Since its invention, penicillin has dealt a "heavy blow" to many infectious diseases and remains a highly effective drug for treating a wide range of infections to this day. For example, in dermatology, syphilis is one of the most commonly encountered conditions, and penicillin remains the most effective treatment for syphilis to date.

However, we all know that penicillin injections require a penicillin skin test. Once the penicillin skin test is positive, doctors generally will not prescribe penicillin injections. Everyone fears allergic reactions, and once an allergy occurs, no one can bear the responsibility.

Many hospitals also perform a saline control test when administering penicillin to determine whether the reaction is a penicillin allergy. If the skin test is negative, we doctors will prescribe penicillin injections. Benzathine penicillin intramuscular injections for syphilis treatment are extremely painful, as anyone with experience in this area knows—they likely never want to go through it again. If the skin test is strongly positive or the patient even shows signs of an allergic reaction, further penicillin injections are obviously not possible. However, in ambiguous cases where the skin test site appears slightly red, some stricter doctors and nurses may interpret it as positive, and the outpatient doctor cannot proceed with further treatment.

What should we do when encountering such cases in outpatient clinics? The patient might say, "I’ve taken penicillin before, more than once, and I’m not allergic." However, if the penicillin skin test at this hospital is positive, we doctors generally cannot prescribe penicillin because even if we do, the electronic system will reject it. In such cases, we usually advise the patient to go to another hospital for a repeat skin test, as different hospitals may use penicillin from different manufacturers or batches. By trying multiple hospitals, the patient may eventually find one where the test passes. After all, penicillin is the most effective and cost-efficient treatment for syphilis.

There is another scenario: the patient says, "My penicillin skin test is positive, but I don’t remember if I’ve ever taken penicillin. I just remember that when I was young, the penicillin skin test was positive, and the doctor didn’t dare give me penicillin." This presents a very tricky problem. Although we doctors know penicillin is highly effective and that a positive penicillin skin test isn’t always truly positive, do we dare take the risk of administering a penicillin injection in this situation? If an allergic reaction occurs, who will take responsibility? Even if the patient says, "It’s fine, I’ll take the risk," once the risk materializes, things aren’t so simple anymore—it could lead to a terrifying outcome. Therefore, in most cases, we use alternative medications to treat syphilis, although their effectiveness may not be as good.

In my career, many years ago, I encountered a middle-aged male patient with typical primary syphilitic chancre. He said he had a positive penicillin skin test and couldn't recall whether he had ever taken penicillin, but in any case, his doctor dared not prescribe penicillin. I was also afraid, worried about adverse reactions. What to do? I suggested he try a skin test at another hospital, but he didn’t want to go. Ultimately, it was decided to treat him with oral doxycycline, but he responded poorly to doxycycline, and the chancre continued to progress, with the area becoming increasingly swollen and painful. After about a week, I discussed with him whether he would consider undergoing a penicillin skin test at our hospital. He agreed, willing to share the risk, and I documented the situation truthfully in his medical record. The result was a positive penicillin skin test, but without an allergic reaction. I advised him to go to Ditan Hospital for a penicillin skin test, and he accepted. Unexpectedly, the penicillin skin test performed at the dermatology department of Ditan Hospital was negative, and he was treated with long-acting penicillin, once a week for three consecutive weeks. The swelling basically subsided, and the chancre was well controlled. One month after treatment, the chancre resolved, and the titer also dropped significantly.

In summary, penicillin remains the most effective drug for treating syphilis to date and offers the best cost-effectiveness. If penicillin can be used, it should be the treatment of choice. A history of a positive penicillin skin test does not necessarily mean a penicillin allergy. Under the guidance of a doctor and by sharing the risk together, a penicillin skin test may be considered. If the skin test is negative, penicillin treatment can proceed. If the skin test is positive, trying skin tests at several other hospitals might be worthwhile—perhaps one will turn out negative. Of course, in cases of confirmed penicillin allergy, a penicillin skin test should not be performed, and it is best to switch to other drugs for treatment.