Most important clinical features are: pachydermia (thickening and wrinkling of the skin), furrowing of the face and scalp, periostosis (swelling of periarticular tissue and shaggy periosteal new bone formation of long bones) and digital clubbing (enlargement of fingertips).
Overview of signs [1][5][7][8] The locally acting mediator prostaglandin E2 (PGE2) plays a role in the pathogenesis of PDP.
[citation needed] Apart from elevated PGE2 levels, studies in patients with hypertrophic osteoarthropathy also showed increased plasma levels of several other mediators, such as Von Willebrand factor and vascular endothelial growth factor (VEGF).
[citation needed] Von Willebrand factor is a marker of platelet and endothelial activation.
[14] This suggests that the activation of endothelial cells and platelets play an important role in the pathogenesis of PDP.
[16] VEGF promotes angiogenesis (growth of new blood vessels) and differentiation of osteoblasts, which can explain the clubbing and excessive fibroblast formation in PDP patients.
[20] This syndrome occurs if both copies of either gene are mutated (autosomal recessive inheritance)[citation needed] The easiest way to diagnose PDP is when pachydermia, finger clubbing and periostosis of the long bones are present.
For example, to exclude secondary hypertrophic osteoarthropathy, any signs of cardiovascular, pulmonary, hepatic, intestinal and mediastinal diseases must be absent.
However, it is not a very specific method, because other diseases share the same skin alterations with PDP, such as myxedema and hypothyroidism.
For example, thyrotropin and growth hormone levels should be examined to exclude thyroid acropachy and acromegaly.
[3] When clubbing is observed, it is helpful to check whether acroosteolysis of distal phalanges of fingers is present.
[9] Additionally, HPGD mutation analyses are relatively cheap and simple and may prove to be useful in early investigation in patients with unexplained clubbing or children presenting PDP-like features.
[9][25] For the follow-up of PDP disease activity, bone formation markers such as TAP, BAP, BGP, carbodyterminal propeptide of type I procallagen or NTX can play an important role.
[3] Other biomarkers that can be considered are IL-6 and receptor activator of NF-κB ligand (RANKL), which are associated with increased bone resorption in some patients.
[1][7] The effective treatment for PDP is currently unknown due to the lack of controlled data and is largely based on case reports.
[citation needed] Conventional PDP drug treatment to decrease inflammation and pain includes NSAIDs and corticosteroids.
[30] Since PGE2 is likely to be involved in periosteal bone formation and acroosteolysis, this is why these drugs can alleviate the polyarthritis associated with PDP.
[4] In addition, NSAIDs and corticosteroids decrease formation of inflammatory mediators, reducing inflammation and pain.
It is a monoclonal antibody that blocks the biological action of TNF-α (tumor necrosis factor-alpha).
[4] In isolated cases, tamoxifen was effective in PDP treatment, especially for bone and joint pain.
[4][21] Tamoxifen and several of its metabolites competitively bind to estrogen receptors on tissue targets, producing a nuclear complex that decreases DNA synthesis.
[33] For example, isotretinoin, the most effective drug to treat acne, improves cosmetic features by inducing apoptosis within human sebaceous glands.
[36] It is suggested that colchicine inhibit chemotactic activity of leukocytes, which leads to reduction of pachydermia.
[1] Life expectancy may be normal, despite patients getting many functional and cosmetic complications, including restricted motion, neurologic manifestations and leonine facies.
[1] The autosomal dominant model of inheritance with penetrance and variable expression is confirmed in about half of the families, associated with the incomplete form.