1366
Side-effects, structure, and H2-receptor
antagonists SIR,-We have observed an allergic manifestation in response to H2-receptor antagonists (ranitidine, nizatidine, and
three
famotidine) but not to cimetidine and roxatidine in a 47-year-old woman with reflux oesophagitis and duodenitis but no evidence of Helicobacter pylori. Maculopapular eruptions on abdomen and chest spread to the limbs when ranitidine or famotidine were given. After a washout period, cimetidine was tried; no side-effects appeared. After a second wash-out roxatidine was given, again with no problems. H
CH,
Chemical structures of different H2-receptor
Shaded areas represent lateral chains bond to furan thiazole ring (famotidine and nizatidine)
ring (ranitidine)
Inspection of the chemical structures of H2-receptor antagonists shows that ranitidine (a furan derivative) and famotidine and nizatidine (with a thiazole ring) have similar side-chains to the ring structures (figure). We hypothesised a role for these side-chain structures in the development of adverse reaction. With the patient’s consent, and after a further wash-out period, we gave her nizatidine (not given previously) observing the same pruriginous skin manifestation. Return to cimetidine was necessary. Prick tests produced local reactions with ranitidine, famotidine, and nizatidine but not with cimetidine, roxatidine, and saline solution. ANTONIO BOSSI GIANCARLO ROMEO ANTONIO PEZZOLI
Division of Internal Medicine,
Antineuronal antibodies and subacute
paraneoplastic neuropathy SiR,—Paraneoplastic disorders of the nervous system mainly encephalitis, subacute cerebellar degeneration, encephalomyelitis, and sensorimotor neuropathy.l Recent studies have emphasised the diagnostic value of antineuronal antibodies in include limbic
these conditions.2,3 We report
an
unusual subacute
motor
neuropathy, in which only the presence of anti-Hu antibodies in plasma and cerebrospinal fluid (CSF) led to early discovery of the cause.
A 59-year-old woman with a history of smoking complained in December, 1991, of a weak right arm. Neurological examination on Jan 6, 1992, revealed a clear-cut deficit of the extensors of forearm, wrist, and fingers and abolition of the tricipital relfex on the right. Otherwise there was no motor deficit; cutaneous plantar reflexes were flexor; all sensory modalities were preserved; and her general condition was good. 2 days later, muscle weakness had progressed to All tendon reflexes
absent. Main leg. electrophysiological abnormalities consisted of reduced motor nerve velocities of the four limbs. There was no metabolic or endocrine disorder, and no toxic exposure was found. CSF contained 1 cell/)µl, 1-82 g protein/I, and the IgG index suggested local immunoglobulin synthesis. CSF glucose and gram stain and culture, serological tests for viruses, and chest X-rays were normal or negative. On Jan 13 she required respiratory assistance because of both
arms
frequent
and the left
were
apnoea, indicating bilateral phrenic palsy. An 2 weeks later showed much slowed motor and
electromyograph
F. SELLAL E. MONLUN CH. BERTON H. LEVENES
antagonists.
or to
Treviglio General Hospital, 24047 Treviglio, Italy
nerve velocities except in the left arm, with diffuse spontaneous activity. A chest computed tomographic (CT) scan gave no evidence of lung neoplasm. An anti-Hu antibody was then identified in serum (titre 8000) and CSF (4000), leading to a thorough chest investigation. 3 bronchoscopies with cytological and histological examination were normal but a second chest CT scan, on March 17, demonstrated a small right hilar nodule with two satellite adenopathies. Biopsy under CT control provided histological evidence of small-cell lung carcinoma (SCLC). Finding the cause of a polyneuropathy is often frustrating when there is no obvious disorder such as diabetes, uraemia, or alcoholism. Paraneoplastic syndromes are rarely the cause and their diagnosis is difficult because neurological manifestations may appear several years before discovery of the underlying neoplasm and because they can mimic or be mimicked by other diseases. Moreover, until recently specific neoplastic markers have not been available. Since 1986 several antineuronal autoantibodies have been identified in the serum and CSF of patients with paraneoplastic encephalomyelitis or sensory neuropathy.2,4 Among these, anti-Hu appears to be consistently associated with SCLC with high specificity for paraneoplastic neuropathy (99%) and moderate sensitivity (38%).3 When the cause of a polyneuropathy has yet to be found, as in our case, the presence of anti-Hu is a valuable clue to a possible underlying SCLC, prompting the physician to ask for more thorough investigations, even invasive ones, to find evidence of lung carcinoma and begin specific treatment.
sensory
Neurology Service I, Medical Resuscitation Service, and Anti-Poison Centre, Hôpitaux Universitaires de Strasbourg, 67091 Strasbourg, France
A. JAEGER
1. Delattre JY, Davila L,
Vega F, Poisson M. Auto-immunité et syndromes neurologiques paranéoplasiques. Rev Neurol 1991; 147: 549-56. 2. Graus F, Cordon-Cardo C, Posner JB. Neuronal antinuclear antibody in sensory neuropathy from lung cancer. Neurology 1985; 35: 538-43. 3. Moll JWB, Henzen-Logmans SC, Splinter TAW, van der Burg MEL, Vecht CHJ. Diagnostic value of anti-neuronal antibodies for paraneoplastic disorders of the nervous system. J Neurol Neurosurg Psychiatry 1990; 53: 940-43. 4. Anderson NE, Rosenblum MK, Graus F, Wiley RG, Posner JB. Autoantibodies in paraneoplastic syndromes associated with small-cell lung cancer. Neurology 1988; 38: 1391-98.
Urapidil and enuresis SIR,-Dr Jonville and colleagues (March 14, p 688) report persistent enuresis in 2 patients on urapidil. We have also seen enuresis with urapidil in 2 of 12 patients with essential hypertension. In these 2 patients (1 male, 1 female, aged under 60) dose of urapidil was increased from 30 mg twice daily to 60 mg twice daily one week after starting treatment, because of poor control of blood pressure. Three days after increasing the dose both patients started to complain of enuresis. One week later after persistent and troublesome enuresis, the dose of urapidil was reduced to 30 mg twice daily and a calcium-channel blocker was added to control blood pressure. Three days after dose reduction enuresis disappeared. The remaining 10 patients were on urapidil 30 mg twice daily throughout the study period of six weeks and none had enuresis. In this study, eneuresis was seen only in the 2 patients on a higher dose of urapidil. Accumulation of the drug probably took place in the 72 h after the dose was increased and lessened when the dose was reduced. Department of Cardiology, Hypertension Research Centre, Mayo Hospital, Lahore, Pakistan, and King Edward Medical College, Lahore
SHAHID KARIM MOHAMMUD ZUBAIR
CORRECTION Pressure on the eco-seams-In this editorial (May 23, p 1265) the reference in paragraph two line eight should have been number 2, and the third sentence of paragraph four should have begun "To negate a 3% growth rate ...".
Side-effects, structure, and H2-receptor
antagonists SIR,-We have observed an allergic manifestation in response to H2-receptor antagonists (ranitidine, nizatidine, and
three
famotidine) but not to cimetidine and roxatidine in a 47-year-old woman with reflux oesophagitis and duodenitis but no evidence of Helicobacter pylori. Maculopapular eruptions on abdomen and chest spread to the limbs when ranitidine or famotidine were given. After a washout period, cimetidine was tried; no side-effects appeared. After a second wash-out roxatidine was given, again with no problems. H
CH,
Chemical structures of different H2-receptor
Shaded areas represent lateral chains bond to furan thiazole ring (famotidine and nizatidine)
ring (ranitidine)
Inspection of the chemical structures of H2-receptor antagonists shows that ranitidine (a furan derivative) and famotidine and nizatidine (with a thiazole ring) have similar side-chains to the ring structures (figure). We hypothesised a role for these side-chain structures in the development of adverse reaction. With the patient’s consent, and after a further wash-out period, we gave her nizatidine (not given previously) observing the same pruriginous skin manifestation. Return to cimetidine was necessary. Prick tests produced local reactions with ranitidine, famotidine, and nizatidine but not with cimetidine, roxatidine, and saline solution. ANTONIO BOSSI GIANCARLO ROMEO ANTONIO PEZZOLI
Division of Internal Medicine,
Antineuronal antibodies and subacute
paraneoplastic neuropathy SiR,—Paraneoplastic disorders of the nervous system mainly encephalitis, subacute cerebellar degeneration, encephalomyelitis, and sensorimotor neuropathy.l Recent studies have emphasised the diagnostic value of antineuronal antibodies in include limbic
these conditions.2,3 We report
an
unusual subacute
motor
neuropathy, in which only the presence of anti-Hu antibodies in plasma and cerebrospinal fluid (CSF) led to early discovery of the cause.
A 59-year-old woman with a history of smoking complained in December, 1991, of a weak right arm. Neurological examination on Jan 6, 1992, revealed a clear-cut deficit of the extensors of forearm, wrist, and fingers and abolition of the tricipital relfex on the right. Otherwise there was no motor deficit; cutaneous plantar reflexes were flexor; all sensory modalities were preserved; and her general condition was good. 2 days later, muscle weakness had progressed to All tendon reflexes
absent. Main leg. electrophysiological abnormalities consisted of reduced motor nerve velocities of the four limbs. There was no metabolic or endocrine disorder, and no toxic exposure was found. CSF contained 1 cell/)µl, 1-82 g protein/I, and the IgG index suggested local immunoglobulin synthesis. CSF glucose and gram stain and culture, serological tests for viruses, and chest X-rays were normal or negative. On Jan 13 she required respiratory assistance because of both
arms
frequent
and the left
were
apnoea, indicating bilateral phrenic palsy. An 2 weeks later showed much slowed motor and
electromyograph
F. SELLAL E. MONLUN CH. BERTON H. LEVENES
antagonists.
or to
Treviglio General Hospital, 24047 Treviglio, Italy
nerve velocities except in the left arm, with diffuse spontaneous activity. A chest computed tomographic (CT) scan gave no evidence of lung neoplasm. An anti-Hu antibody was then identified in serum (titre 8000) and CSF (4000), leading to a thorough chest investigation. 3 bronchoscopies with cytological and histological examination were normal but a second chest CT scan, on March 17, demonstrated a small right hilar nodule with two satellite adenopathies. Biopsy under CT control provided histological evidence of small-cell lung carcinoma (SCLC). Finding the cause of a polyneuropathy is often frustrating when there is no obvious disorder such as diabetes, uraemia, or alcoholism. Paraneoplastic syndromes are rarely the cause and their diagnosis is difficult because neurological manifestations may appear several years before discovery of the underlying neoplasm and because they can mimic or be mimicked by other diseases. Moreover, until recently specific neoplastic markers have not been available. Since 1986 several antineuronal autoantibodies have been identified in the serum and CSF of patients with paraneoplastic encephalomyelitis or sensory neuropathy.2,4 Among these, anti-Hu appears to be consistently associated with SCLC with high specificity for paraneoplastic neuropathy (99%) and moderate sensitivity (38%).3 When the cause of a polyneuropathy has yet to be found, as in our case, the presence of anti-Hu is a valuable clue to a possible underlying SCLC, prompting the physician to ask for more thorough investigations, even invasive ones, to find evidence of lung carcinoma and begin specific treatment.
sensory
Neurology Service I, Medical Resuscitation Service, and Anti-Poison Centre, Hôpitaux Universitaires de Strasbourg, 67091 Strasbourg, France
A. JAEGER
1. Delattre JY, Davila L,
Vega F, Poisson M. Auto-immunité et syndromes neurologiques paranéoplasiques. Rev Neurol 1991; 147: 549-56. 2. Graus F, Cordon-Cardo C, Posner JB. Neuronal antinuclear antibody in sensory neuropathy from lung cancer. Neurology 1985; 35: 538-43. 3. Moll JWB, Henzen-Logmans SC, Splinter TAW, van der Burg MEL, Vecht CHJ. Diagnostic value of anti-neuronal antibodies for paraneoplastic disorders of the nervous system. J Neurol Neurosurg Psychiatry 1990; 53: 940-43. 4. Anderson NE, Rosenblum MK, Graus F, Wiley RG, Posner JB. Autoantibodies in paraneoplastic syndromes associated with small-cell lung cancer. Neurology 1988; 38: 1391-98.
Urapidil and enuresis SIR,-Dr Jonville and colleagues (March 14, p 688) report persistent enuresis in 2 patients on urapidil. We have also seen enuresis with urapidil in 2 of 12 patients with essential hypertension. In these 2 patients (1 male, 1 female, aged under 60) dose of urapidil was increased from 30 mg twice daily to 60 mg twice daily one week after starting treatment, because of poor control of blood pressure. Three days after increasing the dose both patients started to complain of enuresis. One week later after persistent and troublesome enuresis, the dose of urapidil was reduced to 30 mg twice daily and a calcium-channel blocker was added to control blood pressure. Three days after dose reduction enuresis disappeared. The remaining 10 patients were on urapidil 30 mg twice daily throughout the study period of six weeks and none had enuresis. In this study, eneuresis was seen only in the 2 patients on a higher dose of urapidil. Accumulation of the drug probably took place in the 72 h after the dose was increased and lessened when the dose was reduced. Department of Cardiology, Hypertension Research Centre, Mayo Hospital, Lahore, Pakistan, and King Edward Medical College, Lahore
SHAHID KARIM MOHAMMUD ZUBAIR
CORRECTION Pressure on the eco-seams-In this editorial (May 23, p 1265) the reference in paragraph two line eight should have been number 2, and the third sentence of paragraph four should have begun "To negate a 3% growth rate ...".
