CASE REPORT
Uncommon Responses of Segmental Vitiligo to MelanocyteKeratinocyte Transplantation Procedure Prescilia Isedeh, Ahmed Al Issa, Henry W. Lim, Smita S. Mulekar, and Sanjeev V. Mulekar Background: Patients with segmental vitiligo (SV), unlike those with nonsegmental vitiligo (NSV), have a more predictable course and are more responsive to surgery. Objective: To report 10 patients with SV treated with the melanocyte-keratinocyte transplantation procedure (MKTP), who responded with unusual responses not previously reported in the literature. Methods: This is a retrospective, observational study that reports 10 patients with SV who underwent the MKTP between May 2003 and May 2012. Results: Two patients had successful repigmentation after split-thickness skin grafting after failure of the MKTP. Two patients developed a hypopigmented ring at a margin of the MKTP-treated area. One patient had complete repigmentation after a second MKTP. Two patients developed koebnerization of the recipient site. Three patients developed new vitiligo patches in previously unaffected areas after the MKTP. Conclusions: Uncommon and even suboptimal responses can occur following the MKTP in SV patients. There is a need for studies to provide better understanding and outcomes for SV patients undergoing the MKTP. Contexte: Les patients atteints de vitiligo segmentaire (VS) connaissent une e´volution plus pre´visible et une re´action plus importante a` la chirurgie que ceux qui sont atteints de vitiligo non segmentaire. Objectif: L’article vise a` faire e´tat de 10 patients atteints de VS et traite´s par une transplantation de me´lanocytes avec ke´ratinocytes (TMK), qui ont pre´sente´ des re´actions inhabituelles, jamais signale´es dans la documentation. Me´thode: Il s’agit d’une e´tude d’observation re´trospective, qui expose le cas de 10 patients atteints de VS et traite´s par une TMK, entre mai 2003 et mai 2012. Re´sultats: Une repigmentation re´ussie s’est produite apre`s une greffe de demi-e´paisseur pratique´e a` la suite de l’e´chec d’une TMK chez deux patients. Un anneau hypopigmente´ est apparu sur un bord de la re´gion traite´e par une TMK chez deux autres patients. Une repigmentation comple`te s’est produite apre`s une deuxie`me TMK chez un patient. Le phe´nome`ne de Ko¨bner a e´te´ observe´ au lit re´cepteur de la transplantation chez deux patients. Enfin, de nouvelles plaques de vitiligo sont apparues dans des re´gions auparavant e´pargne´es, apre`s une TMK, chez trois autres patients. Conclusions: Des re´actions inhabituelles et meˆme sous-optimales a` la TMK peuvent se produire chez des patients atteints de VS. Aussi faudrait-il poursuivre les recherches afin de mieux comprendre l’affection et de mieux pre´voir les re´sultats de la TMK chez les patients atteints de VS.
EGMENTAL VITILIGO (SV) can be classified separately from ‘‘vitiligo.’’ The latter was initially used as an umbrella term for all nonsegmental forms of vitiligo (NSV). On the other hand, mixed vitiligo is a separate entity in which segmental and nonsegmental vitiligo are present in the same patient.1 SV usually presents early in life, spreads rapidly within the segment, and then stabilizes; once established, further progression is rare or does not occur.1–3 Leukotrichia is more commonly associated with SV than with NSV.3,4 Unlike NSV, the course of SV is more predictable. Treatment of SV consists of topical therapies and phototherapy. If medical treatment is unsatisfactory,
S
From the Multicultural Dermatology Center, Department of Dermatology, Henry Ford Hospital, Detroit, MI; National Center for Vitiligo & Psoriasis, Riyadh, Saudi Arabia; and Shetty Nursing Home, Mumbai, India. Address reprint requests to: Sanjeev V. Mulekar, MD, National Center for Vitiligo & Psoriasis, PO Box 300320, Riyadh 11372, Saudi Arabia; e-mail: [email protected].
DOI 10.2310/7750.2014.14061 # 2014 Canadian Dermatology Association
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surgical treatment should be considered.5 The surgical therapies can result in either complete or partial repigmentation, which might in some instances warrant repeat transplant surgery. Surgical procedures consist of tissue grafting such as split-thickness skin grafts (STSGs), punch grafts/minigraft, epidermal grafts/blister roof grafts, and cellular grafting such as cultured and noncultured cellular transplantation, also known as the melanocyte-keratinocyte transplantation procedure (MKTP).6–10 The STSG technique has the highest pooled success rate of 87%, whereas blister grafting has repigmentation rates ranging from 80 to 90%.11–14 The percentage of repigmentation reported with cultured techniques ranges from 75 to 84% in patients with SV and 30 to 54% in those with NSV.15,16 From the experience of one of the authors (S.V.M.), which has been published, approximately 85% of patients with SV who had the MKTP achieved greater than 95% repigmentation, with a low recurrence rate occurring in these vitiligo patients.6 Thus, SV patients are ideal candidates for surgical treatment, whereas patients with NSV, as reported by Mulekar and Huggins and colleagues, have less successful response rates, with only approximately 55% achieving greater than 95% repigmentation, and the recurrence rate was more than for those with SV after undergoing the MKTP.6,17,18 However, there have been several observations in patients with SV that show deviation from the previously described predictable course. The history and outcomes after MKTP of these 10 patients are described as individual cases (Table 1).
Methods This is a retrospective case series of 10 patients with SV who were treated with the MKTP and other surgical techniques between May 2003 and May 2012 and who responded with unusual and suboptimal responses. These patients were treated by one of the authors (S.V.M.) at his vitiligo clinic in Mumbai, India. All of these patients,
retrospectively, signed a consent form to agree to have their cases included in this study. The MKTP begins with the preparation of cellular suspension. Then a small shaved skin sample, up to onetenth the size of the recipient area, is incubated, and cells are mechanically separated using trypsin–ethylenediaminetetraacetic acid (EDTA) solution and then centrifuged to prepare epidermal cell suspension, which is placed onto the recipient area. The technique of the MKTP has been described in detail.19–22 For the STSG technique, the grafts of epidermis along with a portion of dermis harvested most commonly from the gluteal region or thigh are placed on the depigmented recipient site. The STSG technique has been described in detail.23,24 Punch grafting is performed using a 1.5 to 2 mm punch, and the recipient chambers are punched out on or very close to the border of the lesion at a distance of 5 to 8 mm from each other and at a depth of 2 to 3 mm. Full-thickness punch grafts are harvested very close to each other from the donor site (gluteal region/upper thigh) using a biopsy punch of the same size as the recipient site. The punch graft technique has been described in detail.25–28
Case Reports Case 1: Complete Failure of Repigmentation with MKTP and Successful Repigmentation with STSG This patient was a male in his late twenties with a 3-year history of SV affecting the left aspect of his lower lip to his neck. The areas were clinically stable for 2 years prior to his first unsuccessful MKTP in August 2011. In February 2012, the patient received 12 1.5 mm punch grafts as a minigraft test and STSG to his upper chin. In August 2012, the patient received STSG to the remaining lower aspect of his chin and affected neck and after 1 month was found to have a greater than 75% repigmentation. In January 2013, more than 90% repigmentation was observed.
Table 1. Overview of Cases Case No. 1 2 3 4 and 5 6 to 8 9 and 10
MKTP Repigmentation
STSG
Complete failure Successful repigmentation Partial Successful repigmentation in remaining area Complete failure, but complete repigmentation with repeat MKTP Koebnerization of recipient site New depigmented patches in previously unattached area in the same segment Hypopigmented ring at margin
MKTP 5 melanocyte-keratinocyte transplantation procedure; STSG 5 split-thickness skin grafting.
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Case 2: Partial Repigmentation with MKTP and Successful Repigmentation in the Remaining Area with STSG This patient was a male in his late thirties with a 5-year history of mixed vitiligo (segmental and focal) affecting the right aspect of his scalp, forehead, temporal area, upper eyelid, and right foot, which was 76 cm2 in total area. The patient was clinically stable for 4 years before undergoing MKTP in June 2010. Post–MKTP, the patient showed 42% repigmentation. In January 2011, the patient underwent a second MKTP, for which a total area of 44 cm2 was treated, but there was no improvement. In May 2011, the patient underwent STSG on the same 44 cm2 area. In February 2012, he underwent a second STSG for the remaining affected areas. In April 2012, the patient was noted to have almost complete repigmentation. Case 3: Complete Repigmentation with Repeat MKTP This patient was a male in his thirties with a 2-year history of mixed vitiligo (segmental and focal) affecting his left periorbital area and right forearm. The total area affected was 32.75 cm2. The patient underwent the MKTP in October 2007 after 1 year of clinical stability. In January 2008, the patch on the right forearm was completely repigmented, with no repigmentation of the periorbital lesion. In June 2008, the patient underwent a second MTKP for the left periorbital area, and during his 2-month follow-up visit, he was found to have excellent results. By May 2009, the patient had more than 95% repigmentation in the periorbital area. Cases 4 and 5: Koebnerization of Recipient Site in Patients Treated with MKTP Case 4 was a male in his twenties with a 5-year history of SV affecting the left aspect of his lower back. In May 2010,
the patient underwent the MKTP for the entire affected area, including hypopigmented and dyschromic areas, after 4 years of clinical stability. During the patient’s 3-month follow-up, a Wood’s lamp examination revealed pigmentation of the treated areas and mottled depigmentation and hyperpigmentation of the donor site. When the patient was seen in March 2011, he had experienced gradual repigmentation of the donor site. As of September 2012, the patient continues to have repigmentation without any treatment. Case 5 was a male in his late twenties with a 14-year history of SV affecting the left aspect of the perioral area, lip, chin, and neck along the jawbone (Figure 1A). The patient underwent the MKTP on May 2012 for the entire depigmented, hypopigmented, and mottled areas after 13 years of clinical stability. During the patient’s 2-month follow-up, there were new depigmented areas within the affected, treated segment (Figure 1B). The patient was seen 1 month later, and the depigmented areas began repigmenting. As of October 2012, the patient continued to have repigmentation, but two new depigmented patches have still not repigmented (Figure 1C). Cases 6 to 8: New Patches in Previously Unaffected Area after MKTP but Located in Same Segment Case 6 was a male in his late twenties with a 1-year history of SV affecting the medial aspect of his left eyebrow, left nasal bridge, and left malar prominence. The total area affected was 30 cm2. The patient underwent MKTP for the entire area after 6 months of clinical stability. During a 4-month follow-up visit, the patient was found to have a 6 cm2 of repigmented areas on the left aspect of his nose and the medial aspect of his eyebrow. He was also noted to have an expansion of depigmentation on the bridge of his nose and malar prominence and new depigmented patches
Figure 1. Case 5. A, Before the melanocyte-keratinocyte transplantation procedure (MKTP). B, Two months post-MKTP with koebnerized new lesions. C, Six months post-MKTP. Canadian Dermatology Association | Journal of Cutaneous Medicine and Surgery, Vol 19, No 2 (March/April), 2015: pp 177–181
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on the left nasolabial area. The patient was advised to undergo repeat MKTP. Case 7 was a teenage male with a 4-year history of SV affecting the right nasal bridge and below the right lower eyelid. The patient underwent MKTP in June 2007 after 3 years of clinical stability. He was seen in April 2008 and was found to have new lesions in other areas but in the same segment. In November 2008, these new lesions were noted to have a 30% improvement. Current medications include prednisolone and pimecrolimus cream. Case 8 was a female in her twenties with an 8-year history of SV affecting the left aspect of her forehead, lower eyelid, nose, and malar cheek. The total area affected was 29.50 cm2. The patient underwent the MKTP in August 2006 after 7 years of clinical stability. In March 2007, the patient underwent repeat MKTP of the 8.50 cm2 affected area. She had greater than 70% repigmentation after repeat MKTP in this area. The patient had three more MKTPs, between May 2008 and August 2011, without any improvement. Cases 9 and 10: Hypopigmented Ring at Margin of MKTP-Treated Areas Case 9 was a teenage female with a 3-year history of SV affecting the left aspect of her lower nose and cheek. The patient underwent MKTP in May 2003 after 2 years of clinical stability. By November 2003, the patient had greater than 90% repigmentation. In March 2004, repeat MKTP was done for the borders of the previously treated area. In February 2005, the patient had a third MKTP for a hypopigmented ring at the margins. As of December 2006, there had been no change in the hypopigmented ring. Case 10 was a teenage female with an 11-year history of SV affecting the left aspect of her chin, her neck, and behind her left ear who was treated with the MKTP in July 2007 after 10 years of clinical stability. The patient was found to have a hypopigmented ring at the margin. She underwent two more MKTPs, between May and November 2008, for the hypopigmented rings. In February 2011, the patient underwent an epidermal graft to treat three hypopigmented rings. During follow-up of the grafts, there had been no change in the hypopigmented ring.
Discussion and Conclusion The etiology of SV is elusive. SV and NSV are part of the same disease spectrum, but SV could have a polygenic background as well.29 It is difficult to fully explain the 180
suboptimal results in these clinically stable SV patients based on present concepts of the pathogenesis of the disease. It is possible that trypsinization of the transplanted cell may have a damaging effect on these cells. The morphology and immunologic competence of cells in suspension have not been studied. There is a need to study these aspects to improve the MKTP technique. Earlier it was argued that replacement of genetically abnormal cells and concomitant absence of autoinflammation/autoimmunity is responsible for good and long-term stabilization of epidermal cell suspension in SV compared to NSV. However, our observations support the notion that other triggering factors, such as a neurogenic and autoinflammatory component extending locally beyond the area demarcated by developmental lines, cannot be ruled out.30 Additionally, it has been suggested that the CD8 + melanocyte–specific T cell–mediated immune response as observed in NSV plays a role in SV with associated halo nevi.31 It is possible that this immune process may not affect the whole segment, but it may be restricted to part of the segment. Clinical stability does not exclude an active autoimmune process. Transplanted melanocytes may have the potential to attract T cells, which in turn destroy the melanocytes. Overall, SV may have an overlap with NSV at the clinical, genetic, and etiopathologic levels and may not be a separate entity.32 SV is the least researched and least understood entity, and its pathogenesis remains elusive. Overall, further basic science and clinical research studies are necessary for better understanding of the pathogenesis of SV and to provide better outcomes for vitiligo patients undergoing the MKTP.
Acknowledgments Financial disclosure of authors and reviewers: None reported.
References 1. Ezzedine K, Lim HW, Suzuki T, et al. Vitiligo Global Issues Consensus Conference Panelists. Revised classification/nomenclature of vitiligo and related issues: the Vitiligo Global Issues Consensus Conference. Pigment Cell Melanoma Res 2012;25:E1– 13, doi:10.1111/j.1755-148X.2012.00997.x. 2. Falabella R. Repigmentation of segmental vitiligo by autologous minigrafting. J Am Acad Dermatol 1983;9:514–21, doi:10.1016/ S0190-9622(83)70162-3. 3. Hann SK, Lee HJ. Segmental vitiligo: clinical findings in 208 patients. J Am Acad Dermatol 1996;35:671–4, doi:10.1016/S01909622(96)90718-5. 4. Lee DY, Park JH, Lee JH, et al. Is segmental vitiligo always associated with leukotrichia? Examination with a digital portable microscope. Int J Dermatol 2009;48:1262–70.
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5. Lee DY, Choi SC, Lee DY. A proposal for the treatment guideline in segmental vitiligo. Int J Dermatol 2012;51:1274–5. 6. Mulekar SV. Long-term follow-up study of segmental and focal treated by autologous, noncultured melanocytes-keratinocyte cell transplantation. Arch Dermatol 2004;140:1211–5. 7. Mulekar SV, Al Eisa A, Delvi MB, et al. Childhood vitiligo: a longterm study of localized vitiligo treated by noncultured cellular grafting. Pediatr Dermatol 2010;27:132–6, doi:10.1111/j.15251470.2009.00978.x. 8. Lee DY, Lee KJ, Choi SC, et al. Segmental vitiligo treated by the combination of epidermal grafting and systemic corticosteroids. Dermatol Surg 2010;36:575–6, doi:10.1111/j.1524-4725.2010. 01506.x. 9. Lee DY, Park JH, Lee JH, et al. Surgical treatment is indicated in long-duration segmental vitiligo. Dermatol Surg 2010;36:568–9, doi:10.1111/j.1524-4725.2010.01501.x. 10. Lee DY, Park JH, Lee JH, et al. Recurrence of segmental vitiligo after epidermal grafting does not involve epidermal grafting area. Clin Exp Dermatol 2009;35:205–6, doi:10.1111/j.1365-2230.2009.03395.x. 11. Njoo MD, Westerhof W, Bos JD, et al. A systematic review of autologous transplantation methods in vitiligo. Arch Dermatol 1998;134:1543–9. 12. Ko WC, Chen YF. Suction blister epidermal grafts combined with CO2 laser superficial ablation as a good method for treating smallsized vitiligo. Dermatol Surg 2009;35:601–6, doi:10.1111/j.15244725.2009.01098.x. 13. Koga M. Epidermal grafting using the tops of suction blisters in the treatment of vitiligo. Arch Dermatol 1988;124:1656–8, doi:10.1001/ archderm.1988.01670110016003. 14. Gupta S, Shroff S, Gupta S. Modified technique of suction blistering for epidermal grafting in vitiligo. Int J Dermatol 1999;38:306–9. 15. Chen Yu Fu, Yang PU, Hu DH, et al. Treatment of vitiligo by transplantation of cultured pure melanocytes suspension–analysis of 120 cases. J Am Arch Dermatol 2004;51:68–74, doi:10.1016/ j.jaad.2003.12.013. 16. Piangiani E, Risulo M, Andreassi A, et al. Autologous epidermal cultures and narrow-band ultraviolet B in the surgical treatment of vitiligo. Dermatol Surg 2005;31:155–9, doi:10.1097/00042728200502000-00006. 17. Mulekar SV. Melanocyte-keratinocyte cell transplantation for stable vitiligo. Int J Dermatol 2003;4:132–6. 18. Huggins RH, Henderson MD, Mulekar SV, et al. Melanocytekeratinocyte transplantation procedure in the treatment of vitiligo: the experience of an academic medical center in the United States. J Am Acad Dermatol 2012;66:785–93. [Epub 2011 Aug 23], doi: 10.1016/j.jaad.2011.05.002.
19. Falabella R. History and chronology of development of surgical therapies for vitiligo. In: Gupta S, Olsson MJ, Kanwar AJ, Ortonne JP, editors. Surgical management of vitiligo. 1st ed. Oxford (UK): Blackwell Publishing; 2007. p. 41–8. 20. Olsson MJ, Juhlin L. Leucoderma treated by transplantation of a basal cell layer enriched suspension. Br J Dermatol 1998;138:644–8. 21. van Geel N, Ongeane K, De Mil M, Naeyaert JM. Modified technique of autologous noncultured epidermal cell transplantation for repigmenting vitiligo: a pilot study. Dermatol Surg 2001;27:873–6. 22. Mulekar SV, Al Issa A, Al Eisa A. Treatment of vitiligo on difficultto-treat sites using autologous noncultured cellular grafting. Dermatol Surg 2009;35:66–71. 23. Kahn AM, Cohen MJ. Repigmentation in vitiligo patients. Melanocyte transfer via ultra-thin grafts. Dermatol Surg 1998;24: 365–7. 24. Kahn AM, Cohen MJ. Vitiligo: treatment by dermabrasion and epithelial sheet grafting. J Am Acad Dermatol 1995;33:646–8, doi:10.1016/0190-9622(95)91287-8. 25. Falabella R. Surgical approaches for stable vitiligo. Dermatol Surg 2005;32:1277–84, doi:10.1097/00042728-200510000-00003. 26. Falabella R. Treatment of localized vitiligo by autologous minigrafting. Arch Dermatol 1988;124:1649–55, doi:10.1001/archderm.1988.01670110009002. 27. Boersma B, Westerhof W, Bos JD. Repigmentation in vitiligo vulgaris by autologous minigrafting: results in nineteen patients. J Am Acad Dermatol 1995;33:990–5, doi:10.1016/0190-9622(95) 90292-9. 28. Malakar S, Dhar S. Treatment of stable and recalcitrant vitiligo by autologous miniature punch grafting: a prospective study of 1,000 patients. Dermatology 1999;198:133–9, doi:10.1159/000018089. 29. van Geel N, De Lille S, Vandehaute S, et al. Different phenotypes of segmental vitiligo based on a clinical observational study. J Eur Acad Dermatol Venereol 2011;25:673–8, doi:10.1111/j.1468-3083. 2010.03847.x. 30. Taieb A, Morice-Picard F, Jouary T, et al. Segmental vitiligo as the possible expression of cutaneous somatic mosaicism: implications for common non-segmental vitiligo. Pigment Cell Melanoma Res 2008;21:646–52, doi:10.1111/j.1755-148X.2008.00511.x. 31. van Geel N, Mollet IG, De Schepper S. First histopathological and immunophenotypic analysis of early dynamic events in patients with segmental vitiligo associated with halo nevi. Pigment Cell Melanoma Res 2010;23:375–84, doi:10.1111/j.1755-148X.2010.00703.x. 32. Van Geel N, Mollet I, Brochez L, et al. New insights in segmental vitiligo: case report and review of theories. Br J Dermatol 2012;166: 240–6.
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Uncommon Responses of Segmental Vitiligo to MelanocyteKeratinocyte Transplantation Procedure Prescilia Isedeh, Ahmed Al Issa, Henry W. Lim, Smita S. Mulekar, and Sanjeev V. Mulekar Background: Patients with segmental vitiligo (SV), unlike those with nonsegmental vitiligo (NSV), have a more predictable course and are more responsive to surgery. Objective: To report 10 patients with SV treated with the melanocyte-keratinocyte transplantation procedure (MKTP), who responded with unusual responses not previously reported in the literature. Methods: This is a retrospective, observational study that reports 10 patients with SV who underwent the MKTP between May 2003 and May 2012. Results: Two patients had successful repigmentation after split-thickness skin grafting after failure of the MKTP. Two patients developed a hypopigmented ring at a margin of the MKTP-treated area. One patient had complete repigmentation after a second MKTP. Two patients developed koebnerization of the recipient site. Three patients developed new vitiligo patches in previously unaffected areas after the MKTP. Conclusions: Uncommon and even suboptimal responses can occur following the MKTP in SV patients. There is a need for studies to provide better understanding and outcomes for SV patients undergoing the MKTP. Contexte: Les patients atteints de vitiligo segmentaire (VS) connaissent une e´volution plus pre´visible et une re´action plus importante a` la chirurgie que ceux qui sont atteints de vitiligo non segmentaire. Objectif: L’article vise a` faire e´tat de 10 patients atteints de VS et traite´s par une transplantation de me´lanocytes avec ke´ratinocytes (TMK), qui ont pre´sente´ des re´actions inhabituelles, jamais signale´es dans la documentation. Me´thode: Il s’agit d’une e´tude d’observation re´trospective, qui expose le cas de 10 patients atteints de VS et traite´s par une TMK, entre mai 2003 et mai 2012. Re´sultats: Une repigmentation re´ussie s’est produite apre`s une greffe de demi-e´paisseur pratique´e a` la suite de l’e´chec d’une TMK chez deux patients. Un anneau hypopigmente´ est apparu sur un bord de la re´gion traite´e par une TMK chez deux autres patients. Une repigmentation comple`te s’est produite apre`s une deuxie`me TMK chez un patient. Le phe´nome`ne de Ko¨bner a e´te´ observe´ au lit re´cepteur de la transplantation chez deux patients. Enfin, de nouvelles plaques de vitiligo sont apparues dans des re´gions auparavant e´pargne´es, apre`s une TMK, chez trois autres patients. Conclusions: Des re´actions inhabituelles et meˆme sous-optimales a` la TMK peuvent se produire chez des patients atteints de VS. Aussi faudrait-il poursuivre les recherches afin de mieux comprendre l’affection et de mieux pre´voir les re´sultats de la TMK chez les patients atteints de VS.
EGMENTAL VITILIGO (SV) can be classified separately from ‘‘vitiligo.’’ The latter was initially used as an umbrella term for all nonsegmental forms of vitiligo (NSV). On the other hand, mixed vitiligo is a separate entity in which segmental and nonsegmental vitiligo are present in the same patient.1 SV usually presents early in life, spreads rapidly within the segment, and then stabilizes; once established, further progression is rare or does not occur.1–3 Leukotrichia is more commonly associated with SV than with NSV.3,4 Unlike NSV, the course of SV is more predictable. Treatment of SV consists of topical therapies and phototherapy. If medical treatment is unsatisfactory,
S
From the Multicultural Dermatology Center, Department of Dermatology, Henry Ford Hospital, Detroit, MI; National Center for Vitiligo & Psoriasis, Riyadh, Saudi Arabia; and Shetty Nursing Home, Mumbai, India. Address reprint requests to: Sanjeev V. Mulekar, MD, National Center for Vitiligo & Psoriasis, PO Box 300320, Riyadh 11372, Saudi Arabia; e-mail: [email protected].
DOI 10.2310/7750.2014.14061 # 2014 Canadian Dermatology Association
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surgical treatment should be considered.5 The surgical therapies can result in either complete or partial repigmentation, which might in some instances warrant repeat transplant surgery. Surgical procedures consist of tissue grafting such as split-thickness skin grafts (STSGs), punch grafts/minigraft, epidermal grafts/blister roof grafts, and cellular grafting such as cultured and noncultured cellular transplantation, also known as the melanocyte-keratinocyte transplantation procedure (MKTP).6–10 The STSG technique has the highest pooled success rate of 87%, whereas blister grafting has repigmentation rates ranging from 80 to 90%.11–14 The percentage of repigmentation reported with cultured techniques ranges from 75 to 84% in patients with SV and 30 to 54% in those with NSV.15,16 From the experience of one of the authors (S.V.M.), which has been published, approximately 85% of patients with SV who had the MKTP achieved greater than 95% repigmentation, with a low recurrence rate occurring in these vitiligo patients.6 Thus, SV patients are ideal candidates for surgical treatment, whereas patients with NSV, as reported by Mulekar and Huggins and colleagues, have less successful response rates, with only approximately 55% achieving greater than 95% repigmentation, and the recurrence rate was more than for those with SV after undergoing the MKTP.6,17,18 However, there have been several observations in patients with SV that show deviation from the previously described predictable course. The history and outcomes after MKTP of these 10 patients are described as individual cases (Table 1).
Methods This is a retrospective case series of 10 patients with SV who were treated with the MKTP and other surgical techniques between May 2003 and May 2012 and who responded with unusual and suboptimal responses. These patients were treated by one of the authors (S.V.M.) at his vitiligo clinic in Mumbai, India. All of these patients,
retrospectively, signed a consent form to agree to have their cases included in this study. The MKTP begins with the preparation of cellular suspension. Then a small shaved skin sample, up to onetenth the size of the recipient area, is incubated, and cells are mechanically separated using trypsin–ethylenediaminetetraacetic acid (EDTA) solution and then centrifuged to prepare epidermal cell suspension, which is placed onto the recipient area. The technique of the MKTP has been described in detail.19–22 For the STSG technique, the grafts of epidermis along with a portion of dermis harvested most commonly from the gluteal region or thigh are placed on the depigmented recipient site. The STSG technique has been described in detail.23,24 Punch grafting is performed using a 1.5 to 2 mm punch, and the recipient chambers are punched out on or very close to the border of the lesion at a distance of 5 to 8 mm from each other and at a depth of 2 to 3 mm. Full-thickness punch grafts are harvested very close to each other from the donor site (gluteal region/upper thigh) using a biopsy punch of the same size as the recipient site. The punch graft technique has been described in detail.25–28
Case Reports Case 1: Complete Failure of Repigmentation with MKTP and Successful Repigmentation with STSG This patient was a male in his late twenties with a 3-year history of SV affecting the left aspect of his lower lip to his neck. The areas were clinically stable for 2 years prior to his first unsuccessful MKTP in August 2011. In February 2012, the patient received 12 1.5 mm punch grafts as a minigraft test and STSG to his upper chin. In August 2012, the patient received STSG to the remaining lower aspect of his chin and affected neck and after 1 month was found to have a greater than 75% repigmentation. In January 2013, more than 90% repigmentation was observed.
Table 1. Overview of Cases Case No. 1 2 3 4 and 5 6 to 8 9 and 10
MKTP Repigmentation
STSG
Complete failure Successful repigmentation Partial Successful repigmentation in remaining area Complete failure, but complete repigmentation with repeat MKTP Koebnerization of recipient site New depigmented patches in previously unattached area in the same segment Hypopigmented ring at margin
MKTP 5 melanocyte-keratinocyte transplantation procedure; STSG 5 split-thickness skin grafting.
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Case 2: Partial Repigmentation with MKTP and Successful Repigmentation in the Remaining Area with STSG This patient was a male in his late thirties with a 5-year history of mixed vitiligo (segmental and focal) affecting the right aspect of his scalp, forehead, temporal area, upper eyelid, and right foot, which was 76 cm2 in total area. The patient was clinically stable for 4 years before undergoing MKTP in June 2010. Post–MKTP, the patient showed 42% repigmentation. In January 2011, the patient underwent a second MKTP, for which a total area of 44 cm2 was treated, but there was no improvement. In May 2011, the patient underwent STSG on the same 44 cm2 area. In February 2012, he underwent a second STSG for the remaining affected areas. In April 2012, the patient was noted to have almost complete repigmentation. Case 3: Complete Repigmentation with Repeat MKTP This patient was a male in his thirties with a 2-year history of mixed vitiligo (segmental and focal) affecting his left periorbital area and right forearm. The total area affected was 32.75 cm2. The patient underwent the MKTP in October 2007 after 1 year of clinical stability. In January 2008, the patch on the right forearm was completely repigmented, with no repigmentation of the periorbital lesion. In June 2008, the patient underwent a second MTKP for the left periorbital area, and during his 2-month follow-up visit, he was found to have excellent results. By May 2009, the patient had more than 95% repigmentation in the periorbital area. Cases 4 and 5: Koebnerization of Recipient Site in Patients Treated with MKTP Case 4 was a male in his twenties with a 5-year history of SV affecting the left aspect of his lower back. In May 2010,
the patient underwent the MKTP for the entire affected area, including hypopigmented and dyschromic areas, after 4 years of clinical stability. During the patient’s 3-month follow-up, a Wood’s lamp examination revealed pigmentation of the treated areas and mottled depigmentation and hyperpigmentation of the donor site. When the patient was seen in March 2011, he had experienced gradual repigmentation of the donor site. As of September 2012, the patient continues to have repigmentation without any treatment. Case 5 was a male in his late twenties with a 14-year history of SV affecting the left aspect of the perioral area, lip, chin, and neck along the jawbone (Figure 1A). The patient underwent the MKTP on May 2012 for the entire depigmented, hypopigmented, and mottled areas after 13 years of clinical stability. During the patient’s 2-month follow-up, there were new depigmented areas within the affected, treated segment (Figure 1B). The patient was seen 1 month later, and the depigmented areas began repigmenting. As of October 2012, the patient continued to have repigmentation, but two new depigmented patches have still not repigmented (Figure 1C). Cases 6 to 8: New Patches in Previously Unaffected Area after MKTP but Located in Same Segment Case 6 was a male in his late twenties with a 1-year history of SV affecting the medial aspect of his left eyebrow, left nasal bridge, and left malar prominence. The total area affected was 30 cm2. The patient underwent MKTP for the entire area after 6 months of clinical stability. During a 4-month follow-up visit, the patient was found to have a 6 cm2 of repigmented areas on the left aspect of his nose and the medial aspect of his eyebrow. He was also noted to have an expansion of depigmentation on the bridge of his nose and malar prominence and new depigmented patches
Figure 1. Case 5. A, Before the melanocyte-keratinocyte transplantation procedure (MKTP). B, Two months post-MKTP with koebnerized new lesions. C, Six months post-MKTP. Canadian Dermatology Association | Journal of Cutaneous Medicine and Surgery, Vol 19, No 2 (March/April), 2015: pp 177–181
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on the left nasolabial area. The patient was advised to undergo repeat MKTP. Case 7 was a teenage male with a 4-year history of SV affecting the right nasal bridge and below the right lower eyelid. The patient underwent MKTP in June 2007 after 3 years of clinical stability. He was seen in April 2008 and was found to have new lesions in other areas but in the same segment. In November 2008, these new lesions were noted to have a 30% improvement. Current medications include prednisolone and pimecrolimus cream. Case 8 was a female in her twenties with an 8-year history of SV affecting the left aspect of her forehead, lower eyelid, nose, and malar cheek. The total area affected was 29.50 cm2. The patient underwent the MKTP in August 2006 after 7 years of clinical stability. In March 2007, the patient underwent repeat MKTP of the 8.50 cm2 affected area. She had greater than 70% repigmentation after repeat MKTP in this area. The patient had three more MKTPs, between May 2008 and August 2011, without any improvement. Cases 9 and 10: Hypopigmented Ring at Margin of MKTP-Treated Areas Case 9 was a teenage female with a 3-year history of SV affecting the left aspect of her lower nose and cheek. The patient underwent MKTP in May 2003 after 2 years of clinical stability. By November 2003, the patient had greater than 90% repigmentation. In March 2004, repeat MKTP was done for the borders of the previously treated area. In February 2005, the patient had a third MKTP for a hypopigmented ring at the margins. As of December 2006, there had been no change in the hypopigmented ring. Case 10 was a teenage female with an 11-year history of SV affecting the left aspect of her chin, her neck, and behind her left ear who was treated with the MKTP in July 2007 after 10 years of clinical stability. The patient was found to have a hypopigmented ring at the margin. She underwent two more MKTPs, between May and November 2008, for the hypopigmented rings. In February 2011, the patient underwent an epidermal graft to treat three hypopigmented rings. During follow-up of the grafts, there had been no change in the hypopigmented ring.
Discussion and Conclusion The etiology of SV is elusive. SV and NSV are part of the same disease spectrum, but SV could have a polygenic background as well.29 It is difficult to fully explain the 180
suboptimal results in these clinically stable SV patients based on present concepts of the pathogenesis of the disease. It is possible that trypsinization of the transplanted cell may have a damaging effect on these cells. The morphology and immunologic competence of cells in suspension have not been studied. There is a need to study these aspects to improve the MKTP technique. Earlier it was argued that replacement of genetically abnormal cells and concomitant absence of autoinflammation/autoimmunity is responsible for good and long-term stabilization of epidermal cell suspension in SV compared to NSV. However, our observations support the notion that other triggering factors, such as a neurogenic and autoinflammatory component extending locally beyond the area demarcated by developmental lines, cannot be ruled out.30 Additionally, it has been suggested that the CD8 + melanocyte–specific T cell–mediated immune response as observed in NSV plays a role in SV with associated halo nevi.31 It is possible that this immune process may not affect the whole segment, but it may be restricted to part of the segment. Clinical stability does not exclude an active autoimmune process. Transplanted melanocytes may have the potential to attract T cells, which in turn destroy the melanocytes. Overall, SV may have an overlap with NSV at the clinical, genetic, and etiopathologic levels and may not be a separate entity.32 SV is the least researched and least understood entity, and its pathogenesis remains elusive. Overall, further basic science and clinical research studies are necessary for better understanding of the pathogenesis of SV and to provide better outcomes for vitiligo patients undergoing the MKTP.
Acknowledgments Financial disclosure of authors and reviewers: None reported.
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