Abstract
Aluminium hydroxide is a well-known adjuvant used in vaccines. Although it can enhance an adaptive immune response to a co-administered antigen, it causes adverse effects, including macrophagic myofasciitis (MMF), subcutaneous pseudolymphoma, and drug hypersensitivity. The object of this study is to demonstrate pediatric cases of aluminium hydroxide-induced diseases focusing on its rarity, under-recognition, and distinctive pathology. Seven child patients with biopsy-proven MMF were retrieved from the Seoul National University Hospital (SNUH) pathology archives from 2015 to 2019. The medical records and immunisation history were reviewed, and a full pathological muscle examination was carried out. The mean age was 1.7 years (8.9–40 months), who had records of vaccination against hepatitis B, hepatitis A, and tetanus toxoid on the quadriceps muscle. The chief complaints were muscle weakness (n = 6), delayed motor milestones (n = 6), instability, dysarthria, and involuntary movement (n = 1), swallowing difficulty (n = 1), high myopia (n = 1), and palpable subcutaneous nodules with skin papules (n = 1). Muscle biopsy showed MMF (n = 6) and pseudolymphoma (n = 1) with pathognomic basophilic large macrophage infiltration, which had distinctive spiculated inclusions on electron microscopy. The intracytoplasmic aluminium was positive for PAS and Morin stains. Distinctive pathology and ultrastructure suggested an association with aluminium hydroxide-containing vaccines. To avoid misdiagnosis and mistreatment, we must further investigate this uncommon condition, and pharmaceutical companies should attempt to formulate better adjuvants that do not cause such adverse effects.
Highlights
Aluminium hydroxide is a well-known adjuvant used in vaccines
These macrophages have obvious and distinctive features, i.e., a large cytoplasm filled with granules containing aluminium hydroxide, which are weakly basophilic on hematoxylin and eosin (H&E) staining, and Periodic Acid Schiff (PAS)-positive
Other aluminium adjuvant-associated diseases include chronic fatigue s yndrome[11], autoimmune syndrome induced by adjuvants (ASIA)[12,13], and Gulf War syndrome (GWS) developed in soldiers following multiple aluminium-containing v accinations[14,15]
Summary
Aluminium hydroxide is a well-known adjuvant used in vaccines It can enhance an adaptive immune response to a co-administered antigen, it causes adverse effects, including macrophagic myofasciitis (MMF), subcutaneous pseudolymphoma, and drug hypersensitivity. The benefit of aluminium hydroxide-based adjuvants is not fully understood, in spite of its long-term usage It has an enhancing effect on the adaptive immune response to a co-administered antigen through repository and pro-phagocytic effects and proinflammatory NOD-like receptor protein 3 (NLRP3) pathway activation[1]. Massive infiltration by aluminium-containing macrophages is the diagnostic hallmark of MMF These macrophages have obvious and distinctive features, i.e., a large cytoplasm filled with granules containing aluminium hydroxide, which are weakly basophilic on hematoxylin and eosin (H&E) staining, and Periodic Acid Schiff (PAS)-positive. MMF itself is aluminium hydroxide induced granulomas in the vaccine injected sites, but it is not a local lesion but manifests severe systemic disease
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