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Letters to the editor
therapy as well. The cells can be derived locally (e.g. fibroblasts, keratinocytes, melanocytes, adipocytes, hair follicle cells, and skin progenitor cells) or systemically (e.g. cells in the bone marrow system). Studies indicate that progenitor cells produce more favorable outcome than differentiated keratinocytes in bioengineered skin.[9]
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The foregoing adjunctive measures may improve many aspects of wound healing in the patient with a leg ulcer. Excitingly, stem cells, especially adipose-derived stromal cells, may be of immense value in healing leg ulcers in the future. The world waits with bated breath for more trailblazing research on the subject and its diverse clinical applications.
Vijay Langer Department of Plastic Surgery, Army Hospital Research and Referral, New Delhi, India Address for correspondence: Prof. Vijay Langer, Department of Plastic Surgery, Army Hospital Research and Referral, New Delhi - 110 010, India. E-mail:
[email protected]
REFERENCES 1. 2.
Majid I. Venous leg ulcers: Other treatments. Indian Dermatol Online J 2014;5:383-85. Singh N, Armstrong DG, Lipsky BA. Preventing foot ulcers in patients with diabetes. JAMA 2005;293:217-28.
Systemic therapy for leg ulcers Sir, The article venous leg ulcer: Systemic therapy by B Nair[1] was very well-written. Systemic therapy for leg ulcerations is usually only supportive to the central theme of management, as has already been brought out by the author very succinctly. Since these are adjuncts to other treatment, there is bound to be an overlap between this article and the one titled “other treatments.” The reader is urged to go through that article and the corresponding letter to the editor for a holistic view. Nutritional supplements have already been covered extensively. Of value is a quick mention of magnesium. This micronutrient functions as a cofactor in enzymes required for protein and collagen synthesis, and is used in some topical wound healing applications. However, as with zinc, its use as a supplement in the general surgical population lacks proven benefit.[2] The principle for the use of venoactive drugs in chronic venous insufficiency associated with leg ulcer is to improve venous tone Indian Dermatology Online Journal - October-December 2014 - Volume 5 - Issue 4
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Ennis WJ, Lee C, Plummer M, Meneses P. Current status of the use of modalities in wound care: Electrical stimulation and ultrasound therapy. Plast Reconstr Surg 2011;127 Suppl 1:93S-102. Ennis WJ, Foremann P, Mozen N, Massey J, Conner-Kerr T, Meneses P. Ultrasound therapy for recalcitrant diabetic foot ulcers: Results of a randomized, double-blind, controlled, multicenter study. Ostomy Wound Manage 2005;51:24-39. Kavros SJ, Miller JL, Hanna SW. Treatment of ischemic wounds with noncontact, low-frequency ultrasound: The Mayo clinic experience, 2004-2006. Adv Skin Wound Care 2007;20:221-6. Thom SR. Hyperbaric oxygen: Its mechanisms and efficacy. Plast Reconstr Surg 2011;127:131S-41. Kavalukas SL, Barbul A. Nutrition and wound healing: An update. Plast Reconstr Surg 2011;127 Suppl 1:38S-43. Rivers JM. Safety of high-level Vitamin C ingestion. Ann N Y Acad Sci 1987;498:445-54. Lee EY, Xia Y, Kim WS, Kim MH, Kim TH, Kim KJ, et al. Hypoxia-enhanced wound-healing function of adipose-derived stem cells: Increase in stem cell proliferation and up-regulation of VEGF and bFGF. Wound Repair Regen 2009;17:540-7. Ko SH, Nauta A, Wong V, Glotzbach J, Gurtner GC, Longaker MT. The role of stem cells in cutaneous wound healing: What do we really know? Plast Reconstr Surg 2011;127 Suppl 1:10S-2. Access this article online Quick Response Code: Website: www.idoj.in DOI: 10.4103/2229-5178.142563
and capillary permeability, although the precise mechanism of action of these drugs is not known. Flavonoids have venotonic properties and act on leukocytes and endothelium, resulting in decreased inflammation and permeability, thus reducing edema.[3] A meta-analysis of randomized prospective studies using micronized purified flavonoid fraction as adjunctive therapy found that venous leg ulcers healed more rapidly.[4] Pharmacotherapy with the exception of pentoxifylline does not benefit venous ulcer healing. Cilostazol (a Type III phosphodiesterase inhibitor) reduces pain and increases walking distance in intermittent claudication, but is not recommended for the treatment of arterial ulcers.[5] A Cochrane review[6] evaluated eight trials on intravenous naftidrofuryl for critical limb ischemia. The drug was not effective in reducing the symptoms. Indications for antibiotic therapy and optimal treatment regimens are ill-defined. Most published guidelines are based on expert opinion rather than evidence-based consensus. Without proven benefit and in the absence of evidence, misuse of systemic antibiotics may place patients at unnecessary risk for significant adverse side effects and may contribute to the increasing emergence of antibiotic
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Letters to the editor
resistance.[7] In chronic wound infection, systemic antibiotics should only be used for the treatment of sepsis, osteomyelitis, cellulitis, lymphangitis, abscess formation, or in the presence of other signs of invasive tissue infection. A recent Cochrane review of antibiotics for chronic venous ulcer concluded that current evidence does not support the use of systemic antibiotics to treat venous leg ulceration.[8] There is evidence that systemic antibiotics are needed only if the patient has features of sepsis in the form of fever, leukocytosis, and quantitative wound biopsy with >105 organisms per g of tissue. Currently, routine use of aspirin is without proven benefit in the treatment of leg ulcers. As has been brought out by the authors, levamisole and mesoglycans may have some role to play in healing leg ulcers. Defibrinating agents have not been shown to improve healing of ischemic ulcers or to reduce the number of amputations.[9] The use of reduction of inflammation with drugs such as doxycycline and nonsteroidal anti-inflammatory drugs, has been studied in animal models and considered for clinical use. However, no substantial clinical data are available to suggest that these agents are beneficial for accelerating the healing of chronic wounds, especially in leg ulcers. Systemic therapy may be of value in ulcers due to uncommon etiology. Prednisolone, cytosporine, intravenous gamma globulin, methotrexate, and azathioprine may be of value in vasculitic ulcers. In pyoderma gangrenosum, apart from steroids that remain the first line of treatment, immunosuppressants such as cyclosporin A, mycophenolate and azathioprine, dapsone, and cytokine blockers like tumor necrosis factor alfa monoclonal antibody. Ulcers due to necrobiosis lipoidica may respond to short-term glucocorticoid treatment with aspirin, dipyridamole, and cyclosporine showing variable results. Leg ulcers in the tropics, principally caused by infectious agents, may either be tropical phagedenic ulcer, veldt sore, Buruli ulcer or erythema induratum (Bazin’s nodular vasculitis). They may respond to systemic antibiotics if warranted.[10] A word about stem cells, the current rage, merits special mention. Systemic injections of granulocyte colony-stimulating factor can mobilize stem cells from bone marrow into the peripheral blood and then to the wound site. This may increase accumulation of collagen and may promise excellent results in terms of wound bed preparation and healing, especially in the leg ulcer.[11] Numerous animal studies and a few pilot studies in human wounds have shown that bone marrow-mesenchymal stem cells (MSCs) can augment wound closure. Still, the primary contribution of MSCs to cutaneous regeneration and the long-term systemic effects of MSCs are yet to be established. In addition, we need to determine whether other types of stem/progenitor cells will be more effective.
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Therefore, more randomized controlled clinical trials need to be undertaken.[12] Systemic therapy for leg ulcers can at best be considered adjunctive. The wound care provider is cautioned to determine possible adverse effects of these drugs conscientiously weigh the risk-benefit ratio and act judiciously.
Vijay Langer Department of Plastic Surgery, Army Hospital Research and Referral, New Delhi, India Address for correspondence: Prof. Vijay Langer, Department of Plastic Surgery, Army Hospital Research and Referral, New Delhi - 110 010, India. E-mail:
[email protected]
REFERENCES 1. 2. 3. 4.
5. 6. 7. 8. 9.
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Nair B. Venous leg ulcer: Systemic therapy. Indian Dermatol Online J 2014;5:374-7. Janis JE, Harrison B. Wound healing: Part I. Basic science. Plast Reconstr Surg 2014;133:199e-207. Raffetto JD, Marston WA. Venous ulcer: What is new? Plast Reconstr Surg 2011;127 Suppl 1:279S-88. Coleridge-Smith P, Lok C, Ramelet AA. Venous leg ulcer: Ameta-analysis of adjunctive therapy with micronized purified flavonoid fraction. Eur J Vasc Endovasc Surg 2005;30:198-208. Crane JS, Cheshire NJ. Chronic ulceration of the leg. Surgery 2007;26:13-6. Smith FB, Bradbury AW, Fowkes FG. Intravenous naftidrofuryl for critical limb ischaemia. Cochrane Database Syst Rev 2000:CD002070. Siddiqui AR, Bernstein JM. Chronic wound infection: Facts and controversies. Clin Dermatol 2010;28:519-26. O’Meara S, Al-Kurdi D, Ovington LG. Antibiotics and antiseptics for venous leg ulcers. Cochrane Database Syst Rev 2008:CD003557. Norgren L, Hiatt WR, Dormandy JA, Nehler MR, Harris KA, Fowkes FG, et al. Inter-Society Consensus for the Management of Peripheral Arterial Disease (TASC II). Eur J Vasc Endovasc Surg 2007;33 Suppl 1:S1-75. Gottrup F, Karlsmark T. Leg ulcers: Uncommon presentations. Clin Dermatol 2005;23:601-11. Iwamoto S, Lin X, Ramirez R, Carson P, Fiore D, Goodrich J, et al. Bone marrow cell mobilization by the systemic use of granulocyte colony-stimulating factor (GCSF) improves wound bed preparation. Int J Low Extrem Wounds 2013;12:256-64. Dabiri G, Heiner D, Falanga V. The emerging use of bone marrow-derived mesenchymal stem cells in the treatment of human chronic wounds. Expert Opin Emerg Drugs 2013;18:405-19.
Access this article online Quick Response Code: Website: www.idoj.in DOI: 10.4103/2229-5178.142565
Indian Dermatology Online Journal - October-December 2014 - Volume 5 - Issue 4
