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Cutaneous vasculitis in Japan
Cutaneous Vasculitis in Japan SADAO IMAMURA, MD TOMOKO FUJIMURA, MD
A
lthough many types of vasculitis are observed in Japan as well as in other countries, Kawasaki disease or mucocutaneous lymph node syndrome and Takayasu arteritis are two unique types of vasculitis seen in Japanese children and adults, respectively. Both diseases were described by Japanese investigators, and their incidences are much higher in Japan than in other nations. These conditions show systemic vasculitis, which may be fatal, but cutaneous manifestations are so common that they are very helpful in establishing accurate diagnosis of these diseases.
Kawasaki Disease Kawasaki disease or mucocutaneous lymph node syndrome was first described by Kawasaki in 1967 in Japanese1 and in 1974 in English.2 This disease is most commonly observed in Japan, but it has also been described in Korea, the United States, and Europe. It usually affects children under 5 years of age, but cases involving older children and adults have also been recognized. This disease is characterized by prolonged fever, polymorphous rash, mucous membrane involvement, and lymph node swelling. Although the disease was initially considered to be a benign illness, accumulation of the cases showed that a considerable number of the patients had coronary artery vasculitis or aneurysms, which were often fatal.
Epidemiology Since Kawasaki’s first description, more than 140,000 patients were reported by 1996 in Japan. Although about 500 new patients were recorded each month, epidemiological outbreaks were reported in 1979, 1982, and 1986. The male-to-female ratio is 1.43:1, and the highest incidence was found at 1 year of age.3
Etiology Many microbacterial agents have been suspected from clinical and epidemiological findings, including rickettsiae, Staphylococcus, Streptococcus, Propiniobacterium acnes, Yersinia, rotavirus, Epstein-Barr virus, parvovirus, retroviruses, and Candida. None of these agents, howFrom the Department of Dermatology Matsue City Hospital, Matsue, Japan; and Graduate School of Medicine, Kyoto University, Kyoto, Japan. Address correspondence to Sadao Imamura, MD, Matsue City Hospital, 101 Nada-machi, Matsue City, Shimane Prefecture, 690-8509, Japan. © 1999 by Elsevier Science Inc. All rights reserved. 655 Avenue of the Americas, New York, NY 10010
ever, have been constantly detected in the lesions. Environmental substances such as house dust mites, mercury and bacterial toxins have also been considered to be responsible as an antigen of allergic reaction, but no constant data have been demonstrated.
Clinical Features This disease begins with an antibiotic-resistant remittent fever over 39°C for more than 5 days. Bilateral conjunctival injection, dry red lips and oral cavity, and a strawberry tongue are associated with this condition. About 80% of the patients develop cervical lymph node swelling. Palmar and plantar erythema associated with indurative edema of the hands and feet characteristically develop in the very early stage of the illness (Fig. 1). Generalized polymorphic eruptions, which are not unique in morphology, and that have been described as macular, maculopapular, urticarial, erythema multiforme-like, scartiniform, and vesiculopustular also develop in more than 80% of the patients (Fig. 2). Although the eruptions are present both on the trunk and extremities, the perineum, buttocks, groin, and lower abdomen are predilection sites. The individual eruption tends to coalesce, followed by desquamation. During the second week of the illness, characteristic peeling starts from the fingertips.
Complications The most important complication of this disease is coronary artery lesions (CALs), which include partial dilatation to aneurysm of the coronary artery. Before the administration of high-dose intravenous gamma globulin (IVGG) treatment, CAL was demonstrated in 40 – 50% of the patients and the mortality rate was over 1%; however, IVGG treatment decreased CAL to 12.1%, and the death rate to 0.08% in 1996 in Japan.3 Other complications including arthritis, arthralgia, diarrhea, and pyuria are seen in over half the patients.
Laboratory Findings No diagnostic laboratory findings have been reported. Leukocytosis with a left shift, increased ESR, and C-reactive protein (CRP), slight to moderate anemia, and thrombocytosis are occasionally seen. 0738-081X/99/$–see front matter PII S0738-081X(99)00071-1
660 IMAMURA AND FUJIMURA
Clinics in Dermatology
Y
1999;17:659 – 662
6. Nonpurulent cervical lymphadenopathy in the acute stage
Other Significant Symptoms or Findings
Figure 1. Kawasaki disease. Indurative edema of the hands and fingers.
Diagnostic Criteria According to the Japanese Kawasaki Disease Research Committee,4 at least five of the six following principal symptoms should be fulfilled for the diagnosis of Kawasaki disease. If coronary aneurysm is recognized by two-dimensional echocardiography or coronary angiography, and other diseases are excluded, the diagnosis of Kawasaki disease can be established by four of the six principal symptoms. 1. Fever lasting 5 days or more 2. Changes in peripheral extremities. Acute stage: indurative edema of hands and feet, erythema of palms and soles. Convalescent stage: membranous desquamation from the fingertips 3. Polymorphous exanthema 4. Bilateral conjunctival injection 5. Changes in lips and oral cavity: reddening of lips, strawberry tongue, diffuse injection of oral and pharyngeal mucosa
Figure 2. Kawasaki disease. Generalized polymorphic eruption.
1. Cardiovascular: auscultation (heart murmur, gallop rhythm, distant heart sound), ECG changes (prolonged PR-QT intervals, abnormal Q-wave, low voltage, ST-T changes, arrhythmias), chest X-ray findings (cardiomegaly), two-dimensional echocardiographic findings (pericardial effusion, coronary aneurysms), angina pectoris-like symptoms, aneurysms of peripheral arteries (axillae, etc) 2. Gastrointestinal tract: diarrhea, vomiting, abdominal pain, swelling of the gall bladder, paralytic ileus, mild jaundice, increased serum transaminase 3. Blood: leukocytosis with shift to the left, thrombocytosis, increased ESR, positive CRP, hypoalbuminemia, increased ␣-2-globulin, slight anemia 4. Urine: proteinuria, increase of leukocytes in sediment 5. Skin: redness and crust formation at the BCG inoculation site, small pustules, transverse furrows of the nails 6. Respiratory: cough, rhinorrhea, abnormal shadow on chest X-ray 7. Joints: pain, swelling 8. Neurological: pleocytosis of mononuclear cells in CSF, convulsion, unconsciousness, facial palsy, paralysis of the extremities
Histological Findings Histology of Kawasaki disease shows necrotizing vasculitis, which is distinguishable from classic polyarteritis nodosa, but indistinguishable from infantile polyarteritis nodosa.5 The coronary artery is most frequently affected, with fusiform aneurysm accompanied by thrombosis, occlusion or stenosis of the lumen. Pulmonary, carotid, iliac, celiac arteries and some veins may also be involved. Arterial lesions can be classified into five stages: (1) endothelial degeneration and increased vascular permeability; (2) edema and degeneration of the media; (3) necrotizing panarteritis; (4) granulation formation; and (5) scar formation. In the early stage, inflammatory tissue consists of neutrophils, eosinophils, lymphocytes, and plasma cells, but fibrinoid necrosis of the media is rare and slight. Histological findings of skin eruptions are not specific, probably because small vessels are not markedly involved. Perivascular mononuclear cell infiltration associated with edema and dilatation of small vessels in the dermis is observed. By electronmicroscopical study, researchers6 observed degenerative changes in the endothelial cells.
Clinics in Dermatology
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1999;17:659 – 662
VASCULITIS IN JAPAN
661
Treatment A high dose of aspirin and gamma globulin are effective in the acute stage. Thirty mg/kg/day of aspirin is recommended during the febril period, which is tapered to 10 mg/kg/day until BSR and CRP are normalized. Intravenous injection of 200 to 400 mg/kg/day gamma globulin for 5 days alone or with aspirin, is beneficial for preventing CAL.7 Systemic corticosteroids or antibiotics are not effective.
Takayasu Arteritis Takayasu arteritis is an uncommon chronic inflammatory disease of unknown etiology; it predominantly involves the aorta and its proximal branches and pulmonary artery. The blood vessels are segmentally involved, leading to both stenotic and ectatic changes in the arterial lumen. This disease was first described as a case report in 1856,8 and ophthalmological findings were reported by in 1908.9 Two large series of cases were described by Japanese cardiologists in 196710 and 1988.11 Recent studies12 suggest that the vascular changes are not confined to large arteries, but may involve smaller vessels including cutaneous vessels, which produce cutaneous manifestations.
Epidemiology This disease is most frequently seen in Japan, Korea, China, Southeast Asia, India, and Mexico. It is less common in Europe and the United States. The estimated incidence of Takayasu arteritis in North America is about 2.6 cases per 1 million people annually.13
Etiology Although the precise etiology of the disease has not been clarified, an autoimmune mechanism has been suggested because of the frequent association with rheumatoid arthritis or other connective tissue diseases. Antiaortic antibodies are demonstrated, but their etiological role is not known.
Clinical Features This disease affects mostly female adults under 40 years of age. In the initial phase, most patients complain of fever, malaise, anorexia, weight loss, night sweats, myalgia, and arthralgia. Cardiopulmonary symptoms such as tachycardia, chest pain, dyspnea, and cough are also common. In the late obliterative phase, patients show a variety of symptoms depending on the involved site of the artery. Cephalic hypoperfusion may produce headaches, dizziness, vertigo, seizures, and visual disturbance. Coronary artery involvement may result in angina pectoris or myocardial infarction. A few patients have complained of abdominal pain due to visceral artery involvement. Physical examination reveals cor-
Figure 3. Takayasu disease. Erythema nodosum-like nodule.
responding bruits over stenotic vessels. Hypertension of the legs with reduced blood pressure in the arms, suggestive of reversed coarctation, is a characteristic feature of this disease.
Cutaneous Manifestations and Histological Findings Cutaneous manifestations reported in patients with Takayasu arteritis are divided into specific and nonspecific ones. Specific manifestations have been reported in 12.5%14 to 18.9%12 of the patients, and included erythema nodosum, erythema induratum, tuberculid eruptions, pyoderma gangrenosum, and eruptions induced by necrotizing or granulomatous vasculitis. Erythema nodosum or erythema nodosum-like nodules are most frequently seen, but most of them are not true erythema nodosum histologically (Fig. 3). They show necrotizing vasculitis with polymorphonuclear leukocytes and fibrinoid necrosis in the blood vessel walls, granulomatous vasculitis, consisting of polymorphonuclear leukocytes, eosinophils, giant cells and fibrinoid necrosis, and/or lobular panniculitis with fat necrosis and septal panniculitis (Fig. 4). Most cases of pyoderma gangrenosum associated with Takayasu arteritis have been reported in Japan, although the reason is unknown.15 Acute or subacute nodules are more frequently seen in the early stage of Takayasu arteritis, whereas pyoderma gangrenosum and tuberculid eruption occur more frequently in the occlusive stage.14 Immunofluorescence may reveal deposition of immunoglobulin and/or complement components at the basement membrane zone or in the walls of the dermal blood vessels.
Clinics in Dermatology
662 IMAMURA AND FUJIMURA
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1999;17:659 – 662
neous lesions of various types. Cyclophosphamide and anticoagulant drugs such as aspirin and dipyridamole are commonly used. In the late obliterative phase, surgical revascularization treatments may be required. Acknowledgments Dr. Atsuhiko Ogino, Kyoto National Hospital, permitted us to use two clinical photographs of Kawasaki disease.
References
Figure 4. Takayasu disease. Granulomatous vasculitis consisting of polymorphonuclear leukocytes, eosinophils, and fibrinoid necrosis.
Laboratory Findings Elevated ESR, mild leukocytosis, and anemia are frequently seen. Elevated levels of immunoglobulin, C-reactive protein, and antistreptolysin-O titers are occasionally seen, but not specific. Aortic angiography is necessary for a full assessment.
Diagnostic Criteria Several criteria for the diagnosis of Takayasu arteritis have been proposed. The following criteria were offered in 1988.11
Obligatory Criterion Age ⬍40 years Two major criteria: 1. Left mid-subclavian artery lesion 2. Right mid-subclavian artery lesion Nine minor criteria: 1. 2. 3. 4. 5. 6. 7. 8. 9.
High ESR Carotid artery tenderness Hypertension Aortic regurgitation or annuloaortic ectasia Pulmonary artery lesion Left mid-common carotid lesion Distal branchiocephalic trunk lesion Descending thoracic aorta lesion Abdominal aorta lesion
In addition to the obligatory criterion, the presence of two major criteria, or one major and two or more minor criteria or four or more minor criteria, suggests Takayasu arteritis.
Treatment Systemic corticosteroids of relatively high doses are most effective for both systemic complaints and cuta-
1. Kawasaki T. Acute febril mucocutaneous lymph node syndrome with unique desquamation of the fingers and toes. Jap J Allerg 1967;16:178 –222 (in Japanese). 2. Kawasaki T, Kosaki F, Okawa S, et al. A new infantile acute febile mucocutaneous lymph node syndrome (MLNS) prevailing in Japan. Pediatrics 1974;54:271– 6. 3. Japan Kawasaki Disease Research Committee. Report of the 14th nationwide survey 1997 (in Japanese). 4. Japan Kawasaki Disease Research Committee. Report of the 8th nationwide survey. Perdiatr Jpn 1985;26:1049 –53 (in Japanese). 5. Landing BH, Larson EJ. Are infantile periarteritis nodosa with coronary artery involvement and fatal mucocutaneous lymph node syndrome the same? Comparison of 20 patients from North America with patients from Hawaii and Japan. Pediatrics 1977;59:651– 62. 6. Hirose S, Hamashima Y. Morphological observations on the vasculitis in the mucocutaneous lymph node syndrome: A skin biopsy of 27 patients. Eur J Pediatr 1978; 129:17–27. 7. Furusho K, Kamiya T, Nakano H, et al. High-dose intravenous gamma globulin for Kawasaki disease. Lancet 1984;ii:1055– 8. 8. Savory WS. Case of a young woman in whom the main arteries of both upper extremities and of the left side of the neck were throughout completely obliterated. Med Chir Trans Lond 1856;39:205–19. 9. Takayasu M. A case with peculiar changes of the central retinal vessels. Acta Soc Ophthal Jpn 1908;12:554 – 8 (in Japanese). 10. Nakao K, Ikeda M, Kimata S, et al. Takayasu’s arteritis: Clinical report of eighty-four cases and immunological studies of seven cases. Circulation 1967;35:1141–55. 11. Ishikawa K. Diagnostic approach and proposed criteria for the clinical diagnosis of Takayasu’s arteriopathy. J Am Coll Cardiol 1988;12:964 –72. 12. Perniciaro CV, Winkelmann RK, Hunder GG, et al. Cutaneous manifestations of Takayasu’s arteritis: A clinicopathologic correlation. J Am Acad Dermatol 1987;17:998 – 1005. 13. Hall S, Barr W, Lie JT, et al. Takayasu arteritis: A study of 32 North American patients. Medicine (Baltimore) 1985; 64:89 –99. 14. Frances C, Boisnic S, Bletry O, et al. Cutaneous manifestations of Takayasu arteritis. Dermatologica 1990;181: 266 –72. 15. Hidano A, Watanabe K. Pyoderma gangrenosum et cardiovasculopathies en particulier arte´rite de Takayasu. Ann Dermatol Venereol 1981;108:13–21.
A
lthough many types of vasculitis are observed in Japan as well as in other countries, Kawasaki disease or mucocutaneous lymph node syndrome and Takayasu arteritis are two unique types of vasculitis seen in Japanese children and adults, respectively. Both diseases were described by Japanese investigators, and their incidences are much higher in Japan than in other nations. These conditions show systemic vasculitis, which may be fatal, but cutaneous manifestations are so common that they are very helpful in establishing accurate diagnosis of these diseases.
Kawasaki Disease Kawasaki disease or mucocutaneous lymph node syndrome was first described by Kawasaki in 1967 in Japanese1 and in 1974 in English.2 This disease is most commonly observed in Japan, but it has also been described in Korea, the United States, and Europe. It usually affects children under 5 years of age, but cases involving older children and adults have also been recognized. This disease is characterized by prolonged fever, polymorphous rash, mucous membrane involvement, and lymph node swelling. Although the disease was initially considered to be a benign illness, accumulation of the cases showed that a considerable number of the patients had coronary artery vasculitis or aneurysms, which were often fatal.
Epidemiology Since Kawasaki’s first description, more than 140,000 patients were reported by 1996 in Japan. Although about 500 new patients were recorded each month, epidemiological outbreaks were reported in 1979, 1982, and 1986. The male-to-female ratio is 1.43:1, and the highest incidence was found at 1 year of age.3
Etiology Many microbacterial agents have been suspected from clinical and epidemiological findings, including rickettsiae, Staphylococcus, Streptococcus, Propiniobacterium acnes, Yersinia, rotavirus, Epstein-Barr virus, parvovirus, retroviruses, and Candida. None of these agents, howFrom the Department of Dermatology Matsue City Hospital, Matsue, Japan; and Graduate School of Medicine, Kyoto University, Kyoto, Japan. Address correspondence to Sadao Imamura, MD, Matsue City Hospital, 101 Nada-machi, Matsue City, Shimane Prefecture, 690-8509, Japan. © 1999 by Elsevier Science Inc. All rights reserved. 655 Avenue of the Americas, New York, NY 10010
ever, have been constantly detected in the lesions. Environmental substances such as house dust mites, mercury and bacterial toxins have also been considered to be responsible as an antigen of allergic reaction, but no constant data have been demonstrated.
Clinical Features This disease begins with an antibiotic-resistant remittent fever over 39°C for more than 5 days. Bilateral conjunctival injection, dry red lips and oral cavity, and a strawberry tongue are associated with this condition. About 80% of the patients develop cervical lymph node swelling. Palmar and plantar erythema associated with indurative edema of the hands and feet characteristically develop in the very early stage of the illness (Fig. 1). Generalized polymorphic eruptions, which are not unique in morphology, and that have been described as macular, maculopapular, urticarial, erythema multiforme-like, scartiniform, and vesiculopustular also develop in more than 80% of the patients (Fig. 2). Although the eruptions are present both on the trunk and extremities, the perineum, buttocks, groin, and lower abdomen are predilection sites. The individual eruption tends to coalesce, followed by desquamation. During the second week of the illness, characteristic peeling starts from the fingertips.
Complications The most important complication of this disease is coronary artery lesions (CALs), which include partial dilatation to aneurysm of the coronary artery. Before the administration of high-dose intravenous gamma globulin (IVGG) treatment, CAL was demonstrated in 40 – 50% of the patients and the mortality rate was over 1%; however, IVGG treatment decreased CAL to 12.1%, and the death rate to 0.08% in 1996 in Japan.3 Other complications including arthritis, arthralgia, diarrhea, and pyuria are seen in over half the patients.
Laboratory Findings No diagnostic laboratory findings have been reported. Leukocytosis with a left shift, increased ESR, and C-reactive protein (CRP), slight to moderate anemia, and thrombocytosis are occasionally seen. 0738-081X/99/$–see front matter PII S0738-081X(99)00071-1
660 IMAMURA AND FUJIMURA
Clinics in Dermatology
Y
1999;17:659 – 662
6. Nonpurulent cervical lymphadenopathy in the acute stage
Other Significant Symptoms or Findings
Figure 1. Kawasaki disease. Indurative edema of the hands and fingers.
Diagnostic Criteria According to the Japanese Kawasaki Disease Research Committee,4 at least five of the six following principal symptoms should be fulfilled for the diagnosis of Kawasaki disease. If coronary aneurysm is recognized by two-dimensional echocardiography or coronary angiography, and other diseases are excluded, the diagnosis of Kawasaki disease can be established by four of the six principal symptoms. 1. Fever lasting 5 days or more 2. Changes in peripheral extremities. Acute stage: indurative edema of hands and feet, erythema of palms and soles. Convalescent stage: membranous desquamation from the fingertips 3. Polymorphous exanthema 4. Bilateral conjunctival injection 5. Changes in lips and oral cavity: reddening of lips, strawberry tongue, diffuse injection of oral and pharyngeal mucosa
Figure 2. Kawasaki disease. Generalized polymorphic eruption.
1. Cardiovascular: auscultation (heart murmur, gallop rhythm, distant heart sound), ECG changes (prolonged PR-QT intervals, abnormal Q-wave, low voltage, ST-T changes, arrhythmias), chest X-ray findings (cardiomegaly), two-dimensional echocardiographic findings (pericardial effusion, coronary aneurysms), angina pectoris-like symptoms, aneurysms of peripheral arteries (axillae, etc) 2. Gastrointestinal tract: diarrhea, vomiting, abdominal pain, swelling of the gall bladder, paralytic ileus, mild jaundice, increased serum transaminase 3. Blood: leukocytosis with shift to the left, thrombocytosis, increased ESR, positive CRP, hypoalbuminemia, increased ␣-2-globulin, slight anemia 4. Urine: proteinuria, increase of leukocytes in sediment 5. Skin: redness and crust formation at the BCG inoculation site, small pustules, transverse furrows of the nails 6. Respiratory: cough, rhinorrhea, abnormal shadow on chest X-ray 7. Joints: pain, swelling 8. Neurological: pleocytosis of mononuclear cells in CSF, convulsion, unconsciousness, facial palsy, paralysis of the extremities
Histological Findings Histology of Kawasaki disease shows necrotizing vasculitis, which is distinguishable from classic polyarteritis nodosa, but indistinguishable from infantile polyarteritis nodosa.5 The coronary artery is most frequently affected, with fusiform aneurysm accompanied by thrombosis, occlusion or stenosis of the lumen. Pulmonary, carotid, iliac, celiac arteries and some veins may also be involved. Arterial lesions can be classified into five stages: (1) endothelial degeneration and increased vascular permeability; (2) edema and degeneration of the media; (3) necrotizing panarteritis; (4) granulation formation; and (5) scar formation. In the early stage, inflammatory tissue consists of neutrophils, eosinophils, lymphocytes, and plasma cells, but fibrinoid necrosis of the media is rare and slight. Histological findings of skin eruptions are not specific, probably because small vessels are not markedly involved. Perivascular mononuclear cell infiltration associated with edema and dilatation of small vessels in the dermis is observed. By electronmicroscopical study, researchers6 observed degenerative changes in the endothelial cells.
Clinics in Dermatology
Y
1999;17:659 – 662
VASCULITIS IN JAPAN
661
Treatment A high dose of aspirin and gamma globulin are effective in the acute stage. Thirty mg/kg/day of aspirin is recommended during the febril period, which is tapered to 10 mg/kg/day until BSR and CRP are normalized. Intravenous injection of 200 to 400 mg/kg/day gamma globulin for 5 days alone or with aspirin, is beneficial for preventing CAL.7 Systemic corticosteroids or antibiotics are not effective.
Takayasu Arteritis Takayasu arteritis is an uncommon chronic inflammatory disease of unknown etiology; it predominantly involves the aorta and its proximal branches and pulmonary artery. The blood vessels are segmentally involved, leading to both stenotic and ectatic changes in the arterial lumen. This disease was first described as a case report in 1856,8 and ophthalmological findings were reported by in 1908.9 Two large series of cases were described by Japanese cardiologists in 196710 and 1988.11 Recent studies12 suggest that the vascular changes are not confined to large arteries, but may involve smaller vessels including cutaneous vessels, which produce cutaneous manifestations.
Epidemiology This disease is most frequently seen in Japan, Korea, China, Southeast Asia, India, and Mexico. It is less common in Europe and the United States. The estimated incidence of Takayasu arteritis in North America is about 2.6 cases per 1 million people annually.13
Etiology Although the precise etiology of the disease has not been clarified, an autoimmune mechanism has been suggested because of the frequent association with rheumatoid arthritis or other connective tissue diseases. Antiaortic antibodies are demonstrated, but their etiological role is not known.
Clinical Features This disease affects mostly female adults under 40 years of age. In the initial phase, most patients complain of fever, malaise, anorexia, weight loss, night sweats, myalgia, and arthralgia. Cardiopulmonary symptoms such as tachycardia, chest pain, dyspnea, and cough are also common. In the late obliterative phase, patients show a variety of symptoms depending on the involved site of the artery. Cephalic hypoperfusion may produce headaches, dizziness, vertigo, seizures, and visual disturbance. Coronary artery involvement may result in angina pectoris or myocardial infarction. A few patients have complained of abdominal pain due to visceral artery involvement. Physical examination reveals cor-
Figure 3. Takayasu disease. Erythema nodosum-like nodule.
responding bruits over stenotic vessels. Hypertension of the legs with reduced blood pressure in the arms, suggestive of reversed coarctation, is a characteristic feature of this disease.
Cutaneous Manifestations and Histological Findings Cutaneous manifestations reported in patients with Takayasu arteritis are divided into specific and nonspecific ones. Specific manifestations have been reported in 12.5%14 to 18.9%12 of the patients, and included erythema nodosum, erythema induratum, tuberculid eruptions, pyoderma gangrenosum, and eruptions induced by necrotizing or granulomatous vasculitis. Erythema nodosum or erythema nodosum-like nodules are most frequently seen, but most of them are not true erythema nodosum histologically (Fig. 3). They show necrotizing vasculitis with polymorphonuclear leukocytes and fibrinoid necrosis in the blood vessel walls, granulomatous vasculitis, consisting of polymorphonuclear leukocytes, eosinophils, giant cells and fibrinoid necrosis, and/or lobular panniculitis with fat necrosis and septal panniculitis (Fig. 4). Most cases of pyoderma gangrenosum associated with Takayasu arteritis have been reported in Japan, although the reason is unknown.15 Acute or subacute nodules are more frequently seen in the early stage of Takayasu arteritis, whereas pyoderma gangrenosum and tuberculid eruption occur more frequently in the occlusive stage.14 Immunofluorescence may reveal deposition of immunoglobulin and/or complement components at the basement membrane zone or in the walls of the dermal blood vessels.
Clinics in Dermatology
662 IMAMURA AND FUJIMURA
Y
1999;17:659 – 662
neous lesions of various types. Cyclophosphamide and anticoagulant drugs such as aspirin and dipyridamole are commonly used. In the late obliterative phase, surgical revascularization treatments may be required. Acknowledgments Dr. Atsuhiko Ogino, Kyoto National Hospital, permitted us to use two clinical photographs of Kawasaki disease.
References
Figure 4. Takayasu disease. Granulomatous vasculitis consisting of polymorphonuclear leukocytes, eosinophils, and fibrinoid necrosis.
Laboratory Findings Elevated ESR, mild leukocytosis, and anemia are frequently seen. Elevated levels of immunoglobulin, C-reactive protein, and antistreptolysin-O titers are occasionally seen, but not specific. Aortic angiography is necessary for a full assessment.
Diagnostic Criteria Several criteria for the diagnosis of Takayasu arteritis have been proposed. The following criteria were offered in 1988.11
Obligatory Criterion Age ⬍40 years Two major criteria: 1. Left mid-subclavian artery lesion 2. Right mid-subclavian artery lesion Nine minor criteria: 1. 2. 3. 4. 5. 6. 7. 8. 9.
High ESR Carotid artery tenderness Hypertension Aortic regurgitation or annuloaortic ectasia Pulmonary artery lesion Left mid-common carotid lesion Distal branchiocephalic trunk lesion Descending thoracic aorta lesion Abdominal aorta lesion
In addition to the obligatory criterion, the presence of two major criteria, or one major and two or more minor criteria or four or more minor criteria, suggests Takayasu arteritis.
Treatment Systemic corticosteroids of relatively high doses are most effective for both systemic complaints and cuta-
1. Kawasaki T. Acute febril mucocutaneous lymph node syndrome with unique desquamation of the fingers and toes. Jap J Allerg 1967;16:178 –222 (in Japanese). 2. Kawasaki T, Kosaki F, Okawa S, et al. A new infantile acute febile mucocutaneous lymph node syndrome (MLNS) prevailing in Japan. Pediatrics 1974;54:271– 6. 3. Japan Kawasaki Disease Research Committee. Report of the 14th nationwide survey 1997 (in Japanese). 4. Japan Kawasaki Disease Research Committee. Report of the 8th nationwide survey. Perdiatr Jpn 1985;26:1049 –53 (in Japanese). 5. Landing BH, Larson EJ. Are infantile periarteritis nodosa with coronary artery involvement and fatal mucocutaneous lymph node syndrome the same? Comparison of 20 patients from North America with patients from Hawaii and Japan. Pediatrics 1977;59:651– 62. 6. Hirose S, Hamashima Y. Morphological observations on the vasculitis in the mucocutaneous lymph node syndrome: A skin biopsy of 27 patients. Eur J Pediatr 1978; 129:17–27. 7. Furusho K, Kamiya T, Nakano H, et al. High-dose intravenous gamma globulin for Kawasaki disease. Lancet 1984;ii:1055– 8. 8. Savory WS. Case of a young woman in whom the main arteries of both upper extremities and of the left side of the neck were throughout completely obliterated. Med Chir Trans Lond 1856;39:205–19. 9. Takayasu M. A case with peculiar changes of the central retinal vessels. Acta Soc Ophthal Jpn 1908;12:554 – 8 (in Japanese). 10. Nakao K, Ikeda M, Kimata S, et al. Takayasu’s arteritis: Clinical report of eighty-four cases and immunological studies of seven cases. Circulation 1967;35:1141–55. 11. Ishikawa K. Diagnostic approach and proposed criteria for the clinical diagnosis of Takayasu’s arteriopathy. J Am Coll Cardiol 1988;12:964 –72. 12. Perniciaro CV, Winkelmann RK, Hunder GG, et al. Cutaneous manifestations of Takayasu’s arteritis: A clinicopathologic correlation. J Am Acad Dermatol 1987;17:998 – 1005. 13. Hall S, Barr W, Lie JT, et al. Takayasu arteritis: A study of 32 North American patients. Medicine (Baltimore) 1985; 64:89 –99. 14. Frances C, Boisnic S, Bletry O, et al. Cutaneous manifestations of Takayasu arteritis. Dermatologica 1990;181: 266 –72. 15. Hidano A, Watanabe K. Pyoderma gangrenosum et cardiovasculopathies en particulier arte´rite de Takayasu. Ann Dermatol Venereol 1981;108:13–21.