What Are These Changes on the Buttocks?

Figure 1. Gross image of patient’s right buttock demonstrating single atrophic depression.

A 45-year-old female presented to the clinic with a slightly tender area on the right buttock for the past 4 months. The patient’s medical history was remarkable for seasonal allergies, cognition and memory problems secondary to traumatic injury. Due to her neurologic problems, the patient could not provide a reliable history. She denied trauma to the affected area and could not recall administration of injection medication to the site of concern. On physical examination, a circular, hypopigmented, pink, depression on the mid-lower aspect of the right buttock without surrounding erythema or secondary lesions was noted (Figure 1).
What is Your Diagnosis?
 

Diagnosis: Focal Lipoatrophy from Steroid Injection 

The patient was diagnosed with localized lipoatrophy, most likely secondary to injection medication. Further inquiry revealed that she had received corticosteroid injections for her seasonal allergies in the past, but it was not accurately documented in her medical record.

Localized lipoatrophy was first described as a distinct entity in 1986 by Peters et al based on clinical and histologic findings; 10 years later Dahl et al proposed the term “involutional lipoatrophy” to better describe the ultrastructural changes.^1,2
Adverse local reactions at the site of corticosteroid injection are well-known; however, the frequency at which they occur is quite infrequent.^3-6 These reactions are generally not serious, but they may be a source of significant stress to the patient and can be challenging for the clinician to diagnose.^5,6 Among the various types of local reactions, localized involution lipoatrophy is among the most common and has a propensity to occur more frequently in premenopausal females than males or females past menopause.^2-4

A study by Goldman in 1962 found that local reactions to steroid injection occurred in less than 0.5% of patients. In this study, these reactions were broadly defined as pain, hemorrhage, infection, pigment changes, hypersensitivity and panniculitis as well as subcutaneous atrophy.⁴ Given the low incidence of local side effects, and great efficacy in the treatment of autoimmune and inflammatory conditions, injection corticosteroids are a mainstay in the dermatologist’s armamentarium.^4,7 Local injection also offers the advantage of maintaining a high local concentration of medicine without subjecting the patient to the side effects associated with systemic therapy.⁷ Indications for local steroid injection are many but may include: localized patches of psoriasis, localized neurodermatitis, keloids, lichen planus, alopecia areata, sarcoid, discoid lupus erythematosus and granuloma annulare.⁴

Clinical Presentation
Atrophy of the subcutaneous fat layer generally occurs within 1 to 3 months post-injection with the absence of antecedent clinical or histological inflammation.^2,3,7,8
On clinical examination, the lesion will generally appear as a well-demarcated, skin-colored, non-tender, round or ellipsoid depression occurring at the site of injection with minimal or no changes to the epidermis (Figures 1 and 2).^2,3

Figure 2. Image demonstrating hypopigmented depression with pinkish hue and lack of secondary lesions without surrounding inflammation.

Depressed areas may also have a background of finely distended blood vessels, hypopigmentation, alopecia or thinning of the skin.^4,7,9  These are typically solitary and occur most frequently at the buttocks and proximal extremities.³  Variation is known to occur as described in an interesting case report by Avilés-Izquierdo et al where a patient developed 2, nearly symmetric, bilateral lesions on the buttocks after receiving only a single corticosteroid injection.¹⁰
Laboratory testing is unremarkable with no specific changes if any.2,8 Cutaneous sloughing can occur in instances where relatively large amounts of steroid are injected superficially.⁴

Pathophysiology and Histologic Changes
The exact cause of focal lipoatrophy after steroid injection is not fully elucidated; however, several mechanisms have been identified that play a role in its pathogenesis: activation of macrophages, concentration of the steroid suspension, anatomical depth of injection and history of autoimmune disease.^2,4,8,11,12
Histopathology of studied cases uniformly demonstrated the subdermal fat layer taking on a resemblance of fetal adipose tissue with attenuated fat lobules of various sizes made up of small adipocytes in a well-vascularized and hyalinized background. Adipocytes may have a signet ring cell appearance. Activated, mucin-positive macrophages were prominent and characteristically disbursed throughout the affected lipocytes. No specific changes on immunofluorescence were observed in studied cases.^2,8,11
The presence of scattered macrophages throughout the atrophic lesions in the absence of other inflammatory cells lends support to the post-injury hypothesis where macrophage activation is implicated as the causal mechanism.¹¹ Activation of macrophages by injection injury produces cytokines that induce involution of the subdermal adipose tissue and subsequently brings forth the clinical findings of epidermal depressions.^2,8,13 The post-injury mechanism hypothesis is consistent with other cases of localized trauma that later developed focal lipoatrophy without a history of steroid injection.¹⁴
Although the above explanation suggests a generic mechanism is responsible for subdermal changes, other studies have shown that the concentration of steroid in suspension may play a direct role in the development of subcutaneous atrophy.⁷ Histologic findings in a number of cases of focal atrophy with a history of steroid injection showed evidence of corticosteroid crystal formation.^4,12 Interestingly, Goldman observed in his study that improvement in atrophy improved in proportion to the gradual disappearance of corticosteroid crystals at the affected site.⁴ However, crystal formation is not always appreciated in patients with clinical findings of lipoatrophy even with a history of steroid injection.^2,11
Other factors that have been cited in the development of local atrophy are the depth of steroid injection and history of autoimmune disease.2,12 Schetman et al observed in a controlled study of 25 male subjects receiving multiple triamcinolone injections of equal concentration, delivery of the steroid into the intradermal layers was much more likely to develop atrophy versus injection of steroid into the deeper subcutaneous layer.¹²
Individuals with history of autoimmune disease were observed to develop atrophy more frequently than patients with no history of such disease; thereby, suggesting an immunodysregulation component may be a factor in localized lipoatrophy post-injection.^2,8,11

Differential Diagnosis
Focal lipoatrophy can occur in the context of other localized traumatic injury as seen with the injection of penicillins and insulin.¹⁴ Minor trauma producing these clinical findings does not necessarily have to be iatrogenic. Focal atrophy has been known to occur in the context of recurrent pressure and even in 1 reported case of massage cupping therapy.^8,14
Clinical presentation of lipoatrophy can occur in certain forms of panniculitis, including lipoatrophic panniculitis and cold panniculitis.^15,16 Solitary morphea profunda is a form of localized scleroderma that may present with findings similar to focal lipoatrophy.¹⁷ In the case of either morphea or panniculitis, the histologic findings, laboratory markers and history are distinct; thereby, emphasizing the need of the clinician to obtain a complete history to guide further diagnostic work-up.^15-18

Our Patient
The patient was informed of her diagnosis and possible options for management. She decided not to follow up with the dermatology clinic; therefore, treatment was not started.

Conclusion
Focal lipoatrophy is an uncommon side effect of corticosteroid injection first appearing 1 to 3 months after injection. The atrophy is reversible but can take over a year for significant improvement to be appreciable without medical treatment. Serial infiltration with normal saline injections has been used in successful treatment of focal atrophy with high patient satisfaction.^7,9

Dr. Longhurst is a PGY1 resident with the department of pathology at Case Western Reserve University in Cleveland, OH.
Ms. Bermudez-Locano is with Golden Valley Health Centers in Modesto, CA.
Dr. Khachemoune, the Section Editor of Derm DX, is with the Department of Dermatology at the State University of New York Downstate in Brooklyn, NY.

Disclosure: The authors report no relevant financial relationships.

References
1. Peters MS, Winkelmann RK. The histopathology of localized lipoatrophy. Br J Dermatol. 1986;114(1):27-36.
2. Dahl PR, Zalla MJ, Winkelmann RK. Localized involutional lipoatrophy: a clinicopathologic study of 16 patients. J Am Acad Dermatol. 1996;35(4):523-528.
3. Fisherman EW, Feinberg AR, Feinberg SM. Local subcutaneous atrophy. JAMA. 1962;179:971-972.
4. Goldman L. Reactions following intralesional and sublesional injections of corticosteroids. JAMA. 1962;182:613-616.
5. Morgan AM. Localized reactions to injected therapeutic materials. Part 1. Medical agents. J Cutan Pathol. 1995;22(3):193-214.
6. Morgan AM. Localized reactions to injected therapeutic materials. Part 2. Surgical agents. J Cutan Pathol. 1995;22(4):289-303.
7. Shumaker PR, Rao J, Goldman MP. Treatment of local, persistent cutaneous atrophy following corticosteroid injection with normal saline infiltration. Dermatol Surg. 2005;31(10):1340-1343.
8. Abbas O, Salman S, Kibbi AG, Chedraoui A, Ghosn S. Localized involutional lipoatrophy with epidermal and dermal changes. J Am Acad Dermatol. 2008;58(3):490-493.
9. Stassiy A, Khachemoune A. Unusual depressed areas on the arm and buttock. JAAPA. 2010;23(11):18.
10. Avilés-Izquierdo JA, Longo-Imedio MI, Hernánz-Hermosa JM, Lázaro-Ochaita P.  Bilateral localized lipoatrophy secondary to a single intramuscular corticosteroid injection. Dermatol Online J. 2006;12(3):17.
11. Ahmed I. Post-injection involutional lipoatrophy: Ultrastructural evidence for an activated macrophage phenotype and macrophage related involution of adipocytes. Am J Dermatopathol. 2006;28(4):334-337.
12. Schetman D, Hambrick GW Jr, Wilson CE. Cutaneous changes following local injection of triamcinolone. Arch Dermatol. 1963;88:820-828.
13. Zalla MJ, Winkelmann RK, Gluck OS. Involutional lipoatrophy: macrophage-related involution of fat lobules. Dermatology. 1995;191(2):149-153.
14. Garg A. Acquired and inherited lipodystrophies. N Engl J Med. 2004;350(12):1220-1234.
15. Shen LY, Edmonson MB, Williams GP, Gottam CC, Hinshaw MA, Teng JM. Lipoatrophic panniculitis: case report and review of the literature. Arch Dermatol. 2010;146(8):877-881.
16. Ter Poorten JC, Hebert AA, Ilkiw R. Cold panniculitis in a neonate. J Am Acad Dermatol. 1995;33(2 Pt 2):383-385.
17. Khelifa E, Masouyé I, Chavaz P, Hauser H, Grillet JP, Borradori L. Primary atrophic solitary morphea profunda. Dermatology. 2008;217(3):207-210.
18. Garg A. Lipodystrophies. Am J Med. 2000;108(2):143-152.

Figure 1. Gross image of patient’s right buttock demonstrating single atrophic depression.

A 45-year-old female presented to the clinic with a slightly tender area on the right buttock for the past 4 months. The patient’s medical history was remarkable for seasonal allergies, cognition and memory problems secondary to traumatic injury. Due to her neurologic problems, the patient could not provide a reliable history. She denied trauma to the affected area and could not recall administration of injection medication to the site of concern. On physical examination, a circular, hypopigmented, pink, depression on the mid-lower aspect of the right buttock without surrounding erythema or secondary lesions was noted (Figure 1).
What is Your Diagnosis?
 

Diagnosis: Focal Lipoatrophy from Steroid Injection 

The patient was diagnosed with localized lipoatrophy, most likely secondary to injection medication. Further inquiry revealed that she had received corticosteroid injections for her seasonal allergies in the past, but it was not accurately documented in her medical record.

Localized lipoatrophy was first described as a distinct entity in 1986 by Peters et al based on clinical and histologic findings; 10 years later Dahl et al proposed the term “involutional lipoatrophy” to better describe the ultrastructural changes.^1,2
Adverse local reactions at the site of corticosteroid injection are well-known; however, the frequency at which they occur is quite infrequent.^3-6 These reactions are generally not serious, but they may be a source of significant stress to the patient and can be challenging for the clinician to diagnose.^5,6 Among the various types of local reactions, localized involution lipoatrophy is among the most common and has a propensity to occur more frequently in premenopausal females than males or females past menopause.^2-4

A study by Goldman in 1962 found that local reactions to steroid injection occurred in less than 0.5% of patients. In this study, these reactions were broadly defined as pain, hemorrhage, infection, pigment changes, hypersensitivity and panniculitis as well as subcutaneous atrophy.⁴ Given the low incidence of local side effects, and great efficacy in the treatment of autoimmune and inflammatory conditions, injection corticosteroids are a mainstay in the dermatologist’s armamentarium.^4,7 Local injection also offers the advantage of maintaining a high local concentration of medicine without subjecting the patient to the side effects associated with systemic therapy.⁷ Indications for local steroid injection are many but may include: localized patches of psoriasis, localized neurodermatitis, keloids, lichen planus, alopecia areata, sarcoid, discoid lupus erythematosus and granuloma annulare.⁴

Clinical Presentation
Atrophy of the subcutaneous fat layer generally occurs within 1 to 3 months post-injection with the absence of antecedent clinical or histological inflammation.^2,3,7,8
On clinical examination, the lesion will generally appear as a well-demarcated, skin-colored, non-tender, round or ellipsoid depression occurring at the site of injection with minimal or no changes to the epidermis (Figures 1 and 2).^2,3

Figure 2. Image demonstrating hypopigmented depression with pinkish hue and lack of secondary lesions without surrounding inflammation.

Depressed areas may also have a background of finely distended blood vessels, hypopigmentation, alopecia or thinning of the skin.^4,7,9  These are typically solitary and occur most frequently at the buttocks and proximal extremities.³  Variation is known to occur as described in an interesting case report by Avilés-Izquierdo et al where a patient developed 2, nearly symmetric, bilateral lesions on the buttocks after receiving only a single corticosteroid injection.¹⁰
Laboratory testing is unremarkable with no specific changes if any.2,8 Cutaneous sloughing can occur in instances where relatively large amounts of steroid are injected superficially.⁴

Pathophysiology and Histologic Changes
The exact cause of focal lipoatrophy after steroid injection is not fully elucidated; however, several mechanisms have been identified that play a role in its pathogenesis: activation of macrophages, concentration of the steroid suspension, anatomical depth of injection and history of autoimmune disease.^2,4,8,11,12
Histopathology of studied cases uniformly demonstrated the subdermal fat layer taking on a resemblance of fetal adipose tissue with attenuated fat lobules of various sizes made up of small adipocytes in a well-vascularized and hyalinized background. Adipocytes may have a signet ring cell appearance. Activated, mucin-positive macrophages were prominent and characteristically disbursed throughout the affected lipocytes. No specific changes on immunofluorescence were observed in studied cases.^2,8,11
The presence of scattered macrophages throughout the atrophic lesions in the absence of other inflammatory cells lends support to the post-injury hypothesis where macrophage activation is implicated as the causal mechanism.¹¹ Activation of macrophages by injection injury produces cytokines that induce involution of the subdermal adipose tissue and subsequently brings forth the clinical findings of epidermal depressions.^2,8,13 The post-injury mechanism hypothesis is consistent with other cases of localized trauma that later developed focal lipoatrophy without a history of steroid injection.¹⁴
Although the above explanation suggests a generic mechanism is responsible for subdermal changes, other studies have shown that the concentration of steroid in suspension may play a direct role in the development of subcutaneous atrophy.⁷ Histologic findings in a number of cases of focal atrophy with a history of steroid injection showed evidence of corticosteroid crystal formation.^4,12 Interestingly, Goldman observed in his study that improvement in atrophy improved in proportion to the gradual disappearance of corticosteroid crystals at the affected site.⁴ However, crystal formation is not always appreciated in patients with clinical findings of lipoatrophy even with a history of steroid injection.^2,11
Other factors that have been cited in the development of local atrophy are the depth of steroid injection and history of autoimmune disease.2,12 Schetman et al observed in a controlled study of 25 male subjects receiving multiple triamcinolone injections of equal concentration, delivery of the steroid into the intradermal layers was much more likely to develop atrophy versus injection of steroid into the deeper subcutaneous layer.¹²
Individuals with history of autoimmune disease were observed to develop atrophy more frequently than patients with no history of such disease; thereby, suggesting an immunodysregulation component may be a factor in localized lipoatrophy post-injection.^2,8,11

Differential Diagnosis
Focal lipoatrophy can occur in the context of other localized traumatic injury as seen with the injection of penicillins and insulin.¹⁴ Minor trauma producing these clinical findings does not necessarily have to be iatrogenic. Focal atrophy has been known to occur in the context of recurrent pressure and even in 1 reported case of massage cupping therapy.^8,14
Clinical presentation of lipoatrophy can occur in certain forms of panniculitis, including lipoatrophic panniculitis and cold panniculitis.^15,16 Solitary morphea profunda is a form of localized scleroderma that may present with findings similar to focal lipoatrophy.¹⁷ In the case of either morphea or panniculitis, the histologic findings, laboratory markers and history are distinct; thereby, emphasizing the need of the clinician to obtain a complete history to guide further diagnostic work-up.^15-18

Our Patient
The patient was informed of her diagnosis and possible options for management. She decided not to follow up with the dermatology clinic; therefore, treatment was not started.

Conclusion
Focal lipoatrophy is an uncommon side effect of corticosteroid injection first appearing 1 to 3 months after injection. The atrophy is reversible but can take over a year for significant improvement to be appreciable without medical treatment. Serial infiltration with normal saline injections has been used in successful treatment of focal atrophy with high patient satisfaction.^7,9

Dr. Longhurst is a PGY1 resident with the department of pathology at Case Western Reserve University in Cleveland, OH.
Ms. Bermudez-Locano is with Golden Valley Health Centers in Modesto, CA.
Dr. Khachemoune, the Section Editor of Derm DX, is with the Department of Dermatology at the State University of New York Downstate in Brooklyn, NY.

Disclosure: The authors report no relevant financial relationships.

References
1. Peters MS, Winkelmann RK. The histopathology of localized lipoatrophy. Br J Dermatol. 1986;114(1):27-36.
2. Dahl PR, Zalla MJ, Winkelmann RK. Localized involutional lipoatrophy: a clinicopathologic study of 16 patients. J Am Acad Dermatol. 1996;35(4):523-528.
3. Fisherman EW, Feinberg AR, Feinberg SM. Local subcutaneous atrophy. JAMA. 1962;179:971-972.
4. Goldman L. Reactions following intralesional and sublesional injections of corticosteroids. JAMA. 1962;182:613-616.
5. Morgan AM. Localized reactions to injected therapeutic materials. Part 1. Medical agents. J Cutan Pathol. 1995;22(3):193-214.
6. Morgan AM. Localized reactions to injected therapeutic materials. Part 2. Surgical agents. J Cutan Pathol. 1995;22(4):289-303.
7. Shumaker PR, Rao J, Goldman MP. Treatment of local, persistent cutaneous atrophy following corticosteroid injection with normal saline infiltration. Dermatol Surg. 2005;31(10):1340-1343.
8. Abbas O, Salman S, Kibbi AG, Chedraoui A, Ghosn S. Localized involutional lipoatrophy with epidermal and dermal changes. J Am Acad Dermatol. 2008;58(3):490-493.
9. Stassiy A, Khachemoune A. Unusual depressed areas on the arm and buttock. JAAPA. 2010;23(11):18.
10. Avilés-Izquierdo JA, Longo-Imedio MI, Hernánz-Hermosa JM, Lázaro-Ochaita P.  Bilateral localized lipoatrophy secondary to a single intramuscular corticosteroid injection. Dermatol Online J. 2006;12(3):17.
11. Ahmed I. Post-injection involutional lipoatrophy: Ultrastructural evidence for an activated macrophage phenotype and macrophage related involution of adipocytes. Am J Dermatopathol. 2006;28(4):334-337.
12. Schetman D, Hambrick GW Jr, Wilson CE. Cutaneous changes following local injection of triamcinolone. Arch Dermatol. 1963;88:820-828.
13. Zalla MJ, Winkelmann RK, Gluck OS. Involutional lipoatrophy: macrophage-related involution of fat lobules. Dermatology. 1995;191(2):149-153.
14. Garg A. Acquired and inherited lipodystrophies. N Engl J Med. 2004;350(12):1220-1234.
15. Shen LY, Edmonson MB, Williams GP, Gottam CC, Hinshaw MA, Teng JM. Lipoatrophic panniculitis: case report and review of the literature. Arch Dermatol. 2010;146(8):877-881.
16. Ter Poorten JC, Hebert AA, Ilkiw R. Cold panniculitis in a neonate. J Am Acad Dermatol. 1995;33(2 Pt 2):383-385.
17. Khelifa E, Masouyé I, Chavaz P, Hauser H, Grillet JP, Borradori L. Primary atrophic solitary morphea profunda. Dermatology. 2008;217(3):207-210.
18. Garg A. Lipodystrophies. Am J Med. 2000;108(2):143-152.