Lymphogranuloma Venereum.

AUGUST 1941 627 LYMPHOGRANULOMA VENEREUM* ARTHURW. GRACE Professor of Dermatology and Syphilology, Long Island College of Medicine is a widespread, contagious, venereal disease of human beings caused by a minute organism. The infective agent enters the body through the skin of the external genitalia without, however, always producing a demonstrable lesion at the portal of It also enter by way of the mucosa of the anal or rectal entry. may canals, and, much less frequently, by extragenital routes. The virus multiplies readily in the lymph nodes draining the affected areas, and probably, also, in the anal and rectal mucosae. It is transmissible to certain laboratory animals. The lesions of lymphogranuloma venereum, are inflammatory in nature, subacute or chronic in quality of reaction, and are often marked by the development of multiple small foci of suppuration. Mortality is low. The disease is systemic with local manifestations appearing chiefly in the anorectal, inguinal and genital regions. It is customary, and convenient, to speak of the disease pictures in these areas as the anorectal, inguinal and genital varieties of lymphogranuloma venereum. There is, however, no evidence of the existence of any difference, other than regional, between the disease in the various sites. Diagnosis of lymphogranuloma venereum. is made, at present, by means of a skin test of a high degree of specificity and sensitivity which has been named after its discoverer, Wilhelm FreP Treatment of the disease with certain members of the sulfonamide series of drugs, notably sulfanilamide and sulfathiazole, has been very successful. The use of these drugs in the treatment of lymphogranuloma venereum has been of the highest value in that, prior to their introduction, there was no adequate remedy for the disease. HISTORY The inguinal variety of lymphogranuloma was the first of the manifestations of this disease to be suspected of being a separate clinical YMPHOGRANULOMAvenereum From the Long Island College Hospital and the Department of Dermatology and Syphilology, Long Island College of Medicine, and The New York Hospital and Department of Medicine, Cornell University Medical College. Aided by a grant from the United States Public Health Service. Read October 24, 1940 in the Graduate Fortnight of The -New York Academy of Medicine. 628 THE BULLETIN entity. John Hunter described, in 1786, a condition in which buboes developed without apparent cause, and were unaffected by mercury. Credit, however, for the earliest definite description belongs to William Wallace who under the title of "indolent primary syphilitic bubo," gave an accurate description of what would now be regarded as a chronic suppurative case of the inguinal. variety of the disease. H. G. KI OtZ4 first called attention to the disease in this country. He reported having seen, in New York City, between the years i879 and i 889, over 120 cases of a clinical entity which can hardly have been other than the inguinal variety of lymphogranuloma. Durand, Nicolas and Favre, in 1913, gave the best clinical and pathological study hitherto published of the inguinal. disease. They believed, erroneously, that the histological picture of lymphogranuloma resembled that of Hodgkin's disease, or lymphogranulomatosis, and proposed the term lymphogranuloma inguinale for the disease. The clinical and pathological manifestations of lymphogranuloma, however, are not peculiar to the disease and accurate identification was not possible until the introduction of the Frei test in 1925. Study and knowledge of the disease have progressed rapidly following Frei's important discovery. In 1928, using the recently developed skin test, Frei and Koppel' showed that a positive reaction was given by persons presenting inflammatory stricture of the rectum. Experimental proof of the lymphogranulomatous etiology of this condition was established in I932 by Ravaut, Levaditi, Lambling and Cachera and Laederich, Levaditi, Mamou and Beauchesne" who isolated a strain of the virus of lymphogranuloma venereum from inflamed rectal tissue. Mocquot, Levaditi and Reinie',9 in 1935, isolated from an inflammatoxy condition of the colon a strain of the virus with which Levaditi, Mollaret and Reinie',11 in the same year, produced the pathological changes characteristic of lymphogranuloma in the rectum of chimpanzees by direct inoculation into the mucosa. The etiological agent of lymphogranuloma venereum was shown to be a virus in I93o by Hellerstr6m and Wasse'n" who inoculated Mac-acus rhems and Macacus cynoino1gus monkeys intracerebrally with suspensions of infected human lymph node. Two years later, Levaditi, Ravaut and Schoen reported the transmission of the disease to mice by the intracerebral route. The mouse has since proved to be a very valuable animal in the study of lymphogranuloma. Strains of the virus have 2 3 5 7 12 Lynph-ogranuloma Venere-um 62 9 TABLE I NEW CASES OF LYMPHOGRANULOMA VENEREUM AND TOTAL NEW IN- AND OUT-PATIENT ADMISSIONS, NEW YORK HOSPITAL, 193440 Year No. of new of L.V. cases Total No. of admissions new Cases of L.V. per 10,000 admissions 1934 26 43419 6.0 1935 23 44123 5.2 1936 31 45977 6.7 1937 35 44484 7.9 1938 35 43411 8.1 1939 28 41895 6.7 1940 34 31447 10.8 (9 months) been maintained by successive mouse passage over a period of years and the infected brain has provided useful material, both as' a source of virus for experimental purposes and for the performance of the Frei test. The etiological agent of lymphogranuloma was undoubtedly first seen by Gay Prieto,13 in 1927 in the form of small cytoplasmic granules in material obtained from infected inguinal nodes. The granules were one micron or less in diameter and appeared frequently in small aggregations. They were also described, and figured, by Findlay 14 who suggested the possibility that they represented the virus. Granules, however, appear sparsely in preparations of animal and human tissue, a fact which made it impossible until recently to procure active suspensions of the virus free from a large proportion of inert material. The work of Rake" and his colleagues, who employed the yolk-sac technique of Cox," has now afforded a means of obtaining rich suspensions of granules. Successive material in tissue culture was observed passage of lymphogranulomatous, 17 by Sanders to increase the potency of the virus as high as one thousand times. STATISTICS OF THEFREQUENCY OF OCCURRENCE OF LymPHOGRANULOMA VENEREUM Lymphogranuloma has been studied at the New York Hospital for the past eight years, for most of the. time in a clinic specially devoted to 630 THE BULLETIN TABLE I I DISTRIBUTION, BY VARIETIES, OF 242 CLINICAL MANIFESTATIONS OF LYMPHOGRANULOMA VENEREUM IN 218 INDIVIDUALS Variety Anorectal Inguinal G enital ........................ .......................... ........................... Asymptomatic Miscellaneous* Includes masses. No (...truncated)