Shigeharu Sano

Brilliant Lake Red R as a cause of pigmented contact dermatitis

Twenty‐three patients suffering from pigmented contact dermatitis caused by cosmetics containing Brilliant Lake Red R were observed. Commercial samples of Brilliant Lake Red R proved to contain many ethyl acetate extractable impurities; 1‐phenylazo‐2‐naphthol and azobenzene were isolated and identified.

Malignant fibrous histiocytoma developing in a burn scar

A case of malignant fibrous histiocytoma (MFH) developing in a burn scar is presented. The patient was burnt at 3 years of age and 25 years later, a rapidly growing tumour developed in the burn scar. MFH was diagnosed by light and electron microscopy and by an immunoperoxidase method. This complication of a burn scar has not been previously reported.

Pigmented contact dermatitis from azo dyes. I. Cross-sensitivity in humans.

Eight patients suffering from pigmented contact dermatitis caused by the commercial Brilliant Lake Red R were patch tested with purified Sudan I and its several chemical analogues. Positive reactions were observed to Sudan I, Orange SS, Brilliant Lake Red R, Vacanceine Red, Yellow OB and Sudan II. Negative patch tests were obtained with Toluidine Red, Permanent Orange, Lithol Red and Sudan III.

Involvement of insulin-like growth factor-I in psoriasis as a paracrine growth factor : dermal fibroblasts play a regulatory role in developing psoriatic lesions

Abstract To investigate the contribution of dermal fibroblasts to the development of psoriasis, we examined the expression of mRNA for insulin-like growth factor-I (IGF-I) and its regulator IGF-I binding proteins (IGFBPs) in psoriatic fibroblasts by RT-PCR. We also studied the effect of inflammatory cytokines including interferon gamma (IFN-γ), tumor necrosis factor alfa (TNF-α), and IFN-α on the expression of IGF-I and IGFBPs in the fibroblasts. Semiquantitative analysis revealed that IGF-I mRNA expression in psoriatic fibroblasts (PF) was significantly higher than in control fibroblasts (CF). However, no significant difference in IGF-I mRNA was shown between nonlesional psoriatic fibroblasts (NF) and CF. Treatment with IFN-α in vitro upregulated IGF-I mRNA in PF and in CF. TNF-α appeared to downregulate IGF-I mRNA in PF but had no effect on CF. IFN-γ did not show a significant effect on IGF-I mRNA levels in any type of fibroblast. IGFBP-3 mRNA was expressed equally in PF and CF, and was not affected by cytokines. The expression of IGFBP-5 mRNA in PF was downregulated by IFN-γ and TNF-α. Taken together, these results indicate that dermal fibroblasts may contribute to the epidermal hyperplasia of psoriasis by promoting keratinocyte proliferation through IGF-I, whose secretion could be modulated by inflammatory cytokines.

Unusual Pigmentation on the Skin over Trunk Bones and Extremities

6 young people (19-31 years old) exhibited unusual light or dark brown, ill-circumscribed or reticular pigmentation distributed over protrudent bones. 5 of them have been using nylon towels and scrub brushes for over 3-10 years. Biopsy specimens showed that the amount of melanin granules in the basal layer was increased and melanophages were scattered in the upper dermis. Inflammatory infiltrates were minimal.

Connective tissue metabolism in culture fibroblasts of a patient with Ehlers-Danlos syndrome type I.

SummaryStudy on connective tissue metabolism was conducted with a patient with Ehlers-Danlos syndrome (E-D) of Type J who visited our institute.The conversion of procollagen into tropocollagen in the medium of cultured fibroblasts was assayed by the chase technique using3H-proline. The conversion was inhibited in the cultured fibroblasts of the patient.The components of glycosaminoglycans in cultured medium and fibroblasts from E-D were within normal ranges, however, the ratio of glycoprotein to glycosaminoglycans of intra-and extra-cellular fractions of E-D fibroblasts was higher than the normal one.These findings suggest that the insufficient maturation of collagen fiber may be considered fundamental disorders of E-D.ZusammenfassungDer Bindegewebsstoffwechsel wird bei einem Patienten mit einem Ehlers-Danlos-Syndrom des Typs I untersucht.Die Umwandlung von Prokollagen in Tropokollagen in die Fibroblastenkultur wurde mittels3H-Prolin durchgeführt. Der Prozeß der Umwandlung wird in der Fibroblastenkultur des Patienten gehemmt.Die Glykosaminoglykane im Kulturmedium und die Fibroblasten des Patienten zeigten keine Abweichung von der Norm, jedoch war das Verhältnis von Glykoproteinen zu Glykosaminoglykanen der intra- und extracellulären Fraktion der Fibroblasten des Patienten höher als bei normalen Patienten.Diese Ergebnisse lassen den Hinweis zu, daß eine ungenügende Reife der Kollagenfaser eine der wesentlichsten Ursachen des Ehlers-Danlos-Syndroms ist.

POSSIBLE BINDING OF EPIDERMOLYTIC TOXIN TO A SUBCELLULAR FRACTION OF THE EPIDERMIS

An in vitro method for assessing the activity of epidermolytic toxin (ET) was developed in this study. It was almost equal in sensitivity to the in vivo assay system in which ET was injected subcutaneously into new‐born mice. By using the in vitro method it was found that ET could induce epidermal splitting after incubation with the skin only for 5 minutes. No epidermolytic activity remained in the reaction mixture. The activity of ET was not abolished by proteinase inhibitors such as Trasylol, ε‐aminocaproic acid or soy bean trypsin inhibitor. It was abolished by an extract from the epidermis of new‐born mice. The inhibitory activity of the extract was preserved by heating at 56°C for 30 minutes. It was destroyed by heating at 80°C for 30 minutes. The activity was found in a subcellular fraction which should contain mitochondria and lysosomes from the epidermal cells. A reduction in the amount of ET was observed in acrylamide gel electrophoresis after incubation of ET with the subcellular fraction. The possible mode of action of ET was discussed.

Cutaneous inflammatory pseudotumour (plasma cell granuloma)

Sir, Topical 5-aminolaevulinic acid (5-ALA) photodynamic therapy (PDT) has become an effective treatment option in dermatology. We report a 70-year-old man who presented with extensive erythematous patches on his abdomen and infiltrated plaques on his arms and neck. These were preceded by extensive figurate and annular erythema on his trunk and limbs for 10 years. He had a history of congestive cardiac failure, atrial fibrillation and chronic obstructive airway disease. Mycosis fungoides (MF) was confirmed histopathologically and he cleared with a course of oral 8-methoxypsoralen (8-MOP) plus ultraviolet A (PUVA). During the next year his MF progressed in extent and he also developed a solitary tumour (1 ́5 1 ́5 cm) on his left posterior thigh. The extensive patch and plaque MF cleared with a further course of oral 8-MOP PUVA, but the nodule remained and became ulcerated and painful over the next 3 months. Biopsy of this tumour showed an ulcerated epidermis with replacement of the subcutaneous tissue by a dense infiltrate of malignant CD31 T cells (Fig. 1a). There was no lymphadenopathy or organomegaly. Blood investigations were normal. Computed tomographic scans of the thorax and abdomen were negative. The tumour was treated with 5-ALA PDT: 5-ALA 20% in a cream base (Aladerm, Crawford Pharmaceuticals, Milton Keynes, U.K.) was applied, under polythene occlusion, to the tumour. Four hours later, excess 5-ALA was wiped off and fluorescence was graded as satisfactory using Woods light. He received 20 J cm at 20 mW cm using a Waldmann PDT lamp (MSR 1200; 580±740 nm). Irradiance was measured using a calibrated handheld meter (International Light 1400A and Selo33/F/W/QND52 detector with spectral shaping and neutral density filters calibrated by D.Taylor, Gloucester, U.K.). He graded pain during treatment as 8/10 but experienced no other adverse effects. The lesion cleared after five consecutive treatments over 12 weeks. Repeat biopsy showed a lymphohistocytic infiltrate but complete clearing of the original infiltrate of malignant T cells (Fig. 1b). During his course of PDT his generalized patch and plaque MF relapsed. The tumour site has remained clear on clinical examination 1 years later. He has required two courses of PUVA therapy for generalized patch and plaque MF during this period. Topical 5-ALA PDT has been proven to be effective for superficial cutaneous cancers, but there are few reports of its use in treating MF. Shanler et al. treated patch/ plaque-stage cutaneous T-cell lymphoma and showed that protoporphyrin IX accumulated within lymphocytic infiltrates; early therapeutic results were promising. Boehncke et al. using an argon laser at 630 nm showed inhibition of proliferation of malignant transformed T cells in vitro and in vivo. Wolf et al. have demonstrated the efficacy of PDT (20% 5-ALA) using a broad-spectrum source (40 J cm at 44 mW cm) in two patients with MF who cleared after four and five PDT treatments, respectively. However, Amman and Hunziker reported a poor response for an infiltrated plaque of MF to just one PDT treatment using an identical regimen. This suggests that multiple treatments are required to obtain a complete histological response. We have demonstrated the benefits of low light dose, low dose rate topical 5-ALA PDT for nodular MF, but a formal study is needed to confirm our findings.

Immunological study on CD3 defective cutaneous T cell lymphoma cells from a patient with Sézary syndrome

Here we investigated the nature of cutaneous T cell lymphoma (CTCL) cells lacking surface CD3. A large number of CD3−CD4 T cells were found in the peripheral blood and lesional skin of a patient with Sézary syndrome, which is a variant of CTCL. Southern blot analysis revealed that a clonal rearrangement of T cell receptor (TCR) genes was detected in the separated CD3−CD4 cells, whereas CD3+CD4 cells showed no clonal rearrangement, indicating that the CD3−CD4 cells represented CTCL cells. However, the CTCL cells expressed TCR with a particular Vβ apart from CD3. The CTCL cells showed significant responses to staphylococcal enterotoxins (SEs) in vitro, although they hardly responded to phytohaemagglutinin, Mycobacterium tuberculosis antigen, and alloantigen. They required antigen‐presenting cells (APC) to respond to SEB. Blocking analyses with MoAbs revealed that they recognized SEB through TCR depending on HLA‐DR and intercellular adhesion molecule‐1 (ICAM‐1). Taken collectively, these results indicate that the CTCL cells lacking surface CD3 could proliferate in response to bacterial superantigens, whereas the responses to conventional antigens were generally suppressed. These results also implied that CTCL could be exacerbated by bacterial infection.

Acidic glycosaminoglycans in skin and urine of a patient with wide-spreaded lichen sclerosus et atrophicus.

SummaryChanges of dermal and urinary acidic glycosaminoglycans in Lichen Sclerosus et Atrophicus (LSA) were investigated with the following results:1.Hyaluronic acid (HA) was excreted in urine of a patient with LSA.2.HA and low sulfate chondroitin were eluted with 0.5 M NaCl by Bio Rad AG 1-×2 (Cl- form) column chromatography.3.Involved dermal tissue contained only about 50% of HA in the skin of a healthy adult.ZusammenfassungDie Veränderung der dermalen und im Urin nachweisbaren sauren Glykosaminoglykane beim Lichen sclerosus et atrophicus zeigten, daß 1. Hyaluronsäure im Urin nachgewiesen wurde, 2. Hyaluronsäure und Niedersulfat-Chondroitin mitteld 0,5 M NaCl durch Bio Rad AG 1-×2 Säulenchromatographie eluiert werden konnte, 3. die veränderte Haut nur etwa 50% der Hyaluronsäure gesunder Probanden enthält.Changes of dermal and urinary acidic glycosaminoglycans in Lichen Sclerosus et Atrophicus (LSA) were investigated with the following results: 1. Hyaluronic acid (HA) was excreted in urine of a patient with LSA. 2. HA and low sulfate chondroitin were eluted with 0.5 M NaCl by Bio Rad AG 1- X 2 (Cl- form) column chromatography. 3. Involved dermal tissue contained only about 50% of HA in the skin of a healthy adult.