24 PEDIATRIC RHEUMATOLOGY M A R C H 2 0 1 0 • R H E U M AT O L O G Y N E W S ASK THE EXPERT Pediatric Vasculitis Poses Diagnostic Challenges S RHEUMATOLOGY NEWS: What are the most frequent systemic vasculitides that affect children? Dr. Gedalia: There are two systemic vasculitides that affect children most frequently: Henoch-Schönlein purpura, a nongranulomatous small-vessel vasculitis, and Kawasaki disease, a mediumsize vessel vasculitis. These are self-limiting diseases. Children do develop such chronic vasculitides as giant cell arteritis, Wegener’s granulomatosis, microscopic polyangiitis, Churg-Strauss syndrome, polyarteritis nodosa, and Takayasu’s arteritis, but these occur much more rarely than they do in adults. RN: What are the most important diagnostic criteria that distinguish these conditions from other inflammatory disorders that might mimic them? Dr. Gedalia: As its name suggests, vasculitis is a condition associated with inflammation of the blood vessels. This arteries and is now the leading cause of Dr. Gedalia: Most children with acquired heart disease in children in the Henoch-Schönlein purpura do well with United States. The disease affects mostly supportive care and observation because infants and young children, and rarely this is a self-limiting disease, from which teenagers. It is characterized by fever, most patients recover. Some patients, espolymorphic rash, conjunctivitis, mu- pecially those with joint involvement cositis, changes in and painful inflamthe hands and feet, matory soft-tissue The criteria classify the and unilateral cerviedema, require common childhood cal lymphadenopaanalgesics and nonthy. However, the steroidal anti-invasculitides by vessel size hallmark of this disflammatory drugs. and histopathology, which is ease is the coronary The arthritis assoartery abnormalities ciated with expected to be useful to (mainly aneurysms) Henoch-Schönlein rheumatologists in practice. that are developed purpura is tranin approximately sient and not asso20%-25% of untreated patients. A patient ciated with any permanent joint disease; with Kawasaki disease has to present with therefore, the use of steroids is reserved fever lasting 5 or more days without oth- for patients with severe gastrointestinal er more reasonable explanation and, ac- involvement. cording to the classification system, must Standard treatment for Kawasaki disfulfill at least four of the following five cri- ease includes intravenous immunoglobteria: ulin treatment (IVIG). In IVIG-resistant Kawasaki disease, treatment with the 씰 Have bilateral conjunctival injection. anti–tumor necrosis factor–alpha agent 씰 Demonstrate at least one mucous membrane change, such as injected or infliximab has been proved effective in fissured lips, injected pharynx, or straw- early studies. ©C USTOM M EDICAL S TOCK P HOTO, A LL R IGHTS R ESERVED ystemic vasculitis is a multisystem process can occur as a primary disorder disease that without proper man- or as secondary to the underlying disagement can be associated with sig- eases. In both situations, vasculitis can nificant morbidity and mortality. Diag- lead to vascular tissue injury such as vasnosing systemic vasculitis in children can cular leak, aneurysm formation, stenosis, be especially challenging, given the wide occlusion, rupture, and necrosis that may impact the involved organ. variation in the type and loThe above disorders have cation of vessel involvement. unique criteria that are helpThe degree of inflammation ful to distinguish them from and the resultant vessel wall other inflammatory diseases damage may also confound and establish the diagnosis. diagnosis. Moreover, the earIn the case of Henochly findings in affected chilSchönlein purpura, the condren—such as fever, skin ledition is a multisystem IgAsions, and inflammation— mediated vasculitis with are neither specific nor senself-limited course affecting sitive for the condition, and ABRAHAM the skin, joints, gastrointestias such can mimic multiple G E D A L I A , M . D. nal tract, and kidneys. Other other childhood infectious organs such as lungs, brain, diseases. Historically, the lack of an acceptable and genitourinary system may be inclassification system for childhood vas- volved. Based on the revised classificaculitis has led rheumatologists to rely on tion system, a patient with Henochadult classification criteria that are sub- Schönlein purpura has to fulfill at least optimal for use in children. In 2006, an two of the following four criteria, as deinternational consensus group of the fined by the American College of European League Against Rheumatism Rheumatology: (EULAR) and the Pediatric Rheumatol- 씰 Exhibit palpable purpura, not related ogy European Society (PRES) proposed a pediatric vasculitis classification that would bring the existing criteria into line with clinical practice (Ann. Rheum. Dis. 2006;65:936-41). The proposed criteria, which are currently being validated, classify the common childhood vasculitides by vessel size and histopathology. This approach is expected to be useful to rheumatologists and pediatricians in practice, as well as to those who are involved in epidemiologic studies and clinical trials of pediatric vasculitis, according to Dr. Abraham Gedalia. In this month’s column, Dr. Gedalia discusses the clinical features, management, and prognosis of the common childhood vasculitides, and offers insight into the most important classification revisions. In this color-enhanced angiogram of a child with Kawasaki disease, note the aneurysms (red) of the weakened small arteries that come off the aorta. to thrombocytopenia. Be age 20 years or younger at disease onset. 씰 Present with abdominal pain, usually with gastrointestinal bleeding. 씰 Have biopsy-proven granulocytes in the vessel wall (arterioles or venules). Detection of the classic, palpable, purpuric rash and its distribution in children improves the accuracy of the diagnosis of Henoch-Schönlein purpura. Skin biopsy is rarely needed, except in very young children (aged 2 years and younger) in whom the rash is not classically distributed. Kawasaki disease is an acute, self-limited, systemic vasculitis of unknown origin that predominantly involves the coronary 씰 berry tongue. 씰 Exhibit at least one extremity change, such as erythema of the palms or soles, edema of the hands or feet, or generalized periungual desquamation. 씰 Present with a polymorphous rash. 씰 Present with cervical lymphadenopathy, with at least one lymph node measuring 1.5 cm or greater in diameter. Patients who have coronary artery involvement (detected on echocardiography) in addition to fever may present with fewer than four of these five criteria; the exact number is currently being determined. RN: What are the primary therapies for vasculitis in children? RN: What is the prognosis for children with these conditions? Dr. Gedalia: The prognosis is good in children with Henoch-Schönlein purpura. However, the long-term outcome of Henoch-Schönlein purpura is complicated when patients develop renal involvement. Among patients with Kawasaki disease, up to 2% die from coronary abnormalities, and 20%-25% of untreated patients develop coronary artery abnormalities or ectasia. In the absence of detectable coronary artery abnormalities, data from long-term followup studies conducted 10-20 years after the onset of Kawasaki disease have shown that patients’ morbidity and mortality are similar to those in the normal pediatric population. RN: What are some of the most pressing short- and long-term challenges in the management of vasculitis in children? Dr. Gedalia: The short-term challenges are to find the most efficacious and safe treatments of the serious manifestations, such as renal involvement in HenochSchönlein purpura and coronary involvement in Kawasaki disease. As affected children are surviving longer—often thanks to the increasing use of biologic agents as second-line treatments after the failure of standard first-line therapies— managing the long-term cardiovascular morbidity in Kawasaki disease patients is a particular challenge. —Diana Mahoney DR. GEDALIA is professor of pediatrics and head of the division of pediatric rheumatology at Louisiana State University Health Sciences Center and Children’s Hospital in New Orleans. He reported having no potential conflicts of interest. Pages 24a—24h佥