1
868 prednisone daily. She responded well; chrysotherapy was reduced to 50 mg every 3 weeks, and corticosteroids were tapered off. After she had been on gold therapy for 3 months she had an itching erythema of the neck and wrist. 7 months later she had a severe maculopapular confluent rash in both antecubital fossae, on the wrists, and underneath the straps of her brassiere and her necklace. She recalled similar reactions to jewellery many years before but she had been wearing jewellery without problems for several years. Biopsy of an erythematous papule was compatible with allergic contact dermatitis. Patch testing evinced a strong reaction to nickel sulphate and cobalt chloride but not to gold chloride. The lesions cleared within a few weeks of discontinuation of chrysotherapy and the patient was again able to wear jewellery without significant skin reactions. When gold was started again the severe maculopapular rashes recurred, disappearing once more when gold was discontinued. Contact hypersensitivity to metallic gold is uncommon and is even rarer after systemic gold treatment. It can be difficult to differentiate gold from nickel contact dermatitis 2-3 Patient B refused patch testing. In patients A and C a gold chloride patch test was negative but both reacted strongly to nickel. 2 patients with contact-dermatitis-like eruption had had dermatitis due to jewellery and we suggest that they had been sensitised to nickel before chrysotherapy and that chrysotherapy was responsible for an exacerbation of the contact hypersensitivity. Two possible explanations come to mind: the impairment of delayed type cutaneous hypersensitivity often seen in rheumatoid arthritis may have been reversed by chrysotherapy,’ or the gold injections were contaminated with nickel in the drug or in the needle.5 Neither in patient A, tested 8 months after the final withdrawal of chrysotherapy, nor in patient C, tested 2 weeks after an intramuscular injection of aurothioglucose, was an anergic response found on assessing cutaneous hypersensitivity to seven common recall antigens. We also measured nickel concentrations in aurothioglucose (’Auromyose’), before and after passage through an injection needle, by inductively coupled plasma atomic emission spectroscopy (Netherlands Energy Research Foundation ECN; measurement error 10%). The amounts were 167 ng/g before and 154 ng/g after passage, indicating that the nickel is more likely to come from the aurothioglucose than from the needle. No data are available on whether such small amounts of nickel can cause sensitisation to nickel or an exacerbation of contact allergy. However, delayed skin allergic reactions to nickel have been reported after intradermal administration of a local anaesthetic contaminated with nickel6,7 and after intravenous infusions via metallic cannulae;8 and Boss et al9 reported a sensitisation rate of 20% from ear piercing. We thank the Dutch League against Rheumatism for fmancial support and the research nurses, Leny Theunisse and Dini Lubberts, for follow-up of the patients. Departments of Rheumatology and Dermatology, University Hospital Nijmegen, 6500 HB Nijmegen, Netherlands MATH J. H. WIJNANDS CHRISTIAN M. PERRET FRANK H. J. VAN DEN HOOGEN LEVINUS B. A.VAN DE PUTTE PIET L. C. M. VAN RIEL 1. Hofmann C, Burg, G, Jung C. Kutane Nebenwirkungen der Goldtherapie. Klinische und histologische Ergebnisse. Z Rheumatol 1986; 45: 100-06. 2. Fowler Jr. IF. Allergic contact dermatitis to gold. Arch Dermatol 1988; 124: 181-82. 3. Walton S, Gandhi MM, Wyatt EH. Snags in gold patch testing. Contact Dermatitis 1988; 18: 248-49 4. Smith MD, Smith A, O’Donnel J, Ahem MJ, Roberts-Thomson PJ. Impaired delayed type cutaneous hypersensitivity in rheumatoid arthritis reversed by chrysotherapy. Ann Rheum Dis 1989; 48: 108-13. 5. Fulton RA, Sturrock RD, Capell H. Another hazard of gold therapy? Ann Rheum Dis 1982; 41: 100-01 6. De Corres LF, Garrastazu MT, Soloeta R, Escayol P. Nickel contact dermatitis in a blood bank. Contact Dermatitis 1982; 8: 32-37. 7. Lachapelle JM, Tennstedt D. An anatomo-clinical study of delayed skin allergic reactions to nickel following intradermal injections of lidocaine with a Dermo-Jet. Contact Dermatitis 1982; 8: 193-99. 8. Stoddart JC, Durh MB. Nickel sensitivity as a cause of infusion reactions Lancet 1960; ii: 741-42. 9. Boss A, Menné T. Nickel sensitization from ear piercing. Contact Dermatitis 1982; 8: 211-13. Absence of cytomegalovirus DNA in kidneys in IgA nephropathy SIR,-There have been several contradictory reports about the detection of cytomegalovirus (CMV) antigen in the mesangial deposits of IgA nephropathy (IgAN)." In these studies immunofluorescence techniques were used to identify CMV antigen in frozen-cut sections of human kidney,1-4 or in-situ hybridisation for viral DNA.s We have used indirect immunofluorescence with monoclonal antibodies to the early and late antigens of CMV (Biotech-Dupont, Billerica, Massachusetts, USA) to investigate a series of 20 kidneys from IgAN patients. All samples were negative, both in the mesangium and in other areas. Heieren et al6 have suggested that CMV might replicate in mesangial cells. If this were so, it would be difficult to detect the antigen beneath the IgA and complement deposits, but CMV DNA might be identifiable. We examined by the polymerase chain reaction (PCR) biopsy samples from 10 of the kidneys we investigated by immunofluorescence. Two pairs of primers were used for each sample after degradation of the proteins by proteinase K. Thirty-five amplification cycles were done with the Perkin-Elmer-Cetus (Norwalk, USA) amplification and temperature control system. Controls included peripheral lymphocyte extracts from CMV-infected transplant patients. These samples had been assessed for positivity by immunofluorescence on lymphocyte cytospins, and CMV infection was confirmed by seroconversion and a positive response to ’Cymevan’ therapy. Amplification products were detected both by direct gel electrophoresis and silver staining on ’Phast’-system minigels (Pharmacia, Uppsala, Sweden) and by dot-blotting (biotinylated oligonucleotides specific for the amplified regions in the’Oncor’ [Gaithersburg, Maryland, USA] non-isotopic system). All amplifications were successful, demonstrated by clear bands and dots yielded by infected lymphocytes. All kidney samples, however, were negative in gel analysis and only 1 produced a faint positive dot with the specific probe. These data accord with reports ruling out CMV in the pathogenesis of IgA nephropathy, and match the observation of 1 in 14 positive on immunofluorescence staining reported by Waldo et al.3 Immunology Laboratory, Faculty of Medicine, 54500 Vandoeuvre les Nancy, France MARIE C. BÉNÉ JIANQING TANG GILBERT C. FAURE 1. Gregory MC, Hammond ME, Brewer ED. Renal deposition of cytomegalovirus antigen in immunoglobulin-A nephropathy. Lancet 1988; i: 11-14. 2. Dueymes M, Mignon-Conté M, Dueymes JM, Vernier I, Conte JJ. Mesangial staining with cytomegalovirus antibodies in IgA nephropathy. Lancet 1988; i: 619. 3. Waldo FB, Britt WJ, Tomana M, Julian BA, Mestecky J. Non-specific mesangial staining with antibodies against cytomegalovirus in immunoglobulin-A nephropathy. Lancet 1988; i: 129-31. 4. Sato M, Kojima H, Shinkai Y, Koshikawa S. Cytomegalovirus and IgA nephropathy. Lancet 1988; ii: 1251. 5. Okamura M, Kanayama Y, Negoro N, Takeda T, Inoue T. Failure to detect cytomegalovirus-DNA in IgA nephropathy by in-situ hybridisation. Lancet 1989; i: 1265. 6. Heieren M, van der Woude FJ, Balfour HH. Cytomegalovirus replicates efficiently in human kidney mesangial cells. Proc Natl Acad Sci USA 1988; 85: 1642-46. CORRECTIONS Effect of heparin, aspirin, or alteplase in reduction ofmyocardialischaemia in refractory unstable angina.-In this article by Prof G. G. Neri Semeriand others (March 17, p 615), the first sentence in the section "Other events" should have ended: "... and 1 non-Q wave myocardial infarction in the alteplase group". D-aminoacids and microwaves. The last paragraph of this letter by Prof G. Lubec (March 31, p 792) should have read "milk formulae were used ... because they provide a well-characterised food model and not to demonstrate the toxicity of microwave treated milk. Data from meat would have changed the calculations in terms of cis-amionacid isomers significantly...".

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868

prednisone daily. She responded well; chrysotherapy was reducedto 50 mg every 3 weeks, and corticosteroids were tapered off. Aftershe had been on gold therapy for 3 months she had an itchingerythema of the neck and wrist. 7 months later she had a severemaculopapular confluent rash in both antecubital fossae, on thewrists, and underneath the straps of her brassiere and her necklace.She recalled similar reactions to jewellery many years before but shehad been wearing jewellery without problems for several years.Biopsy of an erythematous papule was compatible with allergiccontact dermatitis. Patch testing evinced a strong reaction to nickelsulphate and cobalt chloride but not to gold chloride. The lesionscleared within a few weeks of discontinuation of chrysotherapy andthe patient was again able to wear jewellery without significant skinreactions. When gold was started again the severe maculopapularrashes recurred, disappearing once more when gold was

discontinued.Contact hypersensitivity to metallic gold is uncommon and is

even rarer after systemic gold treatment. It can be difficult todifferentiate gold from nickel contact dermatitis 2-3 Patient B refusedpatch testing. In patients A and C a gold chloride patch test wasnegative but both reacted strongly to nickel. 2 patients withcontact-dermatitis-like eruption had had dermatitis due to jewelleryand we suggest that they had been sensitised to nickel beforechrysotherapy and that chrysotherapy was responsible for anexacerbation of the contact hypersensitivity.Two possible explanations come to mind: the impairment of

delayed type cutaneous hypersensitivity often seen in rheumatoidarthritis may have been reversed by chrysotherapy,’ or the goldinjections were contaminated with nickel in the drug or in theneedle.5

Neither in patient A, tested 8 months after the final withdrawal ofchrysotherapy, nor in patient C, tested 2 weeks after an

intramuscular injection of aurothioglucose, was an anergic responsefound on assessing cutaneous hypersensitivity to seven commonrecall antigens. We also measured nickel concentrations in

aurothioglucose (’Auromyose’), before and after passage through aninjection needle, by inductively coupled plasma atomic emissionspectroscopy (Netherlands Energy Research Foundation ECN;measurement error 10%). The amounts were 167 ng/g before and154 ng/g after passage, indicating that the nickel is more likely tocome from the aurothioglucose than from the needle. No data areavailable on whether such small amounts of nickel can causesensitisation to nickel or an exacerbation of contact allergy.However, delayed skin allergic reactions to nickel have been

reported after intradermal administration of a local anaestheticcontaminated with nickel6,7 and after intravenous infusions viametallic cannulae;8 and Boss et al9 reported a sensitisation rate of20% from ear piercing.We thank the Dutch League against Rheumatism for fmancial support andthe research nurses, Leny Theunisse and Dini Lubberts, for follow-up of thepatients.

Departments of Rheumatologyand Dermatology,

University Hospital Nijmegen,6500 HB Nijmegen, Netherlands

MATH J. H. WIJNANDSCHRISTIAN M. PERRETFRANK H. J. VAN DEN HOOGENLEVINUS B. A.VAN DE PUTTEPIET L. C. M. VAN RIEL

1. Hofmann C, Burg, G, Jung C. Kutane Nebenwirkungen der Goldtherapie. Klinischeund histologische Ergebnisse. Z Rheumatol 1986; 45: 100-06.

2. Fowler Jr. IF. Allergic contact dermatitis to gold. Arch Dermatol 1988; 124: 181-82.3. Walton S, Gandhi MM, Wyatt EH. Snags in gold patch testing. Contact Dermatitis

1988; 18: 248-494. Smith MD, Smith A, O’Donnel J, Ahem MJ, Roberts-Thomson PJ. Impaired

delayed type cutaneous hypersensitivity in rheumatoid arthritis reversed bychrysotherapy. Ann Rheum Dis 1989; 48: 108-13.

5. Fulton RA, Sturrock RD, Capell H. Another hazard of gold therapy? Ann Rheum Dis1982; 41: 100-01

6. De Corres LF, Garrastazu MT, Soloeta R, Escayol P. Nickel contact dermatitis in ablood bank. Contact Dermatitis 1982; 8: 32-37.

7. Lachapelle JM, Tennstedt D. An anatomo-clinical study of delayed skin allergicreactions to nickel following intradermal injections of lidocaine with a Dermo-Jet.Contact Dermatitis 1982; 8: 193-99.

8. Stoddart JC, Durh MB. Nickel sensitivity as a cause of infusion reactions Lancet 1960;ii: 741-42.

9. Boss A, Menné T. Nickel sensitization from ear piercing. Contact Dermatitis 1982; 8:211-13.

Absence of cytomegalovirus DNA in kidneysin IgA nephropathy

SIR,-There have been several contradictory reports about thedetection of cytomegalovirus (CMV) antigen in the mesangialdeposits of IgA nephropathy (IgAN)." In these studiesimmunofluorescence techniques were used to identify CMVantigen in frozen-cut sections of human kidney,1-4 or in-situ

hybridisation for viral DNA.sWe have used indirect immunofluorescence with monoclonal

antibodies to the early and late antigens of CMV (Biotech-Dupont,Billerica, Massachusetts, USA) to investigate a series of 20 kidneysfrom IgAN patients. All samples were negative, both in themesangium and in other areas. Heieren et al6 have suggested thatCMV might replicate in mesangial cells. If this were so, it would bedifficult to detect the antigen beneath the IgA and complementdeposits, but CMV DNA might be identifiable. We examined bythe polymerase chain reaction (PCR) biopsy samples from 10 of thekidneys we investigated by immunofluorescence. Two pairs ofprimers were used for each sample after degradation of the proteinsby proteinase K. Thirty-five amplification cycles were done withthe Perkin-Elmer-Cetus (Norwalk, USA) amplification and

temperature control system. Controls included peripherallymphocyte extracts from CMV-infected transplant patients.These samples had been assessed for positivity byimmunofluorescence on lymphocyte cytospins, and CMV infectionwas confirmed by seroconversion and a positive response to’Cymevan’ therapy. Amplification products were detected both bydirect gel electrophoresis and silver staining on ’Phast’-systemminigels (Pharmacia, Uppsala, Sweden) and by dot-blotting(biotinylated oligonucleotides specific for the amplified regions inthe’Oncor’ [Gaithersburg, Maryland, USA] non-isotopic system).All amplifications were successful, demonstrated by clear bands anddots yielded by infected lymphocytes. All kidney samples, however,were negative in gel analysis and only 1 produced a faint positive dotwith the specific probe. These data accord with reports ruling outCMV in the pathogenesis of IgA nephropathy, and match theobservation of 1 in 14 positive on immunofluorescence stainingreported by Waldo et al.3

Immunology Laboratory,Faculty of Medicine,54500 Vandoeuvre les Nancy, France

MARIE C. BÉNÉ

JIANQING TANGGILBERT C. FAURE

1. Gregory MC, Hammond ME, Brewer ED. Renal deposition of cytomegalovirusantigen in immunoglobulin-A nephropathy. Lancet 1988; i: 11-14.

2. Dueymes M, Mignon-Conté M, Dueymes JM, Vernier I, Conte JJ. Mesangialstaining with cytomegalovirus antibodies in IgA nephropathy. Lancet 1988; i: 619.

3. Waldo FB, Britt WJ, Tomana M, Julian BA, Mestecky J. Non-specific mesangialstaining with antibodies against cytomegalovirus in immunoglobulin-Anephropathy. Lancet 1988; i: 129-31.

4. Sato M, Kojima H, Shinkai Y, Koshikawa S. Cytomegalovirus and IgA nephropathy.Lancet 1988; ii: 1251.

5. Okamura M, Kanayama Y, Negoro N, Takeda T, Inoue T. Failure to detectcytomegalovirus-DNA in IgA nephropathy by in-situ hybridisation. Lancet 1989;i: 1265.

6. Heieren M, van der Woude FJ, Balfour HH. Cytomegalovirus replicates efficiently inhuman kidney mesangial cells. Proc Natl Acad Sci USA 1988; 85: 1642-46.

CORRECTIONS

Effect of heparin, aspirin, or alteplase in reduction ofmyocardialischaemiain refractory unstable angina.-In this article by Prof G. G. Neri Semeriandothers (March 17, p 615), the first sentence in the section "Other events"should have ended: "... and 1 non-Q wave myocardial infarction in thealteplase group".

D-aminoacids and microwaves. The last paragraph of this letter

by Prof G. Lubec (March 31, p 792) should have read "milk formulae wereused ... because they provide a well-characterised food model and notto demonstrate the toxicity of microwave treated milk. Data from meatwould have changed the calculations in terms of cis-amionacid isomerssignificantly...".