ANCA-associated and other childhood vasculitides: SAQ

This boy has the pulmonary-renal syndrome of granulomatosis with polyangiitis, and the framework that organises the answer is the Chapel Hill vessel-size classification, the pauci-immune mechanism, and the remission-induction and maintenance framework. [7]

Question 1 (10 marks)

Discuss the classification and the pathogenesis of this condition, the acute management of the pulmonary-renal syndrome, and the remission-induction and maintenance framework. [1]

A full-mark answer reproduces the classification, the mechanism and the induction and maintenance regimen. [6]

Classification and pathogenesis (4 marks). This is granulomatosis with polyangiitis, formerly Wegener granulomatosis. The 2012 Chapel Hill Consensus Conference nomenclature classifies the vasculitides by vessel size, and the ANCA-associated diseases are small-vessel, pauci-immune vasculitides. The EULAR/PRINTO/PRES Ankara 2008 criteria classify childhood granulomatosis with polyangiitis when three of six features are present: granulomatous histology, upper-airway involvement, laryngo-tracheo-bronchial involvement, pulmonary involvement on imaging, ANCA positivity and renal involvement. This boy meets several. The mechanism is the PR3 (c-ANCA) autoantibody binding the primed neutrophil, which degranulates and releases the reactive oxygen species and the neutrophil extracellular traps against the vessel wall, producing the pauci-immune fibrinoid necrosis and the crescentic glomerulonephritis. [3][1]

Acute management of the pulmonary-renal syndrome (3 marks). The pulmonary-renal syndrome is the emergency, because the untreated pauci-immune crescentic glomerulonephritis can destroy the kidneys within days. The child receives the oxygen for the alveolar haemorrhage and the fluid and electrolyte management for the acute kidney injury, with the urgent renal review and the dialysis for the refractory case. The ANCA with the PR3 and MPO assay is sent, the urinalysis and the urine microscopy confirm the red-cell casts, and the renal biopsy is arranged to grade the crescentic injury and exclude the mimics. The induction therapy is started early, often before the biopsy, because the cost of the early immunosuppression in the confirmed case is small against the cost of the delayed treatment. [10][6]

Induction and maintenance (3 marks). The remission induction for the organ or life-threatening disease is rituximab at 375 mg per square metre per week for four weeks, or cyclophosphamide, plus the glucocorticoids as the methylprednisolone pulse followed by the prednisolone. The choice is guided by the phenotype, the fertility, the infection risk and the local protocol. The maintenance to prevent the relapse is the rituximab every six months or the azathioprine at 1.5 to 2.5 mg per kg per day for at least 18 to 24 months, because the disease, especially the PR3-positive form, is relapsing. The trimethoprim-sulfamethoxazole has only a limited adjunctive role for the upper-airway Staphylococcus aureus carriage. [6]

Question 2 (10 marks)

Discuss how your assessment and management would change if he presented instead with an absent radial pulse and hypertension, or with late-onset asthma, eosinophilia and a mononeuritis multiplex. [9]

A full-mark answer reproduces the Takayasu pathway and the eosinophilic granulomatosis with polyangiitis pathway. [5]

The absent radial pulse with hypertension (5 marks). This redirects the diagnosis from the small-vessel ANCA-associated disease to the large-vessel Takayasu arteritis. The examination is the four-limb blood pressure and the pulse assessment, feeling for the pulse deficit and the discrepancy of more than 10 mmHg between the limbs, and auscultating for the bruits over the subclavian, the carotid, the abdominal and the renal arteries. The angiography, by the computed tomography, the magnetic resonance or the conventional method, is the mandatory test, showing the segmental wall thickening, the stenosis, the occlusion and the aneurysms of the aorta and its branches in the skip-lesion distribution. The management is the high-dose glucocorticoid for the active inflammation, tapered with the response, the biologic of the tocilizumab or the infliximab for the refractory disease, and the angioplasty or the surgical bypass for the critical stenosis once the inflammation is controlled. The Kawasaki cross-link is the medium-vessel disease treated with the intravenous immunoglobulin and the aspirin, not the glucocorticoid and the revascularisation. [9][8]

The asthma, eosinophilia and mononeuritis multiplex (4 marks). This is the eosinophilic granulomatosis with polyangiitis, formerly Churg-Strauss syndrome, in its three phases of the allergic asthma, the eosinophilic infiltration and the vasculitic mononeuritis multiplex. The cardiac involvement is the leading cause of death, so the troponin and the echocardiogram are essential to detect the eosinophilic myocarditis and the coronary vasculitis. The management is the high-dose glucocorticoid as the foundation, with the cyclophosphamide for the severe cardiac or the organ or life-threatening disease, and the mepolizumab, the anti-interleukin-5 biologic, for the eosinophilic and the asthma phenotype. The mononeuritis multiplex is often slow to recover and may leave a residual deficit, which is part of the counselling. [5][6]

Synthesis (1 mark). The fellow who holds the Chapel Hill vessel-size classification, the pauci-immune mechanism, the remission-induction and maintenance framework, the Takayasu pathway and the eosinophilic granulomatosis with polyangiitis pathway has the framework that organises the whole management of the childhood vasculitides. [6]