CARDIOVASCULAR JOURNAL OF AFRICA • Vol 24, No 8, September 2013
AFRICA
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histiocyte groups with vacuolated (foamy) cytoplasm between
collagen bundles and fibrotic bands were seen (Fig. 2).
Initially, 80 mg atorvastatin treatment was given. However,
this treatment did not result in adequate decrease in LDL-C
levels. A 40-mg rosuvastatin and 10-mg ezetimibe combination
was then prescribed for the patient.
Discussion
FH was first described by Muller in 1939 and is characterised
by hypercholesterolaemia from birth, the subsequent
development of tendon and cutaneous xanthomas, and premature
atherosclerosis.
1,3
Myant documented that increase in total serum
cholesterol was largely due to LDL-C levels, and Goldstein
and Brown showed that FH results from defective catabolism
of LDL-C caused by dominant mutations in the LDL-R gene.
2,4
Heterozygous and homozygous variants have been described.
The heterozygous form has a prevalence of approximately
1/500 individuals, whereas the homozygous form is very rare
(1/1 000 000).
In the homozygous form, high levels of LDL-C (600–
1 000 mg/dl) can be found between birth and five years of age.
Clinically, this form is characterised by severe xanthomatosis
developing in the first few years of life, multiple types of
xanthomas can occur, and coronary atherosclerosis usually
develops earlier, characteristically before the teenage years.
In the heterozygous form, the cholesterol levels are
approximately twice normal, with values usually in the 270–550
mg/dl range. In this form the xanthomatous lesions develop
during the third to sixth decades.
1,5
Our patient’s clinical characteristics with very high LDL-C
levels, diffuse xanthomas at a young age, strong family history of
hypercholesterolaemia and early onset CAD in family members
were consistent with the homozygous form of FH.
Xanthoma is a deposition of yellowish material formed by
lipids. Tendon xanthomas are firm, skin-coloured subcutaneous
nodules, localised over the proximal finger joints, insertions
of the patellar tendons, and the Achilles tendons. Tendonitis,
peritendonitis or bursitis, trauma, nodules of rheumatic arthritis,
or gout tophi are other frequent conditions that may lead to
tendon thickening, and in such cases, a differential diagnosis
may be difficult. A detailed family and medical history, serum
lipid analysis, and ultrasound of the affected tendon may help in
the differential diagnosis.
5
The aim of the treatment of FH patients is reduction of
plasma LDL-C concentrations to decrease the risk of CAD.
Modern pharmacotherapy can achieve desirable concentrations
of LDL-C in heterozygotes but treatment for homozygotes
remains problematic.
6-8
High-dose atorvastatin, rosuvastatin or
simvastatin should be the initial regimen since these drugs are
more effective than other statins as monotherapy in heterozygotes
with FH.
6,7
To retard the progression of premature coronary and/or
aortic valvular disease, aggressive treatment must begin in
early childhood in homozygotes.
8
LDL-apheresis is the standard
treatment for patients with homozygous FH because it can lower
LDL-C levels in a safe and effective manner. However, the
disadvantages of apheresis include limited availability, high cost,
the duration of the procedure and the need to maintain adequate
vascular access.
Ezetimibe induces a complementary reduction in LDL-C
concentrations. Therefore statins and ezetimibe are classically
used in patients treated with LDL apheresis to achieve LDL-C
goals.
9
Liver transplantation and gene therapy have the potential
for a radical cure but there are too many disadvantages for them
to be the treatment of choice.
6,9
It has been shown that effective LDL apheresis and statin
treatment could prevent the onset of CAD and reduce the size
of the xanthomas.
10
We initiated a high-dose potent statin and
ezetimibe treatment for our patient. However, LDL apheresis
could not be started because of the unavailability of the
technique in our hospital.
Conclusion
The early diagnosis and treatment of FH is crucial, especially
for the prevention of CAD and the development of xanthomas.
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Fig. 2. Histopathological examination of the punch
biopsy specimen stained with haematoxylin and eosin.
Histiocyte groups with vacuolated (foamy) cytoplasm
between collagen bundles and fibrotic bands were seen.
