International Wound Journal ISSN 1742-4801
ORIGINAL ARTICLE
Neuropathic ulcers in leprosy treated with intralesional platelet-rich plasma Elena Conde-Montero1 , Celia Horcajada-Reales1 , Petunia Clavo2 , Irene Delgado-Sillero1 & Ricardo Suárez-Fernández1 1 Department of Dermatology, Hospital Universitario Gregorio Marañón, Madrid, Spain 2 Centro Sanitario Sandoval, Servicio Madrileño de Salud, Madrid, Spain
Key words Leprosy; Neuropathic ulcer; Platelet-rich plasma
Conde-Montero E, Horcajada-Reales C, Clavo P, Delgado-Sillero I, Suárez-Fernández R. Neuropathic ulcers in leprosy treated with intralesional platelet-rich plasma. Int Wound J 2014; doi: 10.1111/iwj.12359
Correspondence to Elena Conde-Montero, MD Department of Dermatology Hospital Universitario Infanta Leonor Madrid Spain E-mail: [email protected]
Abstract Neuropathic ulcers in leprosy represent a therapeutic challenge for clinicians. Chronic ulcers affect patient health, emotional state and quality of life, causing considerable morbidity and mortality in addition to contributing to significant health care costs. The pathogenesis is mainly related to the abnormally increased pressure in areas such as the sole of the foot, secondary to lack of sensation and deformities induced by peripheral sensory-motor neuropathy. Conventional treatment of these wounds can be slow due to their chronic inflammatory state and the senescence of local reparative cells. Platelet-rich plasma (PRP) may restore the healing process, leading to a reparative phase. We present two patients with four neuropathic leprosy ulcers that have responded satisfactory to PRP treatment. PRP therapy has been growing as a viable treatment alternative for chronic ulcers. However, stronger scientific evidence is required to support its potential benefit for use in chronic wounds.
Introduction
Neuropathic ulcers in leprosy represent a therapeutic challenge for clinicians. Chronic ulcers affect patient health, emotional state and quality of life, causing considerable morbidity and mortality in addition to contributing to significant health care costs. The pathogenesis is mainly related to the abnormally increased pressure in areas such as the sole of the foot, secondary to lack of sensation and deformities induced by peripheral sensory-motor neuropathy. There is a lack of high-quality research in the field of ulcer prevention and treatment in leprosy (1). Conventional treatment of these wounds can be slow due to their chronic inflammatory state and the senescence of local reparative cells. Platelet-rich plasma (PRP) therapy has been growing as a viable treatment alternative for chronic ulcers. When growth factors are released, they improve proliferation of mesenchymal stem cells, osteoblasts, fibroblasts, endothelial cells and epidermal cells. Due to its stimulating effect on tissue regeneration, neoangiogenic vascularisation and reepithelisation, PRP may restore the healing process, leading to a reparative phase (2,3). We report two leprosy patients with recalcitrant ulcers that were successfully managed with PRP injections.
Key Messages
• neuropathic ulcers in leprosy represent a therapeutic challenge for clinicians. • conventional treatment of these wounds can be slow due to their chronic inflammatory state and the senescence of local reparative cells. PRP may restore the healing process, leading to a reparative phase. • considering that neuropathic ulcers lack sensitivity, intralesional PRP therapy represents a painless viable treatment alternative • we present two patients with four neuropathic leprosy ulcers that have responded satisfactory to PRP treatment.
Case report Patient 1
A 67-year-old Spanish woman, diagnosed with leprosy and successfully treated 50 years before, was referred to our department for evaluation of a 2 × 1.6-cm plantar neuropathic ulcer of
© 2014 The Authors International Wound Journal © 2014 Medicalhelplines.com Inc and John Wiley & Sons Ltd doi: 10.1111/iwj.12359
1
E. Conde-Montero et al.
Ulcers in leprosy with platelet rich plasma
A
B
C
Figure 1 Clinical aspect of the three plantar ulcers in patient 1, before initiation of treatment with platelet-rich plasma injections: (A) 1-year duration ulcer, December 2012 and (B, C) 6-month duration ulcers, October 2013.
A
B
Figure 2 Patient 1: (A) almost complete ulcer epithelialisation after 9 weekly sessions of platelet-rich plasma injections and (B) complete reepithelialisation of the two more recent ulcers after 12 weekly sessions. Notice the maintained response of the first treated ulcer, at 1-year follow-up.
1-year duration on her left foot (Figure 1A). She had been previously treated with several antibiotics and different bioactive dressings, with progression of the ulcer. The patient was treated with intralesional autologous PRP. A 7-ml blood sample was aspirated and collected in two citrate tubes. The tubes were centrifuged at 160 g for 6 minutes. The blood samples were separated by centrifugation, thus obtaining two parts in each tube: the upper part consisted of 1 ml of platelet-poor plasma, and the lower part consisted of 1 ml of PRP. Platelet-poor plasma was aspirated and dropped. The residual 1 mL of PRP was aspirated from each test tube and prepared for activation by calcium chloride (0⋅1 ml/1⋅0 ml of PRP), thus obtaining 2⋅2 mL of activated PRP. We used 1-ml syringes with a subcutaneous needle. The PRP solution was injected into subcutaneous tissue within the next 10 minutes. It was injected every 0⋅5 cm within a 1-cm 2
radius from the ulcer throughout the ulcer bed, using 0⋅1 ml at each injection site. These injections were weekly repeated. The injected area decreased as the wound size decrease. At week 9, complete epithelialisation of the skin ulcer was observed (Figure 2A). No signs of recurrence were observed 1 month after the cessation of the treatment. The patient was referred 8 months later due to two other new plantar ulcers (2 × 1 and 1⋅3 × 1 cm, respectively) that had been recalcitrant to conventional treatment for the previous 6 months (Figure 1B and C). The initial ulcer continued epithelialisation. Weekly PRP treatment was then started for these two new lesions. Complete reepithelialisation was achieved at week 12 (Figure 2B). At 2 month follow-up, she presented with no plantar ulcers and was following preventive measures.
© 2014 The Authors International Wound Journal © 2014 Medicalhelplines.com Inc and John Wiley & Sons Ltd
E. Conde-Montero et al.
Ulcers in leprosy with platelet rich plasma
A
B
Figure 3 Deep ulcer on the lateral malleolus (patient 2): (A) clinical aspect pre-treatment and (B) excellent response after 9 weekly sessions of platelet-rich plasma injections.
Patient 2
A 73-year-old woman, who had been diagnosed with leprosy and successfully treated 40 years before, presented with a 15-year duration deep ulcer on her right lateral malleolus (Figure 3A). The ulcer (1⋅5 × 0⋅5 cm) had been managed with different ointments, dressings, antibiotics and even surgical interventions. After curettage of the thick hyperkeratotic area surrounding the ulcer, we started weekly PRP treatment (see the procedure above). After nine sessions of PRP injections, fairly complete reepithelialisation was achieved and the treatment was stopped (Figure 3B). No worsening of ulcer has been observed 4 months after the cessation of the treatment. Discussion
Intralesional injection is a recently described method for application of PRP. An experimental study in rabbits concludes that it represents an effective therapeutic option when dealing with non-healing wounds(4). Several studies published on the use of topical autologous PRP for the treatment of neuropathic ulcers, mainly diabetic foot ulcers, suggest that it could represent an effective and efficient treatment option (5). Peripheral nerve regeneration may be stimulated by vascular endothelial growth factor and other growth factors that can be found in PRP preparation. Anjayani et al. have recently reported improvement of peripheral neu-
ropathy sensibility in patients with leprosy after perineural PRP injection (6). We present two patients with four neuropathic leprosy ulcers that have responded satisfactory to PRP treatment. Considering that neuropathic ulcers lack sensitivity, intralesional PRP therapy represents a painless viable treatment alternative. Clinical trials are required to determine the potential benefit of PRP injections in the treatment of leprosy neuropathic ulcers. References 1. Reinar LM, Forsetlund L, Bjørndal A, Lockwood D. Interventions for skin changes caused by nerve damage in leprosy. Cochrane Database Syst Rev 2008;3:CD004833. 2. Arshdeep , Kumaran MS. Platelet-rich plasma in dermatology: boon or a bane? Indian J Dermatol Venereol Leprol 2014;80:5–14. 3. Conde-Montero E, Horcajada-Reales C, Suárez-Fernández R. Utilidad del plasma rico en plaquetas en el tratamiento de las úlceras crónicas de la piel. Piel 2014;29:248–54. 4. Dionyssiou D, Demiri E, Foroglou P, Cheva A, Saratzis N, Aivazidis C, Karkavelas G. The effectiveness of intralesional injection of platelet-rich plasma in accelerating the healing of chronic ulcers: an experimental and clinical study. Int Wound J 2013;10:397–406. 5. Villela DL, Santos VL. Evidence on the use of platelet-rich plasma for diabetic ulcer: a systematic review. Growth Factors 2010;28:111–6. 6. Anjayani S, Wirohadidjojo YW, Adam AM, Suwandi D, Seweng A, Amiruddin MD. Sensory improvement of leprosy peripheral neuropathy in patients treated with perineural injection of platelet-rich plasma. Int J Dermatol 2014;53:109–13.
© 2014 The Authors International Wound Journal © 2014 Medicalhelplines.com Inc and John Wiley & Sons Ltd
3
ORIGINAL ARTICLE
Neuropathic ulcers in leprosy treated with intralesional platelet-rich plasma Elena Conde-Montero1 , Celia Horcajada-Reales1 , Petunia Clavo2 , Irene Delgado-Sillero1 & Ricardo Suárez-Fernández1 1 Department of Dermatology, Hospital Universitario Gregorio Marañón, Madrid, Spain 2 Centro Sanitario Sandoval, Servicio Madrileño de Salud, Madrid, Spain
Key words Leprosy; Neuropathic ulcer; Platelet-rich plasma
Conde-Montero E, Horcajada-Reales C, Clavo P, Delgado-Sillero I, Suárez-Fernández R. Neuropathic ulcers in leprosy treated with intralesional platelet-rich plasma. Int Wound J 2014; doi: 10.1111/iwj.12359
Correspondence to Elena Conde-Montero, MD Department of Dermatology Hospital Universitario Infanta Leonor Madrid Spain E-mail: [email protected]
Abstract Neuropathic ulcers in leprosy represent a therapeutic challenge for clinicians. Chronic ulcers affect patient health, emotional state and quality of life, causing considerable morbidity and mortality in addition to contributing to significant health care costs. The pathogenesis is mainly related to the abnormally increased pressure in areas such as the sole of the foot, secondary to lack of sensation and deformities induced by peripheral sensory-motor neuropathy. Conventional treatment of these wounds can be slow due to their chronic inflammatory state and the senescence of local reparative cells. Platelet-rich plasma (PRP) may restore the healing process, leading to a reparative phase. We present two patients with four neuropathic leprosy ulcers that have responded satisfactory to PRP treatment. PRP therapy has been growing as a viable treatment alternative for chronic ulcers. However, stronger scientific evidence is required to support its potential benefit for use in chronic wounds.
Introduction
Neuropathic ulcers in leprosy represent a therapeutic challenge for clinicians. Chronic ulcers affect patient health, emotional state and quality of life, causing considerable morbidity and mortality in addition to contributing to significant health care costs. The pathogenesis is mainly related to the abnormally increased pressure in areas such as the sole of the foot, secondary to lack of sensation and deformities induced by peripheral sensory-motor neuropathy. There is a lack of high-quality research in the field of ulcer prevention and treatment in leprosy (1). Conventional treatment of these wounds can be slow due to their chronic inflammatory state and the senescence of local reparative cells. Platelet-rich plasma (PRP) therapy has been growing as a viable treatment alternative for chronic ulcers. When growth factors are released, they improve proliferation of mesenchymal stem cells, osteoblasts, fibroblasts, endothelial cells and epidermal cells. Due to its stimulating effect on tissue regeneration, neoangiogenic vascularisation and reepithelisation, PRP may restore the healing process, leading to a reparative phase (2,3). We report two leprosy patients with recalcitrant ulcers that were successfully managed with PRP injections.
Key Messages
• neuropathic ulcers in leprosy represent a therapeutic challenge for clinicians. • conventional treatment of these wounds can be slow due to their chronic inflammatory state and the senescence of local reparative cells. PRP may restore the healing process, leading to a reparative phase. • considering that neuropathic ulcers lack sensitivity, intralesional PRP therapy represents a painless viable treatment alternative • we present two patients with four neuropathic leprosy ulcers that have responded satisfactory to PRP treatment.
Case report Patient 1
A 67-year-old Spanish woman, diagnosed with leprosy and successfully treated 50 years before, was referred to our department for evaluation of a 2 × 1.6-cm plantar neuropathic ulcer of
© 2014 The Authors International Wound Journal © 2014 Medicalhelplines.com Inc and John Wiley & Sons Ltd doi: 10.1111/iwj.12359
1
E. Conde-Montero et al.
Ulcers in leprosy with platelet rich plasma
A
B
C
Figure 1 Clinical aspect of the three plantar ulcers in patient 1, before initiation of treatment with platelet-rich plasma injections: (A) 1-year duration ulcer, December 2012 and (B, C) 6-month duration ulcers, October 2013.
A
B
Figure 2 Patient 1: (A) almost complete ulcer epithelialisation after 9 weekly sessions of platelet-rich plasma injections and (B) complete reepithelialisation of the two more recent ulcers after 12 weekly sessions. Notice the maintained response of the first treated ulcer, at 1-year follow-up.
1-year duration on her left foot (Figure 1A). She had been previously treated with several antibiotics and different bioactive dressings, with progression of the ulcer. The patient was treated with intralesional autologous PRP. A 7-ml blood sample was aspirated and collected in two citrate tubes. The tubes were centrifuged at 160 g for 6 minutes. The blood samples were separated by centrifugation, thus obtaining two parts in each tube: the upper part consisted of 1 ml of platelet-poor plasma, and the lower part consisted of 1 ml of PRP. Platelet-poor plasma was aspirated and dropped. The residual 1 mL of PRP was aspirated from each test tube and prepared for activation by calcium chloride (0⋅1 ml/1⋅0 ml of PRP), thus obtaining 2⋅2 mL of activated PRP. We used 1-ml syringes with a subcutaneous needle. The PRP solution was injected into subcutaneous tissue within the next 10 minutes. It was injected every 0⋅5 cm within a 1-cm 2
radius from the ulcer throughout the ulcer bed, using 0⋅1 ml at each injection site. These injections were weekly repeated. The injected area decreased as the wound size decrease. At week 9, complete epithelialisation of the skin ulcer was observed (Figure 2A). No signs of recurrence were observed 1 month after the cessation of the treatment. The patient was referred 8 months later due to two other new plantar ulcers (2 × 1 and 1⋅3 × 1 cm, respectively) that had been recalcitrant to conventional treatment for the previous 6 months (Figure 1B and C). The initial ulcer continued epithelialisation. Weekly PRP treatment was then started for these two new lesions. Complete reepithelialisation was achieved at week 12 (Figure 2B). At 2 month follow-up, she presented with no plantar ulcers and was following preventive measures.
© 2014 The Authors International Wound Journal © 2014 Medicalhelplines.com Inc and John Wiley & Sons Ltd
E. Conde-Montero et al.
Ulcers in leprosy with platelet rich plasma
A
B
Figure 3 Deep ulcer on the lateral malleolus (patient 2): (A) clinical aspect pre-treatment and (B) excellent response after 9 weekly sessions of platelet-rich plasma injections.
Patient 2
A 73-year-old woman, who had been diagnosed with leprosy and successfully treated 40 years before, presented with a 15-year duration deep ulcer on her right lateral malleolus (Figure 3A). The ulcer (1⋅5 × 0⋅5 cm) had been managed with different ointments, dressings, antibiotics and even surgical interventions. After curettage of the thick hyperkeratotic area surrounding the ulcer, we started weekly PRP treatment (see the procedure above). After nine sessions of PRP injections, fairly complete reepithelialisation was achieved and the treatment was stopped (Figure 3B). No worsening of ulcer has been observed 4 months after the cessation of the treatment. Discussion
Intralesional injection is a recently described method for application of PRP. An experimental study in rabbits concludes that it represents an effective therapeutic option when dealing with non-healing wounds(4). Several studies published on the use of topical autologous PRP for the treatment of neuropathic ulcers, mainly diabetic foot ulcers, suggest that it could represent an effective and efficient treatment option (5). Peripheral nerve regeneration may be stimulated by vascular endothelial growth factor and other growth factors that can be found in PRP preparation. Anjayani et al. have recently reported improvement of peripheral neu-
ropathy sensibility in patients with leprosy after perineural PRP injection (6). We present two patients with four neuropathic leprosy ulcers that have responded satisfactory to PRP treatment. Considering that neuropathic ulcers lack sensitivity, intralesional PRP therapy represents a painless viable treatment alternative. Clinical trials are required to determine the potential benefit of PRP injections in the treatment of leprosy neuropathic ulcers. References 1. Reinar LM, Forsetlund L, Bjørndal A, Lockwood D. Interventions for skin changes caused by nerve damage in leprosy. Cochrane Database Syst Rev 2008;3:CD004833. 2. Arshdeep , Kumaran MS. Platelet-rich plasma in dermatology: boon or a bane? Indian J Dermatol Venereol Leprol 2014;80:5–14. 3. Conde-Montero E, Horcajada-Reales C, Suárez-Fernández R. Utilidad del plasma rico en plaquetas en el tratamiento de las úlceras crónicas de la piel. Piel 2014;29:248–54. 4. Dionyssiou D, Demiri E, Foroglou P, Cheva A, Saratzis N, Aivazidis C, Karkavelas G. The effectiveness of intralesional injection of platelet-rich plasma in accelerating the healing of chronic ulcers: an experimental and clinical study. Int Wound J 2013;10:397–406. 5. Villela DL, Santos VL. Evidence on the use of platelet-rich plasma for diabetic ulcer: a systematic review. Growth Factors 2010;28:111–6. 6. Anjayani S, Wirohadidjojo YW, Adam AM, Suwandi D, Seweng A, Amiruddin MD. Sensory improvement of leprosy peripheral neuropathy in patients treated with perineural injection of platelet-rich plasma. Int J Dermatol 2014;53:109–13.
© 2014 The Authors International Wound Journal © 2014 Medicalhelplines.com Inc and John Wiley & Sons Ltd
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