Mono fer®
`5.4 Literature References: mamula-2002
`
`Pharmacosmos A/S
`
`Jmmml of Pediatric Gn.strm:memfng\ w1tl N11rmin11
`34:286-290 0 March 2002 Lippincoll William' & Wilkin,, Inc, Philadelphia
`
`Total Dose Intravenous Infusion of Iron Dextran for
`Iron-Deficiency Anemia in Children With Inflammatory
`Bowel Disease
`
`Petar Mamula, David A. Piccoli, Susan N. Peck, Jonathan E. Markowitz, and
`Robert N. Baldassano
`
`Division of Gastroe11terology a11d Nutrition, The Children's Hospiwl of Philaclelphia, Philadelphic1, Pennsyll'ania, U.S.A.
`
`ABSTRACT
`Background: Iron-deficiency anemia is a frequent complica(cid:173)
`tion ~n children wjrh inOammatory bowel disease (IBO). Par(cid:173)
`enteral iron therapy is rarely prescribed because of concern
`about potential side effects. The aim of this study was to ret(cid:173)
`rospectively evaluate the safety and efficacy of total dose in(cid:173)
`travenous (TD!) iron therapy.
`Methods: Charts of all the pediatric patients with IBD who
`received TOI iron therapy between February of 1994 and Feb(cid:173)
`ruary of 2000 were reviewed.
`Results: Seventy atients (20 with ulcerative colitis and 50
`with Crohn 1sease) received a total of 119 TOI iron deittran
`infusions. Thirty-four patients qualified for the efi1cacy analy-
`
`sis. The average increase in hemoglobin concentration was
`ensjtjyjty m(cid:173)
`2.9 gldL, (P < 0.0001).
`lev
`immediate h
`actions developed ·
`atients
`of the total number 0
`infusions . None of the reactions \\ s life th
`in and none
`requi re hospua 1zat1on.
`Conclusions: Total dose intravenous infusion of iron deittran
`when appropriately used, is a safe and potentially efficaciou~
`treatment for children w1lh mllammatory bowel disease and
`iron e 1c1ency anemia w o are unresponslVe to or noncompli(cid:173)
`ant with oral iron therapy. JPGN 34:286-290, 2002. Key
`Words: Anemia-Iron-Inflammatory bowel disease. © 2002
`Lippincott Williams & Wilkins, Inc.
`
`Anemia is a common finding in inflammatory bowel
`disease (IBO). It affects between 30% and 70% of pa(cid:173)
`tients and has great impact on the quality of their lives
`(I). The causes of anemia include chronic disease, vita(cid:173)
`min 8 12 deficiency, folate deficiency, medication(cid:173)
`induced bone marrow suppression and macrocytic ane(cid:173)
`mia, hemolysis, and most commonly, iron deficiency
`anemia secondary to intestinal blood loss (2) .
`The treatment for iron deficiency anemia is oral or
`intravenous iron supplementation. Oral supplementation
`is often poorly tolerated, leading to poor compliance (3).
`Although parenteral iron supplementation is available,
`concern about potential side effects limits its administra(cid:173)
`tion.
`Parenteral iron therapy in children with inflammatory
`bowel disease has been described in a small number of
`patients (4). As previously described in an abstract (5),
`we use intravenous iron dextran infusion to treat anemia
`
`Received April 5. 2001; revised Augus1 6, and Oc1ober 30. 2001;
`nccep1ed No,ember 6, 2001.
`Address correspondence and reprinl requcsls lo Dr. Peiar Mamula,
`D"·ision of Gastroenterology and Nu1ri11on , The Children'\ Hospital of
`Philadclphrn. 341h S1ree1 and Civic Cen1er Boulevard, Ph1lndelphin. PA
`1910~. U.S A (c-mntl. Mnnmla@email.chop.edu)
`
`associated with IBD. The aim of this study was to ret(cid:173)
`rospectively review the efficacy and safety of intrave(cid:173)
`nous iron dextran and report our experience.
`
`METHODS
`
`The Institutional Review Board of the Children's Hospital of
`Philadelphia approved this study. A complete list of all patients
`who received total dose intravenous (TOI) iron deittran infu(cid:173)
`sion between February 1994 and February 2000 was obtained
`from the Department of Pharmacy. The list of patients was
`cross-matched with the Children's Hospital of Philadelphia In·
`flammatory Bowel Disease Database, and 70 patients with ei(cid:173)
`ther ulcerative colitis or Crohn disease were identified. Medical
`records, including inpatient and outpatient charts, wer~ re(cid:173)
`viewed. Clinical, radiologic, and histologic data confirmed the
`diagnosis of IBO (6). Documentation of dur.ition, efficacy, and
`side effects of oral iron therapy was not available.
`The diagnosis of iron deficiency anemia was based on ab·
`normally low concentrations of hemoglobin and mean corpus(cid:173)
`cular volume, when corrected for patient's age and seit In
`addition, concentrations of iron, transferrin, and ferritin; trans(cid:173)
`fernn saturation; total iron-binding capacity; and red blood cell
`distribution width were measured in some patients to conlinn
`the diagnosis of iron deficiency anemia.
`
`286
`
`IND 107331
`
`l of5
`
`Pharmacosmos, Exh. 1059, p. 1
`
`

`
`Mono fer®
`5.4 Literature References: mamula-2002
`
`Pharmacosmos A/S
`
`INTRAVENOUS IRON THERAPY FOR ANEMIA IN PEDIATRIC IBD
`
`287
`
`Intravenous iron dextran was administered on an outpatient
`basis in a day medicine unit unless the patient was already
`hospitalized. The dose of iron dextran was determined using the
`following previously published formula (4):
`
`Dose (mg)= 0.66 x Wt (kg) x 100-
`{
`
`(Hgb0 b x 100)}
`Hgbd
`
`where Wl is body weight, Hgb0 b is hemoglobin observed, and
`Hgbd is hemoglobin desired.
`An advanced practice nurse or a physician administered an
`intravenous lest dose of 25 mg iron dextran over 5 to I 0 min(cid:173)
`utes, and the patient was observed for signs of allergic reaction.
`A precalculated dose of epinephrine and diphenhydramine hy(cid:173)
`drochloride was available. If no reaction occurred, the total
`dose of iron dextran was diluted in 200 mL of normal saline
`(t,. 9% NaCl) and administered over 2 hours. Vital signs and
`oral temperature were monitored hourly during the infusion.
`Typical administered iron dose ranged between 500 mg and
`2000 m .
`uring the 6-year study period, two different preparations of
`iron dextran were used, INFeD (Schein Pharmaceutical Inc ..
`Florham Park, NJ, U.S.A.) and Dexferrum (American Regent
`Laboratories, Inc., Shirley, NY, U.S.A.).
`Patients were excluded from the efficacy analysis if
`I) transfusion of blood products or use of erythropoietin oc(cid:173)
`curred within 2 months of the iron dextran infusion,
`;; no follow-up laboratory evaluation was obtained within 2
`months after the iron dexlran infusion, 3) follow-up laboratory
`evaluation was obtained within 2 weeks after the iron dextran
`infusion, 4) patients received multiple infusions, or 5) patients
`did not fulfil the criteria for iron deficiency anemia. The evalu(cid:173)
`ation of intravenous iron dextran efficacy was performed based
`on comparison of preinfusion and postinfusion hemoglobin,
`iron, transferrin, and ferritin concentrations and total iron bind(cid:173)
`ing capacity values, using the Student r test and the Mann(cid:173)
`Whitney test where appropriate. The reference range for hemo(cid:173)
`globin concentration for 6- to 12-year-olds was 11.5 to 15.5
`~ IL; for 12- to 18-year-olds it was 13 to 16 g/dL in boys and
`12 10 16 g/dL in girls. The reference range for mean corpus(cid:173)
`cular volume in 6- to 12-year-olds was 77 to 95 fL in 12- to
`18-year-olds, 78 to 98 fL in boys and 78 to I 02 fL in girls. The
`primary outcome of the study was improved postinfusion he(cid:173)
`moglobin concentration of more than 2 g/dL. Statistical analy(cid:173)
`sis was performed using the statistical package Stata 6.0 (Stata
`Corporation, College Station, TX, U.S.A.).
`
`RESULTS
`
`Seventy patients received a total of 119 TDI iron dex(cid:173)
`tran infusions. Forty-eight patients (69%) received one
`infusion, 13 patients (20%) received 2 infusions, 4 pa(cid:173)
`tients (6%) received 3 infusions, 2 patients (2%) received
`4 infusions, I patient (1 %) received 5 infusions, and
`2 patients (2%) received more than IO infusions.
`Thirty-four patients qualified for the efficacy analysis.
`Table 1 shows age, sex, diagnosis, place of administra(cid:173)
`tion and preinfusion hemoglobin concentration, mean
`corpuscular volume, and iron concentrations.
`The average increase in hemoglobin concentration
`was 2 .9 g/dL (P < 0.0001). The data on preinfusion and
`postinfusion iron concentrations were available in 17 pa(cid:173)
`tients. The difference in preinfusion and postinfusion
`concentrations of transferrin and ferritin, and total iron
`binding capacity were not statistically significant. Table
`2 shows statistical analysis.
`Table 3 describes the side effects of TDI iron dextranl
`and the subsequent required therapy. Eleven allergic re(cid:173)
`actions were recorded (I during the total dose infusion
`and IO during the test dose administration). One patient
`(patient no. 7) had allergic reactions on two separate
`occasions.
`
`DISCUSSION
`
`Patients with lBD are frequently diagnosed with iron
`deficiency anemia (7-9). Between 26% and 37% of adult
`patients with IBD are affected; more patients with ulcer(cid:173)
`ative colitis are affected than are patients with Crohn
`disease. Studies in the pediatric age group are uncommon
`and exact statistics are not available (4,5). The causes of
`iron deficiency anemia are multiple: chronic gastrointes(cid:173)
`tinal blood Joss caused by inflammation, decreased ab(cid:173)
`sorption of iron in patients with small bowel Crohn dis(cid:173)
`ease, and decreased dietary intake (2).
`We will briefly review some of the published efficacy
`data and the side effect profile.
`The gold standard for diagnosing iron deficiency ane(cid:173)
`mia is an iron stain of the bone marrow aspirate (10).
`
`TABLE 1. Patient clwrncreristics
`
`Diagnosis
`
`UC
`
`CD
`
`Patients, n
`Female
`Male
`Age. median in years (range)
`lnpallenl
`Ou1patien1
`Hemoglobin preinl'usion (reference range . 11.5-16 g/dL)
`MCV preinfusion (ref<rence range: 77-102 IL)
`Iron preinfusion (reference range: 25- 140 µ.g/dL)
`
`9
`4
`5
`t 2 l (7.4-15 .8)
`4
`5
`8 4 (SD = l.18)
`68.7 (SD = 7.9)
`10.0 (SD = 2 16)
`
`25
`13
`12
`14. I (6.3-20.8)
`8
`17
`8.96 (SD = l.29)
`70.0 (SD = 9.0)
`12.8 (SD = 9.8)
`
`CD. Cwhn tlisease: UC, ulccraiive coli1is: MCV, mean corpuscular \'Olume.
`
`IND 107331
`
`J p~,/11111· Gm11 ot-ntr:rul Niur. Vu/ 34, No J, Mmd1 2002
`
`2 of5
`
`Pharmacosmos, Exh. 1059, p. 2
`
`

`
`Mono fer®
`5.4 Literature References: mamula-2002
`
`288
`
`P. MMv!ULA ET AL
`
`Pharmacosmos A/S
`
`TABLE 2. Comparative statistical analysis
`
`Preinfus1on
`
`Pos1infus1on
`
`Hemoglobin (gldL, n = 34)
`MCV (IL, n = 34)
`Iron (µg/dL. n = 17)
`
`8.8
`69.7
`11.7
`
`11.7
`79
`40.8
`
`MCV. mean corpuscubr volume; n, number of patients.
`
`P Villue
`
`<0.0001
`<0 0001
`00005
`
`Because bone marrow aspiration is too invasive to be
`used on a regular basis, the accepted and reliable method
`of diagnosis is based on complete blood count and iron
`studies (10). These include serum concentrations of he(cid:173)
`moglobin, mean corpuscular volume, red blood cell dis(cid:173)
`tribution width, ferritin concentration, transferrin satura(cid:173)
`tion nnd serum iron concentration below the laboratory
`reference value for the appropriate age group, increased
`total iron-binding capacity, and an excess of 10% of
`hypochromic cells on peripheral blood smear. Ferritin,
`an acute phase reactant, is often increased in inflamma(cid:173)
`tory diseases such as IBO, making it a less reliable
`marker.
`Iron deficiency anemia is treated with oral, intramus(cid:173)
`cular, or parenteral iron. Parenteral iron first became
`available in 1952 (11 ), and the TDI form was first used
`in 1963. Physicians are often reluctant to use the intra(cid:173)
`venous form of iron, fearing side effects.
`Oral treatment is an efficacious first-line therapy, al(cid:173)
`though it is associated with intolerance in about 20% of
`the patients (3). The intolerance, manifested by nausea,
`constipation, diarrhea, and abdominal discomfort, fre(cid:173)
`quently leads to poor compliance. Oral iron is not as well
`incorporated into red blood cells and takes longer to form
`hemoglobin than does the intravenous form (12) .
`Intramuscular use is associated with discomfort, pain,
`staining of the skin, bleeding, development of sterile ab(cid:173)
`scesses, tissue necrosis, tissue atrophy with ulceration,
`and development of sarcoma at the injection site (13).
`Intravenous iron can be given in multiple doses (fre-
`
`quently used in patients on chronic hemodialysis}, total
`dose infusion, or with total parenteral nutrition. Severa)
`preparations are available for intravenous use in different
`countries, and degradation kinetics, bioavailability, and
`side effect profiles depend on the size of iron complex. In
`the United States, only iron dextran is approved for in(cid:173)
`tramuscular or multiple-dose intravenous application of
`undiluted solution (14).
`Efficacy of intravenous iron therapy is well estab(cid:173)
`lished, and the standard measure of success is increase in
`the hemoglobin concentration. In our study, the average
`increase in concentration of hemoglobin was 2.9 rng/dL,
`which is comparable to the results published in 1982
`(4). Six children with IBD received TDI of iron dextran
`with an average increase in hemoglobin concentration
`of 3.5 g/dL. The same author published. experience with
`14 children receiving parenteral nutrition who received
`TDI of iron dextran with an increase in hemoglobin con(cid:173)
`centration of 2.9 g/dL at 4.8 weeks after the infusion
`(15). Approximately 25% of patients in our study have
`received intravenous iron dextran while hospitalized for
`exacerbation of IBD. Therefore, the concurrent treatment
`could have affected the hemoglobin response. However,
`the response rate to infusion was highly statistically sig(cid:173)
`nificant when calculated separately for outpatient and
`inpatient infusions. The retrospective nature of the study
`made an accurate assessment of the concurrent therapy
`impossible. The possibility of relative erythropoietin de(cid:173)
`ficiency should be considered in patients who do not
`respond to therapy. Erythropoietin therapy is effective in
`selected groups of adult and pediatric patients with IBD
`(9,16,17).
`Hypersensitivity reactions to intravenous iron admin(cid:173)
`istration may be immediate or delayed. Immediate reac(cid:173)
`tions are either of the anaphylactoid type, manifested by
`malaise, itching, urticaria, sweating, myalgia, arthralgia,
`and febrile episodes, or of the anaphylactic type with
`hypotension and circulatory collapse. Delayed reactions
`occur within 24 to 48 hours and may be caused by
`
`TABLE 3. Intravenous iron-dutran side effects and therapy
`
`Side effect
`
`Treatment
`
`Patient
`
`Shortness
`of breath
`
`Muscle
`spasm
`
`Chills
`
`Rash
`
`Hypotension
`
`Carpal
`spasm
`
`Dyphenhyctramine
`
`Epinephrine
`
`IV
`fluids
`
`4
`5
`6
`7
`7
`9
`10
`II
`
`IV. intra\ enous .
`
`J Pt:fio1r GnJfl'c>r:nurol Nuif, \'ul. J.J. No 3. March ?00:!
`
`IND 107331
`
`3 of5
`
`Pharmacosmos, Exh. 1059, p. 3
`
`

`
`Monofer®
`5.4 Literature References: mamula-2002
`
`Pharmacosmos A/S
`
`INTRA VENOUS IRON THERAPY FOR ANEMIA IN PEDIATRIC IBD
`
`289
`
`weeks after infusion, together with liver function tests
`and iron profile studies, to assess the efficacy and ob(cid:173)
`serve for potential toxicity of iron therapy. In the outpa(cid:173)
`tient setting, patients should be contacted within 72 hours
`to document delayed reactions. The activity of the IBD,
`concomitant medications, the rate of infections within
`several weeks after infusion, and the quality of life as(cid:173)
`sessment should be obtained.
`
`In conclusion, this retrospective study suggests that I
`
`I
`
`histamine release (3) . These reactions are manifested
`by lymphadenopathy, myalgia, arthralgia, backache,
`headache, fever, nausea, vomiting, dizziness, and dia(cid:173)
`phoresis and usually resolve within 72 hours after the
`;ron infusion (13). In our study, we observed 11 (9% of
`... tal number of infusions) hypersensitivity reactions.
`Transient hypotension developed in three children, and
`they received treatment with epinephrine. None of the
`reactions was considered life threatening, and none of the
`children required hospitalization. Information about de(cid:173)
`TDI infusion of iron dextran, when appropriately used, is
`layed hypersensitivity reactions was not available. Sev(cid:173)
`a safe and potentially efficacious treatment for children
`eral large studies have addressed the frequency of side
`with IBO and iron deficiency anemia.
`effects. In 481 adults with a total of 2,099 intravenous
`infusions, 26% had reactions, of which 5% limited _grd~ I
`nary activity and 0.6% were life threatening (7}. In a
`.. rudy of 2,400 patients, 1 % to 2% had signitrcaii'i side
`effects (18); and 0.6% to 1.6% of 623 pregnant women in
`another study h~e reactions (19). A review article
`of intravenous use of iron reported a 0.1 % to 0.6% inci(cid:173)
`dence of life-threatening anaphylaxis (20). In 1988,
`Auerbach et al. (21) reported a 40% incidence of delayed
`reactions that resolved in 72 hours. The same author
`recommended using methylprednisolone therapy before
`and after the total intravenous iron infusion, based on a
`decreased rate of side effects in a randomized, controlled
`,1dy of 78 patients (14). We have successfully used
`intravenous iron dextran in four patients who have had
`previous allergic reactions to the test dose of intravenous
`iron. These patients were premedicated with acetamino-
`phen, diphenhydramine, and methylprednisolone, in ac(cid:173)
`cordance with a case report of desensitization protocol
`with corticosteroids, diphenhydramine, and ephedrine
`(22).
`In 156 patients undergoing home dialysis who were
`riven TDI iron, only 3.5% had side effects with the
`; iFeO preparation, whereas 28.6% had reactions (itch(cid:173)
`ing, urticaria, leg and back pain, shortness of breath,
`nausea, vomiting) with Oexferrum (23). We made a
`similar anecdotal observation during the period when
`both preparations were used at our institution. Currently,
`we use only INFeD.
`The risk of infection with intravenous iron therapy
`could be of interest in IBO, especially because many
`patients are already receiving immunosuppressive
`tl1erapy. However, a study of 17 patients showed the
`~ .i ne rate of infections before and after iron infusion (24).
`Interestingly, the observation of decreased interleukin-2
`and interferon--y production has been made in iron over(cid:173)
`load states (24). A low concentration of nontransferrin(cid:173)
`bound iron can inhibit the cloning capacity of CD+ T
`cells and enhance suppressor T cells, theoretically exert(cid:173)
`ing an antiinfiammatory property (24).
`To better evaluate the response to treatment and stan(cid:173)
`dardize the care for patients with IBO who have iron
`c! 'ficiency anemia, a uniform protocol for administering
`i .1ravenous iron should be studied prospectively. Hemo(cid:173)
`globin concentration should be obtained within 4 to 8
`
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`
`I. Gaschc C, Dcjaco C, Watdhoer T. cl at. Intravenous iron and
`crythropoictin for anemia associated with Crohn disease. Ann /11-
`tenr Med 1997;126:782-7.
`2. Sandborn W. Erytliropoicr.in for inflammatory bowel disease. Gas-
`1roe11tero/ogy 1997;112:660-1.
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`nous iron-dcxlran. J Parmrer Enter Nurr !982;6:9-11.
`5. Peck SN, Piccoli DA, Baldassano RN. The safety and efficacy of
`iron dcxtrnn infusions in children with inflammatory bowel disease
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`Nurr 1998;27:487A.
`6. Ogorek CP, Fisher RS. Differentiation between Crohn's disease
`and ulcerative colitis. Med C/i11 North Am 1994;78: 1249-58.
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`13. Kumpf V. Parenteral iron supptemen1:11ion. Nurr C/i11 Pract t 996;
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`t4. Auerbach M, Chaudhry M , Goldman H, el nl. Value of mcthyl(cid:173)
`prcdnisolonc in prcvcniion of the arthrolgia-myalgia syndrome as(cid:173)
`sociated with the tolnl dose infusion of iron dex1ran: a double blind
`randomized trial. J Lab C/in Mtd 1998;131:257-60.
`15. Recd MD, Bertino JS. Halpin TC. Use of intravenous iron dexlran
`injection in children receiving totnt parcnlcrat nutrition. Am J Dis
`Child t 981; 135:829-3 I.
`16. Dohil R, Hassnt E, Wadsworth LD, e1 nt. Recombinnn1 human
`crythropoietin for 1rea1men1 of anemia of chronic disease in chil(cid:173)
`dren with Crohn's disease. J Pediarr 1998:132: 155-9.
`17 Schreiber S, Howaldr S, Schnoor M, Cl nt. Recombinant erythro(cid:173)
`pok1in for the 1rcmmen1 of anomia in inflammatory bowel di~ase .
`N £11gl J Med 1996;334·619-23.
`
`IND 107331
`
`J Pt·tlmt1 Gt.hlnit•mi:ml N1111 . Vol 34. No ), M11rr/1 1002
`
`4 of5
`
`Pharmacosmos, Exh. 1059, p. 4
`
`

`
`Mono fer®
`5.4 Literature References: mamula-2002
`
`Pharmacosmos NS
`
`290
`
`P. MAMULA ET AL
`
`18. WalleNein RO Intravenous iron-dexiran complex. Bloocl 1968;
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`19. Knisi M, Ngwalle EWK, Runyoro DE, el nl. Evaluation of toler(cid:173)
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`mia. Im J Gy11aecol Obstet I 988;26:235-43.
`20. Kumpf VJ, Holland EG. Parenteral iron dextran therapy. Drug
`l111el/1gence and C/i11ical Pharmacy: Tire Annals of Ph11r111aco-
`1/ierapy 1990;24: 162-2.
`21. Auerbach M, Win D. Toler W, el al. Clinical use of the total dose
`
`imravenous infusion of iron dexlran. J Lab Cli11 Med 1988; 111
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`22. Hurvitz H, Kerem E, Gross-Kiesclstcin E, Cl al. Pancytopcnia
`caused by iron-dexlran. Arch Dis Chile/ 1986;61:194-6.
`23. Case G. Maintaining iron balance with 101al-dose infusion of in(cid:173)
`travenous iron dextran. ANNA J 1998:25:65-7.
`24. Vychylil A, Haag-Weber M. Iron status nnd iron supplemcn1a1ion
`in peritoneal dialysis pa1ien1s. Kid11ey !111 1999;55(suppl 69).
`571-8.
`
`Clinical Quiz
`Joseph F. Fitzgerald, NASPGHAN Clinical Quiz Editor; Riccardo Troncone, ESPGHAN Clinical Quiz Editor
`*Judith M. Sondheimer and tSteven Rothenberg, Contributors
`Dil'1<ions of *Gastroe11tuology am/ tSurger)', The Children's Hospital, University of Colorado, Dem·er, Colorado, U.S.A.
`This 8-year-old boy was seen by his primary physiciM for evalu:1tion of nbdominal pain. The child was prt:\'iously he.-.hhy wi1h no chronic medical conditions.
`The pn1n was localized to the midepi:nstrium :md occurred daily. The p:nicnt described the p:iin as shilf'P and sudden. of1cn causing him to slop activities Dnd double
`over. Epi•odcs usually losted lor I 0 to JO minu1cs ond did not prevent the child from oncnding school. He hod c•pericnced no fever, dysphogin. cmcsis, chongc
`in bowel h:ibic. or weight loss. The pntienl reported no el{lrJ:ibdominal symploll\$. The child's physical e.11.:imin01tion w:is completely normal. The screening blood
`counl was normul, and the p:iticnt's stool 1cs1ed negative for occuh blood.
`The child's medic:il histciry was unrem01rkablc. The p:itienl's p:uern:il grandmother has chronic, obs1ructing peptic s1ric1urcs of the esophagus and chronic lung
`disease secondary 10 nspiration.
`The p11ttenl underwent an upper g:is1rointcstinnl series that showed a nonmobilc intralumin:>.I csoph:igeal mass ot lhe di:stal end of the esoph:igus (Fig I A and
`8). Th¢ p:i1icn1 underwent upper g:1~troin1e.s1in.:1l endoscopy, which showed normal mucon in lhe esophagus. s1omnch, nnd duodenum. An ovii:I mnss, obour 4 cm
`lung. caused an indentation or the lower esophageal lumen The endoscope wo.s easily p~ssed beyond 1hc cxtrin.o;ic: m:w.
`Compu1cd 1omogrophy of lhe chest wos performed (Fig 2)
`Question: The most likely diagnosis is'!
`A Lymphomo
`B Bronchogenic cySI
`
`E. Enlnrged benign lymph node
`
`C. Neuroblos1omn
`
`D. Esophoge•I duplicalion
`
`FIG. 1. A and B: Upper gaslrointeslinal series, anlerior/poslerior and lateral projecllons, showing Iha "inlraluminal mass• in lhe middle third or lhe
`esophagus (while arrows).
`
`ANSWER: see page 30 I
`
`FIG. 2. Compuled lomography al !he chesl. The white arrow indicates !he esophageal lumen
`
`J Pedw11 Gns1we11IC'1.,1I Null. Vul 3.J. ;'Vn -'· M11rrl1 2001
`
`IND 107331
`
`5 of5
`
`Pharmacosmos, Exh. 1059, p. 5