Rika Yuliwulandari: Good Morning.
First I would like to thank the organizing committee for inviting me to be here to meet
all of you, and I am also very sorry for the trouble of my throat because of the weather.
So, my talk today would be about Stevens-Johnson syndrome, toxic epidermal necrolysis, or SJS-TEN
study in Indonesia.
So, the purpose of my talk would be to share the current situation of SJS-TEN study in
Indonesia and to share the HLA allele frequencies of SJS-TEN markers in the population and to
introduce our preliminary data of SJS-TEN from several hospitals in Indonesia.
I would like to introduce a little about Indonesia.
Here -- Indonesia is here, span from Sabang until Merauke.
The capital is here in Jakarta.
So, it takes about at least 22 hours by direct flight, if available, from Jakarta to Washington,
D.C.
And according to the government survey in 2010, the number of Indonesian population
is about 240 million.
And it consists of more than 300 ethnics, scattered from eastern part of Indonesia to
western part of Indonesia.
According to an [unintelligible] in 2013, the major ethnics are Javanese people; this
accounts for more than 40 percent.
And then Sudanese people, about 16 percent.
And then Malay people, about 3.7 percent; and Bugis, 2.7 percent.
The rest are the accumulation of various ethnics in Indonesia.
The Javanese and Sudanese people originally lived in Java Island, and the Malay people
originally lived in Sumatra Island, and the Bugis people originally lived in Sulawesi
Island.
How is the current situation of SJS-TEN study in Indonesia?
I divided into two, the first piece on the epidemiology data, and the second piece on
the genetic data.
First, on the epidemiology data.
So far, we are very regret that there is no national epidemiology data of SJS-TEN available,
so the data is very limited in the hospital, and usually, it is provided by request by
some researchers.
But when we ask the data, it is not easy to get the data quickly because most hospitals
in Indonesia currently still use traditional medical records, so rather than electronic
medical records.
And in some big hospitals, like Bali Royal Hospital, they recently have used electronic
medical records, but not all medical record has been input.
And if we research the publication about SJS-TEN in Indonesia, so far I only see one published
data in our national journal about the epidemiology of SJS-TEN in one hospital in Sumatra Island
and one upcoming publication also in our national journal from one hospital in Central Java.
Based on the genetic study, also there is no report about the association of any gene
with SJS-TEN, but our profuse population study have reported HLA A, B, C, and the ARB1 in
the two major populations, and among them at least, there are two potential genetic
markers for SJS-TEN, have been observed in the two most major populations.
They are HLA B*5801; that has been associated with allopurinol induced SJS-TEN.
The frequency in Javanese population is 4.17 percent, and in Sudanese, 5.97 percent.
And for B*1502, that is a genetic marker for carbamazepine-induced SJS-TEN, the frequency
in Javanese more than 16 percent, and in Sudanese almost 11 percent.
So, among all countries in Southeast Asia region, B*1502 has been reported to be a marker
for carbamazepine-induced SJS-TEN, but there is no data in Indonesia.
So, if we compare the presence of B*1502 allele frequency in Indonesia compared to other countries
in Southeast Asia region, so if this study is conducted in Indonesia, probably we also
would find similar results.
So, I would like to show you our preliminary data because of the lack of data about SJS-TEN,
then we [unintelligible] at Royal Hospital and ask about whether they have SJS-TEN patients.
And from several hospitals, mainly from Java Ellen and one from Sumatra, we get these number
of cases.
Like, for the first group is cases of carbamazepine-induced SJS-TEN, the number of cases is 10.
Other drugs induced SJS-TEN will be is eight, and other forms of cutaneous adverse reaction,
41.
So, at that time, I was wondering why it is not easier to find carbamazepine induced SJS-TEN
patients in Indonesia.
In Indonesia, carbamazepine is used in psychiatric and neurologic departments for treating -- in
psychiatric diseases, for treating acute panic, bipolar disorder, and in children for attention-deficit
or hyperactivity disorder, or ADHD, and conduct disease.
For psychiatric diseases, usually carbamazepine is not used as a single drug.
And for neurologic disease, this drug can be used as a single drug, usually to treat
partial and generalized seizure, neuropathic pain, neuralgia trigeminal, post herpes zoster,
herniated nucleus pulpous, and low back pain.
And all of these patients in Indonesia are treated in two types of health service.
First, in the hospital, and the second is in the primary care of our public health services.
There are two different situations.
In the hospital, such as district or central hospitals, the clinician, like psychiatrists
or neurologists, is agreed that carbamazepine is effective and cheap drug.
But in fact, in the clinical practice, they prefer to use valproic acid and phenytoin
because they are frightened of side-effects of carbamazepine.
And the second, in the primary health care, the GP or health worker has limitation in
the knowledge of how to use carbamazepine.
And sometimes, the carbamazepine is not always available in public health service.
Even though it's available, they prefer to use like luminol or phenytoin to treat epilepsy.
I listed some most causative drugs causing SJS-TEN and classified them into eight groups.
The first is anti-viral: in this case nevirapine; and then anti-epileptic: carbamazepine; antibiotic:
cephalosporin, cotrimoxazole, ciprofloxacin, sulfadiazine, amoxicillin, antileprosy, and
dicicyclin.
And of course non-steroidal anti-inflammatory drugs, such as ibuprofen, aspirin, mefenamic
acid, paracetamol, metampiron, and piroxicam; and allopurinol, chloroquine, and then traditional
medicine as is commonly used in Indonesia.
Usually, it consists of a mixture of herbal medicines, and the last is unknown.
And most causative drugs causing other forms of cutaneous adverse reactions is diuretic:
furosemide.
Non-steroidal anti-inflammatory drugs, such as paracetamol, aspilet, [unintelligible],
diclofenac, metampiron, ibuprofen.
For antibiotics: ciprofloxacin, cefadroxil, cefixime, ceftriaxone, erythromycin, oral
anti-tuberculosis, cotrimoxazole, vitamin C. And for antiviral: efavirenz.
Other forms of cutaneous adverse reactions are maculopapular eruption, fixed drug eruption,
and erythroderma.
So, my conclusion is, in the study of SJS-TEN in Indonesia, we are much left behind than
other countries.
So, so far there is not sufficient epidemiology data of SJS-TEN at local, regional, and national
level.
Therefore, further study is needed.
And also, there is no genetic study on SJS-TEN, also needs further study.
And also, there is a lack of sufficient knowledge about drug and side-effects, especially in
public health services.
Therefore, further education, training programs for health workers about drugs of choice and
drugs causing cutaneous adverse reactions, and how to prevent it necessary.
Thank you.
[applause]
Juan Lertora: Thank you very much.
We have a few minutes for questions or comments.
Teri Manolio: Oh, there's one in the back.
Juan Lertora: Yes.
Female Speaker: [inaudible] so much.
I was wondering if you have data with regards to the --
Juan Lertora: Is the microphone on?
I'm sorry.
Teri Manolio: Yeah, it's on; you just have to be a little
closer to it --
Female Speaker: -- with regards to carbamazepine given in
a psychiatric setting, do you have data as to how much of that is inpatient as opposed
to outpatient?
Rika Yuliwulandari: Yeah, if we ask more about it, then we will
get the data.
But at this moment, we still not differentiate whether the outpatient or inpatient.
But I need to inform you that generally the SJS-TEN patients are always hospitalized.
Female Speaker: Okay.
And what is the main adjunct medication that you give with carbamazepine?
Rika Yuliwulandari: I'm sorry, can you please repeat that again?
Female Speaker: The adjunct medication --
Rika Yuliwulandari: The adjunct medication.
Okay, sometimes haloperidol.
And I got information from the clinicians that usually the patients who get SJS-TEN
are because they had the combination between carbamazepine and haloperidol.
Carbamazepine itself, they hardly find SJS-TEN.
Female Speaker: So, the mixture is safe?
Okay.
Rika Yuliwulandari: No, not safe.
If they combine carbamazepine and haloperidol, the patient will tend to go to SJS-TEN.
Female Speaker: Does that increase the serum levels of carbamazepine
in the body?
Rika Yuliwulandari: Yeah.
Female Speaker: Thank you.
Rika Yuliwulandari: Yep.
Juan Lertora: Other questions?
One question that perhaps you could comment on is the turnaround time in terms of the
HLA genotyping in your setting.
Rika Yuliwulandari: [affirmative]
Teri Manolio: What is your turnaround time?
How fast can you get the result back?
Rika Yuliwulandari: How fast to get the result for SJS-TEN --
Teri Manolio: For the genetic marker.
Rika Yuliwulandari: Yes, yes.
Yeah.
For a SJS-TEN study, we would get the data maybe around April?
So, we will get the results soon for SJS-TEN study.
Female Speaker: No, the question was, when you do HLA genotyping,
how long to get the results?
Rika Yuliwulandari: How long?
Oh, one day, two days, we can get the results.
So, in our previous study to genotype A, B and ARB-1, we used [unintelligible].
We got the data within two days.
Juan Lertora: Thank you.
Other questions or comments?
Yes, Teri.
Teri Manolio: I was curious about the antibiotics that caused
-- sorry, this is impossible to see you and talk -- the antibiotics that cause SJS-TEN
in Indonesia.
It looked as though -- maybe you just listed them alphabetically, but it looked like cephalosporins
were more common than cotrimoxazol, or is that not the case?
So, what would be the most common antibiotic that would cause this, do you think?
Rika Yuliwulandari: Well, I don't really have the list of number
of patients for each drug.
I put that in my computer.
But if I compare for cotrimoxazol, there are not many patients.
Teri Manolio: Really?
Because that's quite different from Thailand.
Male Speaker: It's because they don't have SAV [unintelligible]
in Indonesia.
Teri Manolio: They don't have --
Male Speaker: SAV.
Rika Yuliwulandari: SAV.
Teri Manolio: Oh, really?
Male Speaker: SAV [unintelligible].
Teri Manolio: I see.
Male speaker: Only 1 percent of the population has SAV infection,
but Indonesia, they do not have that.
Teri Manolio: So, they don't use it as much, I see.
Great.
Rika Yuliwulandari: Yeah, not much.
Juan Lertora: Other questions or comments?
Otherwise, thank you very much, and we'll continue with the next presentation, summarizing
the experience in the United States, Dr. Steven Leeder.
[end of transcript]