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Giant cell arteritis: A systemic disease with rare cutaneous manifestations
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Giant cell arteritis: A systemic disease with rare cutaneous manifestations Eric W. Baum, M.D., W. Mitchell Sams, Jr., M.D., and R. Rex Payne, M.D. Birmingham, AL Giant cell arteritis is a systemic disease usually occurring in patients in the fifth decade or older, more often in women. Dermatologic manifestations are rare but, when found, are usually expressed as scalp ulcerations or blanching associated with gangrene of the tongue. The dermatologist should be familiar with the entity because it is often more severe when associated with scalp necrosis, and prompt intervention with corticosteroids can prevent catastrophic sequelae. (J AM ACAD DERMATOL6: 1081-1088, 1982.)
Although Hutchinson 1 is credited with describing the first case of temporal arteritis in the medical literature, this disease entity may have been recorded as early as A.O. 940 to 1010 by Ali Ibn Isa in the Tadhkirat. 2 However, it was Horton et al a who first defined this disease as the clinicopathologic entity we recognize today. A number o f names have been used to describe this condition, including temporal arteritis, 1'3 giant cell arteritis, 4 cranial arteritis, 5 giant cell polyarteritis, 6 polymyalgia rheumatica, 7 Horton's disease, 3,s arteritis of the aged, 9 and granulomatous arteritis. 1° As with some other authors, 2,4,11-~3 we prefer the term "giant cell arteritis." Epidemiologic studies confirm that giant cell arteritis is a disease of the elderly. Reported patients range in age from 48 to over 90 years, with the greatest number of patients falling within the age range of 65 to 73 years. 14 Isolated cases have been reported in young and middle-aged adults, but substantiation that these represent true cases of giant cell arteritis is questionable. 's,'6 The disease
is more common in women, by ratios of 3: 1, ~,17 2: 1,18'19 or 65%. '4 Recent studies have demonstrated that the disease is more common than previously thought. 14,'r,20 In 1950 to 1959 there was an average incidence of 5.1/100,000, and in the period from 1970 to 1974 this rose to 17.4/100,000 per year. t4.20 The actual rate may even be higher, since autopsy studies of 889 people without clinically suspected disease demonstrated that 1.7% of patients had giant cell arteritis on biopsy of the temporal artery o r aorta. 14'~° The prevalence of this disease is roughly equal to that of ankylosing spondylitis in the same community studied. 17 Because of the infrequency with which the skin is involved, most articles in the dermatology literature stress how infrequently this disease is encountered by dermatologists. ~,~a,21.~2 Many review articles on the subject fail to mention cutaneous manifestations at all. We present a patient who exhibited some of the more classic symptoms of giant cell arteritis and soon after developed alopecia and ulcerations of the scalp. CASE REPORT
From the Departmentof Dermatology,Universityof Alabama in Birmingham. Reprintrequests to: Dr. R. Rex Payne,7901 Ist AvenueSouth,Suite 202, Birmingham,AL 35206. 0190-9622/82/061081+08500.80/0 © 1982 Am Acad Dermatol
A 73-year-old white woman began complaining of a bandlike pain in the left parietal region, pain on mastication, and sudden onset of tinnitus and vertigo 3 1081
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Fig. 1. Left side of scalp after shaving for biopsy, showing multiple ulcerations with an area of central necrosis within a large ulceration. weeks before hospitalization. When nausea, vomiting, and a decrease in visual acuity occurred, she was admitted to the hospital. Past medical history included a several-year history of hypertension, for which she was being treated with chlorthalidone combined with reserpine (Regroton), 50 mg orally, once per day. Two months previously she had been seen by her private physician for fatigue, joint pain, and a noticeable decrease in stamina when she was performing activities of daily living. At this time, a complete blood count, serum concentrations of iron, and vitamin B ~u levels demonstrated pernicious anemia, which was treated with intramuscular vitamin B ~2 injections. Physical examination on admission revealed a welldeveloped, well-nourished white woman with mild pain in the left parietal area. A bruit was audible in the left carotid artery. Examination of the left side of the scalp revealed early necrosis with superficial ulcerations and hair loss (Fig. 1). Ophthalmologic examination revealed best corrected vision of 20/30 in the right eye and 20/100 in the left. The left pupil was slightly larger than the right, and both pupils were reactive to light. The right visual field was normal, and the left demonstrated an inferior altitudinal defect. The optic disc was normal on the right and pale on the left. Pertinent laboratory results were as follows: erythrocyte sedimentation rate, 54 mm/hr (Westergren method); hemoglobin, 11.2 gm/dl; hematocrit, 35.2%; indices within normal limits; white blood cell count, 5.4%; normal differential; alkaline phosphatase, 199 U/liter;
"y-glutamyl transpeptidase, 159 U/liter; blood glucose level, 118 mg/dl. Liver-spleen scan revealed a normal liver with increased shunting of isotope to the spleen, suggesting mild hepatocellular disease. Upper gastrointestinal series demonstrated a small diverticulum in the distal duodenum. Urinalysis, urine culture, skull x-rays, bone'scan, electrocardiogram, oral cholecystogram, and chest x-ray were all within normal limits. Computerized axial tomography scan of the head revealed some atrophy of the brain but no focal defects. Doppler studies suggested bilateral stenosis of the carotid arteries. A temporal artery biopsy confirmed giant cell arteritis, and the patient was started on oral prednisone, 100 mg daily. Her headaches, joint pain, and tinnitus improved within 2 days. This therapy was continued, and at the time of writing, 1l months after discharge, she was taking 10 mg/day. Although visual acuity was unchanged, her scalp lesions had completely healed. Microscopic findings. Biopsy of the temporal artery showed an inflammatory process that extended through the entire thickness of the artery wall and was composed mainly of lymphocytes and histiocytes. Some of the histiocytes were multinucleated. There was almost complete occlusion of the lumen (Figs. 2 and 3). In the intima there were deposits of fibrinlike material, which was mainly observed in the areas of the internal elastic lamina. By means of a Verhoeff-van Gieson stain, the elastic fibers were found to be noticeably fragmented, with bits of elastic tissue scattered within the inflammatory infiltrate (Fig. 4).
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Fig. 2. Low-power view shows inflammation of all layers of the temporal artery, with multiple small endothelium-lined spaces centrally, resulting from previous thrombosis and recanalization.
The pathology of giant cell arteritis is segmental. For this reason giant cells need not be seen to make the diagnosis. In our patient's biopsy, a few giant cells were seen. Some authors believe that the absence of giant cells signifies a worse prognosis, "a whereas others refute this finding.~7 One author proposed a tuberculous etiology to explain the presence of the giant cells; however, no tubercles or acid-fast bacilli have been demonstrated. There seems to be some accord, however, that the giant cells may be due to a foreign body reaction to the fragmentation of the elastic lamina. T M DISCUSSION The most frequent cutaneous finding in giant cell arteritis is necrosis of the scalp, resulting in
ulceration that may be localized to one side, "~5"2(~ may be bitemporal, La,zT''-'s or may extend to large areas so that the entire scalp may be involved. 2~'2" Of those patients with scalp necrosis, 67% will develop irreversible visual loss, and the mortality rate is 41%, considerably higher than among patients who have giant cell arteritis without scalp necro sis.2:J To the best of our knowledge, scalp ulcerations with necrosis have been documented in only fifteen previous case reports. In the first extensive review of skin manifestations o f giant cell arteritis, Kinmont and McCallure (~included the following less c o m m o n signs of
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Fig, 3. High-power view demonstrating mixed infiltrate of lymphocytes and histiocytes,
some of which are multinucleated. skin involvement: butterfly rash of the face, gangrene of the leg, purpura simulating HenochSchSnlein purpura (allergic vasculitis), purpura and ecchymoses, leg ulcers, painful scalp, lumps with crusting and secondary infection withStaphylococcus aureus, scalp bullae, and tongue changes including gangrene, erythema, necrosis, and sloughing. Other skin findings noted in giant cell arteritis include urticaria, edema, lividity, tender nodules, tortuous and prominent arteries, supravascular pallor, and hyperpigmentation.13 Abundant reports describe changes in the tongue, with objective and subjective findings, including pain, burning, recurrent blanching, redness or erythema, bluish swellings, gangrene, necrosis, and sloughing. 2~'~'~°-34 Severe headache, usually of a dull, boring, or throbbing nature, is the most c o m m o n complaint. However, lancinating pain, which can make combing one's hair or even lying on the affected side of the scalp extremely painful, has been reported. 3s In many cases in which headaches are a prominent symptom, one may find tender, firm, enlarged, palpable, pulseless branches of the su-
perior temporal artery. Associated with the headaches may be periorbital and facial edema. Constitutional complaints include fatigue, malaise, weight loss, myalgia, arthralgia, anorexia, and sweating. Claudication, in the form of pain localized to the jaw, teeth, ear, and zygoma, is significant. Horton, 36 in a later article, believed pain on mastication and relief after resting these muscles to be diagnostic for giant cell arteritis. Visual loss may occur in 42% to 58% of patients with giant cell arteritis. It is usually sudden in onset, partial or complete, and usually permanent. Rarely, episodes of transient visual blurring precede more catastrophic visual impairment. Other ophthalmologic involvement includes ptosis, extraocular muscle palsies, anterior segment necrosis, hypotonia, and visual hallucinations, a7 Neurologic involvement in giant cell arteritis is primarily due to arteritic lesions occurring within the cerebral circulation. Reported manifestations include stroke, coma, dementia, psychosis, confusion, depression, and aneurysms of major arteries .a~ As a consequence of coronary arteritis, clini-
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Fig. 4. Verhoeff-van Gieson stain showing fragmentation of the internal elastic lamina.
cians should be aware of possible myocardial infarctions, bouts of angina pectoris, and even congestive heart failure."° Polymyalgia rheumatica is a clinical syndrome that is closely intertwined with giant cell arteritis, a'~ usually occurs in individuals greater than 50 years of age, and is indicated by pain and stiffness in the proximal muscles of the neck, shoulders, and back. Constitutional complaints of fever, malaise, and weight loss are common. However, in polymyalgia rheumatica, vessels of the scalp are rarely involved, a6,4° A high erythrocyte sedimentation rate, as well as a usually rapid response to systemic steroids, has been reported. 18-20,41,42 Giant cell arteritis may involve arteries of large,
medium, or small <13 size, as well as veins. 14 The most frequent involvement is of large and medium-sized arteries 's,4a from the aortic arch to the scalp, z° The typical histologic picture of giant cell arteritis has been described in arteries in the uterus, 44 legs, 4'~ abdomen, 2 and hand. 4cI The most significant laboratory finding in giant cell arteritis is a moderate to marked increase in the erythrocyte sedimentation rate, sometimes exceeding 100 ram/hour (Westergren method),14 but normal sedimentation rates have been reported even with active disease. 2 Anemia, most often of a hypochromic or normochromic pattern, is also a common finding. Other common laboratory abnormalities are mild to moderate leukocytosis,
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mild thrombocytosis, serum protein electrophoresis (especially a~), decreased serum albumin with an occasional reversal of the albumin-globulin ratio, and increased gamma globulins, complement, and blood fibrinogens. One third of these patients have a mild abnormality in liver function t e s t s , 14'2° manifested as an increased retention of sulfobromophthalein and increased alkaline phosphatase activity. An association with granulomatous hepatitis has been reported. 4r Occasional elevations of serum glutamic-oxaloacetic transaminase and partial thromboplastin time have also been reported. Renal function tests are usually normal, although red cell casts, and occasionally granular, tubular, or hyaline casts, have been reported. 14,20 Antinuclear antibodies are generally absent. This is significant because, in elderly patients, lupus erythematosus may closely simulate the polymyalgia rheumatica syndrome. 48 Angiography of involved vessels may reveal irregular constrictions, dilations, and excessive tortuosity of vessels. 49 Synovial fluid analysis has demonstrated poor mucin clotting and increased leukocytes with an increased percentage o f polymorphonuclear leukocytes, all compatible with a mild inflammation. Synovial biopsy has demonstrated a lymphocytic synovitis. 14,a° Among the etiologic agents proposed for giant cell arteritis are the aging process, '4,2° infectious agents, ~.'4,24 infections leading to thrombosis, 24 a circulating anticoagulant, '~° drugs (sulfonamide, al indomethacin, '~2 allopurinoPa), allergies, 5 allergic reactions to elastic tissue, 2 foreign body reactions, 44'49 Mycoplasma (a pleuropneumonia-like organism) infection, 49 contact with birds (especially parakeets), ~9 familial aggregation--genetic or hereditary, 14,2° immunologic mechanisms TM (both cellular and humoral, and, specifically, an autoimmune mechanism14,19,40). The possibility of an autoimmune mechanism has been supported by the demonstration of increased levels of circulating immune complexes in acute disease 2° and granular deposits of immunoreactive products as seen with immunofluorescence. ,~4 In many patients giant cell arteritis resolves spontaneously,'~"7'4"44"~ but the mortality rate has been reported to be as high as 12%. 49 The usual
cause of death is thrombosis of the cerebral or coronary arteries. 2'49 However, it is likely that rapid institution of corticosteroid therapy has lowered the death rate. Systemic corticosteroids should be administered as soon as the diagnosis is made, since there is strong documentation that prompt steroid therapy may prevent cerebrovascular accidents and myocardial infarctions and may protect the remaining vision of patients with only partial blindness. 2''~5 The initial dose of prednisone should be from 40 to 100 mg/day, but the length of therapy is controversial. Periods from 3 months to 2 years have been recommended. If therapy is to be for short periods of time, slow, gradual reduction of the dosage is advised, since the possibility of recurrence is greatest in the first 2 years. A decrease in the erythrocyte sedimentation rate is the best indication of improvement. Increases in the erythrocyte sedimentation rate should alert the physician to a possible recrudescence. Other therapeutic modalities that have been examined are hyperbaric oxygenation, salicylates, sulfonamides, anticoagulants, amyl nitrite, phenylbutazone, chloroquine, and indomethacin. None of these has proved to be as efficacious as corticosteroid therapy. 2'49 Phenylbutazone has been utilized successfully in polymyalgia rheumatica, but results have been inconsistent. 4°'44 In conclusion, the dermatologist should be aware of the cutaneous manifestations of giant cell arteritis. The aggressive nature of this disease is especially noted when it is associated with scalp ulcerations. 29 Rapid diagnosis and prompt institution of therapy can avert the catastrophic sequelae of stroke, myocardial infarction, and blindness. We express our thanks to Dr. Lanning Kline for his suggestions concerning visual changes and to Dr. Gene Ball for his suggestions regarding polymyalgia rheumatica and liver complications in giant cell arteritis. REFERENCES
1. HutchinsonJ: Diseases of the arteries. Arch Surg (London) 1:323-329, 1890. 2. Hamilton CR Jr, Shelley WM, Tumulty PA: Giant cell arteritis: Including temporal arteritis and polymyalgia rheumatica. Medicine (Baltimore) 50:1-27, 1971. 3. Horton BT, Magath TB, Brown GE: An undescribed form of arteritis of the temporal vessels. Proc Mayo Clin 7:700-701, 1932,
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4. Gilmour JR: Giant-cell chronic arteritis. J Pathol Bacteriol 53:263-277, 1941. 5. Kilbourne ED, Wolff HG: Cranial arteritis: A critical evaluation of the syndrome of "temporal arteritis" with report of a case. Ann Intern Med 24:1-10, 1946. 6. Kinmont PDC, McCallum DI: Skin manifestations of giant-cell arteritis. Br J Dermatol 76:299-308, 1964. 7. Barber HS: Myalgic syndrome with constitutional effects: Polymyalgia rheumatica. Ann Rheum Dis 16: 230-237, 1957. 8. Horton BT, Magath TB: Arteritis of the temporal vessels: Report of seven cases. Proc Mayo Clin 12:548-553, 1937. 9. Paulley JW, Hughes JP: Giant-cell arteritis, or arteritis of the aged. Br Med J 2: 1562-1567, 1960. 10. McMillan GC: Diffuse granulomatous aortitis with giant cells: Associated with partial rupture and dissection of the aorta. Arch Pathol 49:63-69, 1950. i1. Ackerman AB: Histologie diagnosis of inflammatory skin diseases. Philadelphia, 1978, Lea & Febiger, pp. 374-375. 12. Kimmelstiel P, Gilmour MT, Hodges HH: Degeneration of elastic fibers in granulomatous giant cell arteritis (temporal arteritis). Arch Pathol 54:157-168, 1952. 13. Hitch JM: Dermatologic manifestations ~f giant-cell (temporal, cranial) arteritis. Arch Dermatol 101:409415, I970. 14. Hunder GG, Alien GL: Giant cell arteritis: A review. Bull Rheum Dis 29:980-987, 1978-1979. 15. Bethlenfalvay NC, Nusynowitz ML: Temporal arteritis: A rarity in the young adult. Arch Intern Med 114:487489, 1964. 16. Lie JT, Gordon LP, Titus JL: Juvenile temporal arteritis: Biopsy study of four cases. JAMA 234:496-499, 1975. 17. Huston KA, Hunder GG, Lie JT, Kennedy BH, Elveback LR: Temporal arteritis: A 25-year epidemiologic, clinical and pathologic study. Ann Intern Med 88:162167, 1978. 18. Fauchald P, Rygvold O, q)ystese B: Temporal arteritis and polymyalgia rheumatica: Clinical and biopsy findings. Ann Intern Med 77:845-852, 1972. 19. Ettlinger RE, Hunder GG, Ward LE: Polymyalgia rheumatica and giant cell arteritis. Ann Rev Med 29:15-22, 1978. 20. Hunder GG, Hazleman BL: Giant cell arteritis and polymyalgia rheumatica, in Kelly WN, Harris ED Jr, Ruddy S, Sledze CB, editors: Textbook of rheumatology. Philadelphia, 1981, pp. 1189-1196. 21. Barefoot SW, Lund HZ: Temporal (giant-cell) arteritis associated with ulcerations of scalp. Arch Dermatol 93:79-83, 1966. 22. Folan DW: Polymyalgia rheumatica with purpura necrotica of the entire scalp. Cutis 5:278-282, 1969. 23. Morgan GJ Jr, Harris EJ Jr: Prognostic implications of non-giant cell temporal arteritis. Arthritis Rheum 19: 812, 1976. 24. Cooke WT, Cloake PCP, Govan ADT, Colbeck JC: Temporal arteritis: A generalized vascular disease. Q J Med 15:47-75, 1946. 25. Grahame R, Bluestone R, Holt PJL: Recurrent blanching of the tongue due to giant cell arteritis. Ann intern Med 69:781-782, 1968.
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26, Brearley BF, MacDonald JG: Temporal arteritis resulting in infected gangrene of tongue. Br Med J 1:1151-1152, 1961. 27. Clark J: Gangrene of the scalp. Br Med J 2:1160, 1960. 28. Fleischl P, Oldham BE: Temporal (giant-cell) arteritis associated with gangrene of scalp. Br Med J 2:439, 1960. 29. Soderstrom CW, Seehafer JR: Bilateral scalp necrosis in temporal arteritis: A rare complication of Hortoa's disease. Am J Med 61:541-546, 1976. 30. Henderson AH: Tongue pain with giant cell arteritis. Br Meal J 2:337, 1967. 31. Howard SC: Acute parenchymatous glossitis with gangrene of the tongue. Lancet 2:4113-412, 1959. 32. Missen GAK: Gangrene of the tongue. Br Med J 1:1393-1394, 1961. 33. Reed C, Inglis MJ: Acute massive gangrene of tongue. Br Med J 2:575-576, 1965. 34. Pitt P, Wallace I, MacGregor GA: Case report. Br Med J 1:1394, 1961. 35. Russell RWR: Giant-cell arteritis: A review of 35 cases. Q J Med 28:417-489, 1958, 36. Horton BT: Complications of temporal arteritis. Br Med J 1:105-106, 1966. 37. Cullen JF, Coleiro JA: Ophthalmic complications of giant-cell arteritis. Surv Ophthalmol 20:247-260, 1976. 38. Goodman BW Jr: Temporal. arteritis. Am ~ Med 67:839-852, 1979. 39. Alestig K, Ban- J: Giant-cell arteritis: A biopsy study of polymyalgia rheumatica, including one case of Takayasu's disease. Lancet 1: 1228-1230, 1963. 40. MacGregor GA: Giant-cell arteritis without headache. Lancet 2:1160-1163, 1961. 41. Healey LA, Parker F, Wilske KR: Polymyalgia rheumatica and giant cell arteritis. Arthritis Rheum 14:138141, 1971. 42. Harrison MJG, Bevan AT: Early symptoms of temporal artetitis. Lancet 2:638-640, 1967, 43. Rook A, Wilkinson DS, Ebling FJG: Textbook of dermatology, ed. 3. Oxford, 1979, Blackwell Scientific Publications, p. 1075. 44. Polasky N, Polasky SH, Magenheim H, Abrams NR: Giant-cell arteritis: Review and report of a case. JAMA 191:341-343, 1965. 45. Finlayson R, Robinson JO: Giant-cell arteritis of the legs. Br Med J 2:1595-1597, 1955. 46. Bugg EI Jr, Coonrad RW, Grim KB: Giant-cell afteriris--An acute hand syndrome. J Bone Joint Surg 45A: 1269-1272, 1963. 47. Litwack KD, Bohan A, Silverrnan L: Granulomatous liver disease in giant cell arteritis. J Rheumatol 4:307312, 1977. 48. Salem B, Foad I, Sheon RP, Kirsner AB: Systemic lupus erythematosus in the elderly. Arch Intern Med 130:743746, 1972. 49. Andrews JM: Giant-cell ("temporal") arteritis. Neurology 16:963-971, 1966. 50. Whitfietd AGW, Meynell MJ, Fessey BM, Hudson WA: A circulating anticoagulant occurring after temporal arteritis and controlled by corticosteroid therapy, J Clin Pathol 15:357-360, 1962. 51. Lee DK, Andrews JM: Temporal arteritis developing in
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the course of sulfonamide therapy, JAMA 200:720-721, 1967. 52. Kalliom~ki JL, Laur6n PA: Development of temporal arteritis in a patient with rheumatoid arthritis during treatment with indomethacin. Acta Rheum Scand 11: 131-136, 1965. 53. Bailey RR, Neale TJ, Lynn KL: Allopurinol-associated arteritis. Lancet 2:907, 1976,
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54. Bonnetblanc JM, Adenis JP, Queroi M, Rammnert B: lmmunofluorescence in temporal arteritis. N Engl J Med 298:458, 1978. 55. Whitfield AGW, Cooke WT, Jameson-Evans P, Rudd C: Temporal arteritis and its treatment with cortisone and a.c.t.h. Lancet 1:408-412, 1953.
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Giant cell arteritis: A systemic disease with rare cutaneous manifestations Eric W. Baum, M.D., W. Mitchell Sams, Jr., M.D., and R. Rex Payne, M.D. Birmingham, AL Giant cell arteritis is a systemic disease usually occurring in patients in the fifth decade or older, more often in women. Dermatologic manifestations are rare but, when found, are usually expressed as scalp ulcerations or blanching associated with gangrene of the tongue. The dermatologist should be familiar with the entity because it is often more severe when associated with scalp necrosis, and prompt intervention with corticosteroids can prevent catastrophic sequelae. (J AM ACAD DERMATOL6: 1081-1088, 1982.)
Although Hutchinson 1 is credited with describing the first case of temporal arteritis in the medical literature, this disease entity may have been recorded as early as A.O. 940 to 1010 by Ali Ibn Isa in the Tadhkirat. 2 However, it was Horton et al a who first defined this disease as the clinicopathologic entity we recognize today. A number o f names have been used to describe this condition, including temporal arteritis, 1'3 giant cell arteritis, 4 cranial arteritis, 5 giant cell polyarteritis, 6 polymyalgia rheumatica, 7 Horton's disease, 3,s arteritis of the aged, 9 and granulomatous arteritis. 1° As with some other authors, 2,4,11-~3 we prefer the term "giant cell arteritis." Epidemiologic studies confirm that giant cell arteritis is a disease of the elderly. Reported patients range in age from 48 to over 90 years, with the greatest number of patients falling within the age range of 65 to 73 years. 14 Isolated cases have been reported in young and middle-aged adults, but substantiation that these represent true cases of giant cell arteritis is questionable. 's,'6 The disease
is more common in women, by ratios of 3: 1, ~,17 2: 1,18'19 or 65%. '4 Recent studies have demonstrated that the disease is more common than previously thought. 14,'r,20 In 1950 to 1959 there was an average incidence of 5.1/100,000, and in the period from 1970 to 1974 this rose to 17.4/100,000 per year. t4.20 The actual rate may even be higher, since autopsy studies of 889 people without clinically suspected disease demonstrated that 1.7% of patients had giant cell arteritis on biopsy of the temporal artery o r aorta. 14'~° The prevalence of this disease is roughly equal to that of ankylosing spondylitis in the same community studied. 17 Because of the infrequency with which the skin is involved, most articles in the dermatology literature stress how infrequently this disease is encountered by dermatologists. ~,~a,21.~2 Many review articles on the subject fail to mention cutaneous manifestations at all. We present a patient who exhibited some of the more classic symptoms of giant cell arteritis and soon after developed alopecia and ulcerations of the scalp. CASE REPORT
From the Departmentof Dermatology,Universityof Alabama in Birmingham. Reprintrequests to: Dr. R. Rex Payne,7901 Ist AvenueSouth,Suite 202, Birmingham,AL 35206. 0190-9622/82/061081+08500.80/0 © 1982 Am Acad Dermatol
A 73-year-old white woman began complaining of a bandlike pain in the left parietal region, pain on mastication, and sudden onset of tinnitus and vertigo 3 1081
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Journal of the American Academy of Dermato Iogy
Fig. 1. Left side of scalp after shaving for biopsy, showing multiple ulcerations with an area of central necrosis within a large ulceration. weeks before hospitalization. When nausea, vomiting, and a decrease in visual acuity occurred, she was admitted to the hospital. Past medical history included a several-year history of hypertension, for which she was being treated with chlorthalidone combined with reserpine (Regroton), 50 mg orally, once per day. Two months previously she had been seen by her private physician for fatigue, joint pain, and a noticeable decrease in stamina when she was performing activities of daily living. At this time, a complete blood count, serum concentrations of iron, and vitamin B ~u levels demonstrated pernicious anemia, which was treated with intramuscular vitamin B ~2 injections. Physical examination on admission revealed a welldeveloped, well-nourished white woman with mild pain in the left parietal area. A bruit was audible in the left carotid artery. Examination of the left side of the scalp revealed early necrosis with superficial ulcerations and hair loss (Fig. 1). Ophthalmologic examination revealed best corrected vision of 20/30 in the right eye and 20/100 in the left. The left pupil was slightly larger than the right, and both pupils were reactive to light. The right visual field was normal, and the left demonstrated an inferior altitudinal defect. The optic disc was normal on the right and pale on the left. Pertinent laboratory results were as follows: erythrocyte sedimentation rate, 54 mm/hr (Westergren method); hemoglobin, 11.2 gm/dl; hematocrit, 35.2%; indices within normal limits; white blood cell count, 5.4%; normal differential; alkaline phosphatase, 199 U/liter;
"y-glutamyl transpeptidase, 159 U/liter; blood glucose level, 118 mg/dl. Liver-spleen scan revealed a normal liver with increased shunting of isotope to the spleen, suggesting mild hepatocellular disease. Upper gastrointestinal series demonstrated a small diverticulum in the distal duodenum. Urinalysis, urine culture, skull x-rays, bone'scan, electrocardiogram, oral cholecystogram, and chest x-ray were all within normal limits. Computerized axial tomography scan of the head revealed some atrophy of the brain but no focal defects. Doppler studies suggested bilateral stenosis of the carotid arteries. A temporal artery biopsy confirmed giant cell arteritis, and the patient was started on oral prednisone, 100 mg daily. Her headaches, joint pain, and tinnitus improved within 2 days. This therapy was continued, and at the time of writing, 1l months after discharge, she was taking 10 mg/day. Although visual acuity was unchanged, her scalp lesions had completely healed. Microscopic findings. Biopsy of the temporal artery showed an inflammatory process that extended through the entire thickness of the artery wall and was composed mainly of lymphocytes and histiocytes. Some of the histiocytes were multinucleated. There was almost complete occlusion of the lumen (Figs. 2 and 3). In the intima there were deposits of fibrinlike material, which was mainly observed in the areas of the internal elastic lamina. By means of a Verhoeff-van Gieson stain, the elastic fibers were found to be noticeably fragmented, with bits of elastic tissue scattered within the inflammatory infiltrate (Fig. 4).
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Fig. 2. Low-power view shows inflammation of all layers of the temporal artery, with multiple small endothelium-lined spaces centrally, resulting from previous thrombosis and recanalization.
The pathology of giant cell arteritis is segmental. For this reason giant cells need not be seen to make the diagnosis. In our patient's biopsy, a few giant cells were seen. Some authors believe that the absence of giant cells signifies a worse prognosis, "a whereas others refute this finding.~7 One author proposed a tuberculous etiology to explain the presence of the giant cells; however, no tubercles or acid-fast bacilli have been demonstrated. There seems to be some accord, however, that the giant cells may be due to a foreign body reaction to the fragmentation of the elastic lamina. T M DISCUSSION The most frequent cutaneous finding in giant cell arteritis is necrosis of the scalp, resulting in
ulceration that may be localized to one side, "~5"2(~ may be bitemporal, La,zT''-'s or may extend to large areas so that the entire scalp may be involved. 2~'2" Of those patients with scalp necrosis, 67% will develop irreversible visual loss, and the mortality rate is 41%, considerably higher than among patients who have giant cell arteritis without scalp necro sis.2:J To the best of our knowledge, scalp ulcerations with necrosis have been documented in only fifteen previous case reports. In the first extensive review of skin manifestations o f giant cell arteritis, Kinmont and McCallure (~included the following less c o m m o n signs of
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Fig, 3. High-power view demonstrating mixed infiltrate of lymphocytes and histiocytes,
some of which are multinucleated. skin involvement: butterfly rash of the face, gangrene of the leg, purpura simulating HenochSchSnlein purpura (allergic vasculitis), purpura and ecchymoses, leg ulcers, painful scalp, lumps with crusting and secondary infection withStaphylococcus aureus, scalp bullae, and tongue changes including gangrene, erythema, necrosis, and sloughing. Other skin findings noted in giant cell arteritis include urticaria, edema, lividity, tender nodules, tortuous and prominent arteries, supravascular pallor, and hyperpigmentation.13 Abundant reports describe changes in the tongue, with objective and subjective findings, including pain, burning, recurrent blanching, redness or erythema, bluish swellings, gangrene, necrosis, and sloughing. 2~'~'~°-34 Severe headache, usually of a dull, boring, or throbbing nature, is the most c o m m o n complaint. However, lancinating pain, which can make combing one's hair or even lying on the affected side of the scalp extremely painful, has been reported. 3s In many cases in which headaches are a prominent symptom, one may find tender, firm, enlarged, palpable, pulseless branches of the su-
perior temporal artery. Associated with the headaches may be periorbital and facial edema. Constitutional complaints include fatigue, malaise, weight loss, myalgia, arthralgia, anorexia, and sweating. Claudication, in the form of pain localized to the jaw, teeth, ear, and zygoma, is significant. Horton, 36 in a later article, believed pain on mastication and relief after resting these muscles to be diagnostic for giant cell arteritis. Visual loss may occur in 42% to 58% of patients with giant cell arteritis. It is usually sudden in onset, partial or complete, and usually permanent. Rarely, episodes of transient visual blurring precede more catastrophic visual impairment. Other ophthalmologic involvement includes ptosis, extraocular muscle palsies, anterior segment necrosis, hypotonia, and visual hallucinations, a7 Neurologic involvement in giant cell arteritis is primarily due to arteritic lesions occurring within the cerebral circulation. Reported manifestations include stroke, coma, dementia, psychosis, confusion, depression, and aneurysms of major arteries .a~ As a consequence of coronary arteritis, clini-
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Fig. 4. Verhoeff-van Gieson stain showing fragmentation of the internal elastic lamina.
cians should be aware of possible myocardial infarctions, bouts of angina pectoris, and even congestive heart failure."° Polymyalgia rheumatica is a clinical syndrome that is closely intertwined with giant cell arteritis, a'~ usually occurs in individuals greater than 50 years of age, and is indicated by pain and stiffness in the proximal muscles of the neck, shoulders, and back. Constitutional complaints of fever, malaise, and weight loss are common. However, in polymyalgia rheumatica, vessels of the scalp are rarely involved, a6,4° A high erythrocyte sedimentation rate, as well as a usually rapid response to systemic steroids, has been reported. 18-20,41,42 Giant cell arteritis may involve arteries of large,
medium, or small <13 size, as well as veins. 14 The most frequent involvement is of large and medium-sized arteries 's,4a from the aortic arch to the scalp, z° The typical histologic picture of giant cell arteritis has been described in arteries in the uterus, 44 legs, 4'~ abdomen, 2 and hand. 4cI The most significant laboratory finding in giant cell arteritis is a moderate to marked increase in the erythrocyte sedimentation rate, sometimes exceeding 100 ram/hour (Westergren method),14 but normal sedimentation rates have been reported even with active disease. 2 Anemia, most often of a hypochromic or normochromic pattern, is also a common finding. Other common laboratory abnormalities are mild to moderate leukocytosis,
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mild thrombocytosis, serum protein electrophoresis (especially a~), decreased serum albumin with an occasional reversal of the albumin-globulin ratio, and increased gamma globulins, complement, and blood fibrinogens. One third of these patients have a mild abnormality in liver function t e s t s , 14'2° manifested as an increased retention of sulfobromophthalein and increased alkaline phosphatase activity. An association with granulomatous hepatitis has been reported. 4r Occasional elevations of serum glutamic-oxaloacetic transaminase and partial thromboplastin time have also been reported. Renal function tests are usually normal, although red cell casts, and occasionally granular, tubular, or hyaline casts, have been reported. 14,20 Antinuclear antibodies are generally absent. This is significant because, in elderly patients, lupus erythematosus may closely simulate the polymyalgia rheumatica syndrome. 48 Angiography of involved vessels may reveal irregular constrictions, dilations, and excessive tortuosity of vessels. 49 Synovial fluid analysis has demonstrated poor mucin clotting and increased leukocytes with an increased percentage o f polymorphonuclear leukocytes, all compatible with a mild inflammation. Synovial biopsy has demonstrated a lymphocytic synovitis. 14,a° Among the etiologic agents proposed for giant cell arteritis are the aging process, '4,2° infectious agents, ~.'4,24 infections leading to thrombosis, 24 a circulating anticoagulant, '~° drugs (sulfonamide, al indomethacin, '~2 allopurinoPa), allergies, 5 allergic reactions to elastic tissue, 2 foreign body reactions, 44'49 Mycoplasma (a pleuropneumonia-like organism) infection, 49 contact with birds (especially parakeets), ~9 familial aggregation--genetic or hereditary, 14,2° immunologic mechanisms TM (both cellular and humoral, and, specifically, an autoimmune mechanism14,19,40). The possibility of an autoimmune mechanism has been supported by the demonstration of increased levels of circulating immune complexes in acute disease 2° and granular deposits of immunoreactive products as seen with immunofluorescence. ,~4 In many patients giant cell arteritis resolves spontaneously,'~"7'4"44"~ but the mortality rate has been reported to be as high as 12%. 49 The usual
cause of death is thrombosis of the cerebral or coronary arteries. 2'49 However, it is likely that rapid institution of corticosteroid therapy has lowered the death rate. Systemic corticosteroids should be administered as soon as the diagnosis is made, since there is strong documentation that prompt steroid therapy may prevent cerebrovascular accidents and myocardial infarctions and may protect the remaining vision of patients with only partial blindness. 2''~5 The initial dose of prednisone should be from 40 to 100 mg/day, but the length of therapy is controversial. Periods from 3 months to 2 years have been recommended. If therapy is to be for short periods of time, slow, gradual reduction of the dosage is advised, since the possibility of recurrence is greatest in the first 2 years. A decrease in the erythrocyte sedimentation rate is the best indication of improvement. Increases in the erythrocyte sedimentation rate should alert the physician to a possible recrudescence. Other therapeutic modalities that have been examined are hyperbaric oxygenation, salicylates, sulfonamides, anticoagulants, amyl nitrite, phenylbutazone, chloroquine, and indomethacin. None of these has proved to be as efficacious as corticosteroid therapy. 2'49 Phenylbutazone has been utilized successfully in polymyalgia rheumatica, but results have been inconsistent. 4°'44 In conclusion, the dermatologist should be aware of the cutaneous manifestations of giant cell arteritis. The aggressive nature of this disease is especially noted when it is associated with scalp ulcerations. 29 Rapid diagnosis and prompt institution of therapy can avert the catastrophic sequelae of stroke, myocardial infarction, and blindness. We express our thanks to Dr. Lanning Kline for his suggestions concerning visual changes and to Dr. Gene Ball for his suggestions regarding polymyalgia rheumatica and liver complications in giant cell arteritis. REFERENCES
1. HutchinsonJ: Diseases of the arteries. Arch Surg (London) 1:323-329, 1890. 2. Hamilton CR Jr, Shelley WM, Tumulty PA: Giant cell arteritis: Including temporal arteritis and polymyalgia rheumatica. Medicine (Baltimore) 50:1-27, 1971. 3. Horton BT, Magath TB, Brown GE: An undescribed form of arteritis of the temporal vessels. Proc Mayo Clin 7:700-701, 1932,
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4. Gilmour JR: Giant-cell chronic arteritis. J Pathol Bacteriol 53:263-277, 1941. 5. Kilbourne ED, Wolff HG: Cranial arteritis: A critical evaluation of the syndrome of "temporal arteritis" with report of a case. Ann Intern Med 24:1-10, 1946. 6. Kinmont PDC, McCallum DI: Skin manifestations of giant-cell arteritis. Br J Dermatol 76:299-308, 1964. 7. Barber HS: Myalgic syndrome with constitutional effects: Polymyalgia rheumatica. Ann Rheum Dis 16: 230-237, 1957. 8. Horton BT, Magath TB: Arteritis of the temporal vessels: Report of seven cases. Proc Mayo Clin 12:548-553, 1937. 9. Paulley JW, Hughes JP: Giant-cell arteritis, or arteritis of the aged. Br Med J 2: 1562-1567, 1960. 10. McMillan GC: Diffuse granulomatous aortitis with giant cells: Associated with partial rupture and dissection of the aorta. Arch Pathol 49:63-69, 1950. i1. Ackerman AB: Histologie diagnosis of inflammatory skin diseases. Philadelphia, 1978, Lea & Febiger, pp. 374-375. 12. Kimmelstiel P, Gilmour MT, Hodges HH: Degeneration of elastic fibers in granulomatous giant cell arteritis (temporal arteritis). Arch Pathol 54:157-168, 1952. 13. Hitch JM: Dermatologic manifestations ~f giant-cell (temporal, cranial) arteritis. Arch Dermatol 101:409415, I970. 14. Hunder GG, Alien GL: Giant cell arteritis: A review. Bull Rheum Dis 29:980-987, 1978-1979. 15. Bethlenfalvay NC, Nusynowitz ML: Temporal arteritis: A rarity in the young adult. Arch Intern Med 114:487489, 1964. 16. Lie JT, Gordon LP, Titus JL: Juvenile temporal arteritis: Biopsy study of four cases. JAMA 234:496-499, 1975. 17. Huston KA, Hunder GG, Lie JT, Kennedy BH, Elveback LR: Temporal arteritis: A 25-year epidemiologic, clinical and pathologic study. Ann Intern Med 88:162167, 1978. 18. Fauchald P, Rygvold O, q)ystese B: Temporal arteritis and polymyalgia rheumatica: Clinical and biopsy findings. Ann Intern Med 77:845-852, 1972. 19. Ettlinger RE, Hunder GG, Ward LE: Polymyalgia rheumatica and giant cell arteritis. Ann Rev Med 29:15-22, 1978. 20. Hunder GG, Hazleman BL: Giant cell arteritis and polymyalgia rheumatica, in Kelly WN, Harris ED Jr, Ruddy S, Sledze CB, editors: Textbook of rheumatology. Philadelphia, 1981, pp. 1189-1196. 21. Barefoot SW, Lund HZ: Temporal (giant-cell) arteritis associated with ulcerations of scalp. Arch Dermatol 93:79-83, 1966. 22. Folan DW: Polymyalgia rheumatica with purpura necrotica of the entire scalp. Cutis 5:278-282, 1969. 23. Morgan GJ Jr, Harris EJ Jr: Prognostic implications of non-giant cell temporal arteritis. Arthritis Rheum 19: 812, 1976. 24. Cooke WT, Cloake PCP, Govan ADT, Colbeck JC: Temporal arteritis: A generalized vascular disease. Q J Med 15:47-75, 1946. 25. Grahame R, Bluestone R, Holt PJL: Recurrent blanching of the tongue due to giant cell arteritis. Ann intern Med 69:781-782, 1968.
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26, Brearley BF, MacDonald JG: Temporal arteritis resulting in infected gangrene of tongue. Br Med J 1:1151-1152, 1961. 27. Clark J: Gangrene of the scalp. Br Med J 2:1160, 1960. 28. Fleischl P, Oldham BE: Temporal (giant-cell) arteritis associated with gangrene of scalp. Br Med J 2:439, 1960. 29. Soderstrom CW, Seehafer JR: Bilateral scalp necrosis in temporal arteritis: A rare complication of Hortoa's disease. Am J Med 61:541-546, 1976. 30. Henderson AH: Tongue pain with giant cell arteritis. Br Meal J 2:337, 1967. 31. Howard SC: Acute parenchymatous glossitis with gangrene of the tongue. Lancet 2:4113-412, 1959. 32. Missen GAK: Gangrene of the tongue. Br Med J 1:1393-1394, 1961. 33. Reed C, Inglis MJ: Acute massive gangrene of tongue. Br Med J 2:575-576, 1965. 34. Pitt P, Wallace I, MacGregor GA: Case report. Br Med J 1:1394, 1961. 35. Russell RWR: Giant-cell arteritis: A review of 35 cases. Q J Med 28:417-489, 1958, 36. Horton BT: Complications of temporal arteritis. Br Med J 1:105-106, 1966. 37. Cullen JF, Coleiro JA: Ophthalmic complications of giant-cell arteritis. Surv Ophthalmol 20:247-260, 1976. 38. Goodman BW Jr: Temporal. arteritis. Am ~ Med 67:839-852, 1979. 39. Alestig K, Ban- J: Giant-cell arteritis: A biopsy study of polymyalgia rheumatica, including one case of Takayasu's disease. Lancet 1: 1228-1230, 1963. 40. MacGregor GA: Giant-cell arteritis without headache. Lancet 2:1160-1163, 1961. 41. Healey LA, Parker F, Wilske KR: Polymyalgia rheumatica and giant cell arteritis. Arthritis Rheum 14:138141, 1971. 42. Harrison MJG, Bevan AT: Early symptoms of temporal artetitis. Lancet 2:638-640, 1967, 43. Rook A, Wilkinson DS, Ebling FJG: Textbook of dermatology, ed. 3. Oxford, 1979, Blackwell Scientific Publications, p. 1075. 44. Polasky N, Polasky SH, Magenheim H, Abrams NR: Giant-cell arteritis: Review and report of a case. JAMA 191:341-343, 1965. 45. Finlayson R, Robinson JO: Giant-cell arteritis of the legs. Br Med J 2:1595-1597, 1955. 46. Bugg EI Jr, Coonrad RW, Grim KB: Giant-cell afteriris--An acute hand syndrome. J Bone Joint Surg 45A: 1269-1272, 1963. 47. Litwack KD, Bohan A, Silverrnan L: Granulomatous liver disease in giant cell arteritis. J Rheumatol 4:307312, 1977. 48. Salem B, Foad I, Sheon RP, Kirsner AB: Systemic lupus erythematosus in the elderly. Arch Intern Med 130:743746, 1972. 49. Andrews JM: Giant-cell ("temporal") arteritis. Neurology 16:963-971, 1966. 50. Whitfietd AGW, Meynell MJ, Fessey BM, Hudson WA: A circulating anticoagulant occurring after temporal arteritis and controlled by corticosteroid therapy, J Clin Pathol 15:357-360, 1962. 51. Lee DK, Andrews JM: Temporal arteritis developing in
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the course of sulfonamide therapy, JAMA 200:720-721, 1967. 52. Kalliom~ki JL, Laur6n PA: Development of temporal arteritis in a patient with rheumatoid arthritis during treatment with indomethacin. Acta Rheum Scand 11: 131-136, 1965. 53. Bailey RR, Neale TJ, Lynn KL: Allopurinol-associated arteritis. Lancet 2:907, 1976,
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54. Bonnetblanc JM, Adenis JP, Queroi M, Rammnert B: lmmunofluorescence in temporal arteritis. N Engl J Med 298:458, 1978. 55. Whitfield AGW, Cooke WT, Jameson-Evans P, Rudd C: Temporal arteritis and its treatment with cortisone and a.c.t.h. Lancet 1:408-412, 1953.