Case Report: Rubella Virus-Induced Cutaneous Granulomas in Two Pediatric Patients With DNA Double Strand Breakage Repair Disorders – Outcome After Hematopoietic Stem Cell Transplantation

Abstract

We report two patients with DNA repair disorders (Artemis deficiency, Ataxia telangiectasia) with destructive skin granulomas, presumably triggered by live-attenuated rubella vaccinations. Both patients showed reduced naïve T cells. Rapid resolution of skin lesions was observed following hematopoietic stem cell transplantation. However, the patient with AT died due to complications of severe hepatic veno-occlusive disease 6 month after HSCT. Dried blood spots obtained after birth were available from this patient and showed absent T-cell receptor excision circles (TRECs). Therefore, newborn screening may help to prevent patients with moderate T-cell deficiency from receiving live-attenuated rubella vaccine potentially causing granulomas.

Rubella virus‐associated necrotizing neutrophilic granuloma in a patient with common variable immunodeficiency

“…Other reported therapies include the broad‐spectrum antiviral drug nitazoxanide, 11,12 TNF‐alpha and IL‐1R inhibitors, 8 and ribavirin 13 with varying success. Hematopoietic stem cell transplant has been the most effective reported treatment modality with resolution of RuV‐associated granulomas in several patients 8,14 . In our patient where RuV was detected only in neutrophils, we trialed dapsone due to its anti‐neutrophilic property 15 .…”

“…Hematopoietic stem cell transplant has been the most effective reported treatment modality with resolution of RuV-associated granulomas in several patients. 8,14 In our patient where RuV was detected only in neutrophils, we trialed dapsone due to its anti-neutrophilic property. 15 Although topical dapsone was ineffective, the patient had modest gradual improvement with oral dapsone initiated at a low dose with slow up-titration, suggesting that directing pharmacotherapy based on the specific type of rubella infected cells in granulomas (neutrophils in this patient) may yield additional therapeutic benefit.…”

Rubella virus vaccine-induced granulomas: a case in children with ataxia-telangiectasia

“…9 Regression of RG was only seen after hematopoietic stem cell transplantation partly explained by the elimination of rubella-carrying neutrophils and monocytes. 10 The diagnosis of RG is based on characteristic clinical features and skin biopsy with histopathology and IHC or PCR. In immunocompromised children, IHC or PCR should be performed on all idiopathic cutaneous granulomas to elucidate the aetiology and frequency of rubella virus involvement.…”

Monogenic Inborn Errors of Immunity with impaired IgG response to polysaccharide antigens but normal IgG levels and normal IgG response to protein antigens

“…Immune dysregulation and autoimmunity in A-T such as immune thrombocytopenia (ITP), arthritis, and vitiligo is also observed [reviewed in ( 95 )]. Chronic granuloma caused by live rubella vaccine virus have been described predominantly in patients with A-T and other DNA repair disorders [reviewed in ( 104 , 105 )].…”