M. P. Vora, M.B.B.S., Venereal Dept., St. George’s Hospital, Bombay
The Medical Bulletin
Vol. IX, No.12 of 21 st June, 1941; Pages: 382-389
Synonyms - Lymphogranuloma Inguinale, Climatic Bubo, Poradenitis, Lymphopathia Venereum, Lymphogranulomatosis Inguinale, Poradenolymphangitis, Estheomene, Nicolas-Favre Disease, Elephantiasis or Chronic ulceration of the genitalia, Non-tuberculous granuloma, Genito-ano-rectal Syndrome, Chronic Inflammatory Stricture of the rectum etc. Various descriptive names have been suggested; in fact, they have become an object of individual definition and liking. The term L.V. is preferable to the numerous eponyms; moreover it saves confusion with granuloma inguinale, an altogether different condition.
Definition - A human contagious disease, due to an ultra-microscopic filterable virus acquired usually by sexual intercourse and characterised by a small, often transitory initial lesion of the genitalia, followed by the development in the regional lymphatic glands and adjacent connective tissues of a characteristic chronic inflammatory reaction, with the production in the majority of cases, of multiple small foci of suppuration and later on fistulation. The adenopathy, in the male and in a smaller proportion of females, is localised to inguinal or inguino-curo-iliac group of glands, giving rise to what is called Climatic Bubo. But its localization in the intra-pelvic glands is not uncommon in a greater proportion of women and a few men. The disease results in diverse manifestations such as elephantiasis of the male or the female pudenda, chronic ulceration of the vulva, estheomene, and genito-ano-rectal syndrome, warty and polypoid growths in the vulvar and anal region, stricture rectum, etc., depending on the sex of the patient, the site of the primary lesion and the stage of the disease. Constitutional symptoms like fever, headache, lassitude, pains in joints, erythema of the ski n etc. are usually associated with it.
Historical - There is little doubt as regards the early recognition of the disease especially among sailors in the tropical ports. Trousseau recorded a case of this nature as early as 1865. The syndrome was then described by the French scientists, Durand, Nicolas and Favre in 1913. Recent researches by Hallestrom, Stannus and Frei have established the identity of the conditions, formerly described under different names as one disease. Variations are variations of degree and stage in the progress of the disease. With close similarity between them, one cannot help believing, in so far as the clinical and historical data go, that all the manifestations must have the same pathogeny. The introduction of Frei’s intradermal test in 1925 was a landmark of great importance in the diagnosis of the disease. The test is considered to be specific and as a reliable diagnostic criterion. Bowel antigen - a new, practical diagnostic aid - devised by M. Paulson is supposed to be of great importance in determining the presence of infection in the intestinal tissue especially in cases, which have least external evidence of the disease and which are clinically indistinguishable from non-specific ulcerative proctitis, colitis etc.
Aetiology - L.V. is a disease of warm climates and is found all over the world in the tropical and subtropical countries like India, Africa, Ceylon, China, Japan, Australia etc. Heat, high humidity and hot atmosphere seem to be favourable. The filterable virus, which is responsible for the infection, is resistant and remains active for a considerable time at room temperature and even after drying. The usual way of transmission of infection is by way of sexual congress though extra-genital infections are not uncommon. Cases of typical axillary adenopathy following digital primary lesion as the result of an accidental infection are known among doctors. C.E. Snock recorded five cases, all in girls between 4 to 9 years and having their hymens intact; he consequently considered the possibility of infection being carried in some other way than by means of sexual intercourse. In considering the question of infectivity, partner cases are of particular interest. Cases are on record where one party had a very mild or an abortive attack of adenopathy while the other party , whom the former infected, had very severe attack lasting for a year and vice versa. It is believed that the disease is probably most infectious at the time of primary sore. The disease is met with in both sexes though the inguinal bubonic manifestations predominate in the male and pelvic adenopathy with its concomitant signs, predominates in the female. No age is exempt; cases have been noted even in infants 2 to 4 weeks old. However, the greatest incidence is in the 3 rd and the 4 th decades. No race is immune though coloured races are said to have special affinity. The frequency of infection depends on the degree of sexual promiscuity of the population; high incidence, therefore, is found in the metropolitan cities or seaports and among people who are given to excessive sexual relations. Uncleanliness, failure to employ preventive or anti-venereal measures, long or tight prepuce etc. may be regarded as predisposing causes. Two distinct periods of incubation are suggested: - (1) The time which elapses between the infecting coitus and the appearance of the primary lesion; it varies from a few days to three weeks. (2) The period which passes between the infecting coitus and the first demonstrable swelling of the lymph glands; this varies from 8 days to 8 weeks.
Pathology - Although the disease begins as an infection of the skin it is not a skin disease, but a disease of the local lymphatic channels, lymph nodes, and the connective tissue. Involvement of the skin, excepting the primary lesion, is a secondary manifestation while the essential lesions are in the lymph nodes. The causative agent is a specific filterable virus which consists of small cytoplasmic granules, measuring 0.24µ to 0.33µ in diameter. It is usually transmitted venereally. The initial lesion which consists of a small vesicle or an ulcer appears on the glans penis in the male and on the vulva in the female after an incubation period of a few weeks to three weeks. Two to 8 weeks later, lymph nodes draining the area of the primary lesion become enlarged indurated and matted together; the overlying skin becomes adherent and bluish red. After a slow and protected course, the process results in multiple small abscesses which later on burst open to form numerous sinuses. Healing too is equally slow. The clinical picture of the disease varies in the two sexes because of the difference in the site of election for the primary lesion. A primary, so situated in the female, as to drain into the inguinal glands will give rise to inguinal adenitis and a bubo exactly comparable to that in male and the elephantiasis may result exactly in the same way. In women, the primary lesion is more commonly situated in the posterior part of the vulva in the fourchette, vagina or the cervix, with the results that the inguinal glands are missed altogether while the glands situated in the pelvis i.e. perirectal wall and rectovaginal wall, are involved to undergo practically the same pathological changes (short of suppuration) as in the inguinal bubo. On account of this anatomical disposition, early evacuation by suppuration such as takes place in the inguinal bubo is less common or even impossible in the pelvic glands. Thus elephantiasis of the vulva and rectal lesions are more frequent in the female.
The various clinical aspects of the disease on histological examination are found to possess curiously enough, the same series of changes, though varying somewhat in degree. They may be described aptly as granulomatosis of a progressive type. “Macroscopically the extirpated glands consist of conglomeration, with the cut surface in many instances of red to violet tinge. Abscesses are at times observed. The capsule of the gland is thickened and shows vascularisation and infiltration. Microscopic examination discloses the picture of a subacute or subchronic lymphadenitis”. Typical description given by Hellstron runs thus:- “The highly fibrosed altered gland is larded with numerous larger or smaller, rounded, oval or ramified abscesses, surrounded by narrower or broader zone of epitheloid cells, frequently arranged in a palisade form. In addition, the gland is as good as completely filled with granulation tissue consisting of lymphocytes, plasma cells, fibroblasts, epitheloids and fairly large cells with highly colorable nuclei, together with a few medium large giant cells of Langhans type, which are usually situated at the edge of the border of epitheloid cells”. The small epitheloid formations consisting largely of epitheloid and giant cells with necrosis have slightly different structure from that found in syphilis and tuberculosis. A section either of the primary lesion, a lymph gland or the tissue from the elephantiasis of the pudenda will exhibit various stages in one process, patchily disturbed. This close similarity in the histological pictures of the various clinical manifestations of the disease at once reminds us of the specific reaction due to specific virus of L.V. Generalised adenopathy is not known. Enlargement of the liver or the spleen is not observed. Occasional involvement os skin, joints, eyes, meninges etc. with fever, headache, and skin-rashes may suggest the possibility of a systemic infection.
Primary lesion - is usually a small herpetiform vesicle or ulcer circular in shape and hardly bigger than a pin-head. It has clean edges and a red surrounding zone. There is neither infiltration nor induration. The lesion does not itch or pain. It usually heals spontaneously without leaving any scar. It is often looked upon as a mere abrasion and is no longer visible by the time the patient comes under observation for adenitis. Occasionally it may take an aberrant form such as a papule or a nodule. It may occur on any part of the genitals, the commonest site being the coronal sulcus in the male and the fourchette or the posterior vaginal wall in the female. It appears after an incubation period varying from a few days to three weeks.
Adenitis: - The period which passes between the day of infection and the swelling of the inguinal glands is very variable, but averages between 2 to 4 weeks, the extreme limits being a few days to 8 weeks. The intensity and severity of the attack varies greatly in different persons. Adenopathy may be minimal in certain cases, while severe in others. The earliest symptom complained of may be some stiffness or aching in the groin and a swelling involving a single gland or a group of lymph glands. These glands are enlarged, discrete, freely movable under the skin, slightly tender on pressure and unassociated with any changes in the overlying skin. Glands enlarge ‘slowly’ and painlessly. In their early period, they may present a close similarity to the glands of early syphilis. As the days pass, the glands increase in size, till they reach a stage when they either retrogress, ending the process of Poradenitis or develop slowly, over many weeks and may go on to the suppuration. The whole process is very chronic and indolent lasting for many months. The glands first involved are the superior and medial groups of inguinal glands. In more typical cases the whole group of inguinal glands may be involved. Adenitis may be unilateral or bilateral. Later on, periadenitis is marked, the glands become matted together and become fixed to the overlying skin, when it assumes purplish tinge. They then soften and form multiple foci of suppuration and corresponding fistulae. Associated enlargement of the iliac glands is common and often invariable. Though, the same pathological process is at work, suppuration is rare in these glands. The iliac mass, at times, reaches a considerable size and causes pressure symptoms.
Constitutional symptoms, fever, periarticular pains, emanciation, headache, anorexia etc. are constant.
Suppuration - It would be difficult to state the exact proportion of cases which go on to suppuration for the milder cases rarely come under observation. Suppuration is more common in inguinal adenitis than in either pelvic or iliac adenitis. It is more frequent in males than in the females. The inguinal glands may enlarge and reach a considerable size and yet undergo resolution or they may soften with number of foci of suppuration and fistulation. In a few cases the process of adenitis when once started rarely stops short of completion in spite of the treatment. When the suppuration and fistulation is established the picture is practically pathognomic of the disease. There is no ulceration about the mouths of these fistulae; the lips are simple not infiltrated and do not show either undermining or button-like granulation tissue. The discharge from them is small, thick and tenacious. The course of suppuration on an average lasts for about two months but the extremes of 12 to 18 months are not uncommon. Complete recovery of healing is reported in many cases.
Late Manifestations - Elephantiasis of the male external genitals, elephantiasis of the pudenda either hypertrophic or ulcerative type, warty and polypoid growths of the vulva, lobulated or ’bouquet’ anus, proctitis, colitis, chronic inflammatory stricture of the rectum, recto-anal or genito-ano-rectal syndrome, etc, have been noted. For reasons afore mentioned, perirectal lesions occur frequently in females in place of inguinal adenitis which is of a more common occurrence in male. In severe cases the disease causes great destruction not only of the soft part but also of the osseous structures. The manifestations in female may be divided into two distinct types, (1) internal and (2) external. In the internal type the constitutional symptoms are more severe and recover slowly. Examination per vaginum reveals posterior and lateral fornices, tough, resistant and tender on pressure. There may be signs of rectal involvement. In external type various forms have been described according to the prominence of the changes; elephantiasis of the pudendum hypertrophic and ulcerative type, anal and vulval lesions or the combination of either of them.
Inflammatory Stricture of the rectum - is more frequently seen in the females than in the males. It is more often as the result of homosexuality or perversion in the case of males. There is usually a long progressive history and the evidence of the post-suppurative inguinal adenitis. The lesion may be present for a long time without any significance; or there may be complaints of constipation, bleeding from bowels, colicky pains and discharge per rectum. Digital examination per rectum shows stricture at a low position i.e. 3 to 6 cm. above anus. The lesion has infiltrative character and India-rubbery consistency. The mucous membrane on the lesion is intact, whereas the mucous membrane below the stricture and the skin above the anus are commonly the seats of ulceration, and polyposis. The wall of rectum is rigid and thickened. Fistulae may be present below the rectal stricture which may be found alone or associated with vulvar elephantiasis. Together they constitute ‘estheomene or genito-ano-rectal syndrome’. Anus may present lobulated appearance.
Diagnosis - Diagnosis of the disease may be based usually on the clinical findings alone, but for the sake of finality and decisiveness Frei’s intradermal test is often advisable. History of exposure to infection, a small transitory primary lesion, followed by chronic inguinal adenitis resulting in typical suppuration and fistulation is characteristic. The presence of elephantiasis of external genitals, rectal strictureat a low level, and vulval lesions, ulceration and fistulation etc., add further testimony to the previous findings especially in females. The disease is restricted to the local lymphatics and connective tissue. With the exclusion of tuberculosis, filariasis, Hodgkin’s disease, gonorrhoea, syphilis, malignant disease and chancroid and with the positive Frei’s test, the diagnosis of the condition becomes at once easy. However the possibility of a mixed infection should be borne in mind. Because of the manifold aspects of the disease and of the possibility of the lesions remaining insignificant for a long time, every case of genital elephantiasis or rectal stricture needs to be subjected to a critical investigation in regard to the possibility of this specific infection. A singular examination alone will be helpful in arriving at a correct diagnosis in the majority of cases. M. Paulson’s bowel antigen offers a direct and specific method for detecting bowel infection in some cases with little external evidence.
Preparation of Frei’s antigen - The person from whom the antigen is to be prepared must be free from tuberculosis, syphilis, gonorrhoea and chancroids both in the past and in the present. The glands from which pus is to be drawn must have undergone softening but not fistulation. Pure pus (free from blood0 is aspirated aseptically. It is mixed with physiological saline in proportion of 1 to 6, i.e. 1 part of pus plus 6 parts of saline. It is then heated in a water-bath to 60 oC for two hours on the first day and for an hour the following day. It is tested for sterility under aerobic and anaerobic conditions at room and incubation temperatures and then put in sterile ampoules of ½ and 1 c.c. The antigen thus prepared is kept at low temperature and unexposed to light. It remains active for a few months and should be fresh for reliability.
Frei’s Test - The skin on the outer side of the forearm is selected and dis infected with alcohol. 0.1 to 0.2 c.c. Frei’s antigen is injected intracutaneously on one forearm, while the same quantity of normal saline is injected in the corresponding area of the other forearm. Two normal controls are also associated at the same time with antigen and saline; controls are necessary. The results are noted after 48 hours and not before. Positive reaction is known by an inflammatory papule of ½ cm. in diameter, surrounded by a red zone, controls remains unchanged. The test becomes positive about two weeks after the appearance of the primary lesion. A positive reaction indicates the presence of the disease or that the patient had previously suffered from it. Once the patient has become reactive, the reaction often lasts for life.
Prognosis to life is good. Completer restitution to normal health is reported in good many cases. Recovery is so usual that it can be promised in a great majority of case, but the date of recovery is often difficult to forecast. Severe complications are usually not common. In rare cases, septic infection may be super-imposed and prove fatal. In the ulcerative lesions the damage may be considerable, particularly due to the want of effective medication. Prognosis in such cases is doubtful. The chances of successful control of the disease increase with the early institution of treatment. The usual lengthy course of the disease causes chronic ill-health and handicaps the functions of life for a considerable period. Second attack or re infection is not known. Females appear to be particularly dangerous from the point of propagation of disease.
Prophylactic - Circumcision, cleanliness of the genitals, washing the parts thoroughly with soap and water and some antiseptic lotion after every exposure to infection. Regular examination of the prostitutes by intracutaneously test, prophylactic administration of m &B. 693 tablets to the inmates of the brothel etc. may be of value in the prevention of infection and its propagation.
Curative - Various drugs have been tried but the experience does not justify complete confidence in them. There is probably no single drug that has any specific value in this disease. It is true that the use of one or the other method given below controls or aborts the attck most wonderfully in some patients, while in others it fails miserably. Early institution of treatment is essential to obtain best results. Occasionally one meets with cases which progress slowly and steadily to the terminal stage, no matter what treatment one employs. Such cases often tax even the experts’ resources to the utmost. General health, diet, vitamin intake, rest, bowels etc. should be attended in every case.
Treatment of special manifestations : - Primarily lesion does not need special attention except local cleanliness. It heals of its own accord.
Adenitis or bubo - Its formation may be prevented frequently by employing an energetic treatment. When the patient complains of a swelling and pain in the groin, a course of sulphanilamide by mouth is often able to nip in the bud the process of adenopathy. Locally Glycerine-Belladona may be applied. Rest and attention to the bowels, should be paid.
Suppuration and fistulation - When the glands soften and suppurate, the treatment is often times of little avail. This may be due to secondary infection. The disease runs its chronic course. Some authorities advise surgical methods such as incision, scraping, curetting and extirpation. Daily dressing with antiseptics and a course of above injections or oral administration of sulphanilamide may be found useful in accelerating healing.
Elephantiasis of the genitals, rectal stricture, ulcerative lesions etc - In these conditions very little can be done to improve or to cure the patient who becomes a chronic invalid and sufferer.
My thanks are due to Dr. Socrates Noronha M.B.E., D.T.M.H. ( Eng.) D.T.M. (Lond.) Dr. P.V. Gharpure M.D. and Dr. V.V. Gupte M.B.B.S., D.O.M.S. ( Eng.) for their kind assistance and suggestions