- Email: [email protected]
The gender gap in autoimmune disease
CORRESPONDENCE
3
Feinberg WM. Anticoagulation for prevention of stroke. Neurology 1998; 51 (Suppl 3): S20–22.
The gender gap in autoimmune disease Sir—In your Sept 23 news item,1 Michael McCarthy notes that women are two to three times more likely to develop multiple sclerosis and rheumatoid arthritis, and make up 75% of cases of myasthenia gravis. We agree that, in most autoimmune diseases, women are more likely to develop disease than men. However, we wish to make two points—first, myasthenia gravis (MG) seems to be an autoimmune disease with a more complicated and idiosyncratic distribution between the sexes, and second, the 75% value mentioned above is incorrect. Although MG is generally seen as an autoimmune disease with a 2:1 femaleto-male ratio (but not the 3:1 implied by the 75% value mentioned), this ratio refers to the prevalence rather than to the incidence ratio. We have shown that the female-to-male incidence ratio is 1:1, which agrees with the unequal prevalence ratio.2 Specifically, of the 601 incident cases identified in Greece between 1986 and 1997, 301 were women and 300 men. The discrepancy between the incidence and prevalence ratios is clearly related to differences in the average age of onset between women and men (40·1 vs 55·1 years), which, since mortality from MG is very low, means that the theoretical life expectancy after MG onset in women is almost double that in males (40·9 years and 23·4 years, respectively). Since most MG patients never go into total remission, this difference in life expectancy results in a similar difference in disease duration, which would directly affect the apparent prevalence ratio.2 In the same news item,1 J Lee Nelson asks why, if hormones are a key disease factor, we don’t see these diseases peaking in young adults, especially in women, when the concentrations of these hormones are highest. There is, however, a characteristic peak of MG disease in young women in the second and third decades3 that contibutes to the described differences in the average age at onset. However, whether hormones play a critical part in the development of the disease is still unclear. Leker and colleagues4 have shown that sex hormones do not seem to influence susceptibility to and severity of experimental MG. Despite the sex-specific incidence peak
234
in young women, the overall incidence of MG is the same in women and men because of a male-specific peak in old age (in the sixth and seventh decades), the cause of which is unknown. In conclusion, in MG, the expected impact of sex hormones is seen (ie, the female-specific peak at a young age), but a second event (the male-specific peak later in life)3 results in a 1:1 femaleto-male probability of disease development, despite the unequal prevalence ratio. Konstantinos Poulas, *Socrates J Tzartos Department of Biochemistry, Hellenic Pasteur Institute, Athens 11521, Greece (e-mail: [email protected]) 1 2
3
4
McCarthy M. The “gender gap” in autoimmune disease. Lanet 2000; 356: 1088. Poulas K, Tsibri E, Papanastasiou D, et al. Equal male and female incidence of myasthenia gravis. Neurology 2000; 54: 1202–03. Drachman D. Myasthenia gravis. In: Rose N, Mackay I, eds. The autoimmune diseases, 3rd edn. San Diego: Academic Press, 1998: 637–62. Leker RR, Karni A, Brenner T, Weidenfeld J, Abransky O. Effects of sex hormones on experimental autoimmune myasthenia gravis. Eur J Neurol 2000; 7: 203–06.
Wound botulism in the UK Sir—M Jensenius and colleagues (Sept 30, p 1160)1 report a heroin user in Norway who presented with a wobbly head and developed respiratory failure because of wound botulism, although they could not identify the toxin type by mouse bioassay. We saw in the UK, a woman aged 34 years who presented in May, 2000, with pneumonia and respiratory failure requiring intubation and mechanical ventilation for 5 weeks due to toxin type A. Our patient had regularly injected heroin subcutaneously or intramuscularly and 6 months previously had developed injection-related abscesses in both buttocks. On admission she had variable ptosis, an external opthlamoplegia, sluggish papillary responses and severe proximallimb and respiratory-muscle weakness. Tendon reflexes were present throughout with flexor plantar responses. Blood electrolytes and creatine kinase were normal and serum acetylcholine receptor and HIV antibodies were negative. Peripheralnerve conduction was normal but compound muscle action potentials were reduced. Electromyography showed profuse fibrillation and jitter with no incremental response on posttetanic repetitive nerve stimulation. Cerebral spinal fluid was normal. Intravenous edophonium resulted in
partial improvement in the ptosis and ophthalmoplegia but no improvement in limb or respiratory-muscle weakness. She had several skin lesions on the buttocks related to old injection sites, adjacent to one of which was a fluctuant abscess. We diagnosed botulism and treated her with specific antitoxin and high-dose benzylpenicillin. Mouse bioassay confirmed the presence of Clostridium botulinum toxin type A in blood, and toxin-A-producing organisms were grown from pus aspirated from the buttock abscess. The patient made a full recovery. The most common form of botulism seen in the UK results from the ingestion of toxin in food with the last reported cases, in 1998, being caused by contaminated home-preserved mushrooms.2 Wound botulism has been reported in injecting drug users in the USA, who used Mexican black tar heroin.3 Similar cases have been reported from Norway and Switzerland, but those and our case were associated with this form of heroin. Drug users injecting subcutaneously or intramuscularly seem susceptible to clostridial infections; several in the UK were due to C novyi.4 Cases are, however, rare. Other people who frequently inject, such as patients with insulin-dependent diabetes, do not seem prone to this disorder. C botulinum is an obligate anaerobe and spores are unlikely to germinate in healthy tissue, so infection probably occurred from inoculation of tissue devitalised by recent abscesses. Wound botulism should be considered in patients with features compatible with botulism, if there is a recent history of abscess, and when epidemiological investigation suggests that a food-borne cause is unlikely. We agree with Jensenius and colleagues that early treatment with antitoxin and eradication of abscesses are important measures in management but, because of the rarity of botulism, the diagnosis in isolated cases might be delayed. B S Athwal, *A N Gale, M M Brett, B D Youl *Department of Neurosciences, Royal Free Hospital, London NW3 2QG, UK; and Food Safety Microbiology Laboratory, PHLS Central Public Health Laboratory, London 1
2
3
4
Jensenius M, Løvstad RZ, Dhaenens G, Rørvik LM. A heroin user with a wobbly head. Lancet 2000; 356: 1160. Roberts EJ, Wales JM, Brett MM, Bradding P. Cranial-nerve palsies and vomiting. Lancet 1998; 352: 1674. Passaro DJ, Werner SB, McGee J, et al. Wound botulism associated with black tar heroin among injecting drug users. JAMA 1998; 279: 859–63. Christie B. Gangrene bug “killed” 35 heroin users. BMJ 2000; 320: 1690.
THE LANCET • Vol 357 • January 20, 2001
For personal use only. Not to be reproduced without permission of The Lancet.
3
Feinberg WM. Anticoagulation for prevention of stroke. Neurology 1998; 51 (Suppl 3): S20–22.
The gender gap in autoimmune disease Sir—In your Sept 23 news item,1 Michael McCarthy notes that women are two to three times more likely to develop multiple sclerosis and rheumatoid arthritis, and make up 75% of cases of myasthenia gravis. We agree that, in most autoimmune diseases, women are more likely to develop disease than men. However, we wish to make two points—first, myasthenia gravis (MG) seems to be an autoimmune disease with a more complicated and idiosyncratic distribution between the sexes, and second, the 75% value mentioned above is incorrect. Although MG is generally seen as an autoimmune disease with a 2:1 femaleto-male ratio (but not the 3:1 implied by the 75% value mentioned), this ratio refers to the prevalence rather than to the incidence ratio. We have shown that the female-to-male incidence ratio is 1:1, which agrees with the unequal prevalence ratio.2 Specifically, of the 601 incident cases identified in Greece between 1986 and 1997, 301 were women and 300 men. The discrepancy between the incidence and prevalence ratios is clearly related to differences in the average age of onset between women and men (40·1 vs 55·1 years), which, since mortality from MG is very low, means that the theoretical life expectancy after MG onset in women is almost double that in males (40·9 years and 23·4 years, respectively). Since most MG patients never go into total remission, this difference in life expectancy results in a similar difference in disease duration, which would directly affect the apparent prevalence ratio.2 In the same news item,1 J Lee Nelson asks why, if hormones are a key disease factor, we don’t see these diseases peaking in young adults, especially in women, when the concentrations of these hormones are highest. There is, however, a characteristic peak of MG disease in young women in the second and third decades3 that contibutes to the described differences in the average age at onset. However, whether hormones play a critical part in the development of the disease is still unclear. Leker and colleagues4 have shown that sex hormones do not seem to influence susceptibility to and severity of experimental MG. Despite the sex-specific incidence peak
234
in young women, the overall incidence of MG is the same in women and men because of a male-specific peak in old age (in the sixth and seventh decades), the cause of which is unknown. In conclusion, in MG, the expected impact of sex hormones is seen (ie, the female-specific peak at a young age), but a second event (the male-specific peak later in life)3 results in a 1:1 femaleto-male probability of disease development, despite the unequal prevalence ratio. Konstantinos Poulas, *Socrates J Tzartos Department of Biochemistry, Hellenic Pasteur Institute, Athens 11521, Greece (e-mail: [email protected]) 1 2
3
4
McCarthy M. The “gender gap” in autoimmune disease. Lanet 2000; 356: 1088. Poulas K, Tsibri E, Papanastasiou D, et al. Equal male and female incidence of myasthenia gravis. Neurology 2000; 54: 1202–03. Drachman D. Myasthenia gravis. In: Rose N, Mackay I, eds. The autoimmune diseases, 3rd edn. San Diego: Academic Press, 1998: 637–62. Leker RR, Karni A, Brenner T, Weidenfeld J, Abransky O. Effects of sex hormones on experimental autoimmune myasthenia gravis. Eur J Neurol 2000; 7: 203–06.
Wound botulism in the UK Sir—M Jensenius and colleagues (Sept 30, p 1160)1 report a heroin user in Norway who presented with a wobbly head and developed respiratory failure because of wound botulism, although they could not identify the toxin type by mouse bioassay. We saw in the UK, a woman aged 34 years who presented in May, 2000, with pneumonia and respiratory failure requiring intubation and mechanical ventilation for 5 weeks due to toxin type A. Our patient had regularly injected heroin subcutaneously or intramuscularly and 6 months previously had developed injection-related abscesses in both buttocks. On admission she had variable ptosis, an external opthlamoplegia, sluggish papillary responses and severe proximallimb and respiratory-muscle weakness. Tendon reflexes were present throughout with flexor plantar responses. Blood electrolytes and creatine kinase were normal and serum acetylcholine receptor and HIV antibodies were negative. Peripheralnerve conduction was normal but compound muscle action potentials were reduced. Electromyography showed profuse fibrillation and jitter with no incremental response on posttetanic repetitive nerve stimulation. Cerebral spinal fluid was normal. Intravenous edophonium resulted in
partial improvement in the ptosis and ophthalmoplegia but no improvement in limb or respiratory-muscle weakness. She had several skin lesions on the buttocks related to old injection sites, adjacent to one of which was a fluctuant abscess. We diagnosed botulism and treated her with specific antitoxin and high-dose benzylpenicillin. Mouse bioassay confirmed the presence of Clostridium botulinum toxin type A in blood, and toxin-A-producing organisms were grown from pus aspirated from the buttock abscess. The patient made a full recovery. The most common form of botulism seen in the UK results from the ingestion of toxin in food with the last reported cases, in 1998, being caused by contaminated home-preserved mushrooms.2 Wound botulism has been reported in injecting drug users in the USA, who used Mexican black tar heroin.3 Similar cases have been reported from Norway and Switzerland, but those and our case were associated with this form of heroin. Drug users injecting subcutaneously or intramuscularly seem susceptible to clostridial infections; several in the UK were due to C novyi.4 Cases are, however, rare. Other people who frequently inject, such as patients with insulin-dependent diabetes, do not seem prone to this disorder. C botulinum is an obligate anaerobe and spores are unlikely to germinate in healthy tissue, so infection probably occurred from inoculation of tissue devitalised by recent abscesses. Wound botulism should be considered in patients with features compatible with botulism, if there is a recent history of abscess, and when epidemiological investigation suggests that a food-borne cause is unlikely. We agree with Jensenius and colleagues that early treatment with antitoxin and eradication of abscesses are important measures in management but, because of the rarity of botulism, the diagnosis in isolated cases might be delayed. B S Athwal, *A N Gale, M M Brett, B D Youl *Department of Neurosciences, Royal Free Hospital, London NW3 2QG, UK; and Food Safety Microbiology Laboratory, PHLS Central Public Health Laboratory, London 1
2
3
4
Jensenius M, Løvstad RZ, Dhaenens G, Rørvik LM. A heroin user with a wobbly head. Lancet 2000; 356: 1160. Roberts EJ, Wales JM, Brett MM, Bradding P. Cranial-nerve palsies and vomiting. Lancet 1998; 352: 1674. Passaro DJ, Werner SB, McGee J, et al. Wound botulism associated with black tar heroin among injecting drug users. JAMA 1998; 279: 859–63. Christie B. Gangrene bug “killed” 35 heroin users. BMJ 2000; 320: 1690.
THE LANCET • Vol 357 • January 20, 2001
For personal use only. Not to be reproduced without permission of The Lancet.