pachydermoperiostosis pachydermoperiostosis pachydermoperiostosis (pdp) is a rare genetic disorder that affects both bones and skin. other names are primary hypertrophic osteoarthropathy or touraine-solente-golé syndrome. it is mainly characterized by pachyderma (thickening of the skin), periostosis (excessive bone formation) and finger clubbing (swelling of tissue with loss of normal angle between nail and nail bed). pachydermoperiostosisother namesprimary hypertrophic osteoarthropathyspecialtyrheumatology this disease affects more men than women. after onset, the disease stabilizes after about 5–20 years. life of pdp patients can be severely impaired. currently, symptomatic treatments are nsaids and steroids or surgical procedures. in 1868, pdp was first described by friedreich as 'excessive growth of bone of the entire skeleton'. touraine, solente and golé described pdp as the primary form of bone disease hypertrophic osteoarthropathy in 1935 and distinguished its three known forms. symptoms pdp has a number of visible signs. 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). other features include excessive sweating, arthralgia and gastrointestinal abnormalities. an overview of all symptoms is provided in table 2. table 2. overview of signs skin features pachydermia coarse skin oily skin eczema thick hand and foot skin leonine facies furrowing cutis verticis gyrate increased secretion of sebum sebborheic hyperplasia keloid formation bone features periostosis acroosteolysis mylefibrosis thick toe and finger bones widening of bone formation clubbing digital clubbing sweating hyperhidrosis eye features drooping eyelids thick stratum corneum joints arthralgia joint effusion muscles muscle discomfort hair decreased facial and pubic hair vascular peripheral vascular stasis gastrointestinal involvement peptic ulcer chronic gastritis crohn’s disease cause the locally acting mediator prostaglandin e2 (pge2) plays a role in the pathogenesis of pdp. in pdp patients, high levels of pge2 and decreased levels of pge-m (the metabolite of pge2) were observed. pge2 can mimic the activity of osteoblasts and osteoclasts (respectively building and breaking down bone tissue). this is why acroosteolysis and periosteal bone formation can be explained by the action of pge2. furthermore, pge2 has vasodilatory effects, which is consistent with prolonged local vasodilation in digital clubbing. elevated levels of pge2 in pdp patients are associated with mutations of hpgd gene. these patients showed typical pdp symptoms such as digital clubbing and periostosis. the hpgd gene is mapped on chromosome 4q34 and encodes the enzyme hpgd (15-hydroxyprostaglandin dehydrogenase). this enzyme catalyzes the first step in the degradation of pge2 and related eicosanoids. so far, eight different mutations are known leading to a dysfunctional hpgd enzyme in pdp patients. due to these mutations, the binding of the substrate pge2 to hpgd is disrupted. as a result of this, pge2 cannot be transferred into pge-m down and remain present at high concentrations. role of other mediators 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). these substances could also have a role in pdp progression and proliferation. in contrast to hpgd mutations, suspected mutations for these factors have not been reported yet. von willebrand factor is a marker of platelet and endothelial activation. this suggests that the activation of endothelial cells and platelets play an important role in the pathogenesis of pdp. vegf promotes angiogenesis (growth of new blood vessels) and differentiation of osteoblasts, which can explain the clubbing and excessive fibroblast formation in pdp patients. other mediators found in increased concentrations in pdp patients, include osteocalcin, endothelin-1, b-thromboglobulin, platelet-derived growth factor (pdgf) and epidermal growth factor (egf). it has not been described yet what role these mediators have in pdp. genetics two genes have been associated with this condition: hydroxyprostaglandin dehydrogenase 15-(nad) (hpgd) in chromosome 4 (4q34.1) and solute carrier organic anion transporter family member 2a1 (slco2a1) in chromosome 3 (3q22.1-q22.2). this syndrome occurs if both copies of either gene are mutated (autosomal recessive inheritance) diagnosis