|Year : 2014 | Volume
| Issue : 2 | Page : 61-65
Ratna Bimal Basak1, Suhas Ganguli2, Susana Rapaport2
1 Department of Pediatrics and Palliative Care, NY Medical College, NY, USA
2 NY Flushing Hospital Medical Center, NY, USA
|Date of Web Publication||27-Aug-2014|
Ratna Bimal Basak
19, Threef Locust, Greenvale, NY11548
Source of Support: None, Conflict of Interest: None
Pediatric vasculitis is the presence of inflammation of blood vessels. It accounts for 2 - 10% of rheumatology clinic attendance. Henoch-Schonlein purpura is the commonest followed by Kawasaki disease. The diagnosis of vasculitis is challenging as it may manifest to it with myraid of symptom and sign including fever, myalgia, arthritis, nephropathy, skin rashes and skin ulceration. Elevation acute phase reactants with identification of some specific markers are necessary to made the diagnosis.
Keywords: Antinuclear factor, antineutrophil cytoplasmic antibody, C-reactive protein, Churg-Strauss syndrome, Henoch-Schonlein purpura, Kawasaki disease, magnetic resonance angiography, microscopic polyarteritis, rheumatoid factor, Takayasu arteritis, Wegener′s granulomatosis
|How to cite this article:|
Basak RB, Ganguli S, Rapaport S. Pediatric vasculitis. Indian J Paediatr Dermatol 2014;15:61-5
| Introduction|| |
Vasculitis is defined as the presence of inflammation in the blood vessel wall.
The site and size of vessel involvement of the blood vessel and the extent of vascular injury and pathology determine the disease type.
Making a diagnosis of vasculitis is challenging, presenting symptoms may often be nonspecific as fever, malaise, with only elevation of acute phase reactants. A good history must include of recent infections, drug exposure, and family history with physical exam to look for skin rashes, nodules, ulcerations, micro-infarctions, blood pressure in all four limbs and peripheral pulses.
Annual incidence of vasculitis is 20-23/100,000, with primary vasculitis accounting 2-10% of all pediatric rheumatology clinics. Henoch-Schonlein purpura (HSP) accounts almost half of the primary pediatric vasculitis (49%) with Kawasaki disease (KD) the second common (24%) and polyarteritis nodosa (PAN) accounting almost 3%. 
They are classified as in [Table 1].
|Table 1: EULAR/PReS classification of PV according to the size of vessel |
Click here to view
| Predominantly small vessel|| |
They predominantly affect small blood vessel, are antineutrophil cytoplasmic antibody (ANCA) positive except HSP and have renal involvement and treatment related morbidities.
Henoch-Schonlein purpura is a nonthrombocytopenic systemic hypersensitivity vasculitis of childhood. 20/100,000 with a peak age of onset 4-6 years with a higher incidence in Caucasians.  It generally has good prognosis, depends on renal involvement which develops in 5% of patients.
Etiology and pathogenesis
The etiology of HSP is unknown, more prevent in winter and spring. Certain autoimmune factors like complement deficiencies  familial Mediterranean fever and infection like Group A streptococcal infections, Epstein-Barr infections may trigger HSP.  Active disease is characterized by increased the cytokine tumor necrosis factor (TNF-α) and interleukin-6.
The classic presentation of HSP includes lower extremity rash which may be maculopapular that initially blanch then become purpuric so-called palpable purpura [Figure 1]. It may become erythematous plaques or may be erythema multiform like. It is usually symmetrical, in the buttocks and lower extremities but may be seen in arms and face and often come in crops. Subcutaneous edema of hands, feet and scrotum are characteristically seen. Blistering, bullae, necrosis or extensive skin lesions are uncommon.
It affects in 75% of children, can be the presenting feature in a few patients. It is usually localized in knees, ankles and are oligoarticular, self-limited and nondestructive. 
present as colicky abdominal pain, bleeding, intussusception secondary to damage to the vasculature of the gastrointestinal tract. There may red currant jelly, bleeding per rectum and hematemesis. In 10-15% of children, intestinal manifestations may precede the purpura by 2 weeks. 
It may occur in 25-50% of the patients. The most common renal manifestation is microscopic hematuria. There may be associated proteinuria. Rarely nephritis, acute renal failure, end-stage disease may occur. Most children who develop renal disease develop within the first 6 weeks of initial presentation and 97% with 6 months of the illness.  However even with normal urine analysis, testing should be continued for 6 months. 
Unusual clinical features of HSP include scrotal edema, pulmonary hemorrhage, seizures stroke, and mental status changes.
Routine laboratory testing is usually nondiagnostic. There may be leukocytosis, thrombocytosis and the erythrocyte sedimentation rate may be elevated, with associated anemia. Antinuclear antibody, ANCA and Rh factors are negative. Immunoglobulin A (IgA) and IgM are usually elevated, and definite diagnosis is confirmed by biopsy which may show IgA deposition.
Treatment of HSP is largely supportive including analgesics for arthritis, edema, and fever. Scrotal edema may be reduced by elevation. Prospective trials have shown that use of Prednisolone was effective in reducing the severity of abdominal and joint pain and treating renal disease.  In the hospital setting, use of corticosteroids early (starting day 1 or 2) for intestinal complications has been associated with improved outcomes.  Other therapies in acute renal failure like the plasmapheresis, immunosuppressant's such as cyclophosphamide, azathioprine and cyclosporine have been tried with varying success.
Wegener's granulomatosis (WG) is necrotizing granulomatosis small vessel vasculitis involves small and medium vessels of upper and lower respiratory tracts and the kidneys. Mean age of diagnosis is 14 years. Untreated systemic WG, follows a fulminant course with a mean survival of 5 months. 
Necrotizing granulomatosis of small and medium vessels involving renal and pulmonary vessels.
Constitutional features such as fever, malaise, myalgia, arthralgia, and weight loss are present in 90% of patients. Cough, nasal discharge, sinusitis, mucosal ulceration are early features and later pulmonary hemorrhage, nodules, respiratory failure may develop. 85% have upper respiratory disease that may include oral and nasal ulcerations, nasal septum perforations, mastoiditis, hearing loss, and subglottic stenosis. 2/3 patients have renal involvement that include hematuria, proteinuria, glomerulonephritis, and renal failure. Intracranial and peripheral granulomas have been reported. 50% of patients also report conjunctival and corneal lesions, uveitis and invasive orbital pseudotumor. Palpable purpura, granulomatous dermatitis with papules particularly on the extensor surface of elbows is seen. [Table 2] summarizes the classification criterion of WG.
Elevated acute phase reactants, anemia in 75% of patients. Antibodies to ANCA directed to proteinase 3. Biopsy of the tissue helps to confirm the diagnosis.
Daily oral cyclophosphamide with prednisolone for 12 months, then tapered.  Intermittent cyclophosphamide has also been used with less success but fewer toxicities and frequent relapses. Methotrexate, mycophenolate mofetil, leflunomide, intravenous immunoglobulin (IVIG), antithymocyte globulin, tacrolimus have been tried with varying success. The biologics like TNF-α, and etanercept have undergone multicentric trials to sustain remission large controlled studies. 
Churg-Straus syndrome is a granulomatous vasculitis of small sized and medium sized vessels who have associated asthma (90%), sinusitis (75%) or rhinitis. Common cutaneous manifestations are palpable purpura in almost half of the patients, maculopapular rash, rashes resembling erythema multiforme. Very few case reports in pediatric age group are there.
It is a necrotizing nongranulomatous vasculitis typically affecting small vessels of the kidneys and lungs with a peak age of onset between 30 and 50 years.  Very few cases have been reported in pediatric age group. 
| Predominantly medium vessel diseases|| |
Polyarteritis Nodosa and Cutaneous Polyarteritis (PAN & CPA)
Polyarteritis nodosa and cutaneous polyarteritis (CPA) are rare necrotizing vasculitides in pediatric age group. PAN is typically a disease characterized by extensive multisystem involvement of skin, intra-abdominal organs, nervous system, and kidneys. CPA is usually limited to blood vessels of the skin, peripheral nervous system, muscles, and joints.
Even though, PAN is considerably rare in childhood, most cases seem to affect children between ages 9 and 11 years, with equal affliction of boys and girls. PAN is viewed by many experts as severe manifestations of KD. 
The precise etiology of development of PAN is uncertain. However, in adults an association with hepatitis B has been described.  In addition, infectious agents like hepatitis C, Epstein-Barr virus, parvovirus B 19 or cytomegalovirus, Group A and Group B streptococcus have been implicated in the pathogenesis.
Characteristic histological findings include usually necrotizing arteritis with formation of nodules along the small and medium sized blood vessels.  Mesenteric vessels are most frequently involved at bifurcation of vessels. Aneurysm formation is highly characteristic.
Unexplained prolonged fevers, myalgia, musculoskeletal or abdominal pains raise the suspicion of the diagnosis. The classification criteria of PAN have been summarized in [Table 3].
Cutaneous polyarteritis nodosa
It is characterized by absence of major organ system involvement, but may involve skin in the form of subcutaneous nodules, splinter hemorrhages, livido reticularis, digital edema, peripheral ischemia.
Specific laboratory findings
Apart from commonly observed laboratory features, urinalysis reveals sediments depending on degree and nature of glomerulonephritis. ANCA are not as commonly positive as they are in WG or microscopic polyarthritis (MP). Levels of beta-thromboglobulin and factor VIII-related antigens are elevated in active disease and correlates with treatment response.  Confirmatory diagnosis requires skin biopsy. ,
Glucocorticoid is the mainstay of treatment with gradual weaning. , Glucocorticoid failure may be addressed with oral azathioprine or cyclophosphamide therapy. Other modalities include IVIG and plasmapheresis. Penicillin prophylaxis is recommended in patients with positive antistreptolysin O titers is recommended to prevent recurrences.
Cutaneous PAN has a more favorable outcome.
Overview and introduction
Kawasaki disease is an acute self-limiting febrile vasculitis of infants and small children with a special predilection toward coronary arteries presenting as aneurysms and ectasies. ,,
Majority of the patients are below 5 years of age, though rarely it has been described in older children and adults.  The disease is known to occur in both endemic and community - wide epidemic forms in Asia, Europe and Americas of all races. 
Etiology and pathogenesis
The precise cause of KD is unknown, both innate and adaptive arms of immunity have been studies extensively in pathogenesis of this disorders. ,
Clinical manifestations and diagnosis
The disease course can be divided into three phases:
- Acute phase (a period of 10-14 days)
- Subacute phase (approximately 2-4 weeks) and
- Convalescent or recovery phase (months to years).
Diagnosis is by use of clinical criteria in most typical cases as described below [Table 4], no specific laboratory test is useful in confirming a diagnosis.
Laboratory features of Kawasaki disease
There is no specific associated laboratory finding, anemia, thrombocytopenia may be seen. Platelet counts begin to rise usually in the 2 nd week of illness and may reach 1,000,000/cu mm.
Microscopic examination of urine obtained by clean catch method reveals increased leucocytes without evidence of infection. Elevated transaminases and hypoalbuminemia and hydrops of gallbladder leading to obstructive jaundice may be found in a small subset of patients. Cerebrospinal fluid (CSF) exam, rarely done, may reveal pleocytosis without hypoglycorrachia or elevation of CSF protein.
Cardiac manifestations prominent in the acute phase include pericarditis, myocarditis, and involvement of the coronary artery.
The most devastating complication of KD is formation of coronary artery aneurysm and, therefore, deserves special mention.
Treatment with high-dose intravenous with high-dose aspirin; the window for treatment is first 10 days of illness. Some clinicians prefer to continue to treat with high dose aspirin for 2 weeks whereas others decrease the dose after 48 h the patient had become afebrile. The low dose aspirin is continued till 6 weeks, and repeat echocardiography is done at this time. If the latter is normal, aspirin is typically discontinued. Plasma exchange has been reported to be of benefit in IVIG refractory KD. Ulinastatins is a human trypsinogen inhibitor used in Japan as an adjunctive therapy to IVIG resistant KD. Other treatments that have been proposed in this group are corticosteroids and abciximab, and monoclonal antibodies though data on their use is limited. 
Prognosis and long-term care
The overall long-term prognosis of KD correlates completely with extent of coronary involvement. Mortality from KD is low (0.5%) , with majority within the 1 st year after illness.
| Predominantly large vessel|| |
Takayasu arteritis and temporal arteritis, the two major forms of giant cell arteritis, occur infrequently in children and do not have cutaneous lesions. So these are not discussed in this article.
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[Table 1], [Table 2], [Table 3], [Table 4]