False-positive Lyme disease serology in human granulocytic ehrlichiosis

False-positive Lyme disease serology in human granulocytic ehrlichiosis

Figure: Laboratory confirmed

cases

of rubella

reported

to

SCIEH 1983-96

size, the disproportionate increase in young adult males, and the rise in the number of cases in pregnant women, where ascertainment is likely to be good. Rubella infection, once a disease of childhood, has now become a disease of adult males aged 15-34 years who were not targeted by the schoolgirl rubella programme or the measles, mumps, and rubella (MMR) and MR campaigns. Ten to 15% of this cohort of approximately 750 000 are susceptible to rubella2 and infection in adulthood may result in a more severe illness than in childhood. An age shift in rubella incidence was also seen after the introduction of MMR in 1982 in Finland.3 We predict that as the cohort of susceptible males ages, periodic upsurges in rubella are likely to continue over the next decade at least, putting nonimmune pregnant women at risk. During the last UK resurgence of rubella in 1993 there were 25 reports in pregnant women,2 nine of whom were infected by fellow students or by another adult in the home, showing the importance of adult-to-adult transmission. The Chief Medical Officer of Scotland4 has reminded all general practitioners (GPs), medical directors of trusts, and occupational health physicians of the recommendations made in the "Green Book"5 and, in particular, that all health service staff, both men and women should be tested for rubella antibody and those who are seronegative be immunised. The relevance of this advice has been reinforced as three of the cases this year are in GPs. GPs are further asked to consider offering immunisation to the male partner of any nonimmune female patient who is planning a pregnancy or has just become pregnant to reduce further the risk to pregnant women. If the cohort of males currently aged 15-34 years old remains susceptible we predict periodic upsurges in rubella incidence, and a concomitant increase in the number of rubella infections in pregnant women in Scotland over the next few years. *Janet Stevenson, Sarah O’Brien, Peter Christie, John Cowden Scottish Centre for Infection and Environmental Health, Ruchill Hospital,

Glasgow G20 9NB, UK 1 2

3

4 5

Vaccine preventable diseases of childhood, England and Wales: laboratory reports, weeks 04-07/96. Com Dis Rep Wkly 1996; 6: 66-67. Miller E, Tookey P, Morgan-Capner P, et al. Rubella surveillance to June 1994: third joint report for the PHLS and the Congenital Rubella Surveillance Programme. Com Dis Rep Rev 1994; 4: R146-R152. Ukkonen P, Bonsdorff CHV. Rubella immunity and morbidity: effects of vaccination m Finland. Scand J Infect Dis 1988; 20: 255-59. Chief Medical Officer Letter. Rubella. SODH/CMO (96)3. The Scottish Office Department of Health, 1996. The Joint Committee on Vaccination and Immunisation. Immunisation against infectious disease. London: HM Stationery

Office, 1992.

SiR-Human granulocytic ehrlichiosis (HGE) has been identified in Westchester County, NY, USA.’Laboratory evidence of HGE for the first ten cases diagnosed by us in 1995 included Ehrlichia equi antibody seropositivity (100%) and positive PCR on whole blood (70%). None of the patients had clinical manifestations indicative of an alternative diagnosis, such as Lyme disease. Fever was present but not erythema migrans, cranial nerve palsy, or arthritis. It came as a surprise when serological reactivity for Lyme disease was observed by ELISA (Lyme Stat, Whittaker Bioproducts, Walkersville, MD) or immunoblot (Marblot, MarDX Diagnostics Inc, Carlsbad, CA) in all but one case. ELISA was positive or equivocal in six (86%) of the seven patients for whom this test was done (five with seroconversions). Of the eight who developed IgM bands on immunoblot, the mean (SD) number of bands was 5-9 (1-96). Of the five patients who had or developed IgG bands, the mean (SD) number was 3-5 (1-31). Immunoblot from nine of the patients met at least one of the published interpretative criteria for seropositivity.2 60% were positive according to CDC criteria.3 70% of patients were leucopenic and 70% were (white blood cell count <45X109/L) Such thrombocytopenic (platelet count <150X109/L). are almost in results never seen disease. laboratory Lyme Among over 100 culture-confirmed cases of erythema migrans, the prevalence of thrombocytopenia was 2% and leucopenia 3% (unpublished observations). Could clinically inapparent coinfection with Borrelia burgdoiferi explain the Lyme disease serologies? In our area in Westchester County, approximately 25% of nymphal Ixodes scapularis ticks are infected with B burgdoiferi.4 If those local ticks infected with HGE carry at the same rate, then approximately two to three of our ten patients might have been expected to have had coinfection. The probability, however, that at least nine of the ten patients would have been coinfected (at least by the same tick bite) is only 0-00003 (binomial test). This probability is less than 0-03 even if the borrelial infection rate in ticks were assumed to be 50%. Alternatively, false-positive antibody assays for Lyme disease are well documented to occur in a variety of other infections and in autoimmune diseases; this has been attributed to either cross reactivity or to polyclonal B-cell stimulation.5 Our observations imply that the diagnosis of HGE should be entertained in patients from endemic areas during the course of a febrile illness without erythema migrans, even in the face of new seroreactivity for Lyme disease. If empirical antibiotic therapy is prescribed, it should be a tetracycline, rather than a beta-lactam antibiotic, in order to provide coverage for both infections. Proof of true B burgdorferi coinfection will need to rest upon definitive demonstration of the aetiological agent by a means other than Lyme disease

serology (eg, culture). Supported in part by Cooperative Agreement No U50/CCU 210280-02 from the Centers for Disease Control and Prevention (CDC) and Grants No 41508, 41511, and 43135 from the National Institute of Arthritis and Musculoskeletal and Skin Diseases (NIAMSD).

*Gary P Wormser, Harold W Horowitz, J Ira Schwartz, Maria Aguero-Rosenfeld

Stephen Dumler,

*Division of Infectious Diseases, Departments of Medicine, Biochemistry and Molecular Biology, and Pathology, New York Medical College, Valhalla, NY 10595, USA; and Westchester County Medical Center; and Department of Pathology, Johns Hopkins Medical Institutions, Baltimore, MD, USA

1 2

Wormser G, McKenna D, Aguero-Rosenfeld M, et al. Human granulocytic ehrlichiosis—New York 1995. MMWR 1995; 44: 593-95. Grodzicki RL, Steere AC. Comparison of immunoblotting and indirect enzyme-linked immunosorbent assay using different antigen

981

preparation for diagnosing early Lyme disease. J Infect Dis 1988;

3

4

5

157: 790-97. CDC. Recommendations for test performance and interpretation from the Second National Conference on Serological Diagnosis of Lyme Disease. MMWR 1995; 44: 590-91. Maupin GO, Fish D, Zultowsky J, Campos EG, Piesman J. Landscape ecology of Lyme disease in a residential area of Westchester County, New York. Am J Epidemiol 1991; 133: 1105-13. Magnarelli LA. Current status of laboratory diagnosis of Lyme disease. Am J Med 1995; 98 (suppl 4-A): 10S-14S.

growth factor a serum marker for neurological and psychiatric complications in Behçet’s disease? Is

nerve

SiR-Behçet’s disease is an autoimmune vasculitis often involving the CNS and leading to neurological and psychiatric symptoms. As the diagnosis is a clinical one, a serum marker indicating the severity and possibly the course of disease would be useful. We prospectively examined 27 patients (18 women, 9 men; mean age 32-9 years, range 17-56) diagnosed according to the criteria of the International Study Group for Beh4;et’s disease,’ and recorded neurological and psychiatric symptoms. Where appropriate, electroencephalograms, cranial computed tomography, magnetic resonance imaging, and lumbar puncture were done. Serum nerve growth factor (NGF) was measured by a modified two-site enzyme immunoassayZ in patients and age-matched and sex-matched controls (n=27; 17 women, 10 men; mean age 32-6 years, range 22-54). To minimise interassay variations," mean NGF concentration of the corresponding control sera, determined in each assay, was taken as 100%. The measured value of each analysed serum sample was then normalised to a percentage of this value. Data are

presented as mean (SEM). Eight of 27 patients (30%) had neurological involvement: three had recurrent aseptic meningitis, two had meningoencephalitis causing epileptic seizures, two had brainstem encephalitis and one patient had pyramidal tract signs and recurrent syncope. Psychiatric disease was present in five patients (19%): three had depression, one an organic psychosis, and one 27-year-old woman was demented. Three patients without neurological signs had malaise, fever, soft-tissue swelling and arthralgia; and one severe disseminated erythema nodosum. Mean NGF level in control sera was 18-3 (2-8) pg/mL (range 5-74). Mean serum NGF in patients with Behcet’s was 289 (63)% of control (p=0-2, Mann Whitney test). When divided into subgroups, NGF levels in neurologically

patients (n=8) were 468 (165)% of control, those of psychiatrically ill patients (n=5) amounted to 401 (100)% of control (p=025, Kruskal-Wallis analysis) and were not statistically different from controls. However, when the patients were divided into groups of differing severity of systemic illness, those with minor complications (n=21; hospital stay ====1-2 days) had NGF levels of 123 (24)% of control. By contrast, NGF levels of the 6 patients with major systemic complications (2 with meningoencephalitis, 1 brain stem encephalitis, the 3 patients mentioned with generalised arthralgias and soft tissue swellings) were significantly increased to 917 (114)% of control (figure; p<00005, Kruskal-Wallis analysis). NGF serum levels seem not to be a specific marker for CNS involvement as such, but greatly raised levels indicate the severity of systemic illness independently of the type of ill

serum NGF could well be part of autoimmune postulated process underlying Behcet’s possibly as a long-distance immunomodulator.3 A point in favour of this hypothesis would be the increased NGF serum levels observed in other autoimmune diseases such as rheumatoid arthritis4 or lupus erythematosis.5

organ involvement. Raised

the

Maria C Jockers-Scherübl, Christos C Zouboulis, Friedrich Boegner, *Rainer Hellweg *Department of Psychiatry, Department of Dermatology, Department of Neurology, Benjamin Franklin Medical Center, Free University of Berlin, D-14050 Berlin, Germany International Study Group for Behçet’s disease. Criteria for diagnosis of Behçet’s disease. Lancet 1990; 335: 1078-80. 2 Hellweg R, Hock C, Hartung H-D. An improved rapid and highly sensitive enzyme immunoassay for nerve growth factor: technique. J Meth Cell Biol 1989; 1: 43-48. 3 Levi-Montalcini R, DalToso R, della Valle F, Skaper SD, Leon A. Update of the NGF saga. J Neurol Sci 1995; 130: 119-27. 4 Dicou E, Masson C, Jabbour W, Nerriere V. Increased frequency of NGF in sera of rheumatoid arthritis and systemic lupus erythematosus patients. Neuroreport 1993; 5: 321-24. 5. Bracci-Laudiero L, Aloe L, Levi-Montalcini R, et al. Increased levels of NGF in sera of systemic lupus erythematosus patients. Neuroreport 1

1993; 4: 563-65.

Too many

haematologists

on one

aeroplane

SiR-Would the loss of more than 50 haematologists in one crash really "be disastrous for the health service in the UK" (Jan 27, p 274)’? In 1974 the UK Department of Health and Social Security did stop 200 British orthopaedic surgeons flying in one plane to their international congress, but raised no objection when I planned to charter a plane to take hundreds of British gastroenterologists to the world congress in Mexico.

plane

J H Baron British Society of

1

Gastroenterology,

Rees DC. Too many 347: 274.

3 St Andrews Place, London NW1 4LB, UK

haematologists

in

one

aeroplane.

Lancet 1996;

SIR-It is fascinating that Rees’ apparently equates one professor with 10% of a region’s haematological staff. Which region, or professor, was he thinking of? Some cynics (though not me of course) might say one could lose ten professors with little impact on the UK’s haematological service-for are they not usually away at meetings anyway? M M Reid Department of Haematology, Royal Victoria Infirmary, Newcastle upon Tyne NE2 2SU, UK

1

982

Rees DC. Too many 347: 274.

haematologists

in

one

aeroplane. Lancet 1996;