Document Sample
					                                                                                                                                                                                                                                                OCTOBER,             1973

                        DIFFUSE                                            EOSINOPHILIC                                                                    GASTROENTERITIS*
                                             By            HENRY                   I.        GOLDBERG,            M.D.,   DONALD       O’KIEFFE,                                                                   M.D.,I’
                                                                                         MAJ.             EDWIN   H. JENIS,    M.D.,     and
                                                                                             COL.          H. WORTH     BOYCE,     M.D.t
                                                                                                           SAN          FRANCISCO,             CALIFORNIA

 D              IFFUSE      eosinophilic                                           gastroentenitis     is                                    palor,         a palpable       spleen      tip, and minimal                                                       axil-
                 a syndrome      ofpenipheral                                            blood eosino-                                       lary       and inguin al lymphadenopathy.
philia,                 gastric                       and           small                 bowel                   nodular                            Laboratory        studies      included     an initial                                                  hema-
                                                                                                                                              tocrit              of      30         per        cent           and           a      white          blood             cell
deform         i ties       (seen        roentgenognaphically),
                                                                                                                                              count                                 w
                                                                                                                                                                  of i#{231},ooo/mm.’ ith 48 per cent eosino-
and        dense        gastrointestinal             eosinophilic                                                              in-
                                                                                                                                             phils.               Peripheral                    smear,               blood              indices,            serum,
filtration           (detectable          microscopically).                                                                 This
                                                                                                                                             and bone      marrow     iron  studies     indicated    severe
disease                     has          been                reported                     in         6           patients
                                                                                                                                             iron deficiency.       An elevated      level of A2 hemo-
since            its          description                           in      the          late             19305.              Be-            globin    (.6      per cent)    was    present       on hemo-
cause             this            disease                  often           has          a distinct                      noent-               globin               electrophoresis.                          Occult                blood         was        present
genographic                                small                  bowel                 pattern                    accom-                    intermittently                                in          stools;               however,                 multiple
panied                      by       a       gastric                      deformity,                            accurate                     stools               and       duodenal                    drainage                   were         negative             for
roentgenograph                                    ic           interpretation                                      is         fre-           parasites.                    Routine                skin           tests           and      blood        chemis-
quently                      possible.                                                                                                        tries             were       within               normal             limits.             Serum          albumin
         The           purpose                    of         this          paper               is     to         describe                    was           initially                 2.9      gm.        per         cent.           Proctosigmoido-
                                                                                                                                             scopy                 and           barium                 enema                    examination                   were
this             noentgenographic                                            pattern                       of       diffuse
                                                                                                                                             normal.  Upper gastrointestinal                                                           roentgenograms
eosinophilic                         gastroentenitis                                    and          to        illustrate
                                                                                                                                             revealed thickened       valvulae                                                     con niven           tes       and
it                findings                        in 4              patients                        evaluated                   at
                                                                                                                                             separation                         of      the       small              bowel              loops         (Fig.           i).
\Valten              Reed                        General                 Hospital                         oven                the
J)t5t    4              years.                   The              extent                of          small             bowel
involvement                                 in         conjunction                                  with            gastric
involvement                               and               the           complete                 noentgeno-
graphic                      reversibility                               of the                condition                       by
means                   of         corticosteroid                                  therapy                        will           be
stressed.                     Etiology                       and          classification                            of      this
entity             will            also           be          discussed.

                                         REPORT                     OF       CASES

         CASE A        I.          22  old Caucasian
                                           year                enlisted       man
of Mediterranean                   extraction        was seen for evalu-
ation          of     abdominal              complain      ts,     peripheral
eosinophilia,             anemia,           and splenomegaly.                   He
had         experienced            prandial        abdominal            cramps,
nausea,          vomiting         and di arrhea        associated          with a
20       pound                weight              loss            over        a period                    of      2 years.
He        reported                  no       hematemesis,                               hematochezia,                            or
melena.        Roentgenograms             reportedly       were nor-
mal shortly          after      the onset     of his illness.       The
                                                                                                                                             FIG.          i.     Case      I. The              duodenal,    jejunal,                        and ileal           val-
patient       denied       that     he had traveled       outside      of
                                                                                                                                                    vulae              conniventes                 are thickened.                           Separation              of
tile   United      States.       Although     he admitted         to oc-                                                                             bowel   ioops denotes                              thickening              of bowel     wall and
casional                 episodes                     of      “hay            fever,”                 no food      al-                              possibly      mesentery.                              Small              bowel    biopsy      from
lergies,               asthma,                   or         drug           allergies                  were  noted.                                   proximal              jejunum               confirmed               dense            eosinophilic                in-
Physical                     examination                            on        admission                          revealed                           filtration.
     *   From     the         Department                   of Radiology,            University                 of California            School        of    Medicine,            San       Francisco,          California.

     t Division              of Gastroenterology,                         Walter         Reed         General             Hospital,         Washington,                  D.C.
     t Department                  of Pathology,                  Walter         Reed        General            Hospital,          Washington,                  D.C.

VOL.        119,     No.                                                   Diffuse               Eosinophilic                         Gastroenteritis                                                                                   343

The stomach      appeared                                      normal.              Twelve      grams                           otherwise                   the    remainder                        of    the       examination
of fat was present      in a                                 24   hour            stool collection.                             was    within                 normal     limits.
Esophagogas                      troscopy                    revealed                patchy      distal                             Laboratory                      studies      dun ng hospitalization
gastritis             and          a biopsy                   from             this area     showed                             revealed       a                persistent        leukocytosis     (i#{231},ooo-
infiltration                of       the         lamina             propria               with           mature                 o,ooo/mm.’)                       with      o-6o     per cent eosinophils.
eosinophils.                     A         Crosby                  capsule             small                  bowel             Routine                blood          chemistry                     procedures                  revealed
biopsy              from             the    region                   of       the      ligament                        of       reduced               serum           proteins                and        cholesterol.                Fecal
Treitz             showed              eosinophilic                        infiltration         of                   the        fat     determination                    and            d-xylose             absorption      were
lamina             propria.                                                                                                     normal.                Stools           were             negative               for parasites.
      On the basis                      of these              studies,            it was               felt         that        Tuberculin                   skin       tests          were         negative.
this     patient       had        thalassemia           minor     and                                                                  Upper           gastroin             testin       al roen          tgenograms                 dem-
eosinophilic       gastroenteritis.           Consequen       tly, he                                                           onstrated               irregularity                   and         narrowing              of the        dis-
was started        on a trial          dose    of prednisone        I 5                                                         tal antrum       and distortion       of the jejunal     pattern
mg./day.         On this dose            of corticosteroids        his                                                          with     effacement       of the       valvulae,     thickened
symptoms                   improved                   and           his     peripheral                    eosino-               bowel     wall and narrowing             of the lumen         (Fig.
phils         decreased                 from          o       per         cent        to 23        per          cent.           2, 3 and B). Results          ofbarium        enema   examina-
Because              of the             failure           of the eosinophils                                  to de-            tion          were          normal.                 Chest           roentgenograms                           re-
crease          below    20 per     cent,                         he was           treated   empiri-                            vealed           minimal                pleural               effusion             and          thoraco-
cally          with   tetrachloroethylene;                                          no further       re-                        centesis              yielded               clear        yellow            fluid         with        4,000

duction             in     the        eosinophils                    was         noted,            however.                     cells/mm.3,                   97      per       cent          of     which         were           eosino-
Consequently,          the prednisone             was restarted       in                                                        phils.        Small         bowel         biopsy          showed          mucosal
the same       dosage       and over          several     weeks    the                                                          edema         and a heavy               eosinophilic           infiltration          of
peripheral      eosinophils        decreased          to    per cent.                                                           the lamina            propria.
Follow-up        upper       gastrointestinal            roen tgeno-                                                                Two weeks              of nasogastric             suction        and then         a
grams      and small      bowel     biopsy       at this time were                                                              diet of clear liquids                improved            the patient’s          con-
entirely            normal.                                                                                                     dition.       The peripheral                eosinophils          decreased          to
      Over         the      past           4 years,               this      patient           has             had          to   30     per cent.         At the time                of his discharge              the
be       maintained                        on       corticosteroids.                             His           usual            patient         was       able       to tolerate              a regular          diet
daily       maintenance           dosage       has been            mg. of                                                       without          difficulty.          The        roentgenographic                 ap-
prednisone           and     on this       low dose         he has re-                                                          pearance          of the small               bowel         had returned             to
mained          asymptomatic            with     peripheral        eosino-                                                      normal.          A follow-up              small        bowel       biopsy        was
phils      under       10 per      cent     with      no evidence          of                                                   not performed.                Over       the next year the patient
gastrointestinal              bleeding         or     malabsorption.                                                            had a persistently                  elevated          level of peripheral
Discontinuation              of steroid       therapy       has always                                                          blood       eosinophils           (10-20          per cent)        and experi-
resulted         in recurrence         of the symptoms              with    a                                                   enced       intermittent,             mild episodes             of abdominal
concomitant             rise   in   the peripheral           eosinophil                                                         cramping            and diarrhea               associated          witil     a fur-
level.                                                                                                                          ther      increase         of eosinophils.              He treated            these
                                                                                                                                episodes         by abstaining                from food for a day or
      CASE          II.     A      28       year          old        Caucasian                   physician                      two and noted               improvement                within      this period;
was        admitted                  for        evaluation              his-of    a    3 month                                  i6 months             after     onset        of symptoms,                however,
tory     of diarrhea,         abdominal           cramps,         and a                                                         he had a severe                 flare-up           of symptoms              with      a
pound       weight     loss. The abdominal                 cramps      were                                                     marked               rise     of eosinophils.                       He     was      hospitalized
related       to all types         of food ingestion               and the                                                      and given         steroids      which     resulted       in almost     im-
diarrhea        which     followed        shortly      after     meals   re-                                                    mediate       clinical       improvement             and a rapid         re-
sulted      in stool       which      was watery              and brown                                                         duction       in his peripheral               eosinophils.       Steroid
with      considerable           mucus.        Shortly         before   ad-                                                     dosage      was tapered            then     stopped        and the pa-
mission       he noted       early satiety         and postprandial                                                             tient    resumed           a normal       diet;     over     the next
vomiting.        Past     medical       history       was unremark-                                                             years     he noted           only     minimal         and infrequent
able except         for mild seasonal             allergies.       The pa-                                                      symptoms.             His     peripheral         eosinophil        count,
tient specifically          denied      intolerance          to food. He                                                        however,        remains        elevated.
said his father         had “hay          fever”      and his mother
“an         asthmatic                   condition.”                       On      initial          physical                            CASE          III.      A 21             year        old Caucasian                      soldier
examination                      there            was evidence                       of moderate                                developed                   abdominal                   cramps,       nausea,                 and in-
dehydration                      and             hyperactive                      bowel   sounds;                               termittent                   diarrhea,                 while    stationed                   in West
344                                                                        Goldberg,                    O’Kieffe,                jenis        and         Boyce                                                    Oioii:s,                 l7

                                                                                         -                                           I.                                                                .

FIG.          2.    Case         II.     (A)     Concentric                antral        narrowing                   is associated          with      diStortion            of     the     mucosal               fold         pattern            of
       the jejunum.                      Extensive             eosinophilic              infiltration                 may     produce         narrowing             of the        intestinal               lumen         and            efface-
       ment          of     mucosal folds, as well as separation         of bowel      loops   (arrow).   (B) Seven       weeks       after  the abnormal
       small         bowel  roentgenograms           in A were obtained,       the small bowel pattern          had returned          to normal.      This pa-
       tient        had not received       steroids.      The sole method         of treatment       was bowel     rest (nasogastric          suction     for 2
       weeks          with concomitant        intravenous      feeding,    then     I month     of liquid  diet   without      milk).

Germany.                         Since          this        condition                persisted                 for      i      tecture.       Multiple        stools     were negative         for para-
month,                    uncontrolled                       by      anticholinergic     ther-                                 sites.     Duodenal          aspiration         revealed     hookworm
apy,           he was hospitalized                                for further    evaluation.                                   ova,     and the patient            was given        a    day course      of
The           year  before,    while                          stationed       in South  \iet-                                  thiabendazole             resulting         in mild       symptomatic
nam,               he had          developed                   malaria,              which             was       suc-          improvement               and       a decrease           in peripheral
cessfully                   treated.                 The        remainder                    of    his          past           eosinophils          from       50    per cent        to 20 per cent.
medical                   history was                      noncontributory.                        He          gave            Within       2 weeks,       however,          he was again sympto-
no       personal                 or       family            history          of allergy.                                      matic       and peripheral             eosinophils        had returned
       Physical                  examination                      on    admission                 was         unre-            to pretreatment                levels. Stools and duodenal
markable.                        A white               blood           cell     count             of         i #{231},ooo      drainage            this     time          showed            no    parasites;                      tile      pa-
per  mm.’                        with        6o per                 cent        eosinophils                      was           tient    was therefore                      started     on            a daily    dosage                           of
present.                   The           hematocrit                  was       37 per cent                       and            #{231}o prednisone.
                                                                                                                                    mg.                                    Symptomatic                    improvement
blood indices, peripheral                 smear,        serum,         and                                                     was        immediate                 and          the      peripheral                    eosinophil
bone marrow           iron studies confirmed                   iron de-                                                        count         returned              to       normal.
                                                                                                                                                                               Prednisone           dosage
ficiency. Stool guaiacs           ranged        from      1-3+       posi-                                                     was    decreased         to 20 mg.       every      other     day.
tive    for occult        blood.      Intestinal           absorption                                                              With       the decrease          in steroid       dosage        the pa-
proved      to be normal;            upper        gastrointestinal                                                             tient      again      developed        cramps         and peripheral
roen tgenograms,            however,           revealed           diffuse                                                      eosinophils         of 20 per cent.            Small      bowel       roent-
mucosal      thickening        of the small         bowel       and an-                                                        genograms           at this time         showed        irregularity          of
tral irregularity        (Fig.    3, 11-C).        Peroral        biopsy                                                       the small         bowel      pattern      similar       to that       of the
of the             small           bowel             from         a site      near       the       ligament                    initial       study;          a small              bowel           biopsy                revealed                  a
of Treitz revealed dense eosinophilic                                                       in filtration                      moderately                 heavy             infiltration                    of      eosinophils.
of the lamina  propria  with normal                                                     villous       archi-                   Again         multiple              stools         and          duodenal                 aspiration
\OL.   119,     No.     2                              Diffuse         hosi       nophilic      Gastroenteri                  tis                                                           345

revealed           no       parasites.          Empiric           retreatfllent              was     slowly          tapered               to   30      mg.,     to     be       adminis-
with       thiabendazole                 this   time      did    not     improve             tered      every        other          day;        on    this     dose      the       patient
the      abdominal           symptoms         or     decrease        the                     remained          asymptomatic.    Attempts   at decreas-
peripheral         eosinophils.        However,         increase       of                    ing tile       dosage    further resulted in a return                                             of
his daily        dosage      of prednisone          to 40 mg. re-                            symptoms            and a rise in per cent of peripileral
sulted      in disappearance          of his symptoms             and a                      eosinophils.
return       of his peripheral        eosinophil       level to less
than         per cent.    A follow-up        biopsy     showed       the                         CASE         iv.    A       24     year        old     Black         enlisted          man
small      bowel     to be normal.         The steroid          dosage                       noted       the        onset           of      abdominal             cramps,              early
346                                             Goldberg,          O’Kieffe,       jenis       and         Boce                                OCTOBER,      1973

satiety,      and     recurrent         episodes        of nausea          and       The      initial white      blood cell count         was 25,000
vomiting        for   I molltil.      He was treated             with anti-      mm.3        with 69 per cent eosinophils.                 Upper     gas-
cholinergic         drugs      for 2 months           without        relief of   troi 11 testin  al roen tgenograms              revealed      nodular
his ssmptoms              and during        this period          lost 30 lb.     irregularity      of the distal         stomach        and much        of
Past      medical       history      and physical           examination          the small      bowel      (Fig.    4, 1-C).      A barium       enema
were        unremarkable.            The      patient         denied       any   procedure              and    extensive      hematologic            and   mal-
allergies       or specific       food intolerance;              he stated,      absorption             evaluations          disclosed         nothing       ab-
however,          that     one of his brothers                 has “bron-        normal.            Examination            of stools        and     duodenal
chial asthma.”                                                                   drainage           gave      no evidence       of ova      and    parasites.
VOL.       119,        No.         2                                        Diffuse                    Eosinophilic                Gastnoentenitis                                                                                347

Histologic   examination     of the                                                   distal   stomach                        genographic            findings     of eosinophilic        infil-
and a biopsy    of the small   bowel                                                  revealed     heavy                      tration      of the small          bowel   (Fig.    i ; and      ,
eosinophiiic                      infiltration                   of     the          lamina     propria.                      1-C).      Infiltration         of the mucosa       and     lam-
     Diagnosis                     on        the        basis          of these                studies                was     ma         propnia            results            in      regular             nodular              con-
eosinophilic                       gastroentenitis                      ;     tile         patien            t        was
                                                                                                                              tour    defects.        These                       thickened                 valvulae              are
started               on        a daily          dosage               of 40       mg.          prednisone.
                                                                                                                              sharply        outlined                        by          banium--unlike                           the
Dramatic                    improvement                         ensued               and        tile level of
                                                                                                                              appearance                     of          thickened                       folds           due        to
peripheral                      eosinophils                  decreased                    to     7 per cent
within            i    week.             \Vithin             3 weeks,                total        eosinophil                  edema.            More             extensive                    involvement                  of the
count          had          returned                to normal.                   Roentgenograms                               bowel            wall              on         transmural                      involvement
of the            upper                gastrointestinal                          tract           and             histo-       results         in distorted                     valvulae                   with       irregular
logic        examination                           of        the       stomach                   and             small        angulation        and a saw-toothed               contour          of
bowel           yielded                no abnormal                      findings.                 The            pred-        the small       bowel    (Fig.    2z1;    and 3i1).         Infil-
nisone             dosage                was           tapered              to        i        mg.,              to  be       tration     may     be so pronounced             as to efface
taken          every             other          day;         attempts                 to decrease                     the     completely        the valvulae,        resulting        in nan-
steroid               dosage              below              this       level,             however,                    re-    rowing     of the bowel        lumen       (Fig.     2#{237}1);the
sulted          in exacerbation                         of symptoms       and an ni-                                          bowel      at fluoroscopy          may        then       appear
crease          in peripheral                      eosinophils.     At the end of i
                                                                                                                              rigid.         Involvement                          of      the          mesenteny                 and
year         the           patient              is asymptomatic          on his pro-
                                                                                                                              omentum                  may            result             in      separation                of      in-
gram         of        i         mg.         steroid      dosage   taken    alternate
days.                                                                                                                         testinal             loops.          In       those             patients            with         stea-
                                                                                                                              tornhea              from            malabsorption,                           the  barium
                  ROENTGENOGRAPHIC                                            FINDINGS                                        column               may           be somewhat                           segmented      and
     The              roentgenographic                                      abnormalities                                of
diffuse               eosinophilic                       gastroentenitis                               are       typi-
 cal of most infiltrative                  diseases       that involve
 the small          bowel.       Although           the jejunum                is                                                  Eosinophils         in the mucosa         of the gastro-
 most       prominently              involved,2’7”6                 the en-                                                   intestinal        tract     are common.           Massive        in-
 tire    small        bowel        may         be affected,’6              and                                                filtration       of the wall of the stomach                    and
occasionally              the colon.9”2             All of our pa-                                                            small      bowel       by eosinophils,         in association
 tients       exhibited           extensive           duodenal,              je-                                              with an increased               amount     of eosinophils          in
junal,         and       proximal             ileal     involvement.                                                          the peripheral            blood      are hallmark       findings
 Involvement               of the small             bowel         is often                                                    of eosinophilic           gastroentenitis.        Eosinophilic
 associated          with gastric           eosinophilic           infiltra-                                                  gastroentenitis                         has         also          been         called             idio-
 tion.2 In 3 of our cases, there was roentgeno-                                                                               pathic        eosinophilic            infiltration          of the gas-
graphic          evidence           of concomitant                   gastric                                                  trointestinal            tract,      eosinophilic            gastnoduo-
 involvement.              Gastric        involvement              may        be                                              denitis,         eosinophilic               granuloma               of    the
 manifested           by enlargement                 of rugal         folds,4                                                 stomach          and small             intestine,         gastric       sub-
 narrowing           and rigidity            of the antrum,               or a                                                mucosal          granuloma               with       eosinophilic           in-
 bulky        irregular           intraluminal              mass.            Al-                                              filtration,        gastric         lesion        of Loeffien’s          syn-
 though         the antrum              is the major             area        af-                                              drome,         and allergic           gastroenteropathy.
 fected,        the      entire        stomach           may         be in-                                                        Because          the       etiologies           of eosinophilic
volved.4”1          In all         of our patients,              involve-                                                     infiltration         in the gastrointestinal                     tract    are
ment       was limited            to the antrum.              In Case I,                                                      controversial,              some       confusion           exists      as to
patchy         antral       mucosal           abnormalities              were                                                 whether         all of these terms                should      be applied
 noted       by the endoscopist                     and      later        con-                                                to diffuse             full-thickness               gastrointestinal
firmed                by          biopsy                as      areas            of        eosinophilic                       infiltration                  by        eosinophils.                       Review           of      the
infiltration,                      although                     the      an trum                  appeared                    literature              indicates                   3      apparently                   separate
normal                     on       upper                gastrointestinal                                    noent-           pathologic      states.      The                                 first is known        as
genograms.                                                                                                                    allergic  gastroenteropathy,8”6                                        which    occurs
    Thickening                            and        widening                    of the                valvulae               mainly    in the first        and                               second    decades      of
conniventes                            are         the        most            common                         roent-           life. Hypoalbuminemia,                                          hypogammaglobu-
348                                                     Goldberg,                O’Kieffe,       Jenis        and       Boyce                                                    OCTOBER,               1973

linemia,       anemia,         blood      eosinophilia,            and                          gastrointestinal                       symptoms                         are         cramping
small     bowel     eosinophilic        infiltration         limited                            abdominal                pain,      weight    loss, and diarrhea
to the mucosa             are all associated              with     this                         ( as     manifested               by our      patients).        Nausea
condition.       In patients         with allergic           gastro-                            and         vomiting             have    also been       noted,     par-
entenopathy           a definite       history         is given       of                        ticulanly           when             the         stomach                as       well         as        the
allergy,     particularly          to milk        products         and                          small      bowel      is involved.
meat.6’8”2”6        Two ofoun          4 patients          (Cases       i                          Hypoproteinemia                 may       result        in    ab-
 and ii) had only “hay               fever”        type allergies                               dominal          distention          and         swelling          of
without            apparent            food        allergy,            asthma,           on     ankles.6”        Eosinophilic           ascites        has      also
urticania.           The       other          2   had         no    allergic         his-       been      noted     in this disease,           probably         sec-
tory.        All     had       the      same            roentgenographic                        ondary       to senosal      involvement.”6               Eosino-
and histologic            changes     and were            over        20                        philic        pleural            effusion                  was        present                in     I      of

years     of age. At the present                 time,      allergic                            our patients                 (Case                ii),        but        there            was            no
gastroentenopathy               is separated            from       the                          evidence     of            ascites.                   In      extensive                 mucosal
di ffuse      eosinophilic         gastrointesti           nal       in-                        invasion,               malabsorption                               results             in         stea-
volvement          by an established               allergic       his-                          torrhea.”1’                 Duration                      of symptoms                         varies
tory,     almost      sole involvement              of the mu-                                  from       a few             months2”4                      to several                        years.
cosa,     and the high incidence                 in childhood.                                  One patient                 (Case    i)                  had symptoms                           for            2

Allergic           gastroenteropathy                          and      diffuse        eo-       years         before         his           condition                  was        diagnosed;
sinophilic             gastroenteni               tis  without                 associ-          the other       3 had    symptoms              for only      a few
ated      allergy,          however,              have    many              features            months.
in common.                 Caution            should          be    exercised            in         All patients      with      diffuse       eosinophilic        in-
attempting            to classify          definitely           these                       2   volvement         of the         gastrointestinal             tract
processes         as separate          diseases.                                                with    on without         allergic       histories,       have       a
    In     diffuse        eosinophilic             gastroentenitis,                             high percentage         of eosinophils             in the blood,
the     second         pathologic           state,        eosinophils                           ranging             from         o          to        8o      per        cent.            Anemia
are prominent               in all layers             of the bowel                              may          be      frequent.                   In         those             instances                    of
wall      but      mainly        the      submucosa.               About                        eosinophilic       disease       of the intestine           with
one-half        of patients          with      this disease           give                      protein-losing        enteropathy,         serum     proteins
a     history         of      childhood                allergy.”            Eosino-             will     be decreased.1#{176} Immunoglobulin                   A,
philic gastroentenitis                        is a disease   of adults,                         immunoglobulin             G, and        immunoglobulin
the youngest         reported                    patient   (with   i ex-                        M have been reported                to be normal.”
ception)6            was      more        than          20     years        of     age.9             Biopsy    of the small        bowel    in eosinophilic
Beside        allergy        to external             agents,       a sys-                       gastroenteritis                      may                 reveal         a normal_ap-
temic      hypersensitivity                 reaction3’9”6          and a                        pearing             epithelium                           and        preserved        villi,
systemic          manifestation               of Loefilen’s           syn-                      with       eosinophilic             and        plasma-cell          infil-
drome’5          have       been      considered             causes       of                    tration       of the lamina                 propnia        (Fig.   ).2h1

diffuse      eosinophilic           gastroentenitis.                                            The      nature       of these          biopsies,        however,          is
    The      third       disease       state       is local      eosino-                        such that         the extent          of the eosinophilic               in-
philic     granuloma             of the stomach,               which       is                   volvement           throughout              the wall of the in-
probably            a distinctive                entity        separate                         testine       cannot         be fully          appreciated.          The
from the diffuse              involvement             of the gastro-                            depth       of which         the biopsy            specimen       is ob-
intestinal         tract.       It is best            considered          as                    tained        may         be      important,             since     some
granuloma           of the stomach                with eosinophils                              authors        have      stated        that      eosinophilic        gas-
present.        Patients         may or may not have                     an                     troentenitis         is best        classified        by the depth
allergic      history.        This    disease         is localized        to                    of involvement               of the bowel              wall.’2’16    The
the stomach.                                                                                    4 patients          in our series              all had extensive
    In     patients           with        diffuse        eosinophilic                           eosinophilic            infiltration             throughout            the
gastroentenitis             either       on an allergic              basis                      lamina        propnia         of the          small      bowel.      The
or without            evidence         of allergy,           the usual                          sites of biopsy             extended           only     slightly     into
Vot.    119,     No.                                       Diffuse           Fosinophilic            Gastroenteri                            tis                                                               349

the submucosa.           Since     none of the patients
had undergone           a surgical       procedure,        we do
not know        to what     depth     the bowel wall was
    In diffuse     eosinophilic        gastroenteni       tis the
stomach        and small        bowel      wall are grossly
thickened.        The     appearance           is similar       to
that of lymphoma             and regional         enteni          16

Full     thickness                specimens               of the     small        bowel
obtained         at the time of surgical                    operation
have        shown      that      the      intestinal          villi     are
preserved,         but eosinophil               and plasma-cell
infiltration            are        distribu       ted         diffusely
throughout           all layers          of the bowel               wall.
Hypertrophy            ofthe       muscle        layers      may add
to the bowel             thickness.6          The       eosinophilic
infiltration               in       this        disease       is     more         dense
than      in           other         causes           of gastrointestinal
eosinophilia,                    such      as         Hodgkin’s        disease,
carcinoma,                 amebiasis,                 helminthic              disease,
and      regional               entenitis.
                                                                                                  #{149}#{149}1h.#{149}   4#{149}                  -:
                  RESPONSE                TO STEROID         THERAPY
                                                                                                  .‘-,“                             #{149}    .#{149}

    After      systemic                         steroid         therapy,      the
roentgenographic                             evidence         of eosinophilic
infiltration              may            disappear,2’9”2”4              as well           as
                                                                                               FIG.          5.      Microscopic                      section      (Xioo)                  obtained                by
the clinical           symptoms         and the peripheral                                           means            of small                     bowel     biopsy     from                one          patient
eosinophilia.           The mucosal        pattern     has been                                      (Case   iv) demonstrates        dense   eosinophilic     infiltra-
reported         to revert      to normal         as early     as 2                                  tion throughout        the lamina     propria.      The villi, al..
months          after     the start      of steroid      therapy                                     though     harboring      large   numbers       of eosinophils,
                                                                                                     are not              thickened                 or blunted.
and the roentgenographic                    appearance         may
remain        normal        for   years.2     The roentgeno-
graphic        abnormalities         in the small       bowel of                               was              confirmed                           by        repeated                biopsy.                The
the patient           of Case iv reverted           to normal      3                           persistence                        of               eosinophilia                   in        the           small
weeks          after           steroid          therapy        was       initiated.            bowel       in                   one                instance               (Case             iii)           even
Intestinal            motility,           frequently         altered         by                though     roentgenographic                                                and          clinical            find-
the diffuse            transmunal             eosinophilic         infiltra-                   ings   had     reversed,                                       probably                 reflects             that
tion as manifested                     by areas         of spasm           and                 steroid                    therapy                   was        at     a suboptimal                          level
dilatation,              also     returns          to normal             after                 since              an           increased                      daily           dosage               (40        mg.
steroid         therapy.9          Occasionally,            abnormali-                         prednisone)                            led               to    disappearance                          of        the
ties may            still     be seen on roentgenograms                                        eosinophilic                           infiltration.                      It      is     noteworthy
even      though           physical          improvement             is pro-                   that,     in this       patient,      abnormalities                                                         were
nounced.”              In all of our 4 patients,                    steroid                    not      evident         roentgenographically-even
therapy           (varying           from       40    mg. prednisone                           though       steroid      therapy     was incomplete                                                          and
daily       to i 5 mg. daily)                  resulted      in prompt                         eosinophilic         infiltration       was present.                                                         This
reversal           of clinical             symptoms,            noted          as              suggests        that   the extent        of eosinophilic                                                        in-
early        as i week             in i instance             (Case         iv).                filtration                      determines                       the       degree              to         which
The      eosinophilic               infiltration          of the small                         the          abnormality                                 can    be seen           on       roentgeno-
bowel         disappeared               in 2 of our 3 patients                                 grams.
after      steroid          therapy          of 1-3       months;          this                           Two             of     our           patients                  have           been             main-
                                                              Goldberg,               O’Kieffe,      Jenis             and          Boyce                                                              OCTOBER,             1973

 tamed   on prednisone                         (Case            ,           mg. per day            which      may be produced                                                   by eosinophilic       in-
 for 4 years,    and Case                      Iv, i            mg.         every  other           filtration    of the stomach                                                 and small      bowel.
 day for I year)     without                         exacerbation.                    When              The    nodular   contour                                                 defects     produced
 steroid   therapy      was                    withdrawn                      from        3 of     by     dense              eosinophilic                            infiltration                       of mucosa
 the patients       (Cases                     i,      iii,         and       iv),       how-      and      submucosa                                are often sharply                                    defined.
 even,        the     clinical          symptoms                    and      peripheral                  Involvement                                 of the musculanis,                                       serosa,
eosinophilia            reappeared.         The      fourth         pa-                            and          mesenteny                       results                    in      separation                     of the
tient     (Case     II)    has not taken         steroids        for                               bowel     loops.      Gastric                                      involvement             is often
years       and has experienced                mild      intermit-                                 accompanied           b\? small                                      bowel      disease.
tent       abdominal             cramps      and       persistent                                      The roentgenographic                                                 features        are corn-
peripheral        eosinophilia.           Complete         clinical,                               pletely     reversible        as                                   a result        of systemic
histologic,       and noentgenognaphic                  remission                                  steroid              therapy.
is apparently            steroid-dependent.             Although
                                                                                                   Henry    I. Goldberg,    M.D.
the       disease          may          exacerbate,                    it     is   usually         Department      of Radiology,                                      Room                 ,8o-M
not treated      surgically.    Only                                when     steroids              University                of     California,                    San          Francisco
do not effect      relief of intestinal                                obstruction                 San       Francisco,                 California                  94143

is surgery    indicated.                                                                                 The            authors                      thank                 Drs.             Marvin                 Sleis_
                          DIFFERENTIAL               DIAGNOSIS                                     inger           and     Alexander                                  Margulis         for                            their
                                                                                                   mans-             suggestions                                   upon      reviewing                                   the
    Eosinophilic           gastroentenitis                             must      be dif-
ferentiated             roentgenognaphically                                       from
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