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RETROPERITONEAL FIBROSIS AND BROMOCRIPTINE
466
Legionella antibody titres by IF
AT and LA.
serologically documented legionnaires’ disease, 6 acute sera with IFAT < 16 were LA negative and 26 sera with IFAT 16 were LA positive. LA titres were generally proportional to IFAT titres (see figure) although the range was narrower (neat to 32). Seven pooled, high titre (CFT 256) viral sera (influenza A, influenza B, Mycoplasma pmumania, Q fever, mumps, psittacosis, and RSV) and 32 control sera from patients judged on clinical, epidemiological, and serological grounds not to have had legionnaires’ disease (all with IFAT < 16) were all totally negative or showed only trace reaction by LA. It has been suggested that many patients with legionnaires’ disease have circulating antibodies on admission to hospital.3 LA for Legionella antibody may thus be a useful screening test for presumptive cases of legionellosis. Positive sera can be referred quickly to reference laboratories for confirmation by better evaluated tests such as IFAT. The latex reagent is apparently stable for at least 6 months at 4°C, test results are easily read, and sample group equivocal findings may be rapidly repeated. IFAT testing was done by Preston Public Health Laboratories and the pooled viral sera were a gin from the Regional Virus Laboratory, East Birmingham Hospital.
Microbiology Department, St George’s Hospital, Stafford ST16 3AG
MALCOLM G. HOLLIDAY
1.Harrison TG, Taylor AG. Diagnosis of Legionella pneumophila infections by means of formolised yolk sac antigens. J Clin Pathol 1982; 35: 211-14. 2. Harrison TG. Taylor AG. A rapid microagglutination test for the diagnosis of Legionella pneumophila (serogroup 1) infection. J Clin Pathol 1982, 35: 1028-31. 3. Harrison TG. A nasty family from Philadelphia. Med Lab World, September, 1985: 19-23. 4. Holliday MG. Counterimmunoelectrophoresis in the serodiagnosis of Legionnaires’ disease. J Clin Pathol 1983; 36: 446-70. 5. Winn WC. Legionella and legionnaires’ disease: A review. CRC Crit Rev Clin Lab Sci. 6.
1985; 21: 323-81. Sathapatayavongs B, Bohler RB, Wheat LJ, White A, Winn WC, Jr. Rapid diagnosis of legionnaires’ disease by latex agglutination. Am Rev Respir Dis 1983; 127: 559.
7.
Severin WPJ. Latex agglutination in the diagnosis of meningococcal meningitis. J Clin Pathol 1972; 25: 1079-82.
RETROPERITONEAL FIBROSIS AND BROMOCRIPTINE
SIR,—Following the description in 1966 by Graham et all of retroperitoneal fibrosis (RPF) associated with methysergide, two further ergot derivatives, lysergic acid diethylamide (LSD)2,3 and ergotamine,l,3 have also been implicated. RPF due to methyldopa,4 distalgesic,5 phenacetin,6,7 and codeine4 is much less well documented. We describe a case of RPF associated with a fourth ergot derivative, bromocriptine, which has structural similarities with methysergide, LSD, and ergotamine. A 58-year-old man had been treated for Parkinson’s disease with bromocriptine 30 -40 mg daily for 10 years with one short break in 1984 for a trial of levodopa plus carbidopa that was stopped because of a rash.
He presented in January, 1986, with a 4-week history of malaise, loss of appetite, weight loss, back pain, polyuria, polydipsia, and swollen ankles. His jugular venous pressure was raised to 5 cm above the sternal angle. Worsening of his symptoms precipitated hospital admission in March. His oedema had increased and his blood pressure was 180/105 mm Hg. He had a punctate erythematous rash over the ankles. Laboratory findings included haemoglobin 87 g/dl, plateletes 310 x 109fl, erythrocyte mm in the first hour, C-reactive sedimentation rate (ESR>160 protein 67 mg/1, urea 20 mmol/1, creatinine 575 lunol/1 serum immunoglobulins normal, circulating immune complexes not detected, electrophoretic strip slight increase in ot,, el2’ and y, complement C4 45% (normal range 50—120%), C3 93% (60-135%), CH,, 66% (50-125%). A direct Coombs test, autoantibody screen, and rheumatoid factor were normal. Ultrasonography revealed bilateral hydronephrosis with a normal lower urinary tract and prostate. Abdominal computerised tomographic scan and bilateral antegrade ureterograms were consistent with RPF. Bilateral ureterostomy was followed by rapid recovery of renal function and normal blood pressure. At laparotomy typical RPF was found. The postoperative course was complicated by an ischaemic right ureter. He was treated with prednisolone 30 mg daily decreasing to 10 mg by 2 months postoperatively when his ESR was 50 mm, C-reactive protein 16 mg/1, haemoglobin 10.8 g/dl, C3 116%, C4 76%, and CH 79%. Biopsy of the fibrotic tissue revealed dense fibrosis with perivascular inflammatory cells, mainly lymphocytes and plasma cells with some evidence of panniculitis. There was one focus of foreign-body-type giant cells associated with macrophages and fibrous exudate. There were no significant local deposits of immunoglobulins and complement and no evidence of a vasculitis. One theory about the pathogenesis of drug-induced RPF is that serotonin antagonism plays a part,8,9 but bromocriptine is not a serotonin antagonist. The other is that RPF is an idiosyncratic immune response, with ergot alkaloids possibly acting as a hapten.10,11 Only one of the patients reported has shown evidence of systemic immunological abnormality, in the form of a positive direct Coombs test; this patient had been treated with metbyldopa,4 a drug known to induce a positive direct Coombs. Around the area of fibrosis there is often a mononuclear cell infiltrate, occasionally with eosinophilia and vasculitis. The vasculitic changes are however, more often found elsewhere in the body than at the site of RPF,10,12 and without complement or immune complex deposition in the one case in which these were looked for.4 The only drug that our patient was taking was bromocriptine. His clinical features, the absence of systemic immunological abnormality, and the response to steroids are in keeping with previous reports of drug-induced RPF. Department of Neurology, Department of Medicine, Royal Postgraduate Medical School, Hammersmith Hospital, London 12 0HS
JOHN V. BOWLER IAN E. ORMEROD NIGEL J. LEGG
JR, Suby JI, Le Compte PR, Sandowsky NL. Fibrotic disorders associated methysergide therapy for headache. N Engl J Med 1966; 274: 359-68. 2. Aptekar ARG. Possible effects of LSD. N Engl J Med 1970; 283: 765 3. Stecker JF, Rawls HP, Devine CJ, Devine PC. Retroperitoneal fibrosis and ergot derivatives. J Urol 1974; 112: 30-32. 4. Iversen BM, Nordahl E, Thunold S, Johannesen JW, Ofstad J, Willassen T Retroperitoneal fibrosis during treatment with methyldopa. Lancet 1975; ii: 1. Graham
with
303-04.
Critchley JA, Smith MF, Prescott LF. Distalgesic abuse and retroperitoneal fibrosis. Br J Urol 1985; 57: 486-87. 6. MacGregor GA, Jones NF, Barraclough MA, Wing AJ, Cranston WI. Ureteric stricture with analgesic enphropathy. Br Med J 1973; ii: 271-72 7. Lewis CT, Molland EA, Marshall VR, Tressider GC, Blandy JP. Analgesic abuse, ureteric obstruction and retroperitoneal fibrosis. Br Med J 1975; ii: 76-78. 8. Bianchine JR, Macaraeg PVJ, Brandes O. Serotonin and fibrosis. Arch Intern Med 5.
1968; 122: 167-70 9. Persky L, Kursh ED, Feldman S, Resnick MI. Chap 9 in: Walsch PC, Gatten RF, Perlmutter AD, eds. Campbell’s urology, vol 1, 5th ed. Eastbourne. Saunders, 1986: 595-613. 10. Hoffmann WW, Trippel OH. Retroperitoneal fibrosis; aetiological considerations J Urol 1961; 86: 222-32. 11. Weiss JM, Hinman F. Reversible retropentoneal fibrosis with ureteral obstruction associated with the ingestion of Sansert. J Urol 1966; 95: 771-76 12. Jones EA, Alexander MK. Idiopathic retroperitoneal fibrosis associated with arteritis Ann Rheum Dis 1966; 25: 356-60
Legionella antibody titres by IF
AT and LA.
serologically documented legionnaires’ disease, 6 acute sera with IFAT < 16 were LA negative and 26 sera with IFAT 16 were LA positive. LA titres were generally proportional to IFAT titres (see figure) although the range was narrower (neat to 32). Seven pooled, high titre (CFT 256) viral sera (influenza A, influenza B, Mycoplasma pmumania, Q fever, mumps, psittacosis, and RSV) and 32 control sera from patients judged on clinical, epidemiological, and serological grounds not to have had legionnaires’ disease (all with IFAT < 16) were all totally negative or showed only trace reaction by LA. It has been suggested that many patients with legionnaires’ disease have circulating antibodies on admission to hospital.3 LA for Legionella antibody may thus be a useful screening test for presumptive cases of legionellosis. Positive sera can be referred quickly to reference laboratories for confirmation by better evaluated tests such as IFAT. The latex reagent is apparently stable for at least 6 months at 4°C, test results are easily read, and sample group equivocal findings may be rapidly repeated. IFAT testing was done by Preston Public Health Laboratories and the pooled viral sera were a gin from the Regional Virus Laboratory, East Birmingham Hospital.
Microbiology Department, St George’s Hospital, Stafford ST16 3AG
MALCOLM G. HOLLIDAY
1.Harrison TG, Taylor AG. Diagnosis of Legionella pneumophila infections by means of formolised yolk sac antigens. J Clin Pathol 1982; 35: 211-14. 2. Harrison TG. Taylor AG. A rapid microagglutination test for the diagnosis of Legionella pneumophila (serogroup 1) infection. J Clin Pathol 1982, 35: 1028-31. 3. Harrison TG. A nasty family from Philadelphia. Med Lab World, September, 1985: 19-23. 4. Holliday MG. Counterimmunoelectrophoresis in the serodiagnosis of Legionnaires’ disease. J Clin Pathol 1983; 36: 446-70. 5. Winn WC. Legionella and legionnaires’ disease: A review. CRC Crit Rev Clin Lab Sci. 6.
1985; 21: 323-81. Sathapatayavongs B, Bohler RB, Wheat LJ, White A, Winn WC, Jr. Rapid diagnosis of legionnaires’ disease by latex agglutination. Am Rev Respir Dis 1983; 127: 559.
7.
Severin WPJ. Latex agglutination in the diagnosis of meningococcal meningitis. J Clin Pathol 1972; 25: 1079-82.
RETROPERITONEAL FIBROSIS AND BROMOCRIPTINE
SIR,—Following the description in 1966 by Graham et all of retroperitoneal fibrosis (RPF) associated with methysergide, two further ergot derivatives, lysergic acid diethylamide (LSD)2,3 and ergotamine,l,3 have also been implicated. RPF due to methyldopa,4 distalgesic,5 phenacetin,6,7 and codeine4 is much less well documented. We describe a case of RPF associated with a fourth ergot derivative, bromocriptine, which has structural similarities with methysergide, LSD, and ergotamine. A 58-year-old man had been treated for Parkinson’s disease with bromocriptine 30 -40 mg daily for 10 years with one short break in 1984 for a trial of levodopa plus carbidopa that was stopped because of a rash.
He presented in January, 1986, with a 4-week history of malaise, loss of appetite, weight loss, back pain, polyuria, polydipsia, and swollen ankles. His jugular venous pressure was raised to 5 cm above the sternal angle. Worsening of his symptoms precipitated hospital admission in March. His oedema had increased and his blood pressure was 180/105 mm Hg. He had a punctate erythematous rash over the ankles. Laboratory findings included haemoglobin 87 g/dl, plateletes 310 x 109fl, erythrocyte mm in the first hour, C-reactive sedimentation rate (ESR>160 protein 67 mg/1, urea 20 mmol/1, creatinine 575 lunol/1 serum immunoglobulins normal, circulating immune complexes not detected, electrophoretic strip slight increase in ot,, el2’ and y, complement C4 45% (normal range 50—120%), C3 93% (60-135%), CH,, 66% (50-125%). A direct Coombs test, autoantibody screen, and rheumatoid factor were normal. Ultrasonography revealed bilateral hydronephrosis with a normal lower urinary tract and prostate. Abdominal computerised tomographic scan and bilateral antegrade ureterograms were consistent with RPF. Bilateral ureterostomy was followed by rapid recovery of renal function and normal blood pressure. At laparotomy typical RPF was found. The postoperative course was complicated by an ischaemic right ureter. He was treated with prednisolone 30 mg daily decreasing to 10 mg by 2 months postoperatively when his ESR was 50 mm, C-reactive protein 16 mg/1, haemoglobin 10.8 g/dl, C3 116%, C4 76%, and CH 79%. Biopsy of the fibrotic tissue revealed dense fibrosis with perivascular inflammatory cells, mainly lymphocytes and plasma cells with some evidence of panniculitis. There was one focus of foreign-body-type giant cells associated with macrophages and fibrous exudate. There were no significant local deposits of immunoglobulins and complement and no evidence of a vasculitis. One theory about the pathogenesis of drug-induced RPF is that serotonin antagonism plays a part,8,9 but bromocriptine is not a serotonin antagonist. The other is that RPF is an idiosyncratic immune response, with ergot alkaloids possibly acting as a hapten.10,11 Only one of the patients reported has shown evidence of systemic immunological abnormality, in the form of a positive direct Coombs test; this patient had been treated with metbyldopa,4 a drug known to induce a positive direct Coombs. Around the area of fibrosis there is often a mononuclear cell infiltrate, occasionally with eosinophilia and vasculitis. The vasculitic changes are however, more often found elsewhere in the body than at the site of RPF,10,12 and without complement or immune complex deposition in the one case in which these were looked for.4 The only drug that our patient was taking was bromocriptine. His clinical features, the absence of systemic immunological abnormality, and the response to steroids are in keeping with previous reports of drug-induced RPF. Department of Neurology, Department of Medicine, Royal Postgraduate Medical School, Hammersmith Hospital, London 12 0HS
JOHN V. BOWLER IAN E. ORMEROD NIGEL J. LEGG
JR, Suby JI, Le Compte PR, Sandowsky NL. Fibrotic disorders associated methysergide therapy for headache. N Engl J Med 1966; 274: 359-68. 2. Aptekar ARG. Possible effects of LSD. N Engl J Med 1970; 283: 765 3. Stecker JF, Rawls HP, Devine CJ, Devine PC. Retroperitoneal fibrosis and ergot derivatives. J Urol 1974; 112: 30-32. 4. Iversen BM, Nordahl E, Thunold S, Johannesen JW, Ofstad J, Willassen T Retroperitoneal fibrosis during treatment with methyldopa. Lancet 1975; ii: 1. Graham
with
303-04.
Critchley JA, Smith MF, Prescott LF. Distalgesic abuse and retroperitoneal fibrosis. Br J Urol 1985; 57: 486-87. 6. MacGregor GA, Jones NF, Barraclough MA, Wing AJ, Cranston WI. Ureteric stricture with analgesic enphropathy. Br Med J 1973; ii: 271-72 7. Lewis CT, Molland EA, Marshall VR, Tressider GC, Blandy JP. Analgesic abuse, ureteric obstruction and retroperitoneal fibrosis. Br Med J 1975; ii: 76-78. 8. Bianchine JR, Macaraeg PVJ, Brandes O. Serotonin and fibrosis. Arch Intern Med 5.
1968; 122: 167-70 9. Persky L, Kursh ED, Feldman S, Resnick MI. Chap 9 in: Walsch PC, Gatten RF, Perlmutter AD, eds. Campbell’s urology, vol 1, 5th ed. Eastbourne. Saunders, 1986: 595-613. 10. Hoffmann WW, Trippel OH. Retroperitoneal fibrosis; aetiological considerations J Urol 1961; 86: 222-32. 11. Weiss JM, Hinman F. Reversible retropentoneal fibrosis with ureteral obstruction associated with the ingestion of Sansert. J Urol 1966; 95: 771-76 12. Jones EA, Alexander MK. Idiopathic retroperitoneal fibrosis associated with arteritis Ann Rheum Dis 1966; 25: 356-60