Almadori, A

Butler, PEM

Denton, CP

Griffin, MF

Jeon, FHK

Langridge, BJ

English

UCL Discovery

 Autologous lipotransfer can improve the outcomes of localised scleroderma  Sir, Localised scleroderma, also known as mor- phea, presents heterogeneously, from small plaques to extensive linear morphea that can cause joint contracture, limb length dis- crepancy and significant functional impair- ment (1). Morphea further impacts patient quality of life through cosmetic disfigure- ment, with patients reporting embarrass- ment, stigmatisation, along with high rates of anxiety and depression (2).  Treatment options for morphea target the underlying disease process, however, treat- ments for established disfigurement are ex- tremely limited (3). Autologous fat grafting (AFG), also known as autologous lipotrans- fer, is an increasingly popular reconstruc- tive technique with demonstrated utility in the treatment of fibrotic conditions such as systemic sclerosis and radiation-induced fi- brosis (4, 5). AFG is useful for reconstruct- ing soft-tissue volumetric defects, however, recent research has also demonstrated re- generative and antifibrotic properties, pu- tatively through the presence of Adipose Derived Stem Cells (ADSCs) (6). Literature reporting the use of AFG in mor- phea is sparse (3). We report our experience with two patients presenting with morphea predominantly affecting the lower limb. We performed AFG through the technique described by Coleman; in short, fat is har- vested from the abdomen using a cannula connected to a 20ml Luer-Lock syringe, the lipoaspirate is centrifuged at 3000rpm for 3 minutes, with the blood and free oil being discarded before grafting (6). The first patient was a 22-year-old female with linear morphea of the left lower leg, including the groin, posterior knee, dorsum of foot from the age of 11. After successful treatment with methotrexate, she relapsed following the birth of her first child. De- spite increased methotrexate and the addi- tion of multiple systemic and topical treat- ments, her morphea worsened. She required physiotherapy, cognitive behavioural ther- apy and cosmetic camouflage. 48ml of fat was harvested from the abdomen and both thighs and transferred into the left leg using the Coleman technique (6). Despite incom- plete graft retention, the patient was able to stop all systemic treatment for her second pregnancy, with her morphea remaining stable. The second patient was a 29-year-old fe- male with morphea of the left leg, abdomen and arm that started from the age of 17. She was treated with intravenous steroids, topi- cal therapy and phototherapy as she did not tolerate further systemic therapy. Extensive fibroatrophic changes to her left leg and foot resulted in difficulty walking or standing, the need for orthotics, with progressively limited movement of her ankle and knee. AFG was harvested from the abdomen and grafted to the thigh, tibial border, heel and plantar surface of the foot. Despite incom- plete graft retention, the patient experienced improvement in joint mobility which per- sisted at long-term follow-up (Fig. 1). AFG is a minimally invasive, safe technique that utilises a readily available autologous substrate with minimal donor site morbid- ity. Its ability to produce long-term sympto- matic improvements has been demonstrated in other fibrotic conditions (4, 5). The cases we report here demonstrate its potential util- ity as a treatment for morphea, including in severe cases causing functional deficit. The mechanism by which AFG reverses tissue fibrosis is not well understood, how- ever, graft ADSCs are implicated through enhancing angiogenesis, localised immu- nomodulation and inhibition of transform- ing growth factor beta1 (TGF-β1) signal- ling (7). ADSCs are thought to promote tissue angiogenesis indirectly through vascular endothelial growth factor (VEGF) expression and directly through differentia- tion into endothelial cells (8). TGF-β1 is a potent inducer of collagen synthesis and plays a key role in tissue fibrosis; the mech- anism by which AFG reduces its expression is poorly understood, but thought to be the result of paracrine signalling between AD- SCs and fibroblasts (4). AFG has shown significant promise in the treatment of fibrotic conditions. Utilising AFG in the treatment of morphea has, so far, been limited, but promising early re- sults warrant further investigation of this innovative treatment modality and its un- derlying mechanisms. B.J. Langridge1, MBBS, MA(Cantab.), MRCS, FHEA F.H.K. Jeon1, MBBS, MSc A. Almadori1, MBChB, MSc M.F. Griffin1, MBChB, MSc, MRes, MRCS, PhD C.P. Denton2, PhD, FRCP P.E.M. Butler1, MD, FRCS (Plast)  1Department of Plastic Surgery, Royal Free Hospital, London, Charles Wolfson Centre for Reconstructive Surgery, Royal Free Hospital, London, and Division of Surgery & Interventional Science, University College London; 2Centre for Rheumatology, UCL Division of Medicine and Royal Free London NHS Foundation Trust Hospital, London, UK. Please address correspondence to: Dr Benjamin J. Langridge, Department of Plastic and Reconstructive Surgery, Royal Free Hospital, Pond Street, Hampstead, NW3 2QG London, UK. E-mail: b.langridge1@nhs.net  Competing interests: none declared.  References 1. MERTENS JS, SEYGER MMB, THURLINGS RM, RADSTAKE TRDJ, DE JONG EMGJ: Morphea and Eosinophilic Fasciitis: An Update. Am J Clin Der- matol 2017; 18: 491-512. 2. KLIMAS NK, SHEDD AD, BERNSTEIN IH, JACOBE H: Health-related quality of life in morphoea. Br J Dermatol 2015; 172: 1329-37. 3. DE ALBUQUERQUE JV, ANDRIOLO BN, VAS- CONCELLOS MR, CIVILE VT, LYDDIATT A, TRE- VISANI VF: Interventions for morphea. Cochrane Database Syst Rev 2019; 7: CD005027. 4. ALMADORI A, GRIFFIN M, RYAN CM et al.: Stem cell enriched lipotransfer reverses the effects of fibrosis in systemic sclerosis. PLoS One 2019; 14: e0218068. 5. RIGOTTI G, MARCHI A, GALIÈ M et al.: Clini- cal treatment of radiotherapy tissue damage by lipoaspirate transplant: A healing process mediated by adipose-derived adult stem cells. Plast Reconstr Surg 2007; 119: 1409-22. 6. COLEMAN SR: Structural fat grafting: More than a permanent filler. Plast Reconstr Surg 2006; 118 (Suppl.): 108S-120S. 7. RIGOTTI G, MARCHI A, SBARBATI A: Adipose- Derived mesenchymal stem cells: Past, present, and future. Aesthetic Plast Surg 2009; 33: 271-3. 8. HONG KY, YIM S, KIM HJ et al.: The Fate of the Ad- ipose-Derived Stromal Cells during Angiogenesis and Adipogenesis after Cell-Assisted Lipotransfer. Plast Reconstr Surg 2018; 141: 365-75.   Fig. 1. Patient 2 pre- operatively (left) and 5 years post-Autologous Fat Grafting (right), demonstrating sustained improvement in her joint contracture.    

Autologous lipotransfer canimprove the outcomes of localised scleroderma

S-159Letters to the EditorsClinical and Experimental Rheumatology 2021Autologous lipotransfer can improve the outcomes of localised sclerodermaSirs,Localised scleroderma, also known as mor-phea, presents heterogeneously, from small plaques to extensive linear morphea that can cause joint contracture, limb length dis-crepancy and significant functional impair-ment (1). Morphea further impacts patient quality of life through cosmetic disfigure-ment, with patients reporting embarrass-ment, stigmatisation, along with high rates of anxiety and depression (2).Treatment options for morphea target the underlying disease process, however, treat-ments for established disfigurement are ex-tremely limited (3). Autologous fat grafting (AFG), also known as autologous lipotrans-fer, is an increasingly popular reconstruc-tive technique with demonstrated utility in the treatment of fibrotic conditions such as systemic sclerosis and radiation-induced fi-brosis (4, 5). AFG is useful for reconstruct-ing soft-tissue volumetric defects, however, recent research has also demonstrated re-generative and antifibrotic properties, pu-tatively through the presence of Adipose Derived Stem Cells (ADSCs) (6).Literature reporting the use of AFG in mor-phea is sparse (3). We report our experience with two patients presenting with morphea predominantly affecting the lower limb. We performed AFG through the technique described by Coleman; in short, fat is har-vested from the abdomen using a cannula connected to a 20ml Luer-Lock syringe, the lipoaspirate is centrifuged at 3000rpm for 3 minutes, with the blood and free oil being discarded before grafting (6).The first patient was a 22-year-old female with linear morphea of the left lower leg, including the groin, posterior knee, dorsum of foot from the age of 11. After successful treatment with methotrexate, she relapsed following the birth of her first child. De-spite increased methotrexate and the addi-tion of multiple systemic and topical treat-ments, her morphea worsened. She required physiotherapy, cognitive behavioural ther-apy and cosmetic camouflage. 48ml of fat was harvested from the abdomen and both thighs and transferred into the left leg using the Coleman technique (6). Despite incom-plete graft retention, the patient was able to stop all systemic treatment for her second pregnancy, with her morphea remaining stable.The second patient was a 29-year-old fe-male with morphea of the left leg, abdomen and arm that started from the age of 17. She was treated with intravenous steroids, topi-cal therapy and phototherapy as she did not tolerate further systemic therapy. Extensive fibroatrophic changes to her left leg and foot resulted in difficulty walking or standing, the need for orthotics, with progressively limited movement of her ankle and knee. AFG was harvested from the abdomen and grafted to the thigh, tibial border, heel and plantar surface of the foot. Despite incom-plete graft retention, the patient experienced improvement in joint mobility which per-sisted at long-term follow-up (Fig. 1).AFG is a minimally invasive, safe technique that utilises a readily available autologous substrate with minimal donor site morbid-ity. Its ability to produce long-term sympto-matic improvements has been demonstrated in other fibrotic conditions (4, 5). The cases we report here demonstrate its potential util-ity as a treatment for morphea, including in severe cases causing functional deficit.The mechanism by which AFG reverses tissue fibrosis is not well understood, how-ever, graft ADSCs are implicated through enhancing angiogenesis, localised immu-nomodulation and inhibition of transform-ing growth factor beta1 (TGF-β1) signal-ling (7). ADSCs are thought to promote tissue angiogenesis indirectly through vascular endothelial growth factor (VEGF) expression and directly through differentia-tion into endothelial cells (8). TGF-β1 is a potent inducer of collagen synthesis and plays a key role in tissue fibrosis; the mech-anism by which AFG reduces its expression is poorly understood, but thought to be the result of paracrine signalling between AD-SCs and fibroblasts (4).AFG has shown significant promise in the treatment of fibrotic conditions. Utilising AFG in the treatment of morphea has, so far, been limited, but promising early results warrant further investigation of this innova-tive treatment modality and its underlying mechanisms.B.J. Langridge1, MBBS, MA(Cantab.), MRCS, FHEAF.H.K. Jeon1, MBBS, MScA. Almadori1, MBChB, MScM.F. Griffin1, MBChB, MSc, MRes, MRCS, PhDC.P. Denton2, PhD, FRCPP.E.M. Butler1, MD, FRCS (Plast)1Department of Plastic Surgery, Royal Free Hospital, London; Charles Wolfson Centre for Reconstructive Surgery, Royal Free Hospital, London; and Division of Surgery & Interventional Science, University College London;2Centre for Rheumatology, UCL Division of Medicine and Royal Free London NHS Foundation Trust Hospital, London, UK.Please address correspondence to:Benjamin J. Langridge, Department of Plastic and Reconstructive Surgery, Royal Free Hospital, Pond Street, Hampstead, NW3 2QG London, United Kingdom.E-mail: b.langridge1@nhs.netCompeting interests: none declared.© Copyright CliniCal and ExpErimEntal rhEumatology 2021.References  1. MERTENS JS, SEYGER MMB, THURLINGS RM, RADSTAKE TRDJ, DE JONG EMGJ: Morphea and Eosinophilic Fasciitis: An Update. Am J Clin Der-matol 2017; 18: 491-512.  2. KLIMAS NK, SHEDD AD, BERNSTEIN IH, JACOBE H: Health-related quality of life in morphoea. Br J Dermatol 2015; 172: 1329-37.  3. DE ALBUQUERQUE JV, ANDRIOLO BN, VASCON-CELLOS MR, CIVILE VT, LYDDIATT A, TRE-VISANI VF: Interventions for morphea. Cochrane Database Syst Rev 2019; 7: CD005027.  4. ALMADORI A, GRIFFIN M, RYAN CM et al.: Stem cell enriched lipotransfer reverses the effects of fibrosis in systemic sclerosis. PLoS One 2019; 14: e0218068.  5. RIGOTTI G, MARCHI A, GALIÈ M et al.: Clinical treatment of radiotherapy tissue damage by lipoaspirate transplant: A healing process mediated by adipose-derived adult stem cells. Plast Reconstr Surg 2007; 119: 1409-22.  6. COLEMAN SR: Structural fat grafting: More than a permanent filler. Plast Reconstr Surg 2006; 118 (Suppl.): 108S-120S.  7. RIGOTTI G, MARCHI A, SBARBATI A: Adipose-Derived mesenchymal stem cells: Past, present, and future. Aesthetic Plast Surg 2009; 33: 271-3.  8. HONG KY, YIM S, KIM HJ et al.: The fate of the adipose-derived stromal cells during angiogenesis and adipogenesis after cell-assisted lipotransfer. Plast Reconstr Surg 2018; 141: 365-75.Fig. 1. Patient 2 pre-operatively (left) and 5 years post-Autologous Fat Grafting (right), demonstrating sustained improvement in her joint contracture. 

Autologous lipotransfer can improve the outcomes of localised scleroderma

https://discovery.ucl.ac.uk/10125698/7/Almadori_article.pdf

Autologous lipotransfer can improve the outcomes of localised scleroderma

Abstract

Similar works

Full text

Available Versions

UCL Discovery

UCL Discovery