Ö Bas¸aran et al.
Juvenile polyarteritis nodosa associated with toxoplasmosis presenting as Kawasaki disease Özge Bas¸aran,1 Nilgün Çakar,1 Gökçe Gür,1 Abdullah Kocabas¸,2 Belgin Gülhan,3 Fatma S¸emsa Çaycı1 and Banu Acar Çelikel1 Departments of 1Pediatric Nephrology and Rheumatology, 2Pediatric Cardiology and 3Pediatric Infectious Diseases, Ankara Child Health, Hematology, Oncology Education and Research Hospital, Ankara, Turkey Abstract
Polyarteritis nodosa (PAN) is a vasculitis characterized by inflammatory necrosis of medium-sized arteries. Juvenile PAN and Kawasaki disease (KD) both cause vasculitis of the medium-sized arteries, and share common features. They have overlapping clinical features. Treatment should be managed according to the severity of symptoms and persistence of clinical manifestations. Herein is described the case of a 14-year-old boy first diagnosed with KD, who then fulfilled the criteria for juvenile PAN due to the development of severe myalgia, persistent fever, polyneuropathy and coronary arterial dilatation. He also had acute toxoplasmosis at the onset of vasculitis symptoms. The final diagnosis was of juvenile PAN associated with toxoplasmosis infection. Toxoplasma infection can be considered as an etiological agent for PAN and other vasculitis syndromes. Awareness of toxoplasmosis-related PAN facilitates early diagnosis, and instigation of appropriate treatment.
Key words coronary artery lesion, Kawasaki disease, polyarteritis nodosa, toxoplasmosis.
Polyarteritis nodosa (PAN) is a necrotizing vasculitis affecting the small–medium-sized vessels. Classification criteria include biopsy of a small or medium artery showing necrotizing vasculitis or suggestive arteriography (aneurysms, stenosis or occlusion) plus at least two of the following: skin involvement, myalgia or muscle tenderness, hypertension, mono or polyneuropathy and renal impairment.1,2 Given that both PAN and Kawasaki disease (KD) cause vasculitis of medium-sized vessels, they have common clinical and pathological features.3 Herein we present the case of a boy initially diagnosed as having KD and who later had a diagnose of PAN. This case illustrates that a patient can have the clinical features of both PAN and KD. Infection associated with PAN is not unusual in adults but PAN associated with infection is not common among children.1 The present patient also had Toxoplasma infection at the beginning of the symptoms. In this case report, we also would like to underline the possibility of toxoplasmosis being the promoter factor for vasculitic processes. To the best of our knowledge, this is the first pediatric case report of PAN with toxoplasmosis.
Case report A 14-year-old boy presented with a 1 week history of fever, maculopapular rash on the extremities and myalgia. Physical exam indicated unilateral cervical lymph node enlargement Correspondence: Özge Bas¸aran, MD, Department of Pediatric Nephrology and Rheumatology, Ankara Child Health, Hematology, Oncology Education and Research Hospital, Ankara, Turkey. Email: [email protected]
Received 19 July 2013; revised 18 September 2013; accepted 9 October 2013. doi: 10.1111/ped.12241
© 2014 The Authors Pediatrics International © 2014 Japan Pediatric Society
and bilateral conjunctival hyperemia and maculopapular erythematous rash on extremities. On initial laboratory testing, white blood cell count was 15 800/mm3, hemoglobin 12.5 g/dL, hematocrit 35.5%, platelets 298 000/mm3, erythrocyte sedimentation rate 100 mm/h, C-reactive protein 34.65 mg/dL (normal 5 days), the presence of conjunctival hyperemia and maculopapular rash, KD was diagnosed and the patient was started on 80 mg/kg per day aspirin and a total dose of 2 g/kg per day i.v. immunoglobulin (IVIG) therapy. At this stage, echocardiogram was performed, and it was normal. Three days following IVIG therapy, the patient developed recurrent bouts of fever, arthritis, myalgia and elevation of acute phase reactants. Bone marrow aspiration was compatible with infection. On etiological evaluation for prolonged fever, positive toxoplasmosis IgM and IgG were identified (Toxoplasma IgM 2.951, IgG >250). Sabin Feldman test was also positive and pyrimethamine treatment was started. Three days after pyrimethamine, intractable fever and myalgia started again. At this stage he had desquamation on his fingers. Due to concern for active systemic vasculitis he was started on high dose oral corticosteroids (prednisone 60 mg daily). Three weeks following this therapy and approximately 2 months after the first symptoms started, the patient was again admitted to the clinic with severe generalized myalgia. He also had pain particularly on the right arm. Electromyelography indicated peripheral polyneuropathy, and on echocardiography there was right coronary arterial dilatation. Computed tomography coronary angiography showed right coronary artery ectasia measuring 0.6 cm in diameter (Fig. 1). The
Polyarteritis nodosa with toxoplasmosis
Fig. 1 (a) 2-D and (b) 3-D computed tomography angiography showing diffuse ectasia (arrows) of the right coronary artery.
patient met criteria for juvenile PAN due to coronary dilatation, prolonged fever, severe myalgia and polyneuropathy. He was given 1 g i.v. methylprednisolone daily, for 3 subsequent days, followed by high-dose oral corticosteroids (prednisone 60 mg daily). He also had monthly i.v. cyclophosphamide for 6 months. The steroid dose was gradually decreased, and he was still on 10 mg/day prednisone at the time of writing.Acute phase reactants normalized after therapy. Subsequent echocardiogram at the 6th month of treatment indicated minimal septal hypertrophy and regression of diffuse ectasia of the right coronary artery from 6 mm to 3.9 mm in diameter. Also, myocardial perfusion scintigraphy did not show any perfusion defect at the end of the first year of the disease.
Discussion The term ‘vasculitis’ indicates the presence of inflammation in a blood vessel wall. Pathogenesis of vasculitic syndrome is not fully understood and is also a complex process. Genetic, immune, hormonal and environmental factors have been described as triggers of autoimmunity and inflammatory damage to the blood vessels. Infection seems to be the most important environmental factor. Lidar et al. reported on 80 established vasculitis patients and their infection serologies and found a significant association between infection agents and vasculitis compared with the control group.4 Kawasaki disease is an acute systemic vasculitis of unknown origin predominantly affecting infants and young children. The diagnosis is sometimes difficult and differential diagnosis can be broad. The etiologic agent of KD remains unknown, although clinical and epidemiologic features strongly indicate an infectious cause.4 Several etiologic factors have also been proposed in the pathogenesis of PAN. In particular, the association between hepatitis B infection and PAN in adults is well known. This association has been reported in adult patients several times. Before the hepatitis B virus (HBV) vaccination became available, up to 75% of patients with PAN were infected with HBV. In the literature there are cases of PAN and bacterial infection (Streptococcus, Klebsiella, Yersinia, Pseudomonas) and there are also some reports proposing that bacterial super antigens could play a role in some cases.5 Other reports note higher exposure frequency of parvovirus B19, CMV, HIV and hepatitis C.5,6
Toxoplasmosis may cause vasculitis syndromes. Toxoplasmosis with PAN has also been described.4 In 1979, a Japanese woman aged 31 was reported to have PAN associated with acute toxoplasmosis.7 In pediatric patients, however, the relationship between PAN and infection is not clear.8 While the present patient was being investigated for prolonged fever, high antibody titers were observed for Toxoplasma gondii infection, and also the Sabin Feldman test supported the diagnosis. This patient’s toxoplasmosis occurred at the onset of PAN symptoms (fever, myalgia, rash). Also he had no other predisposing factors for PAN. Therefore, toxoplasmosis can be the triggering pathogen for this manifestation, but it is also difficult to explain this vasculitic process in terms of only toxoplasmosis, because a single case is not sufficient for a final decision. The present patient fulfilled the diagnostic criteria for KD with prolonged fever, cervical lymph node enlargement, maculopapular rash, bilateral conjunctival hyperemia and desquamation of hands. Both juvenile PAN and KD have a clinical presentation similar to this. Either disease could present with these features, such as fever and malaise, especially at the beginning of the course. Common clinical features include rash, conjunctivitis, arthritis, aneurysms and abdominal pain.9 The present patient had coronary artery dilatation, which could be related to both KD and PAN. The presence of coronary dilatation led to suspicion for KD, but in the literature there are reports on coronary artery involvement occurring with vasculitic diseases other than KD.3,9,10 The present patient also had persistent vasculitis symptoms, especially severe myalgia, which was more suggestive for PAN and which was the main complaint. He later developed polyneuropathy, one of the classification criteria of childhood PAN. Moreover his age was not compatible with KD given that it is an illness of early childhood. Also the patient was resistant to the IVIG and corticosteroid therapy, and his complaints improved after appropriate management. Based on echocardiographic abnormality, myalgia and polyneuropathy, a diagnosis of PAN was made. With regard to acute toxoplasmosis infection, myalgia can also be seen in up to 8% of patients but the present patient’s myalgia seems unlikely to be explained by only Toxoplasma infection because he had other symptoms.8 © 2014 The Authors Pediatrics International © 2014 Japan Pediatric Society
Ö Bas¸aran et al.
Yamazaki-Nakashimada et al. reported on a 3-year-old girl who fulfilled the criteria for both PAN and KD. In their literature review, they summarized the cases of four patients having the features of both PAN and KD.3 Canares et al. reported on a 16-year-old girl initially diagnosed with atypical KD who then developed coronary artery aneurysms and met the criteria for PAN, similar to the present patient.9 Conclusion
Toxoplasma infection could be considered as an etiological agent for PAN and other vasculitis syndromes. Awareness of Toxoplasma-related PAN can facilitate early diagnosis and instigation of combined immune-suppressive and pyrimethamine therapy. Although myalgia could be observed in approximately 8% of patients with acute toxoplasmosis infection, generalized and resistant myalgia should alert physicians to the possibility of rheumatological disease. Juvenile PAN and KD can present with overlapping clinical manifestations and it is important to recognize this clinical situation. Treatment should be managed according to the severity of symptoms and persistence of clinical manifestations.
References 1 Dillon MJ, Eleftheriou D, Brogan PA. Medium-size-vessel vasculitis. Pediatr Nephrol. 2010; 25: 1641–52.
2 Weiss PF. Pediatric vasculitis. Pediatr. Clin. North Am. 2012; 59: 407–23. 3 Yamazaki-Nakashimada MA, Espinosa-Lopez M, HernandezBautista V, Espinosa-Padilla S, Espinosa-Rosales F. Catastrophic Kawasaki disease or juvenile polyarteritis nodosa? Semin. Arthritis Rheum. 2006; 35: 349–54. 4 Lidar M, Lipschitz N, Langevitz P et al. Infectious serologies and autoantibodies in Wegener’s granulomatosis and other vasculitides: Novel associations disclosed using the Rad BioPlex 2200. Ann. N. Y. Acad. Sci. 2009; 1173: 649–57. 5 Rodríguez-Pla A, Stone JH. Vasculitis and systemic infections. Curr. Opin. Rheumatol. 2006; 18: 39–47. 6 Rodrigo D, Perera R, de Silva J. Classic polyarteritis nodosa associated with hepatitis C virus infection: a case report. J. Med. Case Rep. 2012; 6: 305–6. 7 Dry J, Leynadier F, Henault S, Luboinski J, Niel G. Acute toxoplasmosis with necrotizing vasculitis. Ann. Med. Interne (Paris) 1979; 130: 401–4. 8 Silva CS, Neves Ede S, Benchimol EI, Moraes DR. Postnatal acquired toxoplasmosis patients in an infectious diseases reference center. Braz. J. Infect. Dis. 2008; 12: 438–41. 9 Canares TL, Wahezi DM, Farooqi KM, Pass RH, Ilowite NT. Giant coronary artery aneurysms in juvenile polyarteritis nodosa: A case report. Pediatr. Rheumatol. Online J. 2012; 10: 1. 10 Chung DC, Choi JE, Song YK, Lim AL, Park KH, Choi YJ. Polyarteritis nodosa complicated by chronic total occlusion accompanying aneurysms on all coronary arteries. Korean Circ J. 2012; 42: 568–70.
Ptosis during hematologic malignancy in children Arzu Ekici,1 Ayten Yakut,1 Özcan Bör,2 Sevgi Yimeniciog˘lu,1 Kürs¸at Bora Çarman1 and Suzan Saylısoy3 Departments of 1Pediatric Neurology, 2Pediatric Hematology and 3Radiology, Osmangazi University Medicine Faculty, Eskisehir, Turkey Abstract
Neurological symptoms such as ptosis may develop due to either chemotherapeutic agents or involvement of the central nervous system (CNS) during hematologic malignancy. It is difficult to make this distinction according to clinical symptoms and magnetic resonance imaging findings. If the neurologic symptoms are increased, it is a warning of CNS involvement. Herein are described the clinical and neuroimaging features of three patients with hematologic malignancy who presented with ptosis.
Key words central nervous system, chemotherapeutic agent, hematologic malignancy, neurotoxicity, ptosis. The causes of acute neurological deterioration in children with hematologic malignancy are cerebrovascular disease, central nervous system (CNS) invasion by neoplastic cells, CNS infection, metabolic or electrolyte disturbances and drug neurotoxicity.1 Although chemotherapeutic agents reduce the risk of CNS relapse they also cause neurotoxicity, ranging from minor Correspondence: Arzu Ekici, MD, Akarbas¸ı Mahallesi, S¸ehit Zeynel Toköz Sokak, Önçag˘ Park Sitesi C Blok, Daire:6, Eskisehir, Turkey. Email: [email protected]
Received 4 December 2012; revised 25 July 2013; accepted 9 October 2013. doi: 10.1111/ped.12238
© 2014 The Authors Pediatrics International © 2014 Japan Pediatric Society
cognitive deficits to encephalopathy with dementia or even coma.2 Also, concomitant use of drugs increases the adverse effects.3 Neurological symptoms such as ptosis may develop due to either chemotherapeutic agents or involvement of CNS.1 Herein we describe the clinical and neuroimaging features of three patients with hematologic malignancy who presented with ptosis.
Case reports Case 1
A 9-month-old boy was diagnosed with acute lymphoblastic leukemia (ALL). After the second day of Berlin-Frankfurt-Munich