本稿の前半では，従来，主に魚鱗癬と呼ばれていた非症候性表皮分化疾患（nonsyndromic epidermal differentiation disorder，nEDD）の新国際病名，病型分類について述べる。私たちは３年前から病因，病態についての新知見を反映したnEDDの国際病名，病型分類の改訂に取り組んで来た。今回の改訂では，病因遺伝子と表現型の組み合わせによる新病名システムを採用している。本稿の後半では，体細胞復帰変異によるモザイク健常皮膚からの表皮細胞由来の培養表皮細胞シートを用いたKRT1-nEDD-revertant mosaicの新規治療法開発の試みについて述べる。体細胞において，病因バリアントを有する遺伝子に，さらに変異が起こり，病因遺伝子バリアントが消失する現象は「復帰変異」と呼ばれる。私たちは，KRT1-nEDD-revertant mosaic患者さんの「復帰変異」による健常な皮膚からの自家培養表皮シートを用いて，KRT1-nEDD-revertant mosaicの治療を試みた。

In the first half of this paper, we discuss the new international nomenclature and classification of nonsyndromic epidermal differentiation disorders （nEDDs）, which were previously known mainly as ichthyosis. Over the past three years, we have been working to revise the international nomenclature and classification of nEDDs to reflect recent findings in etiology and pathology. In this revision, a new nomenclature system combining the disease-associated gene with the phenotype has been adopted. In the second half of this paper, we discuss the treatment of KRT1-related nEDD-revertant mosaic using a cultured epidermal autograft derived from the patientʼs own clinically unaffected skin. This unaffected skin resulted from a “revertant mutation,” a phenomenon in which a pathogenic gene variant in somatic cells is corrected by a further mutation, causing the pathogenic gene variant to disappear

【目的】アトピー性皮膚炎では皮膚バリア機能低下が問題となるが，ジファミラスト軟膏が皮膚バリア機能の指標である経皮水分蒸散量（TEWL）や角質水分量（SCH）へ与える影響については報告が少ない。そこでジファミラスト軟膏1.0%を使用し，TEWLおよびSCHへの影響を検討した。【方法】当院の外来を受診した2〜14歳の中等症以上の小児アトピー性皮膚炎患者11名を対象にジファミラスト軟膏1.0%を塗布し，4週間後のTEWLおよびSCH，EASIスコア，POEMスコア，瘙痒NRSを介入前後で評価した。【結果】ジファミラスト軟膏により4週間後のTEWLおよびSCHが有意に改善することが示された。またEASIスコアやPOEMスコア，瘙痒NRSのいずれも有意な改善がみられた。【結論】ジファミラスト軟膏が皮膚バリア機能を高め，小児アトピー性皮膚炎の皮膚状態を改善する可能性を示唆している。

【Objective】Impaired skin barrier function is a defining feature of atopic dermatitis （AD）. Few studies have examined the effects of difamilast ointment on skin barrier function parameters. This study aimed to evaluate the effect of 1.0% difamilast ointment on skin barrier function parameters and clinical severity and symptom measures. 【Methods】Eleven pediatric patients aged 2-14 years with moderate AD were included in the study. All patients were treated with 1.0% difamilast ointment. After 4 weeks of treatment, we measured the following outcomes: transepidermal water loss（TEWL）, stratum corneum hydration （SCH）, Eczema Area and Severity Index （EASI） score, Patient-Oriented Eczema Measure （POEM） score, and pruritus Numerical Rating Scale （pruritus NRS）. 【Results】After 4 weeks of treatment, we found significant improvements in TEWL and SCH （p < 0.001 and p < 0.05, respectively） and significant reductions in EASI scores, POEM scores, and pruritus NRS. 【Conclusion】These findings suggest that difamilast ointment enhances skin barrier function.

乾癬は慢性炎症性皮膚疾患であり，小児期に発症する症例は全体の約1/3とされるが，日本では湿疹との鑑別困難や診断の遅れから実態が不明確である。本研究では2017～2023年度に日本乾癬学会が実施した全国疫学調査データを用いて，小児尋常性乾癬の患者背景，病型，治療実態を解析した。12,917例中，小児症例は204例（1.6%）で，男女比は成人で1.85：1，小児では1.17：1と性差が少なかった。局面型が83%と最多で，罹患範囲はbody surface area（BSA）5%未満が44%と軽症例が多かった。外用療法が中心であったが，難治例ではシクロスポリンや生物学的製剤も用いられていた。本邦では小児乾癬が過小評価されている可能性があり，診断精度向上と治療指針の整備が課題である。

Psoriasis is a chronic inflammatory skin disease. Approximately one-third of cases develop in childhood. However, pediatric psoriasis may be underdiagnosed in Japan due to diagnostic challenges. This study analyzed data from the Japanese Society for Psoriasis Research （2017-2023） to clarify the clinical characteristics of pediatric psoriasis in Japan. Among 12,917 cases of plaque psoriasis, 204 （1.6%） occurred in children aged 0-15 years. The male-to-female ratio in pediatric cases was 1.17:1, showing a smaller sex difference compared with adult cases. Plaque-type psoriasis accounted for 83% of cases, and most patients had mild disease （BSA < 5%）. Topical therapies were the primary treatment, whereas systemic agents, including cyclosporine and biologics, were used in refractory cases. These findings suggest the need for improved early recognition and tailored treatment strategies for pediatric psoriasis in Japan.

症例は2か月女児。出生時より，右大腿屈側〜下腿屈側にかけ島嶼状に分布する色調均一で表面平滑な紅斑がみられ当科紹介受診となった。当初，毛細血管奇形と考え，パルス色素レーザー（Vbeam）照射治療を開始したが，照射による色調改善がみられず，病変は生後6か月頃に軽度浸潤・隆起を伴う角化性紫斑へと変化した。皮膚生検にて，内部に赤血球を含む血管内皮の増生と真皮乳頭部への拡張，軽度の表皮角質増生や隆起がみられ，最終的に母斑様限局性体幹被角血管腫と診断した。保護者希望により転院し，Vbeamレーザー照射を計6回施行後，3歳時に保護者の希望で外科的切除が施行され，再発なく5歳時にフォローオフになったとの報告をうけた。出生時から紅斑としてみられ，徐々に角化傾向を示す場合には，母斑様限局性体幹被角血管腫も念頭に置く必要があると考えた。

A 2-month-old girl was referred to our department for evaluation and treatment of erythema on the right leg. The rash had been present since birth, exhibiting a uniform coloration along the right thigh and lower leg. Capillary malformation was initially suspected, for which we administered dye laser therapy （Vbeam）. However, there was no improvement in coloration. Around 6 months of age, the lesion transformed into keratotic purpura with mild infiltration and elevation. A skin biopsy was performed for diagnostic clarification. Based on clinical and histopathological features, we finally diagnosed angiokeratoma circumscriptum naeviforme. The patient received a total of six additional laser treatments at another hospital. At the age of 3 years, surgical excision was performed, and no recurrence was observed during the follow-up period up to 5 years old. Angiokeratoma circumscriptum naeviforme should also be considered in the differential diagnosis when evaluating an infant patient with an erythematous lesion that is gradually developing keratotic features.

13歳女児。3か月前に右こめかみに皮下硬結を自覚した。皮膚表面は平滑で軽度隆起し，可動性のある20×15㎜の皮下硬結を触知した。自発痛や圧痛はなく，臨床的に石灰化上皮腫を考え切除した。病変は側頭筋内にあり，硬く脆い結節性病変で完全には切除できなかった。病理組織は好酸性の紡錘形細胞が錯綜し，核異型は乏しく，血管増生や赤血球漏出を伴っていた。結節性筋膜炎と診断した。術後2か月半で軽度残存していた硬結は消褪し，1年時点で再発はない。小児期の結節性筋膜炎の発生は少ないが，頭頚部が好発部位とされる。小児の頭頚部の皮下結節では結節性筋膜炎も鑑別に含めるべきである。

A 13-year-old girl presented with a nodule on the right temple, which was noted 3 months earlier. The skin surface was smooth and slightly raised, and a mobile 20 × 15 mm subcutaneous nodule was palpated. The excised lesion was located within the temporalis muscle and was firm and brittle. The lesion was suspected to be partially residual. Pathologically, the lesion was composed of eosinophilic spindle-shaped cells with hypervascularization and erythrocyte leakage, leading to a diagnosis of nodular fasciitis. Mild residual induration resolved 2.5 months after surgery. The predilection site of nodular fasciitis is the extremities in adults, but the head and neck region is more commonly affected in children. Nodular fasciitis should be considered in the differential diagnosis for subcutaneous nodules in the head and neck region of children.

症例は3歳の女児で，両側頬に雀卵斑，手背と足背に色素斑と脱色素斑が混在していた。遺伝子検査により，ADAR1遺伝子のフレームシフト変異（c.1841delG）が確認され，遺伝性対側性色素異常症と診断した。本疾患は，四肢末端に色素斑と脱色素斑が混在する皮膚疾患で，幼少期に出現し思春期前後で安定化することが多い。原因遺伝子はRNA編集酵素ADAR1遺伝子で，常染色体顕性遺伝形式をとる。自験例で確認された変異はこれまでに報告がなく，新規変異と考えた。発端者である父親は，手背にわずかに色むらがある程度であった。

The patient was a 3-year-old girl who presented with ephelides on both cheeks and a mixture of pigmented and depigmented macules on the dorsum of her hands and feet. Genetic testing identified a frameshift mutation （c.1841delG） in the ADAR1 gene, leading to a diagnosis of hereditary dyschromatosis. This rare skin disorder is characterized by a combination of pigmented and depigmented macules on the extremities, typically appearing in childhood and stabilizing around puberty. The causative gene, ADAR1, encodes an RNA-editing enzyme and follows an autosomal dominant inheritance pattern. The mutation identified in this case, c.1841delG, has not been previously reported, suggesting it represents a novel variant. The probandʼs father exhibited only minor pigmentation irregularities on the dorsum of his hands.

15歳，男児。3年前より左下顎の変形を自覚し，近医歯科で経過観察されていた。歯科矯正目的に当院を紹介受診し，CTで左顔面皮下脂肪の減少を指摘され，Parry-Romberg症候群疑いにて当科紹介受診となった。左頬部は大きく陥凹していたが，紅斑や硬化，色素沈着は認めなかった。陥凹部の皮膚組織では真皮深層から皮下脂肪組織にかけてリンパ球や形質細胞の浸潤，皮下脂肪組織の線維化を認めた。小葉性脂肪織炎は認めず，抗核抗体は陰性であった。以上の所見からParry-Romberg症候群と診断した。同疾患は深在性ループスや強皮症等との鑑別が必要となり，組織学的検査を含めた総合的評価が必要である。

A 15-year-old male noticed a deformation of his left mandible three years earlier and had been under observation at a local dental clinic. He was referred to our hospital for orthodontic treatment. CT revealed subcutaneous fat atrophy on the left side of his face. Clinical examination revealed significant indentation on the left cheek, but no notable skin changes, such as erythema, sclerosis, or pigmentation, were identified. Histological examination of the left cheek skin revealed lymphocytes and plasma cell infiltration extending from the deep dermis to the subcutaneous fat, as well as fibrosis of the subcutaneous fat tissue. No evidence of lobular panniculitis was observed. Based on these findings, the patient was diagnosed with Parry-Romberg syndrome. Histological examination is important for differential diagnosis from similar conditions such as lupus profundus and scleroderma.

1歳4か月女児。初診1か月前に手足口病に罹患後，全身に鱗屑，小膿疱を伴う紅斑が拡大した。Very strongクラスのステロイド外用で皮疹は軽快したが，1歳6か月頃から39度前後の発熱を伴う紅斑，膿疱が再燃した。病理組織学検査とあわせ小児汎発性膿疱性乾癬と診断した。シクロスポリン5mg/kg/日内服を開始し，速やかに解熱したが皮疹は残存し，血圧上昇などの副作用が出現した。セクキヌマブ75mg投与を開始したところ，速やかに皮疹は消退し再燃なく経過した。

A 1-year-and-4-month-old girl developed generalized erythema with scale and pustules after having from hand, foot, and mouth disease one month before her first visit to our hospital. We diagnosed generalized pustular psoriasis based on clinical symptoms and skin biopsy. Initially, her symptoms remained stable with topical steroid administration; however, it recurred with erythema and pustules accompanied by a fever of around 39 degrees centigrade from about 1 year and 6 months old. Cyclosporine (5 mg/kg/day) was started. The fever subsided quickly, but rash remained and side effects, such as increased blood pressure, appeared. After switching treatment to secukinumab, the rash resolved rapidly, and no relapse was observed.

患者は６歳，男児。生後１歳頃より左大腿から左下腿にかけて鱗屑，過角化，紅色丘疹を伴う皮疹が出現。皮疹は左片側性にブラシコ線に沿った分節性の線状〜帯状の形態を呈し，さらに左顔面，および胸部へと片側性に拡大したため，当院へ紹介された。皮膚生検の結果，角質増殖を伴う表皮肥厚がみられ，表皮突起は棍棒状に延長し，角層の不全角化と顆粒層の消失も確認された。5年後には両肘および両膝に両側性の非分節性の炎症性角化性局面も多発してきたが瘙痒はなかった。以上より，炎症性線状疣贅状表皮母斑などを鑑別した後に，モザイク病の一型として乾癬を発症しやすいゲノム変化を皮膚に有するsuperimposed linear psoriasisと診断した。ステロイド，ビタミンD3の外用にナローバンドUVB療法を併用して，皮疹は徐々に改善しているため，自験例が今後の本症の診断および治療戦略の一助になると思われたので報告した。

The patient was a 6-year-old male with erythematous, scaly, and hyperkeratotic papules appearing around age one on the left thigh and lower leg, following Blaschko’s lines. The lesions later spread unilaterally to the left face and chest. Skin biopsy revealed epidermal hyperplasia, club-shaped rete ridges, parakeratosis, and loss of the granular layer. By age 10, bilateral non-segmental hyperkeratotic plaques developed on the elbows and knees without pruritus. Based on these findings, we diagnosed superimposed linear psoriasis, a mosaic disorder predisposing affected skin to psoriasis. The patient has been managed with topical corticosteroids, vitamin D3 analogs, emollients, and phototherapy. During more than 10 years of follow-up, the skin lesions have been well controlled.

3歳，女児。生後2か月頃に気づかれた左手背の結節が緩徐に増大したため，前医を受診した。皮膚腫瘍が疑われ，当科を紹介受診した。初診時，左手背の示指MP関節部に弾性やや硬で10×9mm大，高さ3mmのドーム状の淡紅褐色結節を認めた。ダーモスコピーでは淡紅色調の背景に，細い白色ネットワークがみられ，紅色のdots，暗紫色の小湖，白色小点を伴っていた。全切除した病理組織像では，真皮から皮下にかけて結節性に増生する血管成分と，真皮中層での周囲に浮腫性変化を伴うエクリン汗腺の増生を認め，eccrine angiomatous hamartomaと診断した。本症の約4割は出生時より存在しており，約8割の症例で20歳までに発症がみられる。最近，特徴的なダーモスコピー像についても報告があり，診断に有用となる可能性がある。自験例でも同様の所見が得られており，病理組織学的所見とも合致していた。

A 3-year-old girl was referred to our department for treatment of a nodule on the dorsum of her left hand, which was first noticed at the age of 2 months. On the initial visit, a dome-shaped, pale reddish-brown nodule measuring 10 × 9 mm in size was observed on the metacarpophalangeal joint of the left index finger. Dermoscopy showed a whitish network with red and white dots, as well as lacunae. Histopathology showed nodular proliferation of capillary vessels extending from the dermis to the subcutaneous tissue, as well as proliferation of eccrine sweat glands in the mid-dermis accompanied by surrounding edematous changes. The diagnosis was eccrine angiomatous hamartoma. Approximately 40% of these lesions are present at birth, and about 80% of cases manifest by the age of 20. Recent reports have described characteristic dermoscopic features that may facilitate diagnosis. In our case, similar dermoscopic findings were observed, which were consistent with the histopathological findings.