Macrophage activation syndrome in a newborn: report of a case associated with neonatal lupus erythematosus and a summary of the literature

Background Macrophage activation syndrome (MAS) is a life-threatening hyperinflammatory syndrome and is caused by a severely dysregulated immune response. It has rarely been associated with neonatal lupus. Case presentation We present a female neonate with MAS born to a mother who had cutaneous lupus erythematosus with circulating anti-nuclear antibodies (ANA), anti-SSA, anti-SSB and anti-extractable nuclear antigen (anti-ENA) antibodies. Because of neonatal lupus (NLE) with a total atrioventricular block, epicardial pacemaker implantation was required on the sixth day of life. Following surgery she developed non-remitting fever and disseminated erythematous skin lesions. A diagnosis of MAS was made based on these symptoms, with hyperferritinemia, elevated transaminases, hypertriglyceridemia, and a skin biopsy that showed hemophagocytosis. Our patient was treated with steroids for 3 months with good effect. No relapse has occurred. Conclusions MAS is a rare complication of neonatal lupus that may be difficult to diagnose, but needs to be treated promptly. In this article, pathogenesis and overlap of MAS and hemophagocytic lymphohistiocytosis (HLH) has been described. Diagnosis of MAS can be difficult. Different diagnostic criteria are used in both diagnosing MAS and HLH. Validated criteria for diagnosis of MAS in other disease than systemic onset JIA have not been validated yet. In NLE, diagnosing MAS is even more difficult, since skin lesions are already common in NLE. We show the potential additional value of skin biopsy in diagnosing MAS.Transplantation and immunomodulationDevelopmen

Adult-onset autoinflammation caused by somatic mutations in UBA1:A Dutch case series of patients with VEXAS

Background: A novel autoinflammatory syndrome was recently described in male patients who harbored somatic mutations in the X-chromosomal UBA1 gene. These patients were characterized by adult-onset, treatment-refractory inflammation with fever, cytopenia, dysplastic bone marrow, vacuoles in myeloid and erythroid progenitor cells, cutaneous and pulmonary inflammation, chondritis, and vasculitis, which is abbreviated as VEXAS. Objective: This study aimed to (retrospectively) diagnose VEXAS in patients who had previously been registered as having unclassified autoinflammation. We furthermore aimed to describe clinical experiences with this multifaceted, complex disease. Methods: A systematic reanalysis of whole-exome sequencing data from a cohort of undiagnosed patients with autoinflammation from academic hospitals in The Netherlands was performed. When no sequencing data were available, targeted Sanger sequencing was applied in cases with high clinical suspicion of VEXAS. Results: A total of 12 male patients who carried mutations in UBA1 were identified. These patients presented with adult-onset (mean age 67 years, range 47-79 years) autoinflammation with systemic symptoms, elevated inflammatory parameters, and multiorgan involvement, most typically involving the skin and bone marrow. Novel features of VEXAS included interstitial nephritis, cardiac involvement, stroke, and intestinal perforation related to treatment with tocilizumab. Although many types of treatment were initiated, most patients became treatment-refractory, with a high mortality rate of 50%. Conclusion: VEXAS should be considered in the differential diagnosis of males with adult-onset autoinflammation characterized by systemic symptoms and multiorgan involvement. Early diagnosis can prevent unnecessary diagnostic procedures and provide better prognostic information and more suitable treatment options, including stem cell transplantation