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provided by Elsevier - Publisher Connector Journal of Microbiology, Immunology and Infection (2012) 45,22e30
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ORIGINAL ARTICLE Kawasaki disease and HenocheScho¨nlein purpura e 10 years’ experience of childhood vasculitis at a university hospital in Taiwan
Mei-Chen Teng a,b, Li-Chieh Wang a, Hsin-Hui Yu a, Jyh-Hong Lee a, Yao-Hsu Yang a, Bor-Luen Chiang a,*
a Department of Pediatrics, National Taiwan University Hospital, Taipei, Taiwan, ROC b Department of Pediatrics, Min-Sheng General Hospital, Taoyuan, Taiwan, ROC
Received 29 April 2011; received in revised form 10 May 2011; accepted 31 May 2011
KEYWORDS Background/Purpose: To investigate the clinical manifestations, disease activity and prognosis HenocheScho¨nlein in different types of vasculitis. purpura; Methods: The charts of pediatric patients with vasculitis diagnosed from December 1997 to VAAD; December 2007 were retrospectively reviewed. The first clinical manifestations and laboratory Vasculitis-associated results were recorded at the time of diagnosis, and outcome evaluations with history of flare- autoimmune ups were analyzed. disease Results: A total of 508 vasculitis patients were included in this study, of whom 124 had Henoche Scho¨nlein purpura (HSP), and 351 had Kawasaki disease (KD). Hematuria was observed in 79% of recurrent HSP patients at the time of diagnosis, and was associated with an increased risk of relapse (p Z 0.000). In Kawasaki disease, the clinical symptoms with erythematous changes in Bacille Calmette-Gue´rin scars and coronary artery dilatation were more prominent in patients younger than 1 year old, and lymphadenopathy was more common in patients older than 1 year old (p Z 0.001). The risk of coronary dilatation was significant in the patients with an initial presentation of thrombocytosis, and greater in patients younger than 1 year old (p Z 0.027). Thrombocytopenia was more prominent in vasculitis-associated autoimmune diseases. Marked lymphocytosis with increased C-reactive protein levels was significantly noted in urticarial vasculitis patients compared with HSP patients in multivariate logistic regression analysis.
* Corresponding author. Department of Pediatrics, National Taiwan University Hospital, No. 7, Chung-Shan South Road, Taipei, Taiwan, 100, ROC. E-mail address: [email protected] (B.-L. Chiang).
1684-1182/$36 Copyright ª 2011, Taiwan Society of Microbiology. Published by Elsevier Taiwan LLC. All rights reserved. doi:10.1016/j.jmii.2011.09.024 Childhood vasculitis 23
Conclusion: Vasculitis disease activity and prognosis were associated with initial laboratory results and clinical manifestations. Further large-scale clinical trials are warranted to validate these findings. Copyright ª 2011, Taiwan Society of Microbiology. Published by Elsevier Taiwan LLC. All rights reserved.
Introduction frequently as females. Arthritis, present in more than two- thirds of children with HSP, is usually localized to the Vasculitis in childhood is a result of causes ranging from knees and ankles, and appears to be concomitant with idiopathic conditions with primary vessel inflammation to edema. Edema and damage to the vasculature of the syndromes after exposure to recognized antigenic triggers gastrointestinal tract may also lead to intermittent such as infectious agents and drugs causing hypersensitivity abdominal pain that is often colicky in nature. Renal e reactions. Vasculitis is also a component of many autoim- involvement occurs in 25 50% of children and manifests mune diseases. with hematuria, proteinuria, or both. The major compli- Childhood vasculitides are complex, multisystemic dis- cations of HSP are renal involvement, including nephrotic eases,,and include many different types of disease. syndrome, and bowel perforation. One population-based Vasculitis is generally classified as primary, secondary or study indicated that 4% of patients with HSP develop incidental. It is an inflammatory process mediating persistent renal disease and less than 0.1% develop serious destruction of the vessel walls by unknown causes, leading renal disease. to hemorrhage, ischemia and/or infarction.1,2 Primary Wegener’s granulomatosis (WG) is a necrotizing granu- vasculitis syndromes include systemic and cutaneous vari- lomatous small-vessel vasculitis that occurs at all ages and ants, such as idiopathic cutaneous leukocytoclastic vascu- often involves the upper airways, lower respiratory tract litis, HenocheScho¨nlein purpura (HSP), Wegener’s and kidneys. Although most cases occur in adults, children granulomatosis (WG), and ChurgeStrauss syndrome (CSS). can develop WG with a mean age at diagnosis of 6 years, Secondary vasculitis syndromes include vasculitis associ- but it may present as early as 2 weeks of age. There is ated with autoimmune diseases, infections, drug eruptions, a female predominance of 3:1. e malignancies and others involved in small-vessel vasculit- Churg Strauss syndrome is a vasculitis that can cause ides. Incidental vasculitis represents a localized histological chronic sinus lesions. Diagnostic criteria include a history of finding that is the consequence of another pathology, such asthma, circulating eosinophilia and an eosinophilic cuta- as traumatic ulceration or diffuse neutrophilic infiltration1,2 neous vasculitis that often involves lymphadenopathy. (Table 1). There is little information showing an association of disease activity and prognosis with initial laboratory results Takayasu arteritis (TA) is the third-most common form of and clinical symptoms. In this study, we aimed to investi- childhood vasculitis worldwide after HSP and Kawasaki gate this possible association and find factors at the time of disease, with a 2.5:1 female:male ratio. About one-third of diagnosis that were predictive of relapse, and differentiate cases have an onset before 20 years of age, and symptoms their prognostic relevance on the basis of the type of usually appear after 10 years of age, although children as childhood vasculitis. young as 8 months have been affected. Kawasaki disease (KD) is an acute febrile vasculitis of childhood. Approximately 20% of untreated patients develop coronary artery abnormalities. The cause of the illness Methods remains unknown, but epidemiological and clinical features strongly support an infectious origin. The illness occurs Patients predominantly in young children, and 80% of patients are less than 5 years of age. Kawasaki disease causes severe We retrospectively reviewed the charts of vasculitis vasculitis of all blood vessels, but predominantly affects the patients (onset age <18 years) who were admitted to the medium-sized arteries. Prolonged fever is prognostic for the Pediatric Rheumatology Ward of the National Taiwan development of coronary artery disease, and perineal University Hospital, a tertiary referral center, from desquamation has also been noted in the acute phase. December 1997 to December 2007, and who satisfied the Heno¨ch-Schonlein purpura (HSP), also known as 1990 American College of Rheumatology (ACR) criteria anaphylactoid purpura, is a common vasculitis of small based predominately on clinical findings and/or the Chapel vessels with cutaneous and systemic complications. It is the Hill Consensus conference (CHCC),3 which is based on most common cause of nonthrombocytopenic purpura in pathologic criteria for vasculitis. Urticaria vasculitis children. The etiology is unknown, but HSP often follows an patients were diagnosed by skin biopsy results, and the upper respiratory tract infection. HSP occurs more diagnosis of infection associated vasculitis was dependent frequently in children, with most cases occurring between 2 on pathogen culture results or serologic reports. All and 8 years of age, and most frequently in the winter patients were ethnic Chinese. The demographics, clinical months. The overall incidence is estimated to be features, diagnostic evaluations and outcomes of the 14/100,000population, and males are affected twice as patients were recorded. Patients were excluded from the 24
Table 1 Classification of vasculitis Class Name Pathophysiology Characteristics Associated disease Large-vessel vasculitis Giant cell arteritis Granulomatous inflammation Most common over 50 years old Associated with polymyalgia rheumatica Takayasu arteritis Granulomatous inflammation Third-most common form of childhood Associated with connective tissue, vasculitis autoimmune, endocrine Pulseless disease Medium-vessel vasculitis Kawasaki disease Vasculitis of coronary arteries, Occurs usually in children Associated with mucocutaneous aorta and veins may be Potential aneurysm formation lymph node syndrome involved The clinical features of fever persisting for at least 5 days and plus the presence of at least four principal features: exanthem, conjunctival injection without exudate, changes in extremities (erythema or edema), changes in lip and oral cavity, and cervical lymphadenopathy(> 1.5 cm diameter), usually unilateral Rheumatoid vasculitis Distal, symmetric polyneuropathy Occurs in patients who have longstanding rheumatoid arthritis Angiitis of central nervous Repeat angiogram after 4e6 weeks Evident on MRI/histopathology system Small-vessel vasculitis Henoch-Scho¨nlein purpura Necrotizing inflammation, Most common vasculitis in children Associated with arthralgias or IgA-dominant immune deposits Involves skin, gut, and glomeruli arthritis Palpable purpura Hypersensitivity vasculitis Necrotizing inflammation Involves skin, joints Associated with connective tissue (urticaria vasculitis) Leukocytoclastic 40% of these patients have angioedema diseases, autoimmune disorders, Small- to medium-vessel which tends to be painful or burn viral hepatitis, or as a paraneoplastic syndrome Wegener’s granulomatosis Granulomatous inflammation Equal in men and women Necrotizing glomerulonephritis common Necrotizing inflammation Occurs in any age, but most cases occur in cANCA positive adults Strawberry gums are a classic sign e
Churg Strauss syndrome Granulomatous or necrotizing Upper respiratory tract, lungs, heart, pANCA positive al. et Teng M.-C. inflammation (or both) peripheral nerves Asthma history
ANCA Z antineutrophil cytoplasmic antibody; IgA Z immunoglobulin A; MRI Z magnetic resonance imaging. hlho vasculitis Childhood Table 2 Types of unspecific vasculitis Case Type Age Clinical WBC Platelets Neutrophils Lymphocytes CRP ANA C3/C4 Others (y)/ presentation (/mL) ( 103/mL) (/mL) (/mL) (mg/dL) (mg/dL) gender I CSS 14/M Asthma, sinusitis 8740 272 7307 1101 5.82 1:160 164/38 Eos: 25.5% Pleural effusion IgE: 1822 Mononeuritis multiplex II HD 4/F Fever 2860 32 744 829 4.33 1:40 107/21 Biopsy: granulocytes Purpura in a perivascular Rash location Eos: 23% Medication at disease onset III DIV 6/F Purpura 3040 269 1003 1368 3.97 N/A N/A N/A Arthralgia ALL under MTX control** IV DIV 16/F Purpura 7220 226 4282 2137 3.67 1:40 N/A N/A Arthralgia V LV 11/F Chronic, recurrent 4820 301 2612 1711 0.05 1:40 124/24 Biopsy: intraluminal ulcers over thrombosis bilateral lower extremities VI LV 14/F Progressive 7790 169 2392 4417 0.03 1:40 N/A Biopsy: intraluminal erythematous thrombosis change and ulceration over bilateral leg Purpura VII TA 6/M Dyspnea 16,700 293 13,410 1987 5.54 N/A N/A Arteriogram Orthopnea abnormality in Upper descending arteries, extremities left renal artery weakness Subclavian steal phenomenon VIII VGI 10/F Abdominal pain 6720 260 3508 2822 0.07 1:40 133/19 Echo: normal Weight loss IX VGI 9/M Abdominal pain 10,450 202 5998 3459 4.92 1:40 N/A Echo: normal Duodenal ulcer Bloody stools X UV 13/F Purpura, arthritis 8740 272 7307 1101 5.82 1:2560 N/A EBNA(þ) RF:1:5120 (continued on next page) 25 26 M.-C. Teng et al.
study if they were transferred from another hospital or clinic without a description of the initial presentation or Barr male; e laboratory results. Z Diagnostic evaluation and follow-up Epstein We recorded the diagnostic evaluation results at the time Z of vasculitis diagnosis and during vasculitis flares. A relapse
Others vascular damage with perivascular and periadenexa neutrophil infiltrate and nuclear debris was defined as the recurrence of clinical signs/symptoms or the occurrence of new symptoms after an initial remission,
white blood cells. requiring the resumption of immunosuppressive therapy or Z
livedoid vasculitis; M an increased dose. Diagnostic evaluation included complete blood cell and differential cell counts, urinalysis, C-reac- Z (mg/dL) tive protein (CRP), antinuclear antibody, anti-dsDNA anti- body, serum C3 and C4 levels, erythrocyte sedimentation rate (ESR), antiphospholipid antibody (APA), and anti- cardiolipin antibody (ACA). APAs were assayed using drug-induced vasculitis; EBNA ANA C3/C4 an IMUCLONE aPL immunoglobulin (Ig) G enzyme-linked Z immunosorbent assay (ELISA) kit (American Diagnostica, Stamford CT., US) ACAs were assayed using AUTOZYME ACL
immunoglobulin E; LV anticardiolipin IgG and IgM sandwich immunoassays (Cam-
Z bridge Life Sciences Ltd., Cambridgeshire, UK). Hematuria CRP (mg/dL) 1.06 N/A 136/18 N/A was defined as the excretion of more than ten red blood cells per high-power field in a centrifuged urine specimen and/or urine dipstick test OB S one plus. Strauss syndrome; DIV We reviewed the clinical charts for any clinical or e vasculitis of the gastrointestinal tract; WBC laboratory signs of remission or relapse at every visit and Z
Churg recorded the time from disease onset to diagnosis, and Lymphocytes (/ m L) 2180
Z from diagnosis to first relapse.
hypersensitivity vasculitis; IgE Statistical analysis Z 2253 Neutrophils (/ m L) Data with a normal distribution were expressed as the mean SD, and non-normally distributed data were
unspecific vasculitis; VGI expressed as the median (range). Between-group differ- Z m L) C-reactive protein; CSS
female; HD ences in categorical variables were examined using Fisher’s / 3 Z
Z exact test or the Chi-square test. For continuous data,