British Journal of Dertnatology (1978) 98, i.
A concept of difFuse actinic arteritis THE ROLE OF ACTJNIC DAMAGE TO ELASTIN IN 'AGE CHANGE' AND ARTERITIS OF THE TEMPORAL ARTERY AND IN POLYMYALGIA RHEUMATICA JOHN P.O'BRIEN Consulting Pathologist, St Vineent's Hospital, Sydney, Australia Accepted for publication 13 May 1977
SUMMARY
Actinic damage {actinic elastosis) affecting the internal elastic lamina appears to be the prime cause of 'age change' and arteritis of the temporal artery. Resorption and removal of altered elastin (elastolysis) is an integral part of the pathology of actinic damage. Actinic irradiation is probably responsible for the destruction and disappearance ofa vast number of arterioles in elastotic skin. The intimate connection between temporal arteritis and polymyalgia rheumatica prompts the belief that the vascular and other internal malign components of the temporal arteritis j polymyalgia rheumatica syndrome might likewise be due, albeit indirectly, to the same actinic cause. Actinic elastotic damage at the body surface could have this effect by provoking a state of systemic elastolysis. Although ultraviolet (uv) light is often regarded as the sole cause of actinic elastosis, penetrating infrared (heat) irradiation may deserve a large or even a dominant share of the blame.
The obscure origin of temporal artery disease, how and where it begins, has been studied on the basis of two assumptions: (i) That the physical integrity of an artery depends largely on its internal elastic lamina and (2) that the temporal elastic lamina is prone to actinic damage (elastosis), with consequent inflammation and elastolysis (resorption), in much the same manner as pertains to elastic tissue in the dermis. As regards the first assumption, the indispensability of elastic tissue in vessels is instanced by lathyrism, a nutritional disease in which animals develop aneurysms because the formation of elastic tissue is defective (Barrow, Simpson & Miller, 1974). The stretch resistance of the nonnal internal elastic lamina has also been confirmed experimentally by Cook, Salmo & Yates (1975)- That the lamina plays a dominant role in temporal (giant cell) arteritis was originally stressed by Kimmelstiel, Gilmour & Correspondence address: The Pathology Laboratory, The Medical Centre, 66 High Street, Randwick, 2031, Sydney, Australia. B
I
2
J.P.O'Brien
Hodges (1952) in their classic paper and has since been reasserted (Heptinstall, Porter & Barkley, 1954; Smith, 1969; Parker et al., 1975). The second assumption is an extension of the hypothesis of actinic granuloma of the skin, a focal infiammatory disorder that displays persistent nodules and aimular lesions (O'Brien, 1975). I have submitted that actinic granuloma is a specific entity in which the degenerate, 'elastotic' fibres of actinically-damaged ('aged') skin (Fig. t) are resorbcd by an elastolytic giant cell inflammatory reaction of distinctive pattern (Fig. 2). I have also proposed (O'Brien, 1975, 1976) that actinic granuloma is related to certain disorders affecting African Negroes, namely granuloma multiforme (Allenby & Wilson Jones, 1969) and post-inflammatory elastolysis and cutis laxa (PECL) (Verhagen & Woerdeman, 1975). In attempting to translate the actinic granuloma hypothesis from skin to vessel it is mandatory first to establish that the temporal artery does in fact suffer actinic damage (actinic elastosis) of essentially the same nature as that found in the skin. To determine this question, a 'random' series of 100 temporal arteries (right, left or both) was collected from routine autopsies. The subjects were 39 men and 25 women with an age range of 2391 years. TECHNIQUE
After marking the deep aspect with Indian ink, the plane of tissue containing the superficial temporal artery in its 'exposed' course across the hairless forehead (Fig. 9) was dissected away from the under surface of the reflected anterior craniotomy flap. Having cross-sectioned the tissue in multiple blocks, the slides were stained by a specially modified haematoxylin-eosin procedure (O'Brien, 1975) to display the characteristically blue 'elastotic' fibres. Special stains, including elastic stains, were also employed. FINDINGS
Only 17 internal elastic laminae in the series appear quite normal throughout their entire circumference in all sections. The remaining 83 show typical actinic elastosis of varying degree, the damaged lamina being distinctly blue and often replicated (Figs 4-7). Even more striking is the selective localisation of the damage within the vessel wall; in 44 arteries the lamina is definitely more elastotic in the 'weather' side of the vessel, that is, in the aspect exposed to the environment, than it is in its deep or cranial side. Often only the 'weather* side is damaged (Fig. 5 and Fig. 9 inset). In no instance does the change appear worse in the deepmost lamina. The entire latnina is equally elastotic in 39 and in some of these has been transformed into a jumble of shattered fragments. One vessel displays commencing infiammatory infiltration and is thrombosed (Fig. 7). In many, the lamina has undergone elastolysis in whole or in part, again with a bias for the 'exposed' aspect (Figs 6 and 7). The disorder of the lamina reveals a simple time gradient, the oldest subjects having the most damage. A definite age of onset cannot be established from this study but, of the 8 subjects less than 50 years old, 4 show frank elastosis. The earliest detectable change is in a 31-year-oId male. According to my findings, actinic elastosis of the lamina precedes and merges into 'age change' of the temporal artery as described by Ainsworth, Gresham & Balmforth (1961) and by Lie, Brown& Carter (1970). 'Age change' is the broad term commonly used to denote all the degenerative and proliferative reactions that tnay come to impair both the muscle and the elastic tissue of the artery. In the end, fibrosis tends to dominate.* • Ainsworth er al. (1961) and Lie er al. (1970) did not describe actinic elastosis of the lamina. This disparity could be due to different staining techniques. Also, as stated at the outsetj my investigation was undertaken specifically to assess the presence and role of actinic elastosis in the artery.
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A concept of difFuse actinic arteritis THE ROLE OF ACTJNIC DAMAGE TO ELASTIN IN 'AGE CHANGE' AND ARTERITIS OF THE TEMPORAL ARTERY AND IN POLYMYALGIA RHEUMATICA JOHN P.O'BRIEN Consulting Pathologist, St Vineent's Hospital, Sydney, Australia Accepted for publication 13 May 1977
SUMMARY
Actinic damage {actinic elastosis) affecting the internal elastic lamina appears to be the prime cause of 'age change' and arteritis of the temporal artery. Resorption and removal of altered elastin (elastolysis) is an integral part of the pathology of actinic damage. Actinic irradiation is probably responsible for the destruction and disappearance ofa vast number of arterioles in elastotic skin. The intimate connection between temporal arteritis and polymyalgia rheumatica prompts the belief that the vascular and other internal malign components of the temporal arteritis j polymyalgia rheumatica syndrome might likewise be due, albeit indirectly, to the same actinic cause. Actinic elastotic damage at the body surface could have this effect by provoking a state of systemic elastolysis. Although ultraviolet (uv) light is often regarded as the sole cause of actinic elastosis, penetrating infrared (heat) irradiation may deserve a large or even a dominant share of the blame.
The obscure origin of temporal artery disease, how and where it begins, has been studied on the basis of two assumptions: (i) That the physical integrity of an artery depends largely on its internal elastic lamina and (2) that the temporal elastic lamina is prone to actinic damage (elastosis), with consequent inflammation and elastolysis (resorption), in much the same manner as pertains to elastic tissue in the dermis. As regards the first assumption, the indispensability of elastic tissue in vessels is instanced by lathyrism, a nutritional disease in which animals develop aneurysms because the formation of elastic tissue is defective (Barrow, Simpson & Miller, 1974). The stretch resistance of the nonnal internal elastic lamina has also been confirmed experimentally by Cook, Salmo & Yates (1975)- That the lamina plays a dominant role in temporal (giant cell) arteritis was originally stressed by Kimmelstiel, Gilmour & Correspondence address: The Pathology Laboratory, The Medical Centre, 66 High Street, Randwick, 2031, Sydney, Australia. B
I
2
J.P.O'Brien
Hodges (1952) in their classic paper and has since been reasserted (Heptinstall, Porter & Barkley, 1954; Smith, 1969; Parker et al., 1975). The second assumption is an extension of the hypothesis of actinic granuloma of the skin, a focal infiammatory disorder that displays persistent nodules and aimular lesions (O'Brien, 1975). I have submitted that actinic granuloma is a specific entity in which the degenerate, 'elastotic' fibres of actinically-damaged ('aged') skin (Fig. t) are resorbcd by an elastolytic giant cell inflammatory reaction of distinctive pattern (Fig. 2). I have also proposed (O'Brien, 1975, 1976) that actinic granuloma is related to certain disorders affecting African Negroes, namely granuloma multiforme (Allenby & Wilson Jones, 1969) and post-inflammatory elastolysis and cutis laxa (PECL) (Verhagen & Woerdeman, 1975). In attempting to translate the actinic granuloma hypothesis from skin to vessel it is mandatory first to establish that the temporal artery does in fact suffer actinic damage (actinic elastosis) of essentially the same nature as that found in the skin. To determine this question, a 'random' series of 100 temporal arteries (right, left or both) was collected from routine autopsies. The subjects were 39 men and 25 women with an age range of 2391 years. TECHNIQUE
After marking the deep aspect with Indian ink, the plane of tissue containing the superficial temporal artery in its 'exposed' course across the hairless forehead (Fig. 9) was dissected away from the under surface of the reflected anterior craniotomy flap. Having cross-sectioned the tissue in multiple blocks, the slides were stained by a specially modified haematoxylin-eosin procedure (O'Brien, 1975) to display the characteristically blue 'elastotic' fibres. Special stains, including elastic stains, were also employed. FINDINGS
Only 17 internal elastic laminae in the series appear quite normal throughout their entire circumference in all sections. The remaining 83 show typical actinic elastosis of varying degree, the damaged lamina being distinctly blue and often replicated (Figs 4-7). Even more striking is the selective localisation of the damage within the vessel wall; in 44 arteries the lamina is definitely more elastotic in the 'weather' side of the vessel, that is, in the aspect exposed to the environment, than it is in its deep or cranial side. Often only the 'weather* side is damaged (Fig. 5 and Fig. 9 inset). In no instance does the change appear worse in the deepmost lamina. The entire latnina is equally elastotic in 39 and in some of these has been transformed into a jumble of shattered fragments. One vessel displays commencing infiammatory infiltration and is thrombosed (Fig. 7). In many, the lamina has undergone elastolysis in whole or in part, again with a bias for the 'exposed' aspect (Figs 6 and 7). The disorder of the lamina reveals a simple time gradient, the oldest subjects having the most damage. A definite age of onset cannot be established from this study but, of the 8 subjects less than 50 years old, 4 show frank elastosis. The earliest detectable change is in a 31-year-oId male. According to my findings, actinic elastosis of the lamina precedes and merges into 'age change' of the temporal artery as described by Ainsworth, Gresham & Balmforth (1961) and by Lie, Brown& Carter (1970). 'Age change' is the broad term commonly used to denote all the degenerative and proliferative reactions that tnay come to impair both the muscle and the elastic tissue of the artery. In the end, fibrosis tends to dominate.* • Ainsworth er al. (1961) and Lie er al. (1970) did not describe actinic elastosis of the lamina. This disparity could be due to different staining techniques. Also, as stated at the outsetj my investigation was undertaken specifically to assess the presence and role of actinic elastosis in the artery.
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