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linked immunoassay (EIA, DAKO, UK). This was divided, after collection, into two aliquots. The first was taken to the laboratory where a 2 mL aliquot was frozen for the LCR test and a 15 mL aliquot was immediately used for amplified EIA. The second aliquot was held at room temperature for 24 h in the clinic before being taken to the laboratory. This sample was frozen at ⫺20⬚C before being tested by LCR. A spun deposit for direct fluorescent antibody (DFA) was prepared from each aliquot. DFA in our hands is more sensitive than culture (unpublished data). All samples were examined blinded. The results are shown below: Method

DFA positive DFA negative

FVU 1 (frozen within 4 h)

FVU 2 (frozen after 24 h)

LCR positive

LCR negative

LCR positive

LCR negative

37 4

0 82

32 2

5* 84†

*initially DFA positive, LCR positive. †2 initially DFA negative, LCR positive.

LCR identified four additional positives which we were unable to confirm. However when the urine sample was left for 24 h at room temperature, seven LCR positive samples became non-reactive. No sample which was negative on freshly frozen samples became LCR positive when left for 24 h before being frozen. 35 men were chlamydia-positive by EIA at presentation (data not shown) and all were confirmed by DFA testing. The identification of additional positives by LCR is well recognised and these are assumed to be true positives, although this is contentious.4 The improved sensitivity using LCR is one of the principal arguments for the use of this test in screening programmes. The results of our study, which was carried out between June and August, suggest that the sensitivity of the LCR in urine of 93·8% demonstrated by Lee et al2 would not be achievable in a community setting without meticulous adherence to a “cold chain” for sample processing. In this respect our findings are in agreement to those of Ostergaard et al5 who found a FVU sensitivity of 78% in women who returned their specimen by post. The LCR on urine is not the perfect test and in the community would probably be even less so. Whether the sensitivity of the LCR on specimens from other sites would be affected in a similar fashion is unknown. A fall in prevalence of chlamydia in Sweden was achieved by a programme of screening non-urine samples by nonmolecular techniques. Whilst the LCR on non-urine genital specimens is more sensitive than EIA or culture, the total cost of laboratory testing has not been analysed. Enzyme immunoassays vary significantly in both sensitivity and specificity and it is important to use assays with the best performance. The flexibility of the amplified EIA allows the testing of up to 300 samples per day with limited space and a single member of staff. It may be more cost effective to use a reliable and sensitive EIA with an adjusted cut-off negative grey zone (up to 50% of the cut off) to screen women and to confirm all presumptive positive samples by DFA. 1 2

3 4 5

Caul EO, Paul ID, Milne JD, Crowley T. Non-invasive sampling method for detecting Chlamydia trachomatis. Lancet 1989; ii: 1246–47. Lee HH, Chernesky MA, Schachter J, et al. Diagnosis of Chlamydia trachomatis genitourinary infection in women by ligase chain reaction assay of urine. Lancet 1995; 345: 213–16. Johnson AM, Grun L, Haines A. Controlling genital chlamydial infection. BMJ 1996; 313: 1160. Hadgu A. The discrepancy in discrepant analysis. Lancet 1996; 348: 592–93. Østergaard L, Møller JK, Andersen B, Olesen F. Diagnosis of urogenital Chlamydia trachomatis infection in women based on mailed samples obtained at home: multipractice comparative study. BMJ 1996; 313: 1186–89.

Public Health Laboratory, Myrtle Road, Bristol BS2 8EL, UK (E O Caul); The Milne Centre, Bristol Royal Infirmary, Bristol; and Department of Social Medicine, Canynge Hall, Bristol

Vol 349 • April 12, 1997

Henoch-Schönlein syndrome induced by carbidopa/levodopa Gregor Niedermaier, Verena Briner

Data from hospital monitoring systems suggest that druginduced side-effects occur in up to 20% of patients receiving drugs.1 Between 10 and 25% are cutaneous reactions such as maculopapular rashes (70%) and urticaria (30%). Druginduced vasculitis, with or without involvement at other sites, is rare. We report Sinemet (carbidopa 25 mg/levodopa 250 mg, Merck, Sharpe & Dohme Chibret AG) induced HenochSchönlein syndrome in a 68-year-old man with Parkinson’s disease. He presented in 1974 and treatment was initiated with levodopa later combined with bromocriptine. His medication was changed in 1996 because of clinical deterioration. The clinical improvement did not satisfy the patient’s expectations and he devised his own treatment strategy consisting of Sinemet 250/25 mg six times daily, amantadine 100 mg daily, and selegiline 5–7·5 mg daily. He also took hydrochlorothiazide 50 mg/amiloride 5 mg (Moduretic) once daily for ankle oedema and aspirin 100 mg daily. In May 1996, he was admitted (figure) with palpable purpura of the limbs, ankle oedema, arthralgia of one wrist and both knees, and abnormal cramp. A skin specimen showed leucocytoclastic vasculitis. He had microhaematuria, red cell casts, and proteinuria (1·5 g/24 h) with normal renal function. Tests for anti-nuclear antibodies and rheumatoid factors were negative. IgG was 16 g/L (normal 6·9–14 g/L), IgA 4·9 (normal 0·9–4·1 g/L), IgM normal, and immune complex IgG 12 mg/L (normal 1–10 mg/L). Screening for antibodies to viruses, syphilis, mycoplasma, and Lyme disease were negative. All drugs were withdrawn and the skin lesions faded quickly. 2 days later, aspirin, Moduretic, amantadine, and selegiline were restarted. 1 day afterwards Sinemet was added. New skin lesions appeared, especially on the legs, within less than 24 hours and urinary findings suggestive of glomerulonephritis increased. Cessation of Sinemet resulted in rapid fading of the purpura. Sinemet was replaced by Madopar (levodopa 100 mg/benserazide 25 mg) four times daily and the side-effects have not recurred. Sinemetinduced maculopapular rash without vasculitis has been reported.2 Animal studies suggest that antiparkinsonian drugs may modulate the immune response3 although the clinical significance seems slight.4 Drug-induced vasculitis and glomerulonephritis are most

Aspirin

Aspirin

Moduretic

Moduretic

Sinemet

Sinemet

Amantadine

Amantadine

Selegiline

Selegiline

0

1

2

Madopar

3 4 5 6 15 16 17 18 19 20 Hospital admission (days)

Henoch-Schönlein syndrome

Timescale of drug administration in 68-year-old man with Parkinson’s syndrome Sinemet=levodopa 250 mg/carbidopa 25 mg.

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frequently type III hypersensitivity reactions mediated by the deposition of immune complexes in small vessel walls and the glomerulus. Endothelial cells may be targets of immunemediated effects, and also of direct cytotoxicity.5 Drugs associated with leucocytoclastic vasculitis are allopurinol, penicillin, sulphonamides, thiazide diuretics, and quinolones. Henoch-Schönlein purpura may be triggered by aspirin, penicillin, sulphonamides, erythromycin, thiazide diuretics, phenacetin, and paracetamol. Induction of both kinds of side-effects by some drugs raises the question whether a mild allergic response causes skin lesions without clinical evidence of systemic disease and more severe reactions cause clinically overt systemic disease. The present report strongly suggests that carbidopa (or possibly a drug additive) may induce palpable purpura, glomerulonephritis, oedema, arthralgia, and possibly abdominal pain. Therefore, Sinemet should be added to the list of causes of HenochSchönlein syndrome. 1

2 3

4 5

Leape LL, Brennan TA, Laird N. The nature of adverse events in hospitalized patients: results of the Harvard Medical Practice Study II. N Engl J Med 1991; 324: 377–84. Goetz CG. Sinemet skin rash. Clin Neuropharmacol 1984; 7: 107–08. Horvat J, Stojic Z, Jankovic BD. Effect of dopamine, L-dopa, carbidopa and L-dopa/carbidopa on arthus and delayed hypersensitivity skin reactions in the rat. Int J Neurosci 1991; 59: 199–203. Massarotti G, Cassi E. Lupus-like autoimmune syndrome after levodopa and benserazide. BMJ 1979; ii: 552–53. Roujeau JC, Stern RS. Severe adverse cutaneous reactions in drugs. N Engl J Med 1994; 331: 1272–85.

Department of Medicine, Kantonsspital, CH-6000 Lucerne 16, Switzerland (G Niedermaier)

Endoscopic and histological views Top: polypoid lesion with typical appearances of carcinoma of the oesophagus. Bottom: non-caseating, epithelioid granuloma.

Primary tuberculosis of the oesophagus S J Wor t, J M Puleston, P D Hill, G E Holdstock

There are only a few cases of primary tuberculosis of the oesophagus described in the literature.1 We report a 55-yearold Asian man who presented with dysphagia and at endoscopy appeared to have a carcinoma of the oesophagus. The patient reported an 8-month history of weight loss and dysphagia. Endoscopy showed a large, ulcerating, polypoid lesion, 25 cm from his incisors, with appearances typical of a carcinoma (figure, top). Histology of the lesion showed inflammatory exudate in the sub-mucosa with discrete epithelioid granulomas (figure, bottom). No acidfast bacilli were seen. Further questioning revealed a history of fever and night sweats but no known contact with tuberculosis. He had lived in the UK for the past 8 years. Examination was unremarkable and his chest radiograph was normal. A barium swallow confirmed mucosal irregularity, but showed no other abnormality. He had a mild normocytic anaemia with a raised erythrocyte sedimentation rate (30 mm/h). He was also noted to be hyponatraemic (120 mmol/L) and hypoalbuminaemic (30 g/dL). The next day he had a high fever and became drowsy. He was noted to have a transient, partial, left third-nerve palsy. Computed tomograph of his brain showed an area of contrast enhancement around the right sylvian fissure but no other abnormality. There was raised protein (2·44 g/dL) in cerebrospinal fluid and a lymphocytosis (120 cells⫻106/L). A diagnosis of tuberculous meningitis was suspected and antituberculosis treatment was started. Subsequently, gastric washings were found to contain acid-fast bacilli. Mantoux

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test and cultures were negative. He made an uneventful recovery. Most oesophageal tuberculosis appears to be secondary to spread from surrounding structures.2 This patient had a normal chest radiograph and barium swallow showed no evidence of extrinsic involvement. The development of tuberculous meningitis was considered a secondary phenomenon, perhaps related to the biopsy, 10 days earlier. When primary tuberculous oesophagitis does occur it may affect a previously abnormal mucosa.2,3 There was no suggestion of this in our case. The rarity of primary tuberculous oesophagus may be related to oesophageal protective mechanisms such as rapid transit and peristalsis as well as the natural defence of smooth squamous epithelium and swallowed saliva.4 Dysphagia is the most common presenting symptom and the endoscopic appearance often mimics carcinoma.5 This case underlines the important message that tuberculosis should always be considered when cancer is suspected, especially in at-risk populations.These include not only people migrating from endemic areas but also the increasing number of individuals infected with HIV. 1

Mokoena T, Shama DM, Ngakane H, Bryer JV. Oesophageal tuberculosis: a review of eleven cases. Postgrad Med J 1992; 68: 110–15. 2 Sinha SN, Tesar P, Seta W, Sengupta SK. Primary oesophageal tuberculosis. Br J Clin Pract 1988; 42: 391–94. 3 Leotta SMG, Elsborg L. Localised tuberculosis of the oesophagus: a rare condition. J Intern Med 1995; 238: 77–79. 4 Qureshi H, Ahmad W, Zuberi S, Aziz S, Jamal Q. Tuberculosis of the oesophagus. J Pak Med Assoc 1992; 42: 278–79. 5 Damtew B, Frengley D, Wolinsky E, Spagnuolo PJ. Oesophageal tuberculosis: mimicry of gastrointestinal malignancy. Rev Infect Dis 1987; 9: 140–46. Department of Gastroenterology, Hillingdon Hospital, Uxbridge UB8 3NN, UK (S J Wor t)

Vol 349 • April 12, 1997