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A case of polymyositis associated with Kawasaki disease
A Case of Polymyositis Associated with Kawasaki Disease Hideo Sugie, MD, Yoko Sugie, MD, Miyuki Ichimura, MD, Yoshito Mizuno, MD, Mitsuhiro Nishida, MD and Yoshio Igarashi, MD
We report a 3-year-old boy with proximal painful muscle weakness associated with Kawasaki disease. The muscle biopsy revealed inflammatory cell infiltration with vasculopathy. This unique coexistence of polymyositis and Kawasaki disease is quite uncommon and suggests a newly recognized complication during Kawasaki disease. Sugie H, Sugie Y, Ichimura M, Mizuno Y, Nishida M, Igarashi Y. A case of polymyositis associated with Kawasaki disease. BrainDev 1985; 7: 513-5
Kawasaki disease, firstly described by Kawasaki in 1967, is characterized by a systemic febrile illness associated with cervical lymphadenopathy, conjunctivitis, reddness and fissuring of the lips and an erythematous rash. Various complications have already been reported , in particular, cardiovascular disturbances have been well documented . However , neuromuscular manifestations associated with Kawasaki disease are quite rare. We performed a muscle biopsy in a 3-year-old boy presenting proximal painful muscle weakness during a typical clinical course of Kawasaki disease. Case Report The patient was a 3-year-old boy who had been a product of a normal pregnancy and delivery.
From the Department of Pediatrics, Hamamatsu University School of Medicine, Hamamatsu, Shizuoka. Received for pUblication: February 25, 1985. Accepted for publication: June 5,1985.
Key words: MCLS, Kawasaki disease, polymyositis, angiopathy, inflammatory myopathy. Correspondence address: Hideo Sugie, MD, Department of Pediatrics, Hamamatsu University School of Medicine, 3600 Handa-cho, Hamamatsu 431-31, Shizuoka.
There was no family history of any neuromuscular disorders. He had been in good health until he developed acute febrile illness with conjunctivitis. The fever did not respond to oral antibiotics (ampicillin, 50 mg/kg). Two days after the onset of fever, cervical lymphnode swellings and an erythematous rash were noticed . At this time he was admitted to our hospital for further evaluation. On admission, his body temperature was 39.6°C, pulse rate 160/min , respiration rate 40/ min and blood pressure 106/65 mmHg. Physical examination revealed an irritable boy with bilateral conjunctivitis, reddness and fissuring of the lips, cervical lymphadenopathy, injected oral mucosa, a strawberry tongue and an erythematous rash in the trunk and extremities. Immediately after admission, a diagnosis of Kawasaki disease was made and oral salicylates (50 mg/ kg) were commenced instead of antibiotics . 9 days after the onset of the illness , he complained of myalgia especially in the bilateral quadriceps. He stood only with broad based position, never jumped and walked only with support. In addition, he could arise from a sitting position with Gowers' maneuver. Neurological examination revealed diffuse muscle weakness of all extremities, being greater proximal than distal. Cranial nerves were intact. Deep tendon reflexes were normal. There were
Table 1 Morphometric analysis of th e
capillaries
Endothelial fraction of capillaries area (%)
Number of vesicles (/JJ,m')
Control (38 capillaries)
26.1
±
3.2
30.1
This patient (12 capillaries)
62.3
±
5.1 *
12.3 ±3. 1*
±
5.9
Values indicate mean ± SE *p < 0.01. . Fig 1 Perivascular and occasional peri/endomysia I cell infiltrations (mainly consisting of mononuclear leucocytes) (H&E 250 x).
Method A needle muscle biopsy was performed on the left quadriceps muscle with local anesthesia and prepared for histochemistry and electron microscopy. Histological and histochemical studies included hematoxylin-eosin (H&E), modified Gomori trichrome, oil red 0 , PAS , NADH tetrazolium reductase (NADH-TR), SDH and myosin ATPase with preincubation at pH 9 .4 , 4.6 and 4 .2. Morphometric analysis of endomysial capillaries was performed according to Jerusalem et al [1] using Image Analyzer System of Video Plan (Kontron Co Ltd).
Fig 2 Two endomysial capillaries showing prolifera-
tive endothelial cells with decreased pinocytotic vesicles. Pericyte showed possible hypertrophy. (original mag. 6,000 x). .
no myotonia , fasciculation or clonus. AT 15th illness day, membranous desquamation was noted from the fingertips. Laboratory test results on admission were as follows : RBC 3 8, 50,000/mm3, platelets 520,000/mm 3, WBC 23 ,500/mm3, erythrocyte sedimentation rate (ESR) 71/1 hour, CRP 3+, ASLO 160 units, SGOT 117 IU, S-GPT 46 IU and S-LDH 489 IU. SoCK determined when proximal muscle weakness was firstly noticed was 152 IU (normal: less than 50 IU). Electromyography (EMG) showed a myopathic change with fibrillation potentials at rest. Coronary aneurysm was demonstrated by echocardiography 10 days after the onset. A needle muscle biopsy was performed 2 weeks after the onset of Kawasaki disease when Gowers' sign was still evident.
514 Brain & Development, Vol 7, No 5, 1985
Results The muscle biopsy specimen obtained by the needle procedure contained about 800 muscle fibers and was enough for histochemical evaluation. Multiple cryostat sections revealed mild distortion of the fascicular architecture with generalized type 2 fiber atrophy. Inflammatory cell infiltrations (mainly mononuclear leucocytes) were noticed in perivascular area and in peri/endomysial spaces (Fig 1). Occasional fiber necrosis and angulated fibers with NADH-TR hyperreactivity were also demonstrated. Perifascicular atrophy was not noticed. Electronmicroscopy showed that endomysial capillaries con tained proliferative endothelial cells and decreased pinocytotic vesicles (Fig 2). Morphometric analysis of endomysial capillaries confirmed the increased percentage of the endothelial cell fractions (Table I). Some capillaries had only a slit like lumen. Approximately 20 endomysial capillaries were evaluated, however, "undulating tubules" were not found.
Discussion Various complications including coronary aneurysm , hydrops of gall bladder , arthralgia, aseptic pyuria and mild hepatitis associated with Kawasaki disease have been described . In addition, neurological manifestations such as aseptic meningitis, facial palsy, cerebrovascular disturbances and Reye like syndrome have been reported [2]. Our case showed proximal painful muscle weakness suggesting inflammatory myopathy although S-CK was not evidently elevated. The diagnosis of polymyositis/dermatomyositis is essentially based upon a clinical manifestation combined with muscle histology and S-CK may be consistently normal [3] . Therefore, we diagnosed that this patient had polymyositis associated with Kawasaki disease. The muscle biopsy of our patient confirmed the inflammatory response within the muscle tissue with vascular involvement. Antiinflammatory steroids were not commenced in our patient because the coexistence of polymyositis was thought to be a possible complication of Kawasaki disease which is usually self limiting in nature [4]. Complete recovery of neuromuscular manifestations was confirmed 2 months after the onset. Systemic angiopathy as a causative factor of Kawasaki disease has been proposed, and Hamashima reported that the alterations in microvessels (capillaries, arterioles and venules) occurs earliest, reaches a peak within about 10 days of illness [5]. Our muscle biopsy was performed at the 14th illness day, therefore the pathological changes of the capillaries seen in our patient might relevant to the early vascular change occurred in Kawasaki disease . Vascular involvement has also been
demonstrated in childhood polymyositis/ dermatomyositis , and " undulating tubules" , especially in endothelial cells, have been frequently noticed . Considering the spontaneous clinical recovery without steroids; and the absence of joint contracture and "undulating tubules" in our patient, the mechanism of devel opment of myositis in Kawasaki disease might be somewhat different from that in so-called childhood polymyositis/ dermatomyositis. Koutras reported two cases with myositic manifestations during Kawasaki disease , however , muscle biopsy was not performed in either case [6] . Probably, neuromuscular manifestations have been easily overlooked because of the severe febrile illness. We should be aware of the possible coexistence of polymyositis and Kawasaki disease. Further detailed clinical observations and case accumulation will be necessary to clarify this matter. References 1. Jerusalem F, Rakusa M, Engel AG, Macdonald RD. Morphometric analysis of skeletal muscle capillary ultrastructure in inflammatory myopathies. J Neurol Sci 1974 ;23: 391-402. 2. Asoh S, Watanabe J. Neurological complications in Kawasaki disease (in Japanese). Nihon Shonika Gakkai Zasshi (Tokyo) 1984;37:541-8. 3. Dubowitz V. Muscle disorders in childhood. London: Saunders Co. Ltd, 1978:202-22. 4. Kawasaki T, Kosaki F, Okawa S, Shigematsu I, Yanagawa H. A new infantile acute febrile mucocu taneous lymphnode syndrome (MCLS) prevailing in Japan. Pediatrics 1974;54 :271-6. 5. Hamashima Y. Kawasaki disease. Trans Soc Pathol Jpn 1977;66:59-92. 6 . Koutras AK. Myositis with Kawasaki disease. Am J Dis Child 1982; 136:78-9.
SUf{ie et al: Polymyositis and Kawasaki disease 515
We report a 3-year-old boy with proximal painful muscle weakness associated with Kawasaki disease. The muscle biopsy revealed inflammatory cell infiltration with vasculopathy. This unique coexistence of polymyositis and Kawasaki disease is quite uncommon and suggests a newly recognized complication during Kawasaki disease. Sugie H, Sugie Y, Ichimura M, Mizuno Y, Nishida M, Igarashi Y. A case of polymyositis associated with Kawasaki disease. BrainDev 1985; 7: 513-5
Kawasaki disease, firstly described by Kawasaki in 1967, is characterized by a systemic febrile illness associated with cervical lymphadenopathy, conjunctivitis, reddness and fissuring of the lips and an erythematous rash. Various complications have already been reported , in particular, cardiovascular disturbances have been well documented . However , neuromuscular manifestations associated with Kawasaki disease are quite rare. We performed a muscle biopsy in a 3-year-old boy presenting proximal painful muscle weakness during a typical clinical course of Kawasaki disease. Case Report The patient was a 3-year-old boy who had been a product of a normal pregnancy and delivery.
From the Department of Pediatrics, Hamamatsu University School of Medicine, Hamamatsu, Shizuoka. Received for pUblication: February 25, 1985. Accepted for publication: June 5,1985.
Key words: MCLS, Kawasaki disease, polymyositis, angiopathy, inflammatory myopathy. Correspondence address: Hideo Sugie, MD, Department of Pediatrics, Hamamatsu University School of Medicine, 3600 Handa-cho, Hamamatsu 431-31, Shizuoka.
There was no family history of any neuromuscular disorders. He had been in good health until he developed acute febrile illness with conjunctivitis. The fever did not respond to oral antibiotics (ampicillin, 50 mg/kg). Two days after the onset of fever, cervical lymphnode swellings and an erythematous rash were noticed . At this time he was admitted to our hospital for further evaluation. On admission, his body temperature was 39.6°C, pulse rate 160/min , respiration rate 40/ min and blood pressure 106/65 mmHg. Physical examination revealed an irritable boy with bilateral conjunctivitis, reddness and fissuring of the lips, cervical lymphadenopathy, injected oral mucosa, a strawberry tongue and an erythematous rash in the trunk and extremities. Immediately after admission, a diagnosis of Kawasaki disease was made and oral salicylates (50 mg/ kg) were commenced instead of antibiotics . 9 days after the onset of the illness , he complained of myalgia especially in the bilateral quadriceps. He stood only with broad based position, never jumped and walked only with support. In addition, he could arise from a sitting position with Gowers' maneuver. Neurological examination revealed diffuse muscle weakness of all extremities, being greater proximal than distal. Cranial nerves were intact. Deep tendon reflexes were normal. There were
Table 1 Morphometric analysis of th e
capillaries
Endothelial fraction of capillaries area (%)
Number of vesicles (/JJ,m')
Control (38 capillaries)
26.1
±
3.2
30.1
This patient (12 capillaries)
62.3
±
5.1 *
12.3 ±3. 1*
±
5.9
Values indicate mean ± SE *p < 0.01. . Fig 1 Perivascular and occasional peri/endomysia I cell infiltrations (mainly consisting of mononuclear leucocytes) (H&E 250 x).
Method A needle muscle biopsy was performed on the left quadriceps muscle with local anesthesia and prepared for histochemistry and electron microscopy. Histological and histochemical studies included hematoxylin-eosin (H&E), modified Gomori trichrome, oil red 0 , PAS , NADH tetrazolium reductase (NADH-TR), SDH and myosin ATPase with preincubation at pH 9 .4 , 4.6 and 4 .2. Morphometric analysis of endomysial capillaries was performed according to Jerusalem et al [1] using Image Analyzer System of Video Plan (Kontron Co Ltd).
Fig 2 Two endomysial capillaries showing prolifera-
tive endothelial cells with decreased pinocytotic vesicles. Pericyte showed possible hypertrophy. (original mag. 6,000 x). .
no myotonia , fasciculation or clonus. AT 15th illness day, membranous desquamation was noted from the fingertips. Laboratory test results on admission were as follows : RBC 3 8, 50,000/mm3, platelets 520,000/mm 3, WBC 23 ,500/mm3, erythrocyte sedimentation rate (ESR) 71/1 hour, CRP 3+, ASLO 160 units, SGOT 117 IU, S-GPT 46 IU and S-LDH 489 IU. SoCK determined when proximal muscle weakness was firstly noticed was 152 IU (normal: less than 50 IU). Electromyography (EMG) showed a myopathic change with fibrillation potentials at rest. Coronary aneurysm was demonstrated by echocardiography 10 days after the onset. A needle muscle biopsy was performed 2 weeks after the onset of Kawasaki disease when Gowers' sign was still evident.
514 Brain & Development, Vol 7, No 5, 1985
Results The muscle biopsy specimen obtained by the needle procedure contained about 800 muscle fibers and was enough for histochemical evaluation. Multiple cryostat sections revealed mild distortion of the fascicular architecture with generalized type 2 fiber atrophy. Inflammatory cell infiltrations (mainly mononuclear leucocytes) were noticed in perivascular area and in peri/endomysial spaces (Fig 1). Occasional fiber necrosis and angulated fibers with NADH-TR hyperreactivity were also demonstrated. Perifascicular atrophy was not noticed. Electronmicroscopy showed that endomysial capillaries con tained proliferative endothelial cells and decreased pinocytotic vesicles (Fig 2). Morphometric analysis of endomysial capillaries confirmed the increased percentage of the endothelial cell fractions (Table I). Some capillaries had only a slit like lumen. Approximately 20 endomysial capillaries were evaluated, however, "undulating tubules" were not found.
Discussion Various complications including coronary aneurysm , hydrops of gall bladder , arthralgia, aseptic pyuria and mild hepatitis associated with Kawasaki disease have been described . In addition, neurological manifestations such as aseptic meningitis, facial palsy, cerebrovascular disturbances and Reye like syndrome have been reported [2]. Our case showed proximal painful muscle weakness suggesting inflammatory myopathy although S-CK was not evidently elevated. The diagnosis of polymyositis/dermatomyositis is essentially based upon a clinical manifestation combined with muscle histology and S-CK may be consistently normal [3] . Therefore, we diagnosed that this patient had polymyositis associated with Kawasaki disease. The muscle biopsy of our patient confirmed the inflammatory response within the muscle tissue with vascular involvement. Antiinflammatory steroids were not commenced in our patient because the coexistence of polymyositis was thought to be a possible complication of Kawasaki disease which is usually self limiting in nature [4]. Complete recovery of neuromuscular manifestations was confirmed 2 months after the onset. Systemic angiopathy as a causative factor of Kawasaki disease has been proposed, and Hamashima reported that the alterations in microvessels (capillaries, arterioles and venules) occurs earliest, reaches a peak within about 10 days of illness [5]. Our muscle biopsy was performed at the 14th illness day, therefore the pathological changes of the capillaries seen in our patient might relevant to the early vascular change occurred in Kawasaki disease . Vascular involvement has also been
demonstrated in childhood polymyositis/ dermatomyositis , and " undulating tubules" , especially in endothelial cells, have been frequently noticed . Considering the spontaneous clinical recovery without steroids; and the absence of joint contracture and "undulating tubules" in our patient, the mechanism of devel opment of myositis in Kawasaki disease might be somewhat different from that in so-called childhood polymyositis/ dermatomyositis. Koutras reported two cases with myositic manifestations during Kawasaki disease , however , muscle biopsy was not performed in either case [6] . Probably, neuromuscular manifestations have been easily overlooked because of the severe febrile illness. We should be aware of the possible coexistence of polymyositis and Kawasaki disease. Further detailed clinical observations and case accumulation will be necessary to clarify this matter. References 1. Jerusalem F, Rakusa M, Engel AG, Macdonald RD. Morphometric analysis of skeletal muscle capillary ultrastructure in inflammatory myopathies. J Neurol Sci 1974 ;23: 391-402. 2. Asoh S, Watanabe J. Neurological complications in Kawasaki disease (in Japanese). Nihon Shonika Gakkai Zasshi (Tokyo) 1984;37:541-8. 3. Dubowitz V. Muscle disorders in childhood. London: Saunders Co. Ltd, 1978:202-22. 4. Kawasaki T, Kosaki F, Okawa S, Shigematsu I, Yanagawa H. A new infantile acute febrile mucocu taneous lymphnode syndrome (MCLS) prevailing in Japan. Pediatrics 1974;54 :271-6. 5. Hamashima Y. Kawasaki disease. Trans Soc Pathol Jpn 1977;66:59-92. 6 . Koutras AK. Myositis with Kawasaki disease. Am J Dis Child 1982; 136:78-9.
SUf{ie et al: Polymyositis and Kawasaki disease 515