Hypertrophic Osteoarthropathy Workup

Updated: Jan 13, 2021
  • Author: Vishnuteja Devalla, MD; Chief Editor: Herbert S Diamond, MD  more...
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Laboratory Studies

The erythrocyte sedimentation rate may be elevated in persons with pachydermoperiostosis and is often elevated in those with secondary hypertrophic osteoarthropathy (HOA). [18] .

Serum alkaline phosphatase levels may be elevated secondary to periosteal new bone formation. [18] These bone markers can be used to monitor disease activity. Isolated reports have shown an increase in some bone formation markers and resorption such as TAP, BAP, BGP, carboxyterminal propeptide of type I procollagen, or NTX (see N-Terminal Telopeptide) in patients with either primary or secondary HOA, suggesting that measurement could be useful for monitoring disease activity. 

Biallelic HPGD mutations are found in most patients with typical primary HOA. Sequencing of the HPGD gene is a highly specific first-line investigation for patients presenting in this way, particularly during childhood. [96]  This gene codes for 15-hydroxyprostaglandin dehydrogenase, the main enzyme of prostaglandin degradation; consequently, homozygous individuals with this mutation show elevated levels of prostaglandin E2 and its metabolite, PGE-M, which suggests that its measurement can be useful in early investigations of patients with HOA.

If a joint effusion is present, the synovial fluid is noninflammatory (cell count < 500/µL), with a predominantly lymphocytic and monocytic infiltrate. Synovial histology shows hypercellularity and vascular thickening without inflammatory cell infiltration. 

An evaluation for the underlying condition is warranted in patients with possible secondary HOA. Presence of the characteristic features should prompt an intensive search for an underlying malignant disease, usually of thoracic organs. [7]


Imaging Studies

Radiologic findings are periostitis and symmetrical thickening of distal tubular bones, particularly the tibia, fibula, radius, and ulna. Bilateral and symmetrical periostosis are frequently observed as a marked irregular periosteal ossification of the tibias and fibulas. [26]  Distinguishing between clubbed and nonclubbed fingers using plain radiography is possible. [97]  Plain radiographs show 2 types of changes: bone formation with hypertrophy and bone dissolution with acro-osteolysis. [16]  Acro-osteolysis may be seen in the distal tufts in patients with long-standing HOA.

Periosteal thickening occurs along the shafts of long and short bones, initially appearing in the distal diaphyseal regions of the long bones. Periosteal changes are seen as a continuous thin line of sclerotic new bone separated from the cortex by a radiolucent space. Over time, the periosteal new bone thickens and fuses with the cortex, and the process extends proximally to the diaphysis and metaphysis. These changes are most commonly observed in the tibia, radius, ulna, fibula, and femur. Primary hypertrophic osteoarthropathy is distinguished by more exuberant periosteal new bone formation that extends to the epiphyseal regions. [18]  However, there are documented cases of HOA without radiographically detectable periostitis. [76]

Radionuclide bone scan using technetium (Tc) 99m polyphosphate shows increased uptake of the tracer in the periosteum, often appearing pericortical and linear in nature. This technique is the most sensitive tool for the detection and evaluation of the extent ofnmHOA; it can delineate the subtleties in progression and regression of the disease when findings from plain radiographs are doubtful. [76] The clubbed digits may also show increased uptake in early passage flow studies, as depicted in the images below. [18, 64]

Clubbing associated with hypertrophic osteoarthrop Clubbing associated with hypertrophic osteoarthropathy can be classified into 3 topographical groups (ie, symmetrical, unilateral, unidigital). This is symmetrical clubbing; it involves all the fingers.
Joint symptoms of hypertrophic osteoarthropathy ra Joint symptoms of hypertrophic osteoarthropathy range from mild to severe arthralgias that involve the metacarpal joints, wrists, elbows, knees, and ankles. The range of motion of affected joints may be slightly decreased. When effusions are present, they usually involve the large joints (eg, knees, ankles, wrists).

Angiography findings may demonstrate hypervascularization of the finger pads. [98, 22]

For more information, see Imaging in Hypertrophic Osteoarthropathy


Histologic Findings

Biopsy of the skin and bone marrow may show an exacerbated proliferation of fibroblasts, which are associated with diffuse epidermal hyperplasia and lymphohistiocytic infiltration with collagen redistribution. 

Histopathologic findings of the eyelid include sebaceous gland hyperplasia, enlargement of sweat glands, thickening of the dermis with an increase in collagen content, deposition of mucin, and perivascular lymphocytic infiltration. [99]