Pachydermoperiostosis

Pachydermoperiostosis (PDP), also known as primary hypertrophic osteoarthropathy, is a rare disease of the skin and bones that has clear genetic predisposition and well-defined clinical features. PDP is characterised by the presence of exuberant skin hypertrophy that, at the most distal parts of the extremities, takes a drumstick configuration. This deformity is conventionally known as digital clubbing. In advanced stages, skin hypertrophy may also be present in the head with furrowing of the facial features and eyelids ptosis. Another characteristic feature of the disease is periosteal proliferation of the long bones.

Abnormal vascular endothelial growth factor and/or genetically determined prostaglandins overexpression may play a key role on its pathogenesis.

No therapy has been shown to be effective in reversing hypertrophic changes. When bone pain is present, non-steroidal anti-inflammatory drugs are frequently useful. Isolated case reports have described that bisphosphonates may ease recalcitrant bone pain.

Pachydermoperiostosis (PDP), also known as primary hypertrophic osteoarthropathy, is a rare disease of the skin and bones that has clear genetic predisposition and well-defined clinical characteristics. People who suffer from PDP typically display the following abnormalities: A unique bulbous deformity at the tip of the digits conventionally known as digital clubbing, periosteal proliferation of the tubular bones and various degrees of hypertrophy and/or hyperhidrosis of the skin .

Clinical setting

Most patients with PDP are male, the male/female proportion being 9:1. PDP is clearly a familial disease. One-third of affected individuals recognise a close relative with similar digital deformity. The form of inheritance has not been well-defined. Both autosomic-dominant and autosomic-recessive patterns have been described .

Digital clubbing is the most conspicuous clinical feature of PDP and it is evident in the overwhelming majority of cases. Clubbing may be apparent since birth or may appear during adolescence. In mild cases, digital clubbing may be the only feature of the disease. In more advanced instances, skin hypertrophy may also be present in the head with furrowing of the skin producing coarsening of the facial features and eyelids ptosis. The furrowing may involve the scalp, where it is known as cutis verticis gyrata. Typically, the skin of affected individuals is oily. Acne and increased perspiration (hyperhidrosis) are frequent .

Some patients complain of bone and joint pain. Such pain is deep seated and is located preferentially in the lower extremities. Thickening of the tubular bones may be appreciated in those areas not covered by muscle such as the wrists and ankles. The lower part of the legs may take a cylindrical shape known as ‘elephant leg’ ( Fig. 1 ). Synovial effusion may be evident in the knees. It may be more difficult to define the presence of effusion at the wrist or ankle level due to the surrounding soft-tissue swelling. Synovial fluid examination reveals a thick viscous fluid with no inflammatory cell exudation. Histology of affected skin areas reveals oedema, localised endothelial hyperplasia and excessive collagen deposition .

A variety of associated features have been described in PDP such as cranial suture defects, males with female escutcheon and hypertrophic gastropathy. A curious clinical palindrome occurs in some PDP cases; they display as late complication, diseases that in other circumstances are known to generate hypertrophic osteoarthropathy (HOA). It has been shown that many years after the onset of their PDP, some patients may develop inflammatory bowel disease or myelofibrosis. These two conditions are known to generate secondary HOA. Similar palindrome occurs in cases of patent ductus arteriosus. In such instances, closure of the ductus arteriosus has no effect on the osseous changes .

Laboratory and imaging studies

At present, there is no clinical laboratory test to confirm the presence of PDP. In the future, hydroxyprostaglandin dehydrogenase gene mutation may become a useful diagnostic study .

Of utmost importance for the correct assessment of PDP are plain radiographs of the extremities, which may detect abnormalities in an asymptomatic patient. Primary and secondary HOAs display similar abnormalities . Long-standing clubbing is characterised by a bone remodelling process that takes the form of acro-osteolysis ( Fig. 2 ) or, more frequently, tuftal overgrowth ( Fig. 3 ) . Characteristically, the bone changes of clubbing are observed first at the toes; fingers are affected in advanced cases. Periostosis is an orderly, evolutionary process that depends on the chronicity of the illness. It progresses in three dimensions: in the number of affected bones, in the site of involvement of a given bone and in the shape of the periosteal apposition. In mild cases, few bones are affected (usually tibias and fibulas), periostosis is limited to the diaphysis and it has a monolayer configuration ( Fig. 4 ). In advanced cases, all tubular bones are affected: in addition to the diaphysis, the metaphysis and epiphysis are also involved and the periostosis takes on an irregular configuration ( Fig. 5 ). Periostosis has a symmetric distribution and evolves in a centripetal fashion. Typically is preservation of joint space and the absence of erosions or para-articular osteopenia .

Laboratory and imaging studies

At present, there is no clinical laboratory test to confirm the presence of PDP. In the future, hydroxyprostaglandin dehydrogenase gene mutation may become a useful diagnostic study .

Of utmost importance for the correct assessment of PDP are plain radiographs of the extremities, which may detect abnormalities in an asymptomatic patient. Primary and secondary HOAs display similar abnormalities . Long-standing clubbing is characterised by a bone remodelling process that takes the form of acro-osteolysis ( Fig. 2 ) or, more frequently, tuftal overgrowth ( Fig. 3 ) . Characteristically, the bone changes of clubbing are observed first at the toes; fingers are affected in advanced cases. Periostosis is an orderly, evolutionary process that depends on the chronicity of the illness. It progresses in three dimensions: in the number of affected bones, in the site of involvement of a given bone and in the shape of the periosteal apposition. In mild cases, few bones are affected (usually tibias and fibulas), periostosis is limited to the diaphysis and it has a monolayer configuration ( Fig. 4 ). In advanced cases, all tubular bones are affected: in addition to the diaphysis, the metaphysis and epiphysis are also involved and the periostosis takes on an irregular configuration ( Fig. 5 ). Periostosis has a symmetric distribution and evolves in a centripetal fashion. Typically is preservation of joint space and the absence of erosions or para-articular osteopenia .