21

1. Croft CB, Wilkinson AR. Ulceration of the mouth, pharynx, and larynx in Crohn’s disease of the intestine. Br J Surg 1972; 59: 249-52. 2. Basu MK, Asquith P, Thompson RA, Cooke WT. Oral manifestations of Crohn’s disease. Gut 1975; 16: 249-54. 3. Issa MA. Crohn’s disease of the mouth. Br Dent J 1971; 130: 247-48. 4. Schiller KFR, Golding PL, Peebles RA, Whitehead J. Crohn’s disease of the mouth and lips. Gut 1971; 12: 864-65. 5. Frankel DH, Mostofi RS, Loriniz AL. Oral Crohn’s disease: report of two cases in brothers with metallic dysgeusia and a review of the literature. J Am Acad Dermatol 1985; 112: 260-68. 6. Williams AJK, Wray D, Ferguson A. The clinical entity of orofacial Crohn’s disease. Q J Med 1991; 79: 451-58. 7. Scully C, Cochran KM, Russell RI, et al. Crohn’s disease of the mouth: an indicator of intestinal involvement. Gut 1982; 23: 198-201. 8. Wiesenfeld D, Ferguson MM, Mitchell DN, et al. Orofacial granulomatosis—a clinical and pathological analysis. Q J Med 1985; 54: 101-13. 9. Levenson MJ, Ingerman M, Grimes C, Anand V. Melkersson-Rosenthal syndrome. Arch Otolaryngol 1984; 110: 540-2. 10. James J, Patton DW, Lewis CJ, et al. Orofacial granulomatosis and clinical atopy. J Oral Med 1986; 41: 29-30. 11. Sweatman MC, Tasker R, Warner JO, et al. Oro-facial granulomatosis response to elemental diet and provocation by food additives. Clin Allergy 1986; 16: 331-38. 12. Pryce DW, King CM. Orofacial granulomatosis associated with delayed hypersensitivity to cobalt. Clin Exp Dermatol 1990; 15: 384-96. 13. Worsaae N, Christensen KC, Schiodt M, et al. Melkersson-Rosenthal syndrome and cheilitis granulomatosa. Oral Surg 1982; 54: 404-13. 14. Hering H, Scheid P. Kritische Bemerkungen zum MelkerssonRosenthal-syndrom als Teilbild des Morbus Besnier-BoeckSchaumann. Arch Dermatol Syph (Berlin) 1954; 197: 344-82. 15. Lindelof B, Eklund A, Liden S. Kveim test reactivity in MelkerssonRosenthal syndrome (cheilitis granulomatosa). Acta Derm Venerol 1985; 65: 443-45. 16. Shehade SA, Foulds IS. Granulomatous cheilitis and a positive Kveim test. Br J Dermatol 1986; 115: 619-22. 17. Orlando MR, Atkins JS. Melkersson-Rosenthal syndrome. Arch Otolaryngol Head Neck Surg 1990; 116: 728-29. 18. Greene RM, Rogers RS. Melkersson-Rosenthal syndrome: a review of 36 patients. J Am Acad Dermatol 1989; 21: 1263-70. 19. Field EA, Tyldesley WR. Oral Crohn’s disease revisited-a 10 year review. Br J Oral Maxillofac Surg 1989; 27: 114-23. 20. Madanes AZ, Farber M. Danazol. Ann Intern Med 1982; 96: 625-30. 21. Podmore P, Burrows D. Clofazimine—an effective treatment for Melkersson-Rosenthal syndrome or Miescher’s cheilitis. Clin Exp Dermatol 1986; 11: 173-78. 22. Allen CM, Camisa C, Hamzeh S, Stephens L. Cheilitis granulomatosa: report of six cases and review of the literature. J Am Acad Dermatol

1990; 23: 444-50.

Noise and

hearing loss

The UK National Study of Hearing has shown that, after age, the most common aetiological factor associated with permanent hearing loss in men is noise exposure;’ the same is true of tinnitus.2 In the USA, about 28 million people have impaired hearing and about half of these cases are at least partly attributable to damage from exposure to loud sounds.3 Hazardous noise exposure is by far the most common preventable cause of hearing loss, and has therefore attracted much research,4industrial health activity ,** standardisation,6 and legislation.Last year the National Institutes of Health in Bethesda held a consensus conference on the subject and subsequently issued a consensus statement.3 Noise-related hearing impairment can occur at any age; even young infants may be affected. The disability is often accompanied by tinnitus, which can be very troublesome. Loud short-lived sounds—eg, from an explosion or gunfire--can lead to immediate, severe, and permanent loss of hearing; this condition is known as acoustic trauma. Chronic exposure to less

intense, hazardous sounds—eg,

work or during leisuretime activities-results in a gradual diminution of hearing sensitivity of which the victim is initially unaware. The latter disorder is noise-induced hearing loss (NIHL). In NIHL, each exposure to noise damages a few hair cells. As exposure continues, more and more hair cells are damaged and some are destroyed. The cells are not replaced after destruction. For reasons that are unclear, there are considerable differences in susceptibility to noise damage between individuals, between ears, and at different times within the same individual. Hearing loss is measured with pure-tone audiometry, by which auditory thresholds are determined at various frequencies. The first audiometric sign of NIHL in each ear is usually loss of sensitivity at higher frequencies, maximal at 3, 4, or 6 kHz but with less loss at 8 kHz, hence the characteristic notch configuration. This notch may be eliminated with further hearing loss from noise or ageing, so the presence or absence of NIHL cannot be firmly established from the audiogram alone. Both ears are usually affected, but often not to the same at

extent.

As the consensus statement points out, although the energy in speech is largely contained within the low frequency range, much of the information required to understand speech resides within the higher frequencies, and is therefore inaudible to patients with NIHL. Other associated dysfunctions—eg, of frequency and temporal resolution-cause particular hearing difficulties with background noise, competing voices, or room reverberation. Permanent hearing loss is common with sound levels above 85 dB(A) and exposure of 8 h/day for many years.Thus, the often cited 90 dB(A) level does not imply safety, but is a compromise limiting the potential hazard. To predict the likelihood of NIHL one requires knowledge of typical durations and the number of exposures. The trade-off between noise level and exposure duration has been defmed

intemationally6,7 by the total-energy concept; a doubling of noise exposure duration is regarded as equivalent to a 3 dB increase in noise level. Nevertheless, some American regulations use 5 dB per doubling of duration, whereas a more recent analysis of worldwide epidemiological data8 casts doubt on any simple rule. With noise levels above 140 dB peak, as in acoustic trauma, far more damage is liable to result than is predicted from the energy concept. As a rule of thumb, hazardous noise should be suspected if the listeners find communication difficult while exposed to the sound, or if they experience ringing in the ears and/or sounds seem muffled after they leave the sound exposure area. The acoustic energy of the sound reaching the ear, not its source, is the most important factor-at work, at school, at home, or during leisure activities.9,10 With regard to prevention, the NIH consensus report draws four conclusions. Personal hearing protection should be used whenever hazardous

22

unavoidable. Vigorous enforcement of existing regulations would substantially reduce the risk of workplace NIHL. Application of existing techniques to source noise control would greatly reduce sound levels at the ear. A comprehensive programme of education on the causes and prevention of NIHL should be developed and disseminated, and one group who should not be neglected are school-age children, especially with respect to amplified music. The report identifies twelve directions for future research, to which one could add a thirteenth-the need for better definition and measurement of hearing disability, which should lead to a more equitable and universally acceptable method of assessment. The deliberations over the past 5 years of the UK exposures

are

Inter-Society Working Group on Hearing Disability expected to be published next year and to provide an important step forward in this direction. are

1. Davis AC. The

disability

prevalence of hearing impairment and reported hearing Int J Epidemiol 1989; 18:

among adults in Great Britain.

911-17. 2. Coles R, Smith P, Davis A. The relationship between noise-induced hearing loss and tinnitus, and its management. In: Berglund B, Lindvall T, eds. New advances in noise research, part 1. Stockholm: Swedish Council for Building Research, 1990: 87-112. 3. US Department of Health and Human Services. Noise and hearing loss. NIH Consensus Development Conference, Consensus Statement 8(1), 1990. 4. Kryter KD. The effects of noise on man. 2nd ed. London: Academic Press, 1985. 5. Tempest W, ed. The noise handbook. London: Academic Press, 1985. 6. International Organization for Standardization. Acoustics— determination of occupational noise exposure and estimation of noise-induced hearing impairment. ISO 1999.2: 1989. 7. Council of the European Communities. Directive of May 12, 1986 on the

of workers from the risks related to exposure to noise at work. 8. Robinson DW. Noise exposure and hearing: a new look at the experimental data. Health and Safety Executive Contract Research report 1/1987. London: HM Stationery Office, 1987. 9. MRC Institute of Hearing Research. Damage to hearing arising from leisure noise: a review of the literature. Report to UK Health and Safety Executive. London HM Stationery Office, 1985. Summarised Br J Audiol 1986; 20: 157-64. 10. Rice CG, Rossi G, Olina M. Damage risk from personal cassette players. Br J Audiol 1987; 21: 279-88.

protection

Ribavirin for

HIV—continuing smoke,

not much fire Amid the general sense of urgency, felt by medical scientists and patients alike, to find effective treatments for human immunodeficiency virus (HIV) infection, the story of ribavirin for this purpose is curious indeed. The drug was first shown to have in vitro activity against HIV in 1984,1 and clinical trials were initiated in 1985 in various infected subgroups. These trials were poorly designed by today’s standards, with vague entry criteria, inadequate sample sizes, and haphazard clinical follow-up and data reporting. The design flaws partly arose from limited knowledge of the natural history of HIV disease and were compounded by inexperience in the design and conduct of clinical investigations in this new

illness.

Results of these early efforts continue to be controversial. A brief placebo-controlled trial2 in patients with diffuse lymphadenopathy (a population now regarded as part of the symptomless HIV disease subgroup) showed a significant clinical benefit, with fewer cases of AIDS in those receiving ribavirin. Nevertheless, the extremely high progression rates in both groups—eg, 18-7% in the placebo group over the 7-month study period-suggested the incorrect entry of patients with more advanced, symptomatic disease. Moreover, despite randomisation, more patients with severely depressed CD4 cell counts were entered into the placebo arm of the trial. Perhaps the most damaging criticism of this trial, however, was the allegation, publicly expressed by the Food and Drug Administration (FDA) Commissioner, Frank Young, at the third international conference on AIDS in 1987, that the investigators had a financial conflict of interest. These suspicions were never publicly confirmed or refuted. By contrast, a second early US trial of ribavirin in patients with established symptomatic HIV disease did not show a useful clinical effect. In neither trial was there any significant antiviral effect, and if anything ribavirin diminished CD4 counts. In this issue (p 6), Dr Gatell and colleagues in Spain report the results of another clinical trial in which no clinical or laboratory benefit was detected. So why the continuing interest in ribavirin as an HIV treatment? Why has the drug been licensed for this purpose in several countries, including Ireland? Part of the answer must lie in the acknowledged shortcomings of other antiretroviral agents. Zidovudine is not completely effective in inhibiting HIV replication and has been associated with the development of in-vitro resistance in patients with advanced HIV disease. This drug was first used only in advanced disease, and in doses now recognised as excessive, and consequently it gained a reputation as a toxic and expensive agent. Moreover, because zidovudine was rapidly accepted by the medical "establishment", it became a target for those who felt that they were being exploited in the increasing commercialisation of this new disease. By contrast, ribavirin was regarded as the "little guy" and it acquired an underground panache (at least in the USA) when many people imported the drug (with the tacit FDA approval) for their own use or for friends. In its favour was subjective toxicity much less than that of zidovudine, or of other nucleoside analogues including dideoxyinosine and dideoxycytidine. Where do we go from here? Although enthusiasm for ribavirin has waned, enough questions have been raised to stimulate further, definitive, clinical trials. In view of the earlier suspicions, such studies should be designed and conducted with maximum independence from the drug’s manufacturer. This independence should extend to the analysis and reporting of trial data, which should be centralised and, of course, blinded. Investigators and patient