- Email: [email protected]
HLA SEGREGATION RATIOS
745
hyperactive reflexes and bilateral Babinski signs, but had normal electromyograms and nerve conduction studies in all limbs. Reports of polyneuropathies in glue sniffers have usually involved mixtures of toluene and other solvents. Goto et aI.3 describe a motor predominant polyneuropathy in four people who "huffed" a mixture of chloroprene, n-hexane, toluene, and MEK. They ascribed the toxicity to the toluene exposure because the predominantly motor polyneuropathy was atypical of the usual mixed or mostly sensory polyneuropathy seen in pure n-hexane exposure. In another study4 car painters with chronic low level exposure to solvents containing toluene, xylene, butyl acetate, and white spirit had slower nerve-conduction velocities than did matched controls. I suggest that the neurotoxicity in AuBuchon’s patient arose from the synergistic effects of the ketone solvents and toluene. This patient may have had a genetic predisposition to the toxic effects of solvent exposure. Perhaps there are circumstances of mixed solvent exposure that lead to a pathological picture of acute segmental demyelination rather than to axonal degeneration with secondary demyelination. There have been reports of glue sniffing of solvent mixtures in which the clinical presentation resemble the Guillain-Barre syndrome.5 Despite the fact that a causal relationship between the spray painting and the polyneuropathy is not supported by quantitative estimates of exposure, this case does draw attention to the possibility of severe neurotoxicity arising from the combined effect of a mixture of solvents.
CLINICAL DATA AND PATCH AND CHALLENGE TESTS
with
Department of Neurology, Veterans Administration Outpatient Clinic,
Boston, Massachusetts 02108, U.S.A.
R. H. GOLDMAN
DERMATITIS AS SIDE-EFFECT OF LONG-TERM METOPROLOL
SIR,-Skin reactions
to p-adrenergic blocking drugs other practolol have been reported (for propranolol, oxprenolol, pindolol)6-S and dermatitis as a side-effect of long-term topical therapy with metoprolol has also been described.9 Here we report an eczematous and psoriasiform eruption that. developed in five patients during long-term therapy with metoprolol. To our knowledge these side-effects of oral metoprolol have not yet been recorded in print. Five patients, all men (mean age 59), were seen with eczematous and/or psoriasiform skin reactions during long-term oral treatment with metoprolol (mean duration 7 months). After withdrawal of the drug the skin eruptions disappeared slowly within weeks to months. Investigations and clinical data are summarised in the table. Four patients had patch tests with metoprolol, several other p-adrenergic blocking agents, and the European standard battery. Test concentrations of p-adrenergic blocking agents were as indicated in a previous report.9 In three patients a local or disseminated dermatitis reappeared 1 or 2 weeks after the oral provocation test. Patch tests to metoprolol were positive in only one patient, however; this patient (no. 1) also had a positive patch test to alprenolol, indicating a possible cross-reaction. This 62-year-old man devel-
than
3. Goto I, Matsumura M, Inoue N, Murai Y, Shida K, Santa T, Kuroiwa Y. Toxic polyneuropathy due to glue sniffing. J Neurol Neurosurg Psychiat
1974;37:848-53. 4.
Seppalainen AM, Husman KAJ, Martenson C. Neurophysiological effects of long-term exposure to a mixture of organic solvents. Scand J Work Envir
Health 1978; 4: 304-14. 5. Prockop LD, Alt M, Tison J. "Huffer’s" neuropathy. JAMA 1974; 229:
1083-84. 6. Leonard JC. 7. Cochrane R,
Oxprenolol et
al. Skin
and a psoriasis like eruption. Lancet 1975; i: 630. eruptions associated with propranolol. Archs Derm
1976; 112: 1173-74. 8. Bonerandi JJ, Follona J, Privati J. Apparition d’un psoriasis au cours d’un traitement par beta-bloquants (pindolol). Ann Derm Syph 1976; 103: 604-06. 9. van Joost T, Middelkamp Hup J, Ros RE. Dermatitis as a side effect of long term topical treatment with certain beta-blocking agents. Br J Dermatol (in press).
oped, over the course of several months, an itchy rash consisting of nummular psoriasiform eruptions localised on arms, legs, head, and trunk. He had been taking metoprolol for a year. Other drugs used included nitroglycerine and nitrazepam and, for a short time, alprenolol and isosorbide dinitrate. He was antinuclear factor negative; LE cells negative. Histopathological examination showed a picture of toxicoderma and Immunofluorescence tests of affe cted skin and of negative. After withdrawal of metoprolol the lesions slowly disappeared. After healing we did a provocation test with metoprolol (2 x 50 mg a day). After 6 days widespread skin eruptions reappeared. A positive patch test with metoprolol and alprenolol was found in this case. Some of the adverse reactions may be medicated immunologicallyiO but the mechanism could also be a pharmacological one via blocking of the p-receptors of the cells of the epidermis and a lowering of the intracellular cyclic AMP which results in more mitosis and which could be responsible for the psoriasiform eruption"1 The oral provocation test seemed to be of more value than patch-testing procedures in proving a causal relation between dermatitis and long-term metoprolol. eczema. serum
were
Department of Dermatology, University of Amsterdam, Binnengasthius, Amsterdam, Netherlands
H. A. M. NEUMANN TH. VAN JOOST W. WESTERHOF
HLA SEGREGATION RATIOS
SIR,-Dr Cudworth and his colleagues (Aug. 25, p. 389) observed an excess of HLA Al-B8 haplotypes (63-65% compared with the expected 50%) in the offspring of fathers segregating for this haplotype. The data were significant (p<0-05) for both diabetic and healthy families. Such a large deviation from the expected segregation ratio is unusual and implies either a rapid replacement in the population of other haplotypes by Al-B8 or a less-than-average reproductive performance for individuals with this haplotype. We have typed HLA in a series of families ascertained for a variety of purposes, none known to be related to the segregation of HLA haplotypes. No deviation from the expected 1:1 segregation ratio was observed in the offspring of parents heterozygous for Al-B8 and some other haplotypes. For male heterozygotes the segregation ratio was 45% Al-B8 (26 out of 58), and for females the ratio was 50% (31 out of 62). Department of Psychiatry, Division of Genetics, and Department of Pediatrics, School of Medicine and Dentistry, University of Rochester, Rochester, N.Y. 14642, U.S.A.
LOWELL R. WEITKAMP
10. Amos HE, Lake BG, Artis J. Possible role of antibody specific for a practolol metabolite in the pathogenesis of oculomucocutaneous syndrome. Br Med 11.
J 1978; i: 402-04. Gaylorde PM, Sarkany
I. Side effects of
practolol.
Br
Med J 1975;
i: 435.
hyperactive reflexes and bilateral Babinski signs, but had normal electromyograms and nerve conduction studies in all limbs. Reports of polyneuropathies in glue sniffers have usually involved mixtures of toluene and other solvents. Goto et aI.3 describe a motor predominant polyneuropathy in four people who "huffed" a mixture of chloroprene, n-hexane, toluene, and MEK. They ascribed the toxicity to the toluene exposure because the predominantly motor polyneuropathy was atypical of the usual mixed or mostly sensory polyneuropathy seen in pure n-hexane exposure. In another study4 car painters with chronic low level exposure to solvents containing toluene, xylene, butyl acetate, and white spirit had slower nerve-conduction velocities than did matched controls. I suggest that the neurotoxicity in AuBuchon’s patient arose from the synergistic effects of the ketone solvents and toluene. This patient may have had a genetic predisposition to the toxic effects of solvent exposure. Perhaps there are circumstances of mixed solvent exposure that lead to a pathological picture of acute segmental demyelination rather than to axonal degeneration with secondary demyelination. There have been reports of glue sniffing of solvent mixtures in which the clinical presentation resemble the Guillain-Barre syndrome.5 Despite the fact that a causal relationship between the spray painting and the polyneuropathy is not supported by quantitative estimates of exposure, this case does draw attention to the possibility of severe neurotoxicity arising from the combined effect of a mixture of solvents.
CLINICAL DATA AND PATCH AND CHALLENGE TESTS
with
Department of Neurology, Veterans Administration Outpatient Clinic,
Boston, Massachusetts 02108, U.S.A.
R. H. GOLDMAN
DERMATITIS AS SIDE-EFFECT OF LONG-TERM METOPROLOL
SIR,-Skin reactions
to p-adrenergic blocking drugs other practolol have been reported (for propranolol, oxprenolol, pindolol)6-S and dermatitis as a side-effect of long-term topical therapy with metoprolol has also been described.9 Here we report an eczematous and psoriasiform eruption that. developed in five patients during long-term therapy with metoprolol. To our knowledge these side-effects of oral metoprolol have not yet been recorded in print. Five patients, all men (mean age 59), were seen with eczematous and/or psoriasiform skin reactions during long-term oral treatment with metoprolol (mean duration 7 months). After withdrawal of the drug the skin eruptions disappeared slowly within weeks to months. Investigations and clinical data are summarised in the table. Four patients had patch tests with metoprolol, several other p-adrenergic blocking agents, and the European standard battery. Test concentrations of p-adrenergic blocking agents were as indicated in a previous report.9 In three patients a local or disseminated dermatitis reappeared 1 or 2 weeks after the oral provocation test. Patch tests to metoprolol were positive in only one patient, however; this patient (no. 1) also had a positive patch test to alprenolol, indicating a possible cross-reaction. This 62-year-old man devel-
than
3. Goto I, Matsumura M, Inoue N, Murai Y, Shida K, Santa T, Kuroiwa Y. Toxic polyneuropathy due to glue sniffing. J Neurol Neurosurg Psychiat
1974;37:848-53. 4.
Seppalainen AM, Husman KAJ, Martenson C. Neurophysiological effects of long-term exposure to a mixture of organic solvents. Scand J Work Envir
Health 1978; 4: 304-14. 5. Prockop LD, Alt M, Tison J. "Huffer’s" neuropathy. JAMA 1974; 229:
1083-84. 6. Leonard JC. 7. Cochrane R,
Oxprenolol et
al. Skin
and a psoriasis like eruption. Lancet 1975; i: 630. eruptions associated with propranolol. Archs Derm
1976; 112: 1173-74. 8. Bonerandi JJ, Follona J, Privati J. Apparition d’un psoriasis au cours d’un traitement par beta-bloquants (pindolol). Ann Derm Syph 1976; 103: 604-06. 9. van Joost T, Middelkamp Hup J, Ros RE. Dermatitis as a side effect of long term topical treatment with certain beta-blocking agents. Br J Dermatol (in press).
oped, over the course of several months, an itchy rash consisting of nummular psoriasiform eruptions localised on arms, legs, head, and trunk. He had been taking metoprolol for a year. Other drugs used included nitroglycerine and nitrazepam and, for a short time, alprenolol and isosorbide dinitrate. He was antinuclear factor negative; LE cells negative. Histopathological examination showed a picture of toxicoderma and Immunofluorescence tests of affe cted skin and of negative. After withdrawal of metoprolol the lesions slowly disappeared. After healing we did a provocation test with metoprolol (2 x 50 mg a day). After 6 days widespread skin eruptions reappeared. A positive patch test with metoprolol and alprenolol was found in this case. Some of the adverse reactions may be medicated immunologicallyiO but the mechanism could also be a pharmacological one via blocking of the p-receptors of the cells of the epidermis and a lowering of the intracellular cyclic AMP which results in more mitosis and which could be responsible for the psoriasiform eruption"1 The oral provocation test seemed to be of more value than patch-testing procedures in proving a causal relation between dermatitis and long-term metoprolol. eczema. serum
were
Department of Dermatology, University of Amsterdam, Binnengasthius, Amsterdam, Netherlands
H. A. M. NEUMANN TH. VAN JOOST W. WESTERHOF
HLA SEGREGATION RATIOS
SIR,-Dr Cudworth and his colleagues (Aug. 25, p. 389) observed an excess of HLA Al-B8 haplotypes (63-65% compared with the expected 50%) in the offspring of fathers segregating for this haplotype. The data were significant (p<0-05) for both diabetic and healthy families. Such a large deviation from the expected segregation ratio is unusual and implies either a rapid replacement in the population of other haplotypes by Al-B8 or a less-than-average reproductive performance for individuals with this haplotype. We have typed HLA in a series of families ascertained for a variety of purposes, none known to be related to the segregation of HLA haplotypes. No deviation from the expected 1:1 segregation ratio was observed in the offspring of parents heterozygous for Al-B8 and some other haplotypes. For male heterozygotes the segregation ratio was 45% Al-B8 (26 out of 58), and for females the ratio was 50% (31 out of 62). Department of Psychiatry, Division of Genetics, and Department of Pediatrics, School of Medicine and Dentistry, University of Rochester, Rochester, N.Y. 14642, U.S.A.
LOWELL R. WEITKAMP
10. Amos HE, Lake BG, Artis J. Possible role of antibody specific for a practolol metabolite in the pathogenesis of oculomucocutaneous syndrome. Br Med 11.
J 1978; i: 402-04. Gaylorde PM, Sarkany
I. Side effects of
practolol.
Br
Med J 1975;
i: 435.