Vasculitis
Anti-neutrophil cytoplasmic antibody-associated vasculitides Wegener’s granulomatosis Wegener’s granulomatosis (WG)
• is uncommon in children.
• a necrotizing granulomatous inflammation of small- to medium-sized vessels
• kidneys and upper and lower respiratory tracts.
• biopsies - a microscopic pauci-immune polyangiitis.
• cANCA directed against PR-3.
• nasal and sinus involvement were seen in 100%,
• respiratory disease in 87%,
• arthralgias, ocular findings, or skin or renal involvement each in just over 50%,
• gastrointestinal disease in 41%,
• and CNS involvement in 12%
• subglottic stenosis in almost 50%
cause of WG
• ANCA most likely stabilize adherence of rolling neutrophils to endothelium and activate neutrophils and monocytes to undergo an oxidative burst.
• Activation of phagocytic cells causes increased expression of proinflammatory cytokines (eg, TNF-a and IL-8), with resultant localized endothelial cell cytotoxicity
Upper respiratory symptoms
• Epistaxis, sinusitis, otitis media, or hearing loss.
• Cough, wheezing, dyspnea, and hemoptysis.
• Kidney involvement may initially be asymptomatic.
• Chest radiographs - one third have radiographic abnormalities in asymptomatic children
• diagnosis of WG relies heavily on biopsy
• Necrotizing granulomatous vascular inflammation is strongly suggestive
• cANCA targeted against PR-3 is positive in most patients
• Although this autoantibody is highly specific, it may be found in other diseases, such as cystic fibrosis,
• ANCA titer should not replace a tissue biopsy.
• role of monitoring of ANCA titers as a marker of disease activity is controversial.
• Without immunosuppressive therapy, WG is rapidly progressive and even fatal.
– cyclophosphamide,
– azathioprine, methotrexate, and, more recently, mycophenolate mofetil and.
– TNF-a blockers.
– Preliminary data showed that the anti-TNF agent etanercept did vasculitis in children.
• .
• but infliximab apparently was effective.
• trimethoprim/sulfamethoxazole has been shown to be beneficial.
• perhaps by suppressing upper respiratory infections that might activate vascular inflammation.
Microscopic polyangiitis
A necrotizing vasculitis of the small vessels without.
granuloma formation.
Clinical manifestations;
• kidney and pulmonary involvement,
• focal segmental glomerulonephritis and pulmonary hemorrhage.
• positive pANCA with reactivity to myeloperoxidase (MPO).
Microscopic polyangiitis
• Most patients seem to require cyclophosphamide.
• Milder agents may be adequate for maintaining remissions.
• Most recently, a single 4-week course of rituximab might replace both cyclophosphamide and long-term steroids.
Churg–Strauss syndrome
• CSS is extremely rare in children.
• A prodromal phase of an allergic rhinitis and asthma,
• may persist for many years.
• The second phase - worsening asthma,
• peripheral eosinophilia, and pulmonary infiltrates.
the third or vasculitic phase - systemic vasculitis
• weight loss,
• fever,
• arthralgia,
• myalgia,
• nodular rash,
• neuropathy.
• Asthma symptoms usually subside during the vasculitic phase.
Churg–Strauss syndrome
• Tissue biopsy is generally diagnostic,
• Significant perivascular eosinophilic infiltrates and occasional extravascular granulomas.
• ANCA directed against both PR-3 and MPO may be seen in CSS.
Churg–Strauss syndrome
• An initial aggressive remittive therapy,
• Followed by milder maintenance treatment,
• Most deaths are caused by cardiac involvement,
– followed by severe gastrointestinal and CNS disease.
• exquisitely sensitive to corticosteroids,
Secondary vasculitides
• Infections,
• Medications,
• Systemic diseases.
Secondary vasculitides
• viruses (parvovirus B19, HIV, varicella),
• Rickettsia,
• bacteria,
• fungi,
• mycobacteria,
systemic inflammatory conditions
• SLE, juvenile dermatomyositis [JDMS], juvenile rheumatoid arthritis, sarcoidosis, inflammatory bowel syndrome, tumors), CF.
• Drugs.
• Both leukocytoclastic and necrotizing vasculitis have been reported.
• Removal of the trigger or control of the inciting condition leads to remission of the vasculitis.
Behcet’s disease
• A multisystem inflammatory disorder
• BD is characterized by the triad of
– recurrent oral ulcers,
– genital ulcers,
– and uveitis,
• Any organ system may be involved including
– skin,
– joints
– CNS,
– or gastrointestinal tract,
Behcet’s disease
• Vascular inflammation is often a prominent feature.
• Both arteries and veins may be affected.
• A particular predilection for the venules.
• A propensity for development of thromboses,
• Including deep vein thrombosis and thrombophlebitis.
• Arterial aneurysms may also occur - pulmonary aneurysms.
Behcet’s disease
• BD is thought to occur when an infectious agent triggers an amplified inflammatory response in a genetically susceptible host.
• In the Japanese and Turkish vasculitis populations, in whom the disease is most prevalent, HLA-B51 is a marker for BD.
• and the aberrant cellular immune response seems to involve gd-T cells.
• Antibody-mediated immune mechanisms may also play a role.
Various immunomodulatory agents
• IFN-a,
• thalidomide,
• dapsone,
• steroids,
• cyclophosphamide,
• azathioprine
Periodic fever syndromes
• During the past 5 years,
• novel autoinflammatory conditions caused by mutations in regulators of inflammation have been described.
Summary
• Vasculitis is rare in children,
• Apart from HSP and perhaps KD,
• Most practicing pediatricians will never encounter a case.
Summary
It is important to consider vasculitis as a.
potential cause of;
• unexplained inflammation,
• perplexing rashes,
• or strange combinations of symptoms.
