668

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XANTHOMA

Synonyms.—Xanthelasma (Wilson); Vitiligoidea (Addison and Gull); Fibroma
lipomatodes (Virchow); Fr., Xanthome; Plaques jaunâtres des paupières (Rayer);
Molluscum cholésterique (Bazin).

Definition.—A slightly elevated, flattened, or somewhat rounded,
soft, neoplastic growth of a yellowish color, usually seated as one, several,
or more lesions about the eyelids, and occasionally of more or less general
distribution. There are two varieties observed—xanthoma planum and
xanthoma tuberculatum seu tuberosum; in the former the lesions are
flat or plate-like, and usually seated about the eyelids; in the latter,
rounded and nodular, and somewhat general in distribution (xanthoma
multiplex). This last term is also applied to the mixed type, which,
however, is almost invariably more or less disseminated.

Symptoms.—Xanthoma Planum.¹—This, the macular or plane
variety, is usually seen about the eyelids (xanthoma palpebrarum),
and consists of one, several, or more small or large, round or elongated,
smooth, opaque, yellowish patches, sharply defined and often slightly
raised, and looking not unlike pieces of chamois leather implanted in
the skin. Their first appearance is probably most commonly on or near
the inner canthus on the upper lid, and, it is alleged, more frequently the
lid of the left eye. As a rule, however, when medical attention is directed
to the blemish, the growth is to be seen on the lids of both eyes. From
my own experience I cannot say that the upper is more frequently in­
vaded than the lower. Usually the patches are to be found on both
lids, more or less symmetrically arranged. There may be but several
present, or the eyes may be more or less surrounded by an apparently
continuous band. In most cases, however, there are several closely
contiguous patches, which, unless closely inspected, seem to be fused
into one strip. The growth is smooth, scarcely elevated, soft and com­
pressible, and of a lemon­ or orange-yellow color, more frequently a
dingy lemon hue, which becomes more pronounced when the skin is put
upon the stretch. Examined closely, especially if the skin is stretched,
or with a magnifying-glass, the patch resolves itself into numerous,
crowded, small yellowish spots, each with a minute pinkish or reddish
central point. The surface of the skin overlying the yellow plaques is
apparently normal and free from scaliness. Occasionally, instead of a
yellow hue, a whitish or creamy color is observed, and exceptionally,
especially in some lesions, the color may be much darker than usually
observed—from a dark yellow to a deep brown; a rare instance of the
latter was noted by G. H. Fox,² in which the xanthoma band, in a male,
of eleven years’ duration, was roughly suggestive of an ecchymosis.
Their growth is, as a rule, exceedingly slow, several years or more usually
elapsing before they have attained considerable dimensions. Exception­
ally, in addition to the patches on the eyelids, the spots are also observed

¹ Hutchinson, London Med.-Chirurg. Soc’y Trans., 1871, p. 171, has contributed a
valuable paper on xanthoma palpebrarum, based upon 36 cases under his own care—
cases are detailed and tabulated: he also gives another table of 7 cases observed by
others, of which 3 are of the multiplex variety.

² G. H. Fox, Jour. Cutan. Dis., 1889, p. 103 (case demonstration).

XANTHOMA

669

beyond the lids, on other parts, and even in the mouth; as a rule, however,
in the latter cases the growths are of the nodular type, and sometimes of
mixed character. There are no subjective symptoms, although excep­
tionally occasional itching or burning is experienced.

Xanthoma tuberculatum seu tuberosum (xanthoma multiplex)¹ is, as
the qualifying term signifies, of a nodular character. In most respects
the growths are similar to those of the plane variety, but they are usually
rounded in outline, somewhat elevated, and are either soft or of moder­
ately firm consistence. They are rarely found about the eyes, but on
other parts, and as a rule more or less general in distribution. Excep­
tionally the palms are also involved, presenting a yellowish white, flat­
tened infiltration along the main lines. The growths average a small
pea, but are often crowded together into groups, bunches, or almost
solid plaques. In some cases the nodules are noted to have a pinkish
periphery, especially in their formative period. Exceptionally they may
reach considerable dimensions, usually due to coalescence of several of
the growths. An instance of this kind was observed by Lehzen and
Knauss,² the patient being a child, some of the growths reaching the size
of an egg. Similar tumors, although not quite so large, have also been
observed by Carry and Chambard.³ In general cases certain parts are
most frequently the sites of the lesions, such as the hands, about the el-

¹Xanthoma multiplex—important literature: Committee Report (Hutchinson,
Sangster, and Crocker) of London Patholog. Soc’y, Transactions for 1882, p. 376 (with
an analytic tabulation of 23 cases in adults, with associated jaundice, a tabulation of 5
cases in adults without jaundice, and a tabulation of 8 cases in which the disease was con­
genital or appeared before puberty); Török (“De la nature des xanthomes”), Annales,
1893, pp. 1109 and 1261 (an exhaustive report with references, and a detailed analytic
tabulation of 40 cases of xanthoma multiplex in the adult, and another of 30 cases in
children). These two papers cover the cases pretty fully to date. Among other cases
recorded since: Shepherd, Montreal Med. Jour., 1893-94, vol. xxii, p. 765 (case demon­
stration—adult—jaundice); James, Brit. Med. Jour., 1894, ii, p. 805 (child—congenital)
Feulard, Annales, 1894, p. 544 (child); Thibiérge, ibid., p. 318 (2 boys—brothers);
Stout, Jour. Cutan. Dis., 1894, p. 244 (with illustrations—adult—jaundice); Leslie
Roberts, Brit. Jour. Derm., 1894, p. 148 (adult—no jaundice); Colcott Fox, ibid., 1896
p. 89 (case demonstration—adult, with jaundice—profuse eruption), and 1898, p. 414
(case demonstration—adult, with jaundice and profuse eruption); Whitehouse, “Xan-
thoma Multiplex (Histology of the Palmar Striæ),” Jour. Cutan. Dis., 1904, p. 470
(histologic examination by Johnston), abstracts of several interesting cases reported
during the past few years by Dehot, Richter, Parkes Weber, Leven, McFarland, and
Tennenheim, are given in Jour. Cutan. Dis., 1905, pp. 186-190; Leven’s paper, in
the original, Archiv, 1903, vol. lxvi, p. 61, reviews and analyzes 23 cases from literature,
some of diabetic variety; Pusey and Johnstone, Jour. Cutan. Dis., 1908, p. 552 (case,
approaching the diabetic type, with associated diabetes insipidus); Winfield and Potter,
ibid., 1909, p. 112 (child aged four, beginning in first year; with 2 case illustrations and
1 histologic cut. This case was exhibited at Sixth International Dermatological Con­
gress, and was thought by several to be a case of urticaria pigmentosa; but this, the
writers state, was excluded by their clinical and histologic observations); Cranston
Low, “Xanthoma Tuberosum Multiplex” with Lesions in the Heart and Tendon-
Sheaths, Brit. Jour. Derm., 1910, p. 109, (girl aged 11; case and histolog. illustrations;
good review and bibliography); Sutton, “ Xanthoma Tuberosum Multiplex Mistaken
for Myomatosis Cutis Disseminata,” Jour. Amer. Med. Assoc., July 20, 1912, p. 178
(3 cases with clinical features of myomatosis cutis which proved to be on histologic
examination cases of xanthoma multiplex; refers to published cases of myomatosis
cutis disseminata, with good bibliography).

² Lehzen and Knauss, Virchow’s Archiv, 1889, vol. cxvi, p. 85 (with case illustration
and 4 histologic cuts).

³ Carry, Annales, 1880, p. 64; Chambard, Arch, de phys. norm, et pathol., 1879, P-
691 (with numerous references and 2 colored plates showing disease on palm, penis, and
chin, and 5 colored histologic cuts).

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bows and knees, the buttocks, and the feet; the face, and especially about
the eyes, also frequently shares in the eruption. Occasionally the dis­
tribution or grouping is somewhat unusual or anomalous. In Morrow’s¹
case the lesions, which were somewhat hard, were, for the most part,
limited to the soles, with some lesions about the knees and some pre­
viously upon the palms. In 2 instances—brothers—of somewhat ex­
tensive eruption observed by Mackenzie,² some was disposed in ridges
and lines, and in both cases with an almost continuous band of some width
around the neck.

Jaundice is a usual precursory or associated symptom in xanthoma
multiplex in the adult, although not invariably present; in children, in
whom, however, the malady is less frequent, it is always wanting. The
eruption in the latter is quite extensive, usually more so than in adults,
a most remarkable example of which has been reported in recent years
by Jackson,³ in a young child, covering a greater part of the surface.
In children the eruption exhibits nothing in any way different from that
in adults; while usually abundant, it is sometimes quite scanty, consisting
of but one, several, or more patches, as in the cases referred to by Crocker,⁴
Török, and others; and in some of these instances the patches were small,
several of the patients coming under medical inspection accidentally.
Doubtless some of the reported cases in children have been anomalous
or striking types of nodular pigmented urticaria, and a few possibly
similar to cases recently recorded by McDonagh⁵ as “Nævo-Xanthoma-
endotheliomata,” in which the lesions were distinctly xanthoma-like.
There is no question at all that other organs than the skin can also be
the seat of xanthoma, as shown in some autopsies. The mouth and lips,
as already referred to, sometimes share in the eruption, although seldom
and only to a slight extent. The eye itself, in rare instances, has been
noted to become involved. In von Graefe’s case, quoted by Virchow,⁶
and also referred to by Pye-Smith,⁷ the growths were observed on the
cornea as well as in other parts.

Ordinarily xanthoma develops gradually: xanthoma palpebrarum
always slowly; occasionally, however, in the multiplex variety several
months suffice to show considerable eruption, and exceptionally, as
in Korach’s⁸ case, extensive development was reached in a few weeks.
The course of xanthoma of either variety is chronic and slowly progres­
sive, with but little, if any, tendency to undergo involution, although this

¹ Morrow, Jour. Cutan. Dis., 1893, p. 1 (with colored plate).

² Mackenzie, London Patholog. Soc’y Trans., 1882, p. 370.

³ G. T. Jackson, Jour. Cutan. Dis., 1890, p. 241 (with colored plate, with references
to other general cases).

⁴ Crocker, Diseases of the Skin, third edit., p. 742.

⁵McDonagh, Brit. Jour. Derm., 1912, p. 87 (with case and histologic illustrations;
special form of multiple growths in the skin, which are conspicuous from their yellow
color; sometimes commencing as red tumors, like angiomata, to become yellow later;
present at birth or appearing later; they may persist for many years, but tend to ulti­
mate spontaneous cure; histologic examinations indicate that they are nævi of the
type endothelioma, and owing to a fatty change occurring in the cells during their
dissolution xanthoma-like condition is produced).

⁶ Virchow, Virchow’s Archiv, 1871, vol. lii, p. 504.

⁷Pye-Smith, Guy’s Hosp. Reps., 1877, vol. xxii, p. 97, refers also to various other
xanthoma cases.

⁸Korach, Deutsche med. Wochenschr., 1881, p. 329.

XANTHOMA                                       671

is sometimes observed in a few lesions in the multiplex variety, and ex­
ceptionally this latter has shown a tendency to complete disappearance
(Fagge, F. Smith, Legg, and Kaposi).¹

Etiology.—While xanthoma planum (xanthoma palpebrarum)
and xanthoma multiplex have been thought to be the same disease,—
certainly in their clinical aspects suggestive,—yet they differ in some of
their etiologic factors, and these varieties can be more conveniently con­
sidered separately. Xanthoma palpebrarum is not uncommon and is
essentially a disease of adults, rarely being observed in children, and it is,
moreover, much more frequent in females. Hutchinson’s analytic table
makes the proportion 3 women to 2 men, but this seems much larger than
dermatologic observation would indicate. This careful observer also states
that in half of his cases the patients were subjects of migraine, and one-
sixth had suffered with jaundice. Gouty and rheumatic conditions,
utero-ovarian derangements, and other affections have variously seemed
in certain cases to be of influence, but it is doubtful whether they are more
than accidental, or, at the most, contributory. There is, however, a
factor which is noted sufficiently often to be of probable import, and that
is heredity. In Church’s² cases, often quoted, there were 3 cases in each
of two succeeding generations; and Wilks³ also observed it in mother and
daughter; Fagge⁴ also in mother and daughter, in whose family there
was a history of the malady for four generations. Hutchinson⁵ observed
it in two brothers whose paternal grandfather had also had it.

Xanthoma multiplex is rare, although recorded cases are gradually
approaching a considerable number. It is met with both in children
and adults and in both sexes. In children it may be congenital, or de­
velop in the earlier years of life, and the eyelids do not commonly share
in the eruption nor is jaundice observed. In some of these instances
(children) there seems to be a family prevalence; Mackenzie⁶ had under
observation 3 cases in a family of 7 children, and Startin⁷ a brother and
sister, and Thibiérge⁸ two brothers. The tabulations referred to fur­
nish additional examples.

Jaundice is, as before remarked, often associated with multiple
xanthoma in the adult—in 23 out of the 28 cases tabulated by the London
Pathological Society Committee. Schwimmer⁹ quotes the following
proportions, based, however, upon totals of both varieties combined:
Kaposi, 15 in 27 cases; Chambard, 22 in 58 cases; in 10 consecutive cases
of his own, including 2 cases of xanthoma multiplex, icterus was not
observed in a single instance.

Kaposi, Hardaway, and others are inclined to consider the jaundice
not as a causative factor, but as probably due to development of the

¹ London Path. Soc’y Committee Report (loc. cit.).

² Church, quoted by Mackenzie, London Patholog. Soc’y Trans., 1882, vol. xxxiii
p. 370

³ Wilks, ibid., vol. xix, p. 446 (also quoted by Mackenzie).

⁴ Fagge, quoted by Crocker, Diseases of Skin.

⁵ Hütchinson, loc. cit.

⁶ Mackenzie, loc. cit.

⁷ Startin, London Patholog. Soc’y Trans., 1882, p. 373 (with colored plate).

⁸ Thibiérge, loc. cit.

⁹ Schwimmer, Ziemssen`s Handbook of Diseases of the Skin, p. 577.

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xanthoma growths in the liver, a view which, I believe, has much in its
support. Autopsies have furnished evidence both for and against its
causative influence, the liver often being found uninvolved, and in other
cases exhibiting various diseased conditions. According to Besnier
and a few others, the yellow color is not always due to jaundice, but the
disease itself may be responsible for the cutaneous discoloration—
xanthodermic, as Besnier designates it.

Pathology.—Xanthoma is a benign, connective-tissue, new-
growth development, possibly of mildly inflammatory origin, with con­
comitant or subsequent, but usually partial, fatty degeneration. The
suggestion of a diathesis originating in the digestive apparatus, leading
to hepatic derangement, has been advanced as a pathologic factor; and
Quinquaud’s assumption that there may be, from some unknown cause,
a surcharge of the blood with fatty elements, is practically supported
in part by Pollitzer’s investigations. Under such a supposition the
xanthoma multiplex cases could readily be explained by the additional
determining factor of local irritation, as those sites—hands, elbows,
buttocks, knees, and feet—which are always subject to knocks, frictions,
and the like are the parts upon which the eruption is commonly or most
abundantly seen. Histologic studies made by Pavy, Chambard, Balzer,¹
Touton,² Crocker, Pollitzer,³ Török, and others are all agreed in essential
facts as to conditions found, but differ as to whether or not the process is
primarily an inflammatory one, an opinion supported by Chambard,
Crocker, and others, while Touton is the most insistent as to the opposite
view. Up to recent years there was more or less unanimity as to the
histologic identity of the two types, but Pollitzer’s and Unna’s investiga­
tions indicate that the two types are quite distinctive; Pollitzer believing
xanthoma tuberosum represents an irritative connective-tissue hyper-
plasia, in which the extravasation of cholesterol-fatty-acid-ester present
in excess in the blood, serves as the stimulus; and it is this particular
lipoid which constitutes the greater portion of the fatty substance in the
cells. Excepting sometimes slight thinning and some pigment staining
and deposit of yellowish pigment granules in the rete, the epidermis shows
but little alteration, at times some of the lower rete cells showing slight
atrophic changes and vacuolation. The chief changes are noted in the
corium, especially in the middle and lower layers. Large cells filled with
fat granules and closely aggregated fat-drops having a defined membrane
and a large, sometimes several or more, nuclei, are found lying between
the bundles of connective tissue, constituting the so-called “xanthoma
cells”—“xanthoma giant-cells.” Transition cell-formations are also to
be seen. These cells vary somewhat in size, some being small, others
quite large, and are found in considerable numbers, sometimes massed
together in groups, frequently around and following a blood-vessel; some
may at times be found in the subcutaneous tissue, although this latter

¹ Balzer, Arch, de physiologie, 1884, vol. iv, p. 65 (with references).

² Touton, Archiv, 1885, vol. xii, p. 3, with histologic illustrations and references.

³ Pollitzer, “Nature of the Xanthomata,” New York Med. Jour., 1809, ii, p. 73 (a
histologic study, with II illustrations and references); “ The Nature of Eyelid Xantho-
mata,” Jour. Cutan. Dis., 1910, p. 633, with histologic plates; and Pollitzer and Wile,
ibid., 1912, p. 235 (with histologic plates).

XANTHOMA                                            673

structure is, as a rule, practically unchanged. The glandular structures
show but little alteration. Connective­ tissue increase is usually a pro­
nounced feature, varying considerably in degree.

Pollitzer, from investigations of tissue from xanthoma palpebrarum,
believes the xanthoma cells to be fragments of degenerated muscle-
fibers, and the process a slow, fatty, muscle-fiber degeneration of the
orbicularis muscle—and that it belongs not to the neoplasms, but to the
degenerations, like colloid degeneration of the skin. Unna also considers
this muscle an important factor, believing that the fatty bodies were
simply deposits of a peculiar fatty substance between the muscular and
collagenous bundles into which naked endothelial nuclei had escaped.
The color of xanthoma is assumed to be due to the abundant fat-granules
present. According to investigations by both Török and Unna it would
seem that in xanthoma we have a special form of fat. In autopsies
xanthoma growths have been found in the esophagus, in the trachea and
capsule of spleen, in the liver, aorta, heart, and other situations.

Diagnosis.—The characters of the malady are usually so pro­
nounced that confusion with other diseases is scarcely possible. The
chamois-leather-colored patch or patches about the eyelids, sometimes
band-like and partially or almost completely surrounding it, and occurring
in middle and late adult life, is, for this type, sufficiently diagnostic
Possibly upon hurried examination beginning minute lesions might sug­
gest milium, but this latter is cystic, usually white in color, and if punc­
tured, permits easy expression of the sebaceous contents. Xanthoma
multiplex would scarcely be confused with the xanthoma-like lesions seen
in some cases of urticaria pigmentosa, although this latter affection has
been in a few instances reported as xanthoma. Xanthoma multiplex
lesions are, however, of fairly uniform character as to color, possibly vary­
ing somewhat in shade, whereas in urticaria pigmentosa the active lesions
are distinctly urticarial, and there is usually an urticarial condition of
the skin. Pollitzer¹ has called attention to the possibility of some cases
of multiple dermoid cysts being mistaken for xanthoma, and, in addition
to the one coming under Sangster’s and his own observation, refers to
several similar instances, and suggests, in order to avoid such an error,
the puncturing of a lesion in xanthoma-like eruptions or histologic exami­
nation, a dermoid cyst being thus readily recognized. A fact to be
remembered in xanthoma multiplex is that almost all cases in adults
have an associated jaundice. Its differentiation from xanthoma diabet-
icorum will be considered under this latter disease.

Prognosis.—There is practically no prospect for spontaneous
disappearance of the malady; the several instances already referred to
in which involutionary changes were observed are rare exceptions to the
rule that the disease is persistent, and up to a variable point progressive.
After reaching a certain development the progress seems stayed, and the
growths remain stationary. In some cases, however, of limited extent,
treatment has been effectual in removing the blemish.

Treatment.—Xanthoma palpebrarum may be removed by ex-

¹ Pollitzer, “Multiple Dermoid Cysts Simulating Xanthoma Tuberosum,” Jour.
Cutan. Dis., 1891, p. 281.

43

674

NEW GROWTHS

cision or the curet, and in some instances by mildly caustic applications
and electrolysis. I have employed two methods: The application of
trichloracetic acid and electrolysis. The trichloracetic acid is applied
in scant quantity, limiting it to the area of the disease (only to a small
part at one time if the area is large), and in those of very delicate skin it
should be first tried diluted with an equal part of water; considerable
surface reaction follows in some cases, with superficial crusting. Vaselin
or cold cream can be applied till the irritation subsides and the crust
comes away. A second or third application may be necessary. Some­
times the blemish is thus completely removed, but more commonly only
rendered less conspicuous; sooner or later it shows a disposition to return.
Electrolysis requires a current of 1 to 5 milliampères, the growth being
punctured superficially and, if large, at several points. The operation
in some cases must be repeated at intervals of two to four weeks before
a final result is reached, and in most cases the effect, while favorable, is
not permanent, although more frequently than with the trichloracetic
acid method. If the growth is extensive, but a portion should be treated
at a time. McGuire¹ has reported good results from monochloracetic
acid. Stern’s² method of applying a 10 per cent, solution of corrosive
sublimate in collodion has not met with favor. Morrow,³ in his case of
xanthoma multiplex, used successfully a 25 per cent, salicylic acid plaster,
worn continuously for several days or longer, after which a considerable
part of the growth was found softened and could be readily removed,
after which the part is washed or soaked in hot water, and a plain diachy­
lon ointment applied for a day or two, when the plaster is to be resumed.
Leslie Roberts⁴ employed a somewhat similar application, a compound
salicylated collodion paint: R. Ac. salicylici, 3j (4.); chrysarobini, 5ss
(2.); ol. ricini, 3ss (2.); collod. flex., ad 3j (32.). Evans and Whitehouse
had good results from the x-rays; the latter also from the high-fre­
quency current.

Internal treatment is apparently fruitless in xanthoma, although
Besnier⁵ saw good results from the administration of phosphorus in in­
creasing dosage, given in cod-liver oil, for a few weeks, to be followed by
turpentine.

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