Oshikataetal.BMCResearchNotes2013,6:26 http://www.biomedcentral.com/1756-0500/6/26 CASE REPORT Open Access An adult patient with Henoch-Schönlein purpura and non-occlusive mesenteric ischemia Chiyako Oshikata1, Naomi Tsurikisawa1*, Masakazu Takigawa2, Tomoko Omori2, Satoshi Sugano3, Takahiro Tsuburai1, Hiroyuki Mitomi4, Tamiko Takemura5 and Kazuo Akiyama1 Abstract Background: Onsetof Henoch-Schönleinpurpura (HSP) in middle age is uncommon, and adults withrenalor gastrointestinal involvementpresent withmore severe disease than do similar pediatric patients. Case presentation: We present thecase ofa 69-year-oldmale withHSP who, after treatment with steroids, cyclophosphamide, and continuous intravenous prostaglandinE1 (PGE1), died as a result ofsevere gastrointestinal involvement withnon-occlusive mesenteric ischemia (NOMI). Vascular narrowing associated with the NOMI improved after catheter injection ofPGE1 and prednisolone,but the patient died of bleeding from anexposed small vessel. Atautopsy therewas noactive vasculitisinthejejunal submucosa. Conclusion: Treatment with PGE1 and prednisolone might improvesmall-vessel vasculitis associated withNOMI. Keywords: Henoch-Schönleinpurpura, Intervention, Non-occlusive mesenteric ischemia, Small vessel vasculitis Background Risk factors for NOMI include hypovolemia, hypotension, Henoch-Schönlein purpura (HSP) is characterized by a low cardiac output status, renal or hepatic disease, cardiac leukocytoclastic vasculitis involving the small vessels, surgery, and administration of α-adrenergic agonists, with deposition of immune complexes that contain IgA digoxin, or β-receptor blocking agents [9]. There are [1,2]. Clinical signs include purpura, arthralgia, glome- no published reports of NOMI associated with HSP. rulonephritis, and gastrointestinal involvement [3]. HSP We present a fatal case of HSP in an adult patient who occurs primarily in children [4]. It is uncommon in had severe gastrointestinal involvement with NOMI. After people over the age of 40, and little is known about its treatment with steroids, cyclophosphamide, intravenous natural history in this population [5]. The prognosis for steroids, prostaglandin E1 (PGE1), and continuous intra- patients with childhood-onset HSP is good. However, the venous papaverine hydrochloride, the ischemic change clinical presentation of HSP in adults is severe and the caused by small-vessel vasculitis of the small intestine clinical outcome relatively poor [6]. In particular, deaths improved. Unfortunately, the patient had a poor prognosis have been reported in cases of adult HSP with severe owing to bleeding from an exposed small vessel, although gastrointestinalinvolvement[7,8]. at autopsy he had no apparent active vasculitis in the Non-occlusivemesentericischemia(NOMI)isdefinedas jejunal submucosa. acute mesenteric ischemia through hypoperfusion caused by ongoing splanchnic vasoconstriction, without demon- Case presentation strable occlusion of the mesenteric vasculature [9]. NOMI A 69-year-old Japanese male presented with a history of is a life-threatening vascular emergency that requires early bronchial asthma from age 61 and hypertension from age diagnosisandinterventiontoadequatelyrestoremesenteric 50. He had been treated with inhaled glucocorticosteroids, blood flow and prevent bowel necrosis and patient death. long-acting inhaled β2-agonists, leukotriene modifiers, methylxanthines, and antihypertensives. He was an ex- *Correspondence:[email protected] smoker with a Brinkman Index of 1200. He had noticed 1DepartmentofAllergyandRespirology,NationalHospitalOrganization purpura appearing in both lower extremities without any SagamiharaNationalHospital,18-1Sakuradai,Minami-ku,Sagamihara, precedinginfection,includingupperrespiratorytractinfec- Kanagawa252-0392,Japan Fulllistofauthorinformationisavailableattheendofthearticle tion. He then developed, without fever, edema in both ©2013Oshikataetal.;licenseeBioMedCentralLtd.ThisisanOpenAccessarticledistributedunderthetermsoftheCreative CommonsAttributionLicense(http://creativecommons.org/licenses/by/2.0),whichpermitsunrestricteduse,distribution,and reproductioninanymedium,providedtheoriginalworkisproperlycited. Oshikataetal.BMCResearchNotes2013,6:26 Page2of6 http://www.biomedcentral.com/1756-0500/6/26 lowerextremitiesandarthralgiaintherightfoot.Fourdays onday4revealedirregularulcerationsinthestomachand after the patient had first noticed symptoms, the purpura the duodenum and erythema in the sigmoid colon. The gradually improved. However, he began suffering from ascendingcolonandcecumwerenotobservable,owingto abdominalpain,diarrhea,edemaoftheupperextremities, the presence of a stricture caused by severe edema of the andoliguria. mucosa. However,there werepatchyareasoferythemain On admission, the patient had a body temperature of the sigmoid colon (Figure 3A) and rectum (Figure 3B). 36.9°C, a pulse of 109/min with sinus rhythm, and blood Cutaneous leukocytoclastic vasculitis was confirmed by pressure of 133/78 mm Hg.Physical examination revealed skin biopsy. The patient was diagnosed with HSP on the pretibialpittingedemaanddiffusesmallpalpablepurpuras basis of American College of Rheumatology criteria [10]. onbothlowerextremities(Figure1A,B)andonthelower Computedtomographyoftheabdomenperformedonday abdomen. The patient’s heart and lung sounds were 9 showed severe edematous and dilatational changes in normal. His abdomen was slightly distended, but neither the small intestine and ascites before treatment with muscular guarding nor tenderness was detected. On steroids and cyclophosphamide (Figure 2B). auscultation, the bowel was hypoactive. There was no AfterintravenoustreatmentwithFactorXIIIconcentrate hepatosplenomegaly or existing masses. A neurological (20 mL/day for 3 consecutive days) and prednisolone examination revealed no abnormalities. An electrocardio- sodium succinate (40 mg/day for 13 consecutive days; see gramandX-raysofthechestandabdomenwereessentially Figure4fordosageschedulesofalldrugs), theskinlesions normal. Computed tomography of the patient’s abdomen and abdominal pain disappeared completely. However, demonstrated diffuse thickening of the bowel wall, with gastrointestinalhemorrhageandmildproteinuriaremained target signs in the small intestine and ascites (Figure 2A). (Figure4) anddidnotimproveupon treatment withintra- The white blood cell count was 14,260/μL, hemoglobin venousmethylprednisolone(pulsedoseof1000mg/dayfor was 16.4 g/dL, and C-reactive protein was 22.36 mg/dL. 3 consecutive days) and intravenous cyclophosphamide There was microscopic hematuria and proteinuria. A skin (800mgon1day).Twenty-ninedaysaftertreatmentbegan, biopsytakenfromtherightlegshowedpurpura. the ascites remained, and there were severe edematous Onthesecondhospitalday,abdominalpainandmelena changes in the small intestine (Figure 2C). Colonoscopy in our patient appeared after the purpura improved and confirmedfrankbleedingfromtheascendingsigmoidcolon before treatment with steroids or immunosuppressants. (Figure3C,Dc,d).Neitherbleedingpointsnorvascularoc- Upper and lowergastrointestinal endoscopicinvestigation clusion was detected by mesenteric angiography. However, Figure1Purpura.(A)Diffusesmallpalpablepurpuraonthelowerextremities.(B)Magnifiedview. Oshikataetal.BMCResearchNotes2013,6:26 Page3of6 http://www.biomedcentral.com/1756-0500/6/26 Figure2Computedtomographyoftheabdomen.(A)Computedtomographyoftheabdomenperformedonadmission,showingdiffuse thickeningofthebowelwallwithtargetsignsinthesmallintestineandascites(arrow).(B)Computedtomographyoftheabdomenperformed onday9,showingsevereedematousanddilatationalchangesinthesmallintestineandascites(arrow)beforetreatmentwithsteroidsand cyclophosphamide.(C)Computedtomographyoftheabdomenperformedonday29beforetreatment,showingascites(arrows)thatremained aftertreatmentwithsteroidsandcyclophosphamide.However,thesevereedematouschangesinthesmallintestinewereslightlyimproved relativetoday9. angiography revealed narrowing and irregularities in the papaverinehydrochloride(100mg/h)didnotimprovethe major branches of the superior mesenteric artery and patient’sgastrointestinalhemorrhaging,andrenalfunction absence of blood flow, indicative of NOMI (Figure 5Aa). deteriorated.Hediedonthe33rdhospitalday. On day 30, blood flow in the superior mesenteric artery Examination at autopsy showed widely distributed increased and vascular narrowing improved after catheter jejunoileal ulcers of irregular form. Histopathologic injection of 10 μg of PGE1 and 20 mg of predniso- examinationofthesubmucosaofthejejunumrevealedan lone sodium succinate into the artery (Figure 5B). exposedsmallvessel(Figure6A),aswellasobliterationof After the intervention, proteinuria decreased. How- small vessels and ruptured elastic laminae in the tunica ever, subsequent continuous intra-arterial infusion of externa of those vessels (Figure 6B). There was also an Figure3Colonoscopyfindings.Colonoscopyimagesshowingpatchyerythemainthesigmoidcolon(A)andrectum(B)onday4,before treatmentbegan.(C,D)Colonoscopyimagesshowingfreshbleedingintheascendingsigmoidcolononday29,aftertreatmentwithsteroids andcyclophosphamide. Oshikataetal.BMCResearchNotes2013,6:26 Page4of6 http://www.biomedcentral.com/1756-0500/6/26 Figure4Treatmentandclinicalcourse.Toppanel,dosesandschedulesofdrugtherapies.Middlepanels,clinicalfindings.Abdominalpainand melenaappearedafterimprovementofpurpuraandbeforetreatmentwithsteroidandimmunosuppressants.Thepatient’smelenaand proteinuriadidnotimproveaftertreatmentwithsteroids,cyclophosphamide,infusionofRCC-LR(redcellconcentrates–leukocytesreduced), andintravenousPGE1(prostaglandinE1).Bottompanels,laboratoryfindings.Cre,creatinine;CRP,C-reactiveprotein;Hb,hemoglobin. abundance of fibroblasts under the submucosa of the findings suggest that severe vasospasm due to small-vessel jejunumbutnoregenerationoftheepithelium.Therewas vasculitis before treatment with PGE1 plus steroid had noevidenceofactivevasculitisorthrombosisinthetunica causedwideischemicchangesanddelayedregenerationof media of the superior mesenteric artery (Figure 6C), theepitheliuminthesubmucosaofthesmallintestine.We althoughtherewereedematouschanges(Figure6D).These considered that the primary cause of death was bleeding Figure5Supramesentericarteryangiography.(A)Mesentericangiogramshowingabsenceofbleedingpointsandvascularocclusion,but presenceofnarrowingandirregularityofmajorbranchesofthesuperiormesentericartery.(B)Mesentericangiogramtakenonday30,showing bloodflowandreducedvascularnarrowingaftercatheterinjectionof10μgofPGE1and20mgofprednisolonesodiumsuccinateintothe superiormesentericartery. Oshikataetal.BMCResearchNotes2013,6:26 Page5of6 http://www.biomedcentral.com/1756-0500/6/26 Figure6Autopsyfindings.Biopsysampleswerefixedandstainedwithhematoxylinandeosin.Histopathologyofthejejunalsubmucosashows (A)anexposedsmallvessel(arrow)(x40)and(B)exposedvesselandrupturedelasticlaminaeinthetunicaexternaofthatvessel(x100). Histopathologyofthetunicamediaofthesuperiormesentericarteryshows(C)noactivevasculitisorthrombosisatautopsy(x40),but(D) edematouschange(x200). from an exposed small vessel, without apparent active patientdidnotreceivedrugssuchasα-adrenergicagonists, vasculitis in the jejunal submucosa. Other findings digoxin, or β-receptor blocking agents, which are known were typical of HSP and included mesangial proliferative to precipitate this condition [9]. NOMI has a high morta- glomerulonephritiswithcrescentformation. lity rate, and early diagnosis and treatment are important for improving survival [15]. Early treatment of NOMI Discussion patients with continuous intravenous PGE1 increases AlthoughHSPistypicallyadiseaseofchildren,adultcases survival rates [15,16]. Abdominal pain and melena in our can occur and present as more severe disease. Serious patient appeared after the purpura improved and before complications related to gastrointestinal involvement in- treatment with steroids or immunosuppressants. The cludeintussusception,infarction,andperforation[7,11,12]. patient’s melena and renal dysfunction did not improve HSP patients who are older than 60 years at onset and aftertreatmentwithsteroids,cyclophosphamide,andintra- whohaverenalorgastrointestinalinvolvementhaveapoor venous PGE1 and steroids. At autopsy, an exposed small prognosis [5-8,13]. Some patients with gastrointestinal in- vessel was identified, but there was no evidence of active volvement die despite treatment with steroids and immu- vasculitis in the submucosa of the jejunum. We suspect nosuppressants [8,13]. Among adult patients with HSP, that the treatment for NOMI improved vasodilatation in 24.1% have initial onset with gastrointestinal involvement the submucosa of the small intestine, thus improving the before the cutaneous rash [11], and those manifestations distribution of the locally injected steroid or the ongoing may be helpful for early diagnosis and for selecting systemic steroid and immunosupressant tothe submucosa appropriate management strategies [12]. of the jejunum. We considered that exposure of the small FewreportsofNOMIassociatedwithsmall-vesselvascu- vessel,possiblyasaresultoftheremodelingprocessinthe litis have been published. There has been one case report submucosa,wasthecauseofdeath. of vasculitic lesions that resulted in dialysis-related hypotensionandNOMI,butthiswasassociatedwithgiant Conclusion cell arteritis [14]. NOMI in our patient might have been Treatment of NOMI results in vasodilatation, thus caused by active vasculitis, but it appeared not to have resulting in more effective treatment of the active been caused by hypotension or hypovolemia, and the small-vessel vasculitis associated with HSP. Oshikataetal.BMCResearchNotes2013,6:26 Page6of6 http://www.biomedcentral.com/1756-0500/6/26 Consent 9. OldenburgWA,LauLL,RodenbergTJ,EdmondsHJ,BurgerCD:Acute Writteninformedconsentwasobtainedfromthekinofthe mesentericischemia.Aclinicalreview.ArchInternMed2004, 64:1054–1062. patientforpublicationofthisCaseReportandanyaccom- 10. MillsJA,MichelBA,BlochDA,CalabreseLH,HunderGG,ArendWP, panying images. A copy of the written consent is available EdworthySM,FauciAS,LeavittRY,LieJT,LightfootRW,MasiAT,McShane forreviewbytheEditor-in-Chiefofthisjournal. DJ,StevensMB,WallaceSL,ZvaiflerNJ:TheAmericancollegeof rheumatology1990criteriafortheclassificationofhenoch-schönlein purpura.ArthritisRheum1990,33:1114–1121. Abbreviations 11. ZhangY,HuangX:Gastrointestinalinvolvementinhenoch-schönlein Cre:Creatinine;CRP:C-reactiveprotein;Hb:Hemoglobin;HSP:Henoch- purpura.ScandJGastroenterol2008,43:1038–1043. Schönleinpurpura;NOMI:Non-occlusivemesentericischemia; 12. HuangWK,FanPC,ChenYC,TianYC,KangSC,HsuehS,WuHH,ChangCH, PGE1:ProstaglandinE1;RCC-LR:Redcellconcentrates–leukocytesreduced. FangJT:Henoch-Schönleinpurpurawithintussusceptioninanadult.Am JMedSci2012,344:337–339. Competinginterests 13. TakamatsuK,IkedaY,NakauchiY,KawadaM,HashimotoK,FurihataM: Wedeclarenonon-financialcompetinginterests. Henoch-Schönleinpurpurawithrapidlyprogressiveglomerulonephritis Noneoftheauthorsreceivedgrantsforthisstudy. andfatalintraperitonealhemorrhageinanadult.JpnJNephrol1994, 36:63–68. Authors’contributions 14. KimuraT,KomuraM,OkuboY:Atypicalgiantcellarteritispredominantly COexaminedthepatientandcontributedtomanuscriptpreparation.NT involvingintramuralcoronaryarteries:acaseshowingrefractorydialysis- examinedthepatient,tookpartindiscussionsaboutthepatient,andwas relatedhypotension.HearVessel2012,27:216–220. involvedinmanuscriptpreparationandediting.MTandTOimplemented 15. MitsuyoshiA,ObamaK,ShinkuraN,ItoT,ZaimaM:Survivalin treatmentsandperformeddiagnosticimaging.SSperformedendoscopyof nonocclusivemesentericischemia.Earlydiagnosisbymultidetectorrow thecolon.TTsuburaiwasinvolvedindiscussionsregardingthepatient.HM computedtomographyandearlytreatmentwithcontinuous performedtheautopsyanddiagnosticpathology.TTakemuracontributedto intravenoushigh-doseprostaglandinE1.AnnSurg2007,246:229–235. discussionsandpathologicaldiagnosis.KAcontributedtodiscussions 16. KamimuraK,OosakiA,SugaharaS,MoriS:Survivalofthreenonocclusive regardingthepatient.Allauthorsreadandapprovedthefinalmanuscript. mesentericischemiapatientsfollowingearlydiagnosisbymultidetector rowcomputedtomographyandprostaglandinE1treatment.InternMed 2008,47:2001–2008. Acknowledgements TheauthorsthankMizuhoYamamoto(DepartmentofDermatology,National HospitalOrganizationSagamiharaNationalHospital)andYasuyoTakeshita doi:10.1186/1756-0500-6-26 (DepartmentofNephrology,NationalHospitalOrganizationSagamihara Citethisarticleas:Oshikataetal.:AnadultpatientwithHenoch- Schönleinpurpuraandnon-occlusivemesentericischemia.BMCResearch NationalHospital)fortheirclinicalsupport. Notes20136:26. Authordetails 1DepartmentofAllergyandRespirology,NationalHospitalOrganization SagamiharaNationalHospital,18-1Sakuradai,Minami-ku,Sagamihara, Kanagawa252-0392,Japan.2DepartmentofRadiology,NationalHospital OrganizationSagamiharaNationalHospital,18-1Sakuradai,Minami-ku, Sagamihara,Kanagawa252-0392,Japan.3DepartmentofGastroenterology, NationalHospitalOrganizationSagamiharaNationalHospital,18-1Sakuradai, Minami-ku,Sagamihara,Kanagawa252-0392,Japan.4DepartmentofHuman Pathology,JuntendoUniversity,2-1-1Hongo,Bunkyo-ku,Tokyo113-8421, Japan.5DepartmentofPathology,JapaneseRedCrossMedicalCenter,4-1-22 Hiroo,Shibuya-ku,Tokyo150-8935,Japan. Received:17August2012Accepted:18January2013 Published:23January2013 References 1. LieJTandmembersandconsultantsoftheAmericanCollegeof RheumatologySubcommitteeonClassificationofVasculitis:Illustrated histopathologicclassificationcriteriaforselectedvasculitissyndromes. ArthritisRheum1990,33:1074–1087. 2. 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