- Email: [email protected]
Glutathione deficiency and radiosensitivity in AIDS patients
918
The new technique of large loop diathermy excision of the transformation zone2 is gaining popularity and is likely soon to replace laser vaporisation in many colposcopy clinics. Loop diathermy excision has proved effective, with low morbidity, in the management of patients with abnormal smears.3 One of the main advantages of this treatment is that the transformation zone may be excised in one piece and submitted for histological examination. The advent of large loop diathermy excision calls for a reappraisal of the role of knife conisation under general anaesthesia in patients for whom local destructive therapy is inappropriate. We have investigated the efficacy and morbidity of outpatient conisation with large loop diathermy in women with abnormal cervical smears for whom local destructive therapy was contraindicated. The study was designed as a prospective programme trial with six months’ follow-up, and was done in a hospital-based colposcopy clinic. The study group consisted of 50 patients aged 20-69 years with abnormal cervical smears in whom the squamocolumnar junction could not be seen (n = 40) or in whom there was colposcopic or histological suspicion of invasive disease (n=10). A ’Valleylab force 2’ surgical generator and fine-wire loops were used. The cervical transformation zone was excised under colposcopic control after local infiltration of the cervix with prilocaine (3%) and felypressin (30 IU/1). The raw wound surface was cauterised with a cautery ball, irrespective of any bleeding. Histological examination of the tissues showed no abnormality in 3 patients, koilocytosis alone in 1, CIN 1 in 10, CIN 2 in 14, CIN 3 in 20, and invasive squamous cell carcinoma in 2. Excision margins were free of disease in 37 (74%) patients. In 2, excision was incomplete at the ectocervical margin, in 5 at the endocervical margin, and in 6 excision was incomplete at both margins. 1 of these patients had moderately differentiated squamous cell carcinoma and was treated by radical hysterectomy. Immediate morbidity was slight. 1 patient was admitted with secondary haemorrhage and was managed conservatively. 5 patients had dyskaryotic smears at follow-up: mild dyskaryosis was reported in 3, moderate dyskaryosis in 1, and severe dyskaryosis in 1. Knife conisation under general anaesthesia was not judged necessary in any patient.
We conclude that outpatient conisation with loop diathermy is effective in patients with abnormal cervical smears in whom local destructive therapy is contraindicated. We suggest that this procedure may be an alternative to knife conisation under general anaesthesia. However, further follow-up is required to determine if the long-term outcome compares favourably with knife conisation. Department of Obstetrics and Gynaecology, Walsgrave Hospital, Coventry CV2 2DX, UK
PAUL BYRNE ONOME OGUEH L. J. SANT-CASSIA
DISEASE STATUS AND FREQUENCY OF PNEUMOTHORAX IN PENTAMIDINE-TREATED HIV-POSITIVE HAEMOPHILIACS I
I
I
-
I
PA=pentamidine, pneum-pneumothorax.
patients (table). In all but 1 it was associated with secondary prophylaxis-ie, after PCP 0-5-14 months earlier (diagnosed clinically, without histological confirmation, but responding to high-dose co-trimoxazole). Although all our patients had coughing during administration, no pneumothoraces developed during or immediately after pentamidine treatment. In 3 patients PCP became resistant to treatment and pneumothoraces developed as the final stage of illness. These results may indicate disease in patients surviving
end-stage cystic parenchymal lung recurrent PCP with pentamidine prophylaxis, or possibly a late side-effect of pentamidine administration, since patients receiving primary and secondary prophylaxis were affected. Conversely, none of our 30 symptomfree HIV-positive haemophiliacs have had pentamidine prophylaxis or pneumothorax. Firm conclusions cannot be drawn from this small series, but we would be interested to hear the experience of other centres using similar prophylactic schedules. A. C. CUTHBERT Department of Haematology, D. WRIGHT St James’s University Hospital, B. A. MCVERRY Leeds LS9 7TF, UK Montgomery AG, Debs RJ, Luce JM, et al. Aerosolised pentamidine as sole therapy for Pneumocystis carinii pneumonia in patients with acquired immunodeficiency syndrome. Lancet 1987; ii: 480-83. 2. Leoung GS, Feigal DW, Montgomery AB, et al. Aerosolised pentamidine for prophylaxis against Pneumocystis carinii pneumonia. N Engl J Med 1990; 323: 1.
769-75.
Luesley D, Cullimore J. The treatment of cervical intraepithelial neoplasia. Cancer Surveys 1988; 7: 529-45. 2. Prendeville W, Cullimore J, Norman S. Large loop excision of the transformation zone (LLETZ): a new method of management for women with cervical intraepithelial neoplasia. Br J Obstet Gynaecol 1989; 96: 1345-47 3. Luesley DM, Cullimore J, Redman CWE, et al. Loop diathermy excision of the cervical transformation zone in patients with abnormal smears. Br Med J 1990; 300: 1.
1690-93.
Pneumothorax in
pentamidine-treated haemophiliacs
SIR,-Nebulised pentamidine prophylaxis has strikingly reduced the frequency of Pneumocystis carinii pneumonia (PCP) in patients with AIDS.’ This treatment is generally well tolerated, but side-effects, including coughing and wheezing bouts during administration, are well recognised. Spontaneous pneumothorax has been reported as an uncommon side-effect in a large series.2 However, we now report a high frequency in our haemophiliac population. 13 HIV-positive haemophiliacs with symptoms received nebulised pentamidine prophylaxis every 2-4 weeks (300 mg pentamidine in 3 ml water via a ’System 22’ nebuliser [Medic-Aid] with air at 9 1/min over 10 min, and salbutamol 2-5 mg in 2-5 ml saline immediately beforehand). Pneumothorax developed in 4
Glutathione deficiency and radiosensitivity in AIDS patients SIR,-Several radiation oncologists treating patients with AIDSrelated malignant disease have noted an unusual degree of radiation sensitivity in this group of patients. Since classic Kaposi’s sarcoma (KS) is a radiosensitive tumour, radiotherapy has been used in the treatment of the AIDS-related form ofKS from an early stage in the epidemic.1,2 This treatment has also been used for other AIDSrelated tumours, such as lymphomas. The oropharynx is frequently affected by KS and radiotherapy is used to relieve symptoms of pain, airway obstruction, and dysphagia. It is at this site that an abnormally severe radiation reaction has most often been seen. When conventional daily doses of 1-8-2 Gy are given, acute mucositis often arises when the total dose is 12 Gy or higher. This contrasts with the treatment of oropharyngeal tumours in patients without AIDS in whom one would not expect to see such a reaciton until about half way through treatment (30 Gy). Striking acute radiation reactions of the skin have also (though less frequently) been observed, such as desquamation and hyperpigmentation, to a degree out of proportion to the dose of radiation. Severe reactions on the soles of feet have often been seen in KS after radiation treatment, such that therapy has sometimes had to be interrupted or stopped.
919
radiosensitivity in AIDS patients has not yet been adequately explained. Systemic glutathione values, however, are reduced in HIVpositive individuals5 and this biochemical abnormality might render tissues especially susceptible to damage by ionising radiation. Glutathione is a ubiquitous tripeptide molecule and is the major source of intracellular thiol groups. It plays an important part in cellular defence against the damaging effects of free radicals, This enhanced
which are formed as a result of oxidative stress, such as those caused by radiation. The radiosensitivity of cells depends on the intracellular thiol level. In general, the administration of thiols confers radioprotection, and, conversely, the lowering of intracellular thiols by means of buthionine sulfoximine, which inhibits glutathione synthetase, reduces cellular resistance to radiation-induced damage. Buhl et al5 showed that plasma total and reduced glutathione concentrations in HIV-seropositive individuals were about a third of those in controls. They also found that the level of glutathione in lung epithelial lining fluid in HIV-positive individuals was 60% of that in controls. Buhl et als postulate that since glutathione enhances immune function, glutathione deficiency might contribute to the progressive impairment of immunity seen in HIV infection. N-acetyl-L-cysteine (NAC) inhibits HIV replication, and Roederer et al6 have proposed that it does so by replenishment of intracellular glutathione. It has therefore been suggested that NAC might be a valuable therapeutic agent for AIDS. Although NAC in the treatment of AIDS is as yet untested, it could be of use in the correction of glutathione deficiency in patients undergoing radiotherapy. Whether such an approach would prevent the exaggerated response to radiation, thus allowing administration of full radical doses of radiation, should be investigated. ICRF Molecular Pharmacology Hugh Robson Building, Edinburgh EH8 9XD, UK
Group,
K. A. VALLIS
Cooper JS, Fned PR, Laubenstein LJ Initial observations of the effect of radiotherapy on epidemic Kaposi’s sarcoma. JAMA 1984; 252: 934-35. 2 Spittle MF. A simple and effective treatment for AIDS related Kaposi’s sarcoma. Br Med J 1987; 295: 248-49. 3. Watkins EB, Findlay P, Gelmann E, Lane HC, Zabell A. Enhanced mucosal reactions in AIDS patients receiving oropharyngeal irradiation. Int J Rad Oncol Biol Phys 1
1987; 13: 1403-08.
Stafford ND, Herdman RCD, Forster S, Munro AJ. Kaposi’s sarcoma of the head and neck in patients with AIDS. J Laryngol Otol 1989; 103: 379-82. 5 Buhl R, Holyroyd KJ, Mastrangeli A, et al Systemic glutathione deficiency in symptom-free HIV-seropositive individuals. Lancet 1989; ii: 1294-98. 6. Roederer M, Staal FJT, Raju PA, Ela SW, Herzenberg LA, Herzenberg LA. Cytokine-stimulated human immunodeficiency virus replication is inhibited by N-acetyl-L-cysteine. Proc Natl Acad Sci USA 1990; 87: 4884-88.
4.
Treatment for Kaposi’s sarcoma in HIV-negative, non-homosexual men SIR,-Dr Killeen and Dr Marsh (Feb 2, p 309) describe an HIV-seronegative, non-homosexual man with Kaposi’s sarcoma (KS) whom they treated with a-interferon for reappearance of KS lesions after local radiotherapy. We are surprised that Killeen and Marsh did not mention chemotherapy. The efficacy of systemic1,2 as well as intralesional3 chemotherapy for non-HIV-related KS is well established. With low doses of vinblastine (01 mg/kg per week) Tucker and Winckelmanl achieved favourable response rates in 21
related KS, after failure of local radiotherapy. Using extended field radiotherapy, Holecek et al4 obtained a complete response in 10 (83%) of 12 patients, the only side-effect being a slight induration of the skin. We suggest that for KS in patients without HIV infection, radiotherapy and chemotherapy have to remain the treatment of choice.
Institute of Tropical Medicine, 2000 Antwerp, Belgium
KOEN DE BOECK MICHEL LACHENAL ROBERT COLEBUNDERS
1. Tucker SB, Winkelmann RK. Treatment of Kaposi’s sarcoma with Vinblastine. Arch Dermatol 1976; 112: 958-61. 2. Klein E, Schartz RA, Laar Y. Treatment of Kaposi’s sarcoma with vinblastine. Cancer
1980, 45: 427-31. 3. Odom RB, Goette DK. Treatment of cutaneous Kaposi’s sarcoma with interlesional vincristine. Arch Dermatol 1978; 114: 1693-94. 4. Holecek MJ, Harwood AR. Radiotherapy of Kaposi’s sarcoma. Cancer 1978; 41: 1733-38.
Co-trimoxazole for toxic epidermal necrolysis in AIDS SIR,-Adverse reactions to co-trimoxazole frequently arise in patients with HIV infection.1,2 By contrast, toxic epidermal necrolysis (TEN) is rarely seen in AIDS patients receiving this drug. 3-5 We report a case of histologically documented TEN in a 33-year-old homosexual man with HIV infection, who presented with Pneumocystis carinii pneumonia (PCP). The patient had no cutaneous abnormality at admission and had never received co-trimoxazole. He was given intravenous (iv) co-trimoxazole (120 mg/kg daily), and oral folinic acid (50 mg daily) to prevent bone-marrow toxicity. After nine days of treatment, macular and generalised rash with fever developed. Despite discontinuation of co-trimoxazole and folinic acid, bullae were noted two days later in the mouth and on genital mucous membranes; Nikolsky’s sign was present
on more
than 20% of the skin surface. Corticosteroid
therapy (iv methylprednisolone, 180 mg daily) was then begun. Skin biopsy showed typical TEN with necrolysis of the roof of bullae and lymphoplasmocytosis. He improved with 7 days of corticosteroid therapy, correction of metabolic derangement, and antibiotics. PCP was treated by pentamidine. When clinical signs of severe rash are seen (high fever, mucocutaneous lesions, and Nikolsky’s sign), treatment must be discontinued and correction of metabolic disturbance begun immediately. No data are available on the usefulness of corticosteroid therapy for TEN in AIDS patients receiving co-trimoxazole. The low frequency of TEN in such cases is not clearly understood, but high blood concentrations of cotrimoxazole could account for this.4 Monitoring of serum trimethoprim concentrations could reduce the frequency and severity of toxicity without reducing efficacy.2 E. SENNEVILLE P. LECOCQ Department of Infectious Diseases, University of Lille, Centre Hospitalier de Tourcoing, 59208 Tourcoing, France
F. AJANA C. CHIDIAC Y. MOUTON
(91 %) of 23 patients and Klein et al2 did so in 10 of 12. Both reports included patients with widespread disease. In Klein and
colleagues’2 investigation all patients with the nodular form of the disease (n = 9) had a favourable response. Side-effects associated with such a low dose of vinblastine in patients without HIV infection are minor: transient leucopenia, occasional mental depression, nausea, and phlebitis. In contrast, ot-interferon has major side-effects, such as neutropenia, fever, chills, myalgia, and diarrhoea. Moreover, a-interferon is very expensive; we estimate that the treatment for Killeen and Marsh’s patient cost at least 10 000, wherease vinblastine treatment would probably not have cost more than 700. Extended field radiotherapy is another alternative for non-HIV-
1. Gordin FM, Simon GL, Wofsy CR. Adverse reactions to trimethoprimsulfamethoxazole in patient with the acquired immunodeficiency syndrome. Ann Intern Med 1984; 100: 495. 2 Kovacs JA, Hiemenz JW, Macher AM, et al. Pneumocystis carinii pneumonia: a comparison between patients with the acquired immunodeficiency syndrome and patients with other immunodeficiencies. Ann Intern Med 1984; 100: 663-71. 3. Wharton JM, Coleman DL, Wofsy CB. Trimethoprim-sulfamethoxazole or pentamidine for Pneumocystis carinii pneumonia with acquired immunodeficiency syndrome. Ann Intern Med 1985; 105: 37. 4. Kovacs JA, Masur H. Pneumocystis carinii pneumonia: therapy and prophylaxis. J Infect Dis 1988; 158: 254-59. 5. Sattler FR, Cowan R, Nielsen DM, Ruskin J. Trimethoprim-sulfamethoxazole compared with pentamidine for treatment of Pneumocystis carinii pneumonia in the acquired immunodeficiency syndrome: a prospective, non-crossover study. Ann Intern Med 1988; 109: 280-87.
The new technique of large loop diathermy excision of the transformation zone2 is gaining popularity and is likely soon to replace laser vaporisation in many colposcopy clinics. Loop diathermy excision has proved effective, with low morbidity, in the management of patients with abnormal smears.3 One of the main advantages of this treatment is that the transformation zone may be excised in one piece and submitted for histological examination. The advent of large loop diathermy excision calls for a reappraisal of the role of knife conisation under general anaesthesia in patients for whom local destructive therapy is inappropriate. We have investigated the efficacy and morbidity of outpatient conisation with large loop diathermy in women with abnormal cervical smears for whom local destructive therapy was contraindicated. The study was designed as a prospective programme trial with six months’ follow-up, and was done in a hospital-based colposcopy clinic. The study group consisted of 50 patients aged 20-69 years with abnormal cervical smears in whom the squamocolumnar junction could not be seen (n = 40) or in whom there was colposcopic or histological suspicion of invasive disease (n=10). A ’Valleylab force 2’ surgical generator and fine-wire loops were used. The cervical transformation zone was excised under colposcopic control after local infiltration of the cervix with prilocaine (3%) and felypressin (30 IU/1). The raw wound surface was cauterised with a cautery ball, irrespective of any bleeding. Histological examination of the tissues showed no abnormality in 3 patients, koilocytosis alone in 1, CIN 1 in 10, CIN 2 in 14, CIN 3 in 20, and invasive squamous cell carcinoma in 2. Excision margins were free of disease in 37 (74%) patients. In 2, excision was incomplete at the ectocervical margin, in 5 at the endocervical margin, and in 6 excision was incomplete at both margins. 1 of these patients had moderately differentiated squamous cell carcinoma and was treated by radical hysterectomy. Immediate morbidity was slight. 1 patient was admitted with secondary haemorrhage and was managed conservatively. 5 patients had dyskaryotic smears at follow-up: mild dyskaryosis was reported in 3, moderate dyskaryosis in 1, and severe dyskaryosis in 1. Knife conisation under general anaesthesia was not judged necessary in any patient.
We conclude that outpatient conisation with loop diathermy is effective in patients with abnormal cervical smears in whom local destructive therapy is contraindicated. We suggest that this procedure may be an alternative to knife conisation under general anaesthesia. However, further follow-up is required to determine if the long-term outcome compares favourably with knife conisation. Department of Obstetrics and Gynaecology, Walsgrave Hospital, Coventry CV2 2DX, UK
PAUL BYRNE ONOME OGUEH L. J. SANT-CASSIA
DISEASE STATUS AND FREQUENCY OF PNEUMOTHORAX IN PENTAMIDINE-TREATED HIV-POSITIVE HAEMOPHILIACS I
I
I
-
I
PA=pentamidine, pneum-pneumothorax.
patients (table). In all but 1 it was associated with secondary prophylaxis-ie, after PCP 0-5-14 months earlier (diagnosed clinically, without histological confirmation, but responding to high-dose co-trimoxazole). Although all our patients had coughing during administration, no pneumothoraces developed during or immediately after pentamidine treatment. In 3 patients PCP became resistant to treatment and pneumothoraces developed as the final stage of illness. These results may indicate disease in patients surviving
end-stage cystic parenchymal lung recurrent PCP with pentamidine prophylaxis, or possibly a late side-effect of pentamidine administration, since patients receiving primary and secondary prophylaxis were affected. Conversely, none of our 30 symptomfree HIV-positive haemophiliacs have had pentamidine prophylaxis or pneumothorax. Firm conclusions cannot be drawn from this small series, but we would be interested to hear the experience of other centres using similar prophylactic schedules. A. C. CUTHBERT Department of Haematology, D. WRIGHT St James’s University Hospital, B. A. MCVERRY Leeds LS9 7TF, UK Montgomery AG, Debs RJ, Luce JM, et al. Aerosolised pentamidine as sole therapy for Pneumocystis carinii pneumonia in patients with acquired immunodeficiency syndrome. Lancet 1987; ii: 480-83. 2. Leoung GS, Feigal DW, Montgomery AB, et al. Aerosolised pentamidine for prophylaxis against Pneumocystis carinii pneumonia. N Engl J Med 1990; 323: 1.
769-75.
Luesley D, Cullimore J. The treatment of cervical intraepithelial neoplasia. Cancer Surveys 1988; 7: 529-45. 2. Prendeville W, Cullimore J, Norman S. Large loop excision of the transformation zone (LLETZ): a new method of management for women with cervical intraepithelial neoplasia. Br J Obstet Gynaecol 1989; 96: 1345-47 3. Luesley DM, Cullimore J, Redman CWE, et al. Loop diathermy excision of the cervical transformation zone in patients with abnormal smears. Br Med J 1990; 300: 1.
1690-93.
Pneumothorax in
pentamidine-treated haemophiliacs
SIR,-Nebulised pentamidine prophylaxis has strikingly reduced the frequency of Pneumocystis carinii pneumonia (PCP) in patients with AIDS.’ This treatment is generally well tolerated, but side-effects, including coughing and wheezing bouts during administration, are well recognised. Spontaneous pneumothorax has been reported as an uncommon side-effect in a large series.2 However, we now report a high frequency in our haemophiliac population. 13 HIV-positive haemophiliacs with symptoms received nebulised pentamidine prophylaxis every 2-4 weeks (300 mg pentamidine in 3 ml water via a ’System 22’ nebuliser [Medic-Aid] with air at 9 1/min over 10 min, and salbutamol 2-5 mg in 2-5 ml saline immediately beforehand). Pneumothorax developed in 4
Glutathione deficiency and radiosensitivity in AIDS patients SIR,-Several radiation oncologists treating patients with AIDSrelated malignant disease have noted an unusual degree of radiation sensitivity in this group of patients. Since classic Kaposi’s sarcoma (KS) is a radiosensitive tumour, radiotherapy has been used in the treatment of the AIDS-related form ofKS from an early stage in the epidemic.1,2 This treatment has also been used for other AIDSrelated tumours, such as lymphomas. The oropharynx is frequently affected by KS and radiotherapy is used to relieve symptoms of pain, airway obstruction, and dysphagia. It is at this site that an abnormally severe radiation reaction has most often been seen. When conventional daily doses of 1-8-2 Gy are given, acute mucositis often arises when the total dose is 12 Gy or higher. This contrasts with the treatment of oropharyngeal tumours in patients without AIDS in whom one would not expect to see such a reaciton until about half way through treatment (30 Gy). Striking acute radiation reactions of the skin have also (though less frequently) been observed, such as desquamation and hyperpigmentation, to a degree out of proportion to the dose of radiation. Severe reactions on the soles of feet have often been seen in KS after radiation treatment, such that therapy has sometimes had to be interrupted or stopped.
919
radiosensitivity in AIDS patients has not yet been adequately explained. Systemic glutathione values, however, are reduced in HIVpositive individuals5 and this biochemical abnormality might render tissues especially susceptible to damage by ionising radiation. Glutathione is a ubiquitous tripeptide molecule and is the major source of intracellular thiol groups. It plays an important part in cellular defence against the damaging effects of free radicals, This enhanced
which are formed as a result of oxidative stress, such as those caused by radiation. The radiosensitivity of cells depends on the intracellular thiol level. In general, the administration of thiols confers radioprotection, and, conversely, the lowering of intracellular thiols by means of buthionine sulfoximine, which inhibits glutathione synthetase, reduces cellular resistance to radiation-induced damage. Buhl et al5 showed that plasma total and reduced glutathione concentrations in HIV-seropositive individuals were about a third of those in controls. They also found that the level of glutathione in lung epithelial lining fluid in HIV-positive individuals was 60% of that in controls. Buhl et als postulate that since glutathione enhances immune function, glutathione deficiency might contribute to the progressive impairment of immunity seen in HIV infection. N-acetyl-L-cysteine (NAC) inhibits HIV replication, and Roederer et al6 have proposed that it does so by replenishment of intracellular glutathione. It has therefore been suggested that NAC might be a valuable therapeutic agent for AIDS. Although NAC in the treatment of AIDS is as yet untested, it could be of use in the correction of glutathione deficiency in patients undergoing radiotherapy. Whether such an approach would prevent the exaggerated response to radiation, thus allowing administration of full radical doses of radiation, should be investigated. ICRF Molecular Pharmacology Hugh Robson Building, Edinburgh EH8 9XD, UK
Group,
K. A. VALLIS
Cooper JS, Fned PR, Laubenstein LJ Initial observations of the effect of radiotherapy on epidemic Kaposi’s sarcoma. JAMA 1984; 252: 934-35. 2 Spittle MF. A simple and effective treatment for AIDS related Kaposi’s sarcoma. Br Med J 1987; 295: 248-49. 3. Watkins EB, Findlay P, Gelmann E, Lane HC, Zabell A. Enhanced mucosal reactions in AIDS patients receiving oropharyngeal irradiation. Int J Rad Oncol Biol Phys 1
1987; 13: 1403-08.
Stafford ND, Herdman RCD, Forster S, Munro AJ. Kaposi’s sarcoma of the head and neck in patients with AIDS. J Laryngol Otol 1989; 103: 379-82. 5 Buhl R, Holyroyd KJ, Mastrangeli A, et al Systemic glutathione deficiency in symptom-free HIV-seropositive individuals. Lancet 1989; ii: 1294-98. 6. Roederer M, Staal FJT, Raju PA, Ela SW, Herzenberg LA, Herzenberg LA. Cytokine-stimulated human immunodeficiency virus replication is inhibited by N-acetyl-L-cysteine. Proc Natl Acad Sci USA 1990; 87: 4884-88.
4.
Treatment for Kaposi’s sarcoma in HIV-negative, non-homosexual men SIR,-Dr Killeen and Dr Marsh (Feb 2, p 309) describe an HIV-seronegative, non-homosexual man with Kaposi’s sarcoma (KS) whom they treated with a-interferon for reappearance of KS lesions after local radiotherapy. We are surprised that Killeen and Marsh did not mention chemotherapy. The efficacy of systemic1,2 as well as intralesional3 chemotherapy for non-HIV-related KS is well established. With low doses of vinblastine (01 mg/kg per week) Tucker and Winckelmanl achieved favourable response rates in 21
related KS, after failure of local radiotherapy. Using extended field radiotherapy, Holecek et al4 obtained a complete response in 10 (83%) of 12 patients, the only side-effect being a slight induration of the skin. We suggest that for KS in patients without HIV infection, radiotherapy and chemotherapy have to remain the treatment of choice.
Institute of Tropical Medicine, 2000 Antwerp, Belgium
KOEN DE BOECK MICHEL LACHENAL ROBERT COLEBUNDERS
1. Tucker SB, Winkelmann RK. Treatment of Kaposi’s sarcoma with Vinblastine. Arch Dermatol 1976; 112: 958-61. 2. Klein E, Schartz RA, Laar Y. Treatment of Kaposi’s sarcoma with vinblastine. Cancer
1980, 45: 427-31. 3. Odom RB, Goette DK. Treatment of cutaneous Kaposi’s sarcoma with interlesional vincristine. Arch Dermatol 1978; 114: 1693-94. 4. Holecek MJ, Harwood AR. Radiotherapy of Kaposi’s sarcoma. Cancer 1978; 41: 1733-38.
Co-trimoxazole for toxic epidermal necrolysis in AIDS SIR,-Adverse reactions to co-trimoxazole frequently arise in patients with HIV infection.1,2 By contrast, toxic epidermal necrolysis (TEN) is rarely seen in AIDS patients receiving this drug. 3-5 We report a case of histologically documented TEN in a 33-year-old homosexual man with HIV infection, who presented with Pneumocystis carinii pneumonia (PCP). The patient had no cutaneous abnormality at admission and had never received co-trimoxazole. He was given intravenous (iv) co-trimoxazole (120 mg/kg daily), and oral folinic acid (50 mg daily) to prevent bone-marrow toxicity. After nine days of treatment, macular and generalised rash with fever developed. Despite discontinuation of co-trimoxazole and folinic acid, bullae were noted two days later in the mouth and on genital mucous membranes; Nikolsky’s sign was present
on more
than 20% of the skin surface. Corticosteroid
therapy (iv methylprednisolone, 180 mg daily) was then begun. Skin biopsy showed typical TEN with necrolysis of the roof of bullae and lymphoplasmocytosis. He improved with 7 days of corticosteroid therapy, correction of metabolic derangement, and antibiotics. PCP was treated by pentamidine. When clinical signs of severe rash are seen (high fever, mucocutaneous lesions, and Nikolsky’s sign), treatment must be discontinued and correction of metabolic disturbance begun immediately. No data are available on the usefulness of corticosteroid therapy for TEN in AIDS patients receiving co-trimoxazole. The low frequency of TEN in such cases is not clearly understood, but high blood concentrations of cotrimoxazole could account for this.4 Monitoring of serum trimethoprim concentrations could reduce the frequency and severity of toxicity without reducing efficacy.2 E. SENNEVILLE P. LECOCQ Department of Infectious Diseases, University of Lille, Centre Hospitalier de Tourcoing, 59208 Tourcoing, France
F. AJANA C. CHIDIAC Y. MOUTON
(91 %) of 23 patients and Klein et al2 did so in 10 of 12. Both reports included patients with widespread disease. In Klein and
colleagues’2 investigation all patients with the nodular form of the disease (n = 9) had a favourable response. Side-effects associated with such a low dose of vinblastine in patients without HIV infection are minor: transient leucopenia, occasional mental depression, nausea, and phlebitis. In contrast, ot-interferon has major side-effects, such as neutropenia, fever, chills, myalgia, and diarrhoea. Moreover, a-interferon is very expensive; we estimate that the treatment for Killeen and Marsh’s patient cost at least 10 000, wherease vinblastine treatment would probably not have cost more than 700. Extended field radiotherapy is another alternative for non-HIV-
1. Gordin FM, Simon GL, Wofsy CR. Adverse reactions to trimethoprimsulfamethoxazole in patient with the acquired immunodeficiency syndrome. Ann Intern Med 1984; 100: 495. 2 Kovacs JA, Hiemenz JW, Macher AM, et al. Pneumocystis carinii pneumonia: a comparison between patients with the acquired immunodeficiency syndrome and patients with other immunodeficiencies. Ann Intern Med 1984; 100: 663-71. 3. Wharton JM, Coleman DL, Wofsy CB. Trimethoprim-sulfamethoxazole or pentamidine for Pneumocystis carinii pneumonia with acquired immunodeficiency syndrome. Ann Intern Med 1985; 105: 37. 4. Kovacs JA, Masur H. Pneumocystis carinii pneumonia: therapy and prophylaxis. J Infect Dis 1988; 158: 254-59. 5. Sattler FR, Cowan R, Nielsen DM, Ruskin J. Trimethoprim-sulfamethoxazole compared with pentamidine for treatment of Pneumocystis carinii pneumonia in the acquired immunodeficiency syndrome: a prospective, non-crossover study. Ann Intern Med 1988; 109: 280-87.