Document NEM8V7qx74BGMM1r9aNO18qmp

THIS MATERIAL MAY BE l *50 Cirrhosis of the Liver in Northern India A Ctinkopathotagic Study V. RAMALINGASWAMI, M.D., D.PUl (OXON) K. L. WIO, M B., F.R.C.P. (LONDON) AND 8. K. &AMA, M.D. NEW DELHI. INDIA g Introduction Cirrhosis of the liver is known to be a common condition in India.1 Its morphology and morphogenesis, however, are not entirely clear, due partly to lack of uniformity in the criteria used for distinguishing the various anatomical types. This is evident from a recent careful study in which it has been re ported that, contrary to previous reports, the majority of cases of cirrhosis in Eastern India (Calcutta area) belong to the post necrotic variety.* Autopsy studies alone, unaided by sequen tial clinical studies before death, are of Submitted for publication March 26, 1962; ac cepted April 6, Professor of Medicine (Dr. Wig). Postgraduate student in Medicine (Dr. Sama). Professor of Pathology (Dr. Ramalingaswami). From the Departments of Medicine and Pathol ogy, All-India Institute of Medical Sciences. limited value. At autopsy the process is seen in its end-stages, and a single anatomical type of cirrhosis may be produced by more than one etiological factor. Autopsy studies in India suffer from the further disadvantage that they are most often made on unclaimed bodies belonging to the destitute class and are therefore unrepresentative. In a progres sive, continuing process like cirrhosis, a com bined clinical and pathological study at various stages of the disease is likely to be of value. This is attempted in the present study. It should be noted that the cirrhosis of infancy and early childhood seen with characteristic frequency in India* is not in cluded in this study. Material, Method, and Scope of Study The present communication deals with 46 adult patients admitted to the Institute Hospital with 122 ZUOVWIPZ CIRRHOSIS OF LIVER--INDIA Ml established clinical features of portal hyperten sion, Midi as ipjeiKHiicguly, ascites, ami engorged iiIhIoiiiIiiuI veins. Tlie presence of portal hyperten sion was established in each case hy the demon stration of esophageal varices, of collaterals on splenovenography and/or the presence of a portal pressure, measured as splenic pulp pressure, of 15 mm. of Hg or more. The normal range of splenic pulp pressure under similar conditions with the same baseline was 6-10 mm. Hg. In none of these cases was there any evidence of extraiiepatic ob struction on splenoportal venography. The mode of onset and clinical evolution of the cases was studied in detail, and they were followed up for a period of about 2 years from the date of admission with established portal hypertension. \ Diver biopsies using the Vim-Silverman needle were performed successfully at least once in each case. In 10 cases, adequate biopsies were obtained on 2 or more occasions at intervals ranging from one to 12 months. During the period of study 6 of these cases came to autopsy, and in 2 additional cases, an open wedge biopsy of the liver was ob tained at laparotomy. All this material was fixed in buffered neutral 1096 formalin and paraffin sections were made for various staining procedures. Hema toxylin and eosin, periodic acid-Scliiff. and Gomori's reticulin stains were used as a routine.* From an evaluation of the past history, the mode of onset, clinical progression, and termination of the present illness the cases could be grouped into 3 distinct types. In the account below the broad clinical features of these types and their points of distinction are described followed by the pathologi cal anatomy of the liver in each type. Results The disease was seen most commonly in persons between 20 and 50 years of age, and men were more commonly affected than women (Fig. 1). Most of the patients be longed to the working class, and their nutri tion in this part of the country was considered to be fair. Their daily calorie intake was of the order of about 2,200 to 2,600 with a protein intake of about 50 to 100 gm. They came, in the main, from the rural surround ings of Delhi. Description of Clinical Types Typr I (Jaundice Type).--Thirteen out of 46 cases in the present series belonged to ibis type. All cases gave a definite history of onset of the illness with an acute attack of jaundice. In 8 of them, the illness pro * w rises Fig. 1.---Age and sex distribution of cases. gressed with recurring jaundice and in an average period of one year from the onset had led to an established clinical picture of cirrhosis, with ascites, splenomegaly, and ab dominal vein prominence. In the remaining 5 cases the jaundice cleared completely, and, after a variable asymptomatic period of a few weeks to a few months, it recurred again and their subsequent behavior was similar to that of the above-mentioned 8 case*. Jaundice was a prominent feature of the ill ness in this type. AU except one showed as cites which was moderately severe in a majority of the cases (9 out of 15), quite severe in 2 cases, and mild in one. The spleen was palpable in all cases except one and meas ured on the average 52 cm. from the costal margin. Endocrine disturbances character istic of cirrhosis developed prominently in this type in comparison with the other types, 6 out of 13 cases showing one or another manifestation. The manifestations consisted of gynecomastia (2 cases), spider angiomata' (4 cases), palmar erythema (2 cases), and scanty pubic and axillary hair (3 cases). Hematemesis occurred while the patients were under our care in 4 cases, in one of which it proved fatal, Splenovenography re vealed that the portal and splenic veins were normal in size and free from any block, but all cases showed collaterals (Fig. 2). 123 Ramalingaswami el al. 35* ARCHIVES OF INTERNAL MEDICINE CIRRHOSIS OF LIVER-INDIA Fig. 2.-- Splenoportal venogram showing normal-sized splenic and por tal veins and distorted intraiiepatic vascular pattern. Retrograde flow into the coronary, short gastric and inferior mesenteric veins are visualised (Type I case). an > Fig. 3.--Splenoportal veno gram showing markedly di lated splenic and portal veins with normal intrahcpatic vas cular pattern. Retrograde flow into coronary and short gastric veins can be visual ized (Type III case). Temporary improvement could be obtained in most cases by appropriate therapy, but despite this the course of the disease was one of progressive deterioration and the com monest mode of termination was hepatic coma. Six out of the 7 patients that died in this group during the 2 years' follow-up study had this mode of termination, and, as already stated, the remaining patient died of hematemesis. The average total duration of the illness from its inception to death in the fatal cases was 21.5 months. Of the 5 patients that are alive, the average duration of the illness was 22.5 months. One case could not be followed. Type II (Ascitic Type).--This type con sisted of 17 out of 46 cases. Unlike Type I, the onset in this type was insidious with vague abdominal symptoms, and the first con crete sign was ascites. In a majority of them the ascites was severe. In contrast to Type I, jaundice was either inconspicuous or did not occur at all at any stage of the disease. The spleen was palpable in all but 2 cases and measured on the average 4.7 cm. below the costal margin. Endocrine disturbances de veloped, but with less frequency than in Type I, 3 out of 17 cases showing one or another of these disturbances. Gynecomastia and spider angioma were present in one, scanty pubic and axillary hair in 2 cases. Hematem esis occurred in 4 cases, in 2 of which it proved fatal. On splenovenography there was nu block in the extrahepatic )x>rlal Ix'il, and the portal and splenic vein showed no dilata tion except in one case. Although many cases could be temporarily improved on appropri ate therapy, the disease on the whole followed a relentless downhill course, rapid formation of ascites being the most prominent feature, and the condition terminated most often in hepatic coma as in Type I. Out of 8 patients that died during the 2 years' period of study, in 5 death was due to hepatic coma, in 2 to hematemesis, and in one to superimposed hepatoma. The total duration of the illness was on the average 14 months. In the remain ing 9 patients that are alive, the average dura tion of the illness was 22 months, similar to Type I. Type III (Splenomegalic Type).--This type consisted of 16 cases. While Type I and Type II have considerable overlap in their features including the pathological changes in the liver (see below), this type was unique and quite distinctive. The onset was vague, and splenomegaly was the first feature noted by the patient and remained dominant throughout the illness. It was followed by ascites after a relatively long latent period. The average duration of illness at the time of admission in this ty|>c was of the order of about 8 years in marked contrast to the other types. The spleen was very markedly en larged and measured on the average about 9 Vol. 110, Sen., 1962 121 COOfr^Z cm. from the costal margin. Ascites was mild tation of the biopsy and autopsy specimens in a majority of the cases. Jaundice was also and the precise meaning of the nomenclature not a feature at any stage of the disease. used. The diagnosis of cirrhosis was made if Endocrine disturbances were least conspic- 1 the criteria laid down by the Board for Classi uous, being present in only one out of 16 ' fication and Nomenclature of Cirrhosis of the cases, a patient with gynecomastia. Hematem Liver of the Pan American Congress of Gas esis was also uncommon; it was present in 2 troenterology (1956) were satisfied. In both cases in one of which it proved to be fatal. biopsy and autopsy specimens, portal and On splenovenography, in contrast to the other postnecrotic cirrhosis were recognized ac types, the portal and splenic veins showed cording to the criteria of Smetana.* A further marked dilatation in a majority of the cases subdivision of postnecrotic cirrhosis was at (Fig. 3). There was no demonstrable ob tempted into broad- and fine-band types. If struction to the extrahepatic portal bed. The there was evidence of broad fibrous bands prognosis in this type proved to be much with collapse, stromal condensation, and ap more favorable than in the others. There was proximation of several portal canals as the only one death attributable to hepatic coma major pathological process, it was designated during the 2 year period of observation, one broad-band type of postnecrotic cirrhosis.' If, due to hematemesis, and in 3 others, the death on the other hand, the fibrous bands were fine was attributable to operative procedures. In for the most part, it was designated as fine- the 2 patients that died a natural death, the band type of postnecrotic cirrhosis.' While total duration of the illness was 132 and 44 this subdivision of postnecrotic cirrhosis was months. made in all the autopsies, it was not always Appropriate therapeutic measures brought feasible on needle biopsies. However, if there about prompt relief of symptoms in a ma was evidence in needle biopsies of broad jority of the cases. There was no progressive scars with approximation of portal canals, a deterioration in the manner observed in probable diagnosis of broad-band type of Types I and II, and the average duration of postnecrotic cirrhosis was made. In the cases the illness of the surviving cases is 123 that came to autopsy such an interpretation months. on the basis of the needle biopsy was found Pathologic Anatomy Before presenting the results, it is desirable to set down the criteria used in the interpre to be corroborated. In many needle biopsies the cirrhosis had to be left unclassified. Picture in Type l.--Twelve out of 13 cases showed cirrhosis on biopsy, in 4 of which it 125 Ramalingasmmi el of. BFG36574 I U4 ARCHIVES OF INTERNAL MEDICINE CIRRHOSIS OF UVER--INDIA US Fig. 4.--Persistent hepatitis with portal scarring and portal and intralobular infiltrates; liver biopsy in a Type 1 case. Hematoxylin and eoein; reduced about 25% from mag. X 100. Fig. 5.--Higher magnification of the specimen in Figure 4 to show the diffuse hepatitis, reminiscent of viral hepatitis. Reduced about 25% from mag. X 475. was confirmed at autopsy (Table). The re maining case showed persistent hepatitis with much scarring, not amounting to cirrhosis (Figs. 4 and S). Five out of the 12 cases of cirrhosis also showed evidence of persistent hepatitis in the form of focal degeneration and necrosis of liyer cells, intralobular cel lular infiltrates, moderately severe mono nuclear infiltrates in the fibrous bands, and extension of the inflammatory exudate from the fibrous bands into the surrounding liver parenchyma and into the portal canals con tained within the multilobulated pseudolob ules. In a few cases the degenerating liver cells showed hyaline and acidophil body formation. In the remaining cases of cir rhosis, the picture was quiescent with clearly demarcated pseudolobules sharply separated from the fibrous bands. The liver paren chyma in the pseudolobules was of the regen- erative type with 2-cell-thiclc liver cords; bile, hemosiderin, and lipofuchsin pigments were variably present. In 9 of the 12 cases of cirrhosis, the cir rhosis was of the postnecrotic variety; in 2 it could not be classified (both biopsies), and in one it was portal. Of the postnecrotic group, the majority (7 out of 9) showed evidence of broad-band formation with con siderable collapse as the major pathological process (Figs. 6,7, and 8). In one case, broad and fine bands were equally prominent, pro ducing a mixed type of postnecrotic cirrhosis (Figs. 9 and 10). In the last case the picture was predominantly one of fine-band type of postnecrotic cirrhosis corresponding to Gall's posthepatitic variety.1 Picture in Type II.--Out of 17 cases, defi nite evidence of cirrhosis was present in 9 Hislohgic Feature! of the Liver in the Fig. 6.--Postnecrotic cirrhosis, postcollapse type (Steiner) showing a broad band with collapse and 3 Clinical Type* stromal condensation; autopsy specimen in a Type 1 case Hematoxylin and eosin; reduced about 25% : No. Showing (ho Hint. from mag. X 3a. Poataros in Each Typo Bit*. PoatWOO Olfrboals Pootaacroll* Portal PihJ--Iliad Ponttoot hopaUUa with earring Portal Marring only Minimal aonopadOeohangM Patty ofcanao Trpsi 13 t 1 f 1 Type II Typo III _ -- ---- -- -- -- 11ft -- Total 19 IT 19 Vol. 110, Sept., 1962 126 i $oomsvz Fig. 7.--Section stained with hematoxylin and eosin from the same specimen as in Figure 6 to show the structure of a multilobulated nodule. Re duced about 25% from mag. X 35. only, in 2 of which the diagnosis was con firmed subsequently at autopsy (Table). Five out of these 9 cases belonged to the post necrotic variety, 3 of which were of the broad-band collapse type. One case could not be placed either in the broad- or the fineband groups, and one belonged to the mixed variety. In the remaining 2 cases which showed cirrhosis (all biopsies), the anatom ical type could not be identified with cer tainty. Two other cases in this series showed persistent hepatitis with considerable scar ring, not amounting to cirrhosis, and in 4 others there were either portal or intralobular scars of varying sizes without distortion of the lobular architecture. In one case no sig nificant pathological lesions were found in the liver. As already stated, one of the cases with postnecrotic broad-band type of cirrho- Fig. 8.--A, close-up view of the gross external and o, cut surfaces of the specimen of liver whose microscopic features are shown in Figures 6 and 7. The extreme variation in the size of the regenerat ing nodules and depressed scan are characteristic of postnecrotic cirrhosis (Gall), postcollapse cir rhosis (Steiner). sis also had an associated hepatocellular car cinoma. Picture in Type III.--The pathological picture in this type was totally different from that in Types I and II. Out of 16 cases, there Fig. 9.--Postnecrotic cirrhosis showing a broad band of collapse from a Type I case which showed a mixture of broad and fine banda. Hematoxylin and eosin; reduced about 25% from mag, X 357 Fig. 10.--Same specimen as in Figure 9 showing another area with fine bands. Broad and fine bands were equally prominent in this case. Gomori's reticulin; reduced about 25% from mag. X 35. 12T Ramolinatuwumi el al. SM ARCHIVES OF INTERNAL MEDICINE Fig. U.--Liver biopsy from a Type III case showing porta] scars, tendency to pseudolobulation but no cirrhosis. Goroori's lettculin; reduced about 25% Iran mag. X 35. Fig. 12.--Liver biopsy from a Type III case show ing focal necrosis in the lobule with mononuclear sateUitosis of individual liver cells. Hematoxylin and eoein; reduced about 25% from mag. X 473. was not a single case that showed unequivo cal evidence of cirrhosis (Table). The ma jority (11 out of 16 cases) showed varying degrees of portal and intralobular scarring, in 2 of which it was quite marked but not sufficient enough to distort the liver as in cirrhosis (Pig. 11). The remaining 5 cases showed minimal nonspecific changes in the form of mild inflammatory infiltrates in the lobule and focal degenerative changes in the liver parenchyma (Fig. 12). The general picture in this type can be summarized as one of mild nonspecific prolonged injury to the liver, the reaction of the liver being one of focal degeneration, focal inflammatory-cell collections, mild endothelial reaction, and varying degrees of portal and intralobular scarring. Splenectomy was done in 3 cases, and the histological picture in the spleen resembled so-called early fibrocongestive splenic en largement. There was no evidence of infec tion with malaria or kala-azar. Comment The description given here relates to the clinical material seen in North India and diagnosed on clinical grounds as cirrhosis of the liver. These cases have ascites, spleno megaly, prominent abdominal veins, dilated collateral vascular channels between the por tal and systemic circulation, and elevated portal pressures. And yet from the point of view of their evolution and natural history, they seem to fall into 3 clinical types. The situation is somewhat reminiscent of "chronic nephritis" of earlier times and nephrotic syndrome of more recent times. Of the 3 types, Type III stands out clearly as a distinct entity, and we would like to em phasize its existence and its natural history. It commences with splenomegaly which per sists and increases throughout the course of the disease. It runs an indolent course ex tending over several years, developing in the course of time various manifestations of portal hypertension. The liver shows non specific changes during the greater part of the illness with more or less fibrous scarring, but there is no evidence that cirrhosis eventually develops with lobular distortion and nodular regeneration. These are the cases that have been labeled in the past as "tropical splenomegaly," Band's syndrome, and some have masquer aded as cirrhosis. A malarial etiology has been advocated for such cases.* Some of our cases do give a past history of malaria. How ever, histological examination of the liver and spleen in these does not show evidence of malarial parasites or pigment. Furthermore, the interruption of transmission of malaria through antimalarial operations has been continuously in progress in this part of the country for over 10 years, and, under these conditions, it is unlikely that the splenomegaly is attributable to malarial infection. The fact that the bulk of Type III cases develop undoubted portal hypertension in the Vol. 110, Sept., 1962 m SQQWG'vZ CIRRHOSIS OF LIVER--INDIA 357 course of the disease with mild nonspecific of icteric and nonicteric varieties, respec reactive changes in the liver calls for com tively, must be considered. The clinical and ment. In the Jibsence of obstruction in the histological features of Type I cates are cer extrahcpalic |x>rlal IkiI and of established tainly compatible with the known sequences cirrhotic changes in the liver, the mechanism of unresolved viral hepatitis progressing to of portal hypertension is difficult to explain. cirrhosis. But as the disease progresses, histo Similar cases have been reported from out logical features become more and more non side India,*'1* and it seems probable that specific, and we have no way of knowing that long-continued splenomegaly may in its wake the Type I and Type II pictures are not the bring about circulatory changes in the portal sequelae of some other form of "toxic" bed, leading to portal hypertension. hepatitis. There are several overlapping and distin guishing features between Type I and Type II cases, in the manner of Ellis's nephritic types. In their mode of onset, presence or absence of jaundice and severity of ascites, the 2 types are fairly distinct. In their pace of progression, therapeutic response, and pathological alterations in the liver, there is a considerable overlap and the distinction be comes blurred. Anatomical evidence of cir rhosis was present in a majority of the cases of both types, and postnecrotic cirrhosis was the commonest variety in both. On compar ing the 2 series, however, certain differences become apparent (Table). While all but one case of Type I series showed anatomical cirrhosis, it was present in just over one-half of the rases of Ty|>c II series. Among these, the postnecrotic variety was more common in Type I than in Tyjrc II. Nearly one-half of Type II cases did not show cirrhosis but only Our data in the Delhi area suggest that the cirrhosis here is predominantly of the postnecrotic variety. We have no evidence that malnutrition plays a primary role. Fatty change was conspicuous by its absence at any stage in any of the 3 types. The patients were obviously not malnourished. In a series of 300 medicolegal autopsies in this area, 15 cases belonging to the destitute class were found to have severe and extensive fatty change in the liver, but none of these showed excessive fibrosis or cirrhosis.1* , In the cases presented here, alcohol can be eliminated as an etiological factor. Siderosis is rare. Malaria has not been a health problem in this area for well over 10 years. Bilharziasis does not occur. The significance of native medicines, indigenous herbs, toxins from vegetable sources, and metallic intoxication from the use of metal utensils is unknown. varying degrees of scarring; there was only one case of this nature in Type I series. These differences are of course relative and cannot be applied in the analysis of individual cases. They, however, indicate a difference either in the injurious agent or in its dose or in tissue reaction to injury. It is hardly likely that the same etiological factor is at work in all the 3 types. Type III Summary The clinical features and pathological anat omy of a consecutive series of 46 cases with established signs of portal hypertension and clinically diagnosed as cirrhosis of the liver form the subject matter of this study. Cases showing extrahepatic obstruction on splenoportal venography were excluded. must in any case be considered distinctive. Of The clinical material was not a homogene the hepatotoxic agents, the hepatitis viruses ous entity. From a study of the mode of onset have been receiving much attention in recent and clinical picture, the cases could be classi years. Both postnecrotic 11 and portal cirrho fied into 3 clinical types. sis '* have been reported as following viral hepatitis. It has even tieen stated that a nonicteric altack of he|uililis can progress to cir rhosis.1* The possibility that the Type I and Type II cases are the result of viral hepatitis The clinical and pathological features of each ly|ie are presented and discussed, Type 111 emerges us a unique and distinct group in which splenomegaly is the initial and domi nating feature throughout the illness, while 129 Ramalingastvami et al. archives of internal medicine SSI the liver shows mild, nonspecific changes with no evidence of progression to cirrhosis. Type I and Type II cases show progressive 5. Smetana, H. P.: Histogenesis of Coarse Nod ular Grrhoais, Lab. Invest 5:175-193, 1956. 6. Steiner, P. E.: Precision .in the Classification of Cirrhosis of the Liver, Amer. J. Path. 37:21-47, liver changes with cirrhosis in the majority. There are overlapping as well as distinguish ing features between these 2 types. Cirrhosis, when present, was most com monly of the postnecrotic variety; it was un~ classifiable in some biopsies; portal cirrhosis was rare. The features of each type and probable 1960. 7. Gall, E. A.: Posthepatitic, Postnecrotic, and Nutritional Cirrhosis: A Pathologic Analysis, Amer. J. Path. 36:241-271, 1960. 8. Chaudhuri, R. N-; Saha, T. K.; Basu, S. P. ; Mukherji, A. M., and Rai Chaudhury, M. N.: Chronic Splenomegaly, Indian J. Med. Res. 44:305- 323, 1956. 9. Leather, H. M.: Portal Hypertension and Gross Splenomegaly in Uganda, Brit Med. J. 1 IS etiological factors have been discussed. V. Ramatingaswaml, M.D., Department of Pa thology, All-India Institute of Medical Sciences, New Delhi 16, India. IS, 1961. 10. Tisdale, W. A.; Klatskm, G., and Glenn, W. W. L.: Portal Hypertension and Bleeding Esophageal Varices: Their Occurrence in the Ab sence of Both Intrahepatic and Extrahepatic Ob struction of the Portal Vein, New Engl. J. Med. REFERENCES 1. Menon, T. B., and Annamalai, D. R.: The Incidence of Hepatic Cirrhosis in South India, Indian }. Med. Res. 22:827-835, 1935. 2. Aikat, B. K., and Sengupta, K. P.; Morpho genesis of Cirrhosis of Liver in Adults: The Prob able Mode of Evolution, Indian J. Path. Bact. 261:209-218, 1959. 11. MacDonald, R. A., and Mallory, G. K.: The Natural History of Postnecrotic Cirrhosis: A Study of 221 Autopsy Cases, Amer. J. Med. 24: 334-357, 1958. 12. Baggenstoss, A. H.: Pathological Aspects of the Late Stages of ViraJ Hepatitis, in Hepatitis Frontiers, London, J. 8c A. Churchill, Ltd., 1958, 1:119-132,1958. 3. Liver Diseases Sub-Committee of the Indian Council of Medical Research: Infantile Cirrhosis of the Liver in India, Indian J. Med. Res. 43:723- 750,1955. 4. Armed Forces Institute of Pathology, Manual of Staining Procedures, 1957. p. 113. 13. Klatskin, G.; Subacute Hepatic Necrosis and Postnecrotic Cirrhosis Due to Anicteric Infections with the Hepatitis Virus, Amer. J. Med. 25:333- 358, 1958. 14. Dutta, B. N., and Ramalingaswami, V.: Un published observations. 130 359 Histoplasma Endocarditis Report on a Patient Treated with Amphotericin B, with Review oj Amphotericin B Therapy tor Hijtoplasmojis ROBERT L. PALMER, M.D.; JOSEPH E. GERAC1. M.D., AND BETTY J. THOMAS. M.D., ROCHESTER. MINN. The primary purposes of this paper are: pneumonic infiltrates may be seen. Rarely (1) to report a case of progressive, fatal the disease may progress with dissemination, histoplasmosis treated with amphotericin B fever, lymphadenopathy, and hepatospleno in which the predominant lesion was that of megaly. The chest roentgenogram may not vegetative endocarditis, (2) to discuss briefly ^ show any abnormality during this stage. A the clinical entity of histoplasmosis with par spontaneous remission of the disease after a ticular reference to endocardial involvement, duration of 6 to 8 weeks may occur, but the and (3) to review amphotericin B therapy disease may develop into the second type, for histoplasmosis and Histoplasma endo that of fatal progressive disseminated histo carditis. One other case of Histoplasma endo plasmosis. carditis found at the Mayo Clinic was that This second type of histoplasmosis is char reported by Broders and associates in 1943.* acterized either by slow progressive disease lasting months to years or by a fulminating Clinical Features of Histoplasmosis Histoplasmosis infects various organ sys tems, but particularly the respiratory and gastrointestinal tracts. Lesions of the throat and nasopharynx are often present. Produc tive cough, loss of weight, anemia, leuko penia, sweats, fatigue, chest pain, fever, and chills were listed as the chief clinical mani festations by Vivian and associates reporting on 20 cases seen at the Mayo Clinic.1* Hepatosplenomegaly was a frequent finding. The most common type of the disease is a benign, self-limiting, and apparently asymp rapidly fatal disease with wide dissemina tion. Involvement of the skin and mucous membrane is frequent. It is often a con comitant finding among people suffering from tuberculosis, Hodgkin's disease, chronic leukemia, or similar disease of the reticulo endothelial system. The third type of the disease is chronic progressive pulmonary cavitary histoplasmo sis. This type closely resembles reinfection tuberculosis and is a problem of extreme importance in the country's tuberculosis sanatoria.11 The disease may be sympto matically mild and is characterized by exacer tomatic pulmonary infection with excellent bations and remissions. Hemoptysis is rare. prognosis. Three other types of the disease Roentgenograms may show apical fibrotic in may be found. The first, acute pulmonary filtration progressing to cavitation. Calcified nonfatal histoplasmosis, is characterized by hilar areas are frequently found. Relapses an influenza-like syndrome affecting children are common. Progressive cavitation of the and adults alike. The x-ray findings may range from that of a small single nodule in the lung with hilar adenopathy to that of a large number of miliary lesions. Broncho- lungs usually causes a fatal termination of the disease, with symptoms of increasing respiratory distress, unless treated surgically and with amphotericin B. Submitted for publication March 28, 1962; ac cepted April 5. Fellow in Medicine (Dr. Palmer) ; Section of Medicine (Dr. Geraci); Fellow in Pathology (Dr. Thomas) ; Mayo Clinic and Mayo Foundation. m Report of Case A 50-year-ol.l while male bartender first entered tlie Mayo Clinic on Oct. 25, 1956. Diagnoect of duodenal ulcer, inactive rheumatic heart disease with mitral stenosis, and mild congestive heart failure