939
(eg, ectocervix) may harbour human papillomavirus (HPV) but to expect the epidermis overlying cutaneous Kaposi’s sarcoma lesions to be infected by HPV is to extend those observations too far. To me, the negative result would be the expected one. The Kaposi’s sarcoma lesions may represent blood-borne spread of HPV, and this hypothesis could be tested by repeating Nickoloff and colleagues’ staining methods on visceral Kaposi’s lesions. Surprise is also expressed that an epidermotropic virus (HPV 16) might survive and proliferate in dermal dendritic cells, which would normally be considered foreign territory. In AIDS, where the important background event is secondary immunodeficiency, pathologists should expect the unexpected, though that should not rule out the suggestion about a novel non-epitheliotropic HPV. mucosa
44Woodend Drive,
Glasgow G13 1TQ, UK
JAMES F. BOYD
role of HIV tests.1o Also, endemic KS with concomitant HIV infection is likely to increase as the HIV seroprevalence rate in the population rises, thus further diminishing the role of HIV testing. The overlap and apparent transposition of clinical features and HIV status between endemic and epidemic KS5,10 make the classification of KS difficult. Indeed, in Africa it may not be easy to decide whether HIV seropositive "endemic" KS is misclassified epidemic KS or intercurrently infected endemic KS—or whether seronegative "epidemic" KS is misclassified endemic KS (ie, the aggressive variant)6,7 or epidemic KS. Do endemic and epidemic KS have their separate spectra, both ranging from indolent to aggressive? And what impact does concomitant HIV infection have on endemic KS?
discriminating
University Teaching Hospital, Lusaka, Zambia* *Present address: Lillian Penson Hall, Talbot
SIR,-Dr Huang and colleagues (Feb 29, p 515) speculate about a clinical correlation between HPV infection and Kaposi’s sarcoma (KS). To test this hypothesis we examined data from our longitudinal study of HIV infection in gay men.1 Men were recruited between 1982 and 1984, and there are detailed data on sexually transmitted diseases, including genital warts due to HPV. KS has so far developed in 22 of 65 AIDS patients, 12 of whom had had genital warts; only 9 of the 43 patients without KS had warts (chi-square test, p=001). Gonococcal infection, antibodies to hepatitis B, positive syphilis serology, and non-specific urethritis showed no association with KS. Epidemiological evidence suggests that KS is due at least in part to a sexually transmitted infection .2 The DNA sequence data of Huang et al and the clinical association we have found suggest that a relation between KS and HPV infection should be looked at in greater depth, including more detailed cohort studies that control for confounding variables. Even if the association is only a marker for another agent, or a co-factor, such clues will help to identify the causal agent.
St Mary’s Hospital Medical School, London W2 1PG, UK
MARK GOMPELS G. RILEY J. W. HARRIS A. J. PINCHING
1. Weber JN, Wadsworth J,
Rogers LA, Pinching AJ. Three year prospective study of HTLV-III/LAV infection in homosexual men. Lancet 1986; i: 1179-82. 2. Beral V, Peterman TA, Berkelman RL, Jaffe HW. Kaposi’s sarcoma among persons with AIDS: a sexually transmitted infection? Lancet 1990; 335: 123-28.
Kaposi’s sarcoma epidemiology SiR,—The hypothesis that Kaposi’s sarcoma (KS) could be caused by a yet unidentified sexually transmitted agent’ is gaining support.2,3Although the evidence is formidable,’ it emanates exclusively from western AIDS-related KS. For this idea to embrace African variants it should also explain the incidence and spread of KS on that continent. The epidemiology of African epidemic KS4-6 may be consistent with the hypothesis. That of the endemic variant is not, for three reasons: (1) the male preponderance (more than 10:1) in an almost exclusively heterosexual population; (2) the involvement of sexually inactive children, in whom the sex distribution is almost equal in young children but rises with age to approximate that of adults by 15 years, suggesting a hormonal influence,and (3) its geographical sequestration and age distribution, suggestive of an environmental factor.7 It is curious that epidemic KS and childhood lymphadenopathic endemic KS should have similar clinical behaviour and sex distribution, yet childhood KS is neither HIV related nor likely to be sexually transmitted.6 Because KS in Africa is so protean it is difficult to envisage a unitary pathogenesis or aetiology. Indeed, it has been suggested that the different clinical forms have different causes.8 Endemic and epidemic KS may be histologically identical"’ but the clinical differences are intriguing. These differences were striking in 1983 when epidemic KS was first described’’ but were less so by 1985-86,5,6 such that HIV testing was sometimes required for the distinctions However, recent experience casts doubt on the
PATRICK MATONDO Square, London W2 1TT, UK.
1. Beral
2. 3.
4. 5.
6.
7. 8. 9. 10.
V, Peterman TA, Berkelman RA, Jaffe HW. Kaposi’s sarcoma among persons with AIDS: a sexually transmitted infection? Lancet 1990; 335: 123-28. Friedman-Kien AE, Saltzman BR, Cao Y, et al. Kaposi’s sarcoma in HIV negative homosexual men. Lancet 1990; 335: 969-70. Beral V, Bull D, Jaffe H, et al. Is the nsk of Kaposi’s sarcoma m AIDS patients in Britain increased if sexual partners are from United States or Africa? Br Med J 1991; 302: 624-25 Bayley AC. Aggressive Kaposi’s sarcoma m Zambia. Lancet 1984; i: 1318-20. Bayley AC, Cheingsong-Popov R, Dalgleish AG, Downing RG, Tedder RS, Weiss RA. HTLV III serology distinguishes atypical and endemic Kaposi’s sarcoma in Africa. Lancet 1985; ii: 359-61. Bayley AC. Atypical aggressive Kaposi’s sarcoma in Africa In: Gotlieb GJ, Ackerman AB, eds. Kaposi’s sarcoma: a text and atlas. Philadelphia. Lea & Febiger, 1988: 151-70. Owor R. Conventional Kaposi’s sarcoma in Africa. In: Gotlieb GJ, Ackerman AB, eds. Kaposi’s sarcoma: a text and atlas. Philadelphia: Lea & Febiger, 1988. 143-48. Biggar RJ, Melbye M, Kestems L, et al. Kaposi’s sarcoma in Zaire is not associated with HTLV III infection. N Engl J Med 1984; 311: 1051. Chow JWM, Lucas SB. Endemic and atypical Kaposi’s sarcoma in Africa: histopathological aspects. Clin Exp Dermatol 1990; 15: 253-59. Desmond-Hellman S, Mbidde EK, Kizito A, Heellman NS, Ziegler JL. The value of a clinical definition for epidemic KS in predicting HIV seropositivity in Africa. J Acquired Immune Defic Syndr 1991; 4: 647-51.
Heart disease in myotonic dystrophy SIR,-In your recent editorial (Feb 29) you rightly emphasise the importance of regular review and electrocardiographic monitoring for all patients with myotonic dystrophy, to prevent the serious and often fatal consequences of conduction defects. Our experience is that most such patients seen by us from outside our area are having no regular review, whether by neurologists, cardiologists, or physicians, or even by their family doctors. Two additional points are worth mentioning. First, the high frequency of cardiorespiratory problems after anaesthesia and surgery1 makes it essential that those involved recognise that the patient has myotonic dystrophy, and that preoperative assessment, as well as careful management during and after surgery, is undertaken. Sadly, the risks are still far from being well recognised, as a legal report in The Lancet and subsequent correspondence shows.2,3
Secondly, after the recent isolation of the myotonic dystrophy recognition of the predicted protein product as a protein kinase,4 the gene has proved to be especially strongly expressed in heart muscle. This should allow detailed investigation gene and the
of the nature of the cardiac defect, so frozen cardiac tissue, obtained at necropsy or heart surgery from myotonic dystrophy patients, should be preserved for future study. We may eventually be able to develop a protective therapy that will avoid the principal cause of death in myotonic dystrophy patients. Institute of Medical Genetics, University of Wales College of Medicine, Cardiff CF4 4XN, UK
PETER S. HARPER WILLIAM REARDON
Harper PS. Myotonic dystrophy. London: W B. Saunders, 1989: 114-16. Postoperative monitoring in patients with muscular dystrophy. Lancet 1989; ii: 1053-54. 3. Harper PS. Postoperative complications in myotonic dystrophy. Lancet 1989; ii: 1269. 4. Brook JD, McCurrach ME, Harley GH, et al. The molecular basis of myotonic dystrophy expansion of a trinucleotide (CTG) repeat at the 3’ end of a transcript encoding a protein kinase family member. Cell 1992; 68: 799-808 1.
2 Brahams D.
(eg, ectocervix) may harbour human papillomavirus (HPV) but to expect the epidermis overlying cutaneous Kaposi’s sarcoma lesions to be infected by HPV is to extend those observations too far. To me, the negative result would be the expected one. The Kaposi’s sarcoma lesions may represent blood-borne spread of HPV, and this hypothesis could be tested by repeating Nickoloff and colleagues’ staining methods on visceral Kaposi’s lesions. Surprise is also expressed that an epidermotropic virus (HPV 16) might survive and proliferate in dermal dendritic cells, which would normally be considered foreign territory. In AIDS, where the important background event is secondary immunodeficiency, pathologists should expect the unexpected, though that should not rule out the suggestion about a novel non-epitheliotropic HPV. mucosa
44Woodend Drive,
Glasgow G13 1TQ, UK
JAMES F. BOYD
role of HIV tests.1o Also, endemic KS with concomitant HIV infection is likely to increase as the HIV seroprevalence rate in the population rises, thus further diminishing the role of HIV testing. The overlap and apparent transposition of clinical features and HIV status between endemic and epidemic KS5,10 make the classification of KS difficult. Indeed, in Africa it may not be easy to decide whether HIV seropositive "endemic" KS is misclassified epidemic KS or intercurrently infected endemic KS—or whether seronegative "epidemic" KS is misclassified endemic KS (ie, the aggressive variant)6,7 or epidemic KS. Do endemic and epidemic KS have their separate spectra, both ranging from indolent to aggressive? And what impact does concomitant HIV infection have on endemic KS?
discriminating
University Teaching Hospital, Lusaka, Zambia* *Present address: Lillian Penson Hall, Talbot
SIR,-Dr Huang and colleagues (Feb 29, p 515) speculate about a clinical correlation between HPV infection and Kaposi’s sarcoma (KS). To test this hypothesis we examined data from our longitudinal study of HIV infection in gay men.1 Men were recruited between 1982 and 1984, and there are detailed data on sexually transmitted diseases, including genital warts due to HPV. KS has so far developed in 22 of 65 AIDS patients, 12 of whom had had genital warts; only 9 of the 43 patients without KS had warts (chi-square test, p=001). Gonococcal infection, antibodies to hepatitis B, positive syphilis serology, and non-specific urethritis showed no association with KS. Epidemiological evidence suggests that KS is due at least in part to a sexually transmitted infection .2 The DNA sequence data of Huang et al and the clinical association we have found suggest that a relation between KS and HPV infection should be looked at in greater depth, including more detailed cohort studies that control for confounding variables. Even if the association is only a marker for another agent, or a co-factor, such clues will help to identify the causal agent.
St Mary’s Hospital Medical School, London W2 1PG, UK
MARK GOMPELS G. RILEY J. W. HARRIS A. J. PINCHING
1. Weber JN, Wadsworth J,
Rogers LA, Pinching AJ. Three year prospective study of HTLV-III/LAV infection in homosexual men. Lancet 1986; i: 1179-82. 2. Beral V, Peterman TA, Berkelman RL, Jaffe HW. Kaposi’s sarcoma among persons with AIDS: a sexually transmitted infection? Lancet 1990; 335: 123-28.
Kaposi’s sarcoma epidemiology SiR,—The hypothesis that Kaposi’s sarcoma (KS) could be caused by a yet unidentified sexually transmitted agent’ is gaining support.2,3Although the evidence is formidable,’ it emanates exclusively from western AIDS-related KS. For this idea to embrace African variants it should also explain the incidence and spread of KS on that continent. The epidemiology of African epidemic KS4-6 may be consistent with the hypothesis. That of the endemic variant is not, for three reasons: (1) the male preponderance (more than 10:1) in an almost exclusively heterosexual population; (2) the involvement of sexually inactive children, in whom the sex distribution is almost equal in young children but rises with age to approximate that of adults by 15 years, suggesting a hormonal influence,and (3) its geographical sequestration and age distribution, suggestive of an environmental factor.7 It is curious that epidemic KS and childhood lymphadenopathic endemic KS should have similar clinical behaviour and sex distribution, yet childhood KS is neither HIV related nor likely to be sexually transmitted.6 Because KS in Africa is so protean it is difficult to envisage a unitary pathogenesis or aetiology. Indeed, it has been suggested that the different clinical forms have different causes.8 Endemic and epidemic KS may be histologically identical"’ but the clinical differences are intriguing. These differences were striking in 1983 when epidemic KS was first described’’ but were less so by 1985-86,5,6 such that HIV testing was sometimes required for the distinctions However, recent experience casts doubt on the
PATRICK MATONDO Square, London W2 1TT, UK.
1. Beral
2. 3.
4. 5.
6.
7. 8. 9. 10.
V, Peterman TA, Berkelman RA, Jaffe HW. Kaposi’s sarcoma among persons with AIDS: a sexually transmitted infection? Lancet 1990; 335: 123-28. Friedman-Kien AE, Saltzman BR, Cao Y, et al. Kaposi’s sarcoma in HIV negative homosexual men. Lancet 1990; 335: 969-70. Beral V, Bull D, Jaffe H, et al. Is the nsk of Kaposi’s sarcoma m AIDS patients in Britain increased if sexual partners are from United States or Africa? Br Med J 1991; 302: 624-25 Bayley AC. Aggressive Kaposi’s sarcoma m Zambia. Lancet 1984; i: 1318-20. Bayley AC, Cheingsong-Popov R, Dalgleish AG, Downing RG, Tedder RS, Weiss RA. HTLV III serology distinguishes atypical and endemic Kaposi’s sarcoma in Africa. Lancet 1985; ii: 359-61. Bayley AC. Atypical aggressive Kaposi’s sarcoma in Africa In: Gotlieb GJ, Ackerman AB, eds. Kaposi’s sarcoma: a text and atlas. Philadelphia. Lea & Febiger, 1988: 151-70. Owor R. Conventional Kaposi’s sarcoma in Africa. In: Gotlieb GJ, Ackerman AB, eds. Kaposi’s sarcoma: a text and atlas. Philadelphia: Lea & Febiger, 1988. 143-48. Biggar RJ, Melbye M, Kestems L, et al. Kaposi’s sarcoma in Zaire is not associated with HTLV III infection. N Engl J Med 1984; 311: 1051. Chow JWM, Lucas SB. Endemic and atypical Kaposi’s sarcoma in Africa: histopathological aspects. Clin Exp Dermatol 1990; 15: 253-59. Desmond-Hellman S, Mbidde EK, Kizito A, Heellman NS, Ziegler JL. The value of a clinical definition for epidemic KS in predicting HIV seropositivity in Africa. J Acquired Immune Defic Syndr 1991; 4: 647-51.
Heart disease in myotonic dystrophy SIR,-In your recent editorial (Feb 29) you rightly emphasise the importance of regular review and electrocardiographic monitoring for all patients with myotonic dystrophy, to prevent the serious and often fatal consequences of conduction defects. Our experience is that most such patients seen by us from outside our area are having no regular review, whether by neurologists, cardiologists, or physicians, or even by their family doctors. Two additional points are worth mentioning. First, the high frequency of cardiorespiratory problems after anaesthesia and surgery1 makes it essential that those involved recognise that the patient has myotonic dystrophy, and that preoperative assessment, as well as careful management during and after surgery, is undertaken. Sadly, the risks are still far from being well recognised, as a legal report in The Lancet and subsequent correspondence shows.2,3
Secondly, after the recent isolation of the myotonic dystrophy recognition of the predicted protein product as a protein kinase,4 the gene has proved to be especially strongly expressed in heart muscle. This should allow detailed investigation gene and the
of the nature of the cardiac defect, so frozen cardiac tissue, obtained at necropsy or heart surgery from myotonic dystrophy patients, should be preserved for future study. We may eventually be able to develop a protective therapy that will avoid the principal cause of death in myotonic dystrophy patients. Institute of Medical Genetics, University of Wales College of Medicine, Cardiff CF4 4XN, UK
PETER S. HARPER WILLIAM REARDON
Harper PS. Myotonic dystrophy. London: W B. Saunders, 1989: 114-16. Postoperative monitoring in patients with muscular dystrophy. Lancet 1989; ii: 1053-54. 3. Harper PS. Postoperative complications in myotonic dystrophy. Lancet 1989; ii: 1269. 4. Brook JD, McCurrach ME, Harley GH, et al. The molecular basis of myotonic dystrophy expansion of a trinucleotide (CTG) repeat at the 3’ end of a transcript encoding a protein kinase family member. Cell 1992; 68: 799-808 1.
2 Brahams D.
