Birger Kränke

Cytokine gene polymorphisms in allergiccontact dermatitis

Susceptibility to contact allergy may be influenced by genetically determined alterations in the production of pro‐ and anti‐inflammatory cytokines. This report focuses on functional polymorphisms in the genes encoding for several cytokines involved in the pathogenesis of contact allergic responses, including tumour necrosis factor (TNF)‐α (G–238u2003A, G–308u2003A), interleukin (IL)‐1β (C‐511G, T+u200a3953C), its natural antagonist, the IL‐1 receptor antagonist (VNTR intron 2), and IL‐6 (G–174C). Polymorphisms were investigated by PCR techniques among polysensitized individuals, defined as individuals with confirmed contact sensitization to para‐substituted aryl compounds and at least one other structurally unrelated allergen (nu2003=u200386), and healthy control individuals without a history of eczema (nu2003=u2003310). The distribution of TNFA–308 genotypes was significantly different in these groups (Padjusted= 0.0378). Compared with carriers of 2 wild‐type alleles (TNFA−308*1/1 (*G/G)), carriers of the TNFA–308*1/2 (*G/A) and TNFA–308*2/2 (*A/A) genotypes tended to be more common among polysensitized individuals [ORu2003=u20031.54, 95% CI (0.92–2.55) and ORu2003=u20032.36 (0.84–6.51), respectively]. No significantly different distribution of genotypes was detected at any other polymorphic loci among control individuals without eczema and polysensitized subjects. These findings suggest a possible relationship between the TNFA–308 polymorphism and contact allergy. The results need to be confirmed in future studies.

Multiple sensitivities to metals

Methods and Results In 11,516 eczema patients patch tested in 14 Austrian centres, nickel sulfate (23%), palladium chloride (8%), cobalt chloride (6.8%) and potassium dichromate (3.2%) were among the 7 most frequently reacting allergens (4). Statistical associations (2-sided x2-analysis, p<0.0005) were found for nickel with palladium, cobalt and chromate, as well as cobalt with palladium and chromate (Fig. I); few palladiumor cobalt-positive patients did not react to nickel.

Epidemiological significance of bufexamac as a frequent and relevant contact sensitizer.

Bufexumae‐containing ointments and creams are widely used by many patients with eczematous disorders as an alternative to topical corticosteroids. Recent studies provide evidence of is notable prevalence of contact sensitization in patch test populations. The aim of this study was to assess the frequency of use of this topically‐applied drug by eczema patients in general, and to evaluate its potential to cause allergic contact reactions. 500 routinely patch tested patients (f:m=377:123) were tested with bufexamac 5% and Parfenac® ointment (the only commercial product available in Austria I in addition lo the standard and other series of the German Contact Dermatitis Group. The packaging of the commercial product was shown to the entire study population, to decide whether or not they had ever used this product. In addition, their general practitioner was contacted to verify the anamnestic data. A total of 30 patients agreed (hut they had definitely used bufexamac. 5 others having probably applied it. The indication for and the duration of treatment were noted. Positive and relevant patch test reactions to bufexamac, as well as the bufexamc‐containing ointment, ointment, were seen in 2(1 out of these 35 patients (57%). and sensitization occurred even alter short‐term application. Our study demonstrates that bufexamac has to be assumed lo be a topical drug with a very high sensitization rate in an unselected patch test population (4% of 500 patients), and should therefore be added to the standard series.

Epidemiologische Überwachung von Kontaktallergenen

ZusammenfassungDas Spektrum der wichtigen Kontaktallergene unterliegt einem ständigen Wandel; viele Faktoren beeinflussen die Sensibilisierungsquoten und damit die Entscheidung, eine Substanz in eine Standardreihe aufzunehmen. Im Informationsverbund Dermatologischer Kliniken werden interessante Substanzen über einen gewissen Zeitraum der DKG-Standardserie angehängt und Parameter wie Sensibilisierungsrate, Reaktionsstärke und Relevanz der Testergebnisse ermittelt. In 6xa0Testphasen wurden seit 1996 insgesamt 13xa0Testsubstanzen untersucht. Aufgrund der Ergebnisse wurden Propolis, der Kompositenmix und Bufexamac 1999 sowie Lyral im Jahre 2002 in die Standardreihe aufgenommen. Die Übernahme von Sorbitansesquioleat, Dispers Blau Mix sowie Iodpropinylbutylcarbamat werden diskutiert. Andere Substanzen wie Glutardialdehyd und p-Aminoazobenzol sollten nur in bestimmten (beruflichen) Risikogruppen bzw. bei klinischem Verdacht gezielt getestet werden, wie etwa auch die Steroide Budesonid und Tixocortol.AbstractThe selection of the most important contact allergens is subject to a continuous change. Several factors may influence the sensitization rates and thus the decision, which substances to include in the standard series of the most frequent allergens. The Information Network of Departments of Dermatology adds substances of interest for a certain time period to the standard series in order to evaluate parameters such as sensitization rate, grade of reaction, and clinical relevance of positive reactions. In 6 testing periods starting in 1996, 13 test substances were evaluated. Due to the results, propolis, compositae mix, and bufexamac were included in the standard series in 1999, while lyral was added in 2002. Sorbitansesquioleat, dispers blue mix, and iodopropynyl butylcarbamate are under further discussion. Substances such as glutaraldehyde and p-aminoazobenzole should be tested in certain risk groups only, whereas the steroids budesonide and tixocortol should be tested when clinically suspected.

Reactions to formaldehyde and formaldehyde releasers in a standard series.

Formaldehyde and the 3 formaldehyde-releasing preservatives Bronopol, Germall 115, and quaternium 15 are widely used in water-containing products such as cosmetics, topical medicaments, and industrial materials (1). Formaldehyde, a frequent contact allergen (1-7), has progressively been substituted by safer formaldehyde releasers (1). However, cross-reaction between formaldehyde and formaldehyde releasers in sensitized patients has frequently been reported (8-12).

Tryptase as Severity Marker in Drug Provocation Tests

Background: In the absence of objective symptoms, it is difficult to assess an adverse reaction during drug provocation testing. We evaluated the value of serum tryptase levels to distinguish between positive, negative and, even more important, so-called ‘hysterical’ reactions (conversion symptoms). The latter are occasionally observed in drug provocation tests when the patient experiences ambiguous subjective symptoms. Methods: In a prospective single-center study, 303 patients underwent 785 drug provocation tests. Blood was taken for tryptase measurement on each test day before and after drug challenge, and the changes in serum tryptase levels in patients with no reactions were compared with those who experienced immediate reactions to a drug. Results: Thirty-four of 785 drug provocations were clinically judged as being positive. Despite objective symptoms, median serum tryptase values in the afternoon were even lower than baseline levels. However, this decrease was not statistically significant. In the 751 patients suffering no objective reactions, the median values of posttesting tryptase values were statistically significantly decreased as compared with pretesting values. Conclusions: The measurement of serum tryptase levels does not appear to be helpful to differentiate mild allergic or nonallergic reactions from ‘hysterical’ ones. The milder decrease in the group with objective drug reactions might indicate slight mast cell activation in some patients. More severe clinical drug reactions led to stronger mast cell degranulation. Mild reactions did not increase the tryptase levels consistently.

Großflächige kutan-subkutane Infiltrate als Nebenwirkung von Interferon-beta-Injektion

ZusammenfassungWährend Interferon-alpha und -gamma bereits seit Jahren für einige hämatologisch-onkologische und hepatologische Indikationen angewandt werden, wird Interferon-beta neuerdings speziell zur Therapie der schubförmig verlaufenden multiplen Sklerose eingesetzt. Wir berichten über eine 41jährige Patientin, die nach 8wöchiger Therapie einer multiplen Sklerose mit subkutanen Interferon-beta-Injektionen derbe, handtellergroße, kutan-subkutane, rötliche Infiltrate an den Einstichstellen im Bereich beider Oberschenkel entwickelte. Histologisch zeigten sich ein perivaskuläres lymphoidzelliges Infiltrat in der Dermis und eine diskrete lobuläre lymphoidzellige Entzündungsreaktion in der Subkutis. Während einer 4wöchigen Therapiepause und unter lokaler Steroidapplikation heilten die Hautveränderungen vollständig ab. Nach Wiederaufnahme der subkutanen Injektionen mit reduzierter Dosis traten lediglich Rötungen um die Einstichstellen ohne begleitende Induration oder Schmerzhaftigkeit auf. Während unter Interferon-beta-Therapie leichte Rötungen und Schwellungen an der Einstichstelle relativ häufig sind und Hautnekrosen vereinzelt beschrieben wurden, sind bisher keine Berichte über ausgedehnte, schmerzhafte kutan-subkutane Infiltrate bekannt.SummaryInterferon alpha and gamma have been used to treat several hepatic, hematological and oncological diseases for years. Recently, interferon beta has been introduced as a therapeutic agent in relapsing-remitting multiple sclerosis. A 41-year-old female patient with multiple sclerosis developed non-tender, palm-sized, cutaneous-subcutaneous, reddish infiltrates at the injection sites on her thighs after 8 weeks of treatment with subcutaneous interferon beta injections. Histopathology revealed a perivascular lymphoid infiltrate of the dermis and a subtle lobular lymphoid infiltrate of the subcutis. Interferon beta therapy was discontinued for 4 weeks. With topical corticosteroids, the skin lesions resolved. When subcutaneous injections were resumed at a reduced dose, only erythema around injection sites developed without induration or pain. Slight erythema and swelling at interferon beta injection site are frequent and rare cases of cutaneous necrosis have been described. However, no reports of large, painful, cutaneous-subcutaneous infiltrates after interferon beta therapy have been published.

IgE antibodies to penicillin are indicative for but not conclusive proof of penicillin allergy.

cell lymphoma. Cancer 2000; 89:1835–44. 6 Paul T, Radny P, Kröber SM et al. Intralesional rituximab for cutaneous B-cell lymphoma. Br J Dermatol 2001; 144:1239–43. 7 Kütting B, Bonsmann G, Metze D et al. Borrelia burgdorferi-associated primary cutaneous B-cell lymphoma: complete clearing of skin lesions after antibiotic pulse therapy or intralesional injection of interferon alpha-2a. J Am Acad Dermatol 1997; 36:311–14. 8 Lee LA, Fritz KA, Golitz TJ et al. Second cutaneous malignancies in patients with mycosis fungoides treated with topical nitrogen mustard. J Am Acad Dermatol 1982; 7:590–8. 9 Fragu P, Lemarchand-Venencie F, Benhamou S et al. Long-term effects in skin and thyroid after radiotherapy for skin angiomas: a French retrospective cohort study. Eur J Cancer 1991; 27:1215–22. 10 Davidson T, Westbury G, Harmer CL. Radiation-induced soft-tissue sarcoma. Br J Surg 1986; 73:308–9.

Hymenoptera Venom Allergy: Time Course of Specific IgE Concentrations during the First Weeks after a Sting

Detection of IgE antibodies specific to honeybee or Vespula venoms is an important criterium firstly for the diagnosis of sensitization and secondly for the indication for a specific immunotherapy. Some authors recommend to postpone blood analysis after an insect sting for a certain time because circulating IgE antibodies might be consumed by the allergic reaction, which would result in a false–negative test outcome. We investigated IgE concentrations during the first weeks after an insect sting in 31 patients with an unequivocal history of an anaphylactic reaction after a honeybee (n = 13) or Vespula (n = 18) sting. Blood samples for analysis of specific IgE concentrations (CAP system, Pharmacia Diagnostics, Sweden) were collected within 2 weeks and 5±2 weeks after the insect sting. 12/13 patients with honeybee venom and 14/18 patients with Vespula venom sensitization had CAP classes 1 or higher within the first 2 weeks. Those 5 patients with CAP class 0 within the first 2 weeks had detectable IgE concentrations a few weeks later. We conclude that testing for specific IgE to hymenoptera venoms is in most cases useful even during the first 2 weeks after the hymenoptera sting. This allows early decisions on further diagnostic procedures and the therapeutic way to choose. Patients with no detectable IgE should, however, be retested after a few weeks.

Seasonal influence on patch test results in Central Europe

6. Aggarwal K. Contact allergic purpura to wool dust. Contact Dermatitis 1982: 8: 281-282. 7. Romaguera C, Grimalt F. PPPP syndrome. Contact Dermatitis I 977: 3: I 03. 8. Meding B, Baum H, Bruze M, Roupe G, Trulsson L. Allergic contact dermatitis from diphenylthiourea in Vulkan heat retainers. Contact Dermatitis 1990: 22: 8-12. 9. Van der Veen J P W, Neering H, De Haan P, Bruynzeel D P. Pigmented purpuric clothing dermatitis due to Disperse Blue 85. Contact Dermatitis 1988: 19: 222-223. 10. Meneghini C L, Angelini G. Secondary polymorphic eruptions in allergic contact dermatitis. Dermatologica 198: 163:63-70. 11. Bruynzee1 D P, Van den Hoogenband H M, Koedjik F. Purpuric vasculitis-like eruption in a patient sensitive to balsam of Peru. Contact Dermatitis 1984: 11: 207-209. 12. Goh C L. Erythema multiforme-like and purpuric eruptions due to contact allergy to proflavine. Contact Dermatitis 1987: 17: 53-54. 13. Van Joost Th, Van Ulsen J, Vuzevski V D, Naafs B, Tank B. Purpuric contact dermatitis to benzoyl peroxide. J Am Acad Dermato/1990: 22: 359-361. 14. Shmunes E. Purpuric allergic contact dermatitis to paraphenylenediamine. Contact Dermatitis 1978: 4: 225-229. 15. Romaguera C, Grimalt F, Lecha M. Occupational purpuric contact dermatitis from formaldehyde resins. Contact Dermatitis 1981: 7: 152-153. Contact Dermatitis 1996: 34: 215