CED
Clinical dermatology • Concise report
Clinical and Experimental Dermatology
Lipomembranous changes associated with systemic lupus erythematosus J. S. Kim,1 H. Y. Kim,2 Y. G. Kim,1 J. O. Paek1 and H. J. Yu1 1 Department of Dermatology, Hanyang University Guri Hospital, Guri, Korea; and 2Department of Dermatology, Hanyang University Seoul Hospital, Seoul, Korea
doi:10.1111/ced.12268
Summary
Lipomembranous changes are distinctive histopathological findings, which include the presence of cystic cavities lined by crenulated, hyaline membranes in adipose tissue. It is likely that ischaemia is fundamental to the development of these lesions, and that lipomembranes are formed from the products of degenerating fat cell membranes by some unknown mechanism. Such changes may be seen, although rarely, in many types of subcutaneous inflammatory processes. However, an association with systemic lupus erythematosus (SLE) is rare. We report a patient with SLE who had the histological features of lipomembranous changes associated with vasculopathy.
Lipomembranous changes occur in adipose tissue, and ischaemia due to vascular impairment is thought to be related to the development of these lesions.1 Such changes may be seen in some types of connective tissue disorders; however, an association with systemic lupus erythematosus (SLE) is rare. We report a patient with SLE who had the histological features of lipomembranous changes and vasculopathy.
at titres of 36 and 19 IgG phospholipid units (GPL), respectively, on two occasions, 5 months apart. The patient was taking oral prednisolone 20 mg/day and hydroxychloroquine 300 mg/day. On physical examination, localized reticulated reddish to brownish patches and subcutaneous tender nodules, involving both lower legs, were seen (Fig. 1). On histopathological examination, there was visible necrosis of the vascular walls of medium-sized arteries
Report A 52-year-old woman presented with a 2-year history of change in the skin colour of both legs. She had been diagnosed with SLE 6 months previously, based on the findings of oral ulcer, arthritis and abnormal laboratory test results. At the time, she was positive for antinuclear antibody (titre of 1 : 2560 in a homogenous pattern), anti-Sm, anti-RNP and antidouble stranded DNA (1:106). Laboratory tests for anti-phospholipid syndrome indicated positivity for b2-glycoprotein I-dependent anti-cardiolipin antibodies
(a)
(b)
Correspondence: Dr Joung-Soo Kim, Department of Dermatology, Hanyang University Guri Hospital, Guri, Gyeonggi-Do, 471-701, Korea E-mail: [email protected] Conflict of interest: the authors declare that they have no conflicts of interest. Accepted for publication 21 October 2013
ª 2014 British Association of Dermatologists
Figure 1 (a,b) Localized reticulated reddish to brownish patches
on the lower legs in a patient with systemic lupus erythematosus.
Clinical and Experimental Dermatology (2014) 39, pp319–322
319
Lipomembranous changes associated with SLE J. S. Kim et al.
within the subcutaneous tissue, and hyalinization of perivascular tissue. In the subcutaneous layer, there was degeneration of subcutaneous fat cells with lipomembranous changes that were characterized as microcyst-lined and macrocyst-lined lipomembranes within fat lobules, forming small pseudopapillae. Elastic stain highlighted destruction of the arterial elastic lamina (Fig. 2). However, there were no histological features of concomitant SLE in the epidermis or
(a)
dermis, and findings of lupus panniculitis were not obvious in the subcutis. Computed tomography (CT) angiography did not detect any abnormalities in the patient’s legs. Lipomembranous changes are striking and distinctive alterations in adipose tissue, and were first described in Nasu–Hakola disease.2 Such changes have since been reported in a large number of diseases of unrelated aetiologies, and were encountered in 21% of
(b)
(c)
(d)
Figure 2 (a) The epidermis and dermis did not display features of systemic lupus erythematosus; (b) lipomembranous changes in adi-
pose tissue; (c,d) destruction of vascular walls. Haematoxylin and eosin, original magnification (a) 940; (b) 9200; (c) 9100. (d) Elastic stain, original magnification 9100.
320
Clinical and Experimental Dermatology (2014) 39, pp319–322
ª 2014 British Association of Dermatologists
Lipomembranous changes associated with SLE J. S. Kim et al.
cases of fat necrosis.3 These changes are thought to be associated with traumatic insults or ischaemic alterations due to vascular insufficiency,4 and it has become evident that they do not justify a diagnosis of vascular disease or of a specific panniculitis. The explanation for their formation remains obscure, and several theories have been proposed. According to one view, these changes result from an interaction between residual elements of necrotic fat cells and macrophages, probably as a consequence of inflammatory and ischaemic disorders in fatty tissue.4 The fact that the legs are the most commonly affected site supports the view that antecedent trauma and subsequent interruption of the blood supply are the main causes of the condition. Others have suggested that they may result from a variety of insults to adipose tissue, including infectious, autoimmune and physical processes.5 Lipomembranous changes are seen in numerous connective-tissue disorders, including lupus profundus, morphoea and dermatomyositis. However, there are only four reported cases of such changes associated with SLE. Two of the patients involved had other underlying diseases, namely cytomegalovirus infectionrelated vasculitis and a history of cerebral infarction, respectively.6,7 In the other two cases, the calcification and lipomembranous changes coexisted with lupus erythematosus panniculitis associated with SLE.8,9 Our patient, however, had no other comorbidities, and biopsy specimens did not display any features of lupus panniculitis such as aggregations of lymphocytes in the subcutis, sclerosis of the dermal connective tissues, septolobular panniculitis or mucin deposition. Based on the histological finding of vasculopathy of the medium-sized arteries within the subcutaneous layer, the lipomembranous changes in this patient may have been the result of local ischaemia. Although there were no specific findings on CT angiography, and the laboratory tests did not fit the criteria for antiphospholipid syndrome, we believe that the raised b2-glycoprotein I-dependent anti-cardiolipin antibodiy titre, which frequently accompanies findings in patients with SLE, may be associated with the vasculopathy. We treated the patient with topical steroid, which resulted in slight improvement, and she continues to be followed up regularly. In conclusion, this was a case with lipomembranous changes in the subcutaneous tissues, associated with SLE. This case supports a pathogenic link between vascular injury and lipomembranous changes. Although there is lack of a proven correlation, it is important for dermatologists to be aware of the possibility that lipomembranous changes can occur in patients with SLE.
ª 2014 British Association of Dermatologists
Learning points
•
Lipomembranous changes are distinctive histopathological findings revealing the presence of cystic cavities lined by crenulated, hyaline membranes in adipose tissue. • Lipomembranous changes can be seen in numerous connective-tissue disorders, including lupus profundus, morphoea and dermatomyositis. • These changes appear to result from interaction between residual elements of necrotic fat cells and macrophages, probably as a consequence of inflammatory and ischemic disorders in fatty tissue. • Others have suggested that these changes can result from a variety of insults to adipose tissue, including infectious, autoimmune and physical processes. • This case supports a pathogenic link between vascular injury and lipomembranous changes and, even though there is lack of a clear-cut connection, it is important for dermatologists to be aware of the possibility that lipomembranous changes can be seen in SLE.
References 1 Mii Y, Miyauchi Y, Yoshikawa T et al. Ultrastructural lipid and glycoconjugate cytochemistry of membranes lipodystrophy (Nasu-Hakola disease). Virchows Arch 1991; 419: 137–42. 2 Nasu T, Tsukahara Y, Terayama K. A lipid metabolic disease—”membranous lipodystrophy”—an autopsy case demonstrating numerous peculiar membrane-structures composed of compound lipid in bone and bone marrow and various adipose tissues. Acta Pathol Jpn 1973; 23: 539–58. 3 Alegre VA, Winkelmann RK, Aliaga A. Lipomembranous changes in chronic panniculitis. J Am Acad Dermatol 1988; 19: 39–46. 4 Ahn SK, Lee BJ, Lee SH et al. Nodular cystic fat necrosis in a patient with erythema nodosum. Clin Exp Dermatol 1995; 20: 263–5. 5 Jorizzo JL, White WL, Zanolli MD et al. Sclerosing panniculitis. A clinicopathologic assessment. Arch Dermatol 1991; 127: 554–8. 6 Ramdial PK, Chetty R. Vasculitis-induced membranous fat necrosis. J Cutan Pathol 1999; 26: 405–10. 7 Yamamoto T, Furuhata Y, Tsuboi R. Lipomembranous changes and calcification associated with systemic lupus erythematosus. Clin Exp Dermatol 2007; 32: 278–80.
Clinical and Experimental Dermatology (2014) 39, pp319–322
321
Lipomembranous changes associated with SLE J. S. Kim et al.
8 Biswas A, Byrne JP. Extensive endarteritis obliterans in a case of lupus panniculitis with membranocystic changes and dystrophic calcification: a pathogenetic link? Eur J Dermatol 2007; 17: 550–1.
322
Clinical and Experimental Dermatology (2014) 39, pp319–322
9 Suda T, Hara H, Okada T et al. Coexistence of extensive calcification and membrano-cystic changes in lupus erythematosus panniculitis associated with systemic lupus erythematosus. Eur J Dermatol 2007; 17: 86–8.
ª 2014 British Association of Dermatologists
Clinical dermatology • Concise report
Clinical and Experimental Dermatology
Lipomembranous changes associated with systemic lupus erythematosus J. S. Kim,1 H. Y. Kim,2 Y. G. Kim,1 J. O. Paek1 and H. J. Yu1 1 Department of Dermatology, Hanyang University Guri Hospital, Guri, Korea; and 2Department of Dermatology, Hanyang University Seoul Hospital, Seoul, Korea
doi:10.1111/ced.12268
Summary
Lipomembranous changes are distinctive histopathological findings, which include the presence of cystic cavities lined by crenulated, hyaline membranes in adipose tissue. It is likely that ischaemia is fundamental to the development of these lesions, and that lipomembranes are formed from the products of degenerating fat cell membranes by some unknown mechanism. Such changes may be seen, although rarely, in many types of subcutaneous inflammatory processes. However, an association with systemic lupus erythematosus (SLE) is rare. We report a patient with SLE who had the histological features of lipomembranous changes associated with vasculopathy.
Lipomembranous changes occur in adipose tissue, and ischaemia due to vascular impairment is thought to be related to the development of these lesions.1 Such changes may be seen in some types of connective tissue disorders; however, an association with systemic lupus erythematosus (SLE) is rare. We report a patient with SLE who had the histological features of lipomembranous changes and vasculopathy.
at titres of 36 and 19 IgG phospholipid units (GPL), respectively, on two occasions, 5 months apart. The patient was taking oral prednisolone 20 mg/day and hydroxychloroquine 300 mg/day. On physical examination, localized reticulated reddish to brownish patches and subcutaneous tender nodules, involving both lower legs, were seen (Fig. 1). On histopathological examination, there was visible necrosis of the vascular walls of medium-sized arteries
Report A 52-year-old woman presented with a 2-year history of change in the skin colour of both legs. She had been diagnosed with SLE 6 months previously, based on the findings of oral ulcer, arthritis and abnormal laboratory test results. At the time, she was positive for antinuclear antibody (titre of 1 : 2560 in a homogenous pattern), anti-Sm, anti-RNP and antidouble stranded DNA (1:106). Laboratory tests for anti-phospholipid syndrome indicated positivity for b2-glycoprotein I-dependent anti-cardiolipin antibodies
(a)
(b)
Correspondence: Dr Joung-Soo Kim, Department of Dermatology, Hanyang University Guri Hospital, Guri, Gyeonggi-Do, 471-701, Korea E-mail: [email protected] Conflict of interest: the authors declare that they have no conflicts of interest. Accepted for publication 21 October 2013
ª 2014 British Association of Dermatologists
Figure 1 (a,b) Localized reticulated reddish to brownish patches
on the lower legs in a patient with systemic lupus erythematosus.
Clinical and Experimental Dermatology (2014) 39, pp319–322
319
Lipomembranous changes associated with SLE J. S. Kim et al.
within the subcutaneous tissue, and hyalinization of perivascular tissue. In the subcutaneous layer, there was degeneration of subcutaneous fat cells with lipomembranous changes that were characterized as microcyst-lined and macrocyst-lined lipomembranes within fat lobules, forming small pseudopapillae. Elastic stain highlighted destruction of the arterial elastic lamina (Fig. 2). However, there were no histological features of concomitant SLE in the epidermis or
(a)
dermis, and findings of lupus panniculitis were not obvious in the subcutis. Computed tomography (CT) angiography did not detect any abnormalities in the patient’s legs. Lipomembranous changes are striking and distinctive alterations in adipose tissue, and were first described in Nasu–Hakola disease.2 Such changes have since been reported in a large number of diseases of unrelated aetiologies, and were encountered in 21% of
(b)
(c)
(d)
Figure 2 (a) The epidermis and dermis did not display features of systemic lupus erythematosus; (b) lipomembranous changes in adi-
pose tissue; (c,d) destruction of vascular walls. Haematoxylin and eosin, original magnification (a) 940; (b) 9200; (c) 9100. (d) Elastic stain, original magnification 9100.
320
Clinical and Experimental Dermatology (2014) 39, pp319–322
ª 2014 British Association of Dermatologists
Lipomembranous changes associated with SLE J. S. Kim et al.
cases of fat necrosis.3 These changes are thought to be associated with traumatic insults or ischaemic alterations due to vascular insufficiency,4 and it has become evident that they do not justify a diagnosis of vascular disease or of a specific panniculitis. The explanation for their formation remains obscure, and several theories have been proposed. According to one view, these changes result from an interaction between residual elements of necrotic fat cells and macrophages, probably as a consequence of inflammatory and ischaemic disorders in fatty tissue.4 The fact that the legs are the most commonly affected site supports the view that antecedent trauma and subsequent interruption of the blood supply are the main causes of the condition. Others have suggested that they may result from a variety of insults to adipose tissue, including infectious, autoimmune and physical processes.5 Lipomembranous changes are seen in numerous connective-tissue disorders, including lupus profundus, morphoea and dermatomyositis. However, there are only four reported cases of such changes associated with SLE. Two of the patients involved had other underlying diseases, namely cytomegalovirus infectionrelated vasculitis and a history of cerebral infarction, respectively.6,7 In the other two cases, the calcification and lipomembranous changes coexisted with lupus erythematosus panniculitis associated with SLE.8,9 Our patient, however, had no other comorbidities, and biopsy specimens did not display any features of lupus panniculitis such as aggregations of lymphocytes in the subcutis, sclerosis of the dermal connective tissues, septolobular panniculitis or mucin deposition. Based on the histological finding of vasculopathy of the medium-sized arteries within the subcutaneous layer, the lipomembranous changes in this patient may have been the result of local ischaemia. Although there were no specific findings on CT angiography, and the laboratory tests did not fit the criteria for antiphospholipid syndrome, we believe that the raised b2-glycoprotein I-dependent anti-cardiolipin antibodiy titre, which frequently accompanies findings in patients with SLE, may be associated with the vasculopathy. We treated the patient with topical steroid, which resulted in slight improvement, and she continues to be followed up regularly. In conclusion, this was a case with lipomembranous changes in the subcutaneous tissues, associated with SLE. This case supports a pathogenic link between vascular injury and lipomembranous changes. Although there is lack of a proven correlation, it is important for dermatologists to be aware of the possibility that lipomembranous changes can occur in patients with SLE.
ª 2014 British Association of Dermatologists
Learning points
•
Lipomembranous changes are distinctive histopathological findings revealing the presence of cystic cavities lined by crenulated, hyaline membranes in adipose tissue. • Lipomembranous changes can be seen in numerous connective-tissue disorders, including lupus profundus, morphoea and dermatomyositis. • These changes appear to result from interaction between residual elements of necrotic fat cells and macrophages, probably as a consequence of inflammatory and ischemic disorders in fatty tissue. • Others have suggested that these changes can result from a variety of insults to adipose tissue, including infectious, autoimmune and physical processes. • This case supports a pathogenic link between vascular injury and lipomembranous changes and, even though there is lack of a clear-cut connection, it is important for dermatologists to be aware of the possibility that lipomembranous changes can be seen in SLE.
References 1 Mii Y, Miyauchi Y, Yoshikawa T et al. Ultrastructural lipid and glycoconjugate cytochemistry of membranes lipodystrophy (Nasu-Hakola disease). Virchows Arch 1991; 419: 137–42. 2 Nasu T, Tsukahara Y, Terayama K. A lipid metabolic disease—”membranous lipodystrophy”—an autopsy case demonstrating numerous peculiar membrane-structures composed of compound lipid in bone and bone marrow and various adipose tissues. Acta Pathol Jpn 1973; 23: 539–58. 3 Alegre VA, Winkelmann RK, Aliaga A. Lipomembranous changes in chronic panniculitis. J Am Acad Dermatol 1988; 19: 39–46. 4 Ahn SK, Lee BJ, Lee SH et al. Nodular cystic fat necrosis in a patient with erythema nodosum. Clin Exp Dermatol 1995; 20: 263–5. 5 Jorizzo JL, White WL, Zanolli MD et al. Sclerosing panniculitis. A clinicopathologic assessment. Arch Dermatol 1991; 127: 554–8. 6 Ramdial PK, Chetty R. Vasculitis-induced membranous fat necrosis. J Cutan Pathol 1999; 26: 405–10. 7 Yamamoto T, Furuhata Y, Tsuboi R. Lipomembranous changes and calcification associated with systemic lupus erythematosus. Clin Exp Dermatol 2007; 32: 278–80.
Clinical and Experimental Dermatology (2014) 39, pp319–322
321
Lipomembranous changes associated with SLE J. S. Kim et al.
8 Biswas A, Byrne JP. Extensive endarteritis obliterans in a case of lupus panniculitis with membranocystic changes and dystrophic calcification: a pathogenetic link? Eur J Dermatol 2007; 17: 550–1.
322
Clinical and Experimental Dermatology (2014) 39, pp319–322
9 Suda T, Hara H, Okada T et al. Coexistence of extensive calcification and membrano-cystic changes in lupus erythematosus panniculitis associated with systemic lupus erythematosus. Eur J Dermatol 2007; 17: 86–8.
ª 2014 British Association of Dermatologists
