Hypertrophic Osteoarthropathy

Stephen Savioli, Cristy N. French, Eric A. Walker, Chika Iloanusi Logie, and
Mark D. Murphey

Contents
Etiology . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 2
Prevalence and Epidemiology . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 2
Clinical Presentation . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 3
Pathophysiology . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 4
Manifestations of the Disease . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 5
Radiography and Computed Tomography . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 5
Magnetic Resonance Imaging . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 6
Ultrasound . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 6
Nuclear Medicine . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 7
Positron Emission Tomography Computed Tomography . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 9
Differential Diagnosis . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 9
Synopsis of Treatment Options . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 10
Medical Treatment . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 10
Surgical Treatment . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 10
Key Points . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 12
References . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 12

S. Savioli
ACR Institute for Radiologic Pathology, Silver Spring, MD, USA Abstract
C. N. French Hypertrophic osteoarthropathy (HOA) is characterized by
Penn State Milton S. Hershey Medical Center, Hershey, PA, USA digital clubbing, periosteal proliferation along the long tubu-
e-mail: [email protected]
lar bones, synovitis, and joint effusions. It can be classified
E. A. Walker (*) as either a primary or secondary HOA. The primary form of
Penn State Milton S. Hershey Medical Center, Hershey, PA, USA
the disease, also known as pachydermoperiostosis, is a rare
Uniformed Services University of the Health Sciences, Bethesda, MD, familial disorder with autosomal dominant transmission and
USA
variable degrees of expression more frequently present in
e-mail: [email protected]
males. The secondary form of HOA, formerly known as
C. Iloanusi Logie
hypertrophic pulmonary osteoarthropathy, is related to any
University of Maryland Shore Regional Health, Easton, MD, USA
e-mail: [email protected] one of a large number of underlying conditions, of which
bronchogenic carcinoma is the most common. HOA is
M. D. Murphey
ACR Institute for Radiologic Pathology, Silver Spring, MD, USA present in up to 17% of staging bone scintigrams performed
on patients with lung cancer. The presence of secondary
Uniformed Services University of the Health Sciences, Bethesda, MD,
USA HOA has no prognostic significance in patients with lung
cancer. The pathogenesis of HOA remains uncertain. Theo-
Musculoskeletal Section, Walter Reed National Military Medical
Center, Bethesda, MD, USA ries focus on blood flow, vascular proliferation, a neurogenic
e-mail: [email protected] mechanism, and paraneoplastic syndrome as contributory

© Springer Nature Switzerland AG 2023 1

T. Pope et al. (eds.), Musculoskeletal Imaging,
https://doi.org/10.1007/978-3-030-57376-8_80-1
2 S. Savioli et al.

factors. Evidence suggests platelet-derived growth factor

(PDGF) and vascular endothelial growth factor (VEGF) Cystic fibrosis
may play a role. Periosteal proliferations in the tubular Arteriovenous malformation
bones on radiography or computed tomography are noted, Mesothelioma
with the periosteal reaction morphology suggesting disease Solitary fibrous tumor
severity. Radionuclide bone scintigraphy is more sensitive Pulmonary fibrosis
than radiographs for the detection of periosteal proliferation
in primary and secondary HOA. Epiphyseal involvement is Cardiac
more frequent in primary HOA, likely because it is more
long-standing, as secondary HOA patients often succumb to Cyanotic congenital heart disease
the underlying disease early. Bacterial endocarditis

Keywords Gastrointestinal
Hypertrophic osteoarthropathy · Hypertrophic pulmonary
Inflammatory bowel disease
osteoarthropathy · Primary HOA ·
Cirrhosis
Pachydermoperiostosis · Secondary HOA · Periosteal
Biliary atresia
reaction · Digital clubbing
Esophageal carcinoma
Esophagitis
Polyposis
Etiology
Laxative abuse
Hypertrophic osteoarthropathy (Pierre-Marie–Bamberger syn-
Miscellaneous
drome) is characterized by digital clubbing, periosteal prolif-
eration along the long tubular bones, synovitis, and joint
Nasopharyngeal carcinoma
effusions. It can be classified as either primary (genetic/hered-
Hodgkin lymphoma
itary) or secondary hypertrophic osteoarthropathy.
Vascular graft infection
The primary form of the disease (Fig. 1), also known as
Prostaglandin therapy
pachydermoperiostosis, idiopathic hypertrophic osteoarthro-
pathy, or Touraine-Solente-Gole syndrome [1], is a familial
AIDS
disorder with autosomal dominant transmission and variable
degrees of expression [2].
Fluorosis [medication (voriconazole) or other causes]
The secondary form of hypertrophic osteoarthropathy
(HOA), formerly known as hypertrophic pulmonary
Localized
osteoarthropathy, is related to any one of a large number of
underlying conditions, of which bronchogenic carcinoma is
Aneurysms
the most common [3]. It was first described in 1890 by Marie
Infective arteritis
in patients with chronic lung disease [4]. Multiple
Patent ductus arteriosus
non-pulmonary causes of HOA have now been described,
Hemiplegia
accounting for the change in nomenclature. A summary of
the diseases associated with secondary HOA is presented in
eBox 1.

eBox 1 Processes associated with secondary

hypertrophic osteoarthropathy
Pulmonary Prevalence and Epidemiology

Bronchogenic carcinoma Primary (hereditary / genetic) hypertrophic osteoarthropathy

Metastases (HOA), also called Touraine-Solente-Gole syndrome and
Pulmonary abscess pachydermoperiostosis, is a rare disorder that most commonly
Tuberculosis presents in males by a ratio of 9:1 [2, 5]. Primary HOA is often
Bronchiectasis familial with an autosomal dominant pattern of inheritance and
represents 3–5% of all cases of HOA [6]. Patients with
Hypertrophic Osteoarthropathy 3

Fig. 1 A 28-year-old man with pachydermoperiostosis (primary hyper- (b) A lateral foot radiograph in the same patient demonstrates periosteal
trophic osteoarthropathy). (a) An anteroposterior wrist radiograph reaction along the calcaneus and fifth metatarsal base (arrow)
reveals a significant periosteal reaction along the distal radius (arrow).

pachydermoperiostosis have a relative with a similar illness in nasopharyngeal [29–31], esophageal [32], gastric [33], or pan-
more than 33% of cases [2]. The onset of disease has a bimodal creatic [34, 35] neoplasms, thoracic solitary fibrous tumor
distribution, with one peak during the first year of life and a [36, 37], acquired immunodeficiency syndrome (AIDS)
second peak around the age of puberty. The patient may present [38–40], arteriovenous malformation; polyposis [41], endocar-
with the complete syndrome (pachydermia, periostitis, club- ditis [42, 43], esophagitis [44, 45], voriconazole treatment
bing, and cutis vertices gyrate) or an incomplete manifestations [46], and Erdheim-Chester disease [47].
[7–11]. The major criteria for primary HOA include HOA confined to one or both upper or lower extremities
pachydermia, periostosis, finger clubbing, and the minor has been described as secondary to vascular graft infection of
criteria include hyperhidrosis, arthralgia, hypertrophic gastritis, the aorta or subclavian artery [48–52]. Patent ductus
ptosis, joint effusion, seborrhea, acne, and flushing. The com- arteriosus, aneurysm, and hemiplegia have also been impli-
plete form demonstrates pachydermia, digital clubbing, and cated in localized disease [53].
periostosis; the incomplete form will demonstrate no Secondary HOA may appear in childhood secondary to
pachydermia; and fruste form will have prominent cystic fibrosis [54–57], (Fig. 2) cyanotic congenital heart
pachydermia with few skeletal manifestations [6]. disease [58, 59], Hodgkin disease [60–62], metastasis,
Secondary hypertrophic osteoarthropathy (HOA) related to Crohn disease [63], prostaglandin therapy [64], and primary
lung cancer is relatively common. One study found evidence pulmonary neoplasms.
of HOA in 17% of staging bone scintigrams performed on
patients with lung cancer [12]. On clinical examination, up to
30% of patients with lung cancer have evidence of digital
Clinical Presentation
clubbing [13]. The presence of secondary HOA has no prog-
nostic significance in patients with lung cancer [12]. The age
Primary hypertrophic osteoarthropathy (HOA) or pachyder-
and sex distribution of secondary HOA follow that of the
moperiostosis is characterized by enlargement of the hands
underlying condition. In addition to bronchogenic carcinoma,
and feet with clubbing of the fingers and toes, causing
hypertrophic osteoarthropathy has been described with intra-
convexity of the nails (watch-crystal nail). The skin overly-
thoracic processes, such as mesothelioma (HOA was present in
ing the base of the nail becomes thin and shiny. In the lower
60% of fibrous tumors of the pleura) [14, 15], pulmonary
extremity, soft tissue swelling and bone enlargement can
abscess [16], bronchiectasis [17], emphysema, lipoid pneumo-
lead to a cylindrical appearance with disruption of the nor-
nia, diaphragmatic tumors, and various lung metastases. Case
mal extremity contours. Dramatic skin thickening in the face
reports of HOA secondary to pulmonary tuberculosis [18–20]
and scalp can result in deep furrows and transverse folds
and sarcoidosis [21, 22] are also documented in the literature.
known as cutis verticis gyrata. Additional characteristic
Non-pulmonary causes of HOA have been reported, such as
features of primary HOA include hyperhidrosis of the
cirrhosis or other chronic liver disease [23–25], Crohn disease
extremities and seborrhea of the face, nose, and scalp.
or other gastrointestinal inflammation [26–28], primary
There may be non-pitting cylindrical soft tissue swelling at
4 S. Savioli et al.

Fig. 2 Hypertrophic osteoarthropathy (secondary) in a patient with Oblique and AP radiographs (b) of the left wrist show a smooth,
cystic fibrosis. Anteroposterior radiograph of the chest (a) demonstrates thickened periosteal reaction (hollow arrows) involving the distal radius
hyperinflation as well as interstitial prominence and bronchiectasis. and ulna

the ankles (“elephant legs”) [5]. Life expectancy is normal

in patients with pachydermoperiostosis [65]. Pathophysiology
Secondary HOA may be the initial presentation of bron-
chogenic carcinoma. The presence of bilaterally symmetric The pathogenesis of hypertrophic osteoarthropathy (HOA)
periostosis and digital clubbing should alert the clinician to remains uncertain. The importance of increased blood flow
the possibility of an underlying malignancy. In most patients, in hypertrophic osteoarthropathy has been emphasized. A
the finger deformity is the first manifestation, and as the periosteal reaction has been induced in dogs after the for-
syndrome progresses, periostosis becomes evident. Typically, mation of a fistula between the left atrium and pulmonary
pain and tenderness occur at one or more articulations. The arteries [67]. Localized vascular proliferation and endothe-
knees, ankles, wrists, elbows, and metacarpophalangeal lial cell hyperplasia have been demonstrated histologically
joints are most commonly involved [66]. Both primary and in the soft tissues of patients with HOA [68]. These histo-
secondary HOA may have effusions and synovitis of the logic findings are believed to be related to the presence of
large joints, most likely a secondary reaction to nearby peri- one or more growth factors in the systemic circulation that
osteal pathology. Some patients, particularly those with are normally inactivated in the lungs. Megakaryocytes and
malignant lung tumors, may notice a burning sensation at platelet clumps that are normally fragmented in the lungs
the fingertips and incapacitating bone pain, which could be reach the distal extremities and are thought to cause a local
mistaken for an inflammatory arthritis [5]. tissue reaction via the release of cytokines [69]. Platelet-
derived growth factor (PDGF) and vascular endothelial
growth factor (VEGF) have been proposed as having a
role in clubbing and HOA [70]. A neurogenic component
may also be contributory, as relief of signs and symptoms
can occur after vagotomy [71, 72]. Many believe HOA to be
Hypertrophic Osteoarthropathy 5

a paraneoplastic syndrome caused by humoral factors, such and epiphyses. Epiphyseal involvement (Fig. 1) is more
as estrogen, adrenocorticotropin (ACTH), and growth hor- common in primary HOA likely related to those with sec-
mone, which are known to be excreted by some pulmonary ondary HOA often having a shortened survival time. There is
neoplasms [73].A study of several families with primary a direct relationship between the duration of the disease and
HOA revealed a mutation in the 15-hydroxyprostaglandin the number of bones involved [76]. In primary HOA, the
dehydrogenase gene on chromosome 4q33–q34 that causes tibia, fibula, radius, and ulna are most frequently affected
chronically elevated prostaglandin E2 (PGE2) levels [77], and involvement of the epiphyses is likely related to a
[74, 75]. longer duration of the disease [76]. Involvement of the car-
pals, metacarpals, tarsals, metatarsals, and phalanges is also
frequent. The periosteal reaction may be solid, linear, dense,
Manifestations of the Disease or layered. Thickening of the calvarium and the base of skull
may also be noted [78]. In secondary HOA, the tibia and
Radiography and Computed Tomography fibula are the bones most commonly affected, followed by the
femur, metacarpals, carpus, radius, ulna, metatarsals, and
Periosteal proliferation in the tubular bones is the radio- humerus [79]. The terminal phalanges are usually spared in
graphic hallmark of primary and secondary hypertrophic secondary HOA. Skeletal changes are typically bilateral and
osteoarthropathy and is well demonstrated by radiography symmetric. Unilateral involvement has been reported in cases
and computed tomography (Fig. 3). of secondary HOA distal to sites of vascular graft infection.
The morphology of the periostosis evolves with increasing Bone remodeling can occur in the distal phalanges of
degrees of disease severity [76]. In mild cases, a monolayer patients with long-standing clubbing [80]. The remodeling
of periosteal reaction is present. Multilayer periostosis repre- may be hypertrophic, with “mushroom-like” overgrowth of
sents moderate disease (Fig. 4), and irregular periostosis the tuft, or it may be osteolytic. The age at onset determines
(Fig. 5) indicates severe disease. Ossification of the which type of remodeling occurs. Clubbing that appears
interosseous membrane (usually in the calf) is seen in the during childhood is associated with osteolysis, whereas club-
most severe cases. The longitudinal extent of periostosis bing that develops after puberty is associated with hypertro-
within a given bone also changes over time. Diaphyseal phy [81]. In a finger without clubbing, the distal phalangeal
involvement is the earliest finding. In a more long-standing depth (DPD) is smaller than the interphalangeal depth (IPD).
disease, the periostosis can extend to involve the metaphyses Measurement of the nail bed thickness (>3.0 mm),

Fig. 3 Hypertrophic osteoarthropathy (secondary) in a patient with periosteal reaction (hollow arrows) involving the distal tibia and femur.
non-small cell lung carcinoma. Anteroposterior radiographs of the (a) (c) An axial CT of the chest in the same patient reveals a non-small cell
right ankle and (b) left femur demonstrate a smooth, thick monolayer lung carcinoma in the left perihilar region (arrow)
6 S. Savioli et al.

Fig. 4 A 54-year-old man presented with secondary hypertrophic multilayer periosteal reaction (arrowheads). A posteroanterior chest
osteoarthropathy from lung cancer. Anteroposterior radiographs of the radiograph in the same patient reveals a primary bronchogenic carci-
left ankle (a) and right forearm (b) demonstrate a smooth, thick noma in the right suprahilar region (arrows)

hyponychial angle (>192 degrees), and phalangeal depth reaction. The digital clubbing presents as soft tissue thicken-
ratio (DPD > IPD) have been reported to help identify ing underneath the nail bed and nail root with diffuse contrast
clubbed fingers on the lateral index finger radiograph [82]. enhancement and edema [53].
As connective tissue deposition expands the pulp in the
terminal phalanx in patients with clubbing, this ratio becomes
reversed [83] (Fig. 6). Ultrasound
Joint swelling is a common manifestation of secondary
hypertrophic osteoarthropathy (HOA). Effusions may be On ultrasound (US), the normal bone cortex appears as a
seen on radiographs, typically at the knee or ankle. The smooth, regular, continuous line that is hyperechoic due to
effusions are not inflammatory, and joint space narrowing, the high acoustic impedance mismatch between bone and the
juxta-articular osteoporosis, and erosions are not characteris- surrounding soft tissue [85]. The periosteum covers the outer
tic of HOA. The presence of erosions in a patient with HOA surface of bone, with the exception of the intra-articular
should suggest a concomitant inflammatory arthropathy [81]. surfaces and sesamoid bones as well as the site of tendons,
Joint inflammation is uncommon in pachydermoperiostosis fasciae, and ligament insertion [86]. In healthy adults, the
but may be aggravated by alcohol use [84]. normal periosteum is barely visible with US and appears as a
thin hypoechoic band superficial to the hyperechogenic bone
cortex. In pediatric patients, the thicker hypoechoic perios-
Magnetic Resonance Imaging teum is easily detected with US [85, 87].
Radiographic findings of periosteal reaction are positive
Hypertrophic osteoarthropathy (HOA) associated periosteal only when the periosteum is calcified. Although ultrasound
reaction with MRI imaging typically exhibits low-to-inter- has limited value in assessing bones, it can detect periosteal
mediate signal intensity on T1-weighted images (Fig. 5). On reactions earlier than radiography [87, 88]. The newly formed
fluid-sensitive sequences, imaging often reveals a fine hypo- bone added onto the surface adopts various configurations
intense line representing elevated periosteum, surrounded by depending on the modalities and pace of bone production.
high signal intensity. MR imaging is also useful for identify- HOA is included in the differential for solid, single lamellar,
ing synovial effusions. The contrast enhancement of the
thickened periosteum is often noted. There may be a simple
periosteal elevation or a laminated or an onionskin periosteal
Hypertrophic Osteoarthropathy 7

Fig. 5 Digital clubbing in a 47-year-old man. (a) A lateral radiograph a hyponychial angle greater than 192.0 degrees. A measurement of the
cropped to the third and fourth fingers is used for the following mea- nail bed thickness (c) uses a vertical line perpendicular to the distal
surements. The illustrations use the contour and measurements obtained phalanx at the nail bed. A normal measurement is between 1.75 and
off the third finger in (a). Calculation of the hyponychial angle (b) uses 3.10 mm. (d) The phalangeal depth ratio in a patient with clubbing
the angle of the line AB drawn from the distal digital skin crease to the should show that the distal phalangeal depth (DPD) is larger than the
cuticle and the line BC drawn from the cuticle to the hyponychium interphalangeal depth (IPD). This holds true in this patient as the DPD
(thickened stratum corneum under the nail edge). Clubbed fingers show 19.7 is greater than the IPD 17

and multilamellar periosteal reactions [53, 88]. On US, the Nuclear Medicine
nonmineralized periosteal reaction can appear as hypoechoic
material or a hypoechoic, raised line over the bone cortex. Radionuclide bone scintigraphy is highly sensitive for the
Lamellar mineralized periosteal reaction appears as linear detection of periosteal proliferation in primary and secondary
hyperechoic tissue superficial to the cortex [88] (Fig. 7). hypertrophic osteoarthropathy (HOA). Abnormalities may be
Nevertheless, because US features of disorders of the perios- seen on scintigraphy before they are radiographically appar-
teum are nonspecific, correlation with clinical history and ent. The classic appearance of HOA is diffuse, symmetric,
radiographs is necessary. [53] increased linear uptake along the diaphyseal cortical margins
There is limited description in the literature of the ultra- of tubular bones, known as the “tram line,” “parallel tract,” or
sound findings of hypertrophic osteoarthropathy. One case “double stripe” sign (Figs. 8 and 9) [79]. Associated synovitis
report describes the findings in a 3-year-old girl with primary in secondary HOA may lead to periarticular radiotracer
hypertrophic osteoarthropathy [89]. Ultrasound showed a uptake. Scintigraphy is useful in delineating the extent of
layer of echogenic tissue measuring up to 3 mm in thickness skeletal involvement and in assessing disease progression or
surrounding the femur, tibia, and fibula. This corresponded to response to therapy. Prominent tracer uptake in the digits is
a smooth periosteal reaction in the diaphyseal region on reflective of digital clubbing.
radiographs. The authors hypothesized that the layer of
hyperechoic tissue on ultrasound was related to edema and
inflammation within the tissues surrounding the bone and
periosteum [89].
8 S. Savioli et al.

Fig. 6 A 53-year-old woman with squamous cell carcinoma of the fibula (arrows). Sagittal T1-weighted (TR626/TE17) (c) and axial
maxillary sinus and lung metastases. An oblique radiograph of the T2-weighted (TR4340/TE87) image with fat suppression (d) show an
right ankle (a) demonstrates thick, irregular periostitis (arrows) involv- intermediate signal and thickened irregular periosteal reaction of the
ing the distal tibia, fibula, and metatarsals. A coronal CT image (b) metaphysis of the distal tibia (arrows)
reveals a thickened, irregular periosteal reaction of the distal tibia and
Hypertrophic Osteoarthropathy 9

Fig. 7 Periostitis is related to voriconazole use. The AP radiograph (a) normal periosteum along a humeral diaphysis in a different patient. The
shows a prominent periosteal reaction in the hand, particularly the fifth periosteum is the thin hypoechoic line to the left of the cortex (arrows),
metacarpal and the third middle phalanx (arrows). Doppler ultrasound in and there is no significant Doppler flow. Images a and b were provided
the same patient at the third middle phalanx reveals significant thicken- by Dr. Carissa White
ing of the periosteum and Doppler flow (arrow). For comparison, (c) is

Positron Emission Tomography Computed A and D, infantile cortical hyperostosis, diffuse idiopathic
Tomography skeletal hyperostosis (DISH), fluorosis, and diaphyseal dys-
plasia (Camurati-Engelmann disease). The multifocal nodu-
A reported case using fluorodeoxyglucose (18F-FDG) lar periostitis related to the use of voriconazole, a fluoride-
PET-CT in a patient with adenocarcinoma of the lung containing antifungal medication (or other causes of fluoro-
describes extensive, irregular bilateral periosteal new bone sis), usually does not display digital clubbing. [5] Thyroid
formation in the long bones on the CT examination (Fig. 5). acropachy may arise after treatment of Graves’ disease.
There was also moderately increased diffuse FDG uptake in Patients present with digital clubbing, pretibial myxedema,
the periosteum of the long bones of the legs, with some focal and exophthalmos. The myxedema may resemble the “ele-
sites of more intense FDG uptake in the thicker portions of phant legs” described in other types of HOA. The periosteal
the periosteum [90]. Hypertrophic osteoarthropathy has also reaction noted in thyroid acropachy typically is often lacy,
been described with 18F–sodium fluoride PET-CT as bilateral, fluffy, spiculated, and thick (Fig. 10). It usually involves the
symmetric, diffusely increased osteoblastic activity along the diaphyses of short tubular bones in the hands and feet and
cortical margins of long bones with preservation of the axial most commonly involves the radial side of the first, second,
skeletal and medullary cavities [91]. and fifth metacarpals and the proximal and middle phalanges
of the fingers [53].
Patients with the POEMS syndrome variant of multiple
Differential Diagnosis myeloma (polyneuropathy, organomegaly, endocrinopathy,
monoclonal proteins, and skin changes) may often display
The differentiation of primary from secondary hypertrophic features characteristic of HOA, such as digital clubbing,
osteoarthropathy (HOA) is based on the clinical exclusion of hyperhidrosis, and skin thickening [92].
underlying conditions associated with secondary HOA. A
positive family history [2] and epiphyseal involvement [76]
are present in many cases of primary HOA. The differential
diagnosis of symmetric bilateral periostosis includes shin
splints, venous stasis, thyroid acropachy, hypervitaminosis
10 S. Savioli et al.

Fig. 8 A 79-year-old man who presented to the emergency department uptake with the “parallel tract” sign in the tibia and femora consistent with
with urinary retention. A chest radiograph (not shown) revealed a lung secondary hypertrophic osteoarthropathy. A contrast-enhanced axial CT
mass which was found to be grade 4 non-small cell lung cancer on work- (b) through the chest with soft tissue windows demonstrates a large right
up. Whole-body bone scintigram (a) demonstrates increased radionuclide perihilar lung mass

octreotide [94]. Etoricoxib, a potent prostaglandin inhibitor,

Synopsis of Treatment Options was noted to reverse clubbing and pachydermia in one study
[95]. Various chemotherapeutic agents used in the treatment
Medical Treatment of underlying malignancies have resulted in symptomatic and
radiographic improvement in patients with secondary HOA.
Digital clubbing is typically painless and does not require
therapy. Treatment of hypertrophic osteoarthropathy (HOA)
is directed toward identification and management of the Surgical Treatment
underlying condition. Removal of the primary cause such as
tumor resection, correction of a heart malformation, or suc- The skeletal manifestations of secondary hypertrophic
cessful treatment of infective endocarditis may be followed osteoarthropathy (HOA) typically regress after thoracotomy
by a dramatic regression of all features of the syndrome. for treatment of primary lung cancer [96–98]. HOA changes
Symptomatic HOA is typically treated with nonsteroidal have reversed after resection of an esophageal cancer [32].
anti-inflammatory drugs or oral corticosteroids. Successful There is no need for direct surgical intervention on bones
treatment of refractory cases has been reported with intrave- affected by HOA.
nous bisphosphonates [93] as well as with subcutaneous
Hypertrophic Osteoarthropathy 11

Fig. 9 A 63-year-old woman

with secondary hypertrophic
osteoarthropathy and lung cancer.
Whole-body bone scintigram
reveals increased radionuclide
uptake with the “parallel tract”
sign in the femora (arrows).
Linear cortical uptake is also
present in both tibiae (arrow)
12 S. Savioli et al.

Fig. 10 Radiograph of the right

hand in a patient with thyroid
acropachy. Periosteal thickening
is noted on several metacarpals
(arrows). The periosteal reaction
seen in thyroid acropachy is often
lacy, fluffy, spiculated, and thick.
It usually involves the diaphyses
of short tubular bones in the hands
and feet and most commonly
involves the radial side of the first,
second, and fifth metacarpals, and
the proximal and middle
phalanges of the fingers

4. Marie P. L’osteoarthropathie hypertrophiante pneumonique. Rev

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