Pathologic and Some Diagnostic Features of Histoplasmosis in Patients Entering a Missouri Hospital: Final Report

SUMMARY A study was made of 125 cases of histoplasmosis, at one time or another thought to be histoplasmosis. The preponderant majority of cases were white. Of the 32 with round lesions, 18 were in men with an average age of 45.3 years; 14 were in women with an average age of 46.4 years. Of those with clinical disease, there were 24 men with an average age of 52 years and three women with an average age of 45.0 years. The significant feature is the preponderance of males in the clinically active cases. Most were farmers, many gave a history of raising chickens and some of cleaning out chicken coops. Of the cases with concomitant tuberculosis, there were 11 men and two women with average ages of 44.4 years and 25.5 years, respectively. In the bronchiectasis cases there was a reversal of the sex incidence with nine women and three men and average ages of 32.0 women and 43.0 men, respectively. Women appear to be more prone to develop bronchiectasis with a ratio of nine to three, but men tend to develop active histoplasmosis with a ratio of 40 to 5 with round lesions about equal (18 to 14). Farmers seems to develop disease when they are under greatest pressure, around 50 years of age. The 125 cases are broken down as follows: 123 had surgical resections; one was a culture-positive pleural fluid and one was a culture-positive scalene lymph node with all else negative. There were 11 postmortem examinations. There were 105 cases judged to be histoplasmosis, but in the two cases mentioned above, there was not enough evidence to establish an absolute diagnosis of clinical disease in spite of positive cultures. There were nine other cases where yeast bodies were not found; yet all else pointed to histoplasmosis. That left 94 cases (89.5 per cent) positive on Gomoristain which, taken with two cases having only a positive culture gives a total of 96 cases in which evidence existed of a presumptive or an absolute diagnosis of histoplasmosis. By following the cases for long periods of time especially to resection and postmortem, it increased the percentage of both the Gomori stain and cultures. Of 32 cases of round or "coin" lesions, only two had weakly positive complement fixation reactions, where no cultures or animals were positive and where only the Gomori stain revealed the presence of yeast bodies. There were 27 clinically active cases with the Gomori stain showing the presence of yeast bodies; cultures were found positive in only 64 per cent of cases cultured and the complement fixation and skin reactions much less in effective value. Of 43 clinically active cases, 13 (30.2 per cent) were associated at one time or another with tuberculosis. Of all the cases in which yeast bodies were found, the percentage was 13.5 per cent of acid-fast bacilli. The tuberculosis usually appears first in clinical activity and the histoplasmosis follows or is detected after drugs have cleared up the tuberculosis. This combination is one of the greatest problems in both the diagnosis and treatment of histoplasmosis. Twelve cases of bronchiectasis had associated yeast bodies in an old enlarged and mostly calcified lymph node indicating that there is perhaps a causal relation between the histoplasmosis and the bronchiectasis in certain cases. There were found many other concomitant diseases with histoplasmosis playing either a minor or dominant role at some stage of the process. The most absolute of all methods—finding and growing the organisms is still in what might be called its experimental stage. In encapsulated lesions, even those with active and progressive disease, the organisms were neither grown nor recovered on mouse inoculation after repeated attempts. Of 25 active lesions, with complete records 16 (64 per cent) produced growth; 36.7 per cent with concomitant tuberculosis; and 8.3 per cent with concomitant bronchiectasis. There seem to be phases of the organisms' development in which they cannot be stimulated to growth activity by our present methods. Even from open lesions many were not obtained until a number of trials had been made. Of course, some organisms may not be living. On the other hand, certain lesions yielded growths easily and almost at will. The skin reactions are most specific and indicate the presence of H. capsulatum or the residual effects of an old infection much in the same manner as tuberculin does in tuberculosis. The size of the reaction is important. Many times, in fact most of the time, the tuberculin and histoplasmin reaction are present together—at times, of almost equal intensity. Under these conditions, the problem becomes complex, especially if both reactions are strong. To tell which is predominant, and whether one is quiescent while the other is active, requires further studies to find the respective organisms in lesions, on cultures, or through animal inoculations. There were four cases in which the skin reaction was very strong on the histoplasmin with a negative tuberculin reaction, which pointed clearly to histoplasmosis. All other tests confirmed these findings. Equally significant were four cases with strongly positive tuberculin reactions which helped to clear up the doubts; ultimately the cases were found to be tuberculosis. In a final word it may be said that the skin reactions are specific and useful but have limitations that must be understood. The pathology may be briefly stated as a granulomatous process usually entering by way of the respiratory tract, producing a primary complex similar to tuberculosis, and also becoming systemic, localizing in many organs of the body particularly in the adrenals and spleen. In the lung there are at first nodules and or infiltrates of macrophages, lymphocytes, monocytes, epithelioid giant cells, etc. becoming caseous, forming a coarse granular pus mostly free of polymorphs and on extension erupting into a bronchus resulting in cavity formation. The cavities usually become sloughed out into a slick walled fibrotic membrane that becomes thicker with age. Sometimes the walls are breached in places and frequently the fibroblasts form in a vertical posture in what has been called a "picket fence" formation. Sometimes there are areas of varying sizes of non-caseating granulomatous elements resembling sarcoidosis. It is usually more benign than tuberculosis, but not infrequently becomes a malignant, generalized, and fatal disease. The round lesion is a ball-like mass that forms in onion-ring appearance with rings of fibrosis alternating with calcification. There is a tough callus on the pleural surface but within there may be caseous foci in which yeast bodies may be found. Lymph nodes generally become larger than in tuberculosis, forming many times a mulberry appearance. In spite of the many shades of pathologic change in histoplasmosis, there is nothing specific that can be considered diagnostic any more than that of an acute, subacute, and chronic granulomatous disease. The early diagnosis still must rely on the clinician, roentgenologist, and laboratory technicians. Since there is so much mimicry by histoplasmosis, it leaves the burden of effort on growing the organisms on culture media, getting a strongly positive complement fixation, a large skin reaction, or on rare occasions—a Gomori stain on sputum. There have been only five cases where the organisms have been sufficiently abundant in the sputum to find by the Gomori stain. Finally, it might be said that there is no hard and fast rule of diagnosis. From the very beginning, every case should be studied meticulously, and every test that may throw some light upon the diagnosis should be performed and repeated if necessary. Somewhere along the line, some test may indicate, either presumptively or absolutely, the presence of the disease. There certainly is no short road to salvation. Let it be stated definitely that the last word has not yet been said regarding the many aspects of this protean disease. We are really only on the threshold of its conquest.