Anaphylactic death is more likely to follow injection into a vein than into a muscle, and is less likely the more slowly the drug is absorbed, so that repository penicillins are safer than penicillin in water solution given by injection. Skin allergies, furthermore, are known to have a complex basis, often including emotional factors. A news item in the A.M.A. Journal (Nov. 17, 1969) is headed "The Average Penicillin Allergy is Not an Allergy" and goes on to say that even when skin allergy to penicillin was recorded (in children with "strep throats") benzathine penicillin could usually be given without adverse effect.

Which is not to say that allergy to penicillin does not exist, or that anaphylactic death never happens, but only that the risks are smaller than is commonly supposed.

Another problem in the treatment of syphilis is the development of fever, occasionally as high as 104°, sometimes accompanied by a temporary increase in the severity of the lesions, following a few hours after the first injection of the drug. This so called "therapeutic shock," or Herxheimer reaction, occurred with the arsphenamines as well as with penicillin, and is probably due to rapid destruction of spirochetes and release of their irritating ingredients into the tissues in larger than ordinary amounts. In other words, it may be taken as an indication that the treatment is working. In early syphilis this shock reaction is rare if it ever happens and is never harmful; but in neurosyphilis the symptoms may be alarming and are occasionally serious, and in syphilis of the heart and blood vessels such reactions in very rare instances have been serious and even fatal.

Another problem, which is sometimes too lightly dismissed, is that of so called relapse, that is, of apparent failure of treatment as indicated by reappearance of symptoms some time after presumably complete cure. From the patient's point of view this is obviously an important matter. It has several aspects which we had better look into one by one.

There is no doubt that early infectious syphilis primary and secondary syphilis when treated with adequate amounts of penicillin, in nearly all cases becomes noninfectious in a matter of days after treatment is completed, leaving the patient, once the sores have healed and disappeared, literally as good as new, which is to say, completely cured. The earlier the treatment is given in the course of the disease, the faster this curative process operates. If reagin type blood tests have not yet become positive, they may stay negative, or if positive they revert back to negative. But for a variety of reasons doctors advise fairly long follow up periods. Dr. Pariser, for instance, advises blood tests every month for six or nine months after treatment and every three months after that for "at least two years." The U.S. Public Health Service suggests discharge at the end of one year in treated early infectious syphilis, with blood tests at intervals of one, three, six, and twelve months. When treatment is started during latency, either early or late, or in late syphilis, the follow up period is longer; but even so the U.S.P.H.S. permits discharge two years after treatment. The same rules are applied to syphilis in pregnancy and to congenital syphilis, the follow up period depending on whether the disease is treated in the early infectious stage or later.

Assuming that these rules are based on a proper caution alone, there is little doubt that they complicate the treatment problem from the social point of view that they help to frighten people away from VD treatment. The rules are, to be sure, intended for the private doctor, who presumably has and can hold his patient's confidence, rather than for the public clinic, which often counts itself lucky if it can hold a patient long enough to confirm the diagnosis and give single shot treatment. Nevertheless there are reasons for the caution, although, curiously enough, relapse following adequate treatment of early syphilis is almost certainly not one of them. (see PROBLEMS IN THE TREATMENT OF SYPHILIS PART II)