Yasushi Sugita

Food-dependent exercise-induced anaphylaxis due to ingestion of orange.

Sir, Food-dependent exercise-induced anaphylaxis (FDEIA) is an unusual clinical syndrome of immediate allergic reaction that requires both ingestion of an allergenic food and exercise to induce anaphylaxis (1). Since the first occurrence as a result of exercise and the ingestion of shellfish was published in 1979 (2), foods such as shrimp, shellfish, wheat, celery, tomato, nuts and fruits (including grapes and apples) have been reported in relation to FDEIA (1 – 5). However, citrus fruit such as orange has never been reported as a cause of FDEIA, although it is widely eaten throughout the world. We report the first case of exercise-induced anaphylaxis in association with ingestion of orange.

Interleukin-8 production from cultured human dermal fibroblasts by stimulation with supernatant of cultured human epidermal cells

There is much evidence to support the theory that keratinocytes and dermal fibroblasts actively participate in inflammatory reactions by the production of proinflammatory mediators or cytokines. We investigated the neutrophil chemotactic activity in conditioned media of cultured epidermal cells and dermal fibroblasts, and found that an epidermal cell-derived factor induced fibroblasts to produce a neutrophil chemotactic factor. This neutrophil chemotactic factor was identified as interleukin-8 (IL-8) by the elution position on HPLC and by a neutralization test that uses monoclonal anti-IL-8 antibody (14E4). The epidermal cell-derived factor was fractionated together with thymocyte-proliferating activity on Sephadex G-75 gel chromatography followed by HPLC. It was blocked specifically by anti-interleukin-1 (IL-1) alpha antibody, which indicates that this factor was IL-1 alpha. Since a variety of inflammatory dermatoses is characterized by the infiltration of neutrophils into the skin, induction of IL-8 production in fibroblasts by epidermal cells may play an important role in inflammatory skin diseases.

Correlation between deposition of immuno-components and infiltration pattern of polymorphonuclear leukocytes in the lesions of chronic urticaria.

Urticaria is often associated with perivascular infiltration of leukocytes into the lesions. Although mast cell‐derived chemical mediators are considered to play crucial roles in the infiltration of leukocytes as well as in the dermal edema, other mechanisms for the leukocyte infiltration have not been well defined. This study revealed that approximately 25% of the cases of chronic idiopathic urticaria in whom wheals had continued for more than 12h had deposition of immuno‐components in the lesions, although histological examination of the lesions did not show leukocytoclastic vasculitis. In these lesions with deposition of immuno‐components, both neutrophils and eosinophils had infiltrated at a constant ratio (approximately 2:1), whereas, in the lesions without deposition, a variable population of leukocytes was seen. This result suggests that activation of complements occurs in the lesions of a considerable percentage of patients with chronic idiopathic urticaria and that the complement fragments influence the infiltration patterns of polymorphonuclear leukocytes.

Production of tissue inhibitor of metalloproteinase-1 and -2 by cultured keratinocytes.

The imbalance between metalloproteinases and their inhibitors in tissue remodelling is likely to play an important role in various pathologic conditions. In order to understand the role of keratinocytes in regulating extracellular matrix degradation in skin, we analyzed the production of metalloproteinase inhibitors in keratinocytes. Tissue inhibitor of metalloproteinase-1 (TIMP-1) and tissue inhibitor of metalloproteinase-2 (TIMP-2) mRNA were detected in cultured human keratinocytes and mouse transformed keratinocyte cell line (KCMH-1) cells by RT-PCR. On several column chromatography separation steps of the KCMH-1 conditioned medium, two specific inhibitors for mammalian collagenase were purified showing an Mr of 29 kDa and an Mr of 22 kDa, respectively. The analysis of their N-terminal amino acid sequence revealed that two inhibitors were TIMP-1 and TIMP-2. The final preparation of TIMP-1 had a specific activity of 56000 U/mg and that of TIMP-2 had a specific activity of 26200 U/mg. Our results suggest that keratinocytes take part in tissue remodelling in skin in secreting both TIMP-1 and TIMP-2.

Case of erythrokeratodermia variabilis successfully treated with oral vitamin A

Dear Editor, Erythrokeratodermia variabilis (EKV; Online Mendelian Inheritance in Man no. 133200) is an autosomal dominant or recessive-inherited keratinization disorder, characterized by migratory erythematous patches and fixed hyperkeratotic plaques. In many, but not all cases of EKV, pathogenic mutations have been found in GJB3 or GJB4 that encode connexin (Cx)31 and Cx30.3, respectively. Patients with EKV are treated with topical corticosteroids, salicylic acid, urea and topical/oral retinoids. We herein report a case of EKV which was successfully treated with p.o. administration of vitamin A. A 5-year-old Japanese girl visited our outpatient clinic with a 3-year history of generalized, transient, erythematous, scaly patches and hyperkeratotic plaques. She was born to non-consanguineous, unaffected parents. Histological examination of an erythematous, scaly patch of the right upper arm showed hyperkeratosis with parakeratosis and thickening of the granular cell layer, consistent with EKV. Pityriasis rubra pilaris was ruled out, because no alternating orthokeratosis and parakeratosis in horizontal directions was seen (Fig. 1e). Gene analysis of GJB3 and GJB4 revealed a heterozygous mutation in GJB4 (c.507C>G) previously reported as a polymorphism. Initially, she was treated with topical vitamin D3 analog and corticosteroid, but her symptoms did not improve. At the age of 13 years, she was treated with etretinate following informed consent. Etretinate (0.4–0.6 mg/kg) improved her symptoms, but she discontinued taking the drug due to side-effects, such as cheilitis and hair loss. She was then treated with cyclosporin (2–3 mg/kg), but discontinued it because of gastric distress. At the age of 15 years, she was treated with oral vitamin A at 10 000 U/day, which was gradually increased by 10 000 U/ day every 2 weeks. She showed a substantial improvement in both erythematous patches and hyperkeratotic plaques upon taking 30 000 U/day vitamin A. Her symptoms further improved after increasing the vitamin A dose to 80 000 U/day, without any adverse effects. Following a halving of the vitamin A dose, the symptoms were somewhat exacerbated, but she recovered upon retaking 80 000 U/day vitamin A. As far as our extensive review of the published work has revealed, Wulf et al. first reported the effect of 100 000– 150 000 U/day vitamin A on EKV. However, no other cases of EKV treated with vitamin A have been reported to date, and

A Case of Nevus Lipomatosus Cutaneus Superficialis.

40歳の男性の左臀部に生じたnevus lipomatosus cutaneus superficialisの1例を報告した。腫瘤は広基性弾性軟で, 表面は正常皮膚色であるが中央に紅色調の部分もみられ, dermatofibromaあるいはneurofibromaを疑い, 全摘出を行った。病理組織学的には真皮内の膠原線維間に被膜形成のない結節状の異所性脂肪組織が認められ, 脂肪組織は成熟脂肪細胞よりなっており, 病巣中央では毛包やその周囲に多核白血球やリンパ球, 組織球などの単核細胞浸潤と多核の異物型巨細胞の出現があり, さらに肉芽組織の形成も認められた。以上の組織像より毛包炎, 毛包周囲炎後に脂肪組織のherniationが生じた可能性も想定されたが, 異所性脂肪組織はあたかも血管周囲に増生する像を示しており, 炎症性細胞浸潤や肉芽組織の形成は毛包周囲より大きな範囲を示していたことよりnevus lipomatosus cutaneus superficialisと診断した。限局性にみられた毛包炎, 毛包周囲炎は二次的変化とみなした。なお全摘出後2年以上を経過しているが再発はない。Nevus lipomatosus cutaneus superficialisと診断する際には脂肪組織の増殖が血管周囲に認められるという点が必須の所見と考えられる。