35

the 46 cases that have been described included 11 inwhich facial palsy resulted. Campbell emphasises that,though they are growing, these tumours are pathologicallybenign and .that there is no justification for deliberatesacrifice of the facial nerve. The nerve runs an extremelysuperficial course in young children, but a careful tech-nique should ensure that accidental damage is rare.

Further knowledge of the natural history of the lesion,however, would make it easier to decide whether the

operation is always justified or whether there may be agroup in which it is wisest to delay. The impression isthat this is one of those subjects in which much moreexperience and knowledge must exist than has beenrecorded.

1. Sutton, H. G. Medical Mirror, 1864, 1, 769.2. Babington, B. G. Lancet, 1865, ii, 362.3. Legg, W. Ibid, 1876, ii, 856.4. Rendu, M. Bull. mém. Soc. méd. Hôp., Paris, 1896, 13, 731.5. Osier, W. Johns Hopk. Hosp. Bull. 1901, 12, 333.6. Stefanini, M., Dameshek, W. The Hemorrhagic Disorders.

New York, 1955 ; p. 49.7. Landau, J., Nelken, E., Davis. E. Lancet, 1956, ii, 230.8. Wintrobe, M. M. Clinical Hematology. London, 1951 ;

p. 794.

HEREDITARY HÆMORRHAGIC TELANGIECTASIA

THE odd condition called hereditary haemorrhagictelangiectasia, which can cause serious bleeding frommucous membranes, especially from the nose, has beenknown for a long time. Gawen Sutton,1 in 1864, describedsome curious cases of recurrent epistaxis, and Babington,2in 1865, contributed a letter to our columns brieflylisting members of 5 generations in a single familywho had suffered from epistaxis ; but neither of these

physicians had any clue to the cause of the epistaxis intheir patients. Just 80 years ago Legg 3 gave a paper tothe Royal Medico-Chirurgical Society of London on" a case of haemophilia complicated by multiple naevi " ; ;

we should not now use the name haemophilia, but thereis no doubt about the nævi. This seems to be the firstcase of haemorrhagic telangiectasia to be properlydescribed, though the credit is usually given to Rendu 4in 1896 and Osler 5 in 1901, who really gave an adequatedescription of the disease, noted its hereditary character,and correctly ascribed the haemorrhage to disease of theblood-vessels and not to any abnormality in blood-

clotting.Eponyms are now out of favour, and hereditary

haemorrhagic telangiectasia is the name used in all thetextbooks. There are, as Stefanini and Dameshek 6

point out, two basic vascular abnormalities : in the first.there are localised areas where the walls of the capillariesare extremely thin, being reduced to the endotheliallayer only ; in the second, there are visible dilatationsof arterioles and capillaries which can lead to the forma-tion of arteriovenous aneurysms, especially in the lung.The telangiectases are normally much brighter in colour,with bigger visible vessels, than the spider nævi associatedwith liver disease. Their commonest site is in the nose,but careful inspection of affected patients nearly alwaysreveals them on the lips and tongue, under the nails, andelsewhere in the skin, especially of the face and ears.The commonest form of bleeding is epistaxis, but

haemoptysis, melsena, and hæmaturia are quite frequent.Landau et al. described a family in which conjunctivaland retinal lesions were prominent. The hereditarynature of the abnormality is well established as a simpledominant affecting both sexes. The most strikingexample is that given in Wintrobe’s textbook 8 : a

Mormon with hæmorrhagic telangiectasia had 22 childrenby his 4 wives and 10 of these children were affected intheir turn ; these affected members of the family passedon the disease for another three or four generations, andno less than 82 affected descendants of the originalprogenitor were known in this family when the list wasput together. It is clear from this and other examples

that unaffected individuals do not pass on the disease.There is also some evidence suggesting that the type oflesion is also inherited ; thus, arteriovenous aneurysmsare common in some affected families and never occurin others. The diagnosis of the disease is not difficultif its existence is borne in mind and if the characteristiclesions on the lips, tongue, or face, or under the nailsare sought in every case of recurrent epistaxis, melaena,or other bleeding for which there is no obvious cause.The disease can be quite mild or it can be a serious

burden to the patient because of the gradually increasinganaemia caused by repeated bleeding over many years.The anaemia is of the iron-deficiency type, and, if thecondition has been neglected, it often fails to respond tooral iron and needs parenteral iron for its effectivetreatment. Sometimes blood-transfusion is needed torestore the haemoglobin content of the blood as soon aspossible to a safe level. The seriously affected patientmay lead a miserable existence, always at the mercy of arecurrent haemorrhage that his family doctor may beunable to control; and, if the bleeding is from aninaccessible site like the alimentary tract, admission tohospital and blood-transfusion are inevitable. Thenasal, labial, and buccal telangiectases can be directlyattacked. Several methods of applying pressure havebeen devised, and direct application of a thrombin

spray will often stop the bleeding. Various escharotics,including X rays, radium, and electrocoagulation, havebeen tried, but they nearly always fail because newlesions tend to appear near the site of their application.Cochrane and Leslie,9 however, were able to check

bleeding in a patient with angiomas of the scalp andface by a small dose of contact X rays.A quite different approach has been by way of treat-

ment with cestrogens. This method arose from theobservation that in affected women bleeding seemed tobe worse at the end of the menstrual cycle and sometimessubsided spontaneously shortly after the onset of mens-truation ; so the bleeding was worst at a time whensecretion of cestrogens is low and urinary excretion ofgonadotrophins is relatively increased. Acting on thisidea, Koch et al.10 treated 5 patients with ethinylcestradiol, using doses of 0.25 mg. daily-about ten timesthe dose given to control menopausal symptoms. In

males, 5 mg. daily of methyl testosterone was given tocounteract feminising side-effects. Koch et al. claimedconsiderable success, but Stefanini and Dameshek,6 forexample, found the treatment of no value. Harrison,l1at Guy’s Hospital, has lately re-examined this form oftreatment applied to 4 patients (2 men and 2 women)with typical lesions. He began by giving 0.25 mg.ethinyl cestradiol daily, but gradually increased thedose to 1 mg. daily in both women and 1 of the men ;the men were also given 5 mg. methyl testosterone daily.In spite of these large doses, the only side-effect wasthat 1 of the women had a uterine haemorrhage afterthree months, but this did not recur in spite of continuedtreatment. All the patients were much improved, andthe haemorrhages from the telangiectases were much lesscommon or even stopped altogether. At the time of his

report, Harrison had not stopped the treatment ; Kochet al. found that bleeding returned three weeks afteroestrogens were stopped, and Harrison therefore proposedto reduce the dose gradually to try to find a minimumlevel for each patient; but he had no results to reportat the time.

Sections of tissue from the inferior turbinates weretaken before and after treatment in 2 cases, and theyshowed that the normal columnar epithelium had

changed to a squamous one. It may in fact be this

change which protects the telangiectases from trauma9. Cochrane, T., Leslie, G. Lancet, 1950, i, 255.

10. Koch, H. J., Escher, G. C., Lewis, J. S. J. Amer. med. Ass.1952, 149, 1376.

11. Harrison, D. F. N. Guy’s Hosp. Rep. 1956, 105, 246.

36

and therefore makes them less likely to bleed. The

oestrogen treatment of telangiectasia thus seems worth atrial in severely handicapped patients ; but, as Harrisonemphasises, it is unwise to give 1 mg. of oestrogen a dayfor long periods to young persons, and he suggests thatthe treatment should be restricted to women who havepassed the menopause and to men of comparable age.

1. Dubash, H. J., Teare, D. Brit. med. J. 1946, i, 45.2. Lewes, D. Ibid, 1948, ii, 383.3. Steyn, D. G., Steyn, D. W., van der Westhuizen, G. C. A.,

Louwrens, B. A. S. Aft. med. J. 1956, 30, 885.4. Edible and Poisonous Fungi. Ministry of Agriculture, Fisheries,

and Food Bulletin no. 23. H.M. Stationery Office, 1952.5. Barbour, H. G., Devenis, M. M. Arch. intern. Med. 1919, 24, 617.6. Cochran, J. B. Brit. med. J. 1952, ii, 964.7. Alexander, W. D., Johnson, K. W. M. Clin. Sci. 1956, 15, 594.

TOADSTOOLS

To garner and consume the wild fruits of the earth isa pursuit so innocent and with such happy associationsthat the rare death caused by poisonous fungi is the morebitter to contemplate. Our European neighbours aremore venturesome than we are and are said to pay the

penalty more often.1 2 It surprised us to learn that thesame peril threatens the ignorant in the Union of SouthAfrica and that our own Amanita phalloides may be thespecies responsible. (Is it a native of those parts or achance introduction given in exchange for the nerineand the gladiolus ?) Steyn et awl. describe two disasterswhich ended in the death of 5 out of 9 of those who hadbeen tempted by the prevalence of "mushrooms" in aplace where the arid climate makes them a rarity. The

history and symptoms showed no unusual features, butthe account includes a valuable résumé of the presentknowledge of the toxic effects of fungi other than A.phalloides. There is a satisfying agreement betweenthe pharmacology of the specifically poisonous speciesand the symptoms which they produce. A. phalloidescontains amanitine with a delayed hepatotoxic action,like phosphorus. A. muscaria and A. pantherina containmuscarine (parasympathomimetic) and myceto-atropine(parasympatholytic) : symptoms and treatment will

depend upon which of these antagonists is the moreabundant. Both species, by the way, taste horrid. The

genus Inocybe contains muscarine alone. Besides- these,there are many species described as " sometimes poison-ous

" and that should be warning enough, even thoughone of these is named Helvella esculenta.The traveller in France who finds strange and flabby

shapes on his plate will be comforted if he sees others

eating the same dish ; in some instances his palate willbe rewarded. If on his return he wishes to persuade hiswife to add variety to his diet, he will be foolish if he doesnot arm himself with the Ministry of Agriculture’s guideto epicurean adventure. 4

THYROXINE-LIKE ACTION OF ASPIRIN

As long ago as 1919, Barbour and Devenis 5 showedthat single doses of aspirin caused an increase in bothoxygen consumption and carbon-dioxide output in normalpersons. These observations were confirmed a few yearsago by Cochran,6 and now Alexander and Johnson haveshown that the low basal oxygen consumption (B.M.R.)of patients with myxœdema can be restored to normalby giving aspirin in doses of about 8 g. (gr. 120) daily.They also showed that their patients’ serum-cholesterollevels fell during treatment with aspirin. The twomeasurements of B.M.R. and serum-cholesterol are norm-ally taken as the best objective index of response tothyroid-hormone treatment ; and in both these respectsAlexander and Johnson’s patients responded as well toaspirin as they did to triiodothyronine. But they didnot feel any better : although warmer, they were still

sluggish and sleepy ; skin and voice remained charac-teristic of the myxcedematous state ; and they did notlose weight. These observations recall Dodds and

Robertson’s demonstration 8 that dinitro-o-cresol can

restore the B.M.R. to normal, without changing the clinicalsigns of myxœdema-although in this instance the analogywith thyroxine is less close, because dinitrophenols donot affect the serum-cholesterol, 9 Alexander andJohnson’s work shows clearly that neither a rise in B.M.R.nor a fall in serum-cholesterol, even occurring simul-

taneously, can be regarded as specific effects of the thyroidhormones.Alexander and Johnson have drawn certain practical

conclusions from their findings. Two of their patientshad angina, which was apparently unaffected by the risein B.M.R. brought about by aspirin, although it becameworse when an approximately equal rise was inducedwith triiodothyronine. They go on to suggest that amixture of aspirin with very small doses of triiodothyro.nine or thyroxine might be rational treatment for thosedifficult cases of myxoedema in which angina is induced(or aggravated) by thyroid preparations. But it is hard tosee that such patients would be any better off after theconsumption of large doses of aspirin, for Alexander andJohnson showed that it does not make them feel anybetter. The only hypothetical benefit from this combinedtreatment would come from the lowering of the serum.cholesterol level. There is certainly some as yet undefinedassociation between serum-cholesterol levels and theoccurrence of coronary atherosclerosis ; but it is notknown whether lowering the serum-cholesterol level

actually retards the development of coronary disease.At the moment, this hypothesis, interesting though it is,hardly seems to justify imposing on patients the side.effects of large doses of aspirin.

In a further suggestion of more immediate practicalimportance, Alexander and Johnson point out that

patients with rheumatic heart-disease are .often treatedwith large doses of aspirin, and that in some cases theincrease in metabolic rate induced by aspirin may addconsiderably to the burden on the heart. This is clearlysomething that needs investigation, but in the meantimeit seems desirable not to prolong aspirin medication inacute rheumatism after the rheumatic - process hassubsided.

8. Dodds, E. C., Robertson, J. D. Lancet, 1933, ii, 1197.9. Cutting, W. C., Ryfand, D. A., Tanifer, M. L. J. clin. Invest.

1934, 13, 547.10. Further contributions would be welcome, and are likely to be

quickly used : the aim is to distribute immediately small sumsfor emergency needs. Cheques should be made out to TheEditor and crossed "Hungarian Doctors Account."

THE REFUGEES

OF the two-score medical refugees who have so farreached these shores from Hungary, some plan to remainhere and others to continue their journey. All are

anxious for news of when they can travel or how theymay obtain employment here.Employment.-The Ministry of Health has not announced

any special arrangements for the employment of refugeedoctors in British hospitals ; but there is reason to hope thatregional boards will establish temporary supernumerary posts.Inquiries regarding professional opportunities here and overseasmay be addressed to the British Medical Association’s Inter-national Medical Visitors Bureau, B.M.A. House, TavistockSquare, London, W.C.1 (tel. Euston 4499).Finance.- Refugees who have left official transit camps and

hostels rnay apply to the local office of the National AssistanceBoard for regular grants. Those needing money for specialexpenses, such as clothes and necessary journeys, shouldwrite to the Lancet office, where a small fund has been startedfor this purpose.lo

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Accommodation.-We are in touch with medical householdswho have offered accommodation to Hungarian colleagues,and will try to find a temporary home for anyone needing it.

Inquiries or requests for help should be addressed eitherto this office or to Brigadier H. A. Sandiford, M.C.,medical director of the B.M.A.’s International MedicalVisitors Bureau.