A CAJM article on Xanthoma Tendinosum.The formation of xanthomata in tendons occurs typically as part of a familial disorder associated with an elevation of the total plasma cholesterol. In those cases where the tendinous deposits are small in size and few in number, the cholesterol level is usually only moderately raised, extensive deposits being more commonly associated with much higher levels. It is therefore of interest to have encountered a patient with a severe degree of xanthoma tendinosum whose plasma cholesterol was in the normal range

Bloom, Kennth R.

Jacobs, Peter

Suzman, Moses M.

Central African Journal of Medicine

English

IDS OpenDocs

The Cent ra l  Afr ican
Journal of Medicine
Volume 14 JANUARY, 1968 No. 1
Xanthoma Tendinosum
THE INFLUENCE OF ANAEMIA ON 
PLASMA CHOLESTEROL LEVELS 
BV
PETER JACOBS,* m .d . (Rand.), f .c .p . (S.A.)
Clinical Tutorial Registrar, Department of Medicine, 
University of the Witwatersrand, and the 
Johannesburg General Hospital;
KENNETH R. BLOOM, m .b ., b .c h . (Rand.)
House Physician, Johannesburg General Hospital, pre­
sently Medical Registrar, Cautisthoracic Unit, General 
Hospital, Johannesburg.
AND
MOSES M. SUZMAN, m .d ., f .r .c .p .
Physician, Johannesburg General Hospital, presently in 
the Department of Medicine, University of Washington 
School of Medicine, Seattle, Washington, U.S.A.
The formation of xanthomata in tendons occurs 
typically as part of a familial disorder associated 
with an elevation of the total plasma cholesterol. 
In those cases where the tendinous deposits are 
small in size and few in number, the cholesterol 
level is usually only moderately raised, extensive 
deposits being more commonly associated with 
much higher levels. It is therefore of interest 
to have encountered a patient with a severe 
degree of xanthoma tendinosum whose plasma 
cholesterol was in the normal range.
C ase R epo rt
The patient, a 39-year-old white housewife, was 
admitted to the medical wards of the Johannes­
burg General Hospital because of haemorrhage 
from the gastrointestinal tract; in the six hours 
preceding admission she had passed two large 
melaena stools and immediately on admission 
vomited about one pint of fresh blood. For 
several days before this the patient had con­
sumed large quantities of acetosalicylic acid to 
relieve her dysmenorrhoea, a practice which she 
had followed regularly since her menarche at 
16 years of age.
For 10 years the patient had suffered inter­
mittent attacks of painful swelling of the small 
joints of her hands and feet, at times the latter 
being severe enough to prevent her from walk­
ing. During the same period of time firm 
nodules in the tendons on the dorsum of her
* Eli Lilly Medical Research Fellow.
hands and at the back of her heels had ap­
peared; these had been slowly increasing in size.. 
Her mother, who died of an acute myocardial 
infarction at the age of 68, and an elder sister 
had similar nodules on their hands and ankles. 
Both women, together with her younger brother 
and her eldest son, experienced arthritic pains.
On examination the patient was pale and a 
well-marked bilateral corneal arcus was noted. 
The blood pressure was 125/60 mm. Hg. A grade 
2/6 aortic ejection systolic murmur was audible 
at the base of the heart. The achilles tendons 
were markedly thickened (Fig. 1) and firm non- 
tender nodules were present in the extensor 
tendons of the index and middle fingers of both 
hands (Fig. 2). Varicose veins were prominent 
in the left leg and a chronic stasis ulcer was 
present just above the left medial malleolus. 
Rectal examination showed only the presence 
of melaena stool.
Fig. 1—Photograph illustrating grossly thickened Achilles
tendons.
1
January, 1968 X A N T H O M A  TENTOINOSUM The Central AfricanJournal of Medicine
Fig. 2—Photograph to demonstrate extensive involve­
ment of extensor tendons with xanthomata.
Investigations on admission showed the fol­
lowing: Haemoglobin, 9.5 gm. per cent.; total 
leucocyte count, 7,100 per cu.mm., neutrophiles, 
68 per cent.; monocytes, 5 per cent.; lympho­
cytes, 24 per cent., and eosinophiles 3 per cent.; 
platelets, 460,000 per cu.mm.; prothrombin 'index, 
98 per cent.; bleeding and clotting times were 
both normal. Serum iron was 20 micrograms 
per cent, and unsaturated iron binding capacity 
380 micrograms per cent. Blood sugar was 
92 mg. per cent., fasting total lipids were 630 
mg. per cent., total cholesterol 236 mg. per cent:, 
free cholesterol 62 mg. per cent., and a 
cholesterol: phospholipid ratio of 1.02. Fatty 
acids were 322 mg. per cent., triglycerides 35 mg. 
per cent., beta-lipoproteins 60 per cent, and beta- 
cholesterol 79 per cent. The serum protein 
bound iodine was 7 micrograms per cent.
Electrocardiographic abnormalities were con­
fined to a 2 mm. plane depression of the ST 
segments and inverted T waves in V 3, V 4, V 5 
and V 6.
Detailed radiological investigations of the 
gastrointestinal tract failed to reveal any abnor­
mality to account for- the bleeding. In view of
the clear history of salicylate ingestion and the j 
negative barium studies, it appeared most likely [
that the haemorrhage was due to acute gastric i
erosion. The patient responded well to treat- I 
ment with anticholinergics and blood transfusion; j 
a course of oral iron therapy was started before J 
she was discharged from hospital. \
♦Biopsies were carried out on the tendon { 
nodules, and sections from these showed typical j 
clefts (Fig. 3) which remained after dissolution (
of cholesterol crystals during histological prepara­
tion. In addition, numerous foam or xanthoma 
cells were seen, together with polymorphonuclear 
leucocytes, lymphocytes and histiocytes (Fig. 4).
The “touton” giant cells characteristic of young, 
active lesions were not seen; the fibrosis present 
indicated that these lesions were in a stage of 
involution. \
* Reported by Dr. H. E. van der Merwe and Dr. N. S. F. 
Proctor, Department of Histopathology at the South 
African Institute for Medical Research.
Fig; 3—Low power view of xanthomatous deposit in 
tendon sheath. Note the clefts normally occu­
pied by cholesterol crystals.
2
January, 1968 X A N T H O M A  T E N D IN O S U M T he Central AfricanJ ournal of Medicine
D isc u ssio n
Tiie interest of this case lies in the association 
of a normal lipogram with marked corneal arcus, 
an extreme degree of tendinous xanthoma forma­
tion and a very strong family history of the 
latter condition.
In view of the widespread xanthomatous de­
posits a marked elevation of the blood cholesterol 
could reasonably have been expected. However, 
as this was not a feature on admission, it was 
considered possible that the level may have 
fallen consequent upon the development of iron- 
deficiency anaemia due to chronic blood loss 
from the gastrointestinal tract. Support for this 
hypothesis was obtained by documenting the rise 
in plasma cholesterol, to pathologically high 
levels, as the haemoglobin had returned to nor­
mal (Fig. 5). These observations are in accord 
with earlier work (MacAdam and Shiskin, 1923), 
which indicated that disturbances in cholesterol 
metabolism frequently accompany anaemia. This 
association was most apparent in pernicious 
anaemia (Gibson and Howard, 1923; Muller,
Fig. 4—High power view of xanthomatous lesion show­
ing numerous xanthoma cells and “cholesterol 
clefts.”
Fig. 5—Graphs illustrating the close relationship between 
elevation of plasma cholesterol level and correc­
tion of anaemia.
1930a), where the cholesterol, and frequently 
plasma lecithin-phosphorus, were decreased dur­
ing relapse, but rose as remission was inaugurated; 
this rise in cholesterol often developed before 
significant alterations had occurred in the con­
centration of erythrocytes or haemoglobin and 
was proportional to the rate of remission.
Muller and Heath (1933) stressed that choles­
terol is' also low in chronic blood loss anaemia 
and rises gradually to normal limits when treat­
ment with iron is instituted. It is of some 
interest that isolated acute blood loss anaemia 
affects lipids and cholesterol differently to 
chronic blood loss. Thus, in both experimental 
animals (Louhija, 1965) and in man (Campbell, 
1925), there is a rise in lipids and cholesterol 
immediately following haemorrhage. Under­
standably, in those patients where acute blood 
loss was superimposed upon Chronic iron defi­
ciency, an intermediate pattern emerged upon 
study.
The mechanism by which this lowering of 
plasma cholesterol is brought about remains
3
January, 1968 XANTHOMA TENDINOSUM T h e  Central African
J ournal of MEbiciNE
obscure, but it has been suggested (Muller, 
1930b) that the fall may reflect changes in the 
functional activity of the reticuloendothelial sys­
tem. In this regard it is of some interest that 
cholesterol tends to be reduced in haemolytic 
states where increased blood destruction and bile 
formation point to accelerated activity in this 
system of cells. Similarly, in pernicious anaemia, 
the accelerated blood destruction and biliru- 
binaemia decrease with the onset of the clinical 
and haematological remission, at a time when 
the plasma cholesterol starts to increase. Fur­
thermore, the anaemia caused by chronic blood 
loss is associated with excess haemolysis (Huser, 
Rieber and Berman, 1967) and here, likewise, 
a similar mechanism may be operative in de­
pressing plasma cholesterol values. Additional 
support for the relationship of cholesterol meta­
bolism to cell proliferation in the bone marrow 
can be inferred from the low values found in 
chronic myelogenous leukaemia (Muller, 1930b) 
and in acute infectious diseases like pneumonia 
(Kipp, 1920).
These observations, even though not fully 
understood, may have significance for the patho- 
jgenesis and management of atherosclerosis and 
its complications, since the latter are widely held 
to be among the chief consequences of familial 
hypercholesterolaemia a n d  other hyperlipid- 
aemias. Thus, assuming that the high levels 
of blood fats do actually promote these patho­
logical changes, it may be speculated that in 
chronic blood loss anaemia, such complications 
would be less likely to ensue. In other words, 
individuals who, in ordinary circumstances, would 
have high blood fats and cholesterol by reason 
of dietary or genetic predisposition, may have 
normal lipids while they remain anaemic; it 
follows that such a group might consequently 
enjoy a certain amount of protection from the 
results. of their metabolic derangement.
Furthermore, evidence is now accumulating in 
suDport of the association between myocardial 
infarction and elevation in the blood haematocrit 
(McDonough, Hames, Garrison, Stulb, Lichtman 
and Hefelfinger, 1965; Burch and De Pasquale, 
1962) and, indeed, phlebotomy has been used 
as a means of treatment in patients with erythro- 
cvtosis and ischaemic heart disease (Burch and 
De Pasquale.' 1963). In considering the available 
evidence it seems reasonable to suggest that re­
peated venesections may have a place in manage­
ment of selected Datients with atherosclerosis: 
short term effects being related to reduction in 
haematocrit, while induction and long term 
maintenance of iron deficiency may favourably 
influence the level of plasma cholesterol.
That this inverse correlation' between hyper­
cholesterolaemia and anaemia is far from abso­
lute is exemplified by those patients with very 
high lipid and cholesterol levels while severely 
anaemic from such conditions as the nephrotic 
syndrome. In these cases it may be that the 
function of the reticuloendothelial system is im­
paired as a result of concurrent infection. 
Nevertheless, it remains uncertain whether this 
association between anaemia and the plasma 
cholesterol level applies only to cases having 
significant liplid abnormalities in the first place, 
or whether it1 has, in addition, any relevance for 
normocholesterolaemic subjects.
Su m m a r y
A young female with well-established xanthoma 
tendinosum presented with anaemia due to 
salicylate-induced gastrointestinal tract haemorr­
hage. Initially, the lipogram was normal, but 
pathological elevation of cholesterol followed 
correction of her anaemia. This phenomenon 
appears to have been well studied some 30 years 
ago, but, more recently, seems to have been less 
frequently recognised. The implication of this 
association in respect of the pathogenesis and 
management of patients with atheroscleroses is 
briefly discussed.
REFERENCES
1. Burch, G. E. & De Pasquale, N. P. (1962). Am. 
J. Med., 32, 161 (Editorial).
2. Burch, G. E. & De Pasquale, N. P. (1963). Arch.. 
Int. Med., Ill, 687.
3. Campbell, J. M. H. (1925). Quart. J. Med., 18, 
393.
4. G ibson, R. B. & H oward, C. P. (1923). Arch. hit. 
Med., 32, 1.
5. H user, H. J., R ieber, E. E. & Berman, A. R. 
(.1967). J. Lab. Clin. Med., 69, 405.
6. Kipp, H. A. (1920). J. Biol. Chem., 44, 215.
7. Louhija, A. (1965). Ann. Med. Exp. Fenn., 43, 
(Supp. 2), 1.
8. MacAdam, W. & Shiskin, C. (1923). Quart. J. 
Med., 16, 193.
9. M cD onough, J. R., Hames, C. G., Garrison, G. E.,
Stulb, S. C., L ichtman, M. A. & H efelfinger, 
D. C. (1965). I. Chron. Dis., 18, 243.
10. M uller, G. L. (1930a). Am. J. Med. Sc., 179, 316.
11. M uller, G. L. (1930b). Med., 9, 119.
12. Muller, G. L. & H eath, C. W. (1933). Arch. Int.
Med., 52, 288.
Acknowledgments
The photography was done by the photographic 
unit of the Department of Medicine and photo­
micrographs by the South African Institute for 
Medical Research. Dr. H. van Wyk, Medical 
Superintendent, Johannesburg General Hospital, 
granted permission to publish.
4
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