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clinical improvement. The increase may be due to competitionbetween PCA and GSH for the protein-binding sites, PCA thusliberating protein-bound GSH.

Oslo Sanitetsforenings Rheumatism Hospital,Oslo 1, Norway EIMAR MUNTHE

Institute of Clinical Biochemistry,Rikshospitalet University Hospital,Oslo

GRO GULDALEGIL JELLUM

PROGRESSIVE SYSTEMATISED LEIOMYOMA

SiR,-Leiomyomas are among the most ubiquitous oftumours since they arise from smooth muscle. They may occurin any organ. In their most dramatic form they are found aslarge tumours in the uterine wall or oesophagus. Yet there isanother version appearing as small papules which remain clini-cally undetected in sites other than the skin. We present anexample of episodic bouts of pain in a patient whose life-longsymptoms would have been inexplicable had the causal leio-myomas been present in any organ other than the skin. Incases of persistent recurrent attacks of pain in areas wheresmooth muscle abounds the possibility of occult leiomyomasshould be borne in mind.

This 41-year-old female first noted reddish papules on herarms and chest at the age of 12. Over three decades these hadslowly extended, becoming larger, more numerous, and con-fluent. There are now hundreds of them, affecting the extensorsurfaces of both upper and lower arms, the upper chest andback, and the neck (fig. 1). The forearms have shown growthsfor the past 5 years only. The lesions are the sites of episodicbouts of pain in response to cooling, rubbing, or scratching theskin and in response to stress (she may be awakened by anattack of pain associated with an alarming dream).

Initial diagnoses included vitamin A deficiency, naevi, andsteatocystoma multiplex, but four biopsies have clearly estab-lished the diagnosis of leiomyoma. These biopsy specimensuniformly showed almost complete replacement of the dermalconnective tissue by fascicles of smooth muscle tissue. The ar-rangement of the fascicles and the cytology mimics the arrec-tor pili muscle of the hair follicles of the skin (fig. 2).

Fig. 1---Close view of upper arm studded with irregular, dis-crete, and confluent reddish papules.

Fig. 2-Skin of arm, showing smooth muscle tissue extendingthroughout dermis.

(Reduced to -! x 100.)

At age 27, the patient had had a hysterectomy because ofpainful leiomyomas of the uterus. Her general health has beenexcellent and her routine blood studies were normal.

Ice cube contact with the lesions on the arm for 15 s was

followed by blanching, the appearance of "goose flesh" eleva-tions on the skin, and severe prolonged pain localised to thesite of contact.

Treatment has never been prescribed.Leiomyomas are fascinating because they do things. They

may visibly contract or blanch, and they hurt when stimulatedphysically by trauma or cold or pharmacologically by adrener-gic agents.1-3 Uterine leiomyomas have receptors for cestrogensas well as the enzyme systems for metabolising restrogen.4,5Cutaneous and uterine leiomyomas may elaborate erythropoie-tin and in turn cause clinical erythrocytosis.6The most instructive feature of leiomyomas, however, is in

the fact that they produce real pain when they contract in re-sponse to any of the smooth muscle stimuli. The pain appar-ently results from compression of the nerve trunks coursingwithin the smooth muscle bundles of the tumour.?The appearance of our patient’s growths at inenarche and

their insidious progressive systematised extension over the nextthree decades suggests that they may be oestrogen related.Uterine leiomyomas (this patient’s became clinically evident atan early age) show a growth response associated with the hor-

1. Fisher WC, Helwig EB. Leiomyomas of the skin. Arch Dermatol 1963; 88:510-20.

2. Montgomery H, Winkelmann RK. Smooth muscle tumors of the skin. ArchDermatol 1959; 79: 32-41.

3. Jansen LH, Driessen FML. Leiomyoma cutis. Br J Dermatol 1958; 70:446—51.

4. Pollow K, Geilfusz J, Boquoi E, Pollow B. Estrogen and progesterone bind-ing proteins in normal human myometrium and leiomyoma tissue. J ClinChem Clin Biochem 1978; 16: 503-11.

5. Pollow K, Sinnecker G, Boquoi E, Pollow B. In vitro conversion of Estra-diol—17&bgr; into estrone in normal human myometrium and leiomyoma. JClin Chem Clin Biochem 1978; 16:493-502.

6. Eldor A, Even-Paz Z, Polliack A. Erythrocytosis associated with multiplecutaneous leiomyomata Report of a case with demonstration of erythropoietic activity in the tumor. Scand J Hæmatol 1976; 16: 245-49.

7. Mann PR. Leiomyoma cutis: An electron microscope study. Br J Dermatol1970; 82: 463-69.

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monal changes of pregnancy or the oestrogen in contracep-tives.8

Although no treatment has been tried, the possibility ofovariectomy could be considered as well as adrenergic blockingagents and smooth muscle relaxants. Tranquillisers to reducestress-related attacks of pain have been used with success inone patient.9 Excision, the treatment of choice for solitary orlarge lesions, is not feasible in our patient.

Perhaps our patient offers us more than we can offer her.She provides us with a paradigm of how small clinically occultgrowths within the body may account for long-term persistentfocal attacks of pain of completely undetermined nature. Suchsmall growths, although clinically non-demonstrable, are

nevertheless common. In one series of fifty carefully examinedstomachs, 46% had small leiomyomas.’" Their role in abdomi-nal pain could be an appreciable one.

Department of Dermatology,School of Medicine,University of Pennsylvania,Philadelphia, Pennsylvania 19104, U.S.A.

WALTER B. SHELLEYMARGARET G. WOOD

RISK OF CONTACT INFECTION AFTERINTRANASAL RUBELLA VACCINATION

SIR,-In forceful terms Dr Ingalls (April 14 and Oct. 13)has put forward "... a solution to the problem of the rubella-immunity gap in a preparation of RA27/3 for intranasal ad-ministration only." Professor Banatvala and his colleagues(May 5) support the choice of RA27/3 but reject the need forintranasal administration. However, this debate has turned onthe level and type of immunity evoked and has not consideredthe question of how administration by a new route (i.e., in-tranasally) affects a matter which is crucial to the safe use ofthe vaccine-namely, contact spread.The climate of opinion in Britain regarding the risks of

rubella vaccination in association with pregnancy seems tohave been influenced unduly by two reports from the U.S.A.describing series of inadvertent vaccinations in pregnancywithout evident harm to the full-term baby, but without mentionof the vaccine strains administered in these cases.1,2 Far too littleis known of the factors determining teratogenicity to warrantprediction of the risk associated with one rubella vaccine fromthe results of administration in pregnancy of another strain of

quite distinct derivation. Yet, by omission of details of the vac-cine types and of their respective numbers, these reports en-courage just such an extrapolation. The reports seem to com-pound the error by setting an upper limit to the risk attendantupon vaccination in pregnancy by combining data concerningmore than one vaccine. We in Britain are not justified in tak-ing reassurance in these observations until there are enoughdata relevant to the Cendehill strain (used both here and in theU.S.A.) to enable its performance to be assessed separatelyfrom that of the HPV strain (until its recent withdrawal usedextensively in the U.S.A. but not at all in Britain). Thesesources1,2 can shed no light upon the behaviour of the subcu-taneously administered RA27/3 vaccine, widely used in Britainbut only recently licensed in the U.S.A; and no data are avail-able on the intranasal administration of the RA27/3 vaccine inpregnancy.

In the absence of definitive evidence of lack of teratogenicitythe safe use of all rubella vaccines depends, and will in practice

8. Gompel C, Silverberg SG. Pathology in gynecology and obstetrics, 2nd ed.Philadelphia: J. B. Lippincott, 1977.

9. Fox SR. Leiomyomatosis cutis. N Eng J Med 1960; 263:1248-50.10. Ritchie AC. The classification, morphology, and behaviour of tumours. In:

Florey L, ed. General pathology. Philadelphia: W. B. Saunders, 1970.1. Preblud S, Nieburg PI, Hinman AR. Rubella vaccination and pregnancy. Br

Med J 1978; ii: 9602. Modlin JF, Herrmann K, Brandling-Bennett AD, Eddins DL, Hayden GF.

Risk of congenital abnormality after inadvertent rubella vaccination ofpregnant women. N Engl J Med 1976; 294:972-74.

DISTRIBUTION OF VIRUS TITRES ASCRIBED TO RESPIRATORY

SECRETIONS

n= number of vaccinees.

continue to depend, upon avoidance of administration in preg-nancy ; and, equally important, upon lack of communicabilityof the vaccine infection from non-pregnant vaccinees to their

possibly pregnant contacts. We present here some comparativedata on the titres of virus found post-vaccination in the respira-tory secretions of three groups of young women. 21 studentswere given the Cendehill vaccine subcutaneously, 8 the RA27/3vaccine subcutaneously, and another 9 the RA27/3 vaccine in-tranasally. Nose and throat swabs and nasal washings weretaken daily from day 7 to day 17 after vaccination, a periodcovering the time of maximal virus shedding. Similar speci-mens were taken from 3 cases infected with wild type rubellavirus. Although the intensity of sampling of the three groupsof vaccinees was the same, the 9 intranasally inoculated womengave by far the greatest number of positive specimens. Thetable shows the distribution of virus titres ascribed to the posi-tive specimens from each group. This distribution varied fromgenerally low titres in the Cendehill subcutaneous group, ris-ing through the RA27/3 subcutaneous group to the RA27/3 in-tranasal group where a degree of overlap with titres found inspecimens from natural rubella occurred.

Such figures cannot, of course, show that infection of con-tacts will occur following intranasal inoculation with RA27/3vaccine. But these substantial levels of excretion in conjunc-tion with the known ability of RA27/3 to infect by the respira-tory route in low inocula3 clearly demand that before the vac-cine can be licensed for general use intranasally, contact trialsmust have been organised on a scale sufficient to show thatcontact spread is at most very uncommon. In fact the presentposition is that whereas the current vaccines were licensed forsubcutaneous use on the basis of the cumulative evidence ofcontact studies from many parts of the world and involvingaltogether thousands of susceptible contacts, the trials involv-ing intranasal administration of RA27/3 vaccine have been ona limited scale.’.5 Furthermore, they include one report of sero-conversion in a contact. 6

Do these contact trials provide adequate support for whatwould be effectively a new procedure? It would be unwise to

3. Plotkin SA, Ingalls TH, Farquhar JD, Katz M. Intranasally administeredrubella vaccine. Lancet 1968; ii: 934-37.

4. International Symposium on Rubella Vaccines. Symp Ser Immunol Standard1968;no.11.

5. Proceedings of the International Conference on Rubella Immunisation. AmJ Dis Child 1969; 118: 155-410.

6. Saidi S, Naficy K. Subcutaneous and intranasal administration of RA27/3rubella vaccine alone and in conjunction with live attenuated measles vac-cine. Am J Dis Child 1969; 118:209-12.