increased consistency and diminished sensitiveness result in a huge enlargement, such as occurred in no of one or both testicles, to indurative atrophy of the less than ten instances in this report. base of the tongue, leukoplakia and the like, and Pain in the left hypochondrium likewise is present, scarring and deflection of the epiglottis, to scars of though variation in the site of the pain differs some¬ the pharyngeal vault, to perforation of the nasal sep¬ what. In three cases the pain was described as diffuse tum, to the presumptively syphilitic nature of aortic throughout the abdomen, then localizing in the left régurgitation, to the ophthalmoscopic signs of chorio- hypochondrium, and in a fourth as "in the region of retinitis pigmentosa, and similar discoverable signs of the stomach." The character of the pain varied from syphilis, any one or any combination of which, as the a dull ache to a sharp colic, with all degrees of grada¬ case may be, is less apt to lead one astray than the tion between. The pain is usually superficial and spon¬ results of a Wassermann reaction. These and like taneous, but may be deep and provokable. It is fre¬ signs were sought by the clinicians of the generation quently exaggerated by changes in position, and may that passed with Delafield and the elder Janeway ; but radiate along the phrenic nerve or into the left the generation that holds the responsibility of the shoulder.2 A sensation of weight in the left hypo¬ future is being inculcated with an almost reverential, chondrium was often complained of, a violent hauling respect for artificial methods that neither clinician nor to the left exaggerated by inspiration, or a tingling, pathologist can explain or control. shooting or beating sensation in the same region.3 The pain is probably due to irritation or interference with CONCLUSIONS the structures the Wasser¬ immediately surrounding , 1. Depending on the antigen employed, the since this organ is not very sensitive. Total infarction mann in as carried out at reaction the living patient, of the spleen may occur, however, without any pain, a result in from 31 Bellevue Hospital, gives negative as in one case here reported and in three of those in to 56 per cent, of cases in which the characteristic the literature. anatomic signs of syphilis are demonstrable at Tenderness is usually associated with the pain, and necropsy. is present in the left The tenderness reaction in the is hypochondrium. 2. The Wassermann living patient may come on suddenly and may continue for many in 30 cent, cases in it positive at least per of which days, or there may be occasional tenderness in the left is not possible to demonstrate any of the anatomic side.4 lesions of syphilis at necropsy. The presence of apparently depends on the disease to which the spleen alterations are concomitant. When this is due to an obstruction of the splenic- THE DIAGNOSIS OF INFARCTION OF THE vessels by thrombi or emboli that are sterile, fever is ENTIRE SPLEEN absent. But after the spleen has undergone degenera¬ tive changes, bacteria which were already present5 or FRANK NUZUM, B.S., M.D. which make their entrance from some source such as JANESVILLE, WIS. the colon6 multiply rapidly, the organ finally resembles a of pus, and fever occurs. In one of the four Total infarction1 or necrosis of the has bag spleen cases here the Proteus in another received little attention in medical literature. Even reported, mirabilis, the colon bacillus was isolated from the and in the of medicine devote a line to spleen, larger systems only each instance a rise in of from 1 to 2 its consideration. From scattered of temperature reports colliqua- was times the tive necrosis, thrombosis of the degrees present intermittently. Many necrosis, coagulation splenic changes result from or are accompanied by splenic vein, etc., it is evident that a definite symptom- inflammatory changes elsewhere in the body, and atology is associated with these specific affections of under such conditions the fever is often attributable to the spleen. The purpose of this paper, in addition to such factors. In one of our instances a gangrenous or necrosis adding four instances of total infarction cystitis, in another a suppurative pylephlebitis and in is to out the of the spleen to the literature, point pos- a third an amebic dysentery was present and would sibility of the diagnosis of this condition. account for the rise in temperature. The symptoms are pain, tenderness in the left hypo- The vomiting of blood, bright red at times, and chondrium, enlargement of the spleen, occasionally resembling coffee grounds at others, is of frequent fever, and vomiting of blood due to rupture of dilated occurrence. It was present in one of our instances gastric veins. A glance at the literature reveals the and in several from the literature. Ewald7 recorded regularity with which these symptoms are recorded. an example of a large spleen resulting from a throm- The added examples in this report are a repetition of bosed splenic vein, the patient dying as the result of a the former. hemorrhage from the stomach. Following the hemor¬ Whenever the spleen becomes totally infarcted, rhage there was a marked reduction in the size of the enlargement occurs, the weight varying from 300 to spleen. The reasons for bleeding from the stomach 1,300 gm., and the dimensions reaching such propor¬ following or necrosis are well tions as 25 by 15 by 8 cm. The enlargement in all known, and have been substantiated by experiments. of the new cases reported here was noted on physical The splenic changes are accompanied by extensive examination, but was often misleading, it being anastomoses between the splenic and gastro-epiploic assumed that such an enlargement must be due to a vessels. The dilatation of these gastric veins often leukemia or other condition. This fallacy is demon¬ becomes extreme, and the possibility of their rupture • strated the fact that infarction of the spleen may by 2. Lefeuvre: Bull. Soc. anat. de Paris, 1848, p. 193. 3. Durand, M.: Contribution \l=a`\l'\l=e'\tudedes infarctus de la rate, Lille, 1. The term "total infarction" is here used because the condition is 1903, Mason. discussed in the literature, as a rule, under this title. Strictly, total 4. Saundby: Brit. Med. Jour., 1908, 2, 1155. infarction is very rare, most infarcts being "mixed," the blood by 5. Carriere and Vanverts: Arch. d. m\l=e'\d. exper. et d'anat. pathol., imperfectly anastomosing vessels infiltrating the edges to make a red 1899, 11, 48. margin about the place of more total infarction. "Infarction of the 6. Balacescu: M\l=u"\nchen. med. Wchnschr., 1901, 48, 35. entire spleen" is, therefore, a better term. 7. Ewald: Deutsch. med. Wchnschr., 1913, 39, 398.

Downloaded From: http://jama.jamanetwork.com/ by a University of Iowa User on 06/01/2015 is imminent. However, the bleeding in the instance whether the thrombosis was primary in the portal or recorded by Ewald was through a mucous membrane splenic veins. Sometimes, in a general arterial scle¬ of the stomach which did not present gross lesions. rosis, the portal vein is markedly sclerosed. Or a This, too, has-been described before. Experimentally, portal sclerosis may be present even without a general Troell8 found that following ligation of the splenic arterial sclerosis.11 In such instances, Simmons veins, a second procedure is necessary, namely, liga¬ believes that the sclerosis is due to bacterial poisons, tion of the dilated anastomosing vessels in the liga- and the primary splenic enlargement is the result of mentum gastrosplenicum. Likewise, Warthin9 found blood stasis. Syphilis and trauma also have been held that after ligation of the splenic vessels proper, anas¬ as productive of a primary portal sclerosis,12 and may tomoses of the spleen with_ veins of the gastrosplenic be responsible for a portal thrombosis which backs up omentum and of the stomach allowed small islets of into the splenic vein. The thrombus in the portal vein the spleen to live. does not necessarily mean death to the patient, as is In the etiology of total infarction of the spleen, generally believed, since the thrombus may become vascular obliteration has been held responsible ; but the canalized.13 Or the portal vein may remain completely cause of the vascular obliteration must be determined. obliterated without causing death, as Umbra14 found. The important factors here concerned are pressure on A displaced spleen or torsion of the splenic vessels the walls of the splenic vessels by tumors ; torsion of may give rise to splenic infarction. In a series of these vessels in instances of ectopie spleen ; thrombosis twenty-six instances of ectopie spleen collected from of the splenic vessels, and embolism. The emboli the literature, Durso15 found seven in which there had may be (1) exogenous, including microbes, and (2) been complete infarction of the spleen. To these he endogenous, as atheromatous plaques. In one of our added one instance of his own, the body of the organ instances, thrombosis of both the splenic artery and being necrotic and surrounded by a narrow strip of the splenic vein was found; in another, an embolus healthy splenic tissue which obtained its nourishment in the splenic artery from a mitral endocarditis, and from the capsule. He found that rotation of the in a third an extension of a carcinoma into the splenic spleen in dogs produced infarcts of the character of

TABLE 1.—EXAMPLES IN AUTHOR'S SERIES

Cause Symptoms Pathology of Spleen Cause of Death

Obturating thrombus of splenic Pain in left hypochondrium ; Spleen much enlarged and en· 'Diphtheria and gangrenous cys¬ artery and vein vomiting at times; anorexia tirely necrotic titis" and headache for eight weeks; large spleen; intermittent fever, 1-2 degrees; both bright and "coffee ground" blood in vomitus Embolism of splenic artery from All symptoms referable to an Wt., 300 gm, ; "a soft, yellow, "Ulcerative stenosis of rectum; mitral endocarditis ulcerative, amebic colitis necrotic mass not normal at amebic dysentery" any point." Extension of carcinoma into Enlargement of spleen ; pain Wt., 600 gm.; size, 13 by 9 by 8 Carcinoma of stomach with per¬ splenic vein under costal arch cm.; entirely necrotic foration into lesser peritoneal cavity Not determined; overlooked at Pain in left hypochondrium Wt., 210 gm.; organ entirely "Suppurative pylephlebitts; mul¬ necropsy necrotic tiple abscesses of liver"

vein. Thrombosis of the splenic vein was the causa¬ embolie infarcts, and that as a result, severe symptoms tive factor in nine instances recorded in the literature ; became manifest. He determined that the infarction arterial plugging was responsible in five. Occlusion resulted from the circulatory disturbance in the of both the artery and the vein was present twice. branches of the splenic veins. Torsion of these vessels produced a total infarction An embolus lodging in the splenic artery only rarely in nine instances. Pressure on the vein or invasion gives rise to total infarction, in spite of the fact that was found con¬ of it by neoplasms twice. In five, the this artery is an end artery. In one of our instances, dition of the splenic vessels was not determined. however, total infarction resulted from an embolus Thrombosis of the splenic vein has resulted, there¬ coming from thrombi on the mitral valve. fore, in a total splenic infarction more frequently than The pathology of total infarction of the does factor. the thrombus is spleen any other single Usually pri¬ not differ from infarction in any viscus that has a mary in the splenic vein, Bonne10 reporting the first "terminal" blood of the infarcì is this. His is supply. Softening example of explanation frequently quoted, sometimes mistaken for abscess formation, and cannot and is as follows : An infectious process in the spleen be differentiated without the aid of the results in a which in turn an endo- microscope. splenitis, produces In each of our four instances, the changes in the spleen phlebitis. This endophlebitis causes a proliferation of had reached this the the endothelial and leads to thrombus formation. stage, organ being entirely cells, necrotic and a filled with The induration and the disturbances resembling bag purulent splenic circulatory material. In two of the four bacteria of which follow aid in an extension of the thrombus for¬ instances, low virulence were isolated from this mation. material. In approx¬ one half of the in the a In a few examples of totally infarcted spleen, a imately examples literature, portal thrombosis has been found associated with the similar condition was found. In others the spleen was was splenic thrombosis, and it difficult to determine 11. Simmons: Virchows Arch. f. path. Anat., 1912, 207, 360. 12. Heller: Verhandl. d. deutsch. path. Gesellsch., 1904, 41, 182. 8. Troell: Ligation of the Splenic Vessels as a Substitute for Splenec- 13. Edens: Ueber Milzvenenthrombose, Pfortaderthrombose und Ban- tomy in Blood Diseases, Ann. Surg., 1915, 63, 88. tische Krankheit, Mitt. a. d. Grenzgeb. d. Med. u. Chir., 1908, 18, 59. 9. Warthin: Experimental Ligation of the Splenic and Portal Veins 14. Umbra: Beitrag zur Pfortaderobliteration, Mitt. a. d. Grenzgeb. with the Aim of Producing a Form of Splenic Anaemia, Proc. Soc. d. Med. u. Chir., 1901, 7, 487. Exper. Biol. and Med., 1907, 4, 127. 15. Durso: Studio clinico e sperimentale dello infarto splenico nella 10. Bonne: Ein Beitrag zur Kenntniss der Thrombosen der vena rotazione della milza, Policlinico, Rome, 1896, 3 C, 63; abstr., Atti d. lienelis, E. Huth, G\l=o"\ttingen, 1884. r. Accad. Med.-Chir. di Napoli, 1895, 49, 214.

Downloaded From: http://jama.jamanetwork.com/ by a University of Iowa User on 06/01/2015 a "gigantesque" (gigantic) cicatrix, fibrous and infil¬ tumified, other regions having softened and become trated with blood pigment, the third or final phase of cysts filled with necrotic material, and still other por¬ infarcì formation having been reached.3 In some, the tions of the same organ, fibrous and retracted.16 three phases of infarcì formation were represented, and 16. Lefeuvre: Etudes physiologiques et pathologiques sur les infarctus portions of the infarcted spleen being brownish visc\l=e'\raux,Paris, 1867, p. 125.

TABLE 2.—EXAMPLES FROM LITERATURE

Author Reference Cause Symptoms Pathology of Spleen Cause of Death

Bonne, G.: Ein Beitrag Thrombosis of splenic Seized with abdominal Spleen 18 by 11 by 15 zur Kenntnis der vein and its branches; pain ; spleen became cm.; necrotic Thrombosen der vena also of portal vein enlarged ; diarrhea and lienalis, Göttingen. headache developed D.: Tr. Not stated of 36 . Chronic Roileston, H. Thrombosis of splenic . Weight spleen, ; diarrhea Path. Soc. London, vein filled with extensive, 1891-1892, 43, 49 anemic, infarcted areas Same Carcinoma growing into Not stated Not stated Peritoneal carcinomatosi*, and occluding splenic originating in cecum vein Christomanos, . .: Torsion of pedicle and Diffuse Spleen weighed 1,300 Operation with recovery Beitr. z. path. Anat. u. thrombosis of splenic localizing to left of epi¬ gm. ; entirely necrotic z. allg. Path., 1898, vein gastrium 34, 519 Horch: Verhandl. d Torsion of pedicle with Enlargement in left hypo¬ Weight, 2,700 gm.; vein Recovery following splo- deutsch. Gesellsch. f. thrombosis of vein chondrium ; pain on filled with dark clot nectomy Chir., 1885, IO, 63 standing or walking; due to torsion of pedi¬ vomiting of blood cle; cut surface gave appearance of infarct Heurtaux: Bull, et mém. Rotation of spleen with Tumor in abdomen, inter¬ Weight, 615 gm.; a rim Operation with recovery Soc. d. chir., 1893, 19, torsion of vessels mittent fever of healthy tissue sur¬ 752 rounded bulk of the organ, which was necrotic Vetlesen, H. J. : Forh Infarction due to malig Four attacks of pain in "Spleen large"; contained Malignant endocardi' med. Selsk. i Kris nant endocarditis region of left costal four distinct large in¬ with h e m o r r h a g i tiania, 1889, p. 84 margin, each associated farctions corresponding nephritis with splenic enlarge· to clinical history ment Weber, F. P.: Med. Press Complete occlusion of None Weight, 12 oz. ; organ Pulmonary tuberculosis and Circular, 1908, splenic artery by recent converted into one 87, 14 thrombus large infarct Saundby: Brit. Med. Splenic thrombosis fol Tenderness and occa¬ Not demonstrated Did not die Jour., 1908, .3, 1155 lowing pregnancy sional pain in left side with enlarged spleen Edens: Mitt. a. d. Grenz Old thrombosis of splenic Not stated Spleen 25 by 15 by 8 Peritonitis jçeb. d. Med. u. Chir. and portal veins, the cm. ; firm consistency; 1908, 18, 59 former canalized marked increase in fibrous tissue through¬ out Same Not known Sudden pain in left hypo Not known; diagnosis of Recovered chondriurn ; enlarge splenic thrombosis ment of spleen; fever septic infarct for 3 weeks Fisher, W. E.: Proc. Roy Wandering spleen Not stated Wandering spleen en¬ Splenectomy; recovered Soc. Med., London, gorged, owing to trac¬ 1908-1909, 3, Clin, tion on vessels and Sec, 128 with large infarcts Watson and Stewart: Associated with tonsil Tenderness in left side Spleen converted into a Lancet, London, 1912 litis with enlarged spleen sac filled with turbid 3, 877 bloody fluid; strepto¬ cocci found Goldman: Deutsch, med Endocarditis resulting in Pain in region of Spleen 2 by 14 by 7 cm.; Portal thrombosis? Wchnschr., 1913, 39. infarction of the spleen stomach ; large spleen ; tough consistency; or¬ 1542 and thrombosis of the vomiting of blood gan filled with old, fi¬ splenic vein broid infarcts Ewald : Deutsch. med Thromhnsed, partially Large spleen ; fatal hem¬ Spleen 30 by 7 by 6 cm.; Hemorrhage Wchnschr., 1913, 39. canalized splenic vein orrhage from stnmacli, same increase of fibrous 398 followed by reduction tissue in size of spleen Lavastine and Bloch : Atheromatous splenic ar Not stated Weight, 500 gm.; spleen Bronchopneumonia, Bull. et mém. Soc tery pulp entirely filled anat. de Paris, 1914 with infarcts of various 79, 352 ages; one, size of orange Umber: Mitt. a. d. Grenz Complete obliteration of Not stated Marked enlargement; in¬ geb. d. Med. u. Chir., splenic and portal veins crease in fibrous tissue 1901, 7, 487 Hektoeii, L. : Med. News Extensive primary throm- None referable to the Spleen 14 by 9 by 5 cm.; Bronchopneumonia 1894, 1, 325 bosis of al] of the spleen weight, 250 gm. ; firm; splenic veins following filled with anemic and typhoid hemorrhagic infarcts, and all of the vein thrombotic.

Durso, G. : Policlinico Reports one of hio own In most instances pain in Spleen enlarged, in one Rome, 1896, 3-c, 1, 63 and 7 cases collected the left side instance weighing 1,050 from the literature _cf gm. ectopie spleen issncia- ted with infarction and due to torsion of the splenic vessels Lefeuvre : Eludes physio Tnfarciion resulting from Local manifestation hid¬ Spleen enlarged, adher Pericarditis; peritonitis login, ties et pathologiques aortic valve disease den by an acute rheu¬ ing to surrounding sur les infarctus vis¬ matism and a subacute structures, pulp filled céraux, Paris, 1867 peritonitis; severe pain with infarcts, four of in splenic region, how¬ which had softened and ever become comecysts filled gangrenous material Durand, M.: Contribu Infarction resulting from Tenderness on pressure Spleen a "gigantesque" Cerebral hemorrhage tion a l'étuée des in an old typhoid fever in left hypochondrium cicatrix, fibrous and in¬ farctus de la rate, Lille_ filtrated with blood pig¬ 1903, Mason ment

Downloaded From: http://jama.jamanetwork.com/ by a University of Iowa User on 06/01/2015 Following thrombosis or embolism sufficient to cause complex of symptoms which may be caused by various complete occlusion of either the splenic artery or the etiologic factors. splenic vein, the vessel itself undergoes degenerative The importance of recognizing infarction of the changes and becomes obliterated from the point of its spleen of sufficient degree to produce symptoms is evi¬ occlusion onward to its finer terminals. dent in considering the treatment. Whether medical From our examples it is evident that an occlusion of attention is sufficient or whether surgical procedures either the splenic artery or the splenic vein is sufficient are called for depends on several factors. Among to produce total infarction of the spleen. Simultane¬ these are the reaction of the patient to the toxic ous occlusion of both of these vessels, however, is apt material absorbed from a necrotic spleen, and the to result in immediate necrosis of the entire spleen, presence of hemorrhage from dilated gastric veins. and a fatal outcome may follow from the absorption Usually in the total infarction of the spleen, the organ of toxins. The first of our examples illustrates this. is bound to the surrounding structures by firm, fibrous An obturating thrombosis of both the splenic artery adhesions. This increases the difficulty of surgical and the splenic vein resulted in a much enlarged and intervention. Perhaps improved methods from recent entirely necrotic spleen. Death followed in six weeks experiences with splenectomy in pernicious anemia will from continuous absorption of toxic material. help to overcome these difficulties. Similar conclusions have been drawn from experi¬ ments. Carrière and Vanverts17 ligated both vessels SUMMARY in dogs and rabbits, and found that in most instances 1. Total infarction or necrosis of the spleen has gangrene resulted, the spleen becoming a pus sac. been infrequently reported. They held that the spleen normally contains bacteria, 2. Total infarction of the spleen may result from but that these are of low virulence or of none at all. an embolus or a thrombus in either the splenic artery Among these organisms are colon bacilli, diplococci, or the splenic vein ; from the extension of a thrombus staphylococci and streptococci. In ligation of the backward from the portal vein into the splenic vein ; splenic artery alone, gangrene did not result ; and they from pressure on the splenic vessels by a neoplasm ; concluded that since the circulation was not completely from torsion of the splenic vessels when the spleen is interfered with, the spleen cells were able to take care displaced, or from an inflammatory process originating of the bacteria without pus formation. Balacescu6 within the spleen and involving the terminal branches likewise found that when both the artery and the vein of the splenic artery and vein (Bonne's view). were tied, many animals died of absorption of toxins 3. Total infarction of the spleen gives rise to defi¬ from a gangrenous spleen. When one vessel was tied, nite enlargement of the spleen, pain and tenderness in he found that many, adhesions form and that gradually the left hypochondrium, fever, and occasional vomiting bacteria from the intestinal tract admittance into gain of blood, and from these a correct diagnosis may be the spleen. made. discussion of thrombosis is Any splenic incomplete 4. The treatment, whether medical or surgical, without a consideration of the of a rela¬ possibility depends on many factors, such as the condition of the tionship between this condition and the so-called patient and the underlying disease of which the splenic Banti's disease. The exact status of Banti's disease infarction may be either the chief expression or only not been determined. Banti18 assumes that a toxic has a minor part. agent produced in the spleen brings about the changes in the splenic and vessels, finally the three portal stages EXCRETION OF INGESTED PURINS IN of a typical Banti's syndrome resulting. The first stage includes an enlargement of the spleen ; the CHRONIC GOUT second, urinary changes and marked anemia ; the third, A STUDY OF TWO CASES liver changes with ascitës and a gradual increase in the severity of all the symptoms. We now know that JACOB ROSENBLOOM, M.D., Ph.D. some mechanical conditions, such as circulatory dis¬ PITTSBURGH turbances in the and can splenic portal systems, pro¬ It is generally accepted that less exogenous uric acid duce an illness similar to Banti's disease. very is eliminated by persons to than nor- Senator19 is for the statement that subject gout by authority splenic mal persons. It is still whether or not this anemia cannot be differentiated from Banti's disease disputed lessened excretion of exogenous uric acid can be used during the first stage of the latter. Gilbert and for diagnosis. Lereboullet,20 after a review of the subject, decide Vogt, Reach, Soetbeer, Pollak, that Banti's disease does not exist. maintain Mallory, Weinberger They and Yavein have found that in gout the excretion of that the histology of Banti's disease is only that of a is diminished and This is chronic of the and that exogenous purins delayed. passive hyperemia spleen, por¬ not always the case according to Magnus-Levy, Wein- tal hypertension can make a good example of splen¬ traud, Rommel and Pratt. and can also cause the liver found in omegaly changes In a recent article, McClure and Pratt1 present tables Banti's disease. As a result of these and similar con¬ showing a summary of all the observations Isaac21 wonders if Banti's disease is rather a previous clusions, on the exogenous uric acid excretions of normal per- of 17. Carri\l=e`\reand Vanverts: Etudes sur les lesions produits par le liga- sons, patients with chronic arthritis, and of gouty ture exp\l=e'\rimentaledes vaisseaux de la rate, Arch. de m\l=e'\d.exper. et patients. have studied the uric acid excretion in d'anat. 498. They path., 1899, 11, two cases of after the of 18. Banti: The Treatment of Banti's Disease, Folia haemat., 1910, gout feeding sweetbreads. 10, 33. They believe that the retention of uric acid is a 19. Senator: Ueber Anaemia splenica mit Ascites (Bantische Krank- of in the heit), Ber). klin. Wchnschr., 1901, 38, 1145. symptom questionable importance diagnosis 20. Gilbert and Lereboullet, quoted by Cauchois: Spl\l=e'\nom\l=e'\galiechro- of gout. Th\l=e`\sede 1908, p. 92. nique de'origine pylethrombosique, Paris, 1. McClure, C. W., and Pratt, J. H.: A Study of Uric Acid in 21. Isaac: Das Bantische Symptom Komplex und seine Stellung unter Gout, Arch. Int. Med., October, 1917, p. 481. den Splenomegalien, Jahrb. d. ges. Medizin (Schmidt's), 1912, 215, 122.

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