Pachydermoperiostosis

Updated: May 14, 2018
  • Author: Robert A Schwartz, MD, MPH; Chief Editor: William D James, MD  more...
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Overview

Background

Hypertrophic osteoarthropathy is divided into primary and secondary forms. Pachydermoperiostosis (PDP), the primary form, accounts for 5% of all cases of hypertrophic osteoarthropathy. Secondary hypertrophic osteoarthropathy, also called pulmonary hypertrophic osteoarthropathy, is associated with underlying cardiopulmonary diseases and malignancies. [1] This latter condition is not discussed here but may be found in the article Dermatologic Manifestations of Pulmonary Disease.

Pachydermoperiostosis or primary hypertropic osteoarthropathy is a rare hereditary disorder that was first described in 1868. It is characterized by digital clubbing, pachydermia (thickening of the facial skin and/or scalp), and periostosis (swelling of periarticular tissue and subperiosteal new bone formation). Pachydermoperiostosis or primary hypertropic osteoarthropathy is associated with pain, polyarthritis, cutis verticis gyrata, [2] seborrhea, eyelid ptosis, [3, 4] and hyperhidrosis. Touraine et al [5] described 3 forms of pachydermoperiostosis or primary hypertropic osteoarthropathy: (1) a complete form with pachydermia and periostitis, (2) an incomplete form with evidence of bone abnormalities but lacking pachydermia, and (3) a forme fruste with prominent pachydermia and minimal-to-absent skeletal changes.

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Pathophysiology

As reported in 2008, pachydermoperiostosis or primary hypertropic osteoarthropathy has been mapped to band 4q33-q34. Mutations in HPGD, encoding 15-hydroxyprostaglandin dehydrogenase, the main enzyme of prostaglandin degradation, have been identified. [6, 7] Deficiency of the prostaglandin transporter (SLCO2A1) has been characterized as the main cause of primary hypertrophic osteoarthropathy. [8, 9] Mutations in the prostaglandin transporter gene, SLCO2A1, have been documented in Koreans with pachydermoperiostosis. [10] A novel SLCO2A1 mutation in a Lebanese family, [11] a Saudi patient, [9] a Korean family, [12] and a Chinese family [13] have been documented, as have a novel nonsense mutation p.E141* of the SLCO2A1 gene in a Japanese one [14] and a novel homozygous truncating mutation in HPGD described in Turkey. [15]

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Etiology

Pachydermoperiostosis or primary hypertropic osteoarthropathy is often familial. The condition is believed to be inherited in an autosomal dominant pattern with variable penetrance; however, autosomal recessive forms have been reported.

Pachydermoperiostosis or primary hypertropic osteoarthropathy has been mapped to band 4q33-q34, and mutations in HPGD, encoding 15-hydroxyprostaglandin dehydrogenase, the key enzyme of prostaglandin degradation, have been identified. Individuals with homozygous mutations have chronically elevated prostaglandin E2 levels. Milder biochemical and clinical manifestations are found in heterozygous individuals.

Vascular endothelial growth factor is abnormally expressed in some patients with pachydermoperiostosis or primary hypertropic osteoarthropathy.

Increased levels of interleukin 6 and receptor activator of nuclear factor–kappaB ligand (RANKL) have been reported in the serum of a patient with pachydermoperiostosis or primary hypertropic osteoarthropathy during the acute phase of the disease. [16]

Pachydermoperiostosis or primary hypertropic osteoarthropathy has been associated in case reports with a variety of other disorders, including the following:

  • Gastrointestinal pathology, [17] including gastric carcinoma, Crohn disease, peptic ulcer disease, chronic gastritis, Ménétrièr disease, [18] and protein-losing enteropathy [19]

  • Myelofibrosis [20, 21, 22, 23, 24]

  • Gynecomastia [25]

  • Compressive neuropathy

  • Hypoplastic internal genitalia

  • Psoriatic onychopathy [26]

  • Periodontal and alveolar bone abnormalities [27]

  • Spondylolisthesis of the L5-S1 vertebrae

  • Congenital cardiac disease [28, 29]

  • Atherothrombotic brain infarction [30]

  • Osteoporosis [25]

  • Rheumatoid arthritis [31]

  • Ankylosing spondylitis [32]

  • En coup de sabre (a form of localized scleroderma) [33]

In certain instances, several years after the onset pachydermoperiostosis or primary hypertropic osteoarthropathy, diseases generally known to result in secondary hypertrophic osteoarthropathy (Crohn disease, myelofibrosis, and congenital cardiac disease) have been reported to develop in patients with pachydermoperiostosis or primary hypertropic osteoarthropathy. [34]

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Epidemiology

Frequency

United States

Pachydermoperiostosis or primary hypertropic osteoarthropathy is a rare disorder, and the precise incidence is unknown.

International

This rare paraneoplastic syndrome is most frequently associated with lung cancer. By analyzing clinical data of 6,151 patients with advanced lung cancer, a retrospective study found that 1.87% of patients showed characteristics of hypertrophic pulmonary osteoarthropathy. [35]

Race

Pachydermoperiostosis or primary hypertropic osteoarthropathy is more common in African Americans than in whites.

Sex

The male-to-female case ratio is approximately 7:1. Typically, men are affected more severely than women. Women often have milder findings, and their disease may remain undetected.

Age

Pachydermoperiostosis or primary hypertropic osteoarthropathy typically begins during childhood or adolescence and progresses gradually over the next 5-20 years before stabilizing.

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Prognosis

The progression of pachydermoperiostosis or primary hypertropic osteoarthropathy typically ceases after 10 years, but patients may be left with chronic debilitating complications, which include severe kyphosis, restricted motion, and neurologic manifestations. Life expectancy may be normal, except in cases in which severe mental impairment is involved.

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