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Collagenase Clostridium histolyticum Injection for Plantar Fibromatosis (Ledderhose Disease)

Hammoudeh, Ziyad S. M.D.

Plastic and Reconstructive Surgery: September 2014 - Volume 134 - Issue 3 - p 497e–499e
doi: 10.1097/PRS.0000000000000433

Department of Surgery, Wayne State University, 4201 St. Antoine, 6C-UHC, Detroit, Mich. 48201,

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In February of 2010, collagenase Clostridium histolyticum injection was approved by the U.S. Food and Drug Administration for treatment of palmar fibromatosis (Dupuytren contractures) in patients with a palpable cord. In December of 2013, it was approved by the U.S. Food and Drug Administration for the treatment of penile fibromatosis (Peyronie disease) in adult men with a palpable plaque and a curvature deformity of 30 degrees or greater on erection. Dupuytren and Peyronie disease are considered by many to be systemic manifestations of a common progressive fibrotic process that also includes plantar fibromatosis (Ledderhose disease).1,2 There has been substantial evidence in the literature supporting the use of collagenase C. histolyticum for both Dupuytren contracture3 and Peyronie disease.4 However, it was for plantar fibromatosis (Ledderhose disease) has not been previously investigated. This report contains the first known use of collagenase C. histolyticum injection for plantar fibromatosis.

A 72-year-old Caucasian man presented with bilateral plantar pain on ambulation. On examination, the patient had a nodular thickening of the mid-plantar surface proximal to the great toe without flexion contracture bilaterally (Figs. 1 and 2). He had previously undergone a left partial fasciectomy with recurrence of his symptoms; conservative management and steroid injections were also previously attempted without success. The patient was noted to have Dupuytren flexion contractures of bilateral palms, but he did not seek treatment for his hands because they did not cause him pain or substantial functional problems. Considering his prior failed treatments and lack of desire for further surgery, the patient wished to attempt collagenase C. histolyticum injection as an off-label use. Each plantar nodule was injected with XIAFLEX (Auxilium Pharmaceuticals, Inc., Malvern, Pa.) at the standard dosage for a metacarpophalangeal joint (0.58 mg in 0.25 ml of reconstituted solution). The patient was injected on three separate occasions with a greater than 1-month interval between injections. Passive plantar extension to disrupt the fibrotic process could not be performed 24 hours after each treatment in a fashion analogous to that for palmar cords because of the lack of a palpable plantar cord. Plantar fibromatosis characteristically presents as a palpable nodule without the contracture deformity commonly seen in the palms.2 In addition, the rigidity of the dorsal surface of the foot also resists performing such a maneuver in the foot compared with the hand. Unfortunately, after completion of the series of injections, the patient did not have any softening of the plantar nodule and did not report any improvement in pain on ambulation.

Fig. 1

Fig. 1

Fig. 2

Fig. 2

Experimental therapies reported in the literature for plantar fibromatosis include radiotherapy, extracorporeal shock wave therapy, and antiestrogen therapy.5 Although very effective for Dupuytren contractures and Peyronie disease, collagenase C. histolyticum was not effective in treating plantar fibromatosis in this patient. This lack of success is likely attributable to the anatomical properties unique to this disease process in the plantar region (which typically includes a nodule instead of a cord or plaque) rather than specific to this patient. However, additional studies are needed to further evaluate the effectiveness of collagenase C. histolyticum as a treatment modality for plantar fibromatosis.

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The author has no financial interest to declare in relation to the content of this article.

Ziyad S. Hammoudeh, M.D.

Department of Surgery

Wayne State University

4201 St. Antoine, 6C-UHC

Detroit, Mich. 48201

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1. Zgonis T, Jolly GP, Polyzois V, Kanuck DM, Stamatis ED. Plantar fibromatosis. Clin Podiatr Med Surg. 2005;22:11–18
2. van der Veer WM, Hamburg SM, de Gast A, Niessen FB. Recurrence of plantar fibromatosis after plantar fasciectomy: Single-center long-term results. Plast Reconstr Surg. 2008;122:486–491
3. Gilpin D, Coleman S, Hall S, Houston A, Karrasch J, Jones N. Injectable collagenase Clostridium histolyticum: A new nonsurgical treatment for Dupuytren’s disease. J Hand Surg Am. 2010;35:2027–2038.e1
4. Gelbard M, Goldstein I, Hellstrom WJ, et al. Clinical efficacy, safety and tolerability of collagenase Clostridium histolyticum for the treatment of Peyronie disease in 2 large double-blind, randomized, placebo controlled phase 3 studies. J Urol. 2013;190:199–207
5. Veith NT, Tschernig T, Histing T, Madry H. Plantar fibromatosis: Topical review. Foot Ankle Int. 2013;34:1742–1746
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