“Double trouble: The first reported case of evans syndrome following RSV Vaccination” Free

Introduction Evans syndrome is a rare, chronic autoimmune disorder characterized by the simultaneous or sequential occurrence of ITP and AIHA. The syndrome can be primary or secondary, with secondary cases often linked to primary immunodeficiencies, systemic autoimmune and lymphoproliferative disorders, or exposure to certain drugs or vaccines. Genetic studies suggest that an underlying immune dysregulation model, characterized by a high frequency of pathogenic variants in immune regulatory genes, highlights the complexity of Evans syndrome's pathogenesis. Herein we report this case that widens the range of possible immune-mediated hematologic complications after immunization by describing a new instance of Evans syndrome temporally associated with RSV vaccination.

Case Presentation A 66-year-old female with a history of hypertension and hyperlipidemia presented to the hospital with a new-onset petechial rash involving her arms, legs, and face.

Labs showed a platelet count of 2 × 10⁹/L, which was previously normal. The patient denied any history of recent infections, fever, recent travel, sick contacts, prior history of platelet disorders, or known autoimmune disease, or family history of platelet or bleeding disorders. Her home medications included amlodipine, losartan, hydrochlorothiazide, and she reported receiving the RSV vaccine one week before admission.

Repeat workup showed a WBC of 5.4 x 10^9/L, HB of 14.3 g/dL, and a severely reduced platelet count of 1 x 10^9/L, with a normal chemistry panel. HIV and hepatitis panels were negative.

The patient was started on presumed ITP treatment with a 1g/kg dose of IVIG and high-dose dexamethasone 40 mg for 4 days. However, on hospital day 4, the hemoglobin level began to decline from 14.3 to 9.9 g/dL. This was followed by a sudden increase in total bilirubin, low haptoglobin, and elevated LDH, a positive Direct antiglobulin test for IgG (C3d negative), which raised concern for the development of hemolytic anemia.

Further serologic testing showed an ANA titer of 1:80 with a cytoplasmic pattern and 1:40 with a nuclear homogenous pattern. CMV IgG positive, positive EBV IgG, and negative IgM. Cardiolipin IgG <2.0, IgM < 2.0. The hematopathology did not show definitive immunophenotypic evidence of a hematolymphoid neoplasm. A bone marrow biopsy revealed a hypercellular marrow with a 65% cellularity, characterized by an increased immature megakaryocyte fraction that was not clustered and a normal karyotype.

Full-body CT scan reported known lung nodules, unchanged from previous studies, and showed no evidence of lymphadenopathy.

Due to refractory thrombocytopenia, the treatment was shifted to rituximab after the development of hemolytic anemia. The patient received a total of 4 doses weekly, along with a prednisone taper starting at 1 mg/kg, resulting in a slow improvement in her counts back to normal.

Discussion and Conclusion To the best of our knowledge, this is the first case documented of Evans syndrome secondary to RSV vaccination. The hospital course, lack of alternative etiologies, and temporal association are consistent with cases of vaccine-associated Evans syndrome reported after receiving other vaccinations. The elevated prevalence of damaging variation in immune regulatory genes in pediatric cohorts supports the pathophysiological mechanism, which is thought to involve aberrant activation of autoreactive lymphocytes in genetically or immunologically susceptible individuals. Rarely, autoimmune cytopenia can develop as a result of the immune system's reaction to vaccination, especially when adjuvanted protein subunit vaccines are used.

Despite the widespread vaccination, the sporadic occurrence of Evans syndrome, despite its biological plausibility, emphasizes the general safety of RSV vaccines. Evans syndrome has not been identified as a vaccine-related adverse event in early safety data from clinical trials and post-licensure analyses. Knowing the risk-benefit for the vaccine, the risk of immune-mediated hematologic complications remains very low compared to the benefits of vaccination in preventing severe RSV disease in high-risk populations.

Evans syndrome ideally requires multidisciplinary care and long-term monitoring due to its chronic, relapsing nature.

This case highlights the importance of ongoing pharmacovigilance and educating physicians about immune-mediated hematologic complications that can occur post-vaccination, which are rare but potentially severe.