Yasuko SHIOMICHI

Immunoglobulin A (IgA) vasculitis is generally triggered by infectious causes, but it has also been reported after immunisation with various vaccines. Herein, we report two cases of IgA vasculitis after receiving the first or second dose of the Pfizer-BioNTech BNT16B2b2 mRNA vaccine. Two men, aged 22 and 30 years, developed palpable purpura on the extremities and arthritis. One patient also complained of fever and gastrointestinal symptoms. Laboratory findings revealed mild leucocytosis and slightly elevated C-reactive protein levels, although the platelet count and coagulation profile were within normal levels in both cases. Proteinuria and microhaematuria were seen in one patient. Skin biopsies were performed in both patients and revealed leucocytoclastic vasculitis. The deposits of IgA and C3 were shown in immunofluorescence studies in one patient. Both patients were diagnosed with IgA vasculitis and treated with prednisolone, and their symptoms resolved within 1 week after initiation of treatment. The coronavirus disease 2019 mRNA vaccine could trigger IgA vasculitis; however, a coincidence cannot be ruled out.

63 歳，女性。初診 1 年 8 カ月前に前医で左手背の皮下腫瘤を切除され，皮膚線維腫と診断された。初診 6 カ月前に同部位に皮下腫瘤が出現し増大した。同医を受診し，生検で superficial acral fibromyxoma が疑われ，精査加療目的に当科紹介となった。初診時，左手背に約 4×3 cm のドーム状に隆起した皮下腫瘤を認めた。1 cm のマージンをとり，手背腱膜上で切除し，PAT（perifascial areolar tissue）移植および全層植皮術を行った。病理組織学的に，真皮から皮下にかけて表皮との連続性のない比較的境界明瞭な腫瘤性病変を認めた。同部位では粘液線維様の間質を背景として，核異型の目立つ紡錘形もしくは星芒状の線維芽細胞様細胞が索状・花むしろ状に配列・増殖し，偽脂肪芽細胞の混在と炎症細胞浸潤を伴っていた。腫瘍細胞は免疫組織化学染色で vimentin，CD10，CD34，CD68，D2-40 に陽性だった。以上より自験例を myxoinflammatory fibroblastic sarcoma と診断した。術後放射線療法を追加し，再発・転移なく経過している。

66 歳，女性。17 年前に発症した関節リウマチに対し 11 年前よりメトトレキサート（methotrexate：MTX）を内服していた。8 カ月前に右下腿を打撲し同部位に潰瘍を生じたという。改善しないため当科紹介となった。右下腿，右大腿，背部に多発する皮膚潰瘍が認められ，周囲に色素沈着と皮下硬結を伴っていた。また CT では右肺下葉に結節影を認めた。右下腿と背部の皮膚生検で真皮から皮下脂肪織に CD20 陽性の大型異型リンパ球が多数浸潤しており，腫瘍細胞は LMP-1，EBER 陽性で組織学的に EBV 感染を確認した。MTX 中止により皮下硬結の範囲は速やかに縮小し，右大腿と背部の潰瘍は約 1 カ月で上皮化した。肺の結節影も縮小傾向で，病理組織像と臨床経過から MTX 関連リンパ増殖性疾患（methotrexate-associated lymphoproliferative disorders：MTX-LPD）と診断した。右下腿の潰瘍は難治だったため，組織学的にリンパ増殖性疾患の所見のないことを確認し植皮術を行った。その後は寛解を維持し，リンパ増殖性疾患の再発および関節リウマチの増悪はない。MTX-LPD の皮膚潰瘍は多発例が多く，紅斑，結節，腫瘤といった原発疹が存在することを特徴とするが，単発例も存在し下腿は好発部位の一つである。MTX を内服中の患者に下腿潰瘍を生じた場合，MTX-LPD を鑑別に挙げる必要がある。

症例 1：35 歳，女性。初診 4 日前より上肢に自覚症状のない紅斑，同 2 日前には四肢の有痛性紅斑と 40 度の発熱を生じ，翌日近医皮膚科を受診し，当科に紹介され受診した。皮膚生検で結節性紅斑の診断で，ベッド上安静とロキソプロフェン 300 mg/日の内服治療で症状は軽快していたが，経過中に妊娠 4 週が判明した。ロキソプロフェン内服は 3 週間で終了し，アセトアミノフェン内服に変更してさらに 2 週間で治療した。その後妊娠 37 週の正期産，正常産で出産し，皮膚症状の再燃もなかった。症例 2：25 歳，女性，妊娠 24 週。初診 3 週間前より前医で腎盂腎炎のためアモキシシリン内服治療中であった。同 10 日前に左頰部の擦過創周囲に有痛性紅斑が出現し，その後左右の膝，右肘部，左踵部にも同様の紅斑が出現してきた。皮膚生検で結節性紅斑の診断で，入院してベッド上安静のうえ，遷延する腎盂腎炎にセファゾリン点滴も併用しつつ，妊娠中を考慮しアセトアミノフェン 1200 mg/日の内服を開始した。同 2400 mg/日まで増量したが症状制御が不十分で，プレドニゾロン 10 mg/日内服追加により症状は軽快した。退院後，外来にて両薬の漸減終了後も結節性紅斑は再燃なく，妊娠 40 週の正期産，正常産で出産した。本症は妊娠も発症因子のひとつであり，妊婦での発症は妊娠時期や合併症など考慮した慎重な治療選択，他科連携，十分な患者説明，経過フォローが重要である。文献的考察も加え報告する。

We here report a case of psoriasiform drug eruption in which significant improvements in intractable itching and psoriatic lesions were observed only 6 weeks after discontinuing drug-induced lymphocyte stimulation test (DLST)-positive drugs without using any biologics or other systemic treatments. A 33-year-old obese man (body mass index = 36.9) with metabolic syndrome attended our clinic for treatment of intractable psoriasis. He had typical large psoriatic plaques with a Psoriasis Area and Severity Index (PASI) score of 20.7 (Figure 1a), along with extreme itching (numerical rating scale [NRS] score 9). He had no family history of psoriasis and a slight dry skin rash had developed on the nape about 22 months previously in winter, but it resolved once. He had started taking febuxostat for hyperuricemia 14 months previously and developed psoriasis with itching 6 months later, again in winter, but this time the rash continued. He had also started taking ezetimibe and canagliflozin for hyperlipidemia and diabetes 6 months previously and experienced immense exacerbation of the itching and psoriasis 3 months later, with the lesions expanding systemically. Blood tests showed elevations of eosinophils (893/μl), low-density lipoprotein (LDL) cholesterol (145.6 mg/dL), and mild liver dysfunctions. Skin biopsy taken from one such plaque (Figure 1b) showed psoriasis histologically, but eosinophil infiltration and crusting were conspicuous (Figure 1c–e). Because of the extreme itching, elevated eosinophils, drug history, and his concern about the cost of biologics, DLSTs for his current medications were tentatively conducted to possibly rule out a complicated drug eruption. These tests revealed positive results for febuxostat and ezetimibe (stimulation index [SI] 2.3 and 8.2, respectively). Topical therapy with a fingertip unit of a mixture of corticosteroids and vitamin D was not sufficiently effective, but only 6 weeks after switching from the two DLST-positive drugs, the PASI score significantly decreased to 4.5 (Figure 1f), with NRS-itch of 1, therefore, the commencement of treatment with biologics was no longer necessary. His psoriasis did not clear up completely, but he now only uses moisturizers in winter as the symptoms have remained quite mild for the last 2 years. Psoriasiform drug eruption was originally defined as psoriasis caused or aggravated by a drug that occurs via the drug's pharmacological action.1 However, febuxostat and ezetimibe could correct hyperuricemia and/or hyperlipidemia, factors associated with psoriasis, implying that his psoriatic lesions are unlikely to have occurred in that way. Another possible mechanism could be that obesity itself is a risk factor for psoriasis, as shown by a Mendelian randomization study2 and a mouse model.3 Increased interleukin (IL)-23, a key cytokine for psoriasis, within the adipose tissue in people with high LDL cholesterol has also been identified as an inflammatory biomarker.4 In such “pre-psoriatic” individuals with obesity and high LDL cholesterol, such as the present patient, drug allergy-induced itching/scratching is potentially causative of psoriatic lesions via the Koebner phenomenon, presumably upregulating CCL20 and CXCL8 (chemokines for Th17 cells and neutrophils, respectively) in keratinocytes.5 We have been unable to perform another set of DLSTs or other tests to examine possible false-positive results for either drug due to lack of availability of the patient. In conclusion, our findings suggest that, for patients with intractable psoriasis exhibiting intense itching and/or elevated blood eosinophils, DLST might be worthwhile to identify drugs causative of psoriasiform drug eruption and to decrease disease severity, before considering high-cost medications. None declared. Written informed consent for publication and use of photographs was obtained from the patient.