Temporal doppler-flow studies for suspected giant-cell arteritis

antibiotics should be continued in the long term, until achieve cure or delay the progression of the disease.

we

*Josep Ferris i Tortajada, Juan A López Andreu, José Salcede Vivó, Jesús V Sala Lizarraga Departments of

*Paediatrics and Clinical Biopathology, Hospital Infantil "La Fe". Valencia 46009, Spain; and Rehabilitation Service, Hospital General Universitario, Val

1 López-Andreu JA, Ferns J, Canosa CA, Sala-Lizarraga JA. Treatment of late Lyme disease: a challenge to accept. J Clin Microbiol 1994; 32: 1415-16. 2 Burrascano J Jr.

Managing Lyme disease: late-stage Lyme disease: options and guidelines. Int Med Spec 1989; 10: 102-07. Pachner AR, Delaney E. The polymerase chain reaction in the diagnosis of Lyme neuroborreliosis. Ann Neurol 1993; 34: 544-49. Liegner KB. Lyme disease: the sensible pursuit of answers. J Clin Microbiol 1993; 31: 1961-63. treatment

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SIR-I share Vartiovaara’s concern about the diagnosis of Lyme borreliosis, but the patient and his physician often confront the difficulties together. Antibody tests sometimes remain negative even in patients with persistent cultureproven infection with B burgdorferi. However, problems are usually not far away even if the antibody test is positive. It is the doctor’s responsibility to decide whether the symptoms and antibody positivity are related. Antibodies against B burgdorferi can be positive for years in a symptom-free patient without any evidence of living spirochaetes. Clinically, it is therefore useful to gather additional information before making the decision to treat with antibiotics or merely follow the patient. If DNA of the spirochaete is found in the patient, the doctor will know that he is not dealing with a patient with "post-Lyme syndrome" old "serological scars" years after infection. or with Theoretically, patients with positive PCR results are those who most probably will benefit from treatment or retreatment. Without doubt, PCR has opened a new era in infectious disease. Vartiovaara states that it is too expensive for routine use. It is noteworthy that in our laboratory, PCR for B burgdorferi is not expensive-it costs £30. laboratories in many other countries are restricted laws concerning PCR and its use.

However,

by patent

Jarmo Oksi Department of Medical Microbiology, Turku University, FIN-20520 Turku, Finland; and Department of Medicine, Turku University Central Hospital

Thromboembolism and the combined oral

contraceptive pill SIR—There has long been concern about the potential thrombotic risks associated with the use of the combined oral contraceptive pill, which has again been focused upon in recent UK press reports (Sunday Times, May 7, 1995). Indeed package inserts contain a warning of this risk. Although obesity, age, and smoking are well recognised risk factors these might not be the most important factors predisposing to thrombosis. The media reporting of this issue may be missing an important and fundamental pointnamely, the high prevalence of APC (activated protein C) resistance in the general population. APC resistance might underlie the thrombotic tendency seen in many women. APC resistance (factor V Leiden) is now recognised to be the single commonest inherited prothrombotic disorder and can be present in up to 7% of a caucasian population.’ In the heterozygous form the risk of thrombosis is estimated to be increased eight-fold above that of a comparable control population, whereas in heterozygous women using the combined oral contraceptive pill it is raised more than 30fold. More strikingly, in the homozygous form the risk rises

least 50-fold and more than 100-fold in homozygous using the combined oral contraceptive pill.2 Although this argument is equally applicable to other prothrombotic states such as antithrombin, protein C, and protein S deficiency, these disorders are rare in the general population. By contrast, the high background prevalence of APC resistance substantially increases the number of women potentially placed at increased risk by use of the oral contraceptive pill. With the present level of concern this factor alone could merit screening for such a defect before use of the combined oral contraceptive pill. Such screening would be a major undertaking with important cost implications. However, it has the potential to reduce morbidity from thromboembolism seen in association with use of the combined oral contraceptive pill and to provide a degree of reassurance to the women concerned. In addition, knowledge of APC resistance status would enable appropriate counselling of the women identified to be at increased risk with respect to the relative benefits and risks of the combined oral contraceptive pill.

to at

women

*K J Pasi, D J Perry, C A Lee Haemophilia Centre and Haemostasis Unit, Department of Haematology, Royal Free Hospital and School of Medicine, London SW3 2QG, UK Svensson PJ, Dahlback B. Resistance to activated protein C as a basis for venous thrombosis. New Engl J Med 1994; 330: 517-22. Vanderbroucke JP, Koster T, Briet E, Reitsma P, Bertine R, Rosendaal F. Increased risk of venous thrombosis in oral contraceptive users who are carriers of factor V Leiden mutation. Lancet 1994; 344: 1453-57.

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Temporal doppler-flow studies for suspected giant-cell arteritis SIR—Schmidt and colleagues (April 1, p 866) report the value of colour doppler sonography as a so-called new method for the diagnosis of temporal arteritis. They suggest that further studies are necessary to estimate the sensitivity and specificity of the method and whether it is suitable for replacing temporal artery biopsy. We describe our experience of more than ten years of superficial temporal doppler-flow studies (DFS) in suspected giant-cell arteritis. Giant-cell arteritis is characterised by a predisposition for the cranial arteries. The assumption that these arteries are not affected by atheromatous disease and that therefore flow abnormalities could indicate giant-cell arteritis led in 1981 to the first use of temporal blood-flow study by continuouswave doppler in diagnosis of this condition.’ Nevertheless, when restricted to the temporal arteries, the results of DFS were unremarkable in a high proportion of patients with histologically proven giant-cell arteritis. To improve the diagnostic value of DFS, we also examined with ultrasonography ophthalmic and facial arteries. We developed a diagnostic score from 0 to 10, which was the sum of the various isolated findings as follows: Score

Arteries/finding Temporal arteries (maximum 4) Stenosis or no putse Irregularity or decreased flow Ophthalmic arteries (maximum 4) No pulse or asymmetry >50% Moderate decreased flow Facial arteries (maximum No pulse

DFS

2 1 1 1

2) 1

was regarded as positive when the score was 2 or greater. A prospective study was then undertaken to validate this diagnostic score in 80 patients with clinically suspected giant-cell arteritis.2 The patients underwent temporal, ophthalmic, and facial DFS and then temporal artery biopsy.

Giant-cell arteritis was confirmed in 30 patients: 28 (93%) met at least three of the American College of Rheumatology classification criteria for giant-cell arteritis. Diagnosis of polymyalgia rheumatica, without temporal arteritis, was accepted in 44 patients, none of whom fulfilled the American College of Rheumatology classification criteria for giant-cell arteritis, and 70% of whom had had at least one negative temporal artery biopsy. In 6 patients, DFS was not followed by temporal artery biopsy because a different diagnosis had been confirmed in the meantime. The overall results of DFS in the patients with or without giant-cell arteritis were: Positive DFS

Giant-cell arteritis

No

23

10

giant-cell arteritis

Negative DFS 7 40 The sensitivity of DFS was thus 77%, the specificity 80%, and the positive and negative predictive values 70% and 85%, respectively. We conclude that the DFS score in giant-cell arteritis has a higher sensitivity and specificity than the commonly used clinical or biological diagnostic criteria in this disease. It is particularly useful because of its high negative predictive value, but for diagnosis cannot replace temporal artery biopsy which has a better specificity. Whether the morphological abnormalities shown by colour doppler improve the diagnostic accuracy when compared with continuous-wave doppler examination, which is less time consuming, remains to be established.

frequently identified in many white populations’ of the USA, the UK, Denmark, South Africa, Austria, Australia, the Netherlands, Canada, France, Italy, Switzerland, Belgium, and Germany. Yet FDB is rarely reported in other populations, and never found in Finland, the former Soviet Union, and Israel. According to haplotype analysis of the apoB gene, ethnic diversity of FDB frequency suggests that most apoB 3500 mutations are derived from a single common ancestral mutation that occurred at least 10 000 years ago,’ probably in a Caucasian. Our results suggest that the apoB 3500 mutation is a rare cause of genetic hypercholesterolaemia in Japan and are consistent with this explanation. The

apoB

3500 mutation has been

*Atsushi Nohara, Kunimasa Yagi, Akihiro Inazu, Kouji Kajinami, Junji Koizumi, Hiroshi Mabuchi Second Department of Internal Medicine, School of Medicine, Kanazawa Kanazawa 920, Japan

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2

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University,

Myant NB. Familial defective apolipoprotein B-100: a review, including some comparisons with familial hypercholesterolemia. Atherosclerosis 1993; 104: 1-18. Defesche JC, Pricker KL, Hayden MR, van der Ende BE, Kastelein JP. Familial defective apolipoprotem B-100 is clinically indistinguishable from familial hypercholesterolemia. Arch Intern Med 1993; 153: 2349-56. Hansen PS, Rudiger N, Tybjaerg-Hansen A, et al. Detection of the apo-B-3500 mutation (glutamine for arginine) by gene amplification and cleavage with MspI. J Lipid Res 1991; 32: 1229-33. Miserez AR, Laager R, Chiodetti N, et al. High prevalence of familial defective apolipoprotein B-100 in Switzerland. J Lipid Res 1994; 35: 574-83.

*Xavier Puéchal, Michel Chauveau, Charles J Menkès Rhumatologie A, and Service d’Exploration Fonctionnelle Vasculaire, Hôpital Cochin, Université René Descartes, Paris 75674, France *Service de

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Menkès CJ, Branche I, Feldmann JL, Chauveau M, Delbarre F. Application de l’effet Doppler au dépistage de l’artérite de Horton. Nouv Presse Med 1981; 10: 2371. Puéchal X, Chauveau M, Hilliquin P, Perrot S, Job-Deslandre C, Menkès CJ. Superficial temporal Doppler flow studies in suspected giant cell arteritis: validation of a diagnostic score. Arthritis Rheum 1994; 37 (suppl 9): S409 (abstr).

Absence of familial defective apolipoprotein B-100 in Japanese patients with familial hypercholesterolaemia SiR-Familial defective apolipoproteinB-100 (FDB) is a form of genetic hypercholesterolaemia. A single-base substitution (G to A) at nucleotide 10 708 in exon 26 of the apoB-100 gene creates a glutamine for arginine substitution in position 3500 aminoacid, resulting in reduced affinity of low-density lipoproteins (LDL) to the LDL receptor.’ FDB has been shown to be clinically indistinguishable from familial hypercholesterolaemia.2 To estimate the frequency of FDB in the Japanese population, we searched for this apoB mutation among clinically diagnosed 385 heterozygous familial hypercholesterolaemia patients from 350 unrelated families (197 men and 188 women, mean age 45 years). The mean (SD) concentrations of total cholesterol, triglyceride, and high-density lipoprotein cholesterol were 7-73 (2-15), 1-78 (1-11), and 1-27 (0-75) mmol/L, respectively. 85% of the subjects had Achilles tendon xanthoma, and 18% had coronary heart disease. We used PCR followed by cleavage with Mspl to detect the apoB 3500 mutation as described by Hansen et al.3 DNA samples from patients already diagnosed as FDB (provided by N B Myant, Hammersmith Hospital, UK and D R Illingworth, Oregon Health Sciences University, USA) were included in each PCR assay. No individuals with apoB 3500 mutation were detected. 1438

Reversible diabetes in patient with AIDSrelated Kaposi’s sarcoma treated with interferon &agr;-2a SiR-The development of type 1 diabetes in a patient treated with recombinant interferon a-2b for chronic type C hepatitis has been described, but its pathogenesis remains unclear.’1 We describe a reversible insulin-dependent diabetes occurring in an HIV-positive man 2 weeks after recombinant interferon (IFN) a-2a treatment was started for cutaneous

Kaposi’s

sarcoma.

A 54-year-old homosexual man had been positive for HIV-1 antibodies since 1990 without any notable disease in his previous medical history and no familial evidence of diabetes. Cutaneous Kaposi’s sarcoma localised to the fingers and the soles of the feet was diagnosesd in June, 1993. The CD4 cell count was 384/jjbL. In July, 1993, the patient began local radiotherapy and at the same time was started on 500 mg daily zidovudine because of a decline in his CD4 cell count (337/µL). From December, 1993, he was prescribed 10 million units of subcutaneous IFN three times weekly plus 5 million units injected intralesionally twice weekly because of Kaposi’s sarcoma relapse that had occurred 5 months after the end of radiotherapy. At baseline, biochemical analysis was normal and organ and non-organ specific autoantibodies were negative. None of the commonly observed transient side-effects caused by IFN were observed. After 10 days, he had sudden onset of polyuria, polydipsia, and fatigue. Fasting blood glucose was 45 mmol/L and glycosuria was 17-2 mmol/L. IFN a-2a and zidovudine were stopped and a hypoglycaemic diet was introduced without improvement of glycaemia. The patient was admitted to hospital and given regular insulin 30 U plus Lente insulin 15 U per day. At this time, thyroid microsomal, thyroglobulin, and islet-cell autoantibodies were negative. Insulin autoantibodies were just above normal (10-52% compared with normal value of radiobinding assay method <10%) and the C-peptide value was