HI, EVERYONE.
I PUT THIS STAGE ON AND I'M
TRYING TO SHARE WITH YOU SOME OF
MY CASES THAT I STILL HAVE A LOT
OF QUESTIONS AND I WANT TO SHARE
THEM WITH YOU.
DEPENDS ON THE TIME I KNOW WE
ARE BEHIND SO I HAVE CUT THREE
OR FOUR CASES BUT WE CAN GO
THROUGH MAYBE TWO OF THEM.
MY DISCLOSURE.
TALK ABOUT UNDIFFERENTIATED
PATIENT IT IS FREQUENCY
DIFFICULTIES AND MANAGEMENT
HETEROGENEITY RAISING AWARENESS
AS CUMULATING INTEREST OF
STAKEHOLDERS, THOSE ARE THE
PATIENTS THAT ARE HAVING
DIFFICULTIES TO BE IN TRIALS AND
GET APPROVALS USING MEDICATIONS,
WE ALL STRUGGLE WITH THOSE.
THIS IS JUST TO SHOW YOU A
SLIDE, FROM OUR GROUP, TWO
CANADIAN REGISTRIES THAT HAD
DESPITE THE INCREASE IN THE 86%.
SO THE GENETIC TESTING INCREASE
BUT STILL HALF OF THE PATIENTS
IN OUR CLINICS ARE
UNDIFFERENTIATED.
SO THIS IS A CASE SHE IS NOW IN
THE HOSPITAL, SHE HAD HER SECOND
LUNG BIOPSY, SHE HAD
PNEUMOTHORAX.
I'M STRUGGLING TO TREAT HER.
SO AGE 1 PRESENTED FIRST EPISODE
OF ABDOMINAL PAIN AND DIARRHEA
AND KNEE SWELLING SHE WAS HAVING
EYE DISCOMFORT WITH SWELLING,
TARGET ARTERIAL RASHES.
AND THE EPISODES LAST THREE TO
SEVEN DAYS EVERY TWO TO FOUR
WEEKS.
THE INITIAL EPISODES PRECEDED
WITH SKIN INFECTION AND --
THAT'S WHY THEY THOUGHT THIS IS
A REACTOR -- REACTIVE PROCESS.
JUST PACK HISTORY SHE WAS BORN
36 WEEKS HISTORY OF PRENATAL
(INAUDIBLE) REMOVED AT BIRTH
FREQUENT URI NORMAL GROWTH AND
DEVELOPMENT.
SHE HAD IMMUNIZATION AND THERE'S
FAMILY HISTORY THAT MAYBE A
SECOND COUSIN OR FATHER'S SIDE
HAS SIMILAR SYMPTOMS WHO
STRUGGLED WITH SIMILAR SYMPTOMS
AND THYROID AND SILL YAK DISEASE
ON FATHER SIDE AND FIVE HEALTHY
SIMILARRABLINGS.
HER PHYSICAL EXAM FIRST MET, I
THOUGHT SHE HAD MILD
(INDISCERNIBLE) GENETICS DIDN'T
AGREE WITH ME.
MILD INTERMITTENT SPLENOMEGALY
AND DIAGNOSED WITH (INAUDIBLE)
ONE EPISIDE.
HER LAB MILD NEUTROPENIA,
MICROSCOPIC -- ONE TIME GROSS
(INDISCERNIBLE) ELEVATED
PROTOPORPHYRIN, AND LOWISH IGA
LEVELS.
BEFORE SHE CAME TO US SHE HAD A
SKIN BIOPSY WHICH SHOWED TWO
BIOPSIES LOOKING FOR IF THIS IS
HSB LIKE AND IGA DEPOSITION BUT
IT WAS PLASTIC VASCULITIS,
NEGATIVE FOR IMMUNE COMPLEX
POSITION AND SHE WAS SEEN BY
NEPHROLOGY, THEY THOUGHT SHE HAD
SOME
>> MER LEER VIRUS BUT IT WAS A
CYSTITIS.
SHE WAS SEEN BY RHEUMATOLOGY AND
POST INFECTIOUS REACTIVE
VASCULITIS.
SHE WAS SEEN IN CLINIC WITH THIS
RASH AND HISTORY.
AND ACTUALLY AT THAT TIME I
THOUGHT SHE COULD HAVE AN
AUTOINFLAMMATORY CONDITION,
BECAUSEOF HAVING OTHER PATIENTS
I HAVE MAYBE SIX OR SEVEN, IT'S
A CONTROVERSIAL INFLAM ZONE,
PATIENTS ARE DIVERSE, I THOUGHT
SHE COULD HAVE TYPE
AUTOINFLAMMATORY CONDITION.
SO BUT WE THOUGHT IT COULD BE --
TO KNOW SO WE STARTED HER ON
COCOLCHICINE TREATMENT.
SHE HAD PARTIAL RESPONSE TO
THAT, BUT SHE WOULD NEED SHORT
BURST OF PREDNISONE WITH FIRST
SIGN LASTING ONE TO THREE DAYS
OF PREDNISONE, SHE HAD
HOSPITALIZATION, IT'S SEVERE
ABDOMINAL PAIN BUT IT'S NOT
ACUTE ABDOMEN BUT VERY SEVERE
ABDOMINAL PAIN, SHE WOULD BE ON
THE FLOOR SCREAMING.
HE HAD ONE DOCUMENTED
SELF-CORRECTED COLON OSCOPY
ENDOSCOPY, THERE WAS
NON-SPECIFIC INFLAMMATION,
THAT'S THE DOSE THIS IS HOW
STOOLS LOOK LIKE, YOU SEE THE
DIARRHEA SHE WOULD GET, NOER
MALL PLAIN BRAIN AND ABOUT
NOMINAL MRI AND MRA.
BECAUSE OF THE SEVERE ABDOMINAL
PAIN AND (INDISCERNIBLE) THERE
WAS QUESTIONS, SO WE DID ALL THE
TESTING FOR THAT.
WE CAME WITH VARIABLEN KNOWN
SIGNIFICANCE WHICH IS FAMILIAR
TO US, VERY UNKNOWN
SIGNIFICANCE.
THEN ACTUALLY WE DID SEND IN
CANADA, RESEARCH BASIS SHE HAD
THE EXOME SEQUENCING DONE T. HAD
THE SAME MUTATION.
WE ARE NOT SURE IF THIS MUTATION
IS EXPLAINING HER SYMPTOMS.
BECAUSE OF SEQUENCING --
INCREASING OF SYMPTOMS SHE GETS
100-MILLIGRAMS DAILY DURING
EPISODES AND FLAIRS WE ARE
USUALLY TRIGGERED BY INFECTIONS.
THEN SHE HAS VITAL TRIGGERS
PRIMARILY.
AND THEN SHE GETS SIGNAL
WATCHING CAREFULLY OBVIOUSLY
BECAUSE SHE HAD SINGLE ENLARGING
OVARIAN FOLLICLES, HAPPENS AND
GETS ACCUMULATED BACK TO NORMAL.
AND SHE'S BEEN HAVING INCREASING
VIRAL RESPIRATORY INFECTION
WHICH REQUIRES ICU ADMISSION AND
THEN SO SHE WAS BECOMING
HYPOXIC, SHE HAD A BAL -- SHE
WAS TREATED WITH (INAUDIBLE) AND
DOXYCYLCINE.
SHE HAD LUNG BIOPSY A T THE TIME
SHOWING THE INFECTION IT SHOWED
ACUTE AND CHRONIC INFLAMMATION,
NOTHING MUCH I LISTED THERE BUT
NOVAS CULITIS, AND HER SECOND
BIOPSY WHICH WAS DONE TWO DAYS
AGO, SEVERE -- VERY SIMILAR
FINDINGS BUT OXYGEN REQUIREMENT
THERE.
SO WE DECIDED A LITTLE BIT IVIG
AS NEWSPAPER MODULATORY FORB
LUNG DISEASE AND ALSO FOR
INFECTION, MAYBE DECREASING
INFECTIOUS BURDEN BUT SHE --
THOSE SEVERE SIDE EFFECTS
REQUIRES FOUR TO FIVE DAYS
HOSPITALIZATION.
SOMETHING I DO SEE WITH PATIENTS
SEEM TO BE SENSITIVE TO
TRIGGERS, VACCINATIONS,
MEDICATIONS, SO ON.
THAT'S JUST ANECDOTAL EXPERIENCE
THAT I HAVE.
NEUROOVULATION WAS MRI NORMAL,
POSSIBLE -- (INAUDIBLE) BECAUSE
OF SOME OF HER INCORPORATION,
EYE EXAMS NORMAL EXCEPT
CONJUNCTIVITIS DURING FLAIRS.
SHE'S JUST ADMITTED FOR REPEAT
LUNG BIOPSY, SHE HAD IT AND
THERE IS A CONCERN WHICH ARE NOT
READILY AVAILABLE FOR THE
DIFFICULTIES WE ARE FACING IS
THIS LUNG DISEASE PRIMARY OR NOT
RESPONSIVE TO THERAPY, SYSTEMIC
ARTHRITIS, THERE'S DISCUSSION
ABOUT MAYBE BIOLOGICS,
CONTRIBUTING TO THE LUNG
DISEASE.
AND WE WERE TRYING TO SWITCH TO
LONG ACTING ANTI-IL 1 BECOMING
DIFFICULT DAILY INJECTION
HOWEVER SHE NOW HAS CNS
INVOLVEMENT THAT PEN TRANSISSUE
IS SOMETHING THEY NEED TO
CONSIDER.
SO WITH HER THROUGHOUT THE YEARS
COUPLE OF YEARS E HAVE BEEN
HAVING A LOT OF ISSUES WITH HOB
TO CONVINCISH. INSURANCE
COMPANIES, WITH TESTING
ADMISSIONS ALL CHALLENGING.
THIS IS MY PHASE 2, THIS IS IS
NOW SIX MONTHS OLD.
I MET HER AT THREE AND A HALF,
CAME IN WITH FEVER.
POLYAL THRALL GEEIA, POST LYNN,
LESIONS, OCCASIONAL ABDOMINAL
PAIN AND EVIDENCE OF HIGH
SYSTEMIC INFLAMMATION.
THIS IS JUST SHOWING -- SO YOU
CAN SEE THE RASH AND SHE WAS
ALSO HAVING ULCERS HOPE YOU CAN
SEE IT THERE.
HER LEG, WAS QUITE SWOLLEN
COMPARED TO THE LEFT.
ALSO HAVING THIS LOOKING RASH ON
HER LEG. SO SHE HAD WORK UP NO
IDENTIFIED CAUSE FOR HER
INFLAMMATORY RESPONSE.
NOT RELATIVELY NORMAL IMMUNE
SYSTEM EXCEPT SHE HAD 50% TLR
RESPONSE TOLL LIKE RECEPTOR
FUNCTION, SLIGHTLY DECREASING NK
FUNCTION AND CHROMOSOMAL
MICROARRAY SHOWED AREAS OF
HETEROZYGOSITY, SHE HAD RANDOM
INACTIVATION.
INTERESTINGLY OBVIOUSLY FOR THIS
PATIENT HER FATHER THIS HAD
PNEUMOMUTATION AT EXOME C 41, SO
THIS IS THE BACK STORY OF HER
FATHER.
SO WE MANAGED HER SYSTEMIC
TOPICAL STEROIDS, COLCHICINE,
CAME BACK WITH INTEND TO
INCREASE AND EVENTUALLY RETURN,
I STARTED THE CULTURE SCENE AND
THERE WAS A NICE RESPONSE YOU
CAN SEE THE FIRST AND LAST AFTER
COUPLE OF MONTHS, SYSTEMIC
INFLAMMATION.
BECAUSE OF THAT, I STARTED HER
ON ANA KINRA.
SHE DID RESPOND TO THAT BETTER
BUT REQUIRES SHORT COURSE
STEROIDS WHEN SHE HAS FLAIRS.
SO I WROTE HER UP TRYING TO SEE
IF THIS IS RELATED AS WE NEED
MORE PATIENTS THEMSELVES
DEPENDING ON WHERE ROTATION IS S
THEY CAN GET AUTOINFLAMMATORY
RESPONSE OR ALSO THERE ARE
PATIENTS CARRIERS OF SISTERS
MOTHERS CAN DO (INAUDIBLE)
PICTURE.
I'M THINKING THAT IS WHAT SHE IS
HAVING BUT HER -- IS NEGATIVE,
YOU NEED TO LOOK INTO FURTHER SO
THIS IS LIKE IN PUZZLE.
WITH HER, SO WHAT DO I DO WITH
THIS GENETIC INFORMATION OF HER
FATHER, DO I IGNORE THAT OR JUST
TRY TO TIE THIS TOGETHER.
AND NEXT STEPS IF THIS DOESN'T
WORK.
CERTAIN OTHER MALIGNANCIES HOW
DO I MONITOR HER, WHAT TESTING
SHOULD I BE DOING?
WHAT -- BECAUSE OF COMPLEXITIES
THAT INTERACTION WITH OTHER
PROTEINS THAT HAS INHIBITOR
ACTION THAT BINDS AND DEPENDING
ON THAT AND WHERE MUTATION IS,
THE FATHER MUTATION ON EXON 10
SO THAT MIGHT BE DIFFERENT IN
THE PHENOTYPE, THAT'S ESSENTIAL
IN IL 1 AND TNF STIMULATION.
DO I HAVE TIME TO DO PATIENT 3?
CASE 3, THIS IS A BOY I MET WHEN
HE WAS SEVEN AND A HALF YEARS
OLD.
HE DEVELOPS A FEVER AN SORE
THROAT, TIGHT NOSED WITH
TONSILITIS AND TREATED WITH
(INDISCERNIBLE).
HE HAD PERSISTENT SYMPTOMS,
SPLENOMEGALY AND PERIPHERAL --
THREE BOW CYTOPENIA, HE IS
FERRITIN WAS 12,000, ORIGINALLY
RECEPTOR, HE HAD BONE MARROW
BIOPSY, SEEN BY ONCOLOGY FIRST
AND (INAUDIBLE) SO HE WAS
DIAGNOSIS WITH EBT TRIGGERED
HLH.
HE WAS TREATED WITH 2004
PROTOCOL WITH DEXAMETHASONE, AND
COMPLETE RESPONSE, HE RECOVERED
VERY EASILY, AT THE TIME WHAT IS
AVAILABLE WAS THIS SEVEN, EIGHT
YEARS AGO, HLH GENES WERE DONE,
HE HAD NK AND CYTOTOXIC STUDIES
PERFORIN STUDIES WERE NORMAL.
THEN TWO MONTHS LATER HE RETURNS
WITH FEVER, THIS TIME ANKLE
ARTHRITIS, AND ONLY FERRITIN WAS
AVAILABLE SO HE HAD AN EBVPCR
POSITIVITY AGAIN, WE WERE
CONSULTED BECAUSE OF THE -- THEY
DID NOT TAKE THIS AS HLH PLAYER,
SO WE DIAGNOSE WITH SYSTEMIC
JIA, WE TREATED SHORT COURSE OF
STEROID AND ALSO START ON IL 1
INHIBITION.
HE HAD SEVERE SKIN REACTION SO
WE SWITCHED TO (INAUDIBLE) AND
OAR THREE IN IS H WRIST METH
TRAIK SIT WAS ADDED TO HIS --
METHOTREXATE WAS ADDED TO HIS
REGIMEN. OVER TIME GOT BETTER,
I SPACED HIS -- TO EVERY TEN
WEEKS.
I DON'T KNOW IF THAT IS DOING
ANYTHING BUT I CAN TELL YOU THE
REASON.
METHOTREXATE WAS ABLE TO BE AVID
ATHLETE, DOING GREAT, NO IMIS
TOMS.
HE DOES DO MILD CYTOPENIA,
WHETHER ENHE GETS VIRAL
INFECTION, HE GETS SLIGHTLY
ELEVATED FERRITIN AND CYTOPENIA,
NOT TOO SIGNIFICANT BUT LOW
PLATELETS AND WITH NEW TESTING I
FOUND HLH PANEL, LITTLE
SIGNIFICANCE IN ITK, ONE OF THE
HLA GENES THAT CAUSES HLH
RELATED TO SPECIAL CASES EBV
SENSITIVE.
THEN I DECIDE TO -- YOU CAN
QUESTION ME WHILE I DID THAT, I
THINK -- I SENT PID PANEL
BECAUSE AGAIN HE DOESN'T REALLY
-- HE HAS THIS SIGNIFICANT I WAS
LOOKING FOR ANY OTHER COMPONENT
GENES.
SO HE GOT SOME OTHER UNKNOWN
SIGNIFICANCE, IF YOU LOOK AT
SOME OF THESE, PROBABLY ONE HERE
YOU CAN SEE THAT -- BUT SOME OF
THESE ALSO ARE ASSOCIATED WITH
ACTUALLY EBV SENSITIVITY.
FOR ME THE QUESTION THIS PATIENT
IS DOING GREAT SO I NORMALLY IF
I HAVE A SYSTEMIC ARTHRITIS
PATIENT I MAY TRY TO STOP THE
MEDICATION BECAUSE HE'S BEEN IN
REMISSION FOR FOUR YEARS, I WAS
ABLE TO SPACE IT NOT HAVE ANY
OTHER EPISODE.
DESPITE HAVING -- BUT HI DOESN'T
GET SICK OR ANYTHING MAJOR.
BECAUSE STILL CONCERNED HE IS
HAVING EARLY ANTI-GENERAL GOES
UP A LITTLE BIT, IT'S JUST
THERE'S SOMETHING LOTS OF PCR
BUT I'M CONCERNED SO I JUST GOT
STUCK THERE.
BILLION DOLLARS TEN WEEK ANA
KINRA, MY QUESTION WHEN CAN I
STOP TREATMENT.
HE DEVELOPED ANOTHER SEVERE
EPISODE ONE POINT IN HIS LIFE,
SEVERE HLH EPISODE.
GETTING ACTIVATED.
AND WHAT ABOUT ITP ASSOCIAION
WITH MALIGNANCIES?
THAT'S ASSOCIATION THAT THE
PATIENTS ITK IS FOUND IN
LYMPHOMAS AND LEUKEMIAS COULD HE
BE MORE PRONE, DO I SCREEN HIM,
DO I -- HOW DO I MONITOR HIM AND
FOLLOW HIM?
AND HOW OTHER VARIANT BECAUSE
SPECIAL SOME ARE PREDICTED
DISRUPTIVE, THIS IS WHAT WHEN I
GET RESULTS I SIT AND LOOK AT
CHROMOSOME, GENE, I STAND
CHROMOSOMAL MICROARRAY TO SEE
THAT'S OTHER AREAS IN THAT AREA
THAT MAY MAKE THE PHENOTYPE
DIFFERENT.
SO THERE ASSOCIATED MALIGNANCIES
SO WOULD BE HIGHER OR NOT, I
DON'T KNOW.
THESE ARE RATHER DIFFICULT
QUESTIONS THAT WE GO THROUGH
EVERY DAY.
SO AS A SUMMARY, DAY TO DAY WHAT
WE DO IS FOLLOW CLUES, OTHER
DISEASE PARENT YOU SEE BEFORE
AND MEDICATION RESPONSES AS PAUL
MENTIONED.
YOU DO USE LABS, FOLLOWING FOLLOWING THE
USUAL ONES, UNUSUAL ONES AND
UNIQUE ONES AND LOOKING AT THE
GENETICS OBVIOUSLY, THE BIOLOGIC
MARKERS LIKE INTERFERON
SIGNATURE, I WISH IT IS MUCH
MORE AVAILABLE TO ALL THE
CLINICIANS MORE READILY BECAUSE
I THINK THIS IS THE IDEA OF THIS
MEETING TO GETTING TOGETHER TO
TRY TO TACKLE THESE PROBLEM.
I WILL STOP THERE, I HAVE ONE
MORE CASE.
[APPLAUSE]