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Monographs of Topical Drugs that Have Caused Contact Allergy/Allergic Contact Dermatitis
Published in Anton C. de Groot, Monographs in Contact Allergy, 2021
Collagenase clostridium histolyticum is an enzyme produced by the bacterium Clostridium histolyticum and a member of the matrix metalloproteinases that cleaves triple-helical collagen types I, II, and III. It is used as a powder- and-solvent injection kit for the treatment of Dupuytren’s contracture, a condition where the fingers bend towards the palm and cannot be fully straightened, and Peyronie’s disease, a connective tissue disorder involving the growth of fibrous plaques in the soft tissue of the penis. Used in the topical treatment of skin ulcers and severe burns, collagenase is able to digest collagen in necrotic tissue at physiological pH by hydrolysing the peptide bonds of undenatured and denatured collagen. Collagenase thus contributes towards the formation of granulation tissue and subsequent epithelization. The action of collagenase may remove substrates necessary for bacterial proliferation or may permit antibodies, leukocytes, and antibiotics better access to the infected area (1).
Hands
Published in Tor Wo Chiu, Stone’s Plastic Surgery Facts, 2018
Collagenase (clostridium histolyticum) injections are promising. Xiaflex was approved by the FDA in February 2010 for use in DD with a palpable cord (FDA approval for treatment of Peyronie’s disease in 2013). It may be best for MCPJ contractures, but the best indications and longevity remain unclear at this time. An average of 3 injections are needed, with or without ‘finger extension procedures’.
Pharmacotherapy in Peyronie’s disease: a state-of-the-art review on established contemporary and emerging drugs
Published in Expert Opinion on Pharmacotherapy, 2022
Collagenase Clostridium histolyticum (CCH) was first studied in PD in the early 1980s [45,46] and to date, remains the only drug approved specifically for PD [47]. The commercially marketed CCH consists of two isoforms of synergistically acting collagenases, AUX-I and AUX-II which are responsible for the degradation of collagen type I and III, the main contributors to PD plaque formation [47]. Furthermore, studies have shown that CCH directly induces apoptosis of fibroblasts, downregulates the abnormal expression of collagen type I and III, and destroys pathological collagen plaques [47]. In the original IMPRESS (Investigation for Maximal Peyronie’s Reduction Efficacy and Safety Studies) clinical trials, patients received up to 3–4 cycles of two injections of CCH at the point of maximum curvature of the plaque, given between 24 to 72 hours followed by strict instruction on manual penile remodeling [46,47]. Since then, more than 100 studies have been published showing intralesional CCH therapy to improve penile curvature (and erectile function) while reducing plaque volume [48–51].
Pirfenidone as a potential antifibrotic injectable for Dupuytren’s disease
Published in Pharmaceutical Development and Technology, 2022
Suchitra Panigrahi, Amanda Barry, Scott Multner, Gerald B. Kasting, Julio A. Landero Figueroa, Latha Satish, Harshita Kumari
Treatments for DD are only minimally effective. Until now, the treatment mainstay for flexion contractures has been surgical resection (fasciectomy) of the contracted tissue or cords (Davis 2013) with appropriate splinting and hand therapy after surgery. However, this approach has significant risks including damage to digital nerves, blood vessels, and flexor tendons. In addition, it is painful, requires post-operative care, and is associated with high recurrence rates (27–80%) (Rodrigo et al. 1976; Au-Yong et al. 2005). Numerous non-invasive treatment options (Richards 1952; Pittet et al. 1994; Ball et al. 2016) including the administration of intralesional corticosteroids, radiation, and topical creams, yield limited efficacy. More recently, the intranodular injection of collagenase clostridium histolyticum (CCH) and percutaneous needle fasciotomy have been shown to be less invasive techniques (Hurst et al. 2009; van Rijssen et al. 2012; Costas et al. 2017). Approximately 30–50% of patients (Peimer et al. 2015) who received CCH experienced hand swelling, injection site hemorrhage, and pain. Although CCH appears to be a viable non-operative option for DD, contracture recurrence remains an issue (Nayar et al. 2019). Clinically, many of these treatments are still in use with minimal success. Thus, there is an urgent need to develop a local therapy that can mitigate disease progression to contractures and prevent a recurrence.
Future concepts and therapy approaches for Peyronie’s disease
Published in Expert Opinion on Orphan Drugs, 2020
Edward J. Choi, Douglas Schneider, Perry Xu, Farouk M. El-Khatib, Faysal A. Yafi
Amidst the diversity of therapy options, intralesional injections of collagenase Clostridium histolyticum (CCh) is currently the only drug to be approved by the United States Food and Drug Administration (FDA). While CCh has demonstrated good effect with minimal rates of complications, CCh remains ‘off-label’ for patients in the acute phase of PD or if they present with atypical features [21]. In November 2019, CCh was withdrawn from the European Union, extending its unavailability on the international markets including Australia, Asia, and Canada [22]. Without access to CCh, patients are now confronted with the difficult decision to pursue conservative alternatives with less than desirable approval ratings by the major governing urologic societies or undergo invasive operations [23]. In this review, we discuss the evidence on the expanded use of CCh for acute and atypical PD (Table 1) as well as novel, non-surgical treatment options that have been investigated since the FDA first approved of CCh (Table 2–3).