SINGAPORE: A dermatologist who saw a patient with a rash prescribed him an immunosuppressant and a corticosteroid, but failed to tell him about a possible serious side effect of the former and to monitor his condition closely.
As a result, the patient developed blisters in his mouth, darkened skin and hair loss that resulted in him being hospitalised for 10 days.
He had suffered a rare adverse reaction to the immunosuppressant and developed bone marrow suppression that resulted in pancytopenia, a rare condition where counts of red blood cells, white blood cells and platelets are all low.
The patient, who was not named in a judgment published on Aug 1, lodged a complaint with the Singapore Medical Council (SMC), and a disciplinary tribunal ordered that Dr Khoo Boo Peng be suspended for 14 months.
WHAT HAPPENED
According to the judgment, Dr Khoo was practising at Naaman Skin and Laser Centre in April 2020 when he saw the patient for a rash he had on his body for about eight months.
Dr Khoo diagnosed him with prurigo nodules or papules and gave him a steroid injection.
About two weeks later, Dr Khoo prescribed the patient with cyclosporin and methotrexate. The patient felt well about a month later and did not show side effects from the drugs.
However, as the medications were expensive to continue in the long term, they were stopped, and the patient was given an open appointment.
On Jun 12, 2020, the patient relapsed and consulted Dr Khoo again. This time, he prescribed 2mg per kg per day of azathioprine, an immunodepressant, and prednisolone, a corticosteroid.
About two weeks later, the patient sent Dr Khoo an email with two photos of his face, expressing concern that the area of his face below his lips was “a little swollen”, with skin that was darker than normal.
Dr Khoo replied that this was likely due to fluid retention caused by the prednisolone. He said it was temporary and asked the patient to continue his medications.
On Jul 1, 2020, the patient sent another email to Dr Khoo, saying: “The steroid has caused blisters near my lips and mouth sores and (is) probably affecting the tongue and throat as well.”
“It feels painful when I eat and swallow. The darkening of skin is also quite bad,” he said.
He told Dr Khoo that he had brought forward his appointment to see him from Jul 9 to Jul 4 in 2020. Dr Khoo replied that he would see him then.
At 3am the next day, the patient emailed Dr Khoo to ask if he could take a medication known as danzen to treat his painful mouth sores, and was given the green light.
That same day, on Jul 2, 2020, the patient sent further emails about his condition. He attached a photo showing the hair he had lost that morning and said it had never happened before.
“(Please) advise what to do with the steroid. It is killing me. I want to stop but (scared) of the withdrawal symptoms also,” he wrote.
Dr Khoo responded: “I agree with you. Stop.” This was only in reference to the prednisolone, the tribunal heard.
After this email correspondence, the patient consulted Dr Khoo at his clinic on an urgent basis.
It was only then that Dr Khoo told him that the symptoms could be an adverse reaction to azathioprine.
The patient sought treatment at the accident and emergency department of Mount Elizabeth Novena Hospital two days later and was admitted from Jul 4 to Jul 13 in 2020.
He was diagnosed with bone marrow suppression, where the bone marrow’s ability to produce blood cells is reduced, and resulting pancytopenia, a potentially life-threatening condition.
Test results conclusively determined that the patient was a poor metaboliser of azathioprine, and this resulted in the severe complications he suffered.
DOCTOR PLEADS GUILTY
Dr Khoo pleaded guilty to two charges of professional misconduct under the Medical Registration Act for prescribing azathioprine to the patient without ensuring his safety, and for failing to monitor him closely and properly manage his side effects after starting him on the drug.
Before prescribing azathioprine, a reasonable doctor was required to advise the patient on the option for testing to see if the patient is a normal, intermediate or poor metaboliser of the drug.
If a patient chooses not to undergo the tests, a reasonable doctor should adopt a cautious approach and start the patient on the lowest dosage of 1mg per kg per day, to test the patient’s susceptibility to the drug.
Dr Khoo did not do this. Caution was required as there could be serious side effects if a high dose of azathioprine is prescribed to a patient who is a poor metaboliser of the drug, the tribunal heard.
Dr Khoo also failed to schedule close monitoring of the patient and order full blood count tests every week or every two weeks, as well as liver function tests for the first four to six weeks, to manage the risks associated with azathioprine and detect any negative reactions to it.
In mitigation, Dr Khoo said he did ask the patient to come back in two weeks to be monitored for common side effects and take a blood test if necessary.
However, the tribunal noted no written record that Dr Khoo had done this and that the patient had declined.
Given that the medication package insert for azathioprine stated that close blood monitoring was “mandatory”, the tribunal found it “odd” that Dr Khoo did not record this in writing.
In any case, Dr Khoo’s claim was only related to common side effects. He did not inform the patient about the possibility of other serious side effects such as leucopenia, or low white blood cell count.
The tribunal said it appeared that the patient had not been informed that close blood monitoring was mandatory, and he may not have been making a fully informed decision if he really had declined to return in two weeks.
The SMC said that even if it accepted the explanation that the decision to prescribe azathioprine was due to cost concerns, this did not reduce Dr Khoo’s culpability.
They called an expert who said Dr Khoo’s failure to carry out close monitoring had resulted in the patient’s hospitalisation.
While Dr Khoo’s failures did not directly cause the condition, they contributed to the severity and extent of the side effects the patient suffered, said the SMC.
Blood monitoring could have prevented or arrested the adverse reaction at an early stage and reduced the harm caused to the patient, said the SMC.
Dr Khoo “failed to act with the necessary urgency” and promptness after learning of the patient’s symptoms, and this showed “a blatant disregard” for his well-being, said the SMC.
He did not call the patient in for an early review of his symptoms, did not tell him to cease the drug use and did not consider the possibility that the patient was facing an adverse reaction to azathioprine.
DEFENCE ARGUMENTS
Dr Khoo’s lawyers argued that their client’s conduct did not “in and of itself” cause the patient to suffer harm. Instead, the harm was the result of the patient being a poor metaboliser.
They argued that the harm that resulted was not the patient’s pancytopenia, but a “slight delay in treatment” from the time the patient first contacted Dr Khoo until Jul 2, 2020, when the patient went to the clinic and was told to seek help.
The lawyers submitted that the patient was warded for 10 days and did not die, so the level of harm in this case was “slight”.
They also said Dr Khoo’s original intention was to get the patient to return within two weeks, but the patient requested a review in four weeks’ time.
When the patient contacted Dr Khoo, the symptoms “were not obvious signs of an adverse drug reaction to azathioprine”, so Dr Khoo was under the “mistaken impression” that prednisolone was the cause.
TRIBUNAL’S FINDINGS
The tribunal noted that the patient’s white cell count was “extremely low” when admitted to hospital. He was placed on antibiotics and came out of neutropenia – an abnormally low concentration of a certain type of white blood cell – on Jul 12, 2020.
“This was a critical period as the low white blood cell count meant there was potential for immense harm to be caused to the patient through opportunistic infections,” said the tribunal, noting that the high quality of medical care at the hospital “may well have prevented him from suffering even more harm”.
The tribunal was prepared to accept that Dr Khoo was unaware of the guidelines that recommend testing, and that his actions were negligent rather than intentional.
Nevertheless, it was clear that a reasonable practitioner in his position would have been aware of these guidelines.
The guidance on offering two types of testing may have been relatively new, but the tests had been recommended for a year and four years, respectively.
Given that Dr Khoo had implied that he had prescribed the drug to other patients, he ought to have kept himself up to date on the latest guidance, said the tribunal.
The tribunal accepted that the case involved a single prescription and not a sustained course of conduct, and the issue was not with prescribing azathioprine per se but the failure to offer the required testing.
Dr Khoo’s lawyers had submitted that leucopenia is the most common adverse event for azathioprine, while pancytopenia is a rare complication, so it did not occur to Dr Khoo that the patient may be suffering from pancytopenia.
The tribunal noted that azathioprine suppresses the natural immune system, and the most dangerous and potentially life-threatening yet common side effect of suppressing the natural immune system is leucopenia.
Someone suffering from pancytopenia would also be suffering from leucopenia.
“Therefore, even if it did not occur to (Dr Khoo) that the patient was suffering from pancytopenia because it was a rare adverse event, it could not excuse (his) failure to consider the possibility that the patient was suffering from a potentially life-threatening yet common side effect which was leucopenia,” said the tribunal.
The tribunal also noted that if there had been proper monitoring, the patient’s condition may not have required such an extended hospital stay, or even admission at all.
He had received an additional five days of azathioprine dosage from his first report before Dr Khoo asked him to stop taking the drug.
Secondly, Dr Khoo ought to have told the patient to stop both medications once a side effect was reported. This is conventional medical practice, and the tribunal found it “surprising” that Dr Khoo did not do so, given that he claimed he had wanted to monitor the patient for side effects.
“These medications were not essential, and stopping them temporarily pending a full evaluation would not have major repercussions to the patient’s health,” said the tribunal.
If it were not for the patient’s own initiative to go down to the clinic earlier, the harm caused may well have been far worse, the tribunal said.
Other than the suspension, the tribunal also ordered that Dr Khoo be censured, pay the costs of the proceedings and give a written undertaking to the SMC that he would not engage in such conduct in future.
