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

Lowenthal MN, Tombak A, Lowenthal A. Secondary hypertrophic osteoarthropathy (HOA) mimicking primary HOA (pachydermoperiostitis or Touraine-Solente-Golé) syndrome. Isr Med Assoc J. 2004 Jan. 6(1):64. [Medline].
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].
Arinci A, Tümerdem B, Karan MA, et al. Ptosis caused by pachydermoperiostosis. Ann Plast Surg. 2002 Sep. 49(3):322-5. [Medline].
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].
Zhang Z, He JW, Fu WZ, Zhang CQ, Zhang ZL. Mutations in the SLCO2A1 gene and primary hypertrophic osteoarthropathy: a clinical and biochemical characterization. J Clin Endocrinol Metab. 2013 May. 98(5):E923-33. [Medline].
Ayoub N, Al-Khenaizan S, Sonbol H, Albreakan R, AlSufyani M, AlBalwi M. A novel homozygous mutation in the SLCO₂ A1 gene is associated with severe primary hypertrophic osteoarthropathy phenotype in a Saudi patient. Int J Dermatol. 2015 Jan 20. [Medline].
Lee S, Park SY, Kwon HJ, Lee CH, Kim OH, Rhee Y. Identification of the Mutations in the Prostaglandin Transporter Gene, SLCO2A1 and Clinical Characterization in Korean Patients with Pachydermoperiostosis. J Korean Med Sci. 2016 May. 31 (5):735-42. [Medline].
Saadeh D, Kurban M, Ghosn S, Btadini W, Nemer G, Arayssi T, et al. Pachydermoperiostosis genetic screening in Lebanese families uncovers a novel SLCO2A1mutation. J Eur Acad Dermatol Venereol. 2014 Jul 25. [Medline].
Kim HJ, Koo KY, Shin DY, Kim DY, Lee JS, Lee MG. Complete form of pachydermoperiostosis with SLCO2A1 gene mutation in a Korean family. J Dermatol. 2015 Mar 21. [Medline].
Wang L, Yu J, Li Y, Liu X, Zhang Z. [Genetic diagnosis for a Chinese Han family with primary hypertrophic osteoarthropathy]. Zhonghua Yi Xue Yi Chuan Xue Za Zhi. 2015 Apr. 32(2):213-7. [Medline].
Niizeki H, Shiohama A, Sasaki T, Seki A, Kabashima K, Otsuka A, et al. The complete type of pachydermoperiostosis: a novel nonsense mutation p.E141* of the SLCO2A1 gene. J Dermatol Sci. 2014 Sep. 75(3):193-5. [Medline].
Erken E, Köroglu C, Yildiz F, Ozer HT, Gülek B, Tolun A. A novel recessive 15-hydroxyprostaglandin dehydrogenase mutation in a family with primary hypertrophic osteoarthropathy. Mod Rheumatol. 2014 Feb 18. [Medline].
Qian X, Qin J. Hypertrophic pulmonary osteoarthropathy with primary lung cancer. Oncol Lett. 2014 Jun. 7(6):2079-2082. [Medline]. [Full Text].
Rendina D, De Filippo G, Viceconti R, et al. Interleukin (IL)-6 and receptor activator of nuclear factor (NF)-kappaB ligand (RANKL) are increased in the serum of a patient with primary pachydermoperiostosis. Scand J Rheumatol. 2008 May-Jun. 37(3):225-9. [Medline].
Ikeda F, Okada H, Mizuno M, et al. Pachydermoperiostosis associated with juvenile polyps of the stomach and gastric adenocarcinoma. J Gastroenterol. 2004. 39(4):370-4. [Medline].
Lakshmi TS, Rao PN, Nagaria M. Primary pachydermoperiostosis associated with Menetrier's disease. Indian J Dermatol Venereol Leprol. 2001 Sep-Oct. 67(5):256-8. [Medline].
Sethuraman G, Malhotra AK, Khaitan BK, et al. Familial pachydermoperiostosis in association with protein-losing enteropathy. Clin Exp Dermatol. 2006 Jul. 31(4):531-4. [Medline].
Bachmeyer C, Blum L, Cadranel JF, et al. Myelofibrosis in a patient with pachydermoperiostosis. Clin Exp Dermatol. 2005 Nov. 30(6):646-8. [Medline].
Kumar U, Bhatt SP, Misra A. Unusual associations of pachydermoperiostosis: A case report. Indian J Med Sci. 2008 Feb. 62(2):65-8. [Medline].
Saghafi M, Azarian A, Nohesara N. Primary hypertrophic osteoarthropathy with myelofibrosis. Rheumatol Int. 2008 Apr. 28(6):597-600. [Medline].
Ninomiya S, Hara T, Tsurumi H, Kanemura N, Kasahara S, Ogawa Y, et al. Myelofibrosis successfully treated with prednisolone in a patient with pachydermoperiostosis. Intern Med. 2011. 50(19):2207-11. [Medline].
Poormoghim H, Hosseynian A, Javadi A. Primary hypertrophic osteoarthropathy. Rheumatol Int. 2010 Dec 2. [Medline].
Ukinc K, Ersoz HO, Erem C, et al. Pachydermoperiostosis with gynecomastia and osteoporosis: a rare case with a rare presentation. Int J Clin Pract. 2007 Nov. 61(11):1939-40. [Medline].
Fietta P, Manganelli P. Pachydermoperiostosis and psoriatic onychopathy: an unusual association. J Eur Acad Dermatol Venereol. 2003 Jan. 17(1):73-6. [Medline].
Akdeniz BG, Seckin T. Periodontal and alveolar bone abnormalities associated with pachydermoperiostosis. Periodontal Clin Investig. 2001. 23(1):5-10. [Medline].
Levin SE, Harrisberg JR, Govendrageloo K. Familial primary hypertrophic osteoarthropathy in association with congenital cardiac disease. Cardiol Young. 2002 May. 12(3):304-7. [Medline].
Sinha GP, Curtis P, Haigh D, et al. Pachydermoperiostosis in childhood. Br J Rheumatol. 1997 Nov. 36(11):1224-7. [Medline].
Nakajima M, Hirano T, Itoh K, et al. Atherothrombotic brain infarction in a patient with pachydermoperiostosis. Mod Rheumatol. 2008. 18(3):281-4. [Medline].
Diamond S, Momeni M. Primary hypertrophic osteoarthropathy in a patient with rheumatoid arthritis. J Clin Rheumatol. 2007 Aug. 13(4):242-3. [Medline].
Shinjo SK, Borba EF, Gonçalves CR, et al. Ankylosing spondylitis in a patient with primary hypertrophic osteoarthropathy. J Clin Rheumatol. 2007 Jun. 13(3):175. [Medline].
Ozdemir M, Yildirim S, Mevlitoglu I. En coup de sabre accompanied by pachydermoperiostosis: a case report. Clin Exp Rheumatol. 2007 Mar-Apr. 25(2):315-7. [Medline].
Martinez-Lavin M, Vargas A, Rivera-Vinas M. Hypertrophic osteoarthropathy: a palindrome with a pathogenic connotation. Curr Opin Rheumatol. 2008 Jan. 20(1):88-91. [Medline].
Reginato AJ, Schiapachasse V, Guerrero R. Familial idiopathic hypertrophic osteoarthropathy and cranial suture defects in children. Skeletal Radiol. 1982. 8(2):105-9. [Medline].
Seggewiss R, Hess T, Fiehn C. A family with a variant form of primary hypertrophic osteoarthropathy restricted to the lower extremities. Joint Bone Spine. 2003 Jun. 70(3):230-3. [Medline].
Adams B, Amin T, Leone V, Wood M, Kraft JK. Primary hypertrophic osteoarthropathy: ultrasound and MRI findings. Pediatr Radiol. 2016 May. 46 (5):727-30. [Medline].
Hedayati H, Barmada R, Skosey JL. Acrolysis in pachydermoperiostosis. Primary or idiopathic hypertrophic osteoarthropathy. Arch Intern Med. 1980 Aug. 140(8):1087-8. [Medline].
Herbert DA, Fessel WJ. Idiopathic hypertrophic osteoarthropathy (pachydermoperiostosis). West J Med. 1981 Apr. 134(4):354-7. [Medline].
Jajic Z, Jajic I, Nemcic T. Primary hypertrophic osteoarthropathy: clinical, radiologic, and scintigraphic characteristics. Arch Med Res. 2001 Mar-Apr. 32(2):136-42. [Medline].
Fam AG, Chin-Sang H, Ramsay CA. Pachydermoperiostosis: scintigraphic, thermographic, plethysmographic, and capillaroscopic observations. Ann Rheum Dis. 1983 Feb. 42(1):98-102. [Medline].
Santhosh S, Bhattacharya A, Bhadada S, Kaur R, Singh M, Mittal BR. Three-phase skeletal scintigraphy in pachydermoperiostosis. Clin Nucl Med. 2011 Dec. 36(12):e199-201. [Medline].
Wen X, Li Y, Hamblin MR, Jiang X. Facial Manifestations of Pachydermoperiostosis Treated with Botulinum Toxin Type-A: Report of 3 Cases. Acta Derm Venereol. 2017 Feb 22. [Medline].
Bhansali A, Singh R, Sriraam M, et al. Pachydermoperiostitis and bisphosphonates. J Assoc Physicians India. 2006 Apr. 54:340. [Medline].
Guyot-Drouot MH, Solau-Gervais E, Cortet B, et a;. Rheumatologic manifestations of pachydermoperiostosis and preliminary experience with bisphosphonates. J Rheumatol. 2000 Oct. 27(10):2418-23. [Medline].
Maeda H, Kumagai K, Konishi F, et al. Successful treatment of arthralgia with tamoxifen citrate in a patient with pachydermoperiostosis. Rheumatology (Oxford). 2000 Oct. 39(10):1158-9. [Medline].
Okten A, Mungan I, Kalyoncu M, et al. Two cases with pachydermoperiostosis and discussion of tamoxifen citrate treatment for arthralgia. Clin Rheumatol. 2007 Jan. 26(1):8-11. [Medline].
Jojima H, Kinoshita K, Naito M. A case of pachydermoperiostosis treated by oral administration of a bisphosphonate and arthroscopic synovectomy. Mod Rheumatol. 2007. 17(4):330-2. [Medline].
Li SS, He JW, Fu WZ, Liu YJ, Hu YQ, Zhang ZL. Clinical, Biochemical, and Genetic Features of 41 Han Chinese Families With Primary Hypertrophic Osteoarthropathy, and Their Therapeutic Response to Etoricoxib: Results From a Six-Month Prospective Clinical Intervention. J Bone Miner Res. 2017 Apr 20. [Medline].
George L, Sachithanandam K, Gupta A, et al. Frontal rhytidectomy as surgical treatment for pachydermoperiostosis: a case report. J Dermatolog Treat. 2008. 19(1):61-3. [Medline].
Monteiro E, Carvalho P, Silva A, et al. Frontal rhytidectomy: a new approach to improve deep wrinkles in a case of pachydermoperiostosis. Plast Reconstr Surg. 2003 Sep 15. 112(4):1189-91. [Medline].
Seyhan T, Ozerdem OR, Aliagaoglu C. Severe complete pachydermoperiostosis (Touraine-Solente-Golé syndrome). Dermatol Surg. 2005 Nov. 31(11 Pt 1):1465-7. [Medline].
Bruner S, Frerichs O, Raute-Kreinsen U, et al. [Correction of finger clubbing in primary hypertrophic osteoarthropathy (Touraine-Solente-Gole syndrome)]. Handchir Mikrochir Plast Chir. 2007 Apr. 39(2):135-8. [Medline].
Warwas S, Specker C, Jäger M, Landgraeber S. Arthroscopic synovectomy and radiosynoviorthesis: a treatment option for recurrent arthritis symptoms in patients with pachydermoperiostosis. Reumatismo. 2013 May 27. 65(2):82-5. [Medline].

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.

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