Vaccinia gangrenosa and agammaglobulinaemia.

Normally, primary vaccination against smallpox produces a vesicle on an inflamed base in four days, enlarging for a further five days with umbilication, and healing under a scab in about three weeks. Pyogenic infection of the primary lesion is the most common complication of vaccinia. Secondary vaccinal lesions may occur as the result of autoinoculation of adjacent or distant areas of skin. The lesions are scanty and their distribution asymmetrical with a minor constitutional reaction. When more numerous and symmetrically distributed, there is malaise and fever indicating a generalized vaccinia. Its incidence is estimated at about 1 in 25,000 vaccinations (Blank and Rake, 1955), and the lesions, appearing one or two weeks after vaccination, resolve with the primary 'take'. A serious type of generalized vaccinia occurs in the presence of pre-existing skin disease, particularly eczema, and is a variety of Kaposi's varicelliform eruption, better called eczema vaccinatum. The prognosis in this rare complication used to be very serious, but with modern treatment is not so. Approximately 1*78 million persons of all ages, of whom 1-05 million were under the age of 1 year, were primarily vaccinated in England and Wales under the National Health Service, during the fiveyear period 1950-54 (Ministry of Health, Annual Reports of the Chief Medical Officer, 1950-54). Of these, the complication of generalized vaccinia was notified in 78 cases (four notified cases of generalized vaccinia after re-vaccination are for obvious reasons excluded), an incidence of 1 in 22 9 thousand primary vaccinations at all ages. Of the total number, six were cases with pre-existing eczema, i.e., eczema vaccinatum, of which two were fatal. Only two cases of generalized vaccinia, in the absence of pre-existing skin disease, died. The one, a girl, aged 4 months, was reported by Laurance, Cunliffe and Dudgeon (1952) as a case of vaccinia gangrenosa; the other was a female infant who died presumably from the same complication on the forty-third day after primary vaccination (Ministry of Health, Annual Report of the Chief Medical Officer, 1952). In all other cases, recovery was rapid and complete. Rare instances of severe similar forms of generalized vaccinia have been reported from time to time. Hutchinson (1879) first described a fatal case of gangrene of skin following vaccination, and he applied the term 'vaccinia gangrenosa' to his case and to that of Stokes (1880). More recently a total of 13 cases of vaccinia gangrenosa have been reported: (Acland and Fisher (1893); Shortt's case (Shortt, 1933) later detailed by Dible and Gleave (1934); Bigler and Slotkowski (1951); the case reported by Laurance et al. (1952) and later by Hall, Cunliffe and Dudgeon (1953); Laurance et al. (1952) mention three other cases of which they had personal communications; Keidan, McCarthy and Haworth (1953); Kozinn, Sigel and Gorrie (1955) reported another and mentioned four other cases, one of which was ascribed to Barbero, Gray, McNair Scott and Kempe (1954, 1955).) Of the total number, the only authentic case of recovery was that of Barbero et al. (1954, 1955). The other reported case of recovery, mentioned by Laurance et al. (1952) and quoted by Keidan et al. (1953), was assumed for some reason or other to have recovered from the vaccinal lesions. On closer examination, however, it seems probable that the patient's death was related to vaccinia gangrenosa (Dudgeon, 1956). Keidan et al. (1953) first reported agammaglobulinaemia in a case of vaccinia gangrenosa. The patient, a girl, was vaccinated at the age of 8 weeks, and died seven weeks later, after being unsuccessfully treated with post-vaccinal serum and intramuscular injections of gamma globulin. The second case is mentioned by Kozinn et al. (1955) together with the third described by them in a 3-month-old male with extensive metastatic lesions, which was also fatal despite intramuscular injections of gamma