systemic lupus erythematosus, Sjögren syndrome or Behcet disease and granulomatous diseases such as sarcoidosis. In this article, we coin the term ‘BEE syndromes’ to draw attention to the various immune-mediated diseases that affect the brain, eye and ear. We present common disease manifestations and identify key clinical and investigation features.

No abstract