Hypertrophic osteoarthropathy

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Hypertrophic osteoarthropathyis a syndrome characterised by periosteal reaction of the long bones without underlying bone lesion. There are a broad range of manifestations, although typically there is symmetrical involvement of the appendicular skeleton. Accompanying abnormal soft tissue proliferation is variable and may result in clubbing of the fingers and toes.

Hypertrophic osteoarthropathyis largely considered a secondary phenomenon, and nearly always (95-97% of cases) occurs in the setting of a wide variety of other cardiopulmonary, gastrointestinal, endocrine, haematologic, and inflammatory conditions ⁵. When associated with cancer, it is considered a paraneoplastic syndrome. A primary form, pachydermoperiostosis, is due to a heritable genetic mutation that results in similar clinical manifestations, although tend to have more soft tissue findings ⁵.

Terminology

Hypertrophic osteoarthropathy has been given various names including Pierre-Marie syndrome, Bamberger syndrome, osteoarthropatia hypertrophica, Mankowsky syndrome, and Hagner syndrome.

"Hypertrophic osteoarthropathy" may refer to either the primary or secondary syndrome, although general usage implies the secondary form, given the rarity of primary hypertrophic osteoarthropathy (also known as pachydermoperiostosis).

"Hypertrophic pulmonary osteoarthropathy" specifically refers to hypertrophic osteoarthropathy in the setting of a lung disease, and not from other intrathoracic processes such as mediastinal or pleural disease ⁵.

Clinical presentation

Hypertrophic osteoarthropathy has a variable clinical presentation, ranging from asymptomatic morphologic and radiographic findings to pain accompanying the changes of the fingers and toes ⁵.

Pathology

The primary form of hypertrophic osteoarthropathy is due to mutations in the genes encoding 15-hydroxyprostaglandin dehydrogenase and solute carrier organic anion transporter family member 2A1, resulting in abnormal accumulation of prostaglandin E₂ ⁵.

Although the cause of secondary hypertrophic osteoarthropathy is not established, a similar mechanism involving abnormally elevated levels of circulated hormones has been proposed as a potential aetiology. Alternatively, neurogenic aetiology has been proposed ⁵.

Associated disease states include:

lung
- bronchogenic carcinoma
  - non-small cell lung cancer is the strongest malignant association, particularly squamous cell cancer
- pulmonary lymphoma
- lung abscess
- bronchiectasis
- pulmonary metastases (especially from osteosarcoma)
- pleural fibroma
- mesothelioma
- cyanotic congenital heart disease
gastrointestinal tract and liver
idiopathic

Radiographic features

Plain radiograph

Typically seen as long bone metaphyseal and diaphyseal smooth periosteal reaction.

With disease progression, periostitis becomes more prominent or multilayered and extends to the epiphyses¹.

Nuclear medicine

Tc-^99m MDP bone scan

symmetric linear increase in tracer accumulation along diaphyseal and metaphyseal surfaces of long bones ⁴
"tram-track" appearance

~~Differential diagnosis~~

~~General imaging differential considerations include:~~

~~pachydermoperiostosis (primary hypertrophic osteoarthropathy)~~

~~chronic venous insufficiency~~

~~thyroid acropachy~~

~~hypervitaminosis A~~

~~Consider the differential for a~~ ~~smooth periosteal reaction~~.

~~On bone scintigraphy, differentials include:~~

~~normal variant~~
~~lateral cortices of the tibiae often appear with a symmetric linear uptake~~

~~shin splints~~
~~can appear similar, but confined to the tibiae~~

~~chronic venous insufficiency~~

~~can cause symmetrical periosteal uptake~~

~~usually confined to the lower extremities below the knees~~

Treatment

Treatments for primary hypertrophic osteoarthropathy⁶

NSAIDs
corticosteroids
neurotoxin injections
beta-blockers
glycopyrrolate
infliximab

Treatments for secondary hypertrophic osteoarthropathy⁶

tumor resection
radiotherapy
chemotherapy
organ transplantation
bisphosphonates

Differential diagnosis

General imaging differential considerations include:

Consider the differential for a smooth periosteal reaction.

On bone scintigraphy, differentials include:

normal variant
- lateral cortices of the tibiae often appear with a symmetric linear uptake
shin splints
- can appear similar, but confined to the tibiae
chronic venous insufficiency
- can cause symmetrical periosteal uptake
- usually confined to the lower extremities below the knees

Lymphoedema on its own is not known to cause hypertrophic osteoarthropathy.

-<a href="/articles/non-small-cell-lung-cancer-2">non-small cell lung cancer</a> is the strongest malignant association, particularly <a title="Squamous cell carcinoma (lung)" href="/articles/squamous-cell-carcinoma-of-the-lung">squamous cell cancer</a>
+<a href="/articles/non-small-cell-lung-cancer-2">non-small cell lung cancer</a> is the strongest malignant association, particularly <a href="/articles/squamous-cell-carcinoma-of-the-lung">squamous cell cancer</a>
~~-<li><a href="/articles/pleural-fibroma">pleural fibroma</a></li>~~
+<li><a href="/articles/solitary-fibrous-tumour-of-the-pleura">pleural fibroma</a></li>
~~-<li><p>"tram-track" appearance </p></li>~~
~~-</ul><h4>Differential diagnosis</h4><p>General imaging differential considerations include:</p><ul>~~
~~-<li><a title="Pachydermoperiostosis" href="/articles/pachydermoperiostosis">pachydermoperiostosis (primary hypertrophic osteoarthropathy)</a></li>~~
+<li><p>"tram-track" appearance</p></li>
+</ul><h4>Treatment</h4><p>Treatments for primary hypertrophic osteoarthropathy<sup> 6</sup></p><ul>
+<li>NSAIDs</li>
+<li>corticosteroids</li>
+<li>neurotoxin injections</li>
+<li>beta-blockers</li>
+<li>glycopyrrolate</li>
+<li>infliximab</li>
+</ul><p>Treatments for secondary hypertrophic osteoarthropathy<sup> 6</sup></p><ul>
+<li>tumor resection</li>
+<li>radiotherapy</li>
+<li>chemotherapy</li>
+<li>organ transplantation</li>
+<li>bisphosphonates</li>
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+<![endif]--></p><h4>Differential diagnosis</h4><p>General imaging differential considerations include:</p><ul>
+<li><a href="/articles/pachydermoperiostosis">pachydermoperiostosis (primary hypertrophic osteoarthropathy)</a></li>
~~-<li>usually confined to the lower extremities below the knees </li>~~
+<li>usually confined to the lower extremities below the knees </li>
~~-</ul>~~
+</ul><p><a title="Lymphoedema" href="/articles/lymphoedema-1">Lymphoedema</a> on its own is not known to cause hypertrophic osteoarthropathy.</p>

References changed:

6. Bernardo S, Emer J, Burnett M, Gordon M. Hypertrophic Osteoarthropathy Presenting as Unilateral Cellulitis with Successful Treatment Using Pamidronate Disodium. J Clin Aesthet Dermatol. 2012;5(9):37-46. <a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3460662">PMC3460662</a> - <a href="https://www.ncbi.nlm.nih.gov/pubmed/23050033">Pubmed</a>

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Hypertrophic osteoarthropathy