T H E LANCET
bacteriological cultures-are essential. Only in rare circumstances should a test be interpreted outside the clinical setting in which it is done. T h e test merely serves to intensify, confirm, or weaken our suspicion that the patient has the disease. The patient described by Maderazo had apical infiltrates on a chest radiograph. T h e number of diagnostic possibilities is limited, and excluding tuberculosis on the basis of an equivocal skin test was inappropriate. David J Evans, Richard J Barker, *Duncan M Geddes Royal Brompton Hospital, London SW3 6NP. U K
Maderazo EG. Interpreting tuberculosis skin tests. Lancer 1996;348: 832-33. 2 Holden M, Dubin MR, Diamond PH. Frequency of negative intermediate-strength tuberculin sensitivity in patients with active tuberculosis. N E n g l J M e d 1971;285: 1506-09. 3 Odelwo EO.Mantoux test tuberculin reaction in Nigerians. AfrJ Med Med Sci 1994;23: 91-98. 4 Rose DN, Schechter CB, Adler JJ. Interpretation of the tuberculin skin test. J Gen Intern Med 1995; 10: 63542.
with the then new non-sedative H, antagonists terfenedine, and astemizol had n o effect on the pruritus of eczema (measured subjectively as itch and objectively as scratch, with the use of limb meters), whereas old and less potent, but centrally depressive HI-antagonists such as trimeprazine were antipruritic. Furthermore, the central action of antipruritic antihistamines and other drugs is not solely sedative: nocturnal itch-provoked scratch was not suppressed by barbiturates (although they may be amnesic) but was suppressed by anxiolytic benzodiazepines such as nitrazipam and certain other central depressants.’ As Greaves and Wall say, much remains unknown about the mechanism of itch and its control (and certainly, greater use of objective methods of measurement would help’,’), which is why it would be sad if an important therapeutic lesson was lost: the pure HI-antihistamines have no effect on the itch of eczema. Sam Shuster Department of Dermatology, University of Newcastle upon Tyne. Newcastle upon Tyne NE2 ~ B w U, K Greaves MW, Wall I‘D. Pathophysiology of itching. Lancet 1996;348: 93840. 2 Kraus L,Shuster S . Mechanism of action of antipruritic drugs. BMJ 1983;287: 1199-200. 3 Shuster S. Reason and the rash. h c R Inst Great Britain 1981;53: 136-63. 1
Pathophysiology of itching .%-Greaves and Wall (Oct 5, p 938)’ suggest that “opioid p-receptor-dependent processes activate inhibitory circuits in the central nervous system and regulate the extent of intensity and quality of perceived itch”. Although it is true that stimulation of opioid preceptors inhibits pain, the evidence suggests quite the opposite for itch: activation of opioid-dependent pathways (for example, by morphine) has a stimulatory, rather than inhibitory, effect o n itch.” As would be predicted from this observation, molecules that block opioid receptors decrease itching in several clinical and experimental systems;’ this is the converse of what happens with pain, and indicative of the curious, and at least partly reciprocal, relation between the two sensations. Perhaps the same circuits are inhibitory for one and stimulatory for the other, but it is also possible that different circuits are involved. I admit that in the absence of neuroanatomical proof, thinking about pathways of inhibition and disinhibition interacting with agonists and antagonists is akin to working with double and triple negatives, open to multiple theoretical models, and enough to make one’s face,’ if not head, itch.
SIR-We question whether the p-system, as Greaves and Wall’ state, is the only relevant central opioid receptor involved in modulating itching. Our opinion is based on the findings in patients with primary biliary cirrhosis. In this condition there is a sustained rise in plasma concentration of Gopioid agonists (met-enkephalin and leu-encephalin).’ This increase allows these substances to penetrate the blood-brain barrier. Thomton and Losowski’ reported that following first administration of the opioid antagonist nalmefene itch was much alleviated, but the improvement was accompanied by a simultaneous opioid withdrawal reaction. They felt that the improvement in the level of pruritis was probably caused by the inhibition of the opioid substances that had caused the release of pruritic substances. It is of course possible that these centrally active Gagonists contributed to itch by direct action on the central nervous system &receptors, especially since the therapeutic effect of the antagonist occurred with the initial dose.
Jeffrey D Bernhard
*Mark A Gillman, Frederick J Lichtigfeld
Division of Dermatology, University of Massachusetts Medical School, Worcester,
South African Brain Research Institute. Waverley 2090, Johannesburg, South Africa
MA 01655. USA
Greaves MW, Wall PD. Pathophysiology of itching. Lancet 1996;348: 938-40. 2 Thomton JR, Losowski MS. Opioid peptides and primary biliary cirrhosis. BMJ 1988;297: 1501.03. 1
Greaves MW, Wall PD. Pathophysiology of itching. Lancet 1996;348: 93840. Tuckett RP.Neurophysiology and neuroanatomy of pruritus. In: Bemhard JD, ed. Itch: mechanisms and management of pruritus. New York McGraw-Hill, 1994: 1-22. Lemer EA.Chemical mediators of itching. In: Bemhard JD,ed. Itch: mechanisms and management of pruritus. New York: McGraw-Hill, 1994:23-35. Bergasa NV,Jones EA. The pruritus of cholestasis: potential pathogenic and therapeutic implications of opioids. Gastroenterology 1995;108: 1582-88. Thomas DA, Williams GM, Iwata K, Kenshalo DR, Dubner R. Multiple effects of morphine on facial scratching in monkeys. Anesth Analg 1993;17: 933-35.
SIR-In an otherwise useful review, Greaves and Wall’ say “the extent to which [the antipruritic effect of antihistamines in atopic eczema] is attributable to the side-effect of central sedation rather than local histamine antagonism in the skin is unclear”. But the reference cited’ was absolutely clear. It reported that total, or virtually total, HI-blockade in the skin
Vol348 * November 30, 1996
SIR-I believe that Greaves and Wall1 misuse the term tachykinin. They state that “Tachykinins include the neuropeptides substance P, calcitonin gene-related peptide (CGRP), and vasoactive intestinal peptide (VIP)”. Erspamer’ introduced the word tachykinin to describe the promptness of action on smooth muscle (Greek takus=fast) of peptides he isolated from the skin of several species of amphibians and the salivary glands of Eledone, a Mediterranean octopod. Among the peptides he included as members of this family are physalaemin, eledoisin, and kassinin. Substance P is a mammalian tachykinin, as are neurokinin A (substance K) and neurokinin B (neuromedin K). The structural feature usually regarded as a characteristic of this peptide group is a C-terminal sequence of the type Phe-X-Gly-Leu (or Met)-Met-NH,. T h e aminoacid at