3種類のmainstay治療に反応しないCIDP—鑑別ポイントと治療戦略

CIDP Refractory to Three Types of Mainstay Treatments: Differential Diagnosis and Treatment Strategies

慢性炎症性脱髄性多発根ニューロパチー（CIDP）は多様な病態を包含する症候群であり，治療反応性の違いはそれを強く裏付ける。Mainstay治療に抵抗性を示す多くはDADSやMADSAMをはじめとするatypical CIDPであり，特にIgG4自己抗体を病因とする一群は難治性CIDPとして知られる。既存治療では単純血漿交換療法と副腎皮質ステロイドの併用が一定の効果を示すが，将来的にはリツキシマブによる治療開発が期待される。経静脈的免疫グロブリン（IVIg）維持療法下でも短期間で再発を繰り返す免疫グロブリン製剤への治療依存例では，ステロイドや免疫抑制薬のadd-onの効果が期待できる。またこうした症例ではIVIgから皮下注用免疫グロブリン製剤（SCIg）による維持療法のオプション変更も有効である。IgG4サブクラス自己抗体は病因であり病勢を判断し得るバイオマーカーの側面を有する。またNfLは治療適正期を判断するとともに治療効果を判定するうえで有効性が期待できるバイオマーカーである。

Abstract

Chronic inflammatory demyelinating polyradiculoneuropathy (CIDP) is a syndrome constructed by several clinical phenotypes that share chronic inflammatory demyelination in the peripheral nervous system. While the detailed pathogenesis is not elucidated, mainstay induction therapies such as corticosteroids, IVIg, and plasma exchange, are effective for typical CIDP. However, most conventional treatments show inadequate responses in CIDP variants. Furthermore, patients with IgG4-predominant autoantibodies (anti-NF155 Ab, anti-CNTN1 Ab, and so on) show distal-predominant disability and are recognized as refractory CIDP (autoimmune nodopathy). Combining therapeutics with induction of plasma exchange following intermittent high-dose corticosteroids could be adequate for those patients. Besides, as a novel therapeutic option, rituximab is strongly expected to be a first-line for IgG4-positive autoimmune nodopathy. Some patients show relapses before the next IVIg maintenance. We can change from intravenous immunoglobulin per three weeks to weekly subcutaneous induction. Add on corticosteroids or immunosuppressants would also be helpful to the disease stability. Recently, serum NF-L has been a candidate biomarker for secondary axonal damage in CIDP. A high-level Nf-L suggests an active phase of the disease and could indicate the requirement for therapeutic intervention.