NEUROLEPTIC MALIGNANT SYNDROME
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221 NEUROLEPTIC MALIGNANT SYNDROME SIR,-We were interested to read in your issue of Jan 7 (p 49) of other cases of early neuroleptic malignant syndrome (NMS), reported by Dr Mezaki, Dr Domingo, and their colleagues. However, Dr Meyers raises several points concerning the diagnosis of early NMS in our patient which we cannot accept. A catatonic state is not a prerequisite for the diagnosis as he suggests; a severe parkinsonian syndrome is sufficient.1,2 It seems unlikely that an intramuscular injection 17 days earlier would produce a creatine jonase (CK) of 1144 IU/1 falling to 192 IU/I within just 8 days. In many cases of NMS the CK level does not exceed even 1000 IU 11. 2 We accept that the temperature was only slightly raised, but our argument is that this may be so early in NMS, and that earlier diagnosis might allow successful management without recourse to dantrolene. Although pipothiazine injections were continued on a monthly basis, chlorpromazine was decreased and eventually stopped in the month before the onset of NMS, which argues against a "dose-related reaction". Although we used the term "neuroleptic malignant syndrome", as coined by the French workers Delay and Deniker,3 we acknowledge the semantic preference for "malignant neuroleptic syndrome". Department of Neurology, North Manchester General Hospital, Manchester M8 6RB C. E. CLARKE D. SHAND G. M. YUILL M. H. P. GREEN 1. Guzé BH, Baxter LR Neuroleptic malignant syndrome. N Engl J Med 1985; 313: 163-66. 2. Kellam AMP. The neuroleptic malignant syndrome, so-called. Br J Psychiatry 1987; 150: 752-59. 3. Delay J, Deniker P. Drug-induced extrapyramidal syndromes In Vinken PJ, Bruyn GW, eds. Handbook of clinical neurology. Vol VI: diseases of the basal ganglia. Amsterdam. North-Holland, 1968: 248-66. BLASTOCYSTIS HOMINIS CHRONIC DIARRHOEA IN AIDS PATIENTS SiR—HIV-infected patients with chronic diarrhoea and histological or microbiological evidence of infection by Cryptosporidia or Isospora belli can be reported as AIDS cases.! Blastocystis hominis, previously considered a harmless yeast, can cause acute self-limited diarrhoea in immunocompetent hosts2 and should be borne in mind when intestinal infections are sought in immunosuppressed patients. Dr Garavelli and colleagues (Dec 10, p 1364) report two cases of B hominis infection in homosexual men with persistent generalised lymphadenopathy and diarrhoea. We report an HIV-infected homosexual man with oesophageal candidosis and an extranodal immunoblastic lymphosarcoma. He presented with chronic wasting diarrhoea and B hominis infestation. The patient, who was aged 35, had a 14-month history of HIV infection and oesophageal candidosis, and was admitted because of progressive left hemiparesis and weight loss with diarrhoea. He presented with a left Ramsay-Hunt syndrome 3 months before admission. The patient was thin and chronically ill. Hairy leucoplakia was found but there was no rash, thrush, or lymphadenopathy. The liver and spleen were not palpable. The patient was alert and oriented and the retina were normal. Left tendon reflexes were diffusely increased and there was an extensor left plantar response. The CD4 cell count was 90/pl and the CD8 count was 235/1, a CD4/CD8 ratio of 0-38. During the 5 weeks he was an inpatient extranodal, malignant non-Hodgkin’s lymphoma was found. On admission his stool contained a few parasites of Cnardia lamblia and heavy infestation with B hominis. The patient was treated with metronidazole 2 g daily for 5 days, although charrhoea persisted and was attributed then to enteral nutrition. 2 weeks later repeat stool examination revealed B hoininis and Carnpylobacter jejuni. The patient was treated with erythromycin but diarrhoea persisted until death. At necropsy the lymphoma could be classified as immunoblastic sarcoma with hepatic, renal, retroperitoneal, meningeal, and intestinal involvement. No other non-viral infectious agents were found on intestinal examination. Considered for several decades a harmless yeast commensal of the intestine, B hominis is now classified as a pathogenic sporozoa. It has been found in small numbers in faeces, either alone or in association with other intestinal parasites in 7-25% of patients.2 As with Cryptosporidia, when heavy infestation with B hominis occurs in the absence of other causes of intestinal disease, the organism can be considered as pathogenic.’ B hominis infection has been associated with mild prolonged diarrhoea and with recurrent diarrhoea. Garcia et aP showed that two factors were associated with B hominis infection: immunosuppression (56%) and a history of other parasitic infections (25%). As well as Garavelli and colleagues’ two cases, two HIV-infected patients with B hominis diarrhoea have been reported. One case had oesophageal candidosis and the other persistent generalised lymphadenopathy, with CD4 counts of 1 881 III and 355/ut, respectively. But these patients were successfully treated with di-iodohydroxyquinoline 650 mg orally three times per day for 21 days and no sign of relapse was seen on follow-up for 2-3 months. In a study in Chicago of the prevalence of enteric parasites in homosexual men’ B hominis was not found in 372 pooled stool specimens from 274 patients with diarrhoea. High rates of enteric protozoal infections were found: Entamoeba histolytica, coli, or hartmanni, 49%; Endolimax nana, 39%; Giardia lamblia, 8%; and others 4%. B hominis is a potential pathogenic parasite that is not prevalent in homosexual men infected with HIV. The organism can produce mild persistent or recurrent diarrhoea and must be included in the investigation of gastrointestinal disorders in these patients. Further study will determine the importance of B hominis as an indicator of underlying immunodeficiency or of AIDS itself in surveillance and case-definition studies. Infectious Diseases Unit and Microbiology Section, Hospital de Badalona "Germans Trias i Pujol", 08915 Barcelona, Spain J. M. LLIBRE J. TOR J. M. MANTEROLA C. CARBONELL M. Foz 1. Centers for Disease Control. Revision of the CDC Surveillance case definition for acquired immunodeficiency syndrome. MMWR 1987; 36 (suppl 1S): 3-13. 2. Ricci N, Toma P, Furlani M, Caselli M, Gullini S. Blastocystis hominis. a neglected cause of diarrhoea? Lancet 1984; i: 966. 3. Garcia LS, Bruckner DA, Clancy MN Clinical relevance of Blastocystis hominis. Lancet 1984; i: 1233-34. 4 Cross JH. Recent advances in human protozoan parasites of the gastrointestinal tract. Int J Parasitol 1987; 17: 151-58. 5. Causey DM, Eppolito LJ, Leedom JM. Blastocystis hominis diarrhoea in two HIV-infected patients Proceedings of the IV International Conference on AIDS, Stockholm, 1988: 408. 6. Peters CS, Sable R, Janda WM, Chittom AL, Kocka FE. Prevalence of enteric parasites in homosexual patients attending an outpatient clinic. J Clin Microbiol 1986; 24: 684-85. AEROSOLISED PENTAMIDINE SIR,-Dr O’Docherty and colleagues (Dec 3, p 1283) recommend either the ’System 22 Mizer’ (Medic-Aid) or ’Respirgard II’ (Marquest) as the nebulisers of choice for delivery of aerosolised pentamidine. The American respirgard II model is difficult to obtain in the UK so British clinicians will probably be encouraged to use the system 22 mizer. This would be unfortunate because although this nebuliser produced the largest pulmonary deposition of pentamidine, it was associated with a high incidence of adverse effects. These large-airway-related side-effects (cough, breathlessness, bitter taste) may seriously limit treatment in acute episodes of Pneumocystis carinii pneumonia’ and discourage compliance with long-term prophylaxis. Rather than concentrate on total delivery of pentamidine to the lungs, we have targeted drug to site by examining factors favouring selective delivery of pentamidine to alveoli. Alveolar deposition (24 h whole lung retention) and large-airway-related side-effects have been measured following aerosolisation of 150 mg pentamidine isethionate labelled with 99’Tc-Sn-colloid in nine patients with AIDS receiving pentamidine as secondary prophylaxis. Three nebuliser systems producing different droplet size profiles were compared (’Acorn System 22’ [Medic-Aid],
Transcript of NEUROLEPTIC MALIGNANT SYNDROME
221
NEUROLEPTIC MALIGNANT SYNDROME
SIR,-We were interested to read in your issue of Jan 7 (p 49) ofother cases of early neuroleptic malignant syndrome (NMS),reported by Dr Mezaki, Dr Domingo, and their colleagues.However, Dr Meyers raises several points concerning the diagnosisof early NMS in our patient which we cannot accept. A catatonicstate is not a prerequisite for the diagnosis as he suggests; a severeparkinsonian syndrome is sufficient.1,2 It seems unlikely that anintramuscular injection 17 days earlier would produce a creatinejonase (CK) of 1144 IU/1 falling to 192 IU/I within just 8 days. Inmany cases of NMS the CK level does not exceed even 1000 IU 11. 2We accept that the temperature was only slightly raised, but our
argument is that this may be so early in NMS, and that earlierdiagnosis might allow successful management without recourse todantrolene. Although pipothiazine injections were continued on amonthly basis, chlorpromazine was decreased and eventuallystopped in the month before the onset of NMS, which arguesagainst a "dose-related reaction".Although we used the term "neuroleptic malignant syndrome",
as coined by the French workers Delay and Deniker,3 weacknowledge the semantic preference for "malignant neurolepticsyndrome".
Department of Neurology,North Manchester General Hospital,Manchester M8 6RB
C. E. CLARKED. SHANDG. M. YUILLM. H. P. GREEN
1. Guzé BH, Baxter LR Neuroleptic malignant syndrome. N Engl J Med 1985; 313:163-66.
2. Kellam AMP. The neuroleptic malignant syndrome, so-called. Br J Psychiatry 1987;150: 752-59.
3. Delay J, Deniker P. Drug-induced extrapyramidal syndromes In Vinken PJ, BruynGW, eds. Handbook of clinical neurology. Vol VI: diseases of the basal ganglia.Amsterdam. North-Holland, 1968: 248-66.
BLASTOCYSTIS HOMINIS CHRONIC DIARRHOEA INAIDS PATIENTS
SiR—HIV-infected patients with chronic diarrhoea and
histological or microbiological evidence of infection byCryptosporidia or Isospora belli can be reported as AIDS cases.!Blastocystis hominis, previously considered a harmless yeast, cancause acute self-limited diarrhoea in immunocompetent hosts2 andshould be borne in mind when intestinal infections are sought inimmunosuppressed patients. Dr Garavelli and colleagues (Dec 10,p 1364) report two cases of B hominis infection in homosexual menwith persistent generalised lymphadenopathy and diarrhoea. Wereport an HIV-infected homosexual man with oesophagealcandidosis and an extranodal immunoblastic lymphosarcoma. Hepresented with chronic wasting diarrhoea and B hominis infestation.The patient, who was aged 35, had a 14-month history of HIV
infection and oesophageal candidosis, and was admitted because ofprogressive left hemiparesis and weight loss with diarrhoea. Hepresented with a left Ramsay-Hunt syndrome 3 months beforeadmission. The patient was thin and chronically ill. Hairyleucoplakia was found but there was no rash, thrush, or
lymphadenopathy. The liver and spleen were not palpable. Thepatient was alert and oriented and the retina were normal. Lefttendon reflexes were diffusely increased and there was an extensorleft plantar response. The CD4 cell count was 90/pl and the CD8count was 235/1, a CD4/CD8 ratio of 0-38. During the 5 weeks hewas an inpatient extranodal, malignant non-Hodgkin’s lymphomawas found. On admission his stool contained a few parasites ofCnardia lamblia and heavy infestation with B hominis. The patientwas treated with metronidazole 2 g daily for 5 days, althoughcharrhoea persisted and was attributed then to enteral nutrition. 2weeks later repeat stool examination revealed B hoininis andCarnpylobacter jejuni. The patient was treated with erythromycinbut diarrhoea persisted until death. At necropsy the lymphomacould be classified as immunoblastic sarcoma with hepatic, renal,retroperitoneal, meningeal, and intestinal involvement. No othernon-viral infectious agents were found on intestinal examination.
Considered for several decades a harmless yeast commensal of the
intestine, B hominis is now classified as a pathogenic sporozoa. It hasbeen found in small numbers in faeces, either alone or in associationwith other intestinal parasites in 7-25% of patients.2 As withCryptosporidia, when heavy infestation with B hominis occurs in theabsence of other causes of intestinal disease, the organism can beconsidered as pathogenic.’ B hominis infection has been associatedwith mild prolonged diarrhoea and with recurrent diarrhoea. Garciaet aP showed that two factors were associated with B hominisinfection: immunosuppression (56%) and a history of other
parasitic infections (25%).As well as Garavelli and colleagues’ two cases, two HIV-infected
patients with B hominis diarrhoea have been reported. One case hadoesophageal candidosis and the other persistent generalisedlymphadenopathy, with CD4 counts of 1 881 III and 355/ut,respectively. But these patients were successfully treated withdi-iodohydroxyquinoline 650 mg orally three times per day for 21days and no sign of relapse was seen on follow-up for 2-3 months. Ina study in Chicago of the prevalence of enteric parasites inhomosexual men’ B hominis was not found in 372 pooled stoolspecimens from 274 patients with diarrhoea. High rates of entericprotozoal infections were found: Entamoeba histolytica, coli, orhartmanni, 49%; Endolimax nana, 39%; Giardia lamblia, 8%; andothers 4%.B hominis is a potential pathogenic parasite that is not prevalent in
homosexual men infected with HIV. The organism can producemild persistent or recurrent diarrhoea and must be included in theinvestigation of gastrointestinal disorders in these patients. Furtherstudy will determine the importance of B hominis as an indicator ofunderlying immunodeficiency or of AIDS itself in surveillance andcase-definition studies.
Infectious Diseases Unitand Microbiology Section,
Hospital de Badalona"Germans Trias i Pujol",
08915 Barcelona, Spain
J. M. LLIBREJ. TORJ. M. MANTEROLAC. CARBONELLM. Foz
1. Centers for Disease Control. Revision of the CDC Surveillance case definition for
acquired immunodeficiency syndrome. MMWR 1987; 36 (suppl 1S): 3-13.2. Ricci N, Toma P, Furlani M, Caselli M, Gullini S. Blastocystis hominis. a neglected
cause of diarrhoea? Lancet 1984; i: 966.3. Garcia LS, Bruckner DA, Clancy MN Clinical relevance of Blastocystis hominis.
Lancet 1984; i: 1233-34.4 Cross JH. Recent advances in human protozoan parasites of the gastrointestinal tract.
Int J Parasitol 1987; 17: 151-58.5. Causey DM, Eppolito LJ, Leedom JM. Blastocystis hominis diarrhoea in two
HIV-infected patients Proceedings of the IV International Conference on AIDS,Stockholm, 1988: 408.
6. Peters CS, Sable R, Janda WM, Chittom AL, Kocka FE. Prevalence of entericparasites in homosexual patients attending an outpatient clinic. J Clin Microbiol1986; 24: 684-85.
AEROSOLISED PENTAMIDINE
SIR,-Dr O’Docherty and colleagues (Dec 3, p 1283)recommend either the ’System 22 Mizer’ (Medic-Aid) or
’Respirgard II’ (Marquest) as the nebulisers of choice for delivery ofaerosolised pentamidine. The American respirgard II model isdifficult to obtain in the UK so British clinicians will probably beencouraged to use the system 22 mizer. This would be unfortunatebecause although this nebuliser produced the largest pulmonarydeposition of pentamidine, it was associated with a high incidence ofadverse effects. These large-airway-related side-effects (cough,breathlessness, bitter taste) may seriously limit treatment in acuteepisodes of Pneumocystis carinii pneumonia’ and discouragecompliance with long-term prophylaxis.
Rather than concentrate on total delivery of pentamidine to thelungs, we have targeted drug to site by examining factors favouringselective delivery of pentamidine to alveoli. Alveolar deposition(24 h whole lung retention) and large-airway-related side-effectshave been measured following aerosolisation of 150 mg
pentamidine isethionate labelled with 99’Tc-Sn-colloid in ninepatients with AIDS receiving pentamidine as secondaryprophylaxis. Three nebuliser systems producing different dropletsize profiles were compared (’Acorn System 22’ [Medic-Aid],
