- Email: [email protected]
Bilateral facial palsy and meningitis caused by borrelia double infection
combination of levamisole and fluorouracil. J Clin Oncol 1989; 7: 1447-56. Moertel CG, Fleming TR, Macdonald JS, et al. Levamisole and fluorouracil for adjuvant therapy of resected colon cancer. N Engl J Med 1990; 322: 352-58. National Institutes of Health Consensus Conference. Adjuvant therapy for patients with colon cancer and rectal cancer. JAMA 1990; 264: 1444-50. Ghersi D, Parmar MKB, Stewart LA, Marsoni S, Williams CJ. Early ovarian cancer and the Icon trials. Eur J Cancer 1992; 28A: 1297.
2
3
4
Cutaneous T-cell lymphoma and calcitriol and isotretinoin treatment SiR-Anecdotal reports should be met with scepticism in order not to create false hope among patients with diseases otherwise difficult to treat. However, the report on remission of cutaneous T-cell lymphoma with combined calcitriol and acitretin’ was so optimistic that we did not hestitate to try this new treatment in three patients with cutaneous T-cell lymphoma. We used isotretinoin 40 mg daily and calcitriol 1 f.1g daily. Isotretinoin was used instead of acitretin following the report in The Lancet on isotretinoin and calcitriol for precancerous and cancerous skin lesions in four patients.2 After 3 months, however, treatment had to be withdrawn in all three patients because of progression of the
lymphoma. 60-year-old man who had had mycosis fungoides for 18 years presented to us with plaques covering most of the skin surface and in addition three 5-10 cm ulcerating tumours but no extracutaneous disease. Previously he had been treated with topical nitrogen mustard, psoralen ultraviolet A (PUVA), radiotherapy, and retinoids. During the new combination treatment his skin deteriorated, the tumours enlarged, and new tumours appeared. A 61-year-old man who had had cutaneous T-cell lymphoma for 13 years presented with multiple nodules and cutaneous
A
tumours.
He had
never
had
extracutaneous
Bilateral facial palsy and meningitis caused by borrelia double infection SiR-Facial nerve paresis, especially bilateral facial palsy, is a well-known manifestation of Lyme borreliosis. Patients may have meningeal involvement with mild pleocytosis and other inflammatory signs in the cerebrospinal fluid (CSF). Borrelia burgdorferi has been cultivated from the CSF and blood of patients with facial palsy.’ Three genospecies of B burgdorferi sensu lato occurring in Europe are now known to cause human infections.2°3 We describe simultaneous detection of two genospecies by culture in a single patient. A 52-year-old previously healthy man living in an area where Lyme borreliosis is endemic removed an engorged tick from his thigh in the autumn of 1993. No erythema migrans developed. During the first months of 1994, persistent myalgia developed. Anti-inflammatory drugs and physiotherapy provided only marginal relief. In the summer of 1994, he had intermittent photophobia. On Aug 12, 1994, the patient suddenly developed bilateral facial palsy without any other new symptoms. The palsy disappeared completely in 2 weeks. However, daily episodes of myalgia persisted. On Aug 31, 1994, CSF analysis revealed lymphocytic meningitis (table) with greatly raised protein (with 3-4 subfractions) and an increased IgG index (088; normal value <0-60). CSF angiotensin-converting enzyme was normal, whereas lysozyme was raised (061; normal value <0-1). Magnetic resonance imaging of the brain was unremarkable. Results of antibodies against B burgdorferi and of PCR tests (plasma, CSF, Bardour-Stoenner-Kelly II [BSK-11] medium) are shown in the table. On Sept 12, 1994, treatment with cefixime (200 mg orally every 8 h) combined with probenecid (500 mg orally every 8 h) was instituted and continued for 100 days. While on antibiotics he developed mild bilateral iritis. The myalgia resolved in 1 month. CSF and serum samples on Dec 30, 1994, 1 week after the end of antibiotic therapy, showed only borderline abnormalities (table).
manifestations of
the
lymphoma. He had been treated with PUVA, radiotherapy, methotrexate, and retinoids which were unable to control the disease. During treatment with isotretinoin and calcitriol and despite continuation of methotrexate 15 mg per week new tumours appeared and the old tumours increased in size. A 69-year-old plaque stage for
who had had mycosis fungoides 18 years presented with ulcerating skin tumours but without any sign of extracutaneous disease. She had been treated with PUVA, retinoids, interferon a-2b, and for the past 12 months with photopheresis. Because of progression of her disease, the new treatment was instituted. woman
However, during this treatment the skin lesions enlarged and new ulcerations appeared. In these three patients with long-lasting and advanced cutaneous T-cell lymphoma, treatment with isotretinoin and calcitriol was well tolerated without signs of hypercalcaemia. The last patient, however, lost most of her hair. All three, however, deteriorated on treatment, which therefore cannot be recommended. Kristian Thomsen Department of Dermatology, Rigshospitalet, University DK-2100 Copenhagen Ø, Denmark
of
Copenhagen, stncto, sl=sensu lato, Pos=positive, Neg=negatlve, others not tested. *Lyme borreliosis ELISA kit, 2nd generation, DAKO A/S, Glostrup, Denmark; fw!th primers for DNA fragment from flagellin gene; :j:normal value 290-665 mg/L; §DAKO ELISA, Lyme neuroborreliosis krt, Glostrup, Denmark, indices above 0-3 show intrathecal antibody production; mth four primer pairs selected from gene encoding
ss=sensu
1
2
French LE, Ramelet AA, Saurat J-H. Remission of cutaneous T-cell lymphoma with combined calcitriol and acitretin. Lancet 1994; 344: 686-87. Majewski S, Skopinska M, Bollag W, Jablonska S. Combination of isotretinoin and calcitriol for precancerous and cancerous skin lesions. Lancet 1994; 344: 1510-11.
16S rRNA of B
Table:
burgdorferi.1
Laboratory findings 1583
Our patient had concomitant, culture-proven infections with two genospecies of B burgdorferi sensu lato, B garinii and B afzelii. PCR-based evidence of simultaneous infection by two or even three genospecies of B burgdorferi sensu lato has been reported.’ We have found several local ticks harbouring more than one genospecies of B burgdorferi sensu lato (unpublished). It is possible that double infections with borreliae are not very rare, and could be transmitted even by the bite of a single tick. It has been suggested that the three European genospecies, B burgdorferi sensu stricto, B garinii, B have different and afzelii, organotropisms.5 B garinii has been proposed as the main causative agent of Lyme neuroborreliosis.3 It is impossible to say which one of the genospecies in our case was responsible for the clinical disease, or whether both were responsible. CSF and blood may give positive PCR results only transiently or intermittently. The reason for this might be the minimal amounts of spirochaetes and their degradation products occurring sporadically in the CSF and blood. It is also possible that spirochaetes are shed to the circulation only intermittently from their hiding places. Both possibilities stress the importance of repeated testing. The first symptom of infection in our patient was persistent myalgia. Transient photophobia, occurring 2 months before definitive diagnosis, was obviously an ocular manifestation of Lyme borreliosis. It is remarkable that the patient, with marked pleocytosis in the CSF, had no meningeal signs or headache. Without the transient bilateral facial palsy 1 year after onset of the infection, the patient’s central-nervous-system infection would have remained unrecognised and progressed towards more serious sequelae. On the basis of this case, we advocate analysing the CSF of patients even when symptoms are mild. This study was financially supported by the Emil Aaltonen Foundation, the Maud Kuistila Foundation, the Orion Corporation Research Foundation, the Turku University Society, and the Turku University Foundation. We also thank Simo Merne for help in preparation of the
manuscript. *J Oksi, M
Marjamaki,
K
Koski, J Nikoskelainen, M K Viljanen
Department of Internal Medicine, Turku University Central Hospital; *Department of Medical Microbiology, Turku University, FIN-20520 Turku, Finland; and National Public Health Institute, Department in Turku; and Pulssi Neurocentre, Turku
1
2
3
4
5
Nadelman RB, Pavia CS, Magnarelli LA, Wormser GP. Isolation of Borrelia burgdorferi from the blood of seven patients with Lyme disease. Am J Med 1990; 88: 21-26. Baranton G, Postic D, Saint-Girons I, et al. Delineation of Borrelia burgdorferi sensu stricto, Borrelia garinii sp nov, and group VS461 associated with Lyme borreliosis. Int J Syst Bacteriol 1992; 42: 378-83. Demaerschalck I, Benmessaoud A, de Kesel M, et al. Simultaneous presence of different Borrelia burgdorferi genospecies in biological fluids of Lyme disease patients. J Clin Microbiol 1995; 33: 602-08. Marconi RT, Garon CF. Development of polymerase chain reaction primer sets for diagnosis of Lyme disease and for species-specific identification of Lyme disease isolates by 16S rRNA signature nucleotide analysis. J Clin Microbiol 1992; 30: 2830-34. Vandam AP, Kuiper H, Vos K, et al. Different genospecies of Borrelia burgdorferi are associated with distinct clinical manifestations of Lyme borreliosis. Clin Infect Dis 1993; 17: 708-17.
Pruritus SiR-Yamada says (May 20, p 1314) "now pruritis is not hard to describe"; perhaps then the next step is knowing how to spell it, especially since the epidemic of this specific monolectic dyslexia seems to be spreading from the letters columns into the Articles (May 13, p 1198). The Lancet is not alone in this difficulty. Medline from 1966 to May, 1995, reports 4645 cases of pruritus (69 in The Lancet), compared with 174 cases of pruritis (none in The Lancet). The prevalence of the -itis mutation across time (figure) suggests a sudden and virulent outbreak in about 1975, with 1584
-itis - :%-/t
*—*
+
-itus
Figure: Prevalence of the -itis variant of pruritus (shaded bars) percentage of all occurrences of the -itis and -itus forms (solid line) in Medline, 1966-94 as a
subsequent decline, possibly attributable to prophylaxis through spell-checking software. The error perhaps results either from a frontal-lobe-type defect of overinclusion or perseveration from other occurrences of the common -itis suffix, or from a false etymology that itching must result from inflammation, -itis (presumably of the prur-, whatever that may be). Pruritus comes instead from the Latin prurire, to itch, and finds itself in the rather dubious company of coitus, crepitus, detritus, fremitus, introitus, situs, tinnitus, a
and vomitus. Chris McManus Academic Department of Psychiatry, St Mary’s Hospital Medical School, London W2 1PD, UK
SiR-Taniguchi (April 1, p 870) along with Yamada (May 20, p 1314), and their colleagues, are justly concerned about how to describe, not to mention spell, pruritus. Since pruritus is one of the most misspelled words in medicine,’ The Lancet can probably be forgiven for using pruritis (sic) in the title to Yamada’s letter, and the authors must certainly be forgiven since the word (), so far as I can tell, is unambiguous in this regard. On the basis of W V Quine’s proposition that, "faced with two terms for the same thing, one tends to cast about for a distinction", I have argued that semantic distinctions between itch and pruritus should be cast aside At least in English, the words should be used interchangeably, which would give us one less word to misspell, and, perhaps, one less thing to scratch our heads about.3 1
Jeffrey D Bernhard Division of Dermatology, MA 01655, USA
University of Massachusetts Medical School, Worcester,
2
Helm KF, Goldsmith L. The misspelling of pruritus. J Am Acad Dermatol 1989; 4: 705-06. Bernhard JD. A word on "itch" versus "pruritus". In: Bernhard JD, ed.
3
Itch: mechanisms and management of pruritus. New York: McGrawHill, 1994: xiv. Bernhard JD. Does thinking itch? Lancet 1985; i: 589.
1
CORRECTION Is proximal demarcation of ulceratIve colitis determined by territory of the inferior mesenteric artery?—In this paper by M I Hamilton et al (18 March 1995), contrary to the figure legends, all figures referred to different patients.
2
3
4
Cutaneous T-cell lymphoma and calcitriol and isotretinoin treatment SiR-Anecdotal reports should be met with scepticism in order not to create false hope among patients with diseases otherwise difficult to treat. However, the report on remission of cutaneous T-cell lymphoma with combined calcitriol and acitretin’ was so optimistic that we did not hestitate to try this new treatment in three patients with cutaneous T-cell lymphoma. We used isotretinoin 40 mg daily and calcitriol 1 f.1g daily. Isotretinoin was used instead of acitretin following the report in The Lancet on isotretinoin and calcitriol for precancerous and cancerous skin lesions in four patients.2 After 3 months, however, treatment had to be withdrawn in all three patients because of progression of the
lymphoma. 60-year-old man who had had mycosis fungoides for 18 years presented to us with plaques covering most of the skin surface and in addition three 5-10 cm ulcerating tumours but no extracutaneous disease. Previously he had been treated with topical nitrogen mustard, psoralen ultraviolet A (PUVA), radiotherapy, and retinoids. During the new combination treatment his skin deteriorated, the tumours enlarged, and new tumours appeared. A 61-year-old man who had had cutaneous T-cell lymphoma for 13 years presented with multiple nodules and cutaneous
A
tumours.
He had
never
had
extracutaneous
Bilateral facial palsy and meningitis caused by borrelia double infection SiR-Facial nerve paresis, especially bilateral facial palsy, is a well-known manifestation of Lyme borreliosis. Patients may have meningeal involvement with mild pleocytosis and other inflammatory signs in the cerebrospinal fluid (CSF). Borrelia burgdorferi has been cultivated from the CSF and blood of patients with facial palsy.’ Three genospecies of B burgdorferi sensu lato occurring in Europe are now known to cause human infections.2°3 We describe simultaneous detection of two genospecies by culture in a single patient. A 52-year-old previously healthy man living in an area where Lyme borreliosis is endemic removed an engorged tick from his thigh in the autumn of 1993. No erythema migrans developed. During the first months of 1994, persistent myalgia developed. Anti-inflammatory drugs and physiotherapy provided only marginal relief. In the summer of 1994, he had intermittent photophobia. On Aug 12, 1994, the patient suddenly developed bilateral facial palsy without any other new symptoms. The palsy disappeared completely in 2 weeks. However, daily episodes of myalgia persisted. On Aug 31, 1994, CSF analysis revealed lymphocytic meningitis (table) with greatly raised protein (with 3-4 subfractions) and an increased IgG index (088; normal value <0-60). CSF angiotensin-converting enzyme was normal, whereas lysozyme was raised (061; normal value <0-1). Magnetic resonance imaging of the brain was unremarkable. Results of antibodies against B burgdorferi and of PCR tests (plasma, CSF, Bardour-Stoenner-Kelly II [BSK-11] medium) are shown in the table. On Sept 12, 1994, treatment with cefixime (200 mg orally every 8 h) combined with probenecid (500 mg orally every 8 h) was instituted and continued for 100 days. While on antibiotics he developed mild bilateral iritis. The myalgia resolved in 1 month. CSF and serum samples on Dec 30, 1994, 1 week after the end of antibiotic therapy, showed only borderline abnormalities (table).
manifestations of
the
lymphoma. He had been treated with PUVA, radiotherapy, methotrexate, and retinoids which were unable to control the disease. During treatment with isotretinoin and calcitriol and despite continuation of methotrexate 15 mg per week new tumours appeared and the old tumours increased in size. A 69-year-old plaque stage for
who had had mycosis fungoides 18 years presented with ulcerating skin tumours but without any sign of extracutaneous disease. She had been treated with PUVA, retinoids, interferon a-2b, and for the past 12 months with photopheresis. Because of progression of her disease, the new treatment was instituted. woman
However, during this treatment the skin lesions enlarged and new ulcerations appeared. In these three patients with long-lasting and advanced cutaneous T-cell lymphoma, treatment with isotretinoin and calcitriol was well tolerated without signs of hypercalcaemia. The last patient, however, lost most of her hair. All three, however, deteriorated on treatment, which therefore cannot be recommended. Kristian Thomsen Department of Dermatology, Rigshospitalet, University DK-2100 Copenhagen Ø, Denmark
of
Copenhagen, stncto, sl=sensu lato, Pos=positive, Neg=negatlve, others not tested. *Lyme borreliosis ELISA kit, 2nd generation, DAKO A/S, Glostrup, Denmark; fw!th primers for DNA fragment from flagellin gene; :j:normal value 290-665 mg/L; §DAKO ELISA, Lyme neuroborreliosis krt, Glostrup, Denmark, indices above 0-3 show intrathecal antibody production; mth four primer pairs selected from gene encoding
ss=sensu
1
2
French LE, Ramelet AA, Saurat J-H. Remission of cutaneous T-cell lymphoma with combined calcitriol and acitretin. Lancet 1994; 344: 686-87. Majewski S, Skopinska M, Bollag W, Jablonska S. Combination of isotretinoin and calcitriol for precancerous and cancerous skin lesions. Lancet 1994; 344: 1510-11.
16S rRNA of B
Table:
burgdorferi.1
Laboratory findings 1583
Our patient had concomitant, culture-proven infections with two genospecies of B burgdorferi sensu lato, B garinii and B afzelii. PCR-based evidence of simultaneous infection by two or even three genospecies of B burgdorferi sensu lato has been reported.’ We have found several local ticks harbouring more than one genospecies of B burgdorferi sensu lato (unpublished). It is possible that double infections with borreliae are not very rare, and could be transmitted even by the bite of a single tick. It has been suggested that the three European genospecies, B burgdorferi sensu stricto, B garinii, B have different and afzelii, organotropisms.5 B garinii has been proposed as the main causative agent of Lyme neuroborreliosis.3 It is impossible to say which one of the genospecies in our case was responsible for the clinical disease, or whether both were responsible. CSF and blood may give positive PCR results only transiently or intermittently. The reason for this might be the minimal amounts of spirochaetes and their degradation products occurring sporadically in the CSF and blood. It is also possible that spirochaetes are shed to the circulation only intermittently from their hiding places. Both possibilities stress the importance of repeated testing. The first symptom of infection in our patient was persistent myalgia. Transient photophobia, occurring 2 months before definitive diagnosis, was obviously an ocular manifestation of Lyme borreliosis. It is remarkable that the patient, with marked pleocytosis in the CSF, had no meningeal signs or headache. Without the transient bilateral facial palsy 1 year after onset of the infection, the patient’s central-nervous-system infection would have remained unrecognised and progressed towards more serious sequelae. On the basis of this case, we advocate analysing the CSF of patients even when symptoms are mild. This study was financially supported by the Emil Aaltonen Foundation, the Maud Kuistila Foundation, the Orion Corporation Research Foundation, the Turku University Society, and the Turku University Foundation. We also thank Simo Merne for help in preparation of the
manuscript. *J Oksi, M
Marjamaki,
K
Koski, J Nikoskelainen, M K Viljanen
Department of Internal Medicine, Turku University Central Hospital; *Department of Medical Microbiology, Turku University, FIN-20520 Turku, Finland; and National Public Health Institute, Department in Turku; and Pulssi Neurocentre, Turku
1
2
3
4
5
Nadelman RB, Pavia CS, Magnarelli LA, Wormser GP. Isolation of Borrelia burgdorferi from the blood of seven patients with Lyme disease. Am J Med 1990; 88: 21-26. Baranton G, Postic D, Saint-Girons I, et al. Delineation of Borrelia burgdorferi sensu stricto, Borrelia garinii sp nov, and group VS461 associated with Lyme borreliosis. Int J Syst Bacteriol 1992; 42: 378-83. Demaerschalck I, Benmessaoud A, de Kesel M, et al. Simultaneous presence of different Borrelia burgdorferi genospecies in biological fluids of Lyme disease patients. J Clin Microbiol 1995; 33: 602-08. Marconi RT, Garon CF. Development of polymerase chain reaction primer sets for diagnosis of Lyme disease and for species-specific identification of Lyme disease isolates by 16S rRNA signature nucleotide analysis. J Clin Microbiol 1992; 30: 2830-34. Vandam AP, Kuiper H, Vos K, et al. Different genospecies of Borrelia burgdorferi are associated with distinct clinical manifestations of Lyme borreliosis. Clin Infect Dis 1993; 17: 708-17.
Pruritus SiR-Yamada says (May 20, p 1314) "now pruritis is not hard to describe"; perhaps then the next step is knowing how to spell it, especially since the epidemic of this specific monolectic dyslexia seems to be spreading from the letters columns into the Articles (May 13, p 1198). The Lancet is not alone in this difficulty. Medline from 1966 to May, 1995, reports 4645 cases of pruritus (69 in The Lancet), compared with 174 cases of pruritis (none in The Lancet). The prevalence of the -itis mutation across time (figure) suggests a sudden and virulent outbreak in about 1975, with 1584
-itis - :%-/t
*—*
+
-itus
Figure: Prevalence of the -itis variant of pruritus (shaded bars) percentage of all occurrences of the -itis and -itus forms (solid line) in Medline, 1966-94 as a
subsequent decline, possibly attributable to prophylaxis through spell-checking software. The error perhaps results either from a frontal-lobe-type defect of overinclusion or perseveration from other occurrences of the common -itis suffix, or from a false etymology that itching must result from inflammation, -itis (presumably of the prur-, whatever that may be). Pruritus comes instead from the Latin prurire, to itch, and finds itself in the rather dubious company of coitus, crepitus, detritus, fremitus, introitus, situs, tinnitus, a
and vomitus. Chris McManus Academic Department of Psychiatry, St Mary’s Hospital Medical School, London W2 1PD, UK
SiR-Taniguchi (April 1, p 870) along with Yamada (May 20, p 1314), and their colleagues, are justly concerned about how to describe, not to mention spell, pruritus. Since pruritus is one of the most misspelled words in medicine,’ The Lancet can probably be forgiven for using pruritis (sic) in the title to Yamada’s letter, and the authors must certainly be forgiven since the word (), so far as I can tell, is unambiguous in this regard. On the basis of W V Quine’s proposition that, "faced with two terms for the same thing, one tends to cast about for a distinction", I have argued that semantic distinctions between itch and pruritus should be cast aside At least in English, the words should be used interchangeably, which would give us one less word to misspell, and, perhaps, one less thing to scratch our heads about.3 1
Jeffrey D Bernhard Division of Dermatology, MA 01655, USA
University of Massachusetts Medical School, Worcester,
2
Helm KF, Goldsmith L. The misspelling of pruritus. J Am Acad Dermatol 1989; 4: 705-06. Bernhard JD. A word on "itch" versus "pruritus". In: Bernhard JD, ed.
3
Itch: mechanisms and management of pruritus. New York: McGrawHill, 1994: xiv. Bernhard JD. Does thinking itch? Lancet 1985; i: 589.
1
CORRECTION Is proximal demarcation of ulceratIve colitis determined by territory of the inferior mesenteric artery?—In this paper by M I Hamilton et al (18 March 1995), contrary to the figure legends, all figures referred to different patients.