J Cutan Pathol 2014: 41: 771–774 doi: 10.1111/cup.12374 John Wiley & Sons. Printed in Singapore
© 2014 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd
Journal of Cutaneous Pathology
Foreign body giant cell reaction to tarSys™ xenograft Objective A foreign body giant cell (FBGC) reaction may occur in response to implanted xenogenic biomaterials. Here we report a FBGC reaction to the recently introduced xenogenic biomaterial, tarSys™, used for correction of lower eyelid retraction. Method: A retrospective chart review of two patients with FBGC reaction to tarSys™ implantation was performed. Results: Two patients (aged 51, 58 year) with lower eyelid retraction underwent surgical implantation of tarSys™ spacer grafts for correction. Both patients subsequently experienced chronic swelling requiring graft removal. Examination of the specimens showed a palisading FBGC reaction around acellular pink fibrillar material. Conclusion: A FBGC reaction may follow implantation of the tarSys™ xenograft.
William R. Munday1 , Zachary Klett2 , Jennifer M. McNiff3 and Christine Ko3
Keywords: allograft, eyelid, foreign body giant cell reaction, rejection, xenograft
William R. Munday Yale-New-Haven Hospital, Department of Pathology, New Haven, CT, USA Tel: +1 203 785 2759 Fax: +1 203 785 2759 e-mail: [email protected]
Munday WR, Klett Z, McNiff JM, Ko C. Foreign body giant cell reaction to tarSys™ xenograft. J Cutan Pathol 2014; 41: 771–774. © 2014 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd
The foreign body giant cell (FBGC) reaction is the host inflammatory response to a wide range of medical prosthetic implants, including biomedical polymers, allografts and xenografts, and may cause graft failure.1 Notably, the FBGC reaction has caused the degeneration of polymeric biomaterials used for pacemaker lead insulation.2 Additionally, the FBGC reaction may cause encapsulation of implanted materials,3 which is detrimental to extracellular matrix (ECM) scaffolding grafts because successful engraftment depends upon penetration by host cells for appropriate integration, remodeling and tissue regeneration.4 – 6 Furthermore, encapsulation also causes graft site thickening. When this involves the skin, particularly the eyelid, unfavorable cosmetic and dermatologic outcomes will probably ensue, in addition to graft failure.
1
Yale-New Haven Hospital, Department of Pathology, New Haven, CT, USA, 2 Yale-New Haven Hospital, Department of Ophthalmology, New Haven, CT, USA, and 3 Yale School of Medicine, Departments of Dermatology and Pathology, New Haven, CT, USA
Accepted for publication June 7, 2014
A new biomaterial, tarSys™ (IOP Ophthalmics, Costa Mesa, California, USA), has recently been introduced for posterior lamellar grafting of the lower eyelid. TarSys™ is composed of decellularized porcine small intestinal submucosa and functions as a scaffold upon which host cells infiltrate, integrate and remodel for tissue regeneration.7 The material is acquired by cellular denudation of porcine small intestine submucosa, which results in an extracellular matrix consisting of various proteins and collagens.7 Similarly derived xenografts have been used in a variety of clinical settings, such as nasal septal perforation repair and treatment of vaginal prolapse.8,9 The tarSys™ graft is unique, however, because it evidently mirrors the collagen and glycosaminoglycan profile of the tarsal plate, the thick collagenous layer that provides structural integrity to the eyelid in close proximity
771
Munday et al. to the cutaneous layer.7,10 In theory this should reduce the likelihood of graft complications, such as encapsulation, extrusion or premature resorption. Indeed, tarSys™ has shown favorable clinical outcomes at 3 months in a case report of a patient with lagophthalmos,10 at 9 months for repair of lower eyelid malposition,7 and in 32 patients with Graves ophthalmopathy requiring correction of lower lid retraction.11 The tarSys™ xenograft appears promising, yet little is known about histopathologic complications of its use. Here we report two cases in which the tarSys™ implant was found to result in a FBGC reaction necessitating graft removal. Patient 1 A 51-year old male with a past medical history of severe, chronic atopic disease, underwent surgical correction of lower eyelid retraction with implantation of tarSys™ spacer grafts. Several months prior to implantation, the patient underwent surgical tightening of the lower eyelids. After the initial surgery, the eyelids remained constricted and it was decided that a tarSys™ spacer graft would be implanted. Following implantation, the patient developed chronic swelling and focal palpable areas of firmness in both lower eyelids (Fig. 1, top). By 3 months, the cosmetic appearance and chronic swelling warranted removal of the grafts. Following graft removal, the patient’s symptoms subsequently abated (Fig. 1, bottom). The grafts were notably thickened and encapsulated upon ex-plantation (Fig. 2). Histopathologic study of the excised material showed palisading of histiocytes, giant cells and lymphocytes around acellular fibrillar pink material (Fig. 3). This acellular material polarized in the same fashion as human dermal collagen. Patient 2 A 58-year old female with a past medical history of rosacea underwent bilateral correction of lower eyelid retraction with tarSys™. Within days, the patient developed swelling and edema of the right lower eyelid, with symptoms of irritation and pruritus, which persisted for 17 months (Fig. 4, top). At that time the grafted area was removed. Her symptoms subsided with graft removal (Fig. 4, bottom). Notably, the patient did not experience the same symptoms with the left eyelid graft which currently remains in place. The right eyelid graft, upon removal, showed findings similar to case 1 (Fig. 5). In this case,
772
Fig. 1. Before and after removal of lower eyelid tarSys™ grafts. Both lower eyelids appear thickened and the right lower eyelid shows a palpable area of firmness (top). Post ex-plantation, both lower eyelids show smooth contours (bottom).
Fig. 2. Intra-operative photo demonstrating marked encapsulation of the left lower eyelid tarSys™ graft.
the FBGC reaction was most prominent on the periphery of the implant and did not infiltrate the graft. Discussion The tarSys™ biomaterial is composed of small intestinal submucosa and is processed to mimic
Foreign body giant cell reaction
Fig. 3. Foreign body giant cell reaction to tarSys™. Thick porcine collagen matrix is noted to the left of the palisading and infiltrative foreign body response.
the extracellular microenvironment of the tarsus.7,10 This unique material consists primarily of type I collagen, extracellular matrix proteins and glycoproteins; it is largely devoid of porcine cellular products.7 Little is known about the complications of tarSys™ implantation. Here we report FBGC reaction and graft encapsulation in two patients with tarSys™ requiring graft site excision. There are several possible explanations for why our two patients developed adverse reactions to tarSys™. First, an antigenic inflammatory process may have contributed to graft site morbidity. Given the graft is porcine derived, it is conceivable that porcine cellular material survived tissue processing and caused antigenicity. In their study of patients with Graves ophthalmopathy, Liao et al. found that nearly 20% of their patients developed prolonged lower lid swelling with a puffy appearance following tarSys™ implantation. These findings are uncommon in patients receiving non-xenograft implants.11 A second possibility may lie in our patients’ past medical histories. The first patient’s severe atopic disease may have predisposed him to reject the foreign material, while our second patient’s history of rosacea, an inflammatory condition with concomitant immune dysfunction,12 may have
Fig. 4. Before and after removal of the tarSys™ eyelid graft. The right lower eyelid appears enlarged and thickened (top). Immediate post operative photo post ex-plantation (bottom).
Fig. 5. Foreign body giant cell reaction to tarSys™. Thick porcine collagen matrix is noted to the left of the palisading foreign body response.
773
Munday et al. contributed to graft site complication. Both of these conditions, rosacea and atopy, are known to affect the oculocutaneous tissues. Although not performed in the two cases presented here, skin hypersensitivity testing to porcine collagen may be warranted prior to tarSys™ implantation. Interestingly, our second patient experienced graft rejection of only one of the two implants. This raises an interesting question: why would rejection occur at one site, and not the other? Ashley et al. have shown that small intestinal submucosa scaffolds derived from distal vs. proximal portions of the porcine small intestine differ in tissue regeneration quality.13 It is possible that the two tarSys™ grafts were derived from different locations in the porcine small intestine and therefore caused different outcomes. Moreover, host graft response may also depend on the age of the animal from which the scaffold was
derived; scaffolds from younger animals show more effective host tissue remodeling than those derived from older animals.14 An alternative explanation, similar to what has already been discussed, is that not all of the xenogenic cellular material may have been removed from the failed graft. An excellent study exploring the effect of tissue processing on graft outcome, showed that long term response to grafted biomaterials, including chronic inflammation, scarring, fibrosis, encapsulation and site tissue remodeling, may be dependent on the method of biomaterial processing.15 Although both grafts in the second patient were derived from the same manufacturer, the possibility for processing variation should not be ruled out. The tarSys™ graft is a promising xenograft for lower eyelid retraction repair, however, a FBGC reaction to the graft is possible.
References 1. Anderson JM, Rodriguez A, Chang DT. Foreign body reaction to biomaterials. Semin Immunol 2008; 20: 86. 2. Kao WJ, Zhao QH, Hiltner A, Anderson JM. Theoretical analysis of in vivo macrophage adhesion and foreign body gaint cell formation on polydimethylsiloxane, low density polyethylene, and polyetherurethanes. J Biomed Mater Res 1994; 28: 73. 3. Coleman DL, King RN, Andrade JD. The foreign body reaction: a chronic inflammatory response. J Biomed Mater Res 1974; 8: 199. 4. Belcher HJ, Zic R. Adverse effect of porcine collagen interposition after trapeziectomy: a comparative study. J Hand Surg Br Scotl 2001; 26: 159. 5. Cheung D, Brown L, Sampath R. Localized inferior orbital fibrosis associated with porcine dermal collagen xenograft orbital floor implant. Ophthal Plast Reconstr Surg 2004; 20: 257.
774
6. Saray A. Porcine dermal collagen (Permacol) for facial contour augmentation: preliminary report. Aesthetic Plast Surg 2003; 27: 368. 7. Leonard JH, Cohen AJ. Use of the tarSys® for posterior lamellar grafting for lower eyelid malposition. Eur J Plast Surg 2013; 36: 733. 8. Ambro BT, Zimmerman J, Rosenthal M, Pribitkin EA. NAsal septal perforation repair with porcine small intestinal submucosa. Arch Facial Plast Surg 2003; 5: 528. 9. Armitage S, Seman EI, Keirse MJNC. Use of surgisis for treatment of anterior and posterior vaginal prolapse. Obstet Gynecol Int 2012; doi: 10.1155/2012/376251. 10. Borrelli M, Unterlauft J, Kleinsasser N, Geerling G. Decellularized porcine derived membrane (Tarsys®) for correction of lower eyelid retraction. Orbit 2012; 31: 187. 11. Liao SL, Wei YH. Correction of lower lid retraction using tarsys bioengineered
12.
13.
14.
15.
grafts for graves ophthalmopathy. Am J Ophthalmol 2013; 156: 387. Steinhoff M, Schauber J, Leyden JJ. New insights into rosacea pathophysiology: a review of recent findings. J Am Acad Dermatol 2013; 69: S15. Ashley RA, Roth CC, Palmer BW et al. Regional variations in small intestinal submucosa evoke differences in inflammation with subsequent impact on tissue regeneration in the rat bladder augmentation model. BJU Int 2010; 105: 1462. Sicari BM, Johnson SA, Siu BF et al. The effect of source animal age upon the in vivo remodeling characteristics of an extracellular matrix scaffold. Biomaterials 2012; 33: 5524. Valentin JE, Badylak JS, McCabe GP, Badylak SF. Extracellular matrix bioscaffolds for orthopaedic applications a comparative histologic study. J Bone Joint Surg Am 2006; 88: 2673.
© 2014 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd
Journal of Cutaneous Pathology
Foreign body giant cell reaction to tarSys™ xenograft Objective A foreign body giant cell (FBGC) reaction may occur in response to implanted xenogenic biomaterials. Here we report a FBGC reaction to the recently introduced xenogenic biomaterial, tarSys™, used for correction of lower eyelid retraction. Method: A retrospective chart review of two patients with FBGC reaction to tarSys™ implantation was performed. Results: Two patients (aged 51, 58 year) with lower eyelid retraction underwent surgical implantation of tarSys™ spacer grafts for correction. Both patients subsequently experienced chronic swelling requiring graft removal. Examination of the specimens showed a palisading FBGC reaction around acellular pink fibrillar material. Conclusion: A FBGC reaction may follow implantation of the tarSys™ xenograft.
William R. Munday1 , Zachary Klett2 , Jennifer M. McNiff3 and Christine Ko3
Keywords: allograft, eyelid, foreign body giant cell reaction, rejection, xenograft
William R. Munday Yale-New-Haven Hospital, Department of Pathology, New Haven, CT, USA Tel: +1 203 785 2759 Fax: +1 203 785 2759 e-mail: [email protected]
Munday WR, Klett Z, McNiff JM, Ko C. Foreign body giant cell reaction to tarSys™ xenograft. J Cutan Pathol 2014; 41: 771–774. © 2014 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd
The foreign body giant cell (FBGC) reaction is the host inflammatory response to a wide range of medical prosthetic implants, including biomedical polymers, allografts and xenografts, and may cause graft failure.1 Notably, the FBGC reaction has caused the degeneration of polymeric biomaterials used for pacemaker lead insulation.2 Additionally, the FBGC reaction may cause encapsulation of implanted materials,3 which is detrimental to extracellular matrix (ECM) scaffolding grafts because successful engraftment depends upon penetration by host cells for appropriate integration, remodeling and tissue regeneration.4 – 6 Furthermore, encapsulation also causes graft site thickening. When this involves the skin, particularly the eyelid, unfavorable cosmetic and dermatologic outcomes will probably ensue, in addition to graft failure.
1
Yale-New Haven Hospital, Department of Pathology, New Haven, CT, USA, 2 Yale-New Haven Hospital, Department of Ophthalmology, New Haven, CT, USA, and 3 Yale School of Medicine, Departments of Dermatology and Pathology, New Haven, CT, USA
Accepted for publication June 7, 2014
A new biomaterial, tarSys™ (IOP Ophthalmics, Costa Mesa, California, USA), has recently been introduced for posterior lamellar grafting of the lower eyelid. TarSys™ is composed of decellularized porcine small intestinal submucosa and functions as a scaffold upon which host cells infiltrate, integrate and remodel for tissue regeneration.7 The material is acquired by cellular denudation of porcine small intestine submucosa, which results in an extracellular matrix consisting of various proteins and collagens.7 Similarly derived xenografts have been used in a variety of clinical settings, such as nasal septal perforation repair and treatment of vaginal prolapse.8,9 The tarSys™ graft is unique, however, because it evidently mirrors the collagen and glycosaminoglycan profile of the tarsal plate, the thick collagenous layer that provides structural integrity to the eyelid in close proximity
771
Munday et al. to the cutaneous layer.7,10 In theory this should reduce the likelihood of graft complications, such as encapsulation, extrusion or premature resorption. Indeed, tarSys™ has shown favorable clinical outcomes at 3 months in a case report of a patient with lagophthalmos,10 at 9 months for repair of lower eyelid malposition,7 and in 32 patients with Graves ophthalmopathy requiring correction of lower lid retraction.11 The tarSys™ xenograft appears promising, yet little is known about histopathologic complications of its use. Here we report two cases in which the tarSys™ implant was found to result in a FBGC reaction necessitating graft removal. Patient 1 A 51-year old male with a past medical history of severe, chronic atopic disease, underwent surgical correction of lower eyelid retraction with implantation of tarSys™ spacer grafts. Several months prior to implantation, the patient underwent surgical tightening of the lower eyelids. After the initial surgery, the eyelids remained constricted and it was decided that a tarSys™ spacer graft would be implanted. Following implantation, the patient developed chronic swelling and focal palpable areas of firmness in both lower eyelids (Fig. 1, top). By 3 months, the cosmetic appearance and chronic swelling warranted removal of the grafts. Following graft removal, the patient’s symptoms subsequently abated (Fig. 1, bottom). The grafts were notably thickened and encapsulated upon ex-plantation (Fig. 2). Histopathologic study of the excised material showed palisading of histiocytes, giant cells and lymphocytes around acellular fibrillar pink material (Fig. 3). This acellular material polarized in the same fashion as human dermal collagen. Patient 2 A 58-year old female with a past medical history of rosacea underwent bilateral correction of lower eyelid retraction with tarSys™. Within days, the patient developed swelling and edema of the right lower eyelid, with symptoms of irritation and pruritus, which persisted for 17 months (Fig. 4, top). At that time the grafted area was removed. Her symptoms subsided with graft removal (Fig. 4, bottom). Notably, the patient did not experience the same symptoms with the left eyelid graft which currently remains in place. The right eyelid graft, upon removal, showed findings similar to case 1 (Fig. 5). In this case,
772
Fig. 1. Before and after removal of lower eyelid tarSys™ grafts. Both lower eyelids appear thickened and the right lower eyelid shows a palpable area of firmness (top). Post ex-plantation, both lower eyelids show smooth contours (bottom).
Fig. 2. Intra-operative photo demonstrating marked encapsulation of the left lower eyelid tarSys™ graft.
the FBGC reaction was most prominent on the periphery of the implant and did not infiltrate the graft. Discussion The tarSys™ biomaterial is composed of small intestinal submucosa and is processed to mimic
Foreign body giant cell reaction
Fig. 3. Foreign body giant cell reaction to tarSys™. Thick porcine collagen matrix is noted to the left of the palisading and infiltrative foreign body response.
the extracellular microenvironment of the tarsus.7,10 This unique material consists primarily of type I collagen, extracellular matrix proteins and glycoproteins; it is largely devoid of porcine cellular products.7 Little is known about the complications of tarSys™ implantation. Here we report FBGC reaction and graft encapsulation in two patients with tarSys™ requiring graft site excision. There are several possible explanations for why our two patients developed adverse reactions to tarSys™. First, an antigenic inflammatory process may have contributed to graft site morbidity. Given the graft is porcine derived, it is conceivable that porcine cellular material survived tissue processing and caused antigenicity. In their study of patients with Graves ophthalmopathy, Liao et al. found that nearly 20% of their patients developed prolonged lower lid swelling with a puffy appearance following tarSys™ implantation. These findings are uncommon in patients receiving non-xenograft implants.11 A second possibility may lie in our patients’ past medical histories. The first patient’s severe atopic disease may have predisposed him to reject the foreign material, while our second patient’s history of rosacea, an inflammatory condition with concomitant immune dysfunction,12 may have
Fig. 4. Before and after removal of the tarSys™ eyelid graft. The right lower eyelid appears enlarged and thickened (top). Immediate post operative photo post ex-plantation (bottom).
Fig. 5. Foreign body giant cell reaction to tarSys™. Thick porcine collagen matrix is noted to the left of the palisading foreign body response.
773
Munday et al. contributed to graft site complication. Both of these conditions, rosacea and atopy, are known to affect the oculocutaneous tissues. Although not performed in the two cases presented here, skin hypersensitivity testing to porcine collagen may be warranted prior to tarSys™ implantation. Interestingly, our second patient experienced graft rejection of only one of the two implants. This raises an interesting question: why would rejection occur at one site, and not the other? Ashley et al. have shown that small intestinal submucosa scaffolds derived from distal vs. proximal portions of the porcine small intestine differ in tissue regeneration quality.13 It is possible that the two tarSys™ grafts were derived from different locations in the porcine small intestine and therefore caused different outcomes. Moreover, host graft response may also depend on the age of the animal from which the scaffold was
derived; scaffolds from younger animals show more effective host tissue remodeling than those derived from older animals.14 An alternative explanation, similar to what has already been discussed, is that not all of the xenogenic cellular material may have been removed from the failed graft. An excellent study exploring the effect of tissue processing on graft outcome, showed that long term response to grafted biomaterials, including chronic inflammation, scarring, fibrosis, encapsulation and site tissue remodeling, may be dependent on the method of biomaterial processing.15 Although both grafts in the second patient were derived from the same manufacturer, the possibility for processing variation should not be ruled out. The tarSys™ graft is a promising xenograft for lower eyelid retraction repair, however, a FBGC reaction to the graft is possible.
References 1. Anderson JM, Rodriguez A, Chang DT. Foreign body reaction to biomaterials. Semin Immunol 2008; 20: 86. 2. Kao WJ, Zhao QH, Hiltner A, Anderson JM. Theoretical analysis of in vivo macrophage adhesion and foreign body gaint cell formation on polydimethylsiloxane, low density polyethylene, and polyetherurethanes. J Biomed Mater Res 1994; 28: 73. 3. Coleman DL, King RN, Andrade JD. The foreign body reaction: a chronic inflammatory response. J Biomed Mater Res 1974; 8: 199. 4. Belcher HJ, Zic R. Adverse effect of porcine collagen interposition after trapeziectomy: a comparative study. J Hand Surg Br Scotl 2001; 26: 159. 5. Cheung D, Brown L, Sampath R. Localized inferior orbital fibrosis associated with porcine dermal collagen xenograft orbital floor implant. Ophthal Plast Reconstr Surg 2004; 20: 257.
774
6. Saray A. Porcine dermal collagen (Permacol) for facial contour augmentation: preliminary report. Aesthetic Plast Surg 2003; 27: 368. 7. Leonard JH, Cohen AJ. Use of the tarSys® for posterior lamellar grafting for lower eyelid malposition. Eur J Plast Surg 2013; 36: 733. 8. Ambro BT, Zimmerman J, Rosenthal M, Pribitkin EA. NAsal septal perforation repair with porcine small intestinal submucosa. Arch Facial Plast Surg 2003; 5: 528. 9. Armitage S, Seman EI, Keirse MJNC. Use of surgisis for treatment of anterior and posterior vaginal prolapse. Obstet Gynecol Int 2012; doi: 10.1155/2012/376251. 10. Borrelli M, Unterlauft J, Kleinsasser N, Geerling G. Decellularized porcine derived membrane (Tarsys®) for correction of lower eyelid retraction. Orbit 2012; 31: 187. 11. Liao SL, Wei YH. Correction of lower lid retraction using tarsys bioengineered
12.
13.
14.
15.
grafts for graves ophthalmopathy. Am J Ophthalmol 2013; 156: 387. Steinhoff M, Schauber J, Leyden JJ. New insights into rosacea pathophysiology: a review of recent findings. J Am Acad Dermatol 2013; 69: S15. Ashley RA, Roth CC, Palmer BW et al. Regional variations in small intestinal submucosa evoke differences in inflammation with subsequent impact on tissue regeneration in the rat bladder augmentation model. BJU Int 2010; 105: 1462. Sicari BM, Johnson SA, Siu BF et al. The effect of source animal age upon the in vivo remodeling characteristics of an extracellular matrix scaffold. Biomaterials 2012; 33: 5524. Valentin JE, Badylak JS, McCabe GP, Badylak SF. Extracellular matrix bioscaffolds for orthopaedic applications a comparative histologic study. J Bone Joint Surg Am 2006; 88: 2673.
