SYNOVITIS OF THE KNEE

Berruto Massimo, Murgo Antonella*, Ferrua Paolo, Uboldi Francesco, Tradati Daniele, Pasqualotto
Stefano, Marelli Bruno Michele**

SSD Chirurgia Articolare del Ginocchio Istituto Ortopedico Gaetano Pini Milan, Italy

* UOC Reumatologia Istituto Ortopedico Gaetano Pini Milan, Italy

** UOC Dipartimento di Ortotraumatologia Generale e Chirurgie Ortopediche Specialistiche

Istituto Ortopedico Gaetano Pini Milan, Italy

Corrsponding Author: Massimo Berruto Piazza A. Cardinal Ferrari, 1 Milan, Italy. E mail:
massimo.berruto@fastwebnet.it Tel: +390258296797

1 Introduction

Etymologically the word synovitis generally refers to acute or chronic inflammation of the synovial
membrane. Today, however, the term is used to refer to a disease process (not necessarily
inflammatory) that may originate from the synovial membrane and involve the structures of the
joint. Synovitis can have different causes: traumatic, autoimmune, infectious, dysmetabolic or
neoplastic, and it is typically characterised by the presence of varying degrees of swelling, pain,
redness, heat and functional impairment. The knee is a frequent target of this disease and it is the
joint most likely to be affected by special forms of synovitis such as pigmented villonodular
synovitis and synovial chondromatosis. Inflammatory and degenerative joint diseases are usually
diagnosed on the basis of clinical and imaging data. However, these data are not always sufficient,
especially in the event of a monoarticular onset; in such cases, the use of histopathology and a
synovitis score will increase the diagnostic accuracy. There exist various histological scoring
systems for synovitis and the one proposed by Krenn, which is essentially applicable to all forms of
synovitis, is the most commonly used. It is a numerical scoring system based on semi-quantitative
grading of three key features of synovitis: enlargement of the lining cell layer, activation of stromal
cells (as shown by the cellular density of the synovial stroma), and leukocytic infiltrate. Each of
these three components is assigned a score from 0 to 3, resulting in an overall score of between 0
and 9. Through analysis of numerous large samples, mean Krenn scores have been established for
normality (1.0); post-traumatic arthritis (2.0); osteoarthritis (2.0); psoriatic arthritis (3.5); reactive
arthritis (5.0) and rheumatoid arthritis (5.0) [15]. A strong correlation has since emerged between
the synovitis score, immunohistochemistry findings (Ki-67, CD68) and the clinical severity of the
disease [7,26]. Use of the synovitis score has proved to be useful in useful in defining forms lacking
the typical histological features, allowing them to be distinguished on the basis of the intensity and
severity of the synovial inflammation.

2 Synovitis in osteoarthritis

Osteoarthritis of the knee is one of the most common and disabling forms of osteoarthritis, and it is
often complicated by the presence of synovitis. The condition has been estimated to affect around
250 million people worldwide [22]. The prevalence and severity of the synovitis are closely related
to progression of the osteoarthritic process.

2.1 Pathogenic mechanism

The origin of the synovitis is closely correlated with the presence of products of cartilage
breakdown (especically YKL-39 and collagen II) and meniscal degradation and it is part of a
vicious cycle in which pro-inflammatory protein molecules, or cytokines, i.e., chemokines and
adipokines, negatively affect the metabolism of both chondrocytes and synoviocytes. In the course
of osteoarthritis, the synovial membrane can show different degrees of activity. When it is
moderately active it has opaque villi, which are numerically superior to those of a normal synovial
membrane and show a preserved morphology or, at most, some thickening. Instead, in clearly
inflammatory states the membrane is characterised by increased proliferation and hypertrophy of
the villi (the latter due mainly to adipose tissue), and by increased vascularity.

2.2 Clinical presentation and diagnostic approach

Joint effusion is the most direct sign of synovitis; it is often accompanied by tenderness and
restricted movements.

3 Mechanically induced synovitis

Synovitis can arise from mechanical changes whose origin may be congenital, acquired or post-
traumatic (chondral damage, meniscal injury, etc.). Local factors such as biomechanical imbalances
(incorrect distribution of mechanical stress in a varus knee or knee extensor mechanism
malalignment), as well as intra-articular (aseptic necrosis, osteochondritis dissecans, meniscus
disorders) or post-traumatic disorders can cause synovitis and predispose or lead to secondary
osteoarthritis.

3.1 Pathogenic mechanism

The mechanisms underlying the onset of the inflammatory process are the same as those outlined
for primary osteoarthritis. In some cases, trauma can act as a trigger and the inflammation it causes
can result in chronic synovitis that will require appropriate clinical diagnosis. In post-traumatic
synovitis, in particular, the response of the synovial membrane is characterised by increased
vascularity, effusion and swelling. Irritation of the synovial membrane triggers a process of local
inflammation characterised by hypertrophy of the villi, which usually show a plume-like
arrangement, rarely have a fibrin coating, and show increased vascularity.

4 Chondrocalcinosis

Chondrocalcinosis is a condition often associated with osteoarthritis; it is characterised by

deposition of calcium phosphate crystals in the hyaline cartilage, fibrocartilage and synovial
membrane. Not common in young people and frequently associated with a metabolic abnormality,
chondrocalcinosis is categorised in three main categories: idiopathic (sporadic), secondary
(associated with other diseases) and hereditary. It shows a strong association with age, its
prevalence increasing from 3.7% in subjects aged 55-59 years to 17.5% in those aged 80-84 years
[24]. Chondrocalcinosis can be asymptomatic, complicated by repeated episodes of synovitis
(pseudogout), or show a disease course similar to that of chronic rheumatoid-like arthritis. The knee
is the site most frequently affected both by the asymptomatic and the inflammatory form.

4.1 Pathogenic mechanism

The deposition of crystals seems to occur as a result of a change in inorganic pyrophosphate

metabolism, facilitated by a series of factors that interfere with the activity of pyrophosphatase and
raise its concentration (hypomagnesaemia, hypophosphataemia, haemochromatosis,
hyperparathyroidism, Wilson’s disease). The association of chondrocalcinosis with old age is likely
a consequence of age-related changes in the proteoglycans in the cartilage matrix that encourage the
deposition of calcium phosphate crystals. The inflammation is caused by the deposited crystals,
which induce intense irritation of the synovial membrane, a phenomenon characterised by oedema
and infiltration of polymorphonuclear cells, and proliferation of synoviocytes which, in rare cases,
can lead to the formation of the classic synovial pannus (Fig.s 1-2). Indeed, the synovial membrane
appears extremely hyperemic with varying degrees of villous hyperplasia, depending on the
duration of the disease. The deposits can be macroscopically visible at the tips of the villi and
adhering to the articular cartilage and to the menisci. These features can be confirmed
microscopically in sections that, however, must not be treated with formalin or other substances
capable of dissolving the crystals.
5 Synovitis in rheumatoid arthritis

Rheumatoid arthritis (RA) is a chronic, immune-mediated inflammatory disease whose main feature
is the development of persistent and progressive synovitis primarily affecting the diarthrodial
(synovial) joints. RA can evolve into a systemic condition and involve extra-articular structures.
Found all over the world and in all ethnicities, it is the most common form of arthritis. The disease
can occur at any age, although its incidence peaks between the fourth and sixth decades of life.
Women are 2.5 times more likely to be affected than men [17] and the difference between the sexes
decreases with increasing age. The juvenile form can affect children and adolescents under the age
of 16 years. The onset of RA is typically insidious and characterised by involvement of the small
joints (hands, feet); acute polyarticular onsets are less frequent, while acute monoarticular
presentations are rare at disease onset. The knee is frequently affected in the course of the disease
(>50%.)

5.1 Pathogenic mechanism

Rheumatoid arthritis is regarded as an immune-mediated disease that develops in genetically

predisposed individuals. Although the event triggering the onset of RA remains unknown, the
disease-causing agent is thought to bring about an activation of the immune system that in turn
leads to the development of an inflammatory process that subsequently becomes self-perpetuating
and chronic. A role for genetic predisposition is supported by the fact that over 80% of patients
possess the epitope of the HLA-DRB1*04 cluster and those that express two HLA-DRB1* alleles
are at high risk of more severe disease [33]. Environmental factors such as smoking and infections
can influence the development, severity and progression of RA [14]. The disease has a
multifactorial pathogenesis that involves various immune modulators (T cells and B cells) and
different signalling pathways. A complex network of interactions between pro-inflammatory
cytokines, such as TNFα and IL-6, and effector cells is responsible for the joint damage that
originates from the synovial membrane. According to the most recent thinking, synovitis precedes
the onset of the clinical manifestations, even by years, and is caused by the convergence and local
activation of mononuclear cells (including T cells, B cells, plasma cells, dendritic cells,
macrophages and mast cells) and by the activation of angiogenesis. Thickening of the synovial
lining results in a hyperplastic synovial membrane which is transformed into the synovial pannus;
here osteoclasts resorb bone matrix while synoviocytes, chondrocytes and neutrophils break down
cartilage [19,29]. The macroscopic features of the synovial membrane in RA are the presence of
irregularly shaped (bulbous, sessile, polypoid) and oedematous villi. The shape of the villi depends
on the stage of the disease: when the hypertrophy is more advanced the villi, which can be seen to
emerge from an indistinctly and considerably thickened synovial membrane, appear bulkier (club-
shaped) (Fig.s 3-4). The opaque appearance of the villi is due to the thickening of the synovial
living and the high cell infiltration; the vascularity appears increased, with the vessels arranged in
different patterns depending on the intensity of the inflammation and the type of synovitis. The
vascular network generally shows a rectilinear arrangement in RA, while the vessels are tortuous in
synovitis associated with psoriatic arthritis.

5.2 Clinical presentation and diagnostic approach

Synovitis in RA manifests itself through the classic symptoms and signs of inflammation. Effusion
and synovial thickening are readily detected on clinical examination. A popliteal (or Baker’s) cyst
can be present, and its rupture produces signs and symptoms suggestive of thrombophlebitis. In
addition to morning stiffness the patient may also show systemic symptoms: fatigue, weight loss,
fever and myalgia. In advanced and untreated forms the chronic inflammatory process causes
gradual and irreversible tissue damage, and deformity and instability of joints. RA is associated
with the presence of rheumatoid factor (RF) and anti-citrullinated protein antibodies (ACPAs) in the
serum. However, cases can occur in which these autoantibodies are not present. Raised erythrocyte
sedimentation rate (ESR) and C-reactive protein (CRP) levels generally correlate with the degree of
synovial inflammation, although the presence of normal levels of these inflammatory markers is
certainly not a basis for excluding a diagnosis of RA. Laboratory tests may show anaemia,
hypergammaglobulinaemia, hypocomplementaemia, thrombocytosis and eosinophilia. These
abnormalities are usually present in patients with severe polyarticular disease and associated with
high RF and ACPA titres. Synovitis in RA, especially in early or monoarticular phases, requires
differential diagnosis versus other forms of primary inflammatory arthritis such as psoriatic
arthritis, peripheral joint involvement in ankylosing spondylitis, reactive arthritis and
microcrystalline arthritis.

6 Synovitis in psoriatic arthritis

The arthritis that is associated with psoriasis is one of the seronegative spondyloarthropathies, a
heterogeneous group of chronic inflammatory diseases characterised by asymmetric oligoarthritis,
which may be axial or peripheral, and enthesitis, and it is sometimes associated with ocular,
cutaneous, gastrointestinal and systemic complications. RF testing is always negative and there is
always a strong association with the HLA-B27 antigen. In cases with peripheral joint involvement,
the knee is almost always affected.

6.1 Pathogenic mechanism

Synovitis in psoriatic arthritis shares some pathogenic features with synovitis in RA. In genetically
predisposed individuals, various conditions and agents can trigger the onset of psoriasis and/or
psoriatic arthritis. Environmental and immunological factors influence susceptibility to the disease.
Although the pathogenic mechanisms underlying the development of synovitis in the different
forms of arthritis share many similarities, there are differences in the macroscopic morphology. The
synovial membrane in psoriatic arthritis, and in seronegative arthritis generally, is typically
characterised by inflammation associated with the presence of more rounded and elongated villi,
gathered in clusters. The villi usually have a hyperemic centre surrounded by a white halo,
indicating early fibrous involution. The most representative feature is the vascularity, which shows
a distinct pattern of very tortuous “corkscrew-like” vessels with numerous perivascular
haemorrhages [27].

6.2 Clinical presentation and diagnostic approach

In 70% of cases of psoriatic arthritis, the psoriasis is present before the clinical manifestations of the
arthritis, whose onset can be acute and monoarticular (usually involving the knee) or oligoarticular,
in which case patients usually present involvement of the knee together with arthritis and
tenosynovitis of the distal and proximal interphalangeal joints of the fingers (dactylitis). The
arthritis may, in some cases, occur after a trauma, a circumstance that can give rise to diagnostic
errors especially when the psoriasis is occult, i.e. not widespread but limited to specific areas.
Laboratory tests are non-specific and raised ESR and CRP levels are not always consistent with the
intensity of the clinical picture. The synovial fluid is inflammatory, with white blood cell
counts exceeding 5000 cells per mm3. Although it may reveal no peculiar features, examination of
the synovial fluid is useful for distinguishing psoriatic synovitis from mechanical or degenerative
forms. Imaging findings of synovitis in a knee affected by psoriatic arthritis are comparable to those
in a knee with RA. No specific scoring system has been developed for application to ultrasound
findings in psoriatic arthritis; the methods used are based on the systems used for the assessment of
RA.

7 Synovial chondromatosis
Synovial chondromatosis, also called synovial chondrometaplasia or Henderson-Jones syndrome, is
a rare benign neoplastic disorder that consists of a tumour-like abnormality of the synovial
membrane that is characterised by multiple metaplastic cartilaginous nodules, present both in the
subintimal layer and floating freely in the joint space (Fig. 6). It is the most common metaplastic
disease of the knee, occurring most frequently in men aged between 30 and 50 years. The presence
of loose bodies, i.e. loose fragments of bone or cartilage due to osteonecrosis, osteochondral
fractures or osteochondritis dissecans, corresponds to a picture of secondary chondromatosis that
must not be confused with the primary form, given that it does not include the presence of
cartilaginous metaplasia.

7.1 Pathogenic mechanism

The aetiology of synovial chondromatosis is still not clearly defined; what is more, trauma, initially
indicated as a possible risk factor, is no longer considered to trigger the disease [25]. Specific
cytogenetic features seem clearly to indicate a role for clonal proliferation, and not only metaplasia
[20,30]. Macroscopically, the synovial membrane shows numerous blue-grey cartilaginous nodules,
ranging in size from 2 mm to more than 1 cm. These nodules, also occurring freely in the joint
cavity, can show pale yellow areas (expression of a process of ossification) and foci of
endochondral ossification. Through the fusion of several elements, these nodules can form sizeable
clusters and give rise to severe mechanical conflict. The synovial membrane generally appears
hyperemic. Microscopically, the nodules consist of hypercellular hyaline cartilage, embedded in the
synovial connective tissue; the chondrocytes are arranged in small groups, and show widely
variable sizes and nuclear chromaticity, and different degrees of nuclear and cellular atypia. The
differential diagnosis of the condition versus chondrosarcoma is based on the greater extension of
the lesions, the presence of bone erosions, and the loss of the classic cluster-like arrangement of the
chondrocytes. Even though the literature contains descriptions of malignant transformation of
chondromatosis (in up to 5% of cases according to some authors), there is still debate over whether
chondromatosis can undergo a malignant evolution after years of illness or whether, instead, the
literature descriptions actually refer to cases of low-grade malignant chondrosarcoma interpreted as
chondromatosis [2,12,34]. The disease has three histological stages, which may coexist: 1) an initial
stage characterised by active synovitis with nodules of cartilaginous metaplasia; 2) a transition
phase characterised by the presence of intrasynovial cartilaginous nodules and free bodies (loose
cartilaginous nodules); 3) an inactive stage in which the synovitis usually resolves, but there remain
free bodies and a variable amount of joint effusion [21]. Calcification followed by ossification of
the nodules occurs in 70-90% of cases.
7.2 Clinical presentation and diagnostic approach

Clinically, patients present vague and non-specific symptoms: pain, functional limitation, and,
rarely, joint locking. As the lesion develops, there appear swelling and effusion with synovial fluid,
the components of which are all within normal levels. In the absence of timely treatment,
chondromatosis can cause rapidly worsening degenerative processes. The imaging protocol includes
conventional radiography that can be diagnostic in the advanced stages of the disease, when
calcified or ossified free bodies are typically present; worsening osteoarthritis and pressure erosions
are both indirect signs of the disease. CT scans are used to define the extent of the disease and to
detect calcified loose bodies (even small ones) and also initial foci of cartilaginous metaplasia (high
density foci). The use of diagnostic MRI depends on the evolution and size of the calcified
structures. In the absence of free bodies, the differential diagnosis must include pigmented
villonodular synovitis, haemangioma and synovial sarcoma. When free bodies are present,
essentially it is necessary to distinguish primary chondromatosis from the secondary forms
(osteoarthritis, osteochondritis dissecans, osteochondral fractures, neuropathic arthropathy).
Therefore, the diagnosis must always be confirmed histologically.

8 Villonodular synovitis

Pigmented villonodular synovitis is a rare benign proliferative condition that can affect single joints,
tendon sheaths and bursae. It is divided into diffuse and nodular circumscribed forms depending on
the local extension of the disease. The diffuse form can present local aggressiveness but, despite its
destructive potential, does not metastasise; however, it shows a high tendency to relapse. The
presentation is monoarticular although the literature contains reports of multifocal cases. The
disease, in both the diffuse and the circumscribed forms, mainly affects the knee (80% of cases) and
individuals of both sexes in the 3rd-4th decades of life. The annual incidence of the disease was
previously calculated to be 1.8 new cases per million people, and the rate does not appear to have
changed over the years [23].

8.1 Pathogenic mechanism

The pathogenesis of this condition is poorly understood and the study of animal models has shown
the presence of morphologically constant but biologically variable synovitis. There exists evidence
pointing to an exclusively chronic inflammatory origin, while other reports suggest that this is a
neoplastic disease due to chromosomal abnormalities [10,18,32]. The name of the condition reflects
its macroscopic characteristics, with the term pigmented referring to the particular colour of the
lesions (ranging from yellowish to rusty-brown), which is attributable mainly to haemosiderin
deposits in the stroma and the presence of macrophages and synovial lining cells. The
haemosiderin deposits are the consequence of repeated haemorrhages. The term villonodular
describes the peculiar structure of the synovial surface, which is characterised by the presence of
villi and nodules of different sizes and shapes sometimes grouped in areas of increased membrane
thickness (Fig.s 7-8). The nodules consist of villi and fibrous tissue masses covered by hyperplastic
synovial lining cells; it is also possible to observe fibrin clusters which may adhere to the surface of
the synovial membrane or float freely in the joint space (risiform bodies). Microscopic examination
confirms the vigorous proliferation of the synovial lining cells in two directions: towards the joint
cavity and towards subsynovial connective tissue layer. Other key features are the foam cells (of
histiocytic origin), the multinucleated giant cells (phenotypic osteoclast markers) and the
haemosiderin deposits.

8.2 Clinical presentation and diagnostic approach

The symptoms of villonodular synovitis are insidious and non-specific, therefore months can elapse
before it is finally diagnosed. Pain and swelling with effusion are constant findings on clinical
examination, and in the nodular form the masses may be palpable. The effusion will be bloody (if
recent) or xanthochromic, with analysis of the fluid giving non-specific findings (a small increase in
white blood cells and proteins). MRI is a highly diagnostic test for villonodular synovitis; the
haemosiderin deposits alter the intensity of the signal, causing it to be reduced in T2-weighted
images in particular. In T1-weighted sequences, pigmented villonodular synovitis shows signal
heterogeneity: areas of low signal intensity due to the haemosiderin deposits alternate with areas
having a greater fat content that show a higher signal intensity. Most haemosiderin deposits will, in
all usable sequences, show a low signal intensity. There nevertheless remains the problem of
differential diagnosis versus arthropathies with a haemorrhagic and adipose component
(haemophilic arthropathy, synovial haemangioma, haemochromatosis, trauma-related
haemosiderosis). The diagnosis of the condition must therefore be confirmed histologically.

9 Diagnostic and synovial biopsy

A rheumatic disease is diagnosed mainly on the basis of the clinical presentation, blood tests,
imaging and synovial fluid analysis. Nevertheless, in some cases it can be useful to obtain a
synovial tissue sample for confirmatory diagnosis and/or evaluation of the appropriateness of
medical therapy. Synovial biopsy performed as part of a standard arthroscopy procedure has several
advantages over the use of ultrasound-guided techniques or needle biopsy [11], making it possible:

- to evaluate every compartment of the knee and assess the macroscopic appearance of the
diseased synovial membrane.
- to estimate the extent of any chondral damage (useful for staging) and the involvement of
other articular structures (menisci, ligaments)
- to obtain quantitatively and qualitatively valid synovial samples
- to convert the diagnostic procedure into an operative one (synovectomy, excision of local
lesions)

Even though the standard two- or three-portal arthroscopic examination usually allows a complete
evaluation of the joint and collection of an appropriate synovial membrane sample, it can
nevertheless be extended through the use of accessory arthroscopic portals (e.g. posteromedial). In
the presence of diffuse synovitis it is mandatory to take at least six samples from the different
compartments in order to obtain complete synovial mapping and reduce the possibility of sampling
errors [3]. Samples should be taken with appropriate instruments, taking care during the procedure
not to alter the structure of the synovial tissue.

10 Arthroscopic synovectomy

In recent times, arthroscopic synovectomy has become established as the gold standard procedure
for surgical therapy of diffuse synovitis of the knee. It is just as radical as open procedures, but at
the same time less invasive; as a result, it allows earlier joint mobilisation and shorter
hospitalisations, and also reduces the stiffness problems traditionally associated with the open
approach.
At least five portals are needed to perform a complete arthroscopic synovectomy. Consequently, the
patient must be positioned in a way that allows easy access also to the posterior aspect of the knee
(Fig.7). A tourniquet should be used during the procedure, particularly in the presence of a
pathologically hyperaemic synovial membrane, in order to ensure optimal visualisation of the
surgical site and minimise intraoperative bleeding. The procedure starts as a standard two- or three-
portal arthroscopy and should be performed as a systematic exploration of:
 - the suprapatellar pouch: this region, frequently characterised by intense synovial
proliferation, is clearly visualised by keeping the knee in full extension, as is the
patellofemoral joint. Complete synovectomy of this compartment can be performed through
the anteromedial and superomedial portals (Fig.8)
- the medial and lateral parapatellar recesses: by flexing the knee to 20° and using a
standard anteromedial portal (if necessary the portals can be reversed), the exploration and
possible synovectomy procedure is extended to these compartments
- the medial compartment: access to and visualisation of this compartment are obtained by
applying a valgus stress to the extended or slightly flexed knee. It is important to underline
the importance, in this phase, of extending the synovectomy to the meniscal recess, a
frequent site of pathological synovial proliferation.
- the anterior chamber: Together with suprapatellar pouch this is the region that most
frequently shows synovial proliferation, which can be clearly seen with the knee at 90° of
flexion. Synovectomy must be radical in this compartment and it is important not to damage
the cruciate ligaments during removal of their synovial lining (Fig.9).
- the lateral compartment: with the knee in a figure-of-4 position it is possible to evaluate
this compartment and perform synovectomy through the anteromedial portal. As with the
medial compartment, the procedure must be extended to the meniscal recess and popliteal
hiatus (Fig.10)
- the posteromedial compartment: with the knee flexed at 90° this region can be accessed
using a transcondylar approach; then, under arthroscopic guidance, the posteromedial
accessory portal can be created to allow complete synovectomy of the compartment (Fig.11)
- the posterolateral compartment: with the knee flexed and under varus stress, this
compartment can be reached via a transcondylar approach, making it possible to create an
accessory posterolateral portal and complete the procedure in this region. Alternatively, with
the knee flexed at 90° and using a switching stick inserted through a posteromedial portal,
access can be obtained through a trans-septal approach without the need for arthroscopic
control.

Synovectomy can be performed with an arthroscopic shaver (Fig.12) or radiofrequency instrument.

The choice depends on the macroscopic features of the synovitis: a shaver allows radical removal of
hypertrophic synovial membrane at the expense of heavier intra- and post-operative bleeding. The
use of radiofrequencies, on the other hand, allows careful haemostasis of synovial blood vessels.
For this reason, it is advisable to use both instruments together, in order to perform the procedure
quickly and radically while also minimising blood loss. At the end of the procedure a drain is
positioned in the joint; this is removed after 24-48 hours. This procedure has a very low incidence
of intra- and postoperative complications: 3.2% (range 1.1%-6.2%). The most frequent minor
complications are haemarthrosis (3.5%) and superficial infection (2%). Severe postoperative pain
persists for 2-3 weeks in 1.5% of patients. Septic arthritis is a very rare complication (0.5%) [16].
The recurrence rate after arthroscopic synovectomy is very variable and essentially depends on the
extension and aggressiveness of the specific disease. At a mean follow up of 6.9 years, 24.6%
(18.5%-36.2%) of surgically treated patients reported a recurrence of symptoms that were
comparable to or more severe than their pre-operative conditions [16]. The outcome of the
arthroscopic procedure is comparable to that of open surgery in terms of recurrence rate, while the
functional scores, postoperatively and at long-term follow up, have been found to be significantly
superior after arthroscopy [13,35].

11 Open synovectomy

Prior to the introduction of arthroscopy, open synovectomy was considered the gold standard
procedure for the surgical treatment diffuse synovitis; although it is more invasive, it allows
accurate and radical removal of pathological tissue. Current indications for this procedure are
diffuse hyperproliferative conditions not accessible arthroscopically on account of the size or extra-
articular localisation of the lesions. In order to access all the compartments of the knee the
procedure can be performed by performing an anterior arthrotomy, usually medial parapatellar or
mid-vastus, to allow synovectomy of the anterior chambers and suprapatellar pouch, and a posterior
access for the remaining compartments. The choice of an anterior, anterior-posterior, one-step or
two-step approach is determined by the extension and characteristics of the pathology. The two-
step approach is adopted only occasionally, when a one-step procedure is not advisable due to its
invasiveness or the presence of comorbidities.

Open anterior synovectomy

The knee joint is approached through an anteromedial arthrotomy (medial parapatellar or mid-
vastus). It is advisable to use a tourniquet and carry out periarticular vessel haemostasis from the
very beginning of the procedure in order to minimise blood loss given that this can sometimes be
very severe. The synovectomy can be performed through the anterior approach according to the
following sequence: suprapatellar pouch, medial and lateral parapatellar recesses, medial
compartment, anterior chamber and lateral compartment. All the removed tissue must be sent to
pathology for tissue typing and histological analysis (Fig.13). It is advisable to position one or two
intra-articular drains which must be removed 48 hours after the procedure.

Open posterior synovectomy

The patient is positioned in prone decubitus and the site is accessed via a Trickey’s posterior
approach, taking care to obtain good exposure while preserving the popliteal neurovascular bundle.
This approach, if correctly performed, allows good exposure of both the posteromedial and
posterolateral compartments (Fig.14). Since the incidence of cutaneous complications is very high
in this district, the reconstruction and suturing must be carried out with great care, avoiding creating
excessive tightness liable to give rise to stiffness and subsequent range-of-motion limitation
postoperatively.

Even though it allows optimal and rapid exposure of the surgical site the open procedure is
associated with a high rate of complications including: postoperative stiffness (8-32%),
haemarthrosis (8-9%), surgical wound dehiscence and DVT [5,9,36].
Because of the higher incidence of intra- and postoperative complications, which are associated
with the degree of invasiveness, the functional scores of the open procedure are lower than those
recorded after arthroscopic surgery [35]. The reported recurrence rates range from 0% [8] to 15%
[4] and 29% [31]; this high variability can be explained by the heterogeneity of synovitis but also
by the association (mostly in severe cases) of non-surgical therapy (i.e. radiotherapy). Despite the
variability of the results the open procedure is generally regarded as equivalent to arthroscopy in the
surgical treatment of synovitis [1,6,28].

12 Mixed procedures

The open technique can be combined with arthroscopy in certain circumstances. For example, the
presence of pathological tissue in the semimembranosus-gastrocnemius popliteal bursa (a condition
known as a Baker’s cyst) requires a posterior open approach combined with arthroscopic
synovectomy, as allowing pathological tissue to remain inside or in communication with the joint
could increase the recurrence rate of synovitis.
13 Rehabilitation protocol

Patients start a programme of passive and active mobilisation, including the use of CPM, from as
early as the first postoperative day in order to obtain a progressive recovery of their range of
motion. Partial weight bearing with crutches is allowed immediately. The partial weight bearing
stage lasts for at least three weeks after surgery. In the event of postoperative pain or effusion
developing, resumption of full weight bearing must be delayed until the symptoms have resolved.
Once the surgical wounds have healed the patient can undergo hydrokinesitherapy and begin low-
resistance cycling.

14 References

1) Aurégan J, Klouche S, Bohu Y et al. (2014). Treatment of pigmented villonodular synovitis

of the knee. Arthroscopy 30(10): 1327–1341
2) Bertoni F, Unni K, Beabout JW et al. (1991). Chondrosarcomas of the synovium.
Cancer,67(1): 155–162
3) Boyle DL, Rosengren S, Bugbee W et al. (2003). Quantitative biomarker analysis of
synovial gene expression by real-time PCR. Arthritis Res Ther 5(6),: R352–360
4) Byers PD, Cotton RE, Deacon OW (1968) The diagnosis and treatment of pigmented
villonodular synovitis. J Bone Joint Surg Br; 50:290-305
5) Chin KR, Barr SJ, Winalski C et al. (2002) Treatment of advanced primary and recurrent
diffuse pigmented villonodular synovitis of the knee. J Bone Joint Surg Am 84:2192–2202
6) Colman MW , Ye J, Weis KR et al. (2013) Does combined open and arthroscopic
synovectomy for diffuse PVNS of the knee improve recurrence rates? Clin Orthop Relat Res
471(3), 883–890
7) Della Beffa C, Slansky E, Pommerenke C et al. (2013) The relative composition of the
inflammatory infiltrate as an additional tool for synovial tissue classification. PloS One 8(8)
e72494
8) Dines JS, DeBerardino TM, Wells JL et al. (2007) Long-term follow-up of surgically treated
localized pigmented villonodular synovitis of the knee. Arthroscopy 23: 930-937
9) Flandry FC, Hughston JC, Jacobson KE et al. (1994) Surgical treatment of diffuse
pigmented villonodular synovitis of the knee. Clin Orthop Relat Res 300:183–192
 10) Fletcher JA, Henkle C, Atkins L et al. (1992). Trisomy 5 and trisomy 7 are nonrandom
aberrations in pigmented villonodular synovitis: confirmation of trisomy 7 in uncultured
cells. Genes Chromosomes Cancer, 4(3), 264–266
11) Gerlag DM, Tak PP (2013). How to perform and analyse synovial biopsies. Best Pract Res
Clin Rheumatol 27(2), 195–207
12) Hallam P, Ashwood N, Cobb J (2001). Malignant transformation in synovial
chondromatosis of the knee? Knee 8(3), 239–242
13) Isart A, Gelber PE, Besalduch M et al. (2015). High recurrence and good functional results
after arthroscopic resection of pigmented villonodular synovitis. Rev Esp Cir Orthopo
Traumatol 59(6), 400–405
14) Klareskog L, Padyukov L, Alfredsson L (2007). Smoking as a trigger for inflammatory
rheumatic diseases. Curr Opin Rheumatol 19(1), 49–54
15) Krenn V, Morawietz L, Burmester GR et al. (2006). Synovitis score: discrimination between
chronic low-grade and high-grade synovitis. Histopathology 49(4), 358–364
16) Kuzmanova SI, Atanassov AN, Andreev SA et al. (2003). Minor and major complications of
arthroscopic synovectomy of the knee joint performed by rheumatologist. Folia Medica
45(3), 55–59
17) Lee DM, Weinblatt ME (2001). Rheumatoid arthritis. Lancet 358(9285), 903–911
18) Lu KH (2004). Subcutaneous pigmented villonodular synovitis caused by portal
contamination during knee arthroscopy and open synovectomy. Arthroscopy 20(4), e9–e13
19) McInnes IB, Schett G (2007). Cytokines in the pathogenesis of rheumatoid arthritis. Nat
Rev Immunol 7(6), 429–442
20) Mertens F, Jonsson K, Willén H et al. (1996). Chromosome rearrangements in synovial
chondromatous lesions. Br J Cancer 74(2):251–254
21) Milgram JW (1977). Synovial osteochondromatosis: a histopathological study of thirty
cases. J Bone Joint Surg Am 59(6), 792–801
22) Murray CJ, Vos T, Lozano R et al. (2012). Disability-adjusted life years (DALYs) for 291
diseases and injuries in 21 regions, 1990-2010: a systematic analysis for the Global Burden
of Disease Study 2010. Lancet 380(9859): 2197–2223
23) Myers BW, Masi AT (1980). Pigmented villonodular synovitis and tenosynovitis: a clinical
epidemiologic study of 166 cases and literature review. Medicine 59(3): 223–238
24) Neame RL, Carr AJ, Muir K et al (2003). UK community prevalence of knee
chondrocalcinosis: evidence that correlation with osteoarthritis is through a shared association
with osteophyte. Ann Rheum Dis 62(6): 513–518
25) O’Connell JX (2000). Pathology of the synovium. Am J Clin Pathol 114(5): 773–784
26) Pessler F, Ogdie A, Diaz-Torne C et al. (2008) Subintimal Ki-67 as a synovial tissue
biomarker for inflammatory arthropathies. Ann Rheum Dis 67: 162-167
27) Reece RJ, Canete JD, Parsons WJ et al (1999). Distinct vascular patterns of early synovitis in
psoriatic, reactive, and rheumatoid arthritis. Semin Arthritis Rheum 42(7): 1481–1484

28) Rodriguez-Merchan EC (2014) Review article: Open versus arthroscopic synovectomy for
pigmented villonodular synovitis of the knee. J Orthop Surg (Hong Kong) 22(3): 406–408

29) Schett G (2007). Cells of the synovium in rheumatoid arthritis. Osteoclasts. Arthritis Res
Ther 9(1): 203
30) Sciot R, Dal Cin P, Bellemans J et al. (1998) Synovial chondromatosis: clonal chromosome
changes provide further evidence for a neoplastic disorder. Virchows Arch 433(2): 189–191
31) Sharma V, Cheng EY (2009) Outcomes after excision of pigmented villonodular synovitis
of the knee. Clin Orthop Relat Res 467:2852-2858
32) Weckauf H, Helmchen B, Hinz U et al (2004) Expression of cell cycle-related gene products
in different forms of primary versus recurrent PVNS. Cancer Lett 210(1): 111–118
33) Weyand CM, Hicok, KC, Conn DL (1992) The influence of HLA-DRB1 genes on disease
severity in rheumatoid arthritis. Ann Intern Med 117(10): 801–806
34) Wuisman PI, Noorda RJ, Jutte PC (1997). Chondrosarcoma secondary to synovial
chondromatosis. Report of two cases and a review of the literature. Arch Orthop Trauma
Surg 116(5): 307–311
35) Yang B, Liu D, Lin J et al. (2015). Surgical treatment of diffuse pigmented villonodular
synovitis of the knee. Zhongguo Yi Xue Ke Xue Yuan Xue Bao 37(2): 234–239
36) Zvijac JE, Lau AC, Hechtman KS et al. (1999) Arthroscopic treatment of pigmented
villonodular synovitis of the knee. Arthroscopy 15:613–617

Figure captions

Fig.1: Chondrocalcinosis of the lateral compartment involving the lateral meniscus and submeniscal
recess
Fig.2: Hypertrophic rheumatoid synovitis
Fig.3: A characteristically thickened pathological synovial membrane
Fig.4: Synovial chondromatosis: metaplastic loose body
Fig.5: Villonodular synovitis
Fig.6: Villonodular synovitis
Fig.7: Patient positioning allowing access to the posterior compartments of the knee
Fig.8: Synovial hypertrophy in suprapatellar pouch (rheumatoid arthritis)
Fig.9: Synovitis of the anterior chamber involving anterior cruciate ligament synovial lining
Fig.10: Synovitis involving lateral parameniscal recess
Fig.11: Posteromedial portal created under arthroscopic control (transcondylar view)
Fig.12: Synovectomy performed using an arthroscopic shaver
Fig.13: Diffuse villonodular synovitis: surgical specimen
Fig.14: Synovial chondromatosis: open posterior approach