SO I WAS ASKED TO SPEAK TO ADULT
ONSET STILL'S DISEASE.
FAIR AMOUNT OCCUR IN ADULTS, THE
QUESTION IS WHAT DO WE COMMONLY
SEE, MAINLY BECAUSE IT'S THE
MOST COMMON CAUSE
AUTOINFLAMMATORY -- I'M SORRY --
AUTOIMMUNE OR RHEUMATIC CAUSE OF
FEVER OF UNKNOWN ORIGIN, THE
NAME STILL'S DISEASE ALWAYS
COMES UP.
SO IT'S EYE HAO ON THE LIST
HIGH ON THE L
IST WHEN
PATIENTS ARE FALLING UNDER
RHEUMATIC EVALUATIONS, BUT THERE
ARE OTHER THINGS THAT GIVE YOU
FEVER AND I HAVE THOSE LISTED ON
THE LEFT, AND THEY'RE SOMETIMES
CONFUSED WITH ADULT STILL'S
DISEASE.
IF YOU LOOK AT THE SPECTRUM OF
AUTOINFLAMMATORY DISEASE,
THERE'S A FEW THAT
PREFERENTIALLY AFFECT ADULTS AS
WAS JUST MENTIONED, SCHNITZLER'S
SYNDROME, THERE IS THIS ADULT
ONSET OF CAPS AND THAT'S A
MINORITY POPULATION IN THE CAPS
POPULATION, BUT YOU CAN SEE WHEN
YOU START LOOKING AT TRAPS AND
FMF AND SPECIFICALLY -- IT'S A
MINORITY OF ADULTS WHO WILL
MANIFEST AND BE PROVEN TO HAVE
THOSE SPECIFIC DIAGNOSES.
THIS IS A PATIENT THAT I STARTED
WITH, I THINK THIS IS 1982.
SHE WAS 23, SHE WAS PETITE,
FRAIL, BUT FIERCE, ADMITTED TO
THE HOSPITAL AT 6:00 A.M.,
LOOKED VERY, VERY SICK.
WE PUT HER IN THE ICU OR NOT,
SHE PRESENTED WITH A TERRITORY
OF 104, A SED RATE OF 99, WHITE
KOWT OF 20,000, HER LIVER
ENZYMES WERE OFF THE CHARTS.
YOU CAN SEE THAT EARLY ON, SHE
MANIFESTED A REMITTENT PATTERN
OF HIGH SPIKING FEVERS THAT
WOULD OCCUR TWICE A DAY, AND
THEN ONCE WE PUT HER ON IS A
LIST LITS, SHE FELL INTO A
CLASSIC PATTERN FALLING BACK TO
BASELINE, AND IT WASN'T UNTIL
SHE WENT ON STEROIDS IN HIGH
DOSES, STARTED OUT WITH 10, WENT
UP TO 50 OR 60, I THINK, YOU SEE
THAT THE FEVER PATTERN STASHTS
TO STARTS TO
BREAK UP, COMES DOWN IN
MAGNITUDE, SPACES OUT IN
FREQUENCY.
ALONG THE WAY, SHE HAD SED RATES
OVER 100, A WHITE COUNT THAT
WENT UP AS HIGH AS 40,000, SHE
DROPPED HER HEMATOCRIT, AND THIS
WAS NOT HER FIRST DIAGNOSIS.
SHE HAD UNKNOWN DIAGNOSES IN THE
AGES OF 9 TO 12, AND THE
HOSPITAL IN BROOKLYN, SHE WAS
CALLED RHEUMATIC FEVER OR
HEPATITIS AND WHAT NOT, AND HERE
SHE WAS 23, SOME 11 YEARS LATER,
PRESENTING WITH A NEW
PRESENTATION OF WHAT WAS TO BE
ADULT STILL'S DISEASE.
SO WHAT IS STILL'S DISEASE?
IT IS A CYST STE MEMO
INFLAMMATORY, OCCURS AFTER THE
AGE OF 16, ADULT ONSET, AND I
THINK THE MAJORITY OF THESE
REALLY ARE UP TO AGE 35 AS I'LL
SHOW YOU WHY.
IT IS A CONDITION OF QUOTIDIAN
FEVERS, RASHES, ARTHRITIS, SORE
THROAT, SEROSITIS, HIGH WHITE
COUNTS, IT IS A SYNDROME, IT'S
NOT A DIAGNOSIS THAT WE HAVE A
TEST FOR.
WE HAVE TESTS THAT WILL HELP
MAYBE EXCLUDE OTHER THINGS SO WE
NEED TO EXCLUDE OTHER DIAGNOSES.
THIS IS ONE OF THE BIGGEST
PROBLEMS IN THE DIAGNOSIS OF
THIS IN THAT YOU HAVE TO DW GO
THROUGH A PROCESS TO GET TO THIS
DIAGNOSIS.
I THINK IT'S EASILY IDENTIFIABLE
TO THOSE WHO HAVE SEEN THIS,
WHICH IS WHY PEDIATRIC
RHEUMATOLOGISTS ARE MUCH BETTER
AT THIS THAN ARE ADULTS.
IT IS A CONDITION THAT HAS A
SYSTEMIC ONSET, SYSTEMIC
EXACERBATIONS AND SOME WILL OR
WILL NOT HAVE CHRONIC ARTHRITIS
THAT WILL GO ON AND ON AND ON
AND THERE VERY WELL MAY BE
DISEASE-FREE INTERVALS AS WAS
SHOWN FOR THE PATIENT I JUST
PRESENTED.
IF THERE'S ANY DISCUSSION ABOUT
WHETHER SYSTEMIC ONSET JIA AND
ADULT ONSET DISEASE ARE THE
SAME, YOU CAN LOOK AT THIS
COMPARISON, THIS WAS AN EARLY ON
BIG STUDIES, MORE THAN 15
PATIENTS, ABOUT 100 TO 150 IN
EACH GROUP.
YOU CAN SEE LINE BY LINE, THEY
EQUAL IN THEIR PRESENTATION WITH
THE ONLY MAJOR DIFFERENCE BEING
THAT OF THE PRODROMAL SORE
THROAT.
THE PATIENT PRESENTED TO ME
STARTED OUT, HER STORY WAS, SHE
HAD A SORE THROAT, SHE WENT TO
HER FAMILY DOCTOR, SHE GOT AM PI
SI LIN, SHE DEVELOPED A RASH,
THEY SAID, UH-OH, IS IT A
REBEING ATION, IT TURNS OUT IT
WAS HER STILL'S RASH, SHE ENDED
UP IN THE HOSPITAL SOME SEVEN
DAYS LATER.
SO THE CHALLENGES HERE THAT THIS
IS A VERY COMMON CAUSE OF FUO ON
PATIENTS WHO WILL PRESENT WITH
FUO.
IT HAS A CONSIDERABLE AMOUNT OF
MORBIDITY TO IT, THANKFULLY NOT
MUCH IN THE WAY OF MORTALITY.
TTION IT IS A DIAGNOSTIC AND
TREATMENT
CHALLENGE.
ALONG THE WAY THEY WILL OFTEN BE
HOSPITALIZED, OFTEN SEEN BY
OTHER CONSULTANTS BEFORE THEY
WILL BE SEEN BY RHEUMATOLOGISTS,
THEY WILL HAVE SEROSITIS,
TAMPONADE, THEY ARE OFTEN
CONFUSED ABOUT WHETHER THEY HAVE
INFECTIOUS ISSUES GOING ON AT
THE SAME TIME.
MAYBE THE BIG LONG TERM PROBLEM
IS THAT AT LEAST A THIRD SEEM TO
DEVELOP A CHRONIC POLYARTHRITIS
THAT CAN LOOK JUST LIKE
RHEUMATOID ARTHRITIS, BE JUST AS
DAMAGING AND EROSIVE.
HOW COMMON IS THIS CONDITION?
YOU CAN LOOK AT THIS MANY
DIFFERENT WAYS.
I'LL SHOW YOU SOME EPIDEMIOLOGY,
BUT LOOKING AT LARGE SERIES FROM
MAJOR DEPARTMENTS AND MED KALG
MEDICAL
CENTERS, YOU CAN SEE OVER A 20
YEAR PERIOD, FOUR REPORTED
CASES.
LARGE DEPARTMENTS WILL SEE ONE,
MAYBE TWO CASES A YEAR.
THAT'S KIND OF THE NORMAL
OCCURRENCE RATE.
IF YOU LOOK AT FUO SERIES SHOWN
ON THE BOTTOM, YOU CAN SEE THAT
IT RANGES FROM ANYWHERE FROM 5%
TO UP TO 9 OR 11% OF THE CASES
OF FUO MAKING IT THE NUMBER ONE
RHEUMATIC DISEASE OR
MUSCULOSKELETAL CAUSE OF AN FUO.
SO YOU SHOULD SEE THIS, YOU
SHOULD KNOW ABOUT THIS.
THE INCIDENCE RATE IS ABOUT ONE
CASE PER HUNDRED THOUSAND.
IN IN THE UNITED STATES,
SOMEWHERE
AROUND 4,000 CASES.
DEPENDING ON WHERE YOU LIVE, YOU
CAN SEE WHAT THE CASE RATE MAY
BE IN THE CITY BASED ON THE
POPULATION SIZE OF YOUR CITY.
SO WHERE I'M 40, IN DALLAS,
FROM, IN DALLA
S,
THERE MIGHT BE 19 CASES.
I MIGHT SEE TWO OR THREE OF THEM
AND I'M VERY WELL-KNOWN IN
DALLAS AS GUY WHO KNOWS ABOUT
STILL'S DISEASE.
I SEE PATIENTS FROM A LOT OF
OTHER CITY BUT THERE ARE A LOT
OF OTHER CASES BEING SEEN BY
INTERNISTS, INFECTIOUS DISEASE
SPECIALISTS AND OTHER
RHEUMATOLOGISTS IN MY CITY.
SO AT ONSET, THIS IS BASED ON
EARLY REPORTS FROM LIKE 1970 TO
ARCHED AROUND 1980 FAVE WHEN I
MADE THIS, I THINK REPORTS WERE
VERY ACCURATE.
CURRENT REPORTS ARE MIXED IN
WITH A LOT OF OTHER THINGS,
THERE'S A LOT OF BIAS, ERRANT
REPORTS THAT ARE OUT THERE.
I THINK THESE ARE TRUE REPORTS
BECAUSE THEY PRETTY MUCH FIT THE
SYNDROME AS DESCRIBED AT THE NIH
AROUND 1970.
YOU CAN SEE THAT REALLY 76 OR
THREE QUARTERS OF THE CASES
OCCUR BEFORE THE AGE OF 35, WHEN
THEY OCCUR IN THE ADULT
POPULATION.
ABOUT 20% ACTUALLY HAD SOME KIND
OF HISTORY BACK WHEN THEY WERE A
CHILD OF HAVING SOME KIND OF
SYSTEMIC INFLAMMATORY FEBRILE
ILLNESS.
YOU CAN SEE SEX DISTRIBUTION IS
EQUAL BETWEEN MALES AND FEMALES.
ABOVE THE AGE OF 50, IT'S NOT
MANY, IT'S SOMEWHERE ABOUT 9% OF
PATIENTS WILL PRESENT ABOVE THE
AGE OF 50 SO THE OLDER THE
PATIENT IS, THE MORE YOU REALLY
SHOULD DOUBT THIS DIAGNOSIS,
ESPECIALLY SINCE A LOT OF OLDER
PATIENTS HAVE ATYPICAL
PRESENTATION.
THE HALLMARK HERE IS THREE OF
THEM.
YOU REALLY HAVE TO HAVE THOSE TO
START.
AT THE OUTSET, YOU MAY NOT HAVE
ALL THREE OF THOSE.
BUT CERTAINLY IN THE FIRST SIX
MONTHS, YOU WILL IN THE VAST
MAJORITY OF PEOPLE.
QUOTIDIAN FEVER RISES ABOVE
39 DEGREES CENTIGRADE AND
RETURNS TO NORMAL IN THE SAME
DAY.
THE INTERESTING THING I LEARNED
WHEN I WAS DOING A REVIEW OF THE
UNIVERSITY OF PITTSBURGH
PATIENTS AS A RES DENTD, IS THAT
WHEN I ASKED A PATIENT WHEN DID
YOU GET YOUR FEVER, THEY ALL DID
THE SAME THING.
THEY ALL WOULD LOOK AT A CLOCK
ON THE WALL AND THEY WOULD SAY
SOME CRAZY NUMBER LIKE
11:15 P.M. OR 2:21 A.M.
AND IT WAS ALWAYS -- ALMOST
ALWAYS LATE AT NIGHT, SOMETIMES
LATE IN THE AFTERNOON, NEVER IN
THE MORNING.
THERE WAS A TRUE CIRCADIAN
PATTERN TO THEIR DISEASE AND IT
WAS PREDICTABLE.
THEY KNEW IT WAS GOING TO HAPPEN
BECAUSE OF SHAKING -- DRENCH
THEIR BED SHEETS, LOOK PRETTY
GOOD IN THE MORNING.
SO THE FEVER PATTERN IS
IMPORTANT BUT IF YOU READ AND
KNOW ABOUT FEVER PATTERNS,
THEY'RE NOT THAT SPECIFIC.
THERE'S A LOT OF THINGS THAT CAN
LOOK LIKE THIS.
THE SAME CAN BE SAID OF THE
RASH.
I ONCE -- THE AMERICAN ACADEMY
OF DERMATOLOGY, I GOD GOT BOO'D
OFF
STAGE, I SAID 
WHAT'S THE MOST
DISTINCTIVE ASPECT OF THIS
DISEASE AND HOW YOU MAKE THE
DIAGNOSIS?
HE SAID, IT'S THE RASH.
IT IS THAT FAINT SALMON PINK
MACULO PAPULAR AREA OF
COALESCENCE THAT MAY NOT BE
ITCHY AND HAS THE ASSOCIATE
FEATURES WHERE YOU SCRATCH
YOURSELF, YOU GET AN EXAGGERATED
WHEEL AND FLARE, YOU SCRATCH
YOURSELF AND YOU LATER ON GET A
RASH IN THE DISTRIBUTION OF
TRAUMATIZED SKIN.
HE SAID THAT THAT WAS ABSOLUTELY
CHARACTERISTIC.
AGAIN, OLD DERMATOLOGIST SAID
IT'S A MORE BILIFORM VIRAL --
THEY LOOK THE SAME.
AS MUCH AS WE'D LIKE TO MAKE A
LOT ABOUT THIS, IT'S NOT THAT
SPECIFIC BUT AGAIN WHEN YOU
START SHRINKING THESE TOGETHER,
YOU'LL SEE OTHER THINGS.
AGAIN, PRURITUS AND URTICARIA,
40% OF PATIENTS, OTHER THINGS,
ALOPECIA PLAQUES, NOT SO OFTEN.
A LOT OF THEM HAVE A V NECK KIND
OF LOOK THAT LOOKS VERY MUCH
LIKE DERMATOMYOSITIS AND THERE'S
OFTEN CONFUSION BETWEEN ADULT
STILL'S AND PATIENTS WITH
DERMATOMYOSITIS.
HERE'S A VERY FAINT RASH, MOSTLY
OLD PICTURES OF RASHES LOOK LIKE
THEY'RE BROWN OR GREEN OR
SOMETHING BECAUSE YOU HAD REALLY
BAD CAMERAS BACK THEN OR YOU'RE
TAKING REPRODUCTIONS OF JOURNAL
ARTICLES.
THE ARTHRITIS IS IMPORTANT.
ON THE VERY FAR RIGHT IS THE
EXPERIENCE IN 21 PATIENTS AT THE
UNIVERSITY OF PITTSBURGH.
THE ONSET BEING THE FIRST SIX
MONTHS OF DISEASE AND HOW MANY
JOINTS WERE INVOLVED.
SO 11 OUT OF 21 HAD SHOULDER
INVOLVEMENT.
19 OF 21 HAD KNEE INVOLVEMENT.
AND THEN THE COURSE IS AFTER SIX
MONTHS, AND OVER THE COURSE --
YOU CAN SEE THAT EARLY ON, THEY
GET A POLYARTHRITIS, IT'S SMALL
AND LARGE JOINTS BUT LATER ON,
IT TENDS TO BE MOSTLY THE WRIST,
KNEES, ANKLES, MAYBE SHOULDERS,
AND THEN SOME WILL HAVE SMALL
JOINTS AND THOSE ARE THE ONES
THAT ARE GOING TO HAVE CHRONIC
POLYARTHRITIS THAT LOOKS LIKE
R.A.
SO MYALGIAS, ARTHRALGIAS ARE
PREDOMINANT, WHEN THEY'R ACUTE,
HOT, INFLAMMATORY, THEY CAN GET
FLEETING ARTHRITIS TO DEVELOP,
MOST OF THEM WILL DEVELOP A PO
LEGAL ARTHRITIS.
A MONO OR THRIETS?
SORRY, NOT STILL'S DISEASE.
YOU'VE GOT TO WORRY ABOUT THAT.
YOU SHOULD THINK ABOUT OTHER
DIAGNOSES.
CARPAL ANGLO CYST, THEY SAW THIS
UNIQUE PATTERN OF ANKYLOSIS OF
THE WRIST IN A PERICAPITATE
DISTRIBUTION SORT OF
DISTINCTIVE.
I HAVE ABOUT FIVE OF THESE KIND
OF PICTURES THIS IS LK LARRY,
WHEN HE PRESENTED THEM, SEVEN
MONTHS LATER, OOPS, NOT SO
NORMAL, HE'S STARTING TO FUSE,
CAPITATE THE SECOND AND THIRD
META CARPAL OVER HERE, CLEARLY
FUSED TO THE LUNATE AND STARTING
OVER HERE WITH THE SCAPHOID SO
THIS PERI CAPITATE PATTERN OF
DX.
VERY SPECIFIC FOR STILL'S
DISEASE, BUT IF YOU HANG OUT
WITH RADIOLOGISTS AND THEY SAY
WHEN YOU SEE THIS, WHAT DO YOU
SEE IT IN?
YOU LIKELY SEE IT'S A RARE
MANIFESTATION OF R.A., IT'S A
RARE MANIFESTATION OF ARTHRITIS
SO YOU'LL SEE PROBABLY MORE
PERICAPITATE ANKYLOSIS BECAUSE
THEY'RE MUCH MORE COMMON BUT IF
YOU'RE CONSIDERING STILL'S
DISEASE, THIS DEVELOPS IN 50% OF
PATIENTS.
OTHER THINGS THAT ARE
DISTINCTIVE, THE WEIGHT LOSS CAN
BE AS DRAMATIC.
THINGS THAT REALLY GO LIKE THIS
IN STILL'S DISEASE NOT ONLY HOW
THEY FEEL, BUT THEIR WEIGHT
WEIGHT
DROP, HEMO GLOBIN DROPS, ALBUMIN
DROPS, THESE ALL HAPPEN IN A
MATTER OF WEEKS.
SOME WILL HAVE HAD
HEPATODYSFUNCTION,
HEPATOSPLENOMEGALY, PRURITUS,
PERICARDITIS.
MYOCARDITIS IS RARE.
ONE PATIENT I SAW AS A RESIDENT,
BIG PERICARDIAL PLEURAL
EFFUSION, MILD PERIO CAR DIETS
ON BIOPSY.
GOT REPORTED TWICE IN THE
LITERATURE, ONCE FOR THIS, THE
MYOCARDITIS, SECOND, BECAUSE HE
DEVELOPED INFLAMMATORY ORBITAL
SUE TOE TUMOR.
THE LABS ARE EQUALLY
DISTINCTIVE.
THIS IS WHAT USUALLY SCARES THE
CLINICIAN MUCH AS LOOKING AT THE
PATIENT.
THE PATIENTS LOOK SICK AT THE
OUTSET BUT THEIR LABS MAKE THEM&
LOOK WORSE BECAUSE THEY HAVE
THIS TREMENDOUS WHITE COUNT, YOU
CAN SEE THE MEDIAN LEVELS, THE
HIGHEST THAT I'VE EVER SEEN IS
70,000, 73,000 ACTUALLY.
THEY SHOULD BE ZERO NEGATIVE FOR
ANA, THEY SHOULD HAVE A
LEUKOCYTOSIS WITH A STRONG LEFT
SHIFT, ANEMIA CHRONIC DISEASE,
THEY WILL ALL HAVE SOME KIND OF
ELEVATED ACUTE PHASE REACTIVE
AND WE MAKE A BIG DEAL OUT OF
THE HYPERFERRITINEMIA BUT IT'S
ONLY SEEN IN HALF THE PATIENTS.
IT'S NOT THAT SPECIFIC BECAUSE
IRON OVERLOAD STATE, I SEE MORE
VASCULITIS AND LUPUS THAN I SEE
IN STILL'S DISEASE, IF YOU'RE
TALKING ABOUT ACTUAL RAW
NUMBERS.
BUT AGAIN, THIS MAKES PEOPLE
REALLY EXCITED AND THINKING, OH,
IT WILL BE.
MOST -- VARIATIONS IN STILL'S
DISEASE IS GOING TO BE 900, 600,
NOT 25 THOWL, BUT AGAIN, WHEN
CLUE, AND IT MAY HAVE SOME
SPECIFICITY TO IT AND I'LL SHOW
THE DIFFERENTIAL DIAGNOSIS HERE
IS QUITE WIDE.
VIRAL SYNDROME USUALLY MEANS WE
DON'T KNOW, AND THEY RESOLVE IN
WEEKS TO MONTHS.
DERMATOMYOSITIS, REACTIVE
ARTHRITIS, IBD, LEUKEMIA,
LYMPHOMA, THOSE WOULD BE HIGHEST
ON THE LIST WHAT I WOULD SEE.
WHO DIAGNOSES THIS -- PEDIATRIC
DERMATOLOGISTS.
YOU SEE IT, YOU KNOW THE
PATTERN, AND I THINK IT WORKS
OUT MUCH BETTER.
MOST ADULT RHEUMATOLOGISTS GET
THE PATIENT, HAND IT OFF TO
THEM, I THINK, FROM THE I.D.
GUY.
IT TURNS OUT THAT'S NOT TRUE,
THEY GET MORE FROM HOSPITALISTS
BUT THE PATIENT HAS ALREADY BEEN
SEEN BY I.D. AND THEY'VE SAID
SORRY, WE'RE DONE, IT'S NOT AN
OCCULT INFECTION, IT'S PROBABLY
STILL'S DISEASE OR SOME
RHEUMATIC THING, AND THEN THE
RHEUMATOLOGIST GETS INVOLVED.
THEY KNOW THE CRITERIA, THE
PROBLEM IS FLLS YOU'RE IS
UNLESS YOU'RE I
N THIS
ROOM -- I SEE THE MAIN GRIPE
WITH PATIENT WHO HAVE STILL'S
DISEASE, IT'S A DIAGNOSIS THAT'S
THROWN AROUND LIKE NICKELS WHEN
IT SHOULD BE THROWN AROUND LINE
MANHOLE COVERS.
MEANING WHEN THEY HAVE A FEBRILE
ILLNESS, YOU DON'T KNOW WHAT IT
IS, YOU CALL IT STILL'S DISEASE
BECAUSE NO ONE IN THE REAL WORLD
IS APPLYING CRITERIA VERY WELL.
THERE IS A LOT OF
MUSCULOSKELETAL DIAGNOSIS.
TWO STUDIES I FIND INTERESTING,
THIS IS A COHORT OF SYSTEMIC JIA
PATIENTS WHO MET ILR
CLASSIFICATION CRITERIA FOR
SJIA, BUT WHEN THEY LOOKED AT
THEM, HALF OF THEM ACTUALLY HAD
FAILED TO MEET -- I'M CONFUSING
THIS WITH THE SECOND ONE.
SO THEY HAD THE TRIAD BUT HALF
OF THEM FAILED TO MEET THE
CRITERIA FOR -- I GET THOSE
CONFUSED -- FOR ILR CRITERIA
BECAUSE IT ACTUALLY DIDN'T HAVE
A TRUE QUOTIDIAN FEVER.
IN ILR CRITERIA, YOU HAVE TO
HAVE THAT.
ANOTHER REVIEW DONE BY PEOPLE AT
STONEY
STONY BROOK LOOKED AT LITERATURE
REVIEW, THEY ACTUALLY UNDERWENT
GENETIC TESTING AND SAW THAT A
THIRD OF THEM HAD A MONOGENIC
DISORDER IDENTIFIED BY ONE OF
THE GENETIC TESTING THAT WAS
DONE, AND FOUR MORE THAT HAD
EITHER FMM OR TRAPS, SO A TOTAL
OF 35 PATIENTS, I GUESS.
SO THEY ARE OFTEN MISDIAGNOSED
AND THEY MAY GET THERE
EVENTUALLY, I'LL SHOW YOU SOME
EXAMPLES.
I THINK YOU NEED TO KNOW THE
CRITERION.
SO THERE'S YAMAGUCHI CRITERION,
THESE ARE OFTEN USED BECAUSE
THEY WERE TESTED AND HAVE A
SPECIFICITY AND SENSITIVITY
THAT'S HIGH, OVER 90%.
I DON'T KNOW THAT IT'S REALLY
GOING TO HOLD UP, HAD A GOOD
CONTROL GROUP TO COMPARE TO BUT
NONETHELESS, IT'S PRETTY GOOD.
HERE YOU HAVE TO HAVE FIVE OR
MORE CRITERIA AND TWO OF THEM
MUST BE MAJOR, THE MAJORS ARE
FEVER GREATER THAN OR EQUAL TO
39, ARTHRALGIA, AND THAT'S ONLY
FOR ONE WEEK FEVER.
THAT'S A BIT OF A PROBLEM.
AR THRALG JA FOR TWO WEEKS OR
MORE, THE STILL'S RASH, LEUKOFI
LICK -- 80%.
THESE ARE HELPFUL.
MY CRITERIA PUBLISHED ACTUALLY
CAME UP WITH THESE AT PITTSBURGH
IN 1984 PUBLISHED THEM IN 2,000,
HERE I'M GIVING YOU TWO POINTS.
IF YOU HAVE THE FIVE THINGS,
MORE SPECIFIC, SO THE FEVER, YOU
REALLY HAVE TO HAVE.
THE STILL'S RASH, THE
SIMULTANEOUS ELEVATION OF WHITE
COUNT AND SED RATE.
THAT TAKES CARE OF A LOT OF
OTHER PROBLEMS.
BUT BOTH NEED TO BE ELEVATED.
YOU COULD SUBSTITUTE A CR -- YOU
GET ONE POINT FOR ONSET AGE LESS
THAN 35, POLYARTHRITIS, SORE
THROAT, THAT'S PRODROMAL, RES,
LYMPHADENOPATHY OR LFT
ELEVATIONS, SEROSITIS,
CERVICAL/TARSAL ANKYLOSIS, CAN
BE HELPFUL TO BE SEEN.
THE FIRST SIX WEEKS, I THINK
IT'S AT BEST A POSSIBLE
DIAGNOSIS.
WHAT WE FOUND IN PITS
PITTSBURGH IS
THAT YOU CAN PROGNOSTICATE A
LITTLE BIT BASED ON HOW THEY
BEHAVE.
21 PATIENTS, FOUR OF THE 21
PATIENTS HAD SYSTEMIC DISEASE
THAT LASTED MONTHS TO YEARS.
THEY HAD MULTIPLE SPIKES WITH
DISEASE-FREE INTERVALS IN TWO
CASES.
THEN THE SAME PATTERN EXCEPT
THROW IN CHRONIC ARTHRITIS ON
THE BOTTOM, THAT TAKES CARE OF
MOST PATIENTS.
10 WITH POLYSYSTEMIC, ONE WITH
MONO SYSTEMIC CHRONIC ARTICULAR
IN FIVE PATIENTS.
WE SAW THAT IT WAS ARTHRITIS
THAT ACTUALLY DETERMINED THE
LONG TERM OUTCOME AS FAR AS
FUNCTIONAL OUTCOMES AND THAT'S
SHOWN HERE IF YOU DIVIDE THEM UP
BY THE ONSET AND COURSE, YOU CAN
SEE IT'S THESE PATIENTS OVER
HERE WHO HAD A POLYARTICULAR
ONSET AND COURSE WHO ARE MORE
LIKELY TO BE FUNCTIONALLY
IMPAIRED IN LONG TERM FOLLOW-UP.
PATIENTS WITH STILS DO DIE BUT
USUALLY NOT FROM STILS DISEASE
IS WHAT I SAY.
IT'S MORE LIKELY TO BE RELATED
TO COMPLICATIONS OF STEROID
THERAPY, IF YOU'RE DEALING WITH
PEDIATRIC POPULATION, THE
FATALITY RATE WITH MAS IS
ANYWHERE FROM 8 TO 37%, IT CAN
BE VERY HIGH.
SO OBVIOUSLY INFECTION WHEN IT
IS PRESENT, DIC AND LUNG DISEASE
ARE MAJOR CONTRIBUTORS.
A STUDY DONE BY META AND
COLLEAGUES LOOKED AT THE
NATIONAL INPATIENT SERVICE ABOUT
8 MILLION HOSPITALIZATIONINGS.
THEY FOUND 5800 STILL'S PATIENTS
WHO WERE HOSPITALIZED AND FOUND
A MORTALITY RATE OF 2.6%.
IT WAS ABOUT -- I THINK THE
NUMBER WAS ABOUT -- IF YOU WERE
62 AS OPPOSED TO 52, THE AVERAGE
AGE WAS 53, THAT THERE WAS A
HIGHER RATE OF MORTALITY AND IT
WAS ACTUALLY SIX FOLD HIGHER IF
IT WAS AN ASIAN HOSPITALIZATION.
THEY DID HAVE ABOUT 1% EACH OF
MAS CASES, DIC OR TTP, SO THESE
ARE RARE VARIANTS BUT THE SCARY
THINGS THAT DO HAPPEN IN STILL'S
DISEASE.
WHAT DOES IS THIS DUE TO?
CIRCADIAN CYTOKINE, A CIRCADIAN
INFLAMMASOME DISORDER.
IL-1 AS CIRCADIAN RHYTHM TO IT,
SO DOES IL-6.
IL-1 PACK PEAKS HERE ABOUT
8:00 P.M., DROPS DOWN ABOUT 6:00
A.M.
CORTISOL, WHY YOU ALMOST NEVER
SEE FEVER IN STILL'S PATIENTS IN
THE A.M.
THIS IS A PRESENTATION VAN REL
WHO DID IL6 LEVELS HERE PEAKING
AGAIN IN THIS CASE AROUND
8:00 P.M., AND TWO HOURS LATER,
THEY EITHER HAD A FEBRILE SPIKE
AND THIS DROPPED OVERNIGHT AND
AGAIN, SUPPORTING A
CYTOKINE-DRIVEN SIR CIRCADIAN
DISORDER.
THE KEYS TO DIAGNOSIS IS THAT
DAILY CIRCADIAN THING.
THE STILL'S RASH USING CRITERIA,
YOU KNOW, IN RESPONSE TO
IL-1 INHIBITION REALLY IS VERY
HELPFUL, I'VE SEEN PATIENTS WITH
INFECTIONS GET BETTER AND
LYMPHOMA GET BETTER WITH
IL-1 INHIBITION SO IT IS NOT
SPECIFIC, UNTIL WE HAVE A TRUE
TEST, AND THEN WHETHER OR NOT
THEY SHOULD HAVE GENETIC
TESTING, I THINK THE MORE
ATYPICAL THE PATIENT, THE MORE
YOU SHOULD BE DOING GENETIC
TESTING.
WE DO A SORT OF MOLECULAR
PHENOTYPIC ANALYSIS.
VIRGINIA NIGHT TALK ABOUT THIS
TOMORROW, AND USING MICRO ARRAYS
FROM STILL'S PATIENTS, THERE'S A
PATTERN WHICH SHE CALLS THE
SIGNATURE AND IT'S STRONG FOR
INFLAMMATORY SIGNALS, DOWN
REGULATION OF B CELLS AND
T-CELLS AND THIS IS SEEN,
WHEN THEY'RE RED HOT, NE LOOK
EXACTLY LIKE THIS, WHEN YOU
TREAT THEM, IT FADES.
IT DOESN'T GO AWAY.
WHEN IT GOES AWAY, ALL THESE
COLORS GO AWAY, IT'S A BLANK
ANALYSIS MORE OR LESS.
SO IT'S A USEFUL THING IN
FOLLOWING PATIENTS AND WE DO
THAT SERIALLY.
WE DO THAT WHEN A PATIENT HAS
AN -- IT IS A PROBLEM IN GETTING
THIS PAID FOR AND DONE.
MONITORING ARTICULAR DISEASE IS
EASY, SYSTEMIC DISEASE IS HARD.
FEVER, RASH, HEPATOSPLENOMEGALY,
THE FEATURES OF DISEASE.
AGAIN I'LL DO FERRATIN.
THIS NEUTROPHIL TO LYMPHOCYTE
RATIO IS HELPFUL, THIS IS CRP
BETTER THAN ESR.
THIS IS FERRITIN RIGHT HERE,
THIS DOTTED LINE THAT I'M
SHOWING YOU, BUT THE
NEUTROPHIL-LYMPHOSAY THE -- I
LEARNED THAT ALDOLASE IS A
STRONG BIOMARKER FOR
INFLAMMASOME ACTIVITY.
THEIR CPK LEVELS ARE NORMAL AND
IT DOESN'T ALWAYS PARALLEL THEIR
LFTs.
I BELIEVE THERE'S A CONNECTION
BETWEEN ALDOLASE ACTIVITY AND
INFLAMMASOME ACTIVITY.
THESE ARE NOT WIDELY AVAILABLE
AND MAYBE MICRO ARRAYS IN THE
FUTURE.
FEVER IS AN ISSUE.
PATIENTS COME AND SAY I'VE GOT A
FEVER.
AND YOU DON'T KNOW BECAUSE THEY
LOOK PRETTY GOOD TODAY.
I ASK PATIENTS AND I FOLLOWED A
FEW NOW WHERE THEY BUY THIS OFF
OF AMAZON FOR $25, IT'S A PATCH
YOU PUT IN YOUR AXILLA,
BLUETOOTH CONNECTS TO YOUR
PHONE, AND THEY CAN COME IN AND
SHOW YOU WHAT THEIR FEVER
PATTERN IS.
THERE'S NO GUESSING, NO
RECORDING, NO TRYING TO DECIPHER
WHAT THEY PUT ON NOTEPAPER.
THIS CAN BE A USEFUL AND FAIRLY
INEXPENSIVE TOOL.
THE APPROACH IS FAIRLY SIMPLE.
HIGH DOSES OF NONSTEROIDALS
AND/OR STEROIDS.
STILL'S DISEASE SHOULD NOT
RESPOND TO 10 TO 20 MILLIGRAMS A
DAY.
IF THEY HAVE ARTHRITIS, IF THEY
HAVE -- IF THEY'RE NOT DOING
WELL, THEY SHOULD GET A HIGHER
DOSE OF STEROIDS WITH
METHOTREXATE AND I WILL QUICKLY
USE AN IL1 INHIBITOR.
YOUR OPTIONS ARE MANY, YOU CAN
USE AN IL6 INHIBITOR AS WELL,
THESE ARE EXPENSIVE.
I LIKE KINERET FOR ITS FAST
RESPONSE, IF THEY STILL HAVE
ACTIVITY, THEY'LL FLARE WITHIN
THREE DAYS.
THERE IS SOMETHING TO BE SAID
FOR POSSIBLY USING A JAK
INHIBITOR OR -- IF YOU COME FROM
A COUNTRY WHERE IL1 INHIBITORS
ARE NOT AVAILABLE, I HAVE HAD
PEOPLE RESPONDED, BUT THAT'S NOT
BEEN STUDIED.
ARTICULAR DISEASE, YOU TREAT
JUST AS YOU HAVE POLYARTICULAR
JIA OR ADULT R.A. WITH METH TREX
AT COMBINATION THERAPY.
THIS IS WHERE TNF INHIBITORS ARE
USEFUL.
SO I'LL END THERE, YOU CAN READ
MY SUMMATION.
I THINK THAT, AGAIN, THE
ADDITION OF IL-1 AND
IL-6 INHIBITORS HAS BEEN A MAJOR
ADVANCE, I THINK THE CRITERIA
NEED TO BE TESTED AND RE-TESTED
AND WIDELY SPREAD, AND KNOWING
HOW TO MONITOR PATIENTS CAN BE
VERY HELPFUL IN KNOWING WHEN TO
CONTINUE THERAPY OR STOP
THERAPY.
THANK YOU VERY MUCH.
[APPLAUSE]
