  |
|
|
||||
|
||||||
| Journal of the New Zealand Medical Association,
23-April-2004, Vol 117 No 1192
|
||||||
|
Case of myelofibrosis with hypertrophic osteoarthropathy: the
role of platelet-derived growth factor in pathogenesis
Binu John, Heraganahally Subhash, and Kurien
Thomas
Hypertrophic osteoarthropathy (HOA) is a condition
characterised by clubbing of digits—with periostitis, plus articular and
periarticular pain. We report a patient with hypertrophic osteoarthropathy, who
presented with severe anaemia, and was found to also have myelofibrosis
(agnogenic myeloid metaplasia). This extremely rare association is particularly
significant since it lends credence to the theory implicating platelet-derived
growth factor (PDGF) in the pathogenesis of both of these conditions
(myelofibrosis and hypertrophic osteoarthropathy).
Case reportA 27-year-old man presented with
history of breathlessness (on exertion) and fatigue of 2 years’ duration.
There had been gradual painless enlargement of both hands and feet (of 3
years’ duration) with mild pain and swelling involving ankles, wrist, and
knee joints. There was no history of cough with expectoration, haemoptysis,
wheeze, abdominal pain, alteration in bowel habits, melaena or bloody diarrhoea.
He had no history of fever, palpitations, or cardiac disease. There was no
family history of similar illness.
On examination, he had a pulse rate of 80/min and a blood
pressure of 120/80 mmHg. He had pallor with marked clubbing. There was swelling
of distal extremities; both hands and feet were grossly enlarged. Feet appeared
‘elephant like’ (Figure 1). There was no icterus, lymphadenopathy,
or pedal oedema. Chest was clear. The liver was palpable 2 cm below the costal
margin. Spleen was not palpable. There was no free fluid. Examination of the
cardiovascular system was normal.
There was no evidence of effusion of any joint and no
evidence of acromegaly such as prognathism, coarse facial features, change in
voice, or proximal myopathy. Investigations showed haemoglobin 4.7 grams/dL,
with a reticulocyte count of 4.6%. Blood picture revealed ovalocytes and
teardrop cells. The total leucocyte count was 3100/cu mm, with the differential
count showing 68% polymorphs, 16% lymphocytes, and 16% eosinophils. The platelet
count was 182,000/cu mm. The mean corpuscular volume was 73, and erythrocyte
sedimentation rate (ESR) 87mm/hr. Serum calcium, phosphate, alkaline
phosphatase, liver function tests, growth hormone level, and thyroid function
tests were normal.
Radiograph of the chest was normal. The forearms showed
linear periosteal reaction involving radius and ulna bilaterally (Figure 2), and
the lower limbs showed periosteal thickening of bilateral tibia and fibula and
distal soft tissue enlargement (Figure 3). Ultrasonography of the abdomen
revealed hepatosplenomegaly. Attempted bone marrow aspiration revealed a dry
tap. Cellular imprints of the bone marrow trephine biopsy fragment revealed
normoblastic erythroid maturation, diffuse lymphocytosis, and increased
osteoblastic activity. The bone marrow trephine biopsy was consistent with the
cellular phase of myelofibrosis.
Figure 1. Photograph of both lower limbs of a
27-year-old man showing marked enlargement of both legs with swelling of both
ankle joints and clubbing of toes
DiscussionThis patient presented with
hepatosplenomegaly, peripheral cytopaenias, teardrop poikilocytosis, and marrow
fibrosis suggestive of myelofibrosis (AMM). The other disorders that may lead to
this clinical picture (including infections such as tuberculosis—and
metabolic disorders such as renal osteodystrophy, hypoparathyroidism, and
hyperparathyroidism) were ruled out in our patient.
He also had features of hypertrophic osteoarthropathy (HOA),
a clinical syndrome characterised by marked clubbing of the digits;
specifically, enormous hands and feet, arthralgia, and periosteal overgrowth.
There were no cutaneous manifestations of primary hypertrophic osteoarthropathy
(pachydermoperiostosis), such as furrowed forehead, broad nose, prominent
nasolabial folds, and thickened eyelids. There were no clinical or laboratory
evidence of other conditions that are commonly associated with secondary
hypertrophic osteoarthropathy—such as suppurative lung disease, pulmonary
neoplasm, inflammatory bowel disease, colonic neoplasm, congenital cyanotic
heart disease, infective endocarditis, or thyrotoxicosis.
Multiple mediators (including PDGF, prostaglandins,
ferritin, bradykinin, and oestrogen) have been implicated as causes of clubbing
or hypertrophic osteoarthropathy.1 The most
popular theory is that megakaryocytes or large fragments of megakaryocytes in
the systemic circulation, preferentially lodge in the tips of the digits,
because of the prevailing patterns of blood flow. Once stuck there, the cells
release PDGF and other substances that increase endothelial permeability and
activate fibroblasts and other connective tissue
cells.1
The exact aetiology of myelofibrosis is not clear, but one of the most widely
accepted theories is that it results from the liberation of excessive amounts of
growth factors (including PDGF, transforming growth factor-β [TGF-β],
and epidermal growth factor [EGF], which are each contained within platelet and
megakaryocyte α-granules). These can lead to marrow fibroblast expansion
and collagen synthesis. The PDGF content of platelets from AMM patients is known
to be decreased, indicating a release or leakage of such growth
factors.2
There are only three other case reports describing the
association of myelofibrosis and hypertrophic
osteoarthropathy.3–5 In one of these
reports, the authors demonstrated a high proliferative potential of bone marrow
derived fibroblasts in vitro as well as
an increased expression of PDGF-BB binding
sites.3 Thus, the concurrent occurrence of
these two uncommon conditions may be a pointer to the role of PDGF in the
pathogenesis of these conditions.
Author
information: Binu V. John, Consultant, Department of Medicine - Unit 2,
Christian Medical College and Hospital, Vellore, Tamilnadu, India; Heraganahally
S. Subhash, Medical Practitioner, Modbury Public Hospital, Modbury, SA,
Australia; Kurien Thomas, Professor and Head, Department of Medicine - Unit 2,
Christian Medical College and Hospital, Vellore, Tamilnadu, India.
Correspondence: Binu
V. John, Department of Medicine - Unit 2, Christian Medical College and
Hospital, Vellore, Tamilnadu, 632004, India. Fax: +91 416 2232035; email: binuvalsanjohn@hotmail.com
References:
|
|
||||
| | Current
issue | Search journal |
Archived issues | Classifieds
| Hotline (free ads) Subscribe | Contribute | Advertise | Contact Us | Copyright | Other Journals |
|