Riitta Riekki

Patch test reactions to cosmetic allergens in 1995–1997 and 2000–2002 in Finland – a multicentre study

Contact sensitivity to cosmetics is common, but the sensitizing chemicals vary between countries and study periods. The present survey aimed at revealing the recent trends in patch test sensitivity with cosmetic chemicals in Finland. We report a retrospective multicentre survey of patch test reactions focusing on cosmetic‐related substances and comparing the test results in 1995–97 with those in 2000–02. The most striking increases in the frequency of the patch test sensitivity were found with balsam of Peru and propolis from 4.0% to 6.2% (P < 0.001) and from 0.5% to 1.4% (P < 0.001), respectively, whereas the most prominent decreases were found with methylchloro/methylisothiazolinone and chlorhexidine diglugonate from 2.4% to 1.3% (P < 0.001) and from 1.2% to 0.5% (P < 0.001), respectively. The level of patch test sensitivity to methyldibromo glutaronitrile increased, although not significantly, from 1.0% to 1.5%. An increasing tendency was also found with hair dye chemicals 4‐aminophenol and toluene‐2,5‐diamine or toluene‐2,5‐diamine sulfate from 1.3% to 3.8% and from 1.4% to 5.2%, respectively, while such a tendency was not found among permanent wave chemicals. The sensitivity level of fragrance mix remained the same (6% − 7%). We conclude that surveys revealing the state of sensitivity to cosmetic chemicals should be performed periodically in different countries.

Modulation of skin collagen metabolism by irradiation: collagen synthesis is increased in irradiated human skin

Radiation‐induced fibrosis is a common side‐effect of cancer treatment. The pathophysiological events leading to fibrosis are not known in detail. We analysed the effect of therapeutic irradiation on human skin collagen synthesis, skin thickness, gelatinases and their inhibitors. Twenty randomly chosen women who had been treated for breast cancer with surgery and radiation therapy participated in the study. In each patient, the irradiated skin area was compared with a corresponding non‐treated skin area. Suction blister fluid (SBF) and serum samples were analysed for the aminoterminal propeptides of type I and type III procollagens (PINP and PIIINP), tissue inhibitors of matrix metalloproteinases (MMPs) 1 and 2 (TIMP‐1 and TIMP‐2) and MMP‐9 and MMP‐2/TIMP‐2 complex. Skin biopsies were analysed for PINP and immunohistochemical staining was used for PIIINP. In irradiated skin, PINP, PIIINP, TIMP‐1 and MMP‐2/TIMP‐2 complex levels in SBF and the number of PINP‐positive fibroblasts in tissue sections were significantly higher in comparison with non‐treated skin. The levels of TIMP‐2 in irradiated and non‐irradiated skin were similar. MMP‐9 could not be detected in SBF with the assay used. The serum levels of MMP‐9 were higher in the treated subjects than the reference values. The serum values of PINP, PIIINP, TIMP‐1, TIMP‐2 and MMP‐2/TIMP‐2 complex were not significantly affected. These results indicate increased local collagen synthesis and accumulation of connective tissue in irradiated skin. The marked upregulation of collagen synthesis as a result of irradiation offers a possibility to treat this complication with compounds such as topical steroids which downregulate collagen synthesis.

Type I collagen turnover and cross-linking are increased in irradiated skin of breast cancer patients

BACKGROUND AND PURPOSE The effects of radiation therapy on the turnover and structure of type I collagen were studied in irradiated and contralateral skin of 18 breast cancer patients without clinically evident fibrosis. MATERIALS AND METHODS The rates of on-going type I collagen synthesis and degradation were assessed by the aminoterminal propeptide of type I procollagen (PINP) and by two different assays (ICTP and SP4) for the carboxyterminal telopeptide of type I collagen in the soluble tissue extracts, respectively. Also, TIMP-1, TIMP-2 and the MMP-2/TIMP-2 complex were measured in the tissue extracts. Insoluble skin matrices, containing the cross-linked type I collagen fibres, were heat-denatured and digested with trypsin. Then, the variants of the carboxyterminal telopeptide of type I collagen were separated by high performance liquid chromatography (HPLC). The major histidinohydroxylysinonorleucine (HHL)-cross-linked variant was quantified by the SP4 assay, and the minor pyridinoline analogue (PA)-cross-linked telopeptide was quantified by the ICTP assay. RESULTS Both the synthesis and degradation of type I collagen were increased (r=0.906; P<0.001) on the irradiated side, whereas the concentration of the MMP-2/TIMP-2 complex was decreased. In the insoluble tissue digests, the HHL-cross-linked telopeptides of type I collagen, also, when expressed/tissue hydroxyproline, were increased in the irradiated skin. TIMP-1, TIMP-2 or PA-cross-linked telopeptides of type I collagen showed no differences between the two sides. CONCLUSIONS Radiotherapy induces a long-term increase in the turnover of type I collagen and leads to the accumulation of cross-linked type I collagen in skin.

The production of collagen and the activity of mast-cell chymase increase in human skin after irradiation therapy

Abstract:  Fibrosis is a common complication of radiotherapy. The pathogenesis of radiation‐induced fibrosis is not known in detail. There is increasing evidence to suggest that mast cells contribute to various fibrotic conditions. Several mast‐cell mediators have been proposed to have a role in fibrogenesis. Tryptase and chymase, the predominant proteins in mast cells, have been shown to induce fibroblast proliferation and collagen synthesis in vitro. In order to explore the role of mast cells in irradiation‐induced fibrosis, we analyzed skin biopsies and suction blister fluid (SBF) samples from the lesional and healthy‐looking skin of 10 patients who had been treated for breast cancer with surgery and radiotherapy. The biopsies were analyzed histochemically for mast‐cell tryptase, chymase, kit receptor, and tumor necrosis factor‐α. Skin collagen synthesis was assessed by determining the levels of type I and III procollagen amino‐terminal propeptides (PINP and PIIINP) in SBF and using immunohistochemical staining for PINP. Immunohistochemical stainings for prolyl‐4‐hydroxylase reflecting collagen synthesis and chymase immunoreactivity in irradiated and control skin were also performed. The mean level of procollagen propeptides in SBF, which reflects actual skin collagen synthesis in vivo, was markedly increased in irradiated skin compared to corresponding healthy control skin areas. The mean number of PINP‐positive fibroblasts was also significantly increased in the upper dermis of radiotherapy‐treated skin. The number of cells positive for tryptase, chymase and kit receptor was markedly increased in irradiated skin. In addition, using double‐staining techniques, it was possible to demonstrate that in some areas of the dermis, tryptase‐positive mast cells and fibroblasts are closely associated. These findings suggest a possible role of mast cells in enhanced skin collagen synthesis and fibrosis induced by radiotherapy.

Modulation of collagen synthesis and mRNA by continuous and intermittent use of topical hydrocortisone in human skin.

Background  Glucocorticoids have been shown to downregulate collagen synthesis in human skin in vivo, thereby contributing to skin atrophy.

Radiation therapy induces tenascin expression and angiogenesis in human skin.

In analysing radiation-induced connective tissue changes, we studied tenascin expression, elastic fibres, angiogenesis and physio-mechanical properties in irradiated and contralateral healthy skin of radiotherapy-treated breast cancer patients. Skin biopsies were obtained from a radiotherapy-treated skin area and a corresponding non-treated skin area. Haematoxylin-eosin and Verhoeff stainings as well as immunohistochemical stainings for tenascin and factor VIII were performed. Epidermal and total skin thickness, together with the amount of elastic tissue calculated by computerized digital image analysis, were measured. Suction blisters were induced on both skin areas. Transepidermal water loss was analysed. Skin elasticity was also measured. Tenascin expression was found to be increased in irradiated human skin. In haematoxylin-eosin and factor VIlI-stained sections, an increase in the number of blood vessels was detected. Although skin stiffness measured by an elastometer was increased in irradiated skin, no marked difference in the elastic fibres could be found between treated and non-treated skin. The increased tenascin expression could be due to activation of cytokines as a result of irradiation. An increase in angiogenesis could be caused by an activation of angiogenetic factors by irradiation or due to direct radiation damage on blood vessel walls. Our findings suggest that the effects of irradiation tend to accumulate in the dermal parts of skin. The higher skin stiffness values measured by elastometer in irradiated skin could be due to an accumulation of dermal connective tissue as a result of irradiation.

Occupational contact urticaria and rhinitis caused by immediate allergy to palladium salts.

A 50-year-old previously healthy non-smoking laboratory technician, who had worked in catalyst research for 26 years, presented with recurrent urticaria on the hands and the face, and watery rhinitis associated with handling palladium salts at work. When exposed to fine dusts of dried and powdered mixtures containing the palladium nitrate salts Pd(NH3)4(NO3)2 and Pd(NO3)2, she immediately developed itchy facial erythema, which disappeared within hours. Occasional spillages of palladium salt solutions on the patient’s bare forearms caused immediate urticarial wheals to appear on the contact site. She also suffered from watery rhinitis and sneezing, and itching of the eyes, when she was exposed to fine dust of ground materials that contained palladium salts. She had no symptoms suggestive of asthma. She was symptom-free during leisure time and when she handled compounds of other metals, that is, platinum, rhodium, vanadium, and aluminium. Prick testing with common aeroallergens showed sensitization to tree pollens (Table 1). Prick tests with samples of two palladium compounds from the patient’s workplace gave positive results. Control prick tests with tetraamminepalladium(II) hydrogencarbonate (1% aq.) and tetraamminepalladium(II) nitrate (10% aq.) gave no positive reactions in 40 volunteers. In 3 of the volunteers, 2-mm wheals were observed with both palladium compounds, and were interpreted as signs of mild irritation.

Benzyl alcohol allergy mimicking corticosteroid allergy

Conflicts of interest: The authors declare no conflict of interests. erythema and pruritus had appeared at the injection site. She developed no generalized symptoms. She had no history of skin diseases, but reported skin irritation after using perfumed cosmetic products and eardrops containing flumethasone pivalate with clioquinol (Locacorten-Vioform®) and ciprofloxacin with hydrocortisone (Ciproxin-Hydrocortison®) for otitis externa. To exclude allergies, skin tests were performed. Prick tests with methylprednisolone and bupivacaine (without BA) gave negative results. Patch tests were performed with baseline, cosmetic, steroid and fragrance series, and Locacorten-Vioform®, Ciproxin-Hydrocortison® (‘as is’), and ciprofloxacin hydrochloride. Weak positive (+) reactions to neomycin, Myroxylon pereirae resin (balsam of Peru), fragrance mix I, fragrance mix II and farnesol were observed; clioquinol, geraniol, benzyl alcohol and both eardrops gave strong positive (++) reactions. Tixocortol-21-pivalate gave an irritant reaction; allergy was later excluded by a negative provocation test result with hydrocortisone cream.