Granuloma venereum and lymphopathia venereum

GRANULOMA JARRATT

VENEREUM AND LYMPHOPATHIA VENEREUM* P. ROBERTSON, M.D. AND LEE SHARP, M.D. Resident UroIogist, Hillman HospitaI

Associate Urologist, HiIIman and St. Vincent’s Hospitals BIRMINGHAM,

T is unfortunate that the diseases commonIy known as granuIoma inguinaIe and IymphogranuIoma inguinaIe shouId have names so simiIar and confusing yet be so dissimiIar cIinicaIIy and pathoIogicaIIy. In neither instance is the name descriptive of the cIinica1 and pathoIogica1 picture, Ieading one to beIieve that the different phases of the same disease are being described or that different terms are being appIied to the same condition. The term “granuIoma inguinaIe” conveys the impression that the inguinaIe region is covered with granuIating tissue. In our experience the primary Iesion, with two exceptions, has been Iocated on the externa1 genitaIia and has remained there in 80 per cent of the cases. In the remaining 20 per cent, the inguina1 region has been involved usuaIIy as a resuIt of a direct extension of the disease from the externa1 genitaIia (Fig. I). In the Iatter cases the perinea1 and ana regions were invoIved. We fee1 that the cases we have treated were venerea1 in origin, accounting for the predominance of the Iesions on the externa1 genitaIia. We wouId Iike to suggest the term “granuIoma venereum” for “granuIoma inguinaIe ” as it is Iess confusing and more descriptive of the pathoIogy present. The term “ IymphogranuIoma inguinaIe” is aIso confusing, and not descriptive of the clinica and pathoIogica1 picture. From it one gains the impression that the inguina1 Iymph nodes have been converted into granuIating tissue. This is incorrect and misreading. In the maIe and femaIe the primary Iesion occurs on the externa1 genitaIia. In the secondary stage of the

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disease in the maIe, the inguina1 lymph nodes are invoIved, but frequentIy do not progress to the stage of suppuration. In the femaIe, due to the Iocation of the primary Iesion the anorecta1 gIands which Iie between the vagina and rectum are usuaIIy involved and onIy occasionaIIy do those in the inguina1 region become infected. In the femaIe the Iymph drainage from the perineum, the posterior portion of the externa genitalia and vagina is toward the recta1 and not the inguina1 region. We fee1 that the term “ Iymphopathia venereum,“’ as has been previousIy suggested, shouId be substituted for the term “IymphogranuIoma inguinaIe.” With these changes the names wiI1 become Iess confusing and the diseases better understood. GRANULOMA

VENEREUM

GranuIoma venereum was considered originaIIy a tropica disease and fifteen to twenty years ago cases were recognized in southern seaport towns. In Igzo Symmer? reported the first case from BeIIevue HospitaI. During the past few years added interest and study of the disease have shown it to be endemic and becoming generaIized geographicaIIy over the United States. It flourishes in the strata of society where soap and water, and straight Iaced moraIs are not considered a necessity of Iife. The unrest, the breaking of homes, and the Iarge ffoating popuIation that has r&uIted from the depression wiI1 show an increased geographic spread and probabIy an actua1 increase in the disease.

* From the UroIogical Service, HiIIman HospitaI, Birmingham,AIa. 322

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In Birmingham the disease is endemic; none of the cases had Iived in the tropics, few of them had ever been to seaport towns

FIG. I. Granuloma venereum of three years duration; the initia1 Iesion is at the base of the Ieft side of the penis. Note how the Iesion roIIs over the healthy skin, the absence of pigment in the healed suprapubic area, and the Iesion extending. down the Ieft side of the scrotum to the perineum. This patient had received irregular treatment with tartar emetic.

and many of the cases seen had never been outside the immediate vicinity of Birmingham. One case was treated who, while infected with the disease, had traveled over a Iarge portion of the United States. He admitted frequent promiscuous intercourse during this time. It is this type of case which makes it possibIe for the disease to appear in any city or hamlet regardIess of its geographic Iocation. ETIOLOGY

Most authorities consider the incubation period of granuloma venereum to be twenty to thirty days. We beIieve the disease to be venereal in origin. All of our cases were in adults. With two exceptions the initia1 Iesion occurred on the externa1 genitaha. The disease was found aImost excIusiveIy in Negroes who admitted frequent promiscuous intercourse

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and empIoyed no means of prophyIaxis. Extensive Iesions were observed on the face in 2 instances. In the first case the lip and

FIG. 2. Granuloma venereum of five years duration, involving the penis, scrotum and region. extending into the suprapubic IrreguIar treatment with tartar emetic was received.

cheek were invoIved, the infection probabIy contracted through abnorma1 sexua1 practice. TubercuIous sinuses of the maxiIIary region were secondariIy infected from the externa1 genitaIia in the second case. There is some dispute as to the causative organism of granuIoma venereum. The Donovan body, a gram negative, nonmotiIe, encapsulated baciIIus, is generaIIy recognized as being the causative organism and was demonstrated in about 20 per cent of our cases. FrequentIy they cannot be found in cases which respond to the therapeutic test with fuadin or tartar emetic. In the others the diagnosis was confirmed by the rapid and compiete heahng when fuadin was administered. PATHOLOGY

GranuIoma venereum is a chronic disease which destroys the skin and subcutaneous tissue, spreads sIowIy by continuity and contact, but does not invoIve the Iymph

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nodes and deeper structures. Without treatment it may spread from the externa1 genitaIia to the thighs and perineum. In the cases where the inguina1 regions were involved it frequentIy had spread by direct extension (Fig. I). In our experience the inguina1 region has not been an area especiaIIy susceptibIe to the disease. Due to the Iow mentaIity of our patients and the frequency with which they practiced promiscuous intercourse we were unabIe to coIIect any reIiabIe data concerning the incubation period and character of the primary lesion. The disease begins probabIy as a papuIe or pustuIe that breaks into an open uIcer which has a raw, beefy-red, sIightIy raised appearance and faiIs to hea under IocaI treatment. Many smaI1 isIands of epitheliurn can be seen on the raw areas ofthe Iarger Iesions if examined with a magnifying Iens, becoming very prominent when treatment is instituted. The circumference of the Iesion tends to roI1 over the heaIthy skin (Fig. I). The Iesion extends rapidIy when moist surfaces come into intimate contact with one another (Figs. 2 and 3). There is a characteristic fou1, sour, offensive odor and a watery discharge from the Iarger Iesions is aImost diagnostic. SYMPTOMS

The Iesion is reIativeIy painIess but there is an itching and burning of the area, usuaIIy reIieved in twenty-four to fortyeight hours foIIowing the first dose of fuadin. The Iesions that extend into the inguina1, perinea1 and recta1 regions are, at times, painful and incapacitating. In 4 cases the Iesions were so extensive that the patients were bedridden. There is a sIight systemic reaction in advanced cases accompanied by a Iow grade septic temperature, a moderate degree of anemia, loss of weight, maIaise and genera1 weakness. In 2 extensive cases invoIving the penis, scrotum, perinea1 and inguinal regions, the scrotum was enIarged to severa times its norma size. In these cases no vestige of the

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penis couId be discovered, the urine seeming to be voided from the scrotum. Both patients were positive that the penis had not been destroyed but couId not expIain A pseudoeIephantiasis its disappearance. of the scrotum had developed from the proionged uIceration and _ poor Iymph drainage. The indurated scrotum and area around the base of the penis became hypertrophied whiIe the penis remained stationary. In this way the penis had invaginated into the scrotum. FolIowing treatment the penis in each instance could be palpated in the scrotum, in the first case being returned to its norma site by a pIastic operation. The other patient died of peIIagra before the treatment was compIeted. In doing pIastic operations it must be remembered that the scar tissue which repIaces the normal tissue in heaIing is very non-eIastic and avascular. The dense, pedicIe of the skin ffap must be Iarger than that required by norma skin if sIoughing is to be prevented. DIAGNOSIS

The diagnosis of granuIoma venereum is made from the history, the appearance of the Iesion and its failure to hea under IocaI treatment. It is confirmed by the finding of Donovan bodies or the rapid heaIing of the lesion under fuadin or tartar emetic therapy. We were abIe to demonstrate the Donovan bodies in onIy about 20 per cent of our cases, in the remaining 80 per cent the diagnosis was confirmed by the rapid heaIing that foIIowed the administration of fuadin. AI1 Iesions which resembIe those of granuIoma venereum shouId be examined for Donovan bodies, found in scrapings taken from the skin edges of a biopsy specimen that incIudes the epitheIium and raw surface. The specimen is stained with Wright’s or Giemsa’s stain and the Donovan bodies are found in the epithelial ceIIs. The Iesions may be confused with carcinoma, tubercuIosis of the skin, chancroid, syphiIis, mycotic uIcers and chronic non-

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specific ulcers. Scrapings, a biopsy and a Wassermann shouId be taken on a11 these cases. Chancroid is easiIy eIiminated by the

FIG. 3. Same case as Figure 2. View of the under side of the scrotum and perineum. Note absence of pigment in the healed area on the posterior side of the scrotum.

history, appearance of the I&ion and the specific skin reaction of Ito-Reenstierna. It is painfu1, spreads rapidIy, undermines the skin edges and is destructive of the skin and deeper structures. MaIignancy is eIiminated by the history, physica findings and biopsy. It is to be remembered that any combination of these infections may occur in the same individual. Any Iesion that resembIes granuIoma venereum, even if negative for Donovan bodies, shouId be given a tria1 with fuadin, provided a11 other causes have been eIiminated. If it is granuIoma venereum a definite and distinct improvement wiI1 be noted in seven to ten days. TREATMENT

In the treatment of granuIoma venereum, fuadin has given resuIts far superior to those obtained with tartar emetic and evidence of toxicity has not been noticed. When empIoyed the Iesions heaIed 40 per cent quicker than when tartar emetic was used. AI1 Iesions have heaIed rapidIy and compIeteIy and relapses have been reduced to a minimum. The intramuscuIar injection of fuadin simplifies its administration.

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The disadvantages of tartar emetic are its toxicity, reIapses are frequent and compIete heaIing at times does not occur. It can

FIG. 4. Bilateral lymphopathia venereum. Left side shows glistening purpIe color that deveIops when gfands become attached to the skin. Frei test was positive.

onIy be administered by the intravenous route. The Iatter probabIy increases its toxicity and decreases its efficiency because of the rapid absorbtion and eIimination. When tartar emetic is employed in extensive Iesions, they often hea unti1 a smaI1 area remains which refuses to hea1. Since empIoying fuadin this has not occurred. In the Iiterature accompanying fuadin and aIso in severa articIes concerning its use, is outIined what is described as a treatment. This consists of giving about 40 C.C. of the drug over a period of sixteen to eighteen days. This is unfortunate, because the treatment of the disease must be individuaIized. It is IogicaI that it wiI1 require more of the drug to heal an uIcer six inches square than one an inch square. The drug shouId be administered unti1 heaiing is compIete regardless of the amount used unIess toxic symptoms deveIop. Fuadin is given deep into the gIutea1 muscIes three times a week, the first dose being I .s c.c., the second 3 CL., and the third 5 c.c., which is then administered two or three times a week depending upon the size of the Iesion and the rapidity with which it heals. FoIIowing heaIing the drug is given once a week and then every fourteen days for severa weeks to prevent reIapse. With the use of fuadin in this way

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a11 lesions have heaIed and reIapses have not occurred. Twenty-four to forty-eight hours foIlowing the first dose of fuadin the itching and burning wiI1 have begun to disappear. In seven to ten days the raw surface wiI1 have assumed a heaIthy appearance and the watery discharge decreased, or a mistake in diagnosis has been made. The pinpoint areas of epitheIium which are present in the Iarger Iesions wiI1 be noted to be increasing in size and the epitheIium to be rapidIy cIosing in from the edges. These areas of epithelium act as pinch grafts and greatIy reduce the heaIing time. Skin grafting couId probabIy be empIoyed but heaIing has aIways been so rapid that it has not been necessary. The use of warm potassium permanganate (I :8000) soaks wiI1 reduce the offensive odor, make the patient more comfortabIe and does not seem to interfere with heaIing. The new skin is aIways white, the absence of pigment making this very noticeabIe in the Negro (Fig. 3). LYMPHOPATHIA

VENEREUM

Lymphopathia venereum, is an acute, subacute or chronic adenitis, of venerea1 origin (Fig. 4). It was originaIIy considered a tropica or subtropica disease, but is now known to be endemic throughout most of the civiIized worId. ApproximateIy three-quarters of a century ago the disease was recognized and described then as tropica or cIimatic bubo. EIephantiasis vuIva, pseudoeIephantiasis of the penis and scrotum, Iupus vuIva, infIammatory stricture of the rectum, nonvenerea1 bubo, strumous bubo, non-specific bubo, rectal stricture of unknown origin, genitoanorecta1 syndrome, maIignant bubo, etc., are now known to be identica1 with or different phases of Iymphopathia venereum. ETIOLOGY

The causative organism of Iymphopathia venereum is accepted as being a fiIterabIe

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virus. It is a contagious disease acquired veneraIIy, that originaIIy occurred in tropica1 and subtropical countries. It can be transmitted to severa of the lower animaIs by way of subdura1 injections and produces in them an encephaIitis. Levaditi, Marie and Lepine,3 after passing the disease severa times through apes, have successfuIIy transmitted it to paraIytic patients by preputia1 inocuIations. The Iymph node invoIvement in these cases corresponded with the typica case as seen in man. PATHOLOGY

Lymphopathia venereum is a disease of the Iymph channels and nodes. In the advanced case the nodes are firmIy bound together and adherent to the skin, microscopicahy showing muItipIe white areas that are abscesses. The histoIogica1 picture has been recorded in detai1 by NicoIas and Favie, and HeIIerstrom. It is not diagnostic and is easiIy confused with tubercuIosis, syphihs and other infections of the Iymph nodes, probabIy resembIing cIosest tubercuIosis. SYMPTOMS

In the maIe the primary Iesion is usuaIIy situated in or near the coronary suIcus, but may be on the shaft of the penis or within the urethra. It is a smaI1, non-inflamed, painIess uIcer that is often unnoticed. CIinicaIIy it resembIes a cross between a herpes preputiaIis and a chancre, being more crater-Iike and Iess painfu1 than a herpes, smaIIer and not as indurated as a chancre. We have obtained repeated negative examinations for Treponema paIIida and watched the primary Iesion hea without treatment onIy to have the patient return in two to five weeks with an inguina1 adenitis. Due to the Iow mentaIity of the patients and the frequency of promiscuous copuIation we were unabIe to make accurate observations as to the incubation period in the different phases of the disease. We beIieve the primary uIcer ap pears seven to twenty-five days foIIowing

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the infecting coitus and that two to five weeks foIIowing the primary Iesion the Iymph nodes begin to enlarge. OnIy a few females were treated and definite con&sions as to the onset, symptoms and progress of the recta1 involvment couId not be formed. The secondary Iesion in the maIe manifests itseIf by enIargement of the inguina1, and at times, the iIiac Iymph nodes. The adenitis is usuaIIy uniIatera1 but may be biIatera1. If biIatera1 one side appears before the other. In one case there was a continuous chain of infected Iymph nodes that extended across the suprapubic region. At first the gIands are onIy sIightIy painfu1 and increase but IittIe in size. Five to ten days foIIowing their appearance they vary 3 to IO cm. in diameter, are painfu1 and incapacitating, soon becoming firmIy bound together and attached to the skin and underIying fascia, the skin deveIoping gIistening purpIe coIor and has the appearance of having been waxed and poIished (Fig. 4). If treatment is not instituted suppuration with muItipIe sinus formation ensues which exudes a thick yeIIow pus for severa weeks. The French writers beIieve that invoIvment of the iIiac gIands, noted as a mass above and behind Poupart’s Iigament, is pathognomonic of Iymphopathia venereum. In the earIy stages ofthe adenitis the patient often presents the picture of an acute infection, compIains of a genera1 maIaise and fever varying from IOO to IO~‘F., and may be confined to bed. In the female, infection of the anorecta1 gIands between the vagina and rectum may resuIt in tenderness in the Iower quadrants of the abdomen that simuIates an acute saIpingitis. DIAGNOSIS

A uniIatera1 or biIatera1 inguina1 adenitis without a IocaI Iesion to justify its existence suggest Iymphopathia venereum. The patient after a period varying from seven to twenty-five days foIIowing the infecting intercourse notices the appearance of the

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primary lesion. It is a smaI1 shaIIow painIess uIcer which is transitory and frequentIy passes unnoticed and if discovered may not

FIG. 5. Same case as Figure

4; positive Frei test. CommerciaI antigen aIways gives more marked reaction than antigen prepared in a hospital laboratory. Note the absence of reaction where saline was injected.

be considered of importance unti1 the secondary or adenitis stage appears, two to five weeks folIowing the primary uIcer. In 1925 Frei produced an antigen for diagnostic purposes, to date proving to be the most important advance made in the study of the disease. An accurate diagnosis can onIy be made if the Frei test is positive (Fig. 5). At the onset of the disease the test may be negative but wiI1 become positive before the adenitis subsides. In the differentia1 diagnosis, bubo due to the Ducrey baciIlus, syphiIitic bubo, gonorrhea1 bubo, adenitis due to non-specific infections, Hodgkin’s disease, tubercuIous adenitis and maIignant metastases must be eIiminated. Any combination of these diseases may exist with Iymphopathia venereum. Of these, chancroida1 bubo probabIy presents the nearest cIinica1 picture to Iymphopathia venereum. The chancroida1 bubo develops earIier but is more destructive of tissue and produces greater pain. It suppurates into one Iarge cavity which is fiIIed with Iiquid

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pus. If it ruptures, a Iarge painfuI ulcer develops that has a fouI odor and Ducrey baciIIus can be recovered from the pus. In addition the Ito-Reenstierna skin reaction is positive onIy in chancroid. In syphiIis the adenitis is generaIized, the gIands are hard, discrete and do not suppurate. The primary Iesion is of Ionger duration and, if seen earIy, the dark fieId wiI1 be positive. Positive seroIogica1 findings usuaIIy accompany the generaIized adenitis. If the condition cIinicaIIy resembIes Iymphopathia venereum, positive seroIogica1 findings shouId not prevent a diagnosis of Iymphopathia venereum being made, if the Frei test is positive. If the adenitis is genorrheal in origin, the urethra1 smear wiI1 be positive for gram negative intraceIIuIar dipIococci. A non-specific adenitis is accompanied by a baIanitis or an infected area drained by the iIiac or inguina1 lymph nodes. In Hodgkin’s disease the gIands are hard and painIess and the cervica1 and axiIIary regions are usuaIIy invoIved. The blood picture and a section of the gIand confirms the diagnosis. TubercuIous adenitis is a chronic adenitis with sinus formation. The systemic symptoms, x-ray findings, evidence of tuberculosis in other areas, a positive Mantoux and biopsy confirm the diagnosis of tubercuIosis. Metastasis is diagnosed by the biopsy and there being or having been present a maIignant process. In the female the secondary stage of Iymphopathia venereum usuaIIy resuIts in stricture of the rectum and at times eIephantiasis of the vuIva. Our experience with this type of case has been Iimited, as the majority of the patients seen were maIes. The primary Iesion in the femaIe usuaIIy occurs on the posterior portion of the Iabia or vagina. As the Iymph drainage for this area is posterior to the anorectal gIands between the rectum and vagina, invoIvement of these gIands resuIts in scar tissue and stricture of the rectum, generaIIy Iocated 3 to IO cm. from the anus. EIephantiasis of the vuIva is due to bIockage of lymph channeIs. Infection of the inguinal glands may occur in the female.

RecentIy we saw of pain, genera1 temperature with and a strongIy systemic reaction hospitaiization.

a prostitute compIaining maIaise and eIevation of biIatera1 inguina1 adenitis positive Frei test. The was sufficient to require

PREPARATION

OF ANTIGEN

In 1925 Frei reported a specific intraderma1 test for Iymphopathia venereum. The antigen for this test is now prepared commerciaIIy but can easiIy be made in any Iaboratory (Fig. 5). The donor for the pus must be free of tubercuIosis, syphiIis and chancroid and have a positive Frei test. The pus is aspirated from one of the suppurating glands that has not reached the stage of sinus formation. OnIy 1 or 2 c.c. of pus can usuaIIy be obtained and it should be free of bIood. It is diluted five to ten times with steriIe saline, the diIution depending upon the thickness of the pus. The mixture is steriIized at 60” for two hours and the next day for one hour. It is then tested on a known case of Iymphopathia venereum but not the case from which the pus was obtained. If it gives a positive reaction in a known case and a negative reaction in a norma individua1, then it is a satisfactory antigen. It shouId be tested at intervaIs on known cases to be sure it has not become inert. The technique of the test is simiIar to the intradermal tubercuIin test, (Fig. 5), 0.1 C.C. of the antigen being inject intradermaIIy on the ventra1 surface of the forearm and 2 inches from it a contro1 wheal is raised using 0.1 C.C. norma saIine. In twenty-four to seventy-two hours a positive test shows a red, raised papuIe 0.5 to 2 cm. in diameter, whiIe onIy a needle puncture marks the contro1 area. If the test is negative no reaction wiI1 have occurred. A positive test persist seven to ten days and if strongIy positive the center may become necrotic. EarIy in the disease the test may be negative but wiI1 become positive before the adenitis subsides. If the case is cIinicaIIy one of Iymphopathia venereum the test

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use in stricture of the rectum and eIephantiasis of the externa1 genitaIia was too Iimited to draw any accurate concIusions. Where the disease has advanced to this stage IittIe, if any, improvement wiI1 foIIow any form of drug therapy. The deveIopTREATMENT ment of the adenitis with suppuration and The idea1 treatment in Iymphopathia sinus formation was observed in patients venereum shouId produce an earIy decrease receiving active antisyphiIitic treatment. in the pain, tenderness and enlargement of These Iesions heaIed rapidIy and compIeteIy the Iymph nodes and prevent them from when the antisyphiIitic treatment was disprogressing to the stage of suppuration. If continued and fuadin administered. suppuration has aIready occurred, it shouId The foIIowing technique is empIoyed produce a decrease in the discharge and in treating Iymphopathia venereum with compIete heaIing of the sinus tracts. Fuadin fuadin. Five C.C. of fuadin is injected deep approaches these requirements more cIoseIy into the gIutea1 muscles twice a week, the than any form of treatment we have tried. number of injections required depending We did not use it during the primary or upon the stage of the disease when treatuIcer stage because a positive diagnosis ment is begun and the rapidity with which couId not be made at this time. heaIing occurs. The average patient reNumerous types of therapy has been ceived from eight to fifteen injections. advocated for the treatment of IymphoOccasionaIIy a recurrence of the adenitis pathia venereum. The foIIowing are some of was noted when the drug was withdrawn the more popuIar types: TotaI extirpation too earIy. In our cIinic fuadin has proved to of the gIands, incision and drainage after be non-toxic and it is now administered suppuration occurs, high voItage roentgen unti1 a11 possibiIity of recurrence has therapy, foreign protein therapy of various passed. Reinfection has not been noted and types, the intravenous use of Frei antigen, probabIy a Iife immunity is deveIoped. potassium iodide, emetin, mercury, arsenic The primary Iesion is transitory and seIf and tartar emetic. The majority of authors heaIing, few cases were seen unti1 the prefer tartar emetic. The muItipIicity of secondary stage of the disease developed. treatments is proof of their ineffIciency. It was impossibIe to draw any concIusions Our best resuIts have been obtained with regarding the use of fuadin in the primary the intramuscular use of Fuadin. Coutts stage as an accurate diagnosis couId not be and Bianchi,4 of the Medical department made at this tinie. We were unabIe to of ChiIe University, report favorabIy con- determine if its use would prevent the cerning its use. This was the onIy report we secondary adenitis or hasten heaIing of the were abIe to find pertaining to the use of primary uIcer. fuadin in Iymphopathia venereum. Fuadin gave exceIIent resuIts in 75 to 80 per cent of CONCLUSIONS our cases, producing a marked decrease in The prognosis as to Iife in both diseases the duration and symptoms of the secondary stage. In six to eight days the gIands is good. Death did not occur primariIy from begin to diminish in size and become Iess either granuIoma venereum or Iymphopainfu1, suppuration is prevented, a hard pathia venereum. The diseases are inbubo resuIts that reduces in size and Iater capacitating if treatment is not begun disappears. If used in the suppurating stage earIy. Three years ago when the present with sinus formation there is an earIy UroIogicaI Out Patient Department of the HiIIman Hospital was opened, granuIoma Iessening of drainage and healing of the . ” smus tracts occurs m a few treatments. Its venereum was frequentIy seen. With inten-

shouId be repeated at weekly intervaIs unti1 a positive resuIt is obtained or unti1 the adenitis subsides. A positive reaction probabIy persists through Iife.

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sive treatment the frequency of the disease decreased and during the past six months there has not been a singIe admission. Either we are diagnosing Iymphopathia venereum more frequentIy or the disease is on the increase, because the number of cases with a positive Frei test under treatment is constantIy increasing. From this we have concluded that Iymphopathia venereum is more contagious and easier transmitted than granuIoma venereum. In cities where reinfection from the frequent entrance of infected cases does not occur, granuIoma venereum

can be eradicated. These concIusions drawn from treating approximateIy cases granuloma venereum and 200 Iymphopathia venereum.

were 50 cases

REFERENCES I. HOFFMAN, EUGENE F. Lymphopathia venereum or IgmphogranuIoma inguinaIe. Ural. and Cutan. l?ev.~ 37: 786, 1933. 2. SYMMERS. DOUGLAS. Granuloma inguinale in the United’States. J. A. M. A., 74: 1304 (May) 1920. 3. COLE, H. N. LymphogranuIoma inguinaIe, the fourth venerea1 disease. J. A. M. A., IOI: 1o96 (Sept.) 1933. 4. Courrs, W. E. and BIANCHI, T. B. LymphogranuIomatosis venerea and its cIinica1 syndromes. Ural. and Cutan. Rev., 38: 269 (ApriI) 1934.

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