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Perilymphatic subcutaneous fat atrophy and cutaneous depigmentation after periocular triamcinolone acetonide injection in a child
Perilymphatic subcutaneous fat atrophy and cutaneous depigmentation after periocular triamcinolone acetonide injection in a child Emil Anthony T. Say, MD, Carol L. Shields, MD, Carlos Bianciotto, MD, and Jerry A. Shields, MD
Periocular corticosteroid injection is a potent and versatile treatment for uveitic conditions as well as for some ocular tumors. Despite its efficacy, ophthalmologists are wary of documented side effects, some of which can be blinding. Adverse reactions are mostly dependent on route of administration, with glaucoma and cataract formation more often seen in peribulbar and intraocular injections, whereas skin depigmentation and fat atrophy are more frequently related to intradermal or intralesional routes, particularly after injection of capillary hemangioma of infancy. We present a child with perilymphatic linear subcutaneous fat atrophy and depigmentation after sub-Tenon’s fascia injection of triamcinolone acetonide.
Case Report
A
3-month-old African American girl presented with bilateral sporadic retinoblastoma classified as Group E in her right eye and Group D in the left eye by the International Classification of Retinoblastoma.1 Visual acuity was no fix-or-follow in the right eye and fixand-follow in the left. Tumor regression was achieved after 6 cycles of chemoreduction and consolidation. Thirteen months later, localized tumor recurrence in the right eye was managed with iodine-125 plaque radiotherapy. In an effort to protect the right eye from radiation maculopathy and papillopathy, posterior sub-Tenon’s fascia triamcinolone acetonide injection (20 mg/0.5 mL) was administered after discussing with her parents the documented protective effects of periocular steroids after radiotherapy in adults with ocular melanoma and its off-label use in children and obtaining their informed consent. The first dose was given superonasally during plaque placement, the second dose inferotemporally 4 months later, and the third dose inferonasally 6 months later. All injections were through the conjunctiva into the sub-Tenon’s space using a short 30 gauge needle in a tuberculin syringe. Three months after the last dose, linear branching Author affiliations: Ocular Oncology Service, Wills Eye Institute, Thomas Jefferson University, Philadelphia, Pennsylvania Supported in part by a donation from Michael, Bruce and Ellen Ratner, New York, New York (JAS, CLS), Mellon Charitable Giving from the Martha W. Rogers Charitable Trust (CLS), and the Eye Tumor Research Foundation, Philadelphia, Pennsylvania (JAS, CLS). Submitted May 24, 2010. Revision accepted November 22, 2010. Reprint requests: Carol L. Shields, MD, Oncology Service, Suite 1440, Wills Eye Hospital 840 Walnut Street, Philadelphia, PA 19107 (email: [email protected]). J AAPOS 2011;15:107-108. Copyright Ó 2011 by the American Association for Pediatric Ophthalmology and Strabismus. 1091-8531/$36.00 doi:10.1016/j.jaapos.2010.11.010
Journal of AAPOS
depigmentation and atrophy extending laterally from the right lateral canthus was noted (Figure 1). One year after the final dose, the findings remained but were less prominent.
Discussion The ocular lymphatics reside mainly in the conjunctiva and have not been clearly documented in the orbit or globe.2 Conjunctival lymphatics form 2 systems: a superficial network in the conjunctiva and a deep net in the fibrous layer without lymph nodes.2 Conjunctival lymphatic vessels drain primarily to the medial and lateral canthi, then from the medial canthus to the submaxillary lymph nodes, and from the lateral canthus to the preauricular nodes.2 The presence of insoluble corticosteroid crystals within these lymphatic vessels are thought to cause localized lipolysis and skin depigmentation along the perilymphatic skin. Kikuchi and Horikawa3 demonstrated this phenomenon in a patient with perilymphatic skin atrophy and depigmentation following triamcinolone acetonide injection for keloid formation in the upper arm. After injecting alphazurine 2G (patent blue dye) along the linear skin atrophy, there was staining of lymphatic vessels toward the chest consistent with anatomic lymphatic drainage.3 A biopsy performed after the injection showed atrophy of the epidermis and a decreased number of melanin granules and sebaceous glands.3 Our patient received 2 nasal injections that presumably drained to the submandibular nodes with no cutaneous abnormality. She also received one temporal injection 9 months before skin changes in the distribution toward the preauricular nodes. The characteristic linear and branching pattern resembled lymphatic vessels, and its origin from the lateral canthus is consistent with temporal conjunctival lymphatic drainage toward the preauricular lymph node. Intra-articular injections for rheumatoid arthritis have also been reported to cause perilymphatic linear skin atrophy, presumably through drainage to the lymphatic plexus in the bordering synovial membrane.4 Although cases have been reported after intralesional corticosteroid injections (prednisolone tebutate and triamcinolone acetonide) to the forehead for alopecia and the extremities for psoriasis and keloids, this adverse reaction is generally found after intralesional steroid injections to the skin or eyelid, particularly within solid vascular tumors like capillary hemangioma of infancy.4,5 In 886 cases of infantile capillary hemangioma of the skin treated primarily with intralesional
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FIG 1. Three months after the final of 3 posterior sub-Tenon’s fascia injection of 20 mg/0.5 mL triamcinolone acetonide for prevention of radiation retinopathy, the patient developed perilymphatic linear subcutaneous fat atrophy and depigmentation extending from the lateral canthus toward the preauricular lymph nodes.
triamcinolone acetonide injection, skin depigmentation and atrophy were seen in 10% and 11%, respectively.6 Periocular triamcinolone acetonide injection has been used for cystoid macular edema and uveitis.7 Its most common side effects include cataract, glaucoma, and orbital fat prolapse.7,8 In a trial of periocular triamcinolone acetonide for prevention of macular edema after plaque radiotherapy for uveal melanoma in 163 eyes by Horgan and colleagues,8 cataract progression was seen in 30%, increased intraocular pressure in 15%, and orbital fat prolapse in 5%. There were no cases of perilymphatic atrophy or depigmentation, possibly because most patients were white, making detection of skin atrophy and depigmentation more difficult.8 There have been no published reports of cutaneous depigmentation after lymphatics after periocular injections to the best of our knowledge; the patterns of involvement appear very similar to perilymphatic atrophy seen after intralesional injection of periocular infantile capillary hemangioma. Although the definitive means of determining causation is through biopsy, we feel that it is unnecessary in this case. It is distinctly unusual to find perilymphatic linear subcutaneous fat atrophy and skin depigmentation after sub-Tenon’s fascia deep orbital injections, and this finding has not been reported in large clinical trials of more than 100 patients after periocular triamcinolone acetonide injections.8,9 Gallardo and Johnson10 reported a similar case of upper eyelid skin depigmentation and thinning after sub-Tenon’s fascia injection for Adamantiades-Behc¸et
Volume 15 Number 1 / February 2011 disease in a 28-year-old African American patient, but the characteristic linear pattern and branching was absent. In our case, previous radiotherapy applied to the superotemporal region of the globe could have led to fibrosis of superotemporal quadrant lymphatics with subsequent compensatory dilation of inferotemporal quadrant lymphatics that allowed increased drainage into the facial region. Perilymphatic linear subcutaneous fat atrophy and depigmentation can occur following single or multiple injections with a latency period that varies from 2 weeks to several months after the initial injection.5 Although linear subcutaneous fat atrophy and skin hypopigmentation can persist for a year or longer, spontaneous resolution has also been found.5 For this reason, observation with proper reassurance and counseling is suggested as initial management in all patients. The rare but cosmetically significant adverse reactions described in this case are more common after intradermal corticosteroid injection; nevertheless, ophthalmologists should have a basic understanding of conjunctival lymphatics. References 1. Murphree AL. Intraocular retinoblastoma: The case for a new group classification. Ophthalmol Clin N Am 2005;18:41-53. 2. Duke-Elder S, Wybar C. Anatomy of the visual system. In: System of ophthalmology. London: Henry Kimpton; 1965:479-551. 3. Kikuchi I, Horikawa S. Perilymphatic atrophy of the skin: A side effect of topical corticosteroid injection therapy. Arch Ophthalmol 1974; 109:558-9. 4. Friedman SJ, Butler DF, Pittelkow MR. Perilesional linear atrophy and hypopigmentation after intralesional corticosteroid therapy: Report of two cases and review of the literature. J Am Acad Dermatol 1988;19:537-41. 5. Vazquez-Botet R, Reyes BA, Vazquez-Botet M. Sclerodermiform linear atrophy after the use of intralesional steroids for periorbital hemangiomas: A review of complications. J Pediatr Ophthalmol Strabismus 1989;26:124-7. 6. Pandey A, Gangopadhyay AN, Gopal SC, Kumar V, Sharma SP, Gupta DK, et al. Twenty years’ experience of steroids in infantile hemangioma—a developing country’s perspective. J Pediatr Surg 2009;44:688-94. 7. Jermak CM, Dellacroce JT, Heffez J, Peyman GA. Triamcinolone acetonide in ocular therapeutics. Surv Ophthalmol 2007;52:503-22. 8. Horgan N, Shields CL, Mashayekhi A, Salazar PF, Materin MA, O’Regan M, et al. Periocular triamcinolone for prevention of macular edema after plaque radiotherapy of uveal melanoma: A randomized controlled trial. Ophthalmology 2009;116:1383-90. 9. Diabetic Retinopathy Clinical Research Network. Randomized trial of peribulbar triamcinolone acetonide with and without focal photocoagulation for mild diabetic macular edema: A pilot study. Ophthalmology 2007;114:1190-96. 10. Gallardo MJ, Johnson DA. Cutaneous hypopigmentation following a posterior sub-Tenon triamcinolone injection. Am J Ophthalmol 2004;137:779-80.
Journal of AAPOS
Periocular corticosteroid injection is a potent and versatile treatment for uveitic conditions as well as for some ocular tumors. Despite its efficacy, ophthalmologists are wary of documented side effects, some of which can be blinding. Adverse reactions are mostly dependent on route of administration, with glaucoma and cataract formation more often seen in peribulbar and intraocular injections, whereas skin depigmentation and fat atrophy are more frequently related to intradermal or intralesional routes, particularly after injection of capillary hemangioma of infancy. We present a child with perilymphatic linear subcutaneous fat atrophy and depigmentation after sub-Tenon’s fascia injection of triamcinolone acetonide.
Case Report
A
3-month-old African American girl presented with bilateral sporadic retinoblastoma classified as Group E in her right eye and Group D in the left eye by the International Classification of Retinoblastoma.1 Visual acuity was no fix-or-follow in the right eye and fixand-follow in the left. Tumor regression was achieved after 6 cycles of chemoreduction and consolidation. Thirteen months later, localized tumor recurrence in the right eye was managed with iodine-125 plaque radiotherapy. In an effort to protect the right eye from radiation maculopathy and papillopathy, posterior sub-Tenon’s fascia triamcinolone acetonide injection (20 mg/0.5 mL) was administered after discussing with her parents the documented protective effects of periocular steroids after radiotherapy in adults with ocular melanoma and its off-label use in children and obtaining their informed consent. The first dose was given superonasally during plaque placement, the second dose inferotemporally 4 months later, and the third dose inferonasally 6 months later. All injections were through the conjunctiva into the sub-Tenon’s space using a short 30 gauge needle in a tuberculin syringe. Three months after the last dose, linear branching Author affiliations: Ocular Oncology Service, Wills Eye Institute, Thomas Jefferson University, Philadelphia, Pennsylvania Supported in part by a donation from Michael, Bruce and Ellen Ratner, New York, New York (JAS, CLS), Mellon Charitable Giving from the Martha W. Rogers Charitable Trust (CLS), and the Eye Tumor Research Foundation, Philadelphia, Pennsylvania (JAS, CLS). Submitted May 24, 2010. Revision accepted November 22, 2010. Reprint requests: Carol L. Shields, MD, Oncology Service, Suite 1440, Wills Eye Hospital 840 Walnut Street, Philadelphia, PA 19107 (email: [email protected]). J AAPOS 2011;15:107-108. Copyright Ó 2011 by the American Association for Pediatric Ophthalmology and Strabismus. 1091-8531/$36.00 doi:10.1016/j.jaapos.2010.11.010
Journal of AAPOS
depigmentation and atrophy extending laterally from the right lateral canthus was noted (Figure 1). One year after the final dose, the findings remained but were less prominent.
Discussion The ocular lymphatics reside mainly in the conjunctiva and have not been clearly documented in the orbit or globe.2 Conjunctival lymphatics form 2 systems: a superficial network in the conjunctiva and a deep net in the fibrous layer without lymph nodes.2 Conjunctival lymphatic vessels drain primarily to the medial and lateral canthi, then from the medial canthus to the submaxillary lymph nodes, and from the lateral canthus to the preauricular nodes.2 The presence of insoluble corticosteroid crystals within these lymphatic vessels are thought to cause localized lipolysis and skin depigmentation along the perilymphatic skin. Kikuchi and Horikawa3 demonstrated this phenomenon in a patient with perilymphatic skin atrophy and depigmentation following triamcinolone acetonide injection for keloid formation in the upper arm. After injecting alphazurine 2G (patent blue dye) along the linear skin atrophy, there was staining of lymphatic vessels toward the chest consistent with anatomic lymphatic drainage.3 A biopsy performed after the injection showed atrophy of the epidermis and a decreased number of melanin granules and sebaceous glands.3 Our patient received 2 nasal injections that presumably drained to the submandibular nodes with no cutaneous abnormality. She also received one temporal injection 9 months before skin changes in the distribution toward the preauricular nodes. The characteristic linear and branching pattern resembled lymphatic vessels, and its origin from the lateral canthus is consistent with temporal conjunctival lymphatic drainage toward the preauricular lymph node. Intra-articular injections for rheumatoid arthritis have also been reported to cause perilymphatic linear skin atrophy, presumably through drainage to the lymphatic plexus in the bordering synovial membrane.4 Although cases have been reported after intralesional corticosteroid injections (prednisolone tebutate and triamcinolone acetonide) to the forehead for alopecia and the extremities for psoriasis and keloids, this adverse reaction is generally found after intralesional steroid injections to the skin or eyelid, particularly within solid vascular tumors like capillary hemangioma of infancy.4,5 In 886 cases of infantile capillary hemangioma of the skin treated primarily with intralesional
107
108
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FIG 1. Three months after the final of 3 posterior sub-Tenon’s fascia injection of 20 mg/0.5 mL triamcinolone acetonide for prevention of radiation retinopathy, the patient developed perilymphatic linear subcutaneous fat atrophy and depigmentation extending from the lateral canthus toward the preauricular lymph nodes.
triamcinolone acetonide injection, skin depigmentation and atrophy were seen in 10% and 11%, respectively.6 Periocular triamcinolone acetonide injection has been used for cystoid macular edema and uveitis.7 Its most common side effects include cataract, glaucoma, and orbital fat prolapse.7,8 In a trial of periocular triamcinolone acetonide for prevention of macular edema after plaque radiotherapy for uveal melanoma in 163 eyes by Horgan and colleagues,8 cataract progression was seen in 30%, increased intraocular pressure in 15%, and orbital fat prolapse in 5%. There were no cases of perilymphatic atrophy or depigmentation, possibly because most patients were white, making detection of skin atrophy and depigmentation more difficult.8 There have been no published reports of cutaneous depigmentation after lymphatics after periocular injections to the best of our knowledge; the patterns of involvement appear very similar to perilymphatic atrophy seen after intralesional injection of periocular infantile capillary hemangioma. Although the definitive means of determining causation is through biopsy, we feel that it is unnecessary in this case. It is distinctly unusual to find perilymphatic linear subcutaneous fat atrophy and skin depigmentation after sub-Tenon’s fascia deep orbital injections, and this finding has not been reported in large clinical trials of more than 100 patients after periocular triamcinolone acetonide injections.8,9 Gallardo and Johnson10 reported a similar case of upper eyelid skin depigmentation and thinning after sub-Tenon’s fascia injection for Adamantiades-Behc¸et
Volume 15 Number 1 / February 2011 disease in a 28-year-old African American patient, but the characteristic linear pattern and branching was absent. In our case, previous radiotherapy applied to the superotemporal region of the globe could have led to fibrosis of superotemporal quadrant lymphatics with subsequent compensatory dilation of inferotemporal quadrant lymphatics that allowed increased drainage into the facial region. Perilymphatic linear subcutaneous fat atrophy and depigmentation can occur following single or multiple injections with a latency period that varies from 2 weeks to several months after the initial injection.5 Although linear subcutaneous fat atrophy and skin hypopigmentation can persist for a year or longer, spontaneous resolution has also been found.5 For this reason, observation with proper reassurance and counseling is suggested as initial management in all patients. The rare but cosmetically significant adverse reactions described in this case are more common after intradermal corticosteroid injection; nevertheless, ophthalmologists should have a basic understanding of conjunctival lymphatics. References 1. Murphree AL. Intraocular retinoblastoma: The case for a new group classification. Ophthalmol Clin N Am 2005;18:41-53. 2. Duke-Elder S, Wybar C. Anatomy of the visual system. In: System of ophthalmology. London: Henry Kimpton; 1965:479-551. 3. Kikuchi I, Horikawa S. Perilymphatic atrophy of the skin: A side effect of topical corticosteroid injection therapy. Arch Ophthalmol 1974; 109:558-9. 4. Friedman SJ, Butler DF, Pittelkow MR. Perilesional linear atrophy and hypopigmentation after intralesional corticosteroid therapy: Report of two cases and review of the literature. J Am Acad Dermatol 1988;19:537-41. 5. Vazquez-Botet R, Reyes BA, Vazquez-Botet M. Sclerodermiform linear atrophy after the use of intralesional steroids for periorbital hemangiomas: A review of complications. J Pediatr Ophthalmol Strabismus 1989;26:124-7. 6. Pandey A, Gangopadhyay AN, Gopal SC, Kumar V, Sharma SP, Gupta DK, et al. Twenty years’ experience of steroids in infantile hemangioma—a developing country’s perspective. J Pediatr Surg 2009;44:688-94. 7. Jermak CM, Dellacroce JT, Heffez J, Peyman GA. Triamcinolone acetonide in ocular therapeutics. Surv Ophthalmol 2007;52:503-22. 8. Horgan N, Shields CL, Mashayekhi A, Salazar PF, Materin MA, O’Regan M, et al. Periocular triamcinolone for prevention of macular edema after plaque radiotherapy of uveal melanoma: A randomized controlled trial. Ophthalmology 2009;116:1383-90. 9. Diabetic Retinopathy Clinical Research Network. Randomized trial of peribulbar triamcinolone acetonide with and without focal photocoagulation for mild diabetic macular edema: A pilot study. Ophthalmology 2007;114:1190-96. 10. Gallardo MJ, Johnson DA. Cutaneous hypopigmentation following a posterior sub-Tenon triamcinolone injection. Am J Ophthalmol 2004;137:779-80.
Journal of AAPOS