山田 朋子

A 49‐year‐old‐Japanese woman visited us with a 1‐year history of verrucous lesions on the oral mucosa and fingers. Her past medical history was unremarkable except for chilblain in winter. She had no family history of collagen disease. Physical examination showed a well‐defined, hyperkeratotic erythematous plaque with ulceration on the palate and verrucous nodules on the fingers (Fig. 1a,b). She had no butterfly rash or discoid lesions on any other sites. Histology from both oral mucosa and finger revealed similar features; marked hyperkeratosis and acanthosis with perivascular lymphocytic infiltrates in the dermis. Liquefaction degeneration with a few necrotic keratinocytes was also found (Fig. 1c,d). We regarded the patient as verrucous lupus erythematosus (LE). Then, leukopenia (2,820/μl) and thrombocytopenia (67,000/μl) were observed as well as positive antinuclear antibody (ANA). However, the diagnosis of systemic lupus erythematosus (SLE) was not confirmed by the negative finding of anti‐DNA antibody, and the lack of requirements in 1997 updated ACR criteria for SLE validated back at that time. She developed skin ulcers on the left lower leg in the next two months (Fig. 2a). Four months later, laboratory examination revealed leukopenia (2,850/μl), thrombocytopenia (89,000/μl), low C3/C4 level (27 mg/dl, 3 mg/dl, respectively), positivity for ANA (1 : 640, speckled type), and anti‐Sm antibody (1 : 2). Histology of the leg ulcer exhibited no vasculitis but the occlusion of the vessels (Fig. 2b). Direct immunofluorescence revealed IgM, C1q, and C3 depositions on vessel walls as well as linear IgM deposition at basement membrane zone (Fig. 2c). Seven months later, she had seizure attacks. Then, SLE was diagnosed based upon ACR (1997) and SLICC criteria. Even under 2019 EULAR/ACR classification criteria,1 she was classified as SLE from total 24 points scored by the findings of fever (38.9 °C), leukopenia, thrombocytopenia, seizure, low C3/C4, and anti‐Sm antibody. Then, the patient was transported to us for dyspnea and high fever. Methylprednisolone pulse therapy was performed. Chest roentgenogram revealed extensive lung infiltrates. Aspergillus fumigatus was isolated from the sputum. Invasive aspergillosis was diagnosed. She died of multiple organ failure 8 months after the first visit.

症例は41歳女性。当院初診3年2ヵ月前に乳癌に対しドセタキセル治療を、2年7ヵ月前に乳房温存術および放射線照射を受けた。2年前より右上肢リンパ浮腫を生じ、浮腫は左上肢、頸部に拡大。1年10ヵ月前から両上肢、両手部の皮膚硬化が進行、関節拘縮へ発展し、6ヵ月前からRaynaud現象、開口障害が出現し、当科を受診した。びまん皮膚硬化型全身性強皮症と診断し、入院の上、プレドニゾロン内服(20mg/日)を開始、進行する皮膚症状の改善目的にステロイドパルスを追加し、関節拘縮改善を認めた。本例はドセタキセル治療後の発症であり、上腕、前腕に浮腫、皮膚硬化が強く、一般の強皮症の末梢から体幹に拡がる皮膚硬化パターンと異なるため、ドセタキセル誘発皮膚硬化と考えた。一方、抗RNAポリメラーゼIII抗体陽性であり、皮膚硬化進行後にRaynaud現象を認めた経過から一般的な全身性強皮症の特徴を併せもつようになったと推測した。(著者抄録)

Bullous pemphigoid (BP) is a common autoimmune blistering disorder with unknown etiology. Recently, increasing numbers of BP cases which developed under the medication with dipeptidyl peptidase-4 inhibitors (DPP4i), widely used antihyperglycemic drugs, have been reported in published works. Here, we report a case of DPP4i (teneligliptin)-associated BP that developed in a 70-year-old Japanese man. Interestingly, the patient had acquired reactive perforating collagenosis (ARPC), which is also known to be associated with the onset of BP. In the present case, clinical, histopathological and immunological findings suggested that DPP4i rather than ARPC was associated with the onset of BP.

BACKGROUND: Rosacea is a common skin disease and predominantly affects on the face of middle-aged women. It exceptionally occurs on the extrafacial areas such as ear, neck, axilla, and upper extremities, and has been reported as disseminated rosacea. MAIN OBSERVATION: A 40-year-old Japanese female presented with one-month history of erythematous skin eruption with burning sensation on the face, neck, and upper limbs. Physical examination showed rosacea-like eruption on the face as well as multiple papules disseminated on the neck, forearms, and hands. These extrafacial lesions demonstrated papulonecrotic appearance. Bilateral conjunctiva showed marked hyperemic which was consistent with ocular rosacea. Corneal opacity was also seen. Histology of the umbilicated papule on the neck revealed necrobiotic granulomas around the hair follicle with transepidermal elimination. Another tiny solid papule on the forearm suggesting early lesion also demonstrated necrobiosis with palisading granuloma but no transepidermal elimination. Systemic administration of minocycline and topical tacrolimus therapy promptly improved the skin lesions. Topical application of fluorometholone in temporary addition with levofloxacin improved ocular involvement 12 weeks after her 1st visit. The clinical course of the skin lesion and ocular symptoms mostly correlated. Then, the skin lesion and ocular symptoms often relapsed. Rosacea uncommonly associates with the extrafacial involvement as disseminated rosacea. The present case is characterized by the disseminated papulonecrotic lesions of the extrafacial areas histologically showing transepidermal elimination of necrobiotic granulomas. CONCLUSIONS: Dermatologists should recognize that papulonecrotic lesions of the neck and upper extremities might be extrafacial rosacea when the patient has rosacea on the face.

A 61-year-old Japanese man developed bullous skin lesions during topical therapy for psoriasis vulgaris. Physical examination demonstrated numerous tense bullae and scaly erythemas on the trunk and extremities. Histopathology of the skin biopsy demonstrated subepidermal bullae and lymphocytic infiltration with eosinophils in the dermis. Direct immunofluorescence revealed linear deposits of immunoglobulin (Ig)G, IgA and C3 along the basement membrane zone. Indirect immunofluorescence of 1 mol/L NaCl-split skin showed IgG reactivity with both epidermal and the dermal sides. IgM reactivity with both the epidermal and dermal sides was also detected. Enzyme-linked immunosorbent assays showed negative results for both BP180 and BP230. Immunoelectrophoresis of serum and bone marrow aspiration revealed underlying primary macroglobulinemia with M-proteinemia of IgM- type. Immunoblot analysis revealed IgG, but not IgM, antibodies to recombinant protein of BP180 C-terminal domain. We diagnosed the present case as bullous pemphigoid with IgG anti-BP180 C-terminal domain autoantibodies associated with primary macroglobulinemia and psoriasis vulgaris. Systemic administration of prednisolone 30 mg/day resulted in dramatic improvement of both bullous and psoriatic skin lesions. When the bullous and psoriatic lesions relapsed, DRC chemotherapy (dexamethasone, rituximab and cyclophosphamide) for macroglobulinemia was performed. Then, the psoriatic lesions improved and the bullous lesions disappeared. We suggested that the present case may be paraneoplastic syndrome of bullous pemphigoid associated with primary macroglobulinemia and psoriasis vulgaris.

We report a case involving a 62-year-old woman with invivo-bound immunoglobulin (Ig)G and IgA antibodies in both the intercellular space (ICS) and basement membrane zone (BMZ). Her clinical and histopathological features were identical with those of pemphigus vulgaris, while the immunopathological findings suggested IgG/IgA pemphigus. Direct immunofluorescence (IF) showed invivo-bound IgG and IgA antibodies in the ICS and BMZ, whereas indirect IF showed circulating IgG but not IgA antibodies in the ICS and BMZ. The anti-ICS IgG bound to desmoglein-3, while the anti-BMZ antibodies bound to the epidermal side of 1mol/L NaCl-split skin. To the best of our knowledge, only two similar cases have been reported so far. Furthermore, we also examined IgG subclass distribution of the invivo-bound and circulating anti-ICS and BMZ antibodies, and found that IgG1, IgG2 and IgG4 bound to ICS of the lesional skins, while IgG1 and IgG3 bound to the BMZ. The circulating anti-ICS antibodies belonged to IgG1 and IgG4, while the circulating anti-BMZ antibodies to IgG1, IgG2 and IgG4. We report a case involving a 62-year-old woman with invivo-bound immunoglobulin (Ig)G and IgA antibodies in both the intercellular space (ICS) and basement membrane zone (BMZ). Her clinical and histopathological features were identical with those of pemphigus vulgaris, while the immunopathological findings suggested IgG/IgA pemphigus. Direct immunofluorescence (IF) showed invivo-bound IgG and IgA antibodies in the ICS and BMZ, whereas indirect IF showed circulating IgG but not IgA antibodies in the ICS and BMZ. The anti-ICS IgG bound to desmoglein-3, while the anti-BMZ antibodies bound to the epidermal side of 1mol/L NaCl-split skin. To the best of our knowledge, only two similar cases have been reported so far. Furthermore, we also examined IgG subclass distribution of the invivo-bound and circulating anti-ICS and BMZ antibodies, and found that IgG1, IgG2 and IgG4 bound to ICS of the lesional skins, while IgG1 and IgG3 bound to the BMZ. The circulating anti-ICS antibodies belonged to IgG1 and IgG4, while the circulating anti-BMZ antibodies to IgG1, IgG2 and IgG4.

We present clinically peculiar facial discoid lupus erythematosus (DLE) that mimicked tinea faciei. Although DLE is a chronic autoimmune dermatosis, it has a variety of rare clinical presentations, including periorbital DLE, comedonic DLE and hypertrophic DLE recently. In this case, a scaly, erythematous lesion on the eyelid and the central healed, mildly elevated, annularly distributed facial DLE mimicked tinea faciei, complicating our diagnosis.

症例は69歳女性で、自転車走行中に転倒し左下腿を打撲し、徐々に腫脹・疼痛が増強したため、受傷2日後に当科救急搬送となった。既往歴として、49歳時より慢性心不全、慢性心房細動のため、ワルファリンカリウム内服中であった。初診時、左下腿は全周性に腫脹し、下腿外側は緊満性、暗紫紅色の腫瘤を認めた。下肢CTでは左下腿外側に皮下血腫が疑われた。臨床経過、臨床所見、画像所見より、deep dissecting hematomaと診断し、局所麻酔下に血腫除去術を行った。術後は血腫の拡大を認め、2回にわたり血腫除去を行い、その後は陰圧閉鎖療法にて良好な肉芽形成を認め、1ヵ月後にメッシュ植皮を施行した。

症例1:20歳女。鬱病、パニック障害で9ヵ月前から抗てんかん薬を内服していた。全身の皮疹、発熱を主訴とし、内服薬を中止したものの症状が増悪した。抗てんかん薬内服の既往、薬剤中止後も症状が軽快しない経過、発熱、肝機能障害、白血球増多、好酸球増多、血清ヒトヘルペスウイルス(HHV-6)の再活性化を認め、診断基準に照らし合わせ非典型的な薬剤過敏症候群(DIHS)と診断した。プレドニゾロン(PLS)50mg/日、PSLパルス療法で改善が得られた。症例2:89歳女。潰瘍性大腸炎で1ヵ月前からサラゾスルファピリジンを内服していた。症例3:74歳女。てんかんで1年前から抗てんかん薬を服用していた。症例2、3ともに発熱、皮疹を主訴とし、内服薬の中止後も症状が改善しなかった。発熱、体幹の播種状紅斑、リンパ節腫脹、肝機能障害、HHV-6の再活性化を認め、診断基準は満たさないものの、DIHSの疾患概念には合致すると考えた。症例2はPSL40mg/日で、症例3はPSL60mg/日、PSLパルス療法、ガンマグロブリン大量療法で改善が得られた。

A 32-year-old man visited us because of intractable, sever adult atopic dermatitis (AD). He was treated with systemic cyclosporine therapy, resulting in poor control. The patient was innately introverted and expressed few complaints, so the medical staff was not aware of his living environment. One and half year after the first visit, the patient's father came together and told us that his son was social withdrawal. Then he was admitted to our hospital and administered with a short-term systemic steroid therapy. His symptoms improved promptly, and now he remains stable condition with topical steroids and tacrolimus therapy more than one year after discharge from our hospital. The effects of the same treatment considerably improved by listening to the patient's complaints attentively, understanding his psychosocial stressors, and leading to the far better improvement of drug compliance and treatment effect. We came to reaffirm the significance of seeing not only the skin symptoms but also the personality.

31歳女。発熱と左大腿皮下結節が出現・増悪した。腰背部に境界不明瞭な類円形紅斑を伴う胡桃大までの皮下硬結を認め、肝障害とDICを合併していた。皮膚生検で脂肪織中心にlobularに密な細胞浸潤があり、浸潤している細胞はリンパ球様の単核球とやや大型の淡い胞体を持つ組織球が中心であった。単核球に明らかな異型性はなかったが、核塵を伴って貪食像を示す部分も存在した。Cytophagic histiocytic panniculitisと診断し、プレドニゾロン(PSL)60mg/日を開始した。症状は軽快したが、35mg/日までの減量でDICが再燃し、PSL 40mg/日にシクロスポリン(CY)400mg/日を併用することで寛解が得られた。しかし、減量に伴って再燃を繰り返し、生検では血球貪食像と共に異型Tリンパ球が脂肪細胞を取り囲むように配列する所見を認め、皮下脂肪織炎様T細胞リンパ腫と診断した。14年の経過で再燃により6回入院したが、現在はPSL 25mg/日とCY 125mg/日で寛解が維持されている。

69歳, 女性。10歳頃, いろりに転落し, 頭部に熱傷受傷し広範な脱毛瘢痕形成したが, 鬘を使用し家族にさえ隠していた。7年前から, 潰瘍が出現し軽快しなかったが, 突然の意識障害および痙攣発作で当院に緊急入院するまで放置。入院後, 頭部の腫瘤を発見された。頭頂部を覆う, 径約13cmの巨大な噴火口状の腫瘍で, 悪臭, 壊死組織を伴い易出血性で, 中央が拍動性に上下に動いていた。生検で有棘細胞癌と診断。リンパ節転移や遠隔臓器への転移は認められなかったが, 頭部X線やMRI検査により, 骨融解, 硬膜浸潤がみられ, 上矢状静脈洞圧排狭窄があったことから, 根治的な切除不能と診断し, 髄膜炎や痙攣発作の軽減を目的に放射線療法を行った。腫瘤の縮小, 臨床症状の軽快がみられ退院可能となったが, 初診から1年4ヵ月後, 死亡した。

We describe a 33-year-old patient with a giant skin tumor on her right big toe. The tumor was characterized by unusual clinical manifestations including huge size and papillomatous surface. Chronic long-standing irritation as a result of aerobic exercise may have been involved in the development of giant fibrokeratoma with papillomatous surface.

Spontaneous regression of lentigo maligna melanoma (LMM) is well known to occur occasionally. We experienced a possible cass of LMM located from internal canthus to lower eyelid and a red-bean sized black-brown nodule at adjacent bulbar conjunctiva was also present. The apparent continuity was not found between two lesions. In addition, histological findings suggestive of spontaneous regression were not recognized. This discontinuity of two lesions is most possibly explained by spontaneous regression of LMM, although we did not prove clinical and histological continuity. The other possible explanations are that two lesions occurred separately, or that malignant melanoma of bulbar conjunctiva was due to intransit metastasis.

Melanocytic nevi may microscopically associate with clefts or slits of the nests resembling lymphatic or vascular spaces. This unique histologic feature has been known as an artifact of injection or tissue-processing. We present a case of melanocytic nevus with a prominent vascular space-like structure. We also studied whether intralesional injection of local anesthetic could reproduce similar histologic findings. A 45-year-old Japanese female visited us with a solitary, brownish papule on the chest. Histology revealed numerous nests composed of round to oval-shaped nevus cells throughout the entire dermis. In the mid-dermis, nevus cells were lined up in a layer anastomosing and forming a vascular space-like structure. These nevus cells were uniformly stained with vimentin and S100 protein but not with factor VIII-related antigen. They were also positively immunoreactive with anti-type IV collagen and anti-fibronectin. There were no significant differences in staining intensity in the nevus cells between the solid portion and the vascular space-like structure. In the experimental study, eight melanocytic nevi were removed under local anesthesia. The local anesthetic solution was then injected into the excised nevus. Intralesional injection of a considerable volume of local anesthetic was capable of causing slits or clefts of the nests and dermal edema however, it failed to reproduce a vascular space-like structure similar to that in the present case. These findings suggest that a vascular space-like structure in melanocytic nevus is not caused by the injection alone. Some other factor(s) may play a major role in the development of such structures in melanocytic nevus.

A 61-year-old Japanese woman visited the clinic with multiple tender erythematous nodules on the extremities of ten-days duration. She had suffered from intermittent fever (up to 39°C), polyarthralgia, and myalgia on the extremities for the previous 7 days. The patient had also noted scaly erythematous lesions on the palms and soles for a new months. She had received no special drugs before the onset of the skin eruptions. Her past medical history showed no specific illness or allergies and there were no similar disorders in her family. She had not noted genital eruptions during the course of her illness. Thromboplebitis with an underlying systemic disorder was suspected as an initial diagnosis and she was admitted to our hospital for further examination. On admission she was febrile (38.8°C) and complained of malaise. Cutaneous examination revealed widespread tender, erythematous nodules on both forearms, the dorsal surfaces of the hands, and the lower legs. The individual lesions measured 1 to 4 cm in diamater. Some of the nodules were apparently adherent to the superficial veins and were palpable as cord-like lesions. Multiple erythematous plaques with remarkable annular scales and hyperkeratosis, ranging up to 2 cm in diameter, were found also on palms and soles. Her lower legs and ankles revealed moderate edema. No mucosal involvement of the oral cavity or the genital or perianal regions was observed. Pathologic lymph node swelling on the neck, axilla, or groin was absent. Hematologic studies showed a white blood cell count of 7300 per mm3 with 69% neutrophils. Erythrocyte sedimentation rate was 89 mm per hour and C-reactive proteins (CRP) was 12.31 mg per dL. Bleeding and coagulation times were not prolonged. Partial thromboplastin time (PTT), prothrombin time, and the thrombo test were within normal limits. Results of other blood chemical analyses including antinuclear antibody, immune complexes, or complement titer (C3, C4) were within normal limits. Serologic tests for syphilis (STS) e reactive at a titer of 1:640 (complement fixation method) and the titer of Treponema pallidum hemagglutin test (PHA) was reactive to a dilution of 1:5120. Rapid plasma reagin (RPR) and FTA-ABS tests were strongly positive. The specific IgM hemagglutinin test for Treponema pallidum (TPHA-IgM) by enzyme immunoassay was also positive (1.7 unit normal: &lt 0.9 unit). The patient had a negative reaction in tests for the human immunodeficiency virus (HIV). Biopsy specimens of the skin were taken from the right forearm and lower part of the right leg. During the biopsy, it was noted that a subcutaneous nodule of the right forearm was connected to the superficial vein. These two specimens showed identical histologic changes, such as mild acanthosis and perivascular lymphocytic infiltration in the dermis. The vascular lumen of the large vein of the subcutis was occluded by thrombus and polymorphous infiltration composed of predominantly neutrophils, lymphocytes, and histiocytes was observed in the vascular wall. Giant histiocytic cells were found around the thrombosed vein. A few eosinophils and plasma cells were also seen. Direct immunofluorescence study revealed deposition of IgM, C3, and fibrinogen around or in the wall of the dermal vessels in the specimen taken from the lower part of the right leg, whereas it showed negative results in the thrombotic vein. Deposits of immunoglobulin or complement were not observed in the skin section of the right forearm. Treponema pallidum could not be detected in either specimen by immunohistochemical technique using the biotin-streptoavidin method of rabbit anti-Treponema pallidum antibody.