Continuing Education Activity

Plantar fibromatosis is a benign fibroblastic, connective tissue proliferative disorder of the superficial plantar aponeurosis of the foot. It belongs to a family of similar diseases (Peyronie and Dupuytren) first described in 1610 by Plater. George Ledderhose, a German physician, initially described the disease in 1897 following his observation of fifty cases. Ledderhose disease is diagnosed by identifying nodules within the central or medial bands of the plantar fascia of the foot. Presentation is slow, and patients usually present after the disease becomes locally aggressive, causing pain and swelling in the medial non-weight bearing plantar surface of the feet. This activity discusses the diagnosis and treatment of plantar fibromatosis and highlights the role of the interprofessional team. It is a rarer condition than Dupuytren contracture, with which it shares some similarities regarding pathology and epidemiology.

Objectives:

• Identify the etiology of plantar fibromatosis.
• Outline the appropriate evaluation of plantar fibromatosis.
• Review the management options available for plantar fibromatosis.
• Describe the main indications for surgery for plantar fibromatosis, the surgical strategies employed, and potential complications that can arise.

Introduction

Plantar fibromatosis is a benign fibroblastic, connective tissue proliferative disorder of the superficial plantar aponeurosis of the foot. It belongs to a family of similar diseases (Peyronies and Dupytrens) first described in 1610 by Plater.[1] George Ledderhose, a German physician, initially described the disease in 1897 following his observation of fifty cases.[2] Ledderhose disease is diagnosed by identifying nodules within the central or medial bands of the plantar fascia of the foot. Onset is slow, and patients usually present after the disease becomes locally aggressive, causing pain and swelling in the medial non-weight bearing plantar surface of the feet.[3]

Etiology

The exact etiology leading to plantar fibromatosis is unknown.[2][4]

Epidemiology

Plantar fibromatosis is rare, affecting less than 200,000 people in the United States.[3] It typically presents in middle-aged patients, most commonly in the 4th and 5th decades of life. However, there are cases in children, some as young as 9 months, in the literature.[4] The disease is two times more likely to occur in males than females and has an incidence of bilateral foot involvement in approximately 25% of patients. It has been noted as being most common in patients with a history of diabetes, epilepsy, or alcohol use disorder. There may also be a familial inheritance pattern. Ledderhose shares a geographical similarity with Dupuytren, as it is more common in people of northern European descent.[5] It has been found that patients with Dupuytren that require surgery for deformity of their hands are more likely to have Ledderhose disease.[3]

Pathophysiology

The underlying cause of hyperactive proliferating fibroblasts is unknown. It is thought that the cause is possibly related to an increased release of growth factors (such as IGF-1, FGF, PDGF, TGF-B). There have also been reports of increased interleukin 1 alpha and beta.[5]

Histopathology

Proliferating fibroblasts are thought to be the cause of the plantar fascia nodules. These fibroblasts are found in areas surrounded by less cellular fascia with a small collagen supply.[5] The cells are the same size, randomly arranged in a matrix with little vascular supply. The extracellular matrix and cytoskeleton have high amounts of fibronectin and myofibroblasts with a predominance of type III collagen.[1][6]

History and Physical

The classic presentation is that of a slow-growing, painless nodule in the medial or central plantar aponeurosis of the foot that is about 0.5 to 3 cm in diameter. Smaller nodules can present as local pressure points or areas of plantar distension. As the nodules become more locally invasive, they can lead to pain and swelling and eventually lead to trouble with ambulation. Patients commonly present after experiencing increased pain in the plantar surface of the foot after long walks. Specific activities, such as long walks, standing for long periods, specific shoe wear, and walking barefoot, can exacerbate the symptoms.[4] The diagnosis is made clinically by evaluating the plantar surface of the foot for fibromas. There can also be evidence of sclerosis of the plantar fascia as well as plantar contractures. In rare cases, patients can present with toe contractures. The patient's hands should also be evaluated as 15% of patients with Dupuytren have Ledderhose disease. 

The foot should be examined for tenderness over bony prominences and tendon insertions. Hindfoot alignment, as well as the presence of an Achilles or gastrocnemius contracture, should be evaluated as these can contribute to symptoms.[4]

Evaluation

It is also recommended to obtain ultrasound and MRI with contrast imaging to exclude other underlying causes such as lipoma, fibrosarcoma, or cyst. Ultrasound can show the depth and size of nodules. Nodules will appear isoechoic on ultrasound with a heterogeneous appearance. Hyperechoic septa may also be present. No flow is present when Doppler is used with ultrasound. MRI can also be obtained for surgical planning for excision of the plantar fibromas and can also identify the extent of the plantar contractures. Nodules appear well defined on MRI with signal intensity low on T1 images and low to moderate on T2 images.[6] X-rays can be obtained to rule out any underlying bony pathology contributing to patient symptomatology. X-rays can also show any soft tissue calcifications (commonly seen in malignant lesions). A biopsy can also be utilized to rule out malignancy.[5]

Treatment / Management

Conservative Treatment

Multiple non-operative treatment options have been described. Most non-operative treatments are focused on symptom reduction. The first line of treatment should always begin with non-operative modalities prior to any surgical intervention. Along with anti-inflammatories and physical therapy, listed below are some conjunctive therapies that can initially be trialed. The progression of the disease is not changed by non-operative modalities.

Orthotics/Pads

In patients with mild disease with minimal symptoms, pads can be placed inside the shoe to offload the parts of the foot where fibromas are present. Increased padding inside the shoe can also help alleviate mild symptoms.[7] To decrease the stress across the plantar fascia, carbon footplates or rocker bottom shoes can also be used. 

Steroids

There are no studies supporting steroid use in plantar fibromatosis; however, studies have shown benefit in its use in Dupuytren disease. Local injection of steroids is thought to help with symptomatology. Injection should help reduce node and strand size in the plantar fascia.[5] Size reduction can occur over a few months. It is thought that steroids decrease fibroblast activity and increase their apoptosis. These function by decreasing the expression of the VCAM1 gene, which in turn limits the production of pro-inflammatory cytokines, leading to a nodule growth reduction and a decline in inflammation. Pentland et al. describe the use of regular, monthly intralesional steroid injections in one patient over 5 months. The patient presented complaining of difficulty in ambulating, but 4 months following the final injection was able to begin jogging. Complications due to steroid injections include fascial/ tendon rupture and fat atrophy, and skin depigmentation.[8][1]

Verapamil

The drug verapamil is a common calcium channel blocker used for hypertension. In Ledderhose disease, it can be used to promote the activity of collagenase and inhibit collagen production. The benefits are mainly theoretical and derived from studies investigating the treatment of Peyronies disease. The transdermal and intralesional verapamil injection has demonstrated a decrease in plaque size by 55% to 85%. Contact dermatitis is the most common complication of verapamil use.[2][4]

Radiation Therapy

Radiation therapy through electron beam radiation or orthovoltage x-ray can decrease fibroblast activity through disruption of TGF production by fibroblasts. Two cycles with a total dose of 30 Gy are typically used for a week with a 6-week break between the two cycles. Another study shows using 3 Gy per week for 5 weeks, followed by another session 6 weeks out. One study showed a complete node resolution in 33.3% of cases and decreased node size in 54.5% of cases. Side effects from radiation therapy include: (erythema, dry skin). The incidence of malignant transformation of skin is unknown, lacking long-term follow-up.[5][4]

Collagenase

Collagenase derived from Clostridium histolyticum breaks down collagen. The idea of using collagenase injections for Ledderhose disease came from its use in Peyronie and Dupuytren disease. The evidence for collagenase effectiveness is limited. Lehrman et al. described a case report where they used collagenase to inject a 20F recurrent Ledderhose. The patient had failed 3 months of conservative treatment as well as multiple surgical interventions (local excision as well as multiple endoscopic plantar fasciotomies) prior to attempting collagenase. In their study, using a 25G needle, 0.58 mg of collagenase was injected into the palmar fibroma. One-third of the solution was injected centrally, followed by one-third proximal and one-third of the solution injected distally to the central aspect of the fibroma. Twenty-four hours after injection, the patient was brought back to the clinic to break up the fibroma with PROM of the toes as well as massage of the plantar surface of the foot. The patient reported resolution of symptoms up to their last follow-up 33 months after the intervention.[9]

Tamoxifen

Anti-estrogenic drugs are still in the very experimental phases as a possible treatment. It is thought that tamoxifen inhibits TGF-beta expression, which in turn inhibits the proliferative activity of fibroblasts while also decreasing fibroblast maturation and differentiation of myofibroblasts.[5] Studies have demonstrated promise in Dupuytren patients, with up to 20% nodule size regression. However, no studies examine the use of estrogen receptor modulating agents in plantar fibromatosis to date.[4]

Extra Corporeal Shock Wave Therapy (ESWT)

Originally stems from its effective use as a treatment in Peyronie. The original protocol for shock wave therapy was described using 2000 pulses at a frequency of 3 Hz at 7-day intervals for 2 weeks. This study found a softening of nodes in the patients who chose to undergo this treatment option. Its mechanism of action is unclear, but theories include that the mechanical action of the shockwaves leads to an overexpression of TGF beta amongst others, which causes an increased production of extracellular matrix components, reducing the maturation process of the myofibroblasts and restricting tissue contraction.[4] Other theories surmise that the direct damage to the lesion stimulates a healing response, while another suggests that the increase in the vascularity of the lesions leads to lysis of the lesion itself.[6]

Differential Diagnosis

Medial plantar mass differential includes leiomyoma, simple fibroma, liposarcoma, neurofibroma, rhabdomyosarcoma, fibrosarcoma, nodular fasciitis (differential can be ruled out with MRI and/or biopsy).[1]

Surgical Oncology

Surgery

The main indications for surgery include those lesions refractory to conservative treatment as well those affecting the patient's daily activities, including the prevention of walking or difficulty in fitting shoes. Surgical strategy options include (1) local excision, (2) wide excision, or (3) complete fasciectomy. 

1. Local excision: removal of the node, with a recurrence rate up to 60% to 100%
2. Wide excision: removal of the node with margins of 2 cm, with a recurrence rate up to 60%
3. Complete fasciectomy: removal of the plantar fascia, with a recurrence rate of 25%[5]

Subtotal Plantar Fasciectomy  

S-shaped incision made, including all nodules. Dissection is performed to separate subcutaneous tissue from the plantar fascia. Isolate the plantar fascia and find its attachment to the calcaneus. Make an incision through the fascia 1 cm distal to the calcaneus and then dissect out distally to where neurovascular structures can be identified.[10] 

Ran et al. described a couple of cases in two brothers that underwent full-thickness skin grafts with free vascularized upper lateral arm flaps after extensive dermofasciectomy of their Dupuytren and Ledderhose after recurrence after multiple prior surgeries. Besides the recurrence of one plantar nodule on one foot, they had no evidence of recurrence, and the two patients were pain-free. The authors felt this was a good option for patients with severe recurrent disease (such as in diathesis). Recurrence after this procedure is found to be 47% at 13 years.[11]

As described by Souza et al., it is important when planning for surgical intervention to be mindful of incisions over the plantar surface of the foot. Longitudinal or zigzag incisions medial to midline can put the skin at risk for necrosis due to arterial supply patterns to the plantar surface of the foot. Longitudinal incisions can also predispose the skin to form a hypertrophic scar. Incisions over weight-bearing surfaces of the foot can also cause issues as they can lead to pain while walking.[10] 

Staging

Stages of Disease

1. Proliferative phase: increased fibroblast activity 
2. Active/involution phase: maturation of fibroblasts, differentiation of myofibroblasts, increased collagen production
3. Residual phase: reduced collagen and fibroblast maturation[1]

Sammarco and Mangone Classification [5]

• Grade 1: focal lesion, a small area affected, does not involve skin or muscle
• Grade 2: multiple areas, can extend distal/proximal, does not involve skin or muscle
• Grade 3: multiple areas, can extend proximal/distal, involves the skin and/or muscle
• Grade 4: multiple areas, can extend proximal/distal, involves skin and muscle

Prognosis

Ledderhose disease can be treated in the first instance with conservative treatment, with surgery reserved for patients with lesions that do not respond to medical treatments or those with lesions that interfere with their lives, such as the ability to wear shoes or with walking. There is a high rate of recurrence with non-operative and operative treatment options.

Complications

The main complication following treatment is the risk of recurrence of the lesion, which is high for all types of surgery but particularly pronounced for local excision. The recurrence rate appears to be higher in patients with bilateral multiple lesions and family history. Other potential surgical complications include issues related to the wound, such as dehiscence and painful scarring, as well as nerve entrapment. In subtotal fasciectomy, a loss of height of the medial longitudinal arch has also been reported.[12] Damage to plantar nerves can lead to numbness or neuroma formation.[10]

Postoperative and Rehabilitation Care

After surgical intervention: non-weight bearing for 3 weeks until the incision heals. After healing has occurred, full weight-bearing is allowed.

Consultations

Orthopedic surgery for more invasive non-operative treatment and operative management.

Deterrence and Patient Education

There is a high rate of recurrence. The disease has a hereditary component.

Enhancing Healthcare Team Outcomes

The best evidence for the management of plantar fibromatosis is limited to case series, mainly owing to the rare nature of the disorder.

Conservative treatment should be the first line of treatment. Steroid injections and radiotherapy have shown good clinical results, but the benefits compared to side effects are not fully known. Shockwave therapy shows promising results, but further studies are needed to look at outcomes and potential complications. Local excision shows the highest recurrence rate and should be avoided. Subtotal fasciectomy and wide excision should be the only surgical treatment considered for highly symptomatic primary and recurrent lesions.

Review Questions

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References

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Disclosure: Amy Meyers declares no relevant financial relationships with ineligible companies.

Disclosure: Matthew Marquart declares no relevant financial relationships with ineligible companies.