505535
research-article2013
FAIXXX10.1177/1071100713505535Foot & Ankle InternationalVeith et al
Topical Review
Plantar Fibromatosis—Topical Review
Nils T. Veith1, Thomas Tschernig, MD1, Tina Histing, MD2,
and Henning Madry, MD3,4
Level of Evidence: Level V, expert opinion.
Keywords: morbus Ledderhose, Ledderhose disease, plantar fibromatosis, total plantar fasciectomy
Summary
Morbus Ledderhose is a rare hyperproliferative disease of
the plantar fascia, leading to the formation of nodules. Its
origin is unknown. No causal therapy is available, and treat-
ment remains symptomatic. Various therapeutic strategies
to alleviate symptoms are available and are adapted to the
severity of the disease. In early stages, conservative therapy
including nonpharmacological, physical, and pharmaco-
logical treatments is applied. If the disease progresses, irra-
diation of the plantar surface, injections of steroids, shock
wave therapy, and partial or complete fasciectomy as an
ultimate therapy may be indicated. Novel experimental
treatment options including application of fibrinolytic
agents are currently being tested, but no controlled, ran-
domized long-term studies are available. This review aims
to provide a systematic overview of current established pro-
cedures and outlines novel experimental strategies for the
treatment of morbus Ledderhose, including future avenues
to treat this rare disease.
Introduction
Ledderhose disease is a rare hyperproliferative disorder of
unknown origin that leads to formation of nodules in the
nonstructural plantar fascia.16,18 It was initially described
by the German physician Georg Ledderhose in 1897.26
Pain occurs especially after long walks. Men are affected
twice as often as women,9,13 and in 25% of cases, both feet
are affected.18 Ledderhose disease is often associated with
diseases such as frozen shoulder,5 Dupuytren disease,13,18
alcohol addiction, epilepsy,30 diabetes mellitus,11 and
penile fibromatosis.31 Immunohistochemical and ultra-
structural analyses suggest a relationship with morbus
Dupuytren.8,17
Clinical Presentation and Diagnosis
Ledderhose disease is characterized by slow-growing nodes
in the central medial plantar fascia, which can lead to
shrinkage and sclerosis of the entire plantar fascia.18,21 Not
typically, but in rare cases, the fibromatosis leads to toe
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Foot & Ankle International
34(12) 1742­–1746
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DOI: 10.1177/1071100713505535
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contractures.6,9 Symptoms include pain and swelling in the
foot, which can lead to walking disability. The first signs of
the early stage are local pressure and distension. The late
stage is characterized by the formation of nodules and con-
tractures of the plantar fascia.34 Diagnosis is based on clini-
cal examination. Sonography and magnetic resonance
imaging (MRI) can be useful to confirm the diagnosis.32
Radiographs are not necessary to establish the diagnosis,
but the exclusion of bone disease may be indicated.17
Sonography is the diagnostic tool of choice. Biopsies may
be performed to rule out malignancies.
Diagnostic Imaging
Diagnostic imaging enables the clinician to define the
degree of contracture and to eliminate potential differen-
tial diagnoses. As fibrosarcoma and nodular fasciitis are
important differential diagnoses, establishment of the
correct diagnosis is an important step in the treatment of
Ledderhose disease.14 A sonography study examining
size variations has shown that most nodules are located
superficially in the plantar fascia, are fusiform, and are
smaller than 20 mm.4 Sammarco and Mangone34 created
a 4-level classification scheme to assess the operative
procedure (Table 1). Histological and immunohisto-
chemical studies have revealed that proliferating fibro-
blasts are chiefly responsible for the formation of the
nodules in the plantar fascia. Interestingly, these prolifer-
ating fibroblasts are located adjacent to less cellularized
areas of the fascia.8,17
1
Institute of Anatomy, Saarland University, Homburg, Germany
2
Department of Trauma, Hand and Reconstructive Surgery, University of
Saarland, Homburg, Germany
3
Center of Experimental Orthopaedics, Saarland University, Homburg,
Germany
4
Department of Orthopaedic Surgery, Saarland University, Homburg,
Germany
Corresponding Author:
Thomas Tschernig, MD, Institute of Anatomy and Cell Biology,
Kirrberger Straße, 66421 Homburg/Saar, Germany.
Email: thomas.tschernig@uks.eu
Veith et al 1743

Table 1.  Classification by Sammarco and Mangone (Modified).

Grade No. of Lesions Quality of Propagation Infiltration of the Skin and Muscle
I Focal Small area of the plantar fascia affected No skin and muscle infiltration
II Multifocal Distal/proximal propagation possible No skin and muscle infiltration
III Multifocal Distal/proximal propagation possible Skin or muscle infiltration
IV Multifocal Distal/proximal propagation possible Both skin and muscle infiltration

Table 2.  Summary of the Established Forms of Therapy.

Study Technique Approach Results/Adverse Side Effects (ASE)

Meek et al28 Steroid injection Reduction in activity of the A further relapse in 50% of patients within
Pentland and Anderson33 fibroblasts the first 3 years
Ketchum et al (2002)22 ASE: not known
Heyd et al19 X-ray irradiation Reduction in activity of the Reduction of the node after 22.5 months
Seegenschmiedt and Attassi35 fibroblasts in 55.4% of patients
ASE: redness and dry skin
Griffith et al17 Local excision Removal of the node without Relapses in 85%-100% of patients10,38
Beckmann et al3 safety distance ASE: wound-healing disorders
Griffith et al17 Wide excision Removal of the node with 2- to Relapses in 78% of patients10
Beckmann et al3 3-cm safety distance ASE: wound-healing disorders
Griffith et al17 Complete Complete removal of the plantar Relapses in 25% of patients38
Beckmann et al3 fasciectomy fascia ASE: wound-healing disorders and
extension of the foot longitudinal arch34
de Bree et al7 Adjuvant Irradiation of the operatively Hardly any relapses7
  radiotherapy treated areas ASE: functional disability

The reason for the increased activity of fibroblasts is
unknown; an increased release of growth factors is sus-
pected, but it is unclear by which cells and why. Various
studies on the cause of the fibromatosis diseases show a
tendency toward assuming involvement of growth factors
in the pathogenesis of these diseases.25,29,39 An increased
expression of growth factors such as insulin-like growth
factor I, basic fibroblast growth factor, platelet-derived
growth factor, and transforming growth factor-β (TGF-β)
may play a role in the origin of these diseases.25,29,39
Increased expression of interleukin-1α and interleukin-1β
has been reported.1
Ledderhose disease can be classified in 3 phases based
on its activity.12,27 Phase I, called the proliferative phase,
shows histologically increased fibroblastic activity and a
reduction of the collagen network. There are no visible
changes in the plantar fascia at this early stage. Phase II,
also known as the active phase, is characterized by matu-
ration of fibroblasts and increased collagen synthesis.
Macroscopically, the first signs of node formation in the
plantar fascia appear. Phase III, or the residual phase, is
characterized by diminished fibroblastic activity and
reduced collagen maturation. Contractures begin to form
on the sole of the foot.
The choice of treatment depends on the degree of the
pathological alterations and individual symptoms. There
are many therapeutic options which are described in the
following.
Established Therapies
Conservative Treatment
In the early phase of the disease, symptom-oriented ther-
apy can be performed. In less painful stages, anti-inflam-
matory drugs, local corticosteroid injections, and physical
therapy are indicated. Orthopedic insoles can reduce pain
during walking. Because these measures may improve
symptoms but do not prevent the progression of the dis-
ease, they are only justified as long as there is no aggres-
sive node growth. If no pain reduction can be achieved and
a stage of strong fibroblastic activity has been reached,
other therapeutic options that are discussed hereafter
should be considered (Table 2).
Steroid Injections
Local steroid injections in the areas of high activity acceler-
ate the proliferative activity of the fibroblasts and reduce

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1744 Foot & Ankle International 34(12)
Table 3.  Summary of Experimental Therapies.
Authors Technique
Knobloch Extracorporeal shock Treatment of painful lesions with shock waves
et al23 wave therapy (2000 impulses, frequency 3 Hz), preventing
Knobloch and progression
Vogt24
 
Kuhn et al25 Antiestrogen therapy Inhibition of the expression of growth factors
  by tamoxifen
 
their apoptosis.28 The aim of this therapy is to reduce fibro-
matosis nodes and strands in the region of the plantar fascia,
leading to improved mobility and less pain. Volume reduc-
tions of the nodes, as well as an improvement in symptoms,
should occur after 3 to 4 months.33 A study on the treatment
of fibromatosis nodes with the steroid triamcinolone ace-
tonide showed its success (defined as the absence of recur-
rence) with a rate of 50% within the first 3 years.22
X-Ray Irradiation
Radiotherapy reduces the proliferative activity of the
fibroblasts and thus may be a useful treatment option for
the early stages of the disease. Both orthovoltage therapy
and irradiation of affected areas by means of a linear elec-
tron accelerator are available. Usually, 2 irradiation cycles
with a total dose of 30 Gy are performed, each for a dura-
tion of 1 week with an interval of 6 weeks between
them.19,35 After a median follow-up of 22 months, Heyd et
al19 reported a complete remission of the nodes in 33.3%
of cases and a decrease or numerical reduction in 54.5%
of the cases. Nearly 70% of the patients showed a reduc-
tion in pain and an improvement in their gait pattern. A
study by Seegenschmiedt and Attassi35 estimated a 50%
median improvement on the visual analog scale after a
median follow-up of 38 months. Side effects included
temporary (3 months) erythema in 14% of cases; 8% were
affected by dry skin after radiotherapy for periods greater
than 1 year. Long-term studies are lacking, and thus the
risk of malignant changes at the radiation site is not
known.
Surgery
Operative measures are indicated when the above measures
fail to improve symptoms and progression of the disease.
Removal of the aggressively growing node is the target of
operative intervention and should relieve pain as well as
maintain the patient’s ability to walk. Local excision, wide
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Approach Results/Adverse Side Effects (ASE)
After 14 days, an improvement in pain
symptoms
No data on relapse, since long-term results
are lacking
ASE: not known
No patient trials
Tamoxifen inhibited in vitro the release of
transforming growth factor-β.
ASE: not known, since no patient cohort
excision with a safe margin, and complete fasciectomy are
the 3 operative methods of choice.3,13,17
Local excision removes only the affected node. Wide exci-
sion removes the proliferatively active node with a safety mar-
gin of at least 2 cm. The most radical treatment is complete
fasciectomy, in which the entire plantar fascia is removed.
Recurrences have been reported in 25% of patients after
total fasciectomy and in 100% after local resection.38 Van
der Veer et al38 estimated the general recurrence rate for all
3 methods at 60%. Dürr et al10 estimated the rate of recur-
rence of Ledderhose disease after further resection at 78%
and after local resection at 85%. It is mandatory to prevent
a postoperative extension of the foot contour by applying
insoles with exact longitudinal arch support.34
The most frequent complication is impaired wound heal-
ing, especially in cases that have been treated by radiother-
apy. The first therapeutic trials with a combined therapy,
consisting of a complete fasciectomy and adjuvant radio-
therapy, produced satisfactory results with regard to relapse
rates.7 Here, plantar fasciectomy was associated with the
lowest recurrence rate, whereas all tumors recurred follow-
ing incomplete excision or excision of early recurrences. Of
note is that recurrence was rarely observed after adjuvant
radiotherapy, which was, however, associated with an
impaired functional outcome in some cases.7 In view of
these side effects, the authors of this study recommended
adjuvant radiotherapy only for strictly selected cases.7
Experimental Therapies
Extracorporeal Shock Wave Therapy
Interestingly, extracorporeal shock wave therapy (ESWT)
was originally used to treat penile fibromatosis.31 Knobloch
et al23 suggested the use of ESWT to treat Ledderhose dis-
ease. A case report applying ESWT at intervals of 7 days
(2000 pulses, frequency 3 Hz, and energy flux density of
1.24 mJ/mm2) reported pain relief in the majority of patients
after 14 days.24 Softening of the nodes was observed in all
Veith et al 1745
patients, and no side effects were seen. Long-term studies
are not yet available (Table 3).
Antiestrogen Therapy
Therapy with synthetic nonsteroidal antiestrogens such as
tamoxifen is still in the experimental phase. The prolifera-
tive activity of the fibroblasts can be reduced by the inhibi-
tion of TGF-β expression. In vivo data are not yet available,
however, an in vitro study that embedded fibroblasts from
Dupuytren patients in a collagen matrix and exposed the
embedded fibroblasts to TGF-ß for 5 days showed a notably
higher number of contractions compared with the normal
control group.25 Most important, subsequent treatment of
the fibroblasts with tamoxifen showed a marked decrease in
the contractions and TGF-β release in the Dupuytren
group.25 Thus, tamoxifen may be of value in preventing the
progression of the disease.
Conclusion
Because the triggering cause of Ledderhose disease remains
unknown, numerous therapeutic approaches for its treat-
ment are available. Conservative therapy, as indicated in
early phases, may provide pain relief. Progression of the
disease, however, cannot be prevented. Injection of steroids
reduces the activity of the node-forming fibroblasts.
Irradiation mainly leads to a reduction in pain and reduces
the nodes in 50% of the cases. Surgery is the most com-
monly used therapy for the treatment of Ledderhose dis-
ease, the best results being achieved with complete
fasciectomy. Adjuvant radiation leads to serious side effects.
Preclinical and clinical studies are needed to show the
potential benefit of antiestrogen therapy where tamoxifen is
the drug of choice. Some therapeutic principles may also be
borrowed from studies to treat Dupuytren disease, such as
treatment with interferon-γ,36 collagenase,15,20 benzodiaze-
pine injections,37 and needle fasciectomy.2 The applicability
of these therapies for Ledderhose disease has yet to be
established. Further insights into the molecular mechanisms
that lead to this rare disease, together with application of
these and other innovative principles, will lead to an opti-
mized treatment of Ledderhose disease.
Acknowledgements
We thank Andrea Rabung and Ann Soether for their skillful help
with the text and language.
Declaration of Conflicting Interests
The author(s) declared no potential conflicts of interest with
respect to the research, authorship, and/or publication of this
article.
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Funding
The author(s) received no financial support for the research,
authorship, and/or publication of this article.
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