1127 clinical improvement. The increase may be due to competition between PCA and GSH for the protein-binding sites, PCA thus liberating protein-bound GSH. Oslo Sanitetsforenings Rheumatism Oslo 1, Norway Institute of Clinical Biochemistry,
Rikshospitalet University Hospital, Oslo
GRO GULDAL EGIL JELLUM
PROGRESSIVE SYSTEMATISED LEIOMYOMA are among the most ubiquitous of since they arise from smooth muscle. They may occur in any organ. In their most dramatic form they are found as large tumours in the uterine wall or oesophagus. Yet there is another version appearing as small papules which remain clinically undetected in sites other than the skin. We present an example of episodic bouts of pain in a patient whose life-long symptoms would have been inexplicable had the causal leiomyomas been present in any organ other than the skin. In cases of persistent recurrent attacks of pain in areas where smooth muscle abounds the possibility of occult leiomyomas should be borne in mind. This 41-year-old female first noted reddish papules on her arms and chest at the age of 12. Over three decades these had slowly extended, becoming larger, more numerous, and confluent. There are now hundreds of them, affecting the extensor surfaces of both upper and lower arms, the upper chest and back, and the neck (fig. 1). The forearms have shown growths for the past 5 years only. The lesions are the sites of episodic bouts of pain in response to cooling, rubbing, or scratching the skin and in response to stress (she may be awakened by an attack of pain associated with an alarming dream). Initial diagnoses included vitamin A deficiency, naevi, and steatocystoma multiplex, but four biopsies have clearly established the diagnosis of leiomyoma. These biopsy specimens uniformly showed almost complete replacement of the dermal connective tissue by fascicles of smooth muscle tissue. The arrangement of the fascicles and the cytology mimics the arrector pili muscle of the hair follicles of the skin (fig. 2).
1---Close view of upper arm studded with irregular, discrete, and confluent reddish papules.
Fig. 2-Skin of arm, showing throughout dermis. (Reduced to -!x 100.)
smooth muscle tissue
At age 27, the patient had had a hysterectomy because of painful leiomyomas of the uterus. Her general health has been
excellent 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" elevations on the skin, and severe prolonged pain localised to the site of contact. Treatment has never been prescribed. Leiomyomas are fascinating because they do things. They may visibly contract or blanch, and they hurt when stimulated physically by trauma or cold or pharmacologically by adrenergic agents.1-3 Uterine leiomyomas have receptors for cestrogens as well as the enzyme systems for metabolising restrogen.4,5 Cutaneous and uterine leiomyomas may elaborate erythropoietin and in turn cause clinical erythrocytosis.6 The most instructive feature of leiomyomas, however, is in the fact that they produce real pain when they contract in response to any of the smooth muscle stimuli. The pain apparently results from compression of the nerve trunks coursing within the smooth muscle bundles of the tumour.? The appearance of our patient’s growths at inenarche and their insidious progressive systematised extension over the next three decades suggests that they may be oestrogen related. Uterine leiomyomas (this patient’s became clinically evident at an early age) show a growth response associated with the hor1. 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. Arch Dermatol 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 binding proteins in normal human myometrium and leiomyoma tissue. J Clin Chem Clin Biochem 1978; 16: 503-11. 5. Pollow K, Sinnecker G, Boquoi E, Pollow B. In vitro conversion of Estradiol—17&bgr; into estrone in normal human myometrium and leiomyoma.J Clin Chem Clin Biochem 1978; 16:493-502. 6. Eldor A, Even-Paz Z, Polliack A. Erythrocytosis associated with multiple cutaneous leiomyomata Report of a case with demonstration of erythro poietic activity in the tumor. Scand J Hæmatol 1976; 16: 245-49. 7. Mann PR. Leiomyoma cutis: An electron microscope study. Br J Dermatol 1970; 82: 463-69.
the oestrogen in contracep-
DISTRIBUTION OF VIRUS TITRES ASCRIBED TO RESPIRATORY
tried, the possibility of
as well as adrenergic blocking muscle relaxants. and smooth Tranquillisers to reduce agents stress-related attacks of pain have been used with success in one patient.9 Excision, the treatment of choice for solitary or large 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 occult growths within the body may account for long-term persistent focal attacks of pain of completely undetermined nature. Such small growths, although clinically non-demonstrable, are nevertheless common. In one series of fifty carefully examined stomachs, 46% had small leiomyomas.’" Their role in abdominal pain could be an appreciable one.
ovariectomy could be considered
Department of Dermatology, School of Medicine, University of Pennsylvania, Philadelphia, Pennsylvania 19104, U.S.A.
WALTER B. SHELLEY
MARGARET G. WOOD
RISK OF CONTACT INFECTION AFTER INTRANASAL RUBELLA VACCINATION
Dr Ingalls (April 14 and Oct. 13) solution to the problem of the rubella-
has put forward "... a immunity gap in a preparation of RA27/3 for intranasal administration only." Professor Banatvala and his colleagues (May 5) support the choice of RA27/3 but reject the need for intranasal administration. However, this debate has turned on the level and type of immunity evoked and has not considered the question of how administration by a new route (i.e., intranasally) affects a matter which is crucial to the safe use of the vaccine-namely, contact spread. The climate of opinion in Britain regarding the risks of rubella vaccination in association with pregnancy seems to have been influenced unduly by two reports from the U.S.A. describing series of inadvertent vaccinations in pregnancy without evident harm to the full-term baby, but without mention of the vaccine strains administered in these cases.1,2 Far too little is known of the factors determining teratogenicity to warrant prediction of the risk associated with one rubella vaccine from the results of administration in pregnancy of another strain of quite distinct derivation. Yet, by omission of details of the vaccine types and of their respective numbers, these reports encourage just such an extrapolation. The reports seem to compound the error by setting an upper limit to the risk attendant upon vaccination in pregnancy by combining data concerning more than one vaccine. We in Britain are not justified in taking reassurance in these observations until there are enough data relevant to the Cendehill strain (used both here and in the U.S.A.) to enable its performance to be assessed separately from that of the HPV strain (until its recent withdrawal used extensively in the U.S.A. but not at all in Britain). These sources1,2 can shed no light upon the behaviour of the subcutaneously administered RA27/3 vaccine, widely used in Britain but only recently licensed in the U.S.A; and no data are available on the intranasal administration of the RA27/3 vaccine in pregnancy. In the absence of definitive evidence of lack of teratogenicity the safe use of all rubella vaccines depends, and will in practice 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: 960 2. Modlin JF, Herrmann K, Brandling-Bennett AD, Eddins DL, Hayden GF. Risk of congenital abnormality after inadvertent rubella vaccination of pregnant women. N Engl J Med 1976; 294:972-74.
number of vaccinees.
continue to depend, upon avoidance of administration in pregnancy ; and, equally important, upon lack of communicability of the vaccine infection from non-pregnant vaccinees to their possibly pregnant contacts. We present here some comparative data on the titres of virus found post-vaccination in the respiratory secretions of three groups of young women. 21 students were given the Cendehill vaccine subcutaneously, 8 the RA27/3 vaccine subcutaneously, and another 9 the RA27/3 vaccine intranasally. Nose and throat swabs and nasal washings were taken daily from day 7 to day 17 after vaccination, a period covering the time of maximal virus shedding. Similar specimens were taken from 3 cases infected with wild type rubella virus. Although the intensity of sampling of the three groups of vaccinees was the same, the 9 intranasally inoculated women gave by far the greatest number of positive specimens. The table shows the distribution of virus titres ascribed to the positive specimens from each group. This distribution varied from generally low titres in the Cendehill subcutaneous group, rising through the RA27/3 subcutaneous group to the RA27/3 intranasal group where a degree of overlap with titres found in specimens from natural rubella occurred. Such figures cannot, of course, show that infection of contacts will occur following intranasal inoculation with RA27/3 vaccine. But these substantial levels of excretion in conjunction with the known ability of RA27/3 to infect by the respiratory route in low inocula3 clearly demand that before the vaccine can be licensed for general use intranasally, contact trials must have been organised on a scale sufficient to show that contact spread is at most very uncommon. In fact the present position is that whereas the current vaccines were licensed for subcutaneous use on the basis of the cumulative evidence of contact studies from many parts of the world and involving altogether thousands of susceptible contacts, the trials involving intranasal administration of RA27/3 vaccine have been on a limited scale.’.5 Furthermore, they include one report of seroconversion in a contact.6 Do these contact trials provide adequate support for what would be effectively a new procedure? It would be unwise to
3. Plotkin SA, Ingalls TH, Farquhar JD, Katz M. Intranasally administered rubella vaccine. Lancet 1968; ii: 934-37. 4. International Symposium on Rubella Vaccines. Symp Ser Immunol Standard
of the International Conference
Rubella Immunisation. Am
J Dis Child 1969; 118: 155-410. 6. Saidi S, Naficy K. Subcutaneous and intranasal administration of RA27/3 rubella vaccine alone and in conjunction with live attenuated measles vaccine. Am J Dis Child 1969; 118:209-12.