- Email: [email protected]
Necrotising fasciitis
(p=0001).
There
was
no
significant
difference between
observed and expected figures for the groups of clinicians who did smaller numbers of procedures. This analysis of the evidence suggests that some of the experienced clinicians were skilled operators and had significantly fewer failures than would otherwise be expected. However, there are several weaknesses that temper this conclusion. First, in 47% of cases the name of the clinician who did the second quinacrine insertion was not provided. Second, a definitive analysis should take into account the length of follow-up. If the successful clinicians did a proportionally larger number of insertions in the recent past, there would have been little time for failures to show up. It is possible that the more "skilful" clinicians used a different insertion technique, treated older women, or worked where follow-up was less efficient than elsewhere, thus lowering their apparent failure rates. David C Sokal, Robert
Hanenberg
Family Health International, Research Triangle Park, NC 27709, USA
1 Stovall
TG, Ling FW, Henry GM, Ryan GM Jr. Method failures of laparoscopic tubal sterilization in a residency training program: a
2
3
comparison of the tubal ring and spring-loaded clip. JReprod Med 1991; 36: 283-86. Guzman-Serani R, Bernales A, Cole LP. Quinacrine hydrochloride pellets: three-year follow-up on a non-surgical method of female sterilization. Contracept Deliv Syst 1984; 5: 131-35. Bhatt R, Waszak CS. Four-year follow-up of insertion of quinacrine hydrochloride pellets as a means of nonsurgical female sterilization. Fertil Steril 1985; 44: 303-06.
4
5
Vessey M, Huggins G, Lawless M, Yeates D. Tubal sterilization: findings in a large prospective study. Br J Obstet Gynaecol 1983; 90: 203-09. Wilcox LS, Jamison P, Peterson HB, Hughes J. Ten-year pregnancy rates after unipolar and bipolar sterilisation. Presented at 47th Annual Meeting of the American Fertility Society, October, 1991, Orlando, Florida (Abstract O-028).
Necrotising fasciitis SIR—Streptococcal necrotising fasciitis, first described in 20 patients in Peking (Beijing) by F L Meleney in 1924 had an evil reputation, not ameliorated by the advent of penicillin. In the past decade, however, case fatality rates have fallen to 29-33% with surgical debridement or amputation to remove the necrotic tissue combined with early use of benzylpenicillin. A further advance was the use of hyperbaric oxygen. In the past few years our understanding of streptococcal sepsis, with its attendant multiorgan failure and shock, has been revolutionised by the concept of superantigens.1,2 Superantigens, such as SPE-A, SPE-B, and SPE-C, secreted by some strains of beta-haemolytic streptococci cause millions of clones of T cells to be activated instead of just a few. The resultant excessive activation of cytokines, complement, and clotting cascades, plus production of oxygen-free radicals and nitric oxide cause the shock and multiorgan failure. The key roles are played by T4 cells and tumour necrosis factors (TNF) a and &bgr;. The discovery that intravenous immunoglobulin G (IVIGG) can reverse the hyperproliferation of T cells, neutralise superantigens,3 and down-regulate the production of TNF4 prompted us to use IVIGG to treat streptococcal necrotising fasciitis. A 59-year-old woman was referred to our infectious diseases unit in January, 1994, complaining of several days of diarrhoea and vomiting with a painful right shoulder and generally feeling very unwell. She had pyrexia (40°C), her pulse rate was 92/min, respiratory rate 22/min, and blood pressure 160/90 mm Hg. The right shoulder was painful on movement. There was a painful swelling below the right axilla in the chest wall with slight erythema of the overlying
The
skin.
clinical
diagnosis was necrotising fasciitis, probably streptococcal, and she was started on intravenous fluids, intravenous benzylpenicillin, flucloxacillin, and g. The IVIGG on 24 h 25 was the third day. was repeated later and given g The patient had a stormy 72 h. Her blood pressure fell to
ceftriazone, and IVIGG (Sandoglobulin) 12
110/65 mm Hg. She became oliguric 27-6 mmol/L, confused, delirious, and finally comatose with seizures. Examination revealed ohisthotonos with marked neck stiffness. A brain scan and lumbar puncture did not reveal any significant abnormalities. The swelling in the chest wall continued to enlarge and extend to affect the right breast. The overlying skin showed fine desquamation. Signs of pulmonary oedema and a right pleural effusion developed, confirmed on X-ray. Dexamethasone and albumin were added to her therapy. She began to improve and was able to speak. During the second week in hospital she started to shed large pieces of skin from her hands and feet, a hallmark of toxic shock from streptococci. A computerised tomographic scan of the chest showed a large necrotic mass in the right chest wall. Surgical debridement and amputation of the breast were considered but the swelling and pain began to subside and this was not done. She was discharged home after 39 days in hospital and has remained well, although requiring captopril for her
hypertension. When Takei et aP reported on the ability of pooled IgG to neutralise superantigens, the editor of the Journal of Clinical Investigation waxed lyrical on its potential to cure diseases ("Intravenous superantigen-induced IgG: Supertherapy for Superantigens?"). IVIGG was used successfully by Barry et all to treat a patient with streptococcal toxic shock and IgG has been very successful in the treatment of Kawasaki disease, another superantigen-induced disease. Necrotising fasciitis may prove to be another success for this therapy but a double-blind trial of IVIGG would probably be impossible because of ethical considerations and the intense public interest in "the disease that devours flesh". JM
Yong
Infectious Diseases Unit, Harold Wood Hospital, Romford, Essex RM3 OBE, UK
1 2 3
4
5
Zumla A. Superantigens, T cells and microbes. Clin Infect Dis 1992; 15: 313-20. Kotb M. Role of superantigens in the pathogenesis of infectious diseases and their sequelae. Curr Opin Infect Dis 1992; 5: 364-74. Takai S, et al. Intravenous immunoglobulin contains antibodies inhibitory to activation of T cells by staphylococcal toxin superantigens. J Clin Invest 1992; 91: 602-07. Achiron A, et al. Intravenous immunoglobulin treatment of experimental T cell-mediated auto-immune disease. J Clin Invest 1994; 93: 600-05. Barry W, et al. Intravenous immunoglobulin therapy for toxic shock syndrome. JAMA 1992; 267: 3315-16.
Streptococcus pyogenes infection has always potentialy fatal. Despite current UK media interest, there is nothing new or mysterious about these infections and they are probably being encountered albeit infrequently, SIR—Invasive
been
the country. The latter half of the 20th century had sharp fall in the incidence and severity of invasive streptococcal infections-but over the past decade there has been a renewed virulence of this organism, associated with sporadic outbreaks of serious soft-tissue infection and an increase in the frequency of identification of the organism in blood cultures in the USA and UK. Outbreaks of rheumatic fever have also been seen in the USA. This increased pathogenicity is due to a re-emergence of strains producing pyrogenic exotoxin-A.’1 Although most S pyogenes infections respond readily to benzylpenicillin the severest remain resistant. These all
over
seen a
1427
organisms are nearly always sensitive to benzylpenicillin in vitro but are resistant in vivo. This resistance to penicillin therapy has been well recognised for over 40 years and has been variously attributed to the Eagle effect, the poor post.antibiotic effect of penicillin, and the poor duration of action of penicillin. 2,3 Vancomycin and clindamycin both have a very good activity against gram-positive cocci and although streptococcal resistance to clindamycinhas been described it is almost unknown with vancomycin. We have experience of penicillin failure in severe, life-threatening, invasive streptococcal infection and the successful treatment with vancomycin5 and recommend that all severe streptococcal infections should be treated with vancomycin as first-line therapy. R J Holdsworth, D Parratt Ninewells
Hospital, Dundee DD1 9SY, UK
Stevens DL, Tanner MH, Winship J, et al. Severe group A streptococcal infections associated with a toxic-shock like syndrome and scarlet fever toxin A. N Engl J Med 1989; 321: 1-7. 2 Stevens DL, Gibbons AE, Bergstrom R, Winn V. The Eagle effect revisited: efficacy of clindamycin and penicillin in the treatment of streptococcal myositis J Infect Dis 1988; 158: 23-28. 3 Craig WA, Vogelman B. The post-antibiotic effect. Ann Intern Med 1987; 106: 900-02. 4 Kohn J, Evans AJ. Group A streptococci resistant to clindamycin. BMJ 1970; ii: 423. 5 Holdsworth RJ, Smith D, Parratt D, Gunn A. Treatment of invasive Streptococcus pyogenes infection with vancomycin. J R Coll Surg Edinb (in press). 1
Interferon-&agr;2b for disease
refractory ocular Behçet’s
SIR—Behçet’s disease is a multisystem disorder mainly characterised by recurrent oral and genital ulcers, skin lesions, and inflammatory eye disease. Patients with ocular involvement have a poor visual prognosis because of recurrent severe retinal vasculitis with concomitant retinal and optic nerve ischaemia.’1 Current therapy includes high-dose corticosteroids, cyclosporin, azathioprine, and chlorambucil. We report colchicine, cyclophosphamide, 3 patients, all satisfying the International Behçet’s Study Group criteria for Behçet’s disease,2 with previously refractory intraocular inflammation who responded to with interferon-a2b. The first case was a 31-year-old male with ocular Beh4;et’s disease since 1988. Despite treatment with prednisone,
1988 another acute relapse of intraocular inflammation associated with neurological symptoms was halted within days by the combination of prednisone, cyclosporin, and interferon-a2b. Complete remission was observed and all treatment was withdrawn in 1991. Visual acuity in the left eye of 6/18 has since remained stable. A 35-year-old man with ocular Behçet’s disease since 1986 was treated conventionally with varying combinations of prednisone, cyclosporin, azathioprine, chlorambucil, and cyclophosphamide. Despite therapy, useful vision was lost in the right eye in 1991 because of severe necrotising retinitis followed by retinal and optic atrophy. Visual acuity in the left eye decreased to 6/24. Retinitis recurred in the left eye in January, 1994, while the patient was on cyclophosphamide and cyclosporin. Cyclosporin was replaced by interferon-a2b at the above dose, resulting in prompt resolution of the retinitis within a week and improvement of visual acuity from finger counting to 6/12. Beneficial effects of interferon-a in Behçet’s disease have been documented for mucocutaneous lesions and arthritis.’,’ Therapeutic use for ocular manifestations of the disease has been described as case reports, but with contradictory results.3,5 Ocular side-effects of systemic interferon-a therapy have also been reported. Our observations on 3 patients with previously refractory ocular Behçet’s disease provide evidence that interferon-a2b is a new important adjuvant in the management of the disease. However, studies with larger numbers of patients and longer follow-up are needed to determine the exact role of interferon-a2b in the management of sight-threatening complications of Behçet’s disease, and possibly other forms of intraocular inflammatory disease. E J Feron, A Rothova, P M van Hagen, G S Baarsma, M S A Suttorp-Schulten Rotterdam Eye Hospital, PO Box 70030, 3011 BH Rotterdam, Netherlands; Department of Ophthalmo-immunology, Netherlands Ophthalmic Research Institute, Amsterdam; Department of Immunology and Internal Medicine, Academic Hospital Rotterdam, Rotterdam; and F C Donders Institute for Ophthalmology, Utrecht 1 2 3
4
treatment
cyclosporin, azathioprine, cyclophosphamide, colchicine, chlorambucil in varying combinations, disease progressed and visual acuity deteriorated to 6/36 in the right eye and counting fingers in the left eye. In November, 1992,
5
Towler HMA,
Lightman S. Visual prognosis in Behçet’s disease. Ocul Immunol Inflamm 1993; 1: 249-54. International Study Group for Behçet’s disease. Criteria for diagnosis of Behçet’s disease. Lancet 1990; 335: 1078-80. Tsambaos D, Eichelberg D, Goos M. Behçet’s syndrome: treatment with recombinant leukocyte alpha-interferon. Arch Dermatol Res 1986; 278: 335-36. Dündar S, Özcebe OI, Özdemir O, Kirazli S. Alpha-interferon in the treatment of Behçet’s disease. In: Godeau P, Wechsler B, eds. Behçet’s disease. Elsevier Science Publishers, 1993: 665-70. Durand JM, Kaplanski G, Telle H, Soubeyrand J, Paulo F. Beneficial effect of interferon-&agr;2b in Behçet’s disease. Arthritis Rheum 1993; 36: 1025-26.
and
a severe exacerbation of retinitis was treated with interferon-a2b 3 million IU subcutaneously 3 times a week combined with colchicine and a low dose of prednisone. Subsequent complete remission of ocular signs and symptoms has been maintained on this regimen. Discontinuation of interferon injections for one week was immediately followed by a relapse, which responded promptly to restarting the injections. A man aged 42 was treated with combinations of prednisone, cyclosporin, cyclophosphamide, and colchicine for systemic and ocular manifestations of Behçet’s disease since 1979. This did not prevent progression of vaso-occlusive retinitis and vision was subsequently lost in the right eye in 1985. A 3-month course of interferon-a2b at the above dose was added to his therapy with cyclosporin and colchicine, with favourable results on arthritis and uveitis. Disease activity was controlled for 3 years, but in
1428
Take two
glasses of wine and see
me
in the
morning SIR—Ever since the "French paradox" became public, much has been published about those constituents that seem to be responsible for the healthful attributes of wine, particularly cardiovascular wellness.’Several wine constituents, mostly antioxidants, such as the ubiquitous quercetin, epicatechin, and lately, resveratrol, have been either identified or
postulated as decreasing low-density lipoprotein (LDL) and carrying out other protective duties such as aiding the retention of the integrity of membranes.2 In addition, wine and grape components have been found to act as vasorelaxants.’ Furthermore, epidemiological studies indicate that moderate consumption of ethanol decreases LDL and thus the risk of myocardial infarction/ What many who extol the virtues of wine seem to have missed is that
There
was
no
significant
difference between
observed and expected figures for the groups of clinicians who did smaller numbers of procedures. This analysis of the evidence suggests that some of the experienced clinicians were skilled operators and had significantly fewer failures than would otherwise be expected. However, there are several weaknesses that temper this conclusion. First, in 47% of cases the name of the clinician who did the second quinacrine insertion was not provided. Second, a definitive analysis should take into account the length of follow-up. If the successful clinicians did a proportionally larger number of insertions in the recent past, there would have been little time for failures to show up. It is possible that the more "skilful" clinicians used a different insertion technique, treated older women, or worked where follow-up was less efficient than elsewhere, thus lowering their apparent failure rates. David C Sokal, Robert
Hanenberg
Family Health International, Research Triangle Park, NC 27709, USA
1 Stovall
TG, Ling FW, Henry GM, Ryan GM Jr. Method failures of laparoscopic tubal sterilization in a residency training program: a
2
3
comparison of the tubal ring and spring-loaded clip. JReprod Med 1991; 36: 283-86. Guzman-Serani R, Bernales A, Cole LP. Quinacrine hydrochloride pellets: three-year follow-up on a non-surgical method of female sterilization. Contracept Deliv Syst 1984; 5: 131-35. Bhatt R, Waszak CS. Four-year follow-up of insertion of quinacrine hydrochloride pellets as a means of nonsurgical female sterilization. Fertil Steril 1985; 44: 303-06.
4
5
Vessey M, Huggins G, Lawless M, Yeates D. Tubal sterilization: findings in a large prospective study. Br J Obstet Gynaecol 1983; 90: 203-09. Wilcox LS, Jamison P, Peterson HB, Hughes J. Ten-year pregnancy rates after unipolar and bipolar sterilisation. Presented at 47th Annual Meeting of the American Fertility Society, October, 1991, Orlando, Florida (Abstract O-028).
Necrotising fasciitis SIR—Streptococcal necrotising fasciitis, first described in 20 patients in Peking (Beijing) by F L Meleney in 1924 had an evil reputation, not ameliorated by the advent of penicillin. In the past decade, however, case fatality rates have fallen to 29-33% with surgical debridement or amputation to remove the necrotic tissue combined with early use of benzylpenicillin. A further advance was the use of hyperbaric oxygen. In the past few years our understanding of streptococcal sepsis, with its attendant multiorgan failure and shock, has been revolutionised by the concept of superantigens.1,2 Superantigens, such as SPE-A, SPE-B, and SPE-C, secreted by some strains of beta-haemolytic streptococci cause millions of clones of T cells to be activated instead of just a few. The resultant excessive activation of cytokines, complement, and clotting cascades, plus production of oxygen-free radicals and nitric oxide cause the shock and multiorgan failure. The key roles are played by T4 cells and tumour necrosis factors (TNF) a and &bgr;. The discovery that intravenous immunoglobulin G (IVIGG) can reverse the hyperproliferation of T cells, neutralise superantigens,3 and down-regulate the production of TNF4 prompted us to use IVIGG to treat streptococcal necrotising fasciitis. A 59-year-old woman was referred to our infectious diseases unit in January, 1994, complaining of several days of diarrhoea and vomiting with a painful right shoulder and generally feeling very unwell. She had pyrexia (40°C), her pulse rate was 92/min, respiratory rate 22/min, and blood pressure 160/90 mm Hg. The right shoulder was painful on movement. There was a painful swelling below the right axilla in the chest wall with slight erythema of the overlying
The
skin.
clinical
diagnosis was necrotising fasciitis, probably streptococcal, and she was started on intravenous fluids, intravenous benzylpenicillin, flucloxacillin, and g. The IVIGG on 24 h 25 was the third day. was repeated later and given g The patient had a stormy 72 h. Her blood pressure fell to
ceftriazone, and IVIGG (Sandoglobulin) 12
110/65 mm Hg. She became oliguric 27-6 mmol/L, confused, delirious, and finally comatose with seizures. Examination revealed ohisthotonos with marked neck stiffness. A brain scan and lumbar puncture did not reveal any significant abnormalities. The swelling in the chest wall continued to enlarge and extend to affect the right breast. The overlying skin showed fine desquamation. Signs of pulmonary oedema and a right pleural effusion developed, confirmed on X-ray. Dexamethasone and albumin were added to her therapy. She began to improve and was able to speak. During the second week in hospital she started to shed large pieces of skin from her hands and feet, a hallmark of toxic shock from streptococci. A computerised tomographic scan of the chest showed a large necrotic mass in the right chest wall. Surgical debridement and amputation of the breast were considered but the swelling and pain began to subside and this was not done. She was discharged home after 39 days in hospital and has remained well, although requiring captopril for her
hypertension. When Takei et aP reported on the ability of pooled IgG to neutralise superantigens, the editor of the Journal of Clinical Investigation waxed lyrical on its potential to cure diseases ("Intravenous superantigen-induced IgG: Supertherapy for Superantigens?"). IVIGG was used successfully by Barry et all to treat a patient with streptococcal toxic shock and IgG has been very successful in the treatment of Kawasaki disease, another superantigen-induced disease. Necrotising fasciitis may prove to be another success for this therapy but a double-blind trial of IVIGG would probably be impossible because of ethical considerations and the intense public interest in "the disease that devours flesh". JM
Yong
Infectious Diseases Unit, Harold Wood Hospital, Romford, Essex RM3 OBE, UK
1 2 3
4
5
Zumla A. Superantigens, T cells and microbes. Clin Infect Dis 1992; 15: 313-20. Kotb M. Role of superantigens in the pathogenesis of infectious diseases and their sequelae. Curr Opin Infect Dis 1992; 5: 364-74. Takai S, et al. Intravenous immunoglobulin contains antibodies inhibitory to activation of T cells by staphylococcal toxin superantigens. J Clin Invest 1992; 91: 602-07. Achiron A, et al. Intravenous immunoglobulin treatment of experimental T cell-mediated auto-immune disease. J Clin Invest 1994; 93: 600-05. Barry W, et al. Intravenous immunoglobulin therapy for toxic shock syndrome. JAMA 1992; 267: 3315-16.
Streptococcus pyogenes infection has always potentialy fatal. Despite current UK media interest, there is nothing new or mysterious about these infections and they are probably being encountered albeit infrequently, SIR—Invasive
been
the country. The latter half of the 20th century had sharp fall in the incidence and severity of invasive streptococcal infections-but over the past decade there has been a renewed virulence of this organism, associated with sporadic outbreaks of serious soft-tissue infection and an increase in the frequency of identification of the organism in blood cultures in the USA and UK. Outbreaks of rheumatic fever have also been seen in the USA. This increased pathogenicity is due to a re-emergence of strains producing pyrogenic exotoxin-A.’1 Although most S pyogenes infections respond readily to benzylpenicillin the severest remain resistant. These all
over
seen a
1427
organisms are nearly always sensitive to benzylpenicillin in vitro but are resistant in vivo. This resistance to penicillin therapy has been well recognised for over 40 years and has been variously attributed to the Eagle effect, the poor post.antibiotic effect of penicillin, and the poor duration of action of penicillin. 2,3 Vancomycin and clindamycin both have a very good activity against gram-positive cocci and although streptococcal resistance to clindamycinhas been described it is almost unknown with vancomycin. We have experience of penicillin failure in severe, life-threatening, invasive streptococcal infection and the successful treatment with vancomycin5 and recommend that all severe streptococcal infections should be treated with vancomycin as first-line therapy. R J Holdsworth, D Parratt Ninewells
Hospital, Dundee DD1 9SY, UK
Stevens DL, Tanner MH, Winship J, et al. Severe group A streptococcal infections associated with a toxic-shock like syndrome and scarlet fever toxin A. N Engl J Med 1989; 321: 1-7. 2 Stevens DL, Gibbons AE, Bergstrom R, Winn V. The Eagle effect revisited: efficacy of clindamycin and penicillin in the treatment of streptococcal myositis J Infect Dis 1988; 158: 23-28. 3 Craig WA, Vogelman B. The post-antibiotic effect. Ann Intern Med 1987; 106: 900-02. 4 Kohn J, Evans AJ. Group A streptococci resistant to clindamycin. BMJ 1970; ii: 423. 5 Holdsworth RJ, Smith D, Parratt D, Gunn A. Treatment of invasive Streptococcus pyogenes infection with vancomycin. J R Coll Surg Edinb (in press). 1
Interferon-&agr;2b for disease
refractory ocular Behçet’s
SIR—Behçet’s disease is a multisystem disorder mainly characterised by recurrent oral and genital ulcers, skin lesions, and inflammatory eye disease. Patients with ocular involvement have a poor visual prognosis because of recurrent severe retinal vasculitis with concomitant retinal and optic nerve ischaemia.’1 Current therapy includes high-dose corticosteroids, cyclosporin, azathioprine, and chlorambucil. We report colchicine, cyclophosphamide, 3 patients, all satisfying the International Behçet’s Study Group criteria for Behçet’s disease,2 with previously refractory intraocular inflammation who responded to with interferon-a2b. The first case was a 31-year-old male with ocular Beh4;et’s disease since 1988. Despite treatment with prednisone,
1988 another acute relapse of intraocular inflammation associated with neurological symptoms was halted within days by the combination of prednisone, cyclosporin, and interferon-a2b. Complete remission was observed and all treatment was withdrawn in 1991. Visual acuity in the left eye of 6/18 has since remained stable. A 35-year-old man with ocular Behçet’s disease since 1986 was treated conventionally with varying combinations of prednisone, cyclosporin, azathioprine, chlorambucil, and cyclophosphamide. Despite therapy, useful vision was lost in the right eye in 1991 because of severe necrotising retinitis followed by retinal and optic atrophy. Visual acuity in the left eye decreased to 6/24. Retinitis recurred in the left eye in January, 1994, while the patient was on cyclophosphamide and cyclosporin. Cyclosporin was replaced by interferon-a2b at the above dose, resulting in prompt resolution of the retinitis within a week and improvement of visual acuity from finger counting to 6/12. Beneficial effects of interferon-a in Behçet’s disease have been documented for mucocutaneous lesions and arthritis.’,’ Therapeutic use for ocular manifestations of the disease has been described as case reports, but with contradictory results.3,5 Ocular side-effects of systemic interferon-a therapy have also been reported. Our observations on 3 patients with previously refractory ocular Behçet’s disease provide evidence that interferon-a2b is a new important adjuvant in the management of the disease. However, studies with larger numbers of patients and longer follow-up are needed to determine the exact role of interferon-a2b in the management of sight-threatening complications of Behçet’s disease, and possibly other forms of intraocular inflammatory disease. E J Feron, A Rothova, P M van Hagen, G S Baarsma, M S A Suttorp-Schulten Rotterdam Eye Hospital, PO Box 70030, 3011 BH Rotterdam, Netherlands; Department of Ophthalmo-immunology, Netherlands Ophthalmic Research Institute, Amsterdam; Department of Immunology and Internal Medicine, Academic Hospital Rotterdam, Rotterdam; and F C Donders Institute for Ophthalmology, Utrecht 1 2 3
4
treatment
cyclosporin, azathioprine, cyclophosphamide, colchicine, chlorambucil in varying combinations, disease progressed and visual acuity deteriorated to 6/36 in the right eye and counting fingers in the left eye. In November, 1992,
5
Towler HMA,
Lightman S. Visual prognosis in Behçet’s disease. Ocul Immunol Inflamm 1993; 1: 249-54. International Study Group for Behçet’s disease. Criteria for diagnosis of Behçet’s disease. Lancet 1990; 335: 1078-80. Tsambaos D, Eichelberg D, Goos M. Behçet’s syndrome: treatment with recombinant leukocyte alpha-interferon. Arch Dermatol Res 1986; 278: 335-36. Dündar S, Özcebe OI, Özdemir O, Kirazli S. Alpha-interferon in the treatment of Behçet’s disease. In: Godeau P, Wechsler B, eds. Behçet’s disease. Elsevier Science Publishers, 1993: 665-70. Durand JM, Kaplanski G, Telle H, Soubeyrand J, Paulo F. Beneficial effect of interferon-&agr;2b in Behçet’s disease. Arthritis Rheum 1993; 36: 1025-26.
and
a severe exacerbation of retinitis was treated with interferon-a2b 3 million IU subcutaneously 3 times a week combined with colchicine and a low dose of prednisone. Subsequent complete remission of ocular signs and symptoms has been maintained on this regimen. Discontinuation of interferon injections for one week was immediately followed by a relapse, which responded promptly to restarting the injections. A man aged 42 was treated with combinations of prednisone, cyclosporin, cyclophosphamide, and colchicine for systemic and ocular manifestations of Behçet’s disease since 1979. This did not prevent progression of vaso-occlusive retinitis and vision was subsequently lost in the right eye in 1985. A 3-month course of interferon-a2b at the above dose was added to his therapy with cyclosporin and colchicine, with favourable results on arthritis and uveitis. Disease activity was controlled for 3 years, but in
1428
Take two
glasses of wine and see
me
in the
morning SIR—Ever since the "French paradox" became public, much has been published about those constituents that seem to be responsible for the healthful attributes of wine, particularly cardiovascular wellness.’Several wine constituents, mostly antioxidants, such as the ubiquitous quercetin, epicatechin, and lately, resveratrol, have been either identified or
postulated as decreasing low-density lipoprotein (LDL) and carrying out other protective duties such as aiding the retention of the integrity of membranes.2 In addition, wine and grape components have been found to act as vasorelaxants.’ Furthermore, epidemiological studies indicate that moderate consumption of ethanol decreases LDL and thus the risk of myocardial infarction/ What many who extol the virtues of wine seem to have missed is that