Home / Rare Diseases / Pachydermoperiostosis

Pachydermoperiostosis

Last updated: December 01, 2021

Years published: 1992, 2000, 2005, 2008, 2021

Acknowledgment
NORD gratefully acknowledges Sunaina Kapur, MMSc, NORD Editorial
Intern from the Emory University Genetic Counseling Training Program
and Cecelia A. Bellcross, PhD, MS, CGC, Associate Professor, Director,
Genetic Counseling Training Program, Emory University School of
Medicine, for assistance in the preparation of this report.

DISEASE OVERVIEW

Pachydermoperiostosis, also called primary hypertrophic

osteoarthropathy (PHO) is a rare genetic condition. The three main
features are large finger tips (clubbing), thickening of the skin of the
face (pachydermia) and extra sweating (hyperhidrosis). It typically starts
during childhood or adolescence, often around the time of puberty,
and progresses slowly for about ten years.

Pachydermoperiostosis is the complete form of PHO where there is

also unusual thickness of the skin (pacydermia). There are also two
incomplete forms, one with isolated bone problems and skin changes,
and one with pachydermia and minimal or absent new bone growth
(periostosis).

SYNONYMS

primary hypertrophic osteoarthropathy

pachydermoperiostosis syndrome

Rosenfeld-Kloepfer syndrome

Touraine-Solente-Gole syndrome

PHO

SIGNS & SYMPTOMS

PHO is characterized by problems with the growth of skin and bones.

People with PHO usually have coarse facial features with oily, thick,
grooved skin on the face, joint pain, large tips of the fingers and toes
(clubbing) and extra sweating of the hands and feet (hyperhidrosis).

New bone growth (periostosis), often at the ends of the long bones,
causes joint pain. Extra skin on the scalp can be seen that causes deep
grooves or ridges (cutis verticis gyrate).These grooves or ridges usually
occur during the teen years.

Other symptoms can include swelling or pain of the large joints;

drooping eyelids (ptosis); a long-term skin condition that causes dry or
moist scales and a yellowish crust (seborrheic dermatitis); ulcers; long
eyelashes; occasional diarrhea; swelling of hair follicles related to large
open pores of the skin; heart disease present at birth and/or delayed
closure of the space between the bones of the skull (fontanelles).
The symptoms vary between individuals, but overall, males tend to have
more serious symptoms than females. X-rays can help look at features
that are not as noticeable to the naked eye.

CAUSES

For most individuals, the diagnosis of PHO is based on the clinical

features. It is recognized more often in males than females, as males
have more noticeable and severe features. PHO can be inherited, but a
non-genetic form has also been described.

Genetic conditions can be inherited in different ways. Individuals

typically inherit one copy of a gene pair from their mother, and the
other from their father. Genes provide instructions to tell the body how
to function. When there is a harmful change (mutation) in a gene it may
not function normally leading to unusual features and/or conditions.
Autosomal dominant and autosomal recessive inheritance patterns
have been reported for PHO.

There are two genes that have been associated with PHO: HPGD and

SLCO2A1. Mutations in HPGD are associated with autosomal recessive

inheritance and this condition is sometimes abbreviated PHOAR1 or
Touraine-Solente-Gole syndrome.

Recessive genetic conditions occur when an individual inherits one

non-working gene for the same condition from each parent. If an
individual receives one normal gene and one gene with a mutation, the
person will be a carrier for the condition and will usually not show
symptoms. The chance for two carrier parents to both pass the non-
working gene and, therefore, have a child with that condition is 25%
with each pregnancy. The chance to have a child who is a carrier like
the parents is 50% with each pregnancy. The chance for a child to
receive normal working genes from both parents is 25%. The chance is
the same for males and females.

Parents who are closely related by blood (consanguineous) have a

higher chance than unrelated parents to both carry the same non-
working gene, which increases the chance to have children with a
recessive genetic disorder.

PHO caused by mutations in SLCO2A1 can be dominant or recessive.

The recessive form is called PHOAR2. The dominant form is called
PHOAD. Dominant genetic disorders occur when only a single copy of
an abnormal gene is necessary to see symptoms of the condition. The
non-working gene can be inherited from either parent or can be the
result of a new mutation (gene change) in the individual with the
condition. The chance of passing the non-working gene from an
affected parent to child is 50% for each pregnancy. The risk is the same
for males and females. However, with PHOAD, males are more
commonly and often more severely affected.

AFFECTED POPULATIONS

PHO is a rare disorder that affects males more than females with a ratio
of 7:1. This means that for about every 7 males that are diagnosed with
this condition, 1 female is diagnosed. However, since females tend to
have milder symptoms than males, females may go undiagnosed.
DISORDERS WITH SIMILAR SYMPTOMS
Symptoms of the following disorders can be similar to those of
pachydermoperiostosis. Comparing features can be useful to make the
correct diagnosis:

Acromegaly is a rare, slowly progressive, acquired disorder that affects

adults. It is a condition where extra growth hormone causes different
tissues to be become larger than normal and the individual to be taller.
The arms, legs, jaws and face are most often affected. Enlargement of
soft tissues, especially within the heart, is a serious feature of this
condition. (For more information on this disorder choose “acromegaly”
as your search term in the Rare Disease Database.)

Hypertrophic pulmonary osteoarthropathy (Bamberger-Marie disease)

is a rare condition where there is extra growth at the ends of the long
bones and often unusually large fingers and toes (clubbing). This
disorder occurs in people with long-term lung disease, heart disease
and occasionally in other disorders.

Features of PHO can be mistaken for osteoarthropathy (any condition

affecting bones and joints), psoriatic arthritis (arthritis in combination
with psoriasis – red and white patches on the skin), rheumatoid arthritis
(condition that can cause joint damage) and thyroid acropachy
(thickening and swelling of the hands and feet).

DIAGNOSIS

The diagnosis of PHO is made based on clinical features, though

genetic testing can confirm the diagnosis. Major diagnostic criteria
include clubbing of the fingers (digital clubbing) and new bone growth
(periostosis).

STANDARD THERAPIES

Treatment

Treatment is mostly aimed at specific symptoms and is supportive.

Nonsteroidal anti-inflammatory drugs (NSAIDs, such as Advil),
colchicine, or corticosteroids can be taken to decrease bone and joint
pain.

Vagotomy, a surgical procedure in which certain branches of the vagus

nerve are cut, may improve joint pain and swelling. Retinoids can be
used to treat symptoms that involve the skin. Plastic surgery may be
performed to improve facial appearance. Surgery can treat clubbing of
the fingers.

Genetic counseling may be helpful for patients and their families.

CLINICAL TRIALS AND STUDIES

Information on current clinical trials is posted on the Internet at
www.clinicaltrials.gov. All studies receiving U.S. government funding,
and some supported by private industry, are posted on this
government web site.

For information about clinical trials being conducted at the NIH Clinical
Center in Bethesda, MD, contact the NIH Patient Recruitment Office:

Tollfree: (800) 411-1222 TTY: (866) 411-1010 Email: prpl@cc.nih.gov

Some current clinical trials also are posted on the following page on the
NORD website: https://rarediseases.org/living-with-a-rare-

disease/find-clinical-trials/

For information about clinical trials sponsored by private sources,

contact: www.centerwatch.com

For information about clinical trials conducted in Europe, contact:

https://www.clinicaltrialsregister.eu/

REFERENCES
TEXTBOOKS

Fauci AS, Braunwald E, Isselbacher KJ, et al., eds. Harrison’s Principles

of Internal Medicine. 20/E McGraw-Hill Companies. New York, NY;
2018.

Griffiths C, Barker J, Bieiker T et al. Rook’s Textbook of Dermatology.

9th ed. Wiley Blackwell Scientific Publications. London, UK; 2016.

JOURNAL ARTICLES

Xu Y, Zhang Z, Yue H, Li S, Zhang Z. Monoallelic mutations in SLCO2A1

cause autosomal dominant primary hypertrophic osteoarthropathy. J
Bone Miner Res. 2021 Aug;36(8):1459-1468. doi: 10.1002/jbmr.4310.
Epub 2021 May 5. PMID: 33852188.

Marques P, Stelmachowska-Banas M, Collier D, Wernig F, Korbonits M.

Pachydermoperiostosis mimicking the acral abnormalities of
acromegaly. Endocrine 2020; 67(2): 499–500.
Joshi, A., Nepal, G., Shing, Y.K. et al. Pachydermoperiostosis (Touraine–
Solente–Gole syndrome): a case report. J Med Case Reports 2019; 13:
39. https://doi.org/10.1186/s13256-018-1961-z.

Yuan L, Liao RX, Lin YY, et al. Safety and efficacy of cyclooxygenase-2
inhibition for treatment of primary hypertrophic osteoarthropathy: a
single-arm intervention trial. J Orthop Translat. 2019;18:109-118.

Wang Q, Ying-he L, Guo-le L, et al. Primary hypertrophic

osteoarthropathy

related gastrointestinal complication has distinctive clinical and

pathological

characteristics: two cases report and review of the literature. Orphanet

Journal of Rare Diseases. 2019;14:297. https://doi.org/10.1186/s13023-
019-1264-5

Yuan L, Chen X.,Liu Z, Wu D, Lu J, Bao G, Zhang S, Wang L, & Wu Y.

Novel SLCO2A1 mutations cause gender-differentiated

pachydermoperiostosis, Endocrine Connections. 2018; 7(11) 116-1128.

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;32(8):1659-1666.

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.
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;98(5):E923-E933.

Uppal S, Diggle CP, Carr IM, et al. Mutations in 15-hydroxyprostaglandin

dehydrogenase cause primary hypertrophic osteoarthropathy. Nature
Genet. 2008;40: 789-793.

Castori M, Sinibaldi L, Mingarelli R, Lachman RS, Rimoin DL, Dallapiccola

B. Pachydermoperiostosis: an update. Clin Genet. 2005;68(6):477-486.

Pichler G, Eber E, Thalhammer G, et al. Arthralgia and digital clubbing in a

child: hypertrophic osteoarthropathy with inflammatory pseudotumour
of the lung. Scand J Rheumatol. 2004;33:189-91.

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;70:230-33.

Levin SE, Harrisberg JR, Govendragaloo K. Familial primary hypertrophic

osteo-arthropathy in association with congenital heart disease. Cardiol
Young. 2002:12;304-07.

Akdeniz BG, Seekin T. Periodontal and alveolar bone abnormalities

associated with pachydermoperiostosis. Periodontal Clin Investig.
2001:23;5-10.

Jajic Z, Jajic I, Nemeic T. Primary hypertrophic osteoarthropathy:

Clinical, radiologic, and scintigraphic characteristics. Arch Med Res.
2001;32:136-42.
Silveira LH, Martinez-Lavin M, Pineda C, et al. Vascular endothelial
growth factor and hypertrophic osteoarthropathy. Clin Exp Rheumatol.
2000;18:57-62.

Jajic Z, Jajic I, Nemcic T. Hypertrophic osteoarthropathy after

cerebrovascular insult. Clin Exp Rheumatol. 2000;18:262.

Demirpolat G, Sener RN, Stun EE. MR imaging of

pachydermoperiostosis. J Neuroradiol. 1999;26:61-63.

Friedhofer H, Salles AG, Gemperli I, et al. Correction of eyelid anomalies

in pachydermoperiostosis. Ophthal Plas Recontr Surg. 1999;15:137-38.

INTERNET

McKusick VA, ed. Online Mendelian Inheritance in Man (OMIM). The

Johns Hopkins University. https://www.omim.org/entry/167100?

search=167100&highlight=167100 ;

https://www.omim.org/entry/259100?

search=259100&highlight=259100;

https://www.omim.org/entry/614441 Accessed 11/30/21.

Pachydermoperiostosis. Medscape. Updated April 6, 2021. Available at:

https://emedicine.medscape.com/article/1075122-overview Accessed
11/27/2021.
Pachydermoperiostosis. Orphanet. Last update Jan 2011. Available at:
https://www.orpha.net/consor/cgi-bin/Disease_Search_Simple.php?

lng=EN&diseaseGroup=Pachydermoperiostosis Accessed 11/27/2021.

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