Sorafenib in Dupuytren and Ledderhose Disease.

Palmar and plantar fibromatosis are benign proliferative processes which present as a diffuse thickening or nodules of the hands and/or feet and may lead to flexion contractures, pain, and functional impairment known as Dupuytren and Ledderhose diseases, respectively. Current treatments are noncurative and associated with significant morbidity. Here, we report on the outcomes of 5 patients with advanced disease, no longer surgical candidates, treated with sorafenib. Sorafenib exhibited an expected safety profile. All 5 patients demonstrated objective responses as evaluated by a decrease in tumor size and/or tumor cellularity from baseline and all 5 patients reported subjective pain relief and/or functional improvement. Mechanistically, immunohistochemistry revealed patchy positivity for PDGFRß, a known target of sorafenib. The outcomes of these 5 patients suggest the safety and efficacy of a relatively well-tolerated oral agent in the treatment of Dupuytren and Ledderhose diseases and suggest the need for future controlled studies.

Radiotherapy for patients with Ledderhose disease: Long-term effects, side effects and patient-rated outcome.

BACKGROUND: The purpose of this study was to investigate the long-term effects of radiotherapy for patients with Ledderhose disease. METHODS: Questionnaires were sent to all patients with Ledderhose disease who had been treated with radiotherapy at our centre between 2008 and 2017 and who consented to participate. Radiotherapy was performed with orthovolt or electrons in two separate courses of five daily fractions of 3 Gy. The questionnaires addressed items such as pain from Ledderhose disease (Brief Pain Inventory), quality of life (EURO-QOL-5D-5L), long-term side effects, and patients' levels of satisfaction with the effect of treatment. Descriptive statistics and non-parametric tests were used to analyse the results. RESULTS: A total of 102 feet were irradiated in 67 patients (28 men, 39 women). Radiotherapy resulted in significant pain reduction: the mean pain score prior to radiotherapy, collected retrospectively, was 5.7 and 1.7 at time of assessment (p-value < 0.001). The following pain response scores were reported: progressive pain (0%), no change (22%; 22 feet), partial pain response (37%; 38 feet) and complete pain response (absence of pain) (41%; 42 feet). Seventy-eight percent of patients were satisfied with the treatment effect and 57% did not consider radiotherapy burdensome. The scores for societal perspective (0.856) and patients' perspective on quality of life (82.3) were each comparable to the reference values from the Dutch population in the same age category (0.857 and 80.6, respectively). The most commonly reported residual long-term side effect was dryness of the skin (n = 10; 15%). CONCLUSION: Radiotherapy for Ledderhose disease results in long-term pain reduction in the majority of patients and has limited side effects. The treatment is well tolerated, patients feel satisfied, and quality of life is comparable to the reference population.

Follow-up of clinical and sonographic features after extracorporeal shock wave therapy in painful plantar fibromatosis.

BACKGROUND: Extracorporeal shock wave therapy (ESWT) has been used as a safe alternative treatment for refractory musculoskeletal diseases, such as plantar fasciitis, Achilles tendinopathy and gluteal tendinopathy, and various forms of fibromatosis including palmar or penile fibromatosis. However, there is limited published data for clinical and sonographic features of plantar fibromatosis after ESWT. The purpose of this study was to evaluate the long-term clinical outcome of ESWT in ultrasonography-confirmed plantar fibromatosis and ultrasonographic changes of plantar fibroma after ESWT. METHODS: Medical charts of 26 patients (30 feet) with plantar fibromatosis confirmed by ultrasonography were reviewed. Finally, a total of 10 feet who underwent ESWT for "Poor" or "Fair" grade of Roles-Maudsley Score (RMS) and symptoms persisted for >6 months were included in this study. Short-term follow-up was conducted one week after ESWT and long-term follow-up time averaged 34.0 months. The Numerical Rating Scale (NRS) and RMS were collected for the evaluation of clinical features. Follow-up ultrasonography was conducted at long-term follow-up and changes of plantar fibroma was assessed. A greater than 50% reduction in the NRS and achievement of a "good" or "excellent" grade in the RMS were regarded as treatment success. Additionally, medical charts of 144 patients (168 feet) with plantar fasciitis confirmed by ultrasonography were reviewed and subsequently, 42 feet who underwent ESWT with the same protocol were included for the comparison of clinical features. RESULTS: In plantar fibromatosis, baseline NRS (6.2 ± 1.3) and RMS (3.5 ± 0.5) were significantly improved at short-term follow-up (NRS, 1.8 ± 1.0; RMS, 2.0 ± 0.8, P < .001, respectively) and long-term follow-up (NRS, 0.6 ± 1.1; RMS, 1.4 ± 0.8, P < .001, respectively). Treatment success was recorded in seven feet (70.0%) at short-term follow-up and 8 feet (80%) at long-term follow-up, which is comparable to that of the plantar fasciitis group (28 feet, 66.7%; 35 feet, 83.3%, respectively). In long-term follow-up ultrasonography, mean fibroma thickness was reduced from 4.4±1.0 to 2.6±0.8 mm (P = .003); however, length and width were not significantly changed. There were no serious adverse effects. CONCLUSION: While these are preliminary findings, and must be confirmed in a randomized placebo control study, ESWT can have a beneficial long-term effect on pain relief and functional outcomes in painful plantar fibromatosis. However, ESWT is unlikely to affect the ultrasonographic morphology of plantar fibroma, with the exception of reducing the thickness. LEVEL OF EVIDENCE: Level III, retrospective cohort study.

Current concepts about treatment options of plantar fibromatosis: A systematic review of the literature.

BACKGROUND: Plantar fibromatosis, or Ledderhose disease, is a benign and hyperproliferative disease of the plantar aponeurosis. There have been described different therapeutic options regarding plantar fibromatosis, both conservative and surgical. The aim of this review is to systematically analyze conservative and operative treatments of plantar fibromatosis described in literature, evaluating which procedure shows the highest success rate and best functional outcome. METHODS: A systematic review of PubMed, Google Scholar and Cochrane reviews computerized database was performed focusing on the different types of treatments for plantar fibromatosis. Research was performed using the keywords "plantar", "fibromatosis", "Ledderhose", "Dupuytren", "foot" in order to identify all papers regarding the treatment of plantar fibromatosis. In addition, the research was extended to the reference list of the relevant articles. A total of 25 citations were obtained from the research and included. RESULTS: Considering all the studies, 233 patients were included in this systematic review. 5 studies reported conservative treatment of plantar fibromatosis, with a total of 35 patients included. Operative outcomes are reported for 178 patients (92 male, 86 female), with 196 feet treated. CONCLUSIONS: Valid conservative methods are presented in literature, with debated results. Some operative options show high recurrence rate; wide excision is recommended in selected cases. Further clinical trials with well-defined and standardized outcome measurements should be necessary in future to better evaluate success rate and complications of the various procedures.

Clinical, histological and therapeutic modern approach of Ledderhose disease.

Ledderhose disease or plantar fibromatosis is a rare hyperproliferative disorder of the plantar aponeurosis, clinically characterized by nodules situated especially on the medial border of the foot. It is histopathologically associated with Dupuytren's disease. This disease has some risk factors, like old age, alcohol or nicotine abuse, liver dysfunction, trauma or exposure to vibrations and autoimmune disorders, but the exact etiology is still unknown. Even though it is benign, the local manifestations can be aggressive, leading to debilitating deformities and contractures of the toes. Ultrasound and magnetic resonance imaging are used to confirm the diagnosis and to eliminate other disorders. Whenever is possible, the conservative therapies are recommended. Having a high recurrence, Ledderhose disease can be hard to treat, needing multiple surgical interventions. This paper aims to cover all the important aspects of this disease for daily medical practice, from history to clinical manifestations, diagnostic methods and histopathological features, to conservative and surgical treatment modalities.

Plantar Fibromatosis: Pathophysiology, Surgical and Nonsurgical Therapies: An Evidence-Based Review.

Plantar fibromatosis (morbus Ledderhose), an extra-abdominal desmoid tumor of the plantar foot, is a rare benign hyperproliferative disorder of the plantar fascia with an unknown etiology. The main clinical characteristics include slow growing nodules on the medial and central bands of the plantar fascia, which may become painful and negatively affect ambulation. Most established conservative therapies today target symptomatic relief. As symptoms progress, therapies such as injections, shockwave ablation, radiation, and/or surgery may be required. This review aims to provide insight into the pathophysiology of this condition in addition to detailing current and investigational therapies for this disorder. Many therapies have been proven in similar conditions, which could lead to promising treatment options for plantar fibromatosis. LEVELS OF EVIDENCE: Level V: Expert opinion.