Pachydermoperiostosis: Background, Pathophysiology, Epidemiology

Sections

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.

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]

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.^[16]

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.

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.

Clinical Presentation

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Sandoval AR, Robles BJ, Llanos JC, Porres S, Dardón JD, Harrison RM. Cutis verticis gyrata as a clinical manifestation of Touraine-Solente-Gole' syndrome (pachydermoperiostosis). BMJ Case Rep. 2013 Jul 12. 2013:[Medline].
Alves AP, Holanda Filha JG, et al. [Eyelid ptosis associated with pachydermoperiostosis: case report.]. Arq Bras Oftalmol. 2005 May-Jun. 68(3):401-4. [Medline].
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Touraine A, Solente G, Gole L. Un syndrome osteodermopathique: la pachydermie plicaturee avec pachyperiostose ds extremites. Presse Med. 1935. 43:1820-4.
Uppal S, Diggle CP, Carr IM, et al. Mutations in 15-hydroxyprostaglandin dehydrogenase cause primary hypertrophic osteoarthropathy. Nat Genet. 2008 Jun. 40(6):789-93. [Medline].
Nakazawa S, Niizeki H, Matsuda M, Nakabayashi K, Seki A, Mori T, et al. Involvement of prostaglandin E2 in the first Japanese case of pachydermoperiostosis with HPGD mutation and recalcitrant leg ulcer. J Dermatol Sci. 2015 May. 78(2):153-5. [Medline].
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Media Gallery

Clubbed fingernail.
Cutis verticis gyrata. Courtesy of DermNet New Zealand (http://www.dermnetnz.org/assets/Uploads/dermal-infiltrative/cvg2.jpg).

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Author

Robert A Schwartz, MD, MPH Professor and Head of Dermatology, Professor of Pathology, Pediatrics, Medicine, and Preventive Medicine and Community Health, Rutgers New Jersey Medical School; Visiting Professor, Rutgers University School of Public Affairs and Administration

Robert A Schwartz, MD, MPH is a member of the following medical societies: Alpha Omega Alpha, New York Academy of Medicine, American Academy of Dermatology, American College of Physicians, Sigma Xi

Disclosure: Nothing to disclose.

Coauthor(s)

Supriya Goyal, MD Consulting Dermatologist

Supriya Goyal, MD is a member of the following medical societies: Alpha Omega Alpha

Disclosure: Nothing to disclose.

Gregory M Richards, MD Clinical Assistant Professor, Department of Human Oncology, University of Wisconsin School of Medicine and Public Health

Gregory M Richards, MD is a member of the following medical societies: Alpha Omega Alpha, American College of Radiology, American Medical Association, American Roentgen Ray Society, American Society for Radiation Oncology, Radiological Society of North America, American Society of Clinical Oncology

Disclosure: Nothing to disclose.

Rajiv Goyal, MD Radiologist, Department of Radiology, Kaiser Permanente Medical Center

Rajiv Goyal, MD is a member of the following medical societies: American Medical Association, MedChi The Maryland State Medical Society, Radiological Society of North America, Maryland State Medical Society

Disclosure: Nothing to disclose.

Specialty Editor Board

David F Butler, MD Section Chief of Dermatology, Central Texas Veterans Healthcare System; Professor of Dermatology, Texas A&M University College of Medicine; Founding Chair, Department of Dermatology, Scott and White Clinic

David F Butler, MD is a member of the following medical societies: American Medical Association, Alpha Omega Alpha, Association of Military Dermatologists, American Academy of Dermatology, American Society for Dermatologic Surgery, American Society for MOHS Surgery, Phi Beta Kappa

Disclosure: Nothing to disclose.

Van Perry, MD Assistant Professor, Department of Medicine, Division of Dermatology, University of Texas School of Medicine at San Antonio

Van Perry, MD is a member of the following medical societies: American Academy of Dermatology

Disclosure: Nothing to disclose.

Chief Editor

William D James, MD Paul R Gross Professor of Dermatology, Vice-Chairman, Residency Program Director, Department of Dermatology, University of Pennsylvania School of Medicine

William D James, MD is a member of the following medical societies: American Academy of Dermatology, Society for Investigative Dermatology

Disclosure: Serve(d) as a director, officer, partner, employee, advisor, consultant or trustee for: Naked Biome<br/>Received income in an amount equal to or greater than $250 from: Elsevier; WebMD<br/>StatPearls; Editor.

Pachydermoperiostosis

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