The early history and nomenclature of scleroderma and of its differentiation from sclerema neonatorum and scleroedema

The Early History and Nomenclature of Scleroderma and of Its Differentiation From Sclerema Neonatorum and Scleroedema By Thomas

G. Benedek and Gerald P. Rodnan

T

HE terminology that has been applied to scleroderma and to the historically related syndromes sclerema neonatorum and scleroedema developed in a most confusing manner, which this article intends to elucidate. The terminologic turmoil is in great measure attributable to the fact that induration of the skin is a prominent feature common to several diseases that we now recognize as distinct entities, and that most of the original names of these disorders were derived from the Greek root, skleros, meaning “hard.” Although many of the early clinical descriptions are difficult or impossible to interpret, some do permit a plausible retrospective diagnosis to be made. Therefore, we shall also attempt to identify which authors deserve priority for having described cases of scleroderma* and of scleroedema that appear to fulfill modern criteria of these diseases. In the second half of the 18th century, when this history begins, sclerema neonatorum was being described by French and English clinicians. Nevertheless, as influential a dermatologic text as that of Bateman (18 13) fails to cite this disorder under any name.* There are no descriptions from which a diagnosis of scleroderma may be made with confidence prior to the middle third of the 19th century, and this disease continued to be considered a rarity into the present century. Scleroedema, while it undoubtedly was described in the 19th and perhaps in the 18th century, was not distinguished as a separate entity until the beginning of the 20th century. Interest in these diseases, as reflected by literature citations, has changed greatly. The Index Medicus for the 5 yr 1974-l 978 contains a total

*This study is limited to the scleroderma that constitutes a manifestation of progressive systemic sclerosis and does not consider any of the varieties of localized scleroderma.’ From the Division of Rheumarology and Clinical Immunology, Depurtment of Medicine. Universiiy of Pittsburgh School of Medicine and the Vererans Administration Hospital. Pittsburgh, Pa. Address reprint requests to Thomas G. Benedek, M.D., Veterans Administration Hospital. Universily Drive C, Pittsburgh, Pa. 15240. 0 1982 by Grune & Stratton. Inc. 0049-0172/82/1201-0005$02.00/0 52

of 7 entries under sclerema neonatorum, 18 under scleroedema, and 23 columns of entries under generalized scleroderma. SCLEREMA

NEONATORUM

Until the middle of the 19th century, sclerema neonatorum was believed to occur mainly in France. If this assessment were correct, no explanation for such a geographic predilection is apparent. That this was a major pediatric problem is indicated by data from the HBpital des Enfants-trouvks, the Paris hospital for foundlings. According to Tenon, writing in 1788, an average of 600 infants was admitted to this hospital each year and another 400 to the H&e]Dieu with the diagnosis of “enfans gel&” or and “enfans durs,” i.e., sclerema neonatorum, most died.3 The frequency with which this disease was diagnosed gradually diminished, but the mortality rate did not. Between 1808 and 1811, 643 infants thus affected were at the HGpital des Enfans-trouvts, of whom 90% died.4 In 1826,240 infants (4.5% of admissions) received equivalent diagnoses.’ At the St. Catherine Hospital in Milan, 56 infants were admitted with this malady during the first half of 1823 and 62 during the second half of 1824. Forty of the latter were premature, an association that has been confirmed.6 The same disease was diagnosed as “acute sclerosis” at a German lying-in hospital only 53 times between 1828 and 185 l-in 0.2% of full-term and 16.1% of premature infants.’ These statistics clearly relate the etiology of sclerema with both immaturity and inadequacy of perinatal care. Although enfans gelis literally means “frozen baby,” this term was used because the infants appeared to be hypothermic and not because the condition necessarily was initiated by exposure to the cold. That they are in fact hypothermic was documented by H. Roger (1844, Paris).’ The report which, despite its peculiarities, has generally been accepted as the first description of sclerema neonatorum, was entitled “Eighth month live birth, cold and rigid” by J. Usenbenz, a German physician.‘*” On October

7, 1718 a soldier’s

Seminars II)Arthritis andRheumatism,

wife entered

the

Vol. 12, No. 1 (August). 1982

53

hospital in Ulm at the end of the eighth month of pregnancy. Her delivery was difficult and she bore a girl whom the midwife, because of the infant’s extraordinary coldness and because of the hardness which was so severe that one could not indent her cheeks even with strong pressure, viewed as a piece of ice. Her entire body resembled a piece of smoked meat and, were it not that weak respiration identified the presence of life, one would really have taken this child to be a lifeless mass. Otherwise it was well developed and fairly muscular. She was wrapped in warmed linen and was held near the fire in order to gradually warm her. The infant did become warmed, but like a piece of wood, for as smn as one removed it from the fire it again became cold. She remained stiff from head to heels. Due to the general stiffness and immobility of the cheeks she lingered in this condition for a whole day without taking nourishment. The infant died unresponsive and immobile, and without the least cry having been heard from it.

Underwood (1737-1820), a London obstetrician and pediatrician, in 1784 published the first English pediatric textbook. In this he called attention to “a peculiar tightness and hardness of the skin over almost the whole body” and considered this to be a terminal manifestation of a certain kind of infantile dysentery. “This symptom, or perhaps rather disease, somewhat similar to that called hydebound in quadrupeds, has not been mentioned in this view by any writer on the diseases of infants.“” He credited Denman (1733-l 8 15, London), professor of midwifery at Middlesex Hospital, with having called his attention to this disease. In the sixth edition of Underwood’s textbook (18 13), the disease was referred to as skinbound rather than hydebound and was no longer attributed to intestinal dysfunction. Underwood noted: “To me the appearance and feel of the skin have exactly resembled that of a person who has died during a very hard frost.” He believed that it has “been much less common in this kingdom than on the continent, but is equally an hospital disease . . . the disease raging so much in France differs in many respects from ours.“” The description of the alleged difference suggests that many of the French infants about whom Underwood learned actually had tetanus. Despite the common occurrence of this fatal disease in at least some French hospitals, it was first clearly described in France by Andry (1741-1829) in Paris and by Souville in Calais, both in 1788, and in 1790 by Auvity (d. 1821) in Paris.‘3-‘5 Souville preferred to call the disease oedkmatie concrSte (solid edema), while Andry and Auvity introduced endurcissement du tissu

ceflulaire (induration of the cellular tissue, i.e., the subcutaneum). The latter term achieved wider, although temporary, acceptance. According to Denis (1799-1863), Chaussier (1746-l 828) introduced the term scltrtme for this disorder in a public lecture that he gave as physician to the Hospice de la Maternitt in Paris (1804-1815).‘6 In 1815, Bard lauded Chaussier as the outstanding authority on scltrbme, but curiously, none of the latter’s numerous publications deal with this subject.” We have been unable to confirm the assertion of Ballantyne that Chaussier introduced the term in his graduation lecture to the 18 12 class of midwives.‘* It is absent from the published portions of his addresses. The use of sclereme and closely related terms for sclerema neonatorum (Table 1) was criticized both on etymologic grounds and (see next section) because of the several different conditions to which it came to be applied (e.g., scleroderma). For instance, Hennig ( 1825-l 9 11, Leipzig) in 1877 called sclereme a “barbaric name” and proposed sklerysma in its stead. His implied justification was that the former mixed Greek and Latin roots, while the latter is derived entirely from Greek.” Alibert (1768-1837, Paris) in 1817 added some confusion when he applied both sclerema universalis and sclh-bmie (neonatorum) to the same disease. Not until the end of the 19th century was the fully Latinized version of the latter term, sclerema neonatorum, generally accepted to designate the disease of newborns.*’

SCLEROEDEMA

Review of the 19th century publications suggests that scleroedema may have been more prevalent at that time, before it was clearly defined, than the rarity it is at present. The term, but not the description of the disease, was introduced by Soltmann (1844-1912, Leipzig), a pediatrician, in 1882, but was applied by him to the disease for which sclerema neonatorum had by then become the generally accepted name.*’ The earliest description of a patient who may have had scleroedema was published in 1753 by Curzio, a Neapolitan physician. Although many have considered this report to contain the first detailed description of scleroderma, two principal clues favor the diagnosis of scleroedema.

BENEDEK AND RODNAN

54

Table 1. Synonyms

for Sclerema

Author

T.WTl

Neonatorum Introduced

Nationality

Reference

Enfant gel&; enfant durs 18th c.

French

11

Underwood

1784

English

3

(‘cold infant’; ‘hard infant’) Hydebound disease Endurcissement du tissu cellulaire Andry

1780

French

13

Oedematie concrete (hard edema)

Souville

1788

French

14

Sclereme

Chaussier

1812 ?

French

16

Skinbound disease

Underwood

1813

English

12

Sclerema universalis

Alibert

1817

French

20

Scleremie (neonatorum)

Alrbert

1817

(induration of connective tissue)

20

lnduratio telae cellularis (induration of connective tissue)

Betschler

1832

Scleroderma

Betschler

1832

Teleorheuma infantum

Eisenmann

1842

German

Oedema algide (cold edema)

Roger

1844

French

8

Algidite progressive

Hervieux

1855

French

23 24

German

21 21 6

Endurcissement athrepsique Parrot

1877

French

Sclerysma

Hennig

1077

German

19

Scleroedema

Soltmann

1881

German

25

(induration due to inanition)

These are that the symptoms of this 17-yr-old girl included induration of the tongue and that she recovered fully after 11 mo despite having been severely incapacitated by tightening of the skin, Subsidiary indications in favor of scleroedema are the particularly severe involvement of the skin about the neck and lack of mention of any changes in the hands or feet, which typically are spared in scleroedema.26 This case has even been considered an instance of sclerema neonatot-urn, probably based on the hypothesis that this disease, which had not yet been differentiated from scleroderma, was only artificially separated from sclerema by the later age of onset.27,44 A clearer description of scleroedema, which also was categorized as a case of scleroderma in 19th century reviews, was published as a footnote in the chapter on “induration of cellular tissue” (i.e., sclerema neonatorum) in Henke’s pediatric text of 1809. The report follows:** A peasant maid, about 24 years of age, who was employed in the neighboring village of Bubenreuth

and

been healthy, was delivered of a child. According to her she lost her milk in the post-partum period due to a fever, but she recovered fully and had been able to resume her work for several months. On a very hot summer day, when she returned from the field fatigued, she lay down on damp hay in a very cool cellar with her neck and throat bared. . She fell asleep and remained recumbent for several hours. When she awoke she felt a stiffness in her neck which hindered the had always

movement of her head and made it painful. Over several days an induration of the cellular tissue (i.e., subcutaneum) developed which affected the face and the entire upper part of the body to the epigastrium. When I saw this person, steam baths, liniments, fomentations. internal diaphoretics. antimonials and mercurials had already been used for several months, virtually without effect. Only the initial stiffness of the neck had diminished a little, although she could flex the head only very slightly foreward and hardly at all laterally. The face, neck, throat, the not very prominent breasts, all felt as hard as wood and somewhat cold. The color was the normal pale yellow, slightly reddened on the cheeks. The eyelids were so stiff that she could not open them completely, and chewing and swallowing proceeded very slowly and exhaustingly. The lower abdomen and lumbar region retained

the natural

functions remained undisturbed.

softness, and all other

I

have heard that this

condition gradually disappeared spontaneously.

In 1869, Fagge (1838-1883, London) published a lengthy review to determine the diagnostic limits of “Addison’s keloid,” i.e., localized scleroderma. He concluded that:29 “Addison’s Keloid,” instead of being a distinct affection, is, in fact, but a part of a much wider group of cases which are spoken of (chiefly in French and German literature)

under the name of Sclerema,

Scleroma,

or

Scleriasis.

Despite this view, Fagge identified categories of patients in this “wider group” with which we would differ only by considering them to have distinct diseases rather than subsets of one ailment. He found six published cases (Henke,28

SCLERODERMA

55

Thirial,30 Bouchut,3’ Rilliet,32 Gillette33) and at least one unpublished case of his colleague, Gull (18 16-1890) in which “. . . there appears to be a wide difference . . .” from Addison’s keloid. Fagge had then not yet seen such a patient, all of whom we, concurring with Touraine et al. ( 1936),34 consider to have had scleroedema. Before the publication, but after the composition of this paper, Fagge described an unequivocal personally examined case of scleroedema. A 40-yr-old woman in January 1868 “caught cold,” complicated by otitis media. About 1 mo after drainage from the ear had ceased, stiffness began in the neck and gradually but quickly extended round the neck to the chest, down the back, and down each arm

On admission 1868:35

to Guy’s

Hospital

on May

27,

The skin of the neck, back, chest, arms, and face was hard and bacony. The induration commenced posteriorly at the occipital bone above, and extended downwards over the whole back, passing gradually into the healthy skin below, so as to form a triangle below the ribs, with its apex at the coccyx. In front it passed up on to the face, especially the lower jaw and the forehead. It reached downwards over the whole chest, and ceased at the level of the ninth ribs.. The colour of the skin was darker brown than natural, especially that of the face and neck. The natural creases of the face were diminished, producing a marked want of expression. She complained of finding a difficulty in opening her mouth, in consequence of the surrounding stiffness. The eyelids were not affected; and the tongue was likewise free.. . The disease extended down the arms as far as the wrists on the forearms it was less marked than higher up, especially on their flexor surfaces. The hands were quite healthy. The affected parts did not pit even on continued pressure.

There were no visceral findings. Beginning in July her condition improved. She was discharged in August and, as of June 1869:35 The disease is slowly but steadily subsiding. Her face has now a character and expression, which were wanting to it; and the induration is decidedly less. It is still more marked at the back of the neck than anywhere else.

Fagge summarized the relationship his case and those published previously: In four of the six commenced at the of the disease over has been generally three or four of the

between

cases above referred to the affection nape of the neck. The distribution the body in previously recorded cases the same as in my patient. In six cases it is expressly stated that the

rigidity ceased at the wrists, the hands being perfectly free. It has also been before observed, as in my case, to cease definitely at the epigastrium. The prognosis appears to be favorable . the skin has sooner or later returned to its natural state.

Fagge preferred the term scleriasis for these cases, therein following Virchow, who had, however, coined it to designate scleroderma.36 He recognized that Grisolle (1847) (72, vide infra) had been mistaken in considering his patient to have had the same disease as Thirial had described, and that “. . . the transition between scleriasis and Addison’s keloid appears to me to be completed . . . ” by the report of Arning (186 1) (8 1, vide infra). Fagge concluded that:35 the view which accords best with the existing facts is to regard the cases of Thirial, and those of Addison, as the extremes of a series, connected by means of other cases to be found in medical literature. And I would propose that the former cases should be known by the name of Acute Scleriasis, the latter by that of Chronic Scleriasis.

Thus, Fagge conceived of a clinical spectrum of manifestations of one disease, based mainly on the rapidity of development and location of skin lesions, whereby, in modern terminology, the most acute is scleroedema, diffuse scleroderma (progressive systemic sclerosis) is intermediate, and localized scleroderma is most indolent. The concept advocated soon thereafter by Hardy (181 l-l 893, Paris), a dermatologist, deviated only slightly from the foregoing. He divided “sclerodermie” into three categories, rather than specifying a continuum of symptoms: (1) sclerodermie oedemateuse, (2) scltrodermie en plaques, (3) scltrodermie des extremites3’ These would now be called, respectively, scleroedema, localized scleroderma, and diffuse scleroderma (progressive systemic sclerosis). Although Buschke (1868-1943), a dermatologist in Berlin, is usually credited with having distinguished scleroedema from other syndromes and for assigning to this syndrome its now accepted name, only the latter is true. In 1876, Piffard (1842-1910), a New York dermatologist, described the case of a 49-yr-old blacksmith whose illness began with stiffness of the neck and in about 10 days disseminated over the upper extremities and trunk. Piffard saw him 6 wk after the onset, when he “. . . complained of the inconvenience of being encased in an inelastic

56

BENEDEK AND RODNAN

covering which impeded the movement of his arms and compelled the abandonment of his occupation.” To Piffard’s surprise, a biopsy of the affected skin was microscopically normal. The patient was piaced upon small doses of quinine as a placebo, to satisfy him that something was being done for his skin, rather than with a view to a therapeutic result in three months recovery was complete.

Piffard described this patient specifically to distinguish his disease, which he, like Fagge, called scleriasis, from typical scleroderma and concluded perceptively that: Many of the cases of scleroderma heretofore reported have been of this description, and should have been earlier recognized as essentially differing from the chronic, almost incurable, and sometimes fatal disease to which alone I would confine the name of scleroderma.

Piffard undoubtedly was the first to distinguish scleroedema from scleroderma, as well as one of the first to be candid about the use of placebos, but his contribution remained hidden in his textbook of dermatology.38 We concur with the opinion of Jaffe and Winkelmann that many of the early case reports of scleroderma in children are more compatible with scleroedema,39 e.g., girl 15.5, Thirial 1845;3’ girl 9, Rilliet 1848;33 girl 8.5, Gillette 1854.34 Indeed, it is now recognized that at least 33% of the cases of scleroedema occur in children under 11 yr of age, making the term scleroedema adultorum incongruous.40,4’ However, the diagnostic confusion did not end quickly after scleroedema had become a well established diagnosis. For example, “A case of scleroderma diffusa in a girl, nine years of age,” published in 1918, gives an excellent description of an episode of scleroedema that followed an attack of “winter sore throat,” and lasted about 6 mo.42 Pediatric diagnosis is further complicated by the recognition of scleroedema in a few children during the first weeks of life.43 This raises the possibility that some cases that were considered to have suffered nonfatal sclerema neonatorum may actually have had this disease, although another-subcutaneous fat necrosis-is more likely (vide infra). At a meeting of the Berlin Dermatological Society in 1900, Buschke presented a 44-yr-old man who had experienced a bout of influenza 3

mo earlier: after recovery from the influenza a peculiar stiffness appeared in the neck. This stiffness gradually spread to the thorax, the face and the lower extremities, as well as the buttocks.

According to the summary of the discussion, Buschke chose to observe the patient longer before he would venture a diagnosis. Lesser, his chtef, suggested that this was the first case of sclerema neonatorum in an adult; Blaschko considered it a variant of scleroderma; and Heller and Rosenthal considered this to be “acute scIeroderma.“44 Buschke published the case in 1902, beginning with the statement that “In May 1900 I presented a patient . . . with the probable diagnosis of scleroedema.” However, the term first appears in this context in the paper of 1902. He made the distinction from scleroderma as follows:45 The extent to which other cases published under the designation of ‘acute scleroderma’ in part belong here [to scleroedema], can, of course, not be decided retrospectively. The cases called SclCreme or SclCreme of adults by older authors, such as Alibert, Henke [error], and especially Thirial, and those designated ‘scleroderme oedemateuse’ by other authors, such as Hardy and Besnier. or scleremie as a variety of scleroderma, actually have the characteristics of scleroderma and therefore are correctly to be counted as examples of that disease. They correspond to the so-called diffuse scleroderma of German authors. They do not have the symptomatology of our scleroedema we must consider this ailment as a discrete disease because characteristic of scleroderma usually are slight signs of inflammation which occur in the most superficial layers of the skin, and tense edema which can regress gradually, but always into the atrophic condition peculiar to the discase, generally with simultaneous pigmentation. All three signs are lacking here, and in the site where the edema has not regressed it is, so far as is clinically demonstrable, not an atrophy but an hyperplasia of connective tissue that develops.

Buschke was in error in not appreciating that the authors whom he cited here had described the same disease as he, rather than scleroderma, and also in not seizing upon more reliable histopathologic criteria for the identification of the skin of scleroderma. Alternative names to “scleroedema of Buschke” continued to be introduced for several decades (see Table 2). These included Staitinodermie (1 903),46 progressive benign subcutaneous induration (1928),48 benign scltreme of

57

SCLERODERMA

Table 2. Synonyms for Scleroedema Author

Term

Introduced

Nationality

Reference

Acute scleriasis

Fwge

1869

English

35

Scleriasis

Piffard

1876

American

38

Sclbodermie oedemateuse

Hardy

1877

French

37

Scleroedema

Buschke

1902

German

45

Staitinodermie

Baginsky

1903

German

46

Hoffmann

1923

German

47

{doughy skin1 Scleremia adultorum Progressive benign subcutaneous Sellei

1928

Hungarian

48

Benign s&r&me of aponeuroses

Audry, Gadrat

1930

French

49

Benign scleremia

Merenlander. Zand

1935

French

50

Diffuse benign sclerodermiform

Touraine, GoI&

1937

French

51

induration

Soulignac

cellulitis

aponeuroses rodermiform

( 1930),49 and diffuse benign sclecellulitis ( 1937),5’ among others.

THE DIFFERENTIATION OF PROGRESSIVE SYSTEMIC SCLEROSIS IN CHILDHOOD FROM OTHER SYNDROMES

Since sclerema neonatorum was well known in the 19th century and scleroderma was just being discovered, it is not surprising that the latter was confused with the former, particularly in children. Most young patients who were thought to have scleroderma probably had neither sclerema nor scleroderma, but rather scleroedema, or perhaps dermatomyositis.? The most convincing early description of scleroderma in a child antedated the recognition of this disease and dealt with an illness that the author considered to be an example of “induration of the cellular tissue,” i.e., subcutaneum, differing from typical sclerema neonatorum only. because the patient was 11 yr old, rather than a newborn. When Chowne became her physician in London in 1842 this girl had experienced gradually increasing fatigue for about 2 yr. Her mother first noted tightness of the skin and intolerance of cold within the preceding half year.” her manner of walking gave her the appearance, so far as figure and gait were concerned, of a little old woman; her head rather projecting; her shoulders up; her elbows drawn back; her arms half flexed, and her wrists half dropping down. The cheeks had a degree of firmness

TThe first acceptable report of dermatomyositis in childhood, a 7-yr-old boy, was from Vienna. Schiiller A: Polymyositis im Kindesalter. Jahrbuch f. Kinderheilkunde 58:193217, 1903.

and hardness which made them feel like the cheeks of a dead person after the heat has left the body and it has become rigid. They resemble to the touch a substance intermediate between flesh and wax.. The neck and integuments of the upper part of the chest were but slightly affected . . the arm and forearm gave to the touch the same impression as that given by the cheekthe hardness, however, still greater they had, indeed, rather the appearance of being wasted, and of the skin having shrunk even still faster than the substance it invested. Where the parts are less muscular, as on the elbows, wrists, and fingers, the skin has the glossy appearance I have spoken of, as existing on the integument of the forehead. The freedom of movement of both the elbow and wrist is diminished, that of the wrists and fingers particularly the lower extremities are affected like the upper the knee and ankle joints have a degree of rigidity like that affecting the elbows and wrists. . The right and left legs, like the right and left arms, appear to be affected in an equal degree. The ears are less flexible than they are in the healthy state. I have not been able to perceive, either on the cheeks or on any part, indentation from pressure (meaning that kind of indentation with which we are so well acquainted where there is oedema)

Foerster (1822-1865, Wiirzburg) in 1860 performed the first autopsy of a case of scleroderma, a 22-yr-old man who died of pulmonary tuberculosis. Examination of the skin of this patient led him to the hypothesis that sclerema neonatorum and scleroderma differ pathophysiologically. He conceived of the cutaneous alterations of sclerema to require a dual process: infiltration of the subcutaneous connective tissue by serous fluid and a chemical alteration of the subcutaneous fat whereby it becomes firmer. In scleroderma, a proliferative process was invoked? the loose reticular structure of the connective tissue must be converted into a tough, compact one and this can

58

BENEDEK AND RODNAN

probably only occur by means of a proliferation of connective tissue whereby the fibers thicken, the interstices are filled, and the junction between the connective tissue and the corium on the one side and the deeper parts: muscles, fascia, tendons, etc. on the other becomes denser and more rigid. To what an extent a connective tissue proliferation occurs in the corium itself remains uncertain, although such a process seems very probable.

A pathologic differentiation was not accepted quickly. For example, Hennig, writing in 1877, believed that the differences between sclerema neonatorum and scleroderma result merely from the greater delicacy of the neonatal tissues that are affected. Therefore:53 The Scleroma (see adults less severely, insidiously without without reacting so newborns.

Table 6) attacks older children and evolves more slowly and progresses costing the life of the patient and destructively in the vital organs as in

Silbermann (1880, Breslau) advanced a similar argument, elaborated in greater histologic detail, whereby he was probably distinguishing scleroedema rather than sclerema neonatorum from scleroderma. His conclusion was that the rarity and (alleged) reversibility of scleroderma in infancy is due to age-related differences in cutaneous structure.54 Both authors, consistent with contemporary opinion, failed to appreciate the visceral manifestations of scleroderma. Further complicating disease identification, the cases that have often been cited as the first fairly detailed accounts of scleroderma in infancy were, almost certainly, descriptions of yet another disease: subcutaneous fat necrosis. Cruse, a physician to the St. Petersburg (Russia) Foundling Hospital, published such a case in 1876 and republished this with three similar cases 2 yr later. He did not consider them to be the first, but only the youngest instances of juvenile scleroderma, stating that of the first 62 published cases of this disease, 12 were children between 2.5 and 13 yr of age. The first of Cruse’s patients was a newborn girl who was brought to the Foundling Hospital after several hours of exposure to -25%. She weighed 3.3 kg and was well formed. When she was about 1 wk old, the nurse noticed that her cheeks were swollen. A week thereafter, when Dr. Cruse first saw her, he found that: On inspection

the child’s cheeks

appear

thickened,

as

though it were very well nourished. The skin of the cheeks is shiny, somewhat erythematous and traversed by small distended vessels. On palpation both cheeks feel hard and stiff, like a very firmly upholstered leather pillow. There is no pitting edema, the temperature is normal, pinching is impossible. The anterior margin of the induration coincides fairly exactly with the nasolabial crease, posteriorly there is no distinct border, but gradual merging with the normal skin over the zygoma and the edge of the mandible. Otherwise the child is healthy.

Patches of induration appeared on the left extremities, right knee and the abdominal wall until the 38th day. In the sixth week lesions began to soften and this continued until the 49th day, when she died of bronchopneumonia. Cruse was of the opinion that? Without doubt, this was not an ordinary sclerema (socalled sclerema neonatorum). This rather was a case of that rare cutaneous sclerosis which was first described by Thirial as sclerema adultorum. It is well known that this term soon was replaced by the term scleroderma, because it was observed that this sclerosis of the skin is not exclusively peculiar to adults, but also occurs in children.

The three later cases were girls whose disease began in the third and second week of life, and a boy who had numerous foci of cutaneous induration in his seventh week, when he was initially seen. These infants recovered and were transferred to foster homes when they were 3-4 mo old. Cruse now concluded that:56 one will not hesitate to designate these cutaneous indurations as scleroderma (Scl. adultorum). Possible confusion with sclerema neonatorum seems to be excluded firstly by the entirely undisturbed general health of the children we observed. Further points of distinction consist in the focal dissemination, the firm, unyielding consistency and the more or less sharp border of the indurations, which are contrary to the cold, edematous infiltrate of the skin in sclerma neonatorum, where it advances gradually, but usually in continuity over most of the body. The indurations in our cases did not have the appearance of scars, and they also were not attached to the corium as in Keloid [morphoea], but they involved the corium and subcutaneous connective tissue. Thus, we must adhere to the diagnosis of Scleroderma adultorum.

Cruse accurately discerned that these cases differed from sclerema neonatorum, but erred in concluding that this was the same disease as that which Thirial had reported. Cruse had well described a condition that first was suspected to be a discrete disease by Fabyan (1907, Balti-

59

SCLERODERMA

more), who concluded from the autopsy of a 2-wk-old infant who had died accidentally that he had “disseminated subcutaneous fat necrosis without other lesions.“57 Fifteen years later, Bernheim-Karrer (1922, Ztirich) recognized the identity of Cruse’s cases and diseased infants whom he had seen. He biopsied lesions of two infants and found that? Microscopically, the so-called neonatal scleroderma i.e., subcutaneous fat necrosis, is characterized as a disease of the subcutaneous fatty tissue, and actually as a necrosis of this tissue, which is accompanied by a considerable inflammatory reaction. The histologic picture of genuine scleroderma is quite different. In it one finds a homogenizing degeneration or an increased density and partial loss of the connective tissue and subcutaneous inflammation. Thus, the genuine and the neonatal scleroderma are differentiated not only clinically, but microscopically.

Although Bernheim-Karrer continued to use the term “neonatal scleroderma,” he suggested “subcutaneous fat necrosis of the newborn” as a more appropriate designation, and this term has been widely accepted. The principal distinctions between sclerema neonatorum and subcutaneous fat necrosis are shown in Table 3. Cockayne ( 19 16, London) critically reviewed the literature about juvenile scleroderma. Being unaware of subcutaneous fat necrosis, he concluded that Cruse’s cases “are undoubtedly sclerema neonatorum” and believed the same to have been true of many other infantile cases. He accepted 102 cases as “true scleroderma,” including 11 under 1 yr of age, 24 between 1 and 5, 42 between 6 and 10, and 25 between 11 and 13.59 How many of these children had localized forms of scleroderma rather than progressive systemic sclerosis was not specified. The former occurs more frequently in children than the

latter. According to two studies from the Mayo Clinic: 40 of 235 patients (17%) with localized scleroderma had the onset below the age of 11 yr.6’ while progressive systemic sclerosis began under 10 yr of age in only 1.5% of 727 patients6’ The possibility that there is a spectrum of manifestations of a single infantile cutaneous disease bearing some similarities to scleroderma, rather than several diseases, has not been fully disproved. The coincidence of sclerema neonatorum and subcutaneous fat necrosis has been described:* as well as unclassified cases such as one reported by Weidman (1920, Philadelphia) as “congenital scleroderma and sclerodactylia.” The infant had skin that was “hard and immovable over the flexures of all the extremities,” but microscopic examination showed only fibrosis of the subcutis, which is atypical of any of the diseases we are considering.63 Kneschke (1923, Dresden) described a girl on whose pretibial regions tense, glistening skin was noted in the first week of life. By the fifth month the thighs, legs, abdominal wall, and head seemed characteristic of scleroderma. A skin biopsy was compatible with scleroderma and ruled out subcutaneous fat necrosis. However, at 13 mo of age her development continued normally, some lesions had diminished, and none had progressed.64 In a few cases the likelihood of congenital progressive systemic sclerosis seems even more probable. Cockayne described a prematurely born boy whom he observed from the age of 7 to 26 mo.58 at the age of 7 months the infant showed a typical sclerodermia and sclerodactylia of adult type, with some fibrous myositis. The skin of the abdomen and chest was thick, and difficult to pinch up, and the abdomen showed

Table 3. Differentiation Between Sclerema Neonatorum and Subcutaneous Fat Necrosis Sclerema Neonatwum

Subcutaneous

Gestation

Many

onset

First week

Usually

Normal

Poor

General Sites

health

of lesions

premature

Whole

body,

Fat Necrosis

Full term

sparing

palms,

soles,

2-3d

Buttocks,

wk.

thighs,

up to 6 wk

arms,

face

genitalia Appearance

Diffuse,

smooth

induration,

no discol-

oration Histologically

Prognosis

plaques

Noninflammatory, ened Poor

Firm circumscribed

fibrous

fat normal, trabeculae

thick-

in some

Granulomatous cutis Excellent

erythematous

or violaceous

and nodules inflammation

and fat necrosis

in sub-

60

BENEDEK AND RODNAN

pigmentation

in a reticular

pattern.

The legs could not

be fully extended. The skin was thickened and hard over the outer side of the thighs, round the knees, and over the whole of the lower part of the legs. The toes were fixed in a hammer-toe

position, and the nails were atrophic. The

skin of the upper part of both arms was natural, but over the whole of the forearms and hands it was sclerosed. The

fingers were firmly

fixed in flexion.

small and with the wax-like induration

remarkably

appearance.

There was

of the whole of the skin of the face, with

marked atrophy of the lobes of the ears, the alae nasi, and round the mouth, but the mucous membrane tongue had escaped. The skin of the back,

and

buttocks,

groins, scrotum and penis was normal. The muscles of the chest, abdomen and legs were obviously atrophied and fibrous. a sclerema so extensive would almost certainly have proved fatal

and even in the event of recovery

the skin condition would have cleared weeks usual

The distribution in sclerema

occurred

is like

that

.

The

up

within a few

is the exact opposite to that pigmentation

commonly

which

seen in adults

has with

sclerodermia. DIFFUSE

SCLERODERMA SYSTEMIC

(PROGRESSIVE

SCLEROSIS)

We have collected 19 terms that were coined between 1817 and 1877 to designate a disease that in some instances undoubtedly was what we now call progressive systemic sclerosis and in others the as yet unidentified disease, scleroedema (Table 2). Fifteen of the terms include the root “scler” or “skier” (hard). In several instances a term was introduced in relation to one disease which later authors applied to another. For example, the French dermatologist, Alibert, introduced “scltrbmie des adultes,” “scltremie neonatorum,” “scleremia universalis,” and “scleremia circumscripta.” The first of these was adapted from Chaussier’s sclh+mie, whereby he had designated the neonatal syndrome which is now called, after Alibert, sclerema neonatorum. Alibert used the French term on the premise that this was one disease that was rather common in infancy but rare in adults. The brief clinical descriptions of sclhdmie des ad&es that Alibert provided may represent scleroedema, but clearly not diffuse scleroderma. Scleremia universalis was used synonymously with scleremia (neonatorum), while under scleremia circumscripta he gave two adequate descriptions of morphoea (localized scleroderma) .” The earliest use of the term scleroderma we have found appears in a report by Betschler from the Women’s and Children’s Hospital of Breslau,

Germany, from 1832: “lnduratio telae cellulosae (Scleroderma) was observed in a newborn male.“2’ “Scleroderma” was used here as another synonym for sclerema neonatorum. Eisenmann (1842) used the term in the same sense.22 In 1836, Fantonetti (1791-l 877), a Milanese physician, became the first to use “scleroderma” to designate a disease in an adult. However, it is likely that his patient with skleroderma generale actually had scleroedema, since the illness resolved almost completely within several months.@ Thirial (18 10-l 863, Paris) has been credited with the first clear descriptions of scleroderma, we believe erroneously. Like Alibert, Thirial believed that he was describing a relatively benign adult variant of the fulminant neonatal disease and, accordingly, used the terms “sclereme des adultes” and “sclerema adultorum.” He published two cases in 1845 and reported the same information plus a third case in 1847.30.67 The patients were women, 15, 21, and 43 yr of age, who suffered rapidly progressive, diffuse induration involving the skin of the face, neck, thorax, and arms, but sparing the hands, Only the youngest patient remained under observation, and she recovered in about 1 yr. Lack of acral involvement, as well as the abrupt onset of the illness and the progression and distribution of the cutaneous abnormalities are typical of scleroedema, but extraordinary for scleroderma. Several earlier cases, which their authors also believed to represent instances of sclerema neonatorum in older persons, in all probability also were instances of scleroedema (Table 4). It appears that scleroedema was more common prior to the introduction of antibiotics than it is today, and it may be that its decline is attributable to the marked reduction in the frequency of acute infections such as are believed to provoke this disease. On the other hand, even the best of the early descriptions of scleroderma, lacking as they do Raynaud phenomenon or visceral manifestations that are now considered characteristic of progressive systemic sclerosis, should be looked upon as likely, but not unequivocally to have identified this disease. Forget (1800-l 861, Strasbourg) in 1847 reported a case of scleroderma that he had

61

SCLERODERMA

Table 4.

wick

Earliest Reoorts of Probable Cases of Scleroderma

1632/34

1832,

Contractures.

apondylitir.

None.

7 Raynaud

NOW

lndwation

died 1847

dysP”= ChObV”e

1842

1842/l

Startin

1846

1841120

Coneact”res

4v

lCth”OSls Cor”OB

FOrget

1847

1837133

“Rhs”mat,sm”

2mo

Chorionitis, s&ost&nose

1847/50

_

2mo

Charionitis. sclirostbnose

1

Contractures.

of the cellular tissue

cuts&

cuta&

&lsdk

1847

Case No.

72

Chwionitis.

sclirostbxe

cvtanb

73

M

65

1647/65

Chononitis,

sclirost~nose

cuta& 74

F

64

ia47r66

Died I” 2 vr

Chaionitis.

sclirost6nose

cutanb

observed

10 yr earlier:

Mrs. Bruckman, age 33, a servant, entered the hospital on January 18, 1837. She is said to have. enjoyed good health until a few years ago, when she began to suffer with rheumatism; several joints became swollen at different times, and her wrists still carry the traces of numerous applications of leeches and cupping glasses. Today the two wrists are stiff as though partially ankylosed. This stiffness also involves the ankles; it is less pronounced in the elbows and knees; but what is most remarkable is that this seems to be due less to disease of the joints than to a curious condition of the skin, which.. . is hard, tense, shiny, brownish, resembling scar tissue. This same appearance is present over nearly all the body. Thus the face appears sun-burnt, mummified, the countenance has a strange immobility due to the tension of the integument. The skin of the neck is shrivelled like parchment and impedes movement of the head. The upper part of the chest, front and back, offers a smooth, resistant surface, the superficial irregularities being effaces by the tension of the skin. The abdomen is equally flat, shiny, resistant; in short, the skin appears to be too tight to cover the body.

There were no visceral symptoms. Forget believed that he was the first to describe this disease and proposed two names: chorionitis and

scli?rosttnose cutanke. ‘a Forget’s report stimulated Thirial to enlarge upon his paper of 1845 in the belief that his patients had the same disease and with the intent to establish his priority of description.67 Gintrac (1791-l 877, Bordeaux) in the same year argued that neither Thirial nor Forget deserved this distinction by recalling 17th and 18th century accounts (including the case of Curzio) which, however, we consider unlikely to have been instances of scleroderma. His report, “Note sur la sclerodermie,” cited Fantonetti’s paper, “Skleroderma generale,” which had been published in a rather obscure Italian journal in 1836, but it

was this French publication that in effect initiated the use of the term “scleroderma.“70 Although we consider Gintrac to have erred in his identification of earlier reports of cases as scleroderma, we believe that at least three acceptable cases were published prior to 1847, the year in which interest in this disease blossomed. In that year eight reports on this subject appeared, seven in French and one in German. Of these we consider four to be probable instances of scleroderma: Forget, two cases;68”*b$ Briick;” Grisolle, same case as second of Forget;72 Putegnat;73 and the others probable scleroedema: Thirial, three case$’ Bouchut3’ (see Tables 4 and 5). Gintrac” recorded no personal cases. Of the cases of scleroderma reported before 1847, that of Chowne (1842) is summarized in the section on childhood scleroderma. The cases of Brtick” and of Startin” will be reviewed here. Briick’s case is peculiar in that his description suggests both scleroderma and ankylosing spondylitis. The patient was a 34-yr-old butcher who was examined in the hospital of the spa at Driburg, Prussia, in 1832. Briick described the patient, including sketches of the face and hand, in the annual report of that hospital for 1832, which we have been unable to obtain. Stimulated by abstracts of Forget’s cases, he republished his case in 1847, but unfortunately without the illustrations, to which he only refers. At the age of 30 the patient experienced acute, transient dyspnea on a cold morning and,

*On September 25, 1847 Forget submitted a communication about another patient who seems to have had scleroderma, which was published the following year.‘”

BENEDEK AND RODNAN

62

Table 5. Early Reports

A”thOl

Year

of Probable Cases of Scleroedema Previously Considered to Have Been Scleroderma

RE63W”W

sex

Age

CWZW

1753

26

F

17

Henke

1809

28

F

24

Fantonetti’

1836

66

F

30

1845

30

F

21

F 1847

67

F

1847

31

M

32

Thinat

(1, 12) 13)

Bouchut *Diagnosis

Yea Seen 1752

D”W,W” 0W.¶t

When Seen

?

8rmf

7

AC”@

Several months

1830

? W&S

2-3

1833

AC”W

9,ld

15

1844

W&S

3mo

43

1846

Acute

2 mo

1847

AC”M

3 mo

mo

Areas ln”ol”*d Ha”&

Neck

Duratlo”

7

+ t

“Gradually dmppesrd’

+

+

Approximately

+

?

+

Several months

+

“Some months”

+

“lmpm”*me”f

+

11 mc’

6 mo

has beg”“”

is least definite.

Five days later his right wrist became painful and swollen. It soon became stiff and the skin adherent. Next, the entire arm became painful so that he could not move it. The same changes then occurred in the left arm and all of the left fingers became stiff, hard, cold and contracted at the distal joint. Next, the entire vertebral column became partially contracted, the thorax fixed, so that respiration, although painless, was mechanically hindered. The skin over the sternum became firm and immobile. As soon as ankylosis of a joint took place the overlying skin became hard, cold, immobile, nearly insensitive, and perspiration ceased. Indurated areas of skin also formed on the skull and the facial skin eventually became tense. Several months after the upper body was affected the lower extremities became involved, only the toes remaining flexible. The appetite remained fair, bowel and urinary function regular, circulation undisturbed.

After 15 yr the author recalled that the sclerodermatous process (his term) had been especially prominent on the fingers and head. He likened the fingers to wax candles. The face was pale, cool, and rigid, while on the skull the scleroderma predominated on the right side; the skin was firmly adherent to the bregma. Because of the involvement of the vertebral column the patient could not flex; walking was also laborious. Treatment with warm sulfur mud baths resulted in improved mobility. “I then lost contact with the patient, about whose death I learned a few weeks ago. . . .“‘I Startin of London, who had studied with Alibert, described in 1846, under the designation icthyosis cornea, a seemingly definite case of scleroderma that was not noted in any of the comprehensive reviews of this disease.76-79 The patient was a Scottish girl who at the age of 18 began to develop a “contraction of the right arm.” After several months a painful ulcer appeared on the tip of the index finger: and in succession upon the ends of all the fingers; these were very sore and a long time in healing . ; but during this process the fingers gradually contracted, and the wrist became stiff.

Ulcers also formed on the left hand: both around the nails and on the joints of the fingers, which healed gradually, but left the sort of contraction as existed in the right hand and arm.. These small abscesses gradually hardened and obliterated all traces of the abscess leaving a horny point or scale in its place.

After about 12 mo, stiffness spread face, legs, and after a year and a half and chest pain began. Startin first April 1841, after she had been ill yr.75

to the neck, palpitations saw her in for about 2

the skin of the neck, at the sides, was covered in irregular patches with dark stains, which also existed on the chest and other parts of the body. The fingers were very much contracted into the palm ; the nails were also thickened and curved, and the hand and arm felt more like a piece of solid wax, covered by cuticle tightly stretched over it than anything else; there was very little motion in the wrist and elbow joints, and scarcely any in the fingers; many parts of the body also manifested the same hardness and stiffness. The skin around the mouth was so hardened that the part could be opened only by an unusual muscular effort; it felt like moderately flexible pasteboard; this state was also remarkably obvious over the abdominal muscles; the skin, meanwhile, was very little changed from its normal appearance, a few large scales only being apparent about the ankles, wrists and fingers. . yesterday [ 1845, age 241 1 received a letter from her sister. She writes: “My poor sister is now never off the sofa, or her bed, she is so dreadfully reduced by low fainting fits, which of late have troubled her, and are followed by hours of exhaustion; her stiffness, too, increases, so that she soon will become like a piece of bone.

The use of icthyosis cornea by Startin originated in the classification of skin diseases begun by Willan (1757-1812, London) in 1808 and completed by his student, Bateman (1778-1821) in 1813.” In this, ichthyosis was divided into “simplex” and “cornea,” neither of which appear to have had a bearing on scleroderma. Startin sought to elaborate this classification, but seems

SCLERODERMA

63

Table 6. Synonyms for Diffuse “Scleroderma” Author

Term S&&tie

des adultes

Skleroderma

Introduced

Nationality

Reference

Alibert

1817

French

20

Fantonetti

1836

Italian

66

Sclerema adultorum, sclieme

des adultes

Thirial

1845

French

67

lchtyosis cornea

Startin

1846

English

75

Chorionitis

Forget

1847

French

68

Scl6rostenoss cutanee

Forget

1847

French

68

Erytheme chronique

Grisolle

1847

French

72

Scleroderma adultorum

Briick

1847

German

71

Cutis tensa chronica

Fuchs

1854

German

69

Sclereme simple

Gillette

1854

French

33

Scleroma

Foerster

1861

German

52

Sclerosis cutanea simplex

Kijhler

1861

German

83

Hautsklerom

Mosler

1862

German

84

Skleriasis

Virchow

1863

German

36

Cicatrisierendes Hautsclerem Wernicke

1864

German

85

Sclerodermia

An-ring

1864

German

86

Elephantiasis sclerosa

Rasmussen

1867

Danish

87

Dermatosklerosis

Wilson

1869

English

88

Sclerodermie de-sextremites

Hardy

1877

French

37

Progressive systemic sclerosis

Goetz

1945

South African

95

(scarring sclerema of skin)

rather to have perpetuated Willan:$75

a diagnostic

error of

I have only met with one other case recorded, at all resembling Miss H.‘s, and that is copied by Willan in his description of icthyosis cornea, from the Philosophical Transactions: (the Neapolitan case of Dr. Crusio [sic]). This term, like several others,69,83*85,s7 was used by only one or two authors in describing scleroderma (see Table 6). By the 1860s enough cases diagnosed as scleroderma had been published that reviews of the subject began to appear.81V84V89 Some cases, such as those of Thirial, were included consistently, others by only some authors, while some, e.g., the cases of Chowne and of Startin, remained unkown. Unfamiliarity with the clinical spectrum of the disease resulted in the application of diagnostic criteria for scleroderma that would soon become obsolete. For example, Arning, in 186 1, reviewed 24 cases of which he accepted 18 as being true scleroderma. Like other authors, he accepted the cases of Curzio, Henke, those of Thirial, and the child described by Rilliet,32 all of $Willan R: Cutaneous Diseases. London: J. Johnson, 1808. pp 207-210. Willan begins the section on “lcthyosis cornea”: “I never met with an instance of a horny rigidity of the integuments, impeding the motion of the muscles, or joints.” Then the case of “Dr. Crusio” is reprinted.

which upon the accumulation of more clinical experience probably were instances of another disease-scleroedema. He rejected the case of Fantonetti, with which we agree, but also that of B&k, about which we differ. Of particular interest is Arning’s rejection of the two cases of Fiedler (1855).” They were a 20-yr-old woman and a boy of 13.5, both of whom had experienced the onset of their disease at the age of 10. The descriptions are adequate and entirely compatible with scleroderma, despite the early onset. One reason for rejecting this diagnosis in the boy was that he had ulcerations over bony prominences and “In none of the other published cases is such a picture described.” Furthermore, “. . . both cases pertain to individuals from the most miserable and reduced conditions, while other patients have enjoyed relatively good circumstances.” Horteloup (1837-1893, Paris) in his doctoral thesis of 1865 summarized 30 cases of scleroderma, five of which he considered incompletely proven. Two reports, cases of Fournier and Raynaud, had not been published elsewhere. Horteloup credited Gintrac” with the introduction of the term sclhodermie and explained:89” The new name [scltrcdermie], introduced by Gintrac into the medical terminology, has the great advantage of not seeking to specify the precise nature of the malady; it

64

BENEDEK AND RODNAN

indicates simply that the skin, the dermis, is hard; it does not have the disadvantage of suggesting an inflammatory process, like the word chorionitis, or make it appear that the illness observed in adults is the same affection seen in the newborn, as it would if one assigned to it the name scl~r~me. These are the reasons that have led us to take the word scl~rodertnie for the title of our work.

The thesis of Horteloup is of particular importance because it contains a personal communication from his colleague, Raynaud (1834-1881) concerning a patient with sclerodermie and coldinduced “asphyxie locale” -the first description of Raynaud phenomenon in progressive systemic sclerosis:89b Monsieur G , 30 years old, farmer in excellent health until the age of 23 he began to experience numbness of the upper extremities. . The skin of the face became slightly thickened and rigid. But, above all, it is the state of the extremities that fixes one’s attention at first. The fingertips are bent. . In the space of an hour one sees the fingers change color several times, that which is dominant being a ghastly shade of greenish grey. But at moments, for example in the morning when the patient has just arisen, or under the influence of cold, the hands and the wrists take on a blackish color which the patient compares, no doubt with some exaggeration, to the color of his clothing. In addition, and this is quite characteristic, the fingers and the back of the hand are the seat of a kind of sclerema [scltrbme] with thickening of the integument; on the fingers it is quite impossible to wrinkle the skin. One thinks of a piece of cardboard. On the back of the hand it is very difficult even to slide the skin over the underlying parts. The fingers remain half flexed, impossible for the patient to open or to close completely, even aided by another’s hand. In touching the extremities there is a sensation of considerable coldness. The pulse is perceptible in the radial and pedal vessels. One can verify some irregularities that the patient himself has noticed. The patient does not have a syphilitic background. He used to eat rye bread in Savoie, but always in a small amount; he does not think that he ever consumed any spoiled rye [ergotism]. He usually ate wheat bread.

Arnold (Baltimore) in 1869 published “Three Cases of Scleroderma,” the first American report on this topic. The first patient was a man in whom acrosclerosis was described, the second was a young woman with scleroedema, and the third was a man with localized scleroderma.% The first unequivocal American case of progressive systemic sclerosis was reported by Day (New York) in 1870: a 37-yr-old man whose disease had a fulminating course and resulted in his death after only 13 mo.9’ Scleroderma con-

tinued to be considered an even greater rarity in America than in Europe. Thus, Osler (184919 19) stated that he had never seen a case during his tenure at McGill University (187551884) or at the University of Pennsylvania (18841889). In the Johns Hopkins Hospital and his large consulting practice he made the diagnosis of scleroderma in eight patients between 1891 and 1897. One of these, a man with thyrotoxicosis, clearly had pretibial myxedema rather than scleroderma. These patients impressed Osler profoundly and brought forth this poetic characterization:92 In its more aggravated forms diffuse scleroderma is one of the most terrible of all human ills. Like Tithonous,** to “whither slowly,” and like him to be “beaten down and marred and wasted” until one is literally a mummy, encased in an ever-shrinking, slowly contracting skin of steel, is a fate not pictured in any tragedy, ancient or modern.

In the 19th century, the occurrence of visceral disease in patients with scleroderma had been considered to be coincidental. The importance of visceral involvement as an inherent component of this disease was first recognized by Matsui (Tokyo, 1924) based on the findings in five autopsies.94 Appreciation that scleroderma characteristically becomes a disease of multiple organs finally was crystallized by Goetz (Capetown, 1945). In his discussion of the results of the autopsy of a woman who had suffered symptoms of the ailment for 22 yr he coined its modern designation, reasoning as follows:95 Obviously the term ‘scleroderma’ should be abandoned. It is quite evident to-day that we are dealing with a systemic disease neither solely nor primarily involving the skin. ‘Scleroderma’ is only the obvious and striking symptom of a generalized disease and the most serious symptoms actually arise in the viscera.

**The simile about Tithonus appears to have been chosen rather poorly, since the myth pertains to senile deterioration rather than to some sort of constriction. The goddess Eos (Aurora) had aroused the jealousy of Aphrodite (Venus). In revenge, Aphrodite caused Eos to fall in love with Prince Tithonus, a mortal. Eos begged Zeus to make Tithonus immortal, to which he acceded, but she neglected to request that he remain perpetually youthful. Hence, Tithonus eventually deteriorated into senility, but could not die. Because of his repugnance, Bos incarcerated him, but finally, out of pity, he was turned into a cicada (or grasshopper in some versions).”

SCLERODERMA

65

. . It appears therefore to the writer that now is not an inopportune time to abandon the term ‘scleroderma’ which for so long has obstructed investigation into the cause of that disease and to replace it by one more descriptive of the true state of affairs. The term ‘sclerosis’ already being in use, it appears that ‘progressive systemic sclerosis’ would describe the condition adequately until such time as the etiology has been estab-

lished. Scleroderma signs of progressive

is then only one of the symptoms systemic sclerosis.

or

ACKNOWLEDGMENT We are grateful to Dorothy T. Hanks, Reference Librarian of the History of Medicine Division, National Library of Medicine, for assistance in securing copies of many of the works cited in this article.

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