UNITED STATES OF AMERICA WASHINGTON, D. C. Bl9 574 M . L.n oy fw.r J An Undescribed Variety of Hereditary OEderaa. l!Y W. F. MILROY, M. D., PROFESSOR OP CLINICAL MEDICINE AND HYGIENE IN THE OMAHA MEDICAL COLLEGE; PHYSICIAN TO IMMANUEI. HOEPITAL, ETC. REPE1NTBD FROM THK Neto Ifovfc fttrttcal journal for November 5, 1892. cr fls / lAon-'.fAtd- WB3 i Reprinted from the New York Medical Journal for November 5, 1892. AX UNDESCRIBED VARIETY OF HEREDITARY (EDEMA.* By W. F. %MILR(nVM. D., PROFESSOR OF CLINICAL MEDICINE AND HYGIENE IN THE OMAHA MEDICAL COLLEGE ; PHYSICIAN TO IMMANUEL HOSPITAL, ETC. On August 20, 1891, Mr. H. presented himself for examina- tion for life insurance. He was an American, a clergyman, thirty-one years of age, six feet and half an inch in height, and weighed one hundred and seventy-eight pounds. His habits were the best, and he had never been sick in his life. With re- spect to longevity, his family history was excellent. Physical examination revealed nothing abnormal with regard to the thoracic or abdominal viscera. The applicant called my atten- tion to his lower extremities. I found a condition of oedema involving the feet and extending up the legs to the knees. It was, and the patient states had always been, somewhat more marked in the left extremity than in the right. Upon inspec- tion, the leg presented a slightly rosy hue, extending around its whole circumference and involving the whole extremity, gradu- ally disappearing near the knee. When lightly pressed, the color disappeared, but returned quickly when the pressure was removed. Scattered thickly over this base were white spots about the size of a pea. These also were found over every part of the leg as far as the rosy color extended. This appearance of * Read before the Society of the Alumni of Charity Hospital, June 1, 1892. Copyright, 1892, by D. Appleton and Company. 2 A VARIETY OF HEREDITARY (EDEMA the leg, according to the statement of the applicant, is constant. There were no varicose veins and no evidence of bad nutrition, nor was there any tendency to ulceration in any part of the leg. The circumference of the calf of the leg at its largest part was seventeen inches, and the smallest circumference of the ankle was fourteen inches. Deep pressure with the finger over the crest of the tibia, at a point near its middle, produced a depres- sion which was distinctly apparent to both touch and sight ten minutes after the pressure was removed. This will convey an idea of the well-marked character of the oedema. The pitting on pressure was quite evident as far up as the tubercle of the tibia, but not over the patella or above it. Mr. H. stated that this ©edematous enlargement had existed from birth. As he had grown in stature, the (edematous parts had grown so as to preserve the same size relative to the remainder of the body. It had always been free from pain, showed no disposition to ul- cerate, and, in short, had never given him the least inconven- ience. In the evening, if he had been on his feet a good deal during the day, the swelling seemed somewhat greater than in the morning, the skin appearing rather tense. The applicant stated that this enlargement of the extremi- ties was a family characteristic which he had inherited from his mother. Fortunately for the purposes of this study, the family of Mr. II.'s mother is one which has been long in America, and has been productive in New England. In 1883 a member of the family published a neat volume, giving the family history in America for a period of two hundred and fifty years. It should be remarked, however, that the peculiarity now under discussion seems to have entered the family by marriage about 1768. With the aid of this volume and the assistance of members of the family still living, I am able to offer the facts which I pre- sent, feeling that they are thoroughly reliable, though not at every point as complete as could be desired. For convenience I present, in graphic form, a summary of the family historv in- dicating in which individuals the oedema has occurred : UENEALOCilCAL TAHLK SII()\VlX(i HEKKD1TAKY (KDEMA IX TIIK FAMILY OF W. II. A relative of Mrs. i Joseph W., \V. had one en- -, both legs larged leg. enlarged. III. 1. Jiimrs, Unknown. 2. Li/dla. One enlarged leg. 3. So rail. Xornial. 4. Martha. One leg enlarged. 5. Oil re. Xornial. 6. Charity. Both legs enlarged. 7. Sally. One foot and ankle enlarged. 8. Afar;/. Unknown. 9. Julia. One foot and leg enlarged. IV Six children. Three have each one enlarged foot. V. Kleven children. Two have each one enlarged foot. \ Light children. \ Xine children. / One enlarged foot. I All normal. I Five children. ( One enlarged le<; Four children. One enlarged leg. Xine children. One has both legs enlarged ; one has one foot enlarged. Four children. One enlarged foot. Three children. j Two children. One enlarged foot. { Xormal. tour children. ,„,,., , -, , ,, ,., ,. .. \ Thirteen children. One (the applicant), -, .- ■ r u i i i Xornial. both legs enlarged. f Six children. One has one foot en- larged ; one has both feet enlarged. \ Two children. ( Xornial. 4- A VARIETY OF HEREDITARY (EDEMA. First Generation.—-In 1708 Benjamin W. married Olive S. They were both physically normal, but a near relative (probably a sister) of Mrs. W. had an enlarged leg. Second Generation.—Joseph W., son of Benjamin, was born in 1784, and died, at the age of seventy-eight years, of typhoid fever. He had both legs enormously enlarged. Third Generation.—Joseph was twice married and had nine children, as follows: 1. James died at the age of four years, and no information has been able to be obtained in regard to him. 2. Lydia is still living at the age of eighty-two. She has one leg enlarged. 3. Sarah is also living, aged eighty. Her extremities are normal. •4. Twin birth. Martha, who died in infancy, had one leg enlarged. Olive died of u jungle fever " in India at the age of thirty-eight. Both of her extremities were normal. 5. Charity is living at the age of seventy-five. She was born with one enlarged foot. When between twenty and thirty years of age she was thrown from a carriage, sustaining an in- jury in the sound leg. The injury was recovered from without special difficulty, but the leg gradually enlarged from that time until it reached enormous proportions. It has never given her the slightest inconvenience. She has through all her life en- joyed excellent health, and her extraordinary activity has always been a source of wonder to her friends. 6. Sally is living, aged seventy-three. She has one enlarged foot and ankle. 7. Mary died when a young child, and no information has been obtained in regard to her. 8. Julia is living at the age of sixty-six. Both extremities were normal until she was twelve years old. At that time one ankle had the appearance of having been sprained, though she was not aware of having thus injured it. For several weeks she could not walk on account of the distress in this ankle. The lameness was recovered from, though the swelling never disap- peared, but, on the contrary, increased as she grew until it in- volved the foot and leg. It has never caused her any incon- A VARIETY OF HEREDITARY (EDEMA. 5 venience since the time mentioned, when she was twelve years of age. The other leg has remained normal. Fourth Generation.—Lydia, the second daughter, had six children. Of these, the three daughters are normal. The three sons have each one foot somewhat enlarged. Sarah has had eight children, of whom three are living. They were all normal with the exception of one son, who has a large foot. Olive has had five children, of whom the youngest has one enlarged leg, the remainder being normal. Charity has four children. Three of these are normal. The other has one enlarged leg. Sally has two daughters and a son, the former being normal. The son had one enlarged foot. When he reached maturity his testicles began to enlarge, and this progressed to such a degree that he had one of them removed. As the enlargement of the testicles increased, that of the foot diminished until it was re- duced to normal size, and it has since remained normal. Julia had three children by her first husband, all of whom are normal. By her second husband she has one son (the ap- plicant), with both legs and feet greatly enlarged. Fifth Generation.—Of the descendants of Lydia, there are in this generation eleven children, of whom nine are normal. The remaining two, a son and a daughter, have each an enlarged foot. Sarah has nine grandchildren, all normal. Olive has nine grandchildren. A son of her eldest daughter has both legs enlarged, and a son of her eldest son has one foot enlarged. The others are normal. Charity has three grandsons and one granddaughter. One of the sons has one enlarged foot. The remainder are normal. Sally has two grandchildren, both normal. One of these is a son of the individual who had the testicle removed, as already referred to. Julia has had thirteen grandchildren, all normal. Sixth Generation.—Of the three grandsons of Charity men- tioned, the eldest has three children, all normal. The youngest has also three children, of whom the eldest, a son, has one en- 6 A VARIETY OK HEREDITARY (EDEMA. larged foot; and the youngest, a daughter, has both feet en- larged. Of the descendants of Julia, there are in this generation two children, both normal. It thus appears that in the six generations of the family, comprising ninety-seven individuals, there have been twenty- two cases of this deformity, or about twenty-three per cent. of the whole number. Of the twenty-two cases, twelve were males, seven females, and three unknown, appearing to show that it is rather more common among the males than females of the family. In the later generations the percentage of cases is about as large as in the earlier, but there is a de- cided decrease in the extent of the oedema in most of them. Atavism is frequently apparent in the development of the family peculiarity. I have not been able to learn that treatment has been undertaken for the cure of the affec- tion in any case. The invariable characteristics of the disorder have been : (1) Congenital origin with a steady growth corresponding to the normal growth of the body until adult size is at- tained ; (2) the limitation of the oedema to one or both lower extremities, the area involved varying; (3) perma- nence of the oedema ; and (4) entire absence of constitu- tional symptoms, or local symptoms aside from those de- scribed. Three exceptions to the usual course appear. The first of these is the case of Charity in the third generation. Hav- ing been born with one enlarged foot, its growth was char- acterized by the usual phenomena until she reached adult age. When above twenty years old she was thrown from a carriage, sustaining an injury in the sound leo-. The im- mediate effects of the injury passed away within a reason- able time, but from this date the leg began to enlaro-e Hnd continued to do so until it had attained enormous size but A VARIETY OF HEREDITARY (EDEMA. 7 at the same time, in no wise interfering with the health or activity of the individual. The second exception is the case of Julia, also in the third generation. At birth and until she was twelve years of age her extremities were normal. Then, being unaware of having sustained any injury, one of her ankles developed the appearance of having been sprained. The usual signs of a sprain, including pain, tenderness, and swelling, were present to such a degree as to disable her for a number of weeks. < iradually all of the symptoms subsided with the exception of the swelling, and this increased and extended until it involved the foot and leg. It still remains, but never again has it given her any inconvenience. The third exception, and the most remarkable, is that of a male in the fourth generation. Born with one en- larged foot, this grew in the usual manner until he arrived at maturity. Enlargement of the testicles then began and continued until they were so large that it was thought best to remove one of them, and this was done. As the enlarge- ment of the testicles progressed, the abnormal size of the foot diminished until it became normal, and the enlarge- ment has never returned. Unfortunately, the surgeon is dead who performed the castration, and I have been unable to obtain satisfactory information in regard to this most re- markable case. It is a question whether the enlargement of the testicle bore any particular relation to the family pe- culiarity, this not having occurred, so far as I am aware, in anv other member of the family. But the fact remains that no other instance is known in which the oedema disappeared even temporarily. The newness of the city and consequent dearth of medi- cal libraries in Omaha is a serious obstacle in the way of the studv of pathological and other questions here, and in- asmuch as the literature at my command furnished no aid 8 A VARIETY OF HEREDITARY (EDEMA. to an understanding of this case, I wrote an incomplete ac- count of it to Professor Francis Delafield, of New York, and also to Professor William II. Welch, of Baltimore, and I shall take the liberty to quote from these eminent authori- ties. In his reply Professor Welch says : " The case de- scribed in your letter is of extreme interest, and I do not know of one altogether like it recorded in literature. I should be inclined to put it in the category of angeio-neurotic cedemas. The congenital character of the affection and the existence of a similar condition in other members of the family, and the absence of any of the ordinary causes of oedema, speak for this view." Professor Delafield, whose reply was delayed for some time, says : " I have put off answering your letter of August 11th until this late date with the hope that I might be able to give you some infor- mation concerning your very interesting case of dropsy. I have found no reports of identical cases." He offered no suggestion as to the nature of the disorder. I am indebted to Professor Welch for reference to a paper by Professor William Osier upon the subject of Angeio-neurotic (Edema. This was published in the Ameri- can Journal of the Medical Sciences in April, 1888. Pro- fessor Welch also stated that he had shown my account of the case to Professor Osier, who concurred in the opinion that the case is one of angeio-neurotic oedema. Angeio-neurotic oedema is a form of disease which is not so much as mentioned in any text-book or encyclopaedia that I have been able to find in Omaha. Most of my in- formation upon the subject I have obtained from the paper of Professor Osier already referred to, which contains, be- sides an account of his own cases, references to the very limited literature of the subject. A sufficient number of cases have been reported by different writers to show that it is not very uncommon. A VARIETY OF HEREDITARY (EDEMA. 9 Professor Osier describes the attack in one of his cases, that of Mrs. H., as follows: " As long as she can remember she has been subject to at- tacks of transient swelling in various parts—hands or fingers, knee-caps, elbows, buttocks, arm or thigh in fleshy parts, face, or more often the lips alone. The fingers have been so swollen that it was impossible to move them, and once the ring finger was so greatly enlarged that the rina: had to be filed off to pre- vent gangrene. The under lip has been swollen to such a degree that the mouth could not be opened and milk had to be poured in from above. A slight redness or itching of the part is first noticed, or a sensation of heat; the redness is not always pres- ent. The effusion may take place with great rapidity. She often has red spots on various parts of the skin or irregular lines of redness without any swelling. The duration varies from one to four days. There is not much itching, particularly when the swelling is great, but a sense of distention and stiffness. When fully out it does not pit, but does so when going down. Thi attack may come on when she is feeling quite well, or there may be slight indisposition. In all the severer ones there is ab- dominal pain, described as colic, with nausea and often vomiting. There is sometimes headache: no fever. The attacks have no relation to the menstrual flow. She rarely passes two weeks without an attack. She does not think that food has any in- fluence on her case." This case is related as giving a fair idea of the character of the disorder, and Dr. Osier states that a review of the literature shows that all of the cases, in respect to their symptoms and course, are very similar. The hereditary tendency Osier found mentioned by three observers, and it was very marked in the family studied by himself. The most distressing symptom, in most of the cases, is the in- testinal colic, which is so severe as to demand the adminis- tration of morphine. Urticaria, which is a skin disease of neurotic origin, has 10 A VARIETY OF HEREDITARY (EDEMA. been so often found to precede or accompany the attacks of oedema that it is evident there is a close relationship between them. In speaking of the case to Dr. Cifford, he called my attention to the fact that there are certain subjects in whom an (Edematous condition of the eyelids occurs without con- gestion. These attacks are transient, and are provoked by a more or less severe use of the eyes. Quincke is the author of the term "angeio-neurotic oedema," basing the name upon .the theory that the disease is a vaso-motor neurosis by means of which the permea- bility of the vessels is suddenly increased. However, in his letter, to which I have referred, Professor Welch says : " As to the pathology of angeio-neurotic oedema we know nothing. Even our knowledge of the physiology of the vaso-motor nerves does not explain how they could be dis- ordered so as to cause oedema." When the subject was first brought to my notice it oc- curred to me, as a possible explanation, that there might be a congenital absence of valves from the veins of the part affected. I was not aware that such an abnormitv had ever been described, and have not since been able to learn that it has been known to exist. If it did exist, I do not know that it would cause oedema, and, indeed, a more per- fect knowledge of the family history brings to light certain facts that seem at first glance, at least, not readily to har- monize with this theory. There is, in my judgment, no pathological condition with which we are acquainted to which the case which I have related corresponds in a greater degree than what is known as angeio-neurotic oedema. Nevertheless, in most of the fundamental characteristics they are dissimilar. Professor Osier says: " Briefly summarized, the affec- tion in the family which I have studied has the following characteristics: A VARIETY OF HEREDITARY (EDEMA. H ''1. The occurrence of local swellings in various parts of the body, face, hands, arms, legs, genitals, buttocks, and throat. In one instance, possibly in two, death resulted from a sudden oedema glottidis. "2. Associated with the oedema there is almost invaria- bly gastro-intestinal disturbance, colic, nausea, vomiting, and sometimes diarrhoea. " 3. A strongly marked hereditary disposition, the dis- ease having affected members of the family in five genera- tions/' On the contrary, and strongly in contrast with this dis- order in the family which I have studied: 1. So far as known, in every case, with two exceptions only, the oedema was present at birth. 2. The location of the oedema has in every case been limited to one or both lower extremities. 3. The presence of the oedema is persistent, never hav- ing been known to disappear, temporarily or permanently, except in one instance. 4. It has never been attended by constitutional symp- toms, barring the two possible exceptional cases in which its first appearance was subsequent to birth. From these considerations it seems evident that the case under discussion is not one of angeio-neurotic oedema, nor would it seem probable from the history that any functional neurosis could be responsible for the oedema. It is proper to say in this connection that the account of the case upon which Professor Welch based his sugges- tion as to diagnosis was too fragmentary to admit a fair judgment of it. Inasmuch as we know nothing as to the pathology of angeio-neurotic oedema, it may be possible that a correct elucidation of its nature would show that the case in ques- tion belongs in the same category. 12 A VARIETY OF HEREDITARY' (EDEMA. The nature of the primary influences which control the process of transudation is still the subject of dispute among pathologists. That the influence of the nervous system is important, at least in certain cases, is not denied. Never- theless, we are still in so great ignorance of the matter that a discussion of it can give little result of value. In his work on General Pathology Payne remarks : " Dropsy of nerv- ous origin is caused by paralysis of the vaso-motor nerves, causing hyperseinia, which, in combination with some ob- scure factor, leads to effusion." In the case which I have narrated the " obscure factor " appears to be very conspicu- ous. Whether or not the case is one of nervous oedema, it is offered that, with others, sufficient material may be ac- cumulated to render possible an intelligent study of these unusual forms of oedema. REASONS WHY Physicians Should Subscribe FOR The New York Medical Journal, Edited sy FRANK P. FOSTER, M. D., Published by D. APPLETON & CO., 1, 3, & 5 Bond St I. BECAUSE : It is the LEADING JOURNAL of America, and contains more reading-matter than any other journal of its class. 2. BECAUSE : It is the exponent of the most advanced scientific medical thought. 3. BECAUSE: Its contributors are among the most learned medical men of this country. 4. 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