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Systemic lupus erythematosus presenting as fulminating cerebral lupus
chronic renal failure and Turner’s for diagnosis of GH deficiency was not stated. It would seem likely that GH-replete individuals might be at greater risk of this complication but not exclusively so. The diagnosis was made usually within 8 weeks of onset of GH but was reported up to as long as 60 months later. The importance of ophthalmological examinations during the early months of treatment was emphasised, especially if headaches or visual changes were
diagnoses such as syndrome. The basis
reported. and to it may we have the within our be) adopted following procedures clinic. The possibility of BIH is specified within the sharedcare protocol for the family doctor and the warning pattern of symptoms described. Parents are informed that the onset of recurrent headaches should be reported as early as possible to the clinic doctor who will review the child. Fundoscopy is carried out just before GH treatment and at routine reviews during treatment. Finally we would encourage the systematic reporting of all serious adverse medical events on GH treatment to the Committee of Safety for Medicines or appropriate body and to the relevant pharmaceutical company. Headaches are not uncommonly reported by children on GH treatment2 and usually resolve spontaneously. It is not known whether there is an increased prevalence of headaches on GH treatment compared with that on other chronically administered drugs, and this is worthy of further study. Awareness of GH-induced BIH is likely to be of relevance to the use of GH in adult In order
to
diagnose
BIH
as
early
as
possible
minimise risk of serious visual impairment (rare
as
hypopituitarism. *D A Price, P E Clayton, I C Lloyd *Regional Growth Clinic, St Mary’s Hospital, Central Manchester Healthcare NHS Trust, Manchester M13 9WH, UK; and Manchester Royal Eye Hospital
1 Malozowski S, Tanner LA, Wysowski D, Fleming GA. Growth hormone, insulin-like growth factor 1, and benign intracranial hypertension. N Engl J Med 1994; 329: 665-66. 2 Wilton P. Kabi International Growth Study: adverse events report 4. In: Kabi International Growth Study Report 10, 1993: 45-52.
Systemic lupus erythematosus presenting as fulminating cerebral lupus in involvement SiR-Neurological systemic lupus erythematosus (SLE) is common and diverse. Initial presentation with cerebral involvement is rare and can present a diagnostic conundrum.’2 A 23-year-old Asian woman consulted her general practitioner with cervicoparotid swelling. During the subsequent week there was a history of mood change, withdrawal, and neglect of her 8-month-old son, followed by drowsiness, confusion, and headache leading to hospital admission. On examination she was agitated and unable to give a history and had a pyrexia of 39°C with marked parotid swelling but no focal neurological deficit. Computed tomography (CT) showed severe haemorrhagic infarction in the left temporal lobe, more minor infarction in the right temporal lobe, and a further possible infarction in the left frontoparietal region. On lumbar puncture there was an opening pressure of 18 cm of water; cerebrospinal fluid analysis showed 21 white cells (all lymphocytes), red blood cells 31, glucose 2-6 mmol/L (4-8), and protein 1-6 g/L. A diagnosis of encephalitis was made with parotid enlargement raising the possibility of mumps virus. Treatment was initiated with acyclovir, for possible herpes simplex encephalitis, combined with broad spectrum antibiotics.
After 2 days there was no change in her clinical state and she was transferred to the regional neuroscience centre. In view of the cerebral oedema noted on CT scan, intravenous methylprednisolone was instituted at 500 mg daily. Urea,
electrolytes, glucose,
serum
angiotensin-converting
enzyme,
all normal. Total protein g/L, calcium 1-85 mmol/L (uncorrected), phosphate 0-4 mmol/L, C-reactive protein 4 mg/L. Haemoglobin was 9-8 g/dL (mean cell volume 80 fL), white blood count 2-6X10"/L (lymphocytes 1-3X10"/L, granulocytes 1-1X10"/L, and monocytes 128X 109/L. Her 0-2X10"/L), platelets erythrocyte sedimentation rate was 87 mm/h. Coagulation, B12, folate, and bone marrow were normal.
and liver function test results was 79 g/L, albumin 25
were
The presence of markers of systemic disease, including a low albumin suggesting a duration of more than a few days, indicated a more generalised disease process. Further history was forthcoming at this stage. 5 weeks prior to admission she had developed self-limiting polyarthralgia and rash on her legs, and when seen the residual signs were of pharyngeal hyperaemia and a rash on her knee and ankle. A clinical diagnosis of post-streptococcal arthritis was made but an autoantibody profile showed high titres of rheumatoid factor (1/1280) and antinuclear factor (1/2560). This new information raised the possibility of cerebral lupus and the following results were obtained subsequently: antibody titre to dsDNA 1/4800, anti-La 6 (normal 0-2), anti-Ro 9 (0-2), C3 0-9 (0-8-1-8), C4 below 0-8 (0-13-0-43), polyclonal increase in immunoglobulin subclasses, partial thromboplastin time normal, Venereal Diseases Research Laboratory test, and anticardiolipin antibodies negative. Serial titres of antibodies for mumps and herpes simplex virus (HSV) were negative including PCR for HSV antigen in cerebrospinal fluid.
With the addition of high-dose corticosteroid, the patient’s pyrexia settled and her clinical state started to improve; she was obeying simple commands and starting to speak. Haematological indices reverted towards normal and the titre of antinuclear antibodies fell. After 7 days’ treatment with methylprednisolone 500 mg daily, prednisolone was substituted at 60 mg daily. This coincided with further deterioration and she became comatose, flexing to pain (infective screen and C-reactive protein normal). Repeat CT of infarction. Intravenous for a further 8 methylprednisolone given days, followed oral 100 There was further by prednisolone mg daily. so that at transfer she was able walk to and to improvement from the toilet with no obvious motor deficit. There were, however, behavioural problems with faecal incontinence and continued agitation. Cerebral lupus incorporates a diverse spectrum of clinical entities including headache, altered mood, psychosis, chorea, meningitis, seizure, and stroke. Central nervous system involvement occurs at some time in many patients with SLE, occasionally dominating the clinical picture. Psychiatric symptoms can occur early in the disease but other central nervous system manifestations are uncommon at presentation’,2 and present a diagnostic challenge. Delay in diagnosis and treatment can affect patient morbidity and mortality.3 In this case the appropriate treatment was given for the wrong diagnosis. Fever, parotid swelling, higher cerebral dysfunction, lymphocytic meningitis, and the CT appearances of haemorrhage and oedema all seemed to point to a viral or post-viral meningoencephalitis. However, steroid treatment was instituted for cerebral oedema and continued when further results and information became available. Clearly, although it is an uncommon presentation, cerebral lupus should be considered as a differential diagnosis of young female patients presenting with acute scan
showed
extension was
459
organic brain syndromes. This case also emphasises the requirement for prolonged high-dose corticosteroid therapy in the early stages, which in some cases may be continued with a cytotoxic agent. 1
*M P Wise, M Manford, U M Davies Charing Cross Hospital, London W6, UK; *Sir William
Dunn School of
Pathology,
University of Oxford, Oxford OX1 3RE, UK
for meningococcal disease. Nevertheless, our results suggest that pre-admission antibiotic therapy could be beneficial in these patients. We therefore believe that pre-admission antibiotics for sore throat or an upper respiratory tract infection might not only prevent progression of meningococcal disease but might also be, in some patients,
life-saving. *Pere
1 2
3
Mitchell I, Webb M, Hughes RAC, Maisey M, Cameron S. Cerebral lupus. Lancet 1994; 343: 579-82. Feinglass EJ, Arnett FC, Dorsch CA, Zizic TM, Stevens MB. Neuropsychiatric manifestations of systemic lupus erythematosus: diagnosis, clinical spectrum, and relationship to other features of the disease. Medicine 1976; 55: 323-39. Suzuki Y, Kitagawa Y, Matsuoka Y, Fukunda J, Mizushima Y. Severe cerebral and systemic necrotizing vasculitis developing during pregnancy in a case of systemic lupus erythematosus. J Rheumatol
1
2
1990; 17: 1408-11. 3
throat, antibiotics, and progression to meningococcal disease
Sore
SiR-Pether and colleagues (Dec 10, p 1636) ask if treatment for sore throat might halt progression to meningococcal meningitis. We believe that such treatment is not rare, with the frequency of prodromal upper respiratory tract infection in meningococcal disease and the widespread use of extended spectrum antibiotics by general
practitioners. Our experience with 133 adults with meningococcal meningitis and 423 patients of all ages with meningococcal disease supports this view. 66 of 133 adults (50%) with meningococcal meningitis had an illness consistent with upper respiratory tract infection in the 10 days preceding diagnosis. Moreover, 42 patients (32%) had taken antibiotics (usually p-Iactamics) before admission, and preadmission antibiotic therapy was significantly more frequent among patients with upper respiratory tract infection than among those without such infection (42% vs 21%, p=001). However, the mortality rate of patients who had or had not taken pre-admission antibiotic therapy did not differ (7-1% vs 4-4%, p=0-82). From 1987 to 1990, 423 cases of meningococcal disease were diagnosed in Barcelona. Among them, 193 patients (46%) had an upper respiratory tract infection within 10 days of the diagnosis of meningococcal disease, and 184 (44%) were on antibiotics before admission. The prodrome of upper respiratory tract infection was not associated with an increased pre-admission antibiotic use in these patients (46% vs 43%, p=0-53). The case-fatality rate of patients who had or had not received pre-admission antibiotic therapy was 0-5% and 10-5%, respectively (odds ratio, 0-05, 95% CI 0-02-0-41, p
Domingo, Nicolau Barquet, Joan A Caylà
*Department of Internal Medicine, Hospital de la Santa Creu i Sant Pau, 08025 Barcelona, Spain; and CAP Gràcia, Institute Català de la Salut, Institut Municipal de la Salut, Barcelona
4
5
Olcén P, Barr J, Kjellander J. Meningitis and bacteremia due to Neisseria meningitidis: clinical and laboratory findings in 69 cases from Orebro country, 1965-1977. Scand J Infect Dis 1979; 11: 111-19. Haneberg B, Tonjum T, Rodahl K, Gedde-Dahl TW. Factors preceding the onset of meningococcal disease, with special emphasis on passive smoking, stressful events, physical fitness and general symptoms of ill health. NIPH Ann 1983; 6: 169-73. Young LS, LaForce FM, Head JJ, Feeley JC, Bennett JV. A simultaneous outbreak of meningococcal and influenza infections. N Engl J Med 1972; 287: 5-9. Cartwright KAV, Jones DM, Smith AJ, Stuart JM, Kaczmarski EB, Palmer SR. Influenza A and meningococcal disease. Lancet 1991; 338: 554-57. Strang JR, Pugh EJ. Meningococcal infections: reducing the case fatality rate by giving penicillin before admission to hospital. BMJ 1992; 305: 141-43.
Exacerbation of peripheral neuropathy by lamivudine SiR-Lamivudine (3-TC), a nucleoside analogue structurally related to zalcitibine, is in clinical trials for chronic active hepatitis B and HIV infection. Of the currently used nucleoside analogues (zidovudine, didanosine, zalcitibine, and stavudine), lamivudine is the least potent inhibitor of gamma DNA polymerase and the least toxic to mitochondria in vitro.I,2 Consequently, lamivudine has been suggested to be the least neurotoxic.We report an HIV-infected patient who experienced exacerbation of his underlying peripheral neuropathy when treated with lamivudine. A 33-year-old man with AIDS and a low CD4 cell count developed numbness, tingling, and painful paraesthesia in his feet while receiving zidovudine and zalcitibine therapy. When zalcitibine was discontinued 18 months before evaluation, the pain and paraesthesia resolved but numbness persisted. He was left with mild weakness of foot and toe extensors, decreased sensation to pin and light touch up to mid-leg, markedly decreased vibration and position sense in the toes, and absent ankle reflexes. Electrophysiological studies were consistent with a mild sensory and motor axonal neuropathy involving the legs. CSF analysis, vitamin B12, folate, rapid plasma reagin test for syphilis, antinuclear antibody, rheumatoid factor, ganglioside GM1antibody titres, sedimentation rate, and immunofixation electrophresis were normal. The patient began lamivudine therapy at either 300 mg or 600 mg daily. Within 3 weeks, he developed painful burning paraesthesia in his feet extending up his legs and intermittent electrical sensations that increased in intensity as therapy continued. Lamivudine was suspected as the causative agent and was discontinued. Over the next 4 weeks his painful paraesthesia improved, but when rechallenged with lamivudine, symptoms recurred necessitating permanent discontinuation of the drug. The temporal association of the symptoms with lamivudine, improvement after discontinuation, and reappearance after rechallenge strongly suggest that lamivudine is also
diagnoses such as syndrome. The basis
reported. and to it may we have the within our be) adopted following procedures clinic. The possibility of BIH is specified within the sharedcare protocol for the family doctor and the warning pattern of symptoms described. Parents are informed that the onset of recurrent headaches should be reported as early as possible to the clinic doctor who will review the child. Fundoscopy is carried out just before GH treatment and at routine reviews during treatment. Finally we would encourage the systematic reporting of all serious adverse medical events on GH treatment to the Committee of Safety for Medicines or appropriate body and to the relevant pharmaceutical company. Headaches are not uncommonly reported by children on GH treatment2 and usually resolve spontaneously. It is not known whether there is an increased prevalence of headaches on GH treatment compared with that on other chronically administered drugs, and this is worthy of further study. Awareness of GH-induced BIH is likely to be of relevance to the use of GH in adult In order
to
diagnose
BIH
as
early
as
possible
minimise risk of serious visual impairment (rare
as
hypopituitarism. *D A Price, P E Clayton, I C Lloyd *Regional Growth Clinic, St Mary’s Hospital, Central Manchester Healthcare NHS Trust, Manchester M13 9WH, UK; and Manchester Royal Eye Hospital
1 Malozowski S, Tanner LA, Wysowski D, Fleming GA. Growth hormone, insulin-like growth factor 1, and benign intracranial hypertension. N Engl J Med 1994; 329: 665-66. 2 Wilton P. Kabi International Growth Study: adverse events report 4. In: Kabi International Growth Study Report 10, 1993: 45-52.
Systemic lupus erythematosus presenting as fulminating cerebral lupus in involvement SiR-Neurological systemic lupus erythematosus (SLE) is common and diverse. Initial presentation with cerebral involvement is rare and can present a diagnostic conundrum.’2 A 23-year-old Asian woman consulted her general practitioner with cervicoparotid swelling. During the subsequent week there was a history of mood change, withdrawal, and neglect of her 8-month-old son, followed by drowsiness, confusion, and headache leading to hospital admission. On examination she was agitated and unable to give a history and had a pyrexia of 39°C with marked parotid swelling but no focal neurological deficit. Computed tomography (CT) showed severe haemorrhagic infarction in the left temporal lobe, more minor infarction in the right temporal lobe, and a further possible infarction in the left frontoparietal region. On lumbar puncture there was an opening pressure of 18 cm of water; cerebrospinal fluid analysis showed 21 white cells (all lymphocytes), red blood cells 31, glucose 2-6 mmol/L (4-8), and protein 1-6 g/L. A diagnosis of encephalitis was made with parotid enlargement raising the possibility of mumps virus. Treatment was initiated with acyclovir, for possible herpes simplex encephalitis, combined with broad spectrum antibiotics.
After 2 days there was no change in her clinical state and she was transferred to the regional neuroscience centre. In view of the cerebral oedema noted on CT scan, intravenous methylprednisolone was instituted at 500 mg daily. Urea,
electrolytes, glucose,
serum
angiotensin-converting
enzyme,
all normal. Total protein g/L, calcium 1-85 mmol/L (uncorrected), phosphate 0-4 mmol/L, C-reactive protein 4 mg/L. Haemoglobin was 9-8 g/dL (mean cell volume 80 fL), white blood count 2-6X10"/L (lymphocytes 1-3X10"/L, granulocytes 1-1X10"/L, and monocytes 128X 109/L. Her 0-2X10"/L), platelets erythrocyte sedimentation rate was 87 mm/h. Coagulation, B12, folate, and bone marrow were normal.
and liver function test results was 79 g/L, albumin 25
were
The presence of markers of systemic disease, including a low albumin suggesting a duration of more than a few days, indicated a more generalised disease process. Further history was forthcoming at this stage. 5 weeks prior to admission she had developed self-limiting polyarthralgia and rash on her legs, and when seen the residual signs were of pharyngeal hyperaemia and a rash on her knee and ankle. A clinical diagnosis of post-streptococcal arthritis was made but an autoantibody profile showed high titres of rheumatoid factor (1/1280) and antinuclear factor (1/2560). This new information raised the possibility of cerebral lupus and the following results were obtained subsequently: antibody titre to dsDNA 1/4800, anti-La 6 (normal 0-2), anti-Ro 9 (0-2), C3 0-9 (0-8-1-8), C4 below 0-8 (0-13-0-43), polyclonal increase in immunoglobulin subclasses, partial thromboplastin time normal, Venereal Diseases Research Laboratory test, and anticardiolipin antibodies negative. Serial titres of antibodies for mumps and herpes simplex virus (HSV) were negative including PCR for HSV antigen in cerebrospinal fluid.
With the addition of high-dose corticosteroid, the patient’s pyrexia settled and her clinical state started to improve; she was obeying simple commands and starting to speak. Haematological indices reverted towards normal and the titre of antinuclear antibodies fell. After 7 days’ treatment with methylprednisolone 500 mg daily, prednisolone was substituted at 60 mg daily. This coincided with further deterioration and she became comatose, flexing to pain (infective screen and C-reactive protein normal). Repeat CT of infarction. Intravenous for a further 8 methylprednisolone given days, followed oral 100 There was further by prednisolone mg daily. so that at transfer she was able walk to and to improvement from the toilet with no obvious motor deficit. There were, however, behavioural problems with faecal incontinence and continued agitation. Cerebral lupus incorporates a diverse spectrum of clinical entities including headache, altered mood, psychosis, chorea, meningitis, seizure, and stroke. Central nervous system involvement occurs at some time in many patients with SLE, occasionally dominating the clinical picture. Psychiatric symptoms can occur early in the disease but other central nervous system manifestations are uncommon at presentation’,2 and present a diagnostic challenge. Delay in diagnosis and treatment can affect patient morbidity and mortality.3 In this case the appropriate treatment was given for the wrong diagnosis. Fever, parotid swelling, higher cerebral dysfunction, lymphocytic meningitis, and the CT appearances of haemorrhage and oedema all seemed to point to a viral or post-viral meningoencephalitis. However, steroid treatment was instituted for cerebral oedema and continued when further results and information became available. Clearly, although it is an uncommon presentation, cerebral lupus should be considered as a differential diagnosis of young female patients presenting with acute scan
showed
extension was
459
organic brain syndromes. This case also emphasises the requirement for prolonged high-dose corticosteroid therapy in the early stages, which in some cases may be continued with a cytotoxic agent. 1
*M P Wise, M Manford, U M Davies Charing Cross Hospital, London W6, UK; *Sir William
Dunn School of
Pathology,
University of Oxford, Oxford OX1 3RE, UK
for meningococcal disease. Nevertheless, our results suggest that pre-admission antibiotic therapy could be beneficial in these patients. We therefore believe that pre-admission antibiotics for sore throat or an upper respiratory tract infection might not only prevent progression of meningococcal disease but might also be, in some patients,
life-saving. *Pere
1 2
3
Mitchell I, Webb M, Hughes RAC, Maisey M, Cameron S. Cerebral lupus. Lancet 1994; 343: 579-82. Feinglass EJ, Arnett FC, Dorsch CA, Zizic TM, Stevens MB. Neuropsychiatric manifestations of systemic lupus erythematosus: diagnosis, clinical spectrum, and relationship to other features of the disease. Medicine 1976; 55: 323-39. Suzuki Y, Kitagawa Y, Matsuoka Y, Fukunda J, Mizushima Y. Severe cerebral and systemic necrotizing vasculitis developing during pregnancy in a case of systemic lupus erythematosus. J Rheumatol
1
2
1990; 17: 1408-11. 3
throat, antibiotics, and progression to meningococcal disease
Sore
SiR-Pether and colleagues (Dec 10, p 1636) ask if treatment for sore throat might halt progression to meningococcal meningitis. We believe that such treatment is not rare, with the frequency of prodromal upper respiratory tract infection in meningococcal disease and the widespread use of extended spectrum antibiotics by general
practitioners. Our experience with 133 adults with meningococcal meningitis and 423 patients of all ages with meningococcal disease supports this view. 66 of 133 adults (50%) with meningococcal meningitis had an illness consistent with upper respiratory tract infection in the 10 days preceding diagnosis. Moreover, 42 patients (32%) had taken antibiotics (usually p-Iactamics) before admission, and preadmission antibiotic therapy was significantly more frequent among patients with upper respiratory tract infection than among those without such infection (42% vs 21%, p=001). However, the mortality rate of patients who had or had not taken pre-admission antibiotic therapy did not differ (7-1% vs 4-4%, p=0-82). From 1987 to 1990, 423 cases of meningococcal disease were diagnosed in Barcelona. Among them, 193 patients (46%) had an upper respiratory tract infection within 10 days of the diagnosis of meningococcal disease, and 184 (44%) were on antibiotics before admission. The prodrome of upper respiratory tract infection was not associated with an increased pre-admission antibiotic use in these patients (46% vs 43%, p=0-53). The case-fatality rate of patients who had or had not received pre-admission antibiotic therapy was 0-5% and 10-5%, respectively (odds ratio, 0-05, 95% CI 0-02-0-41, p
Domingo, Nicolau Barquet, Joan A Caylà
*Department of Internal Medicine, Hospital de la Santa Creu i Sant Pau, 08025 Barcelona, Spain; and CAP Gràcia, Institute Català de la Salut, Institut Municipal de la Salut, Barcelona
4
5
Olcén P, Barr J, Kjellander J. Meningitis and bacteremia due to Neisseria meningitidis: clinical and laboratory findings in 69 cases from Orebro country, 1965-1977. Scand J Infect Dis 1979; 11: 111-19. Haneberg B, Tonjum T, Rodahl K, Gedde-Dahl TW. Factors preceding the onset of meningococcal disease, with special emphasis on passive smoking, stressful events, physical fitness and general symptoms of ill health. NIPH Ann 1983; 6: 169-73. Young LS, LaForce FM, Head JJ, Feeley JC, Bennett JV. A simultaneous outbreak of meningococcal and influenza infections. N Engl J Med 1972; 287: 5-9. Cartwright KAV, Jones DM, Smith AJ, Stuart JM, Kaczmarski EB, Palmer SR. Influenza A and meningococcal disease. Lancet 1991; 338: 554-57. Strang JR, Pugh EJ. Meningococcal infections: reducing the case fatality rate by giving penicillin before admission to hospital. BMJ 1992; 305: 141-43.
Exacerbation of peripheral neuropathy by lamivudine SiR-Lamivudine (3-TC), a nucleoside analogue structurally related to zalcitibine, is in clinical trials for chronic active hepatitis B and HIV infection. Of the currently used nucleoside analogues (zidovudine, didanosine, zalcitibine, and stavudine), lamivudine is the least potent inhibitor of gamma DNA polymerase and the least toxic to mitochondria in vitro.I,2 Consequently, lamivudine has been suggested to be the least neurotoxic.We report an HIV-infected patient who experienced exacerbation of his underlying peripheral neuropathy when treated with lamivudine. A 33-year-old man with AIDS and a low CD4 cell count developed numbness, tingling, and painful paraesthesia in his feet while receiving zidovudine and zalcitibine therapy. When zalcitibine was discontinued 18 months before evaluation, the pain and paraesthesia resolved but numbness persisted. He was left with mild weakness of foot and toe extensors, decreased sensation to pin and light touch up to mid-leg, markedly decreased vibration and position sense in the toes, and absent ankle reflexes. Electrophysiological studies were consistent with a mild sensory and motor axonal neuropathy involving the legs. CSF analysis, vitamin B12, folate, rapid plasma reagin test for syphilis, antinuclear antibody, rheumatoid factor, ganglioside GM1antibody titres, sedimentation rate, and immunofixation electrophresis were normal. The patient began lamivudine therapy at either 300 mg or 600 mg daily. Within 3 weeks, he developed painful burning paraesthesia in his feet extending up his legs and intermittent electrical sensations that increased in intensity as therapy continued. Lamivudine was suspected as the causative agent and was discontinued. Over the next 4 weeks his painful paraesthesia improved, but when rechallenged with lamivudine, symptoms recurred necessitating permanent discontinuation of the drug. The temporal association of the symptoms with lamivudine, improvement after discontinuation, and reappearance after rechallenge strongly suggest that lamivudine is also