State of the Art in the Treatment of Systemic Vasculitides

Abstract

Anti-neutrophil cytoplasm antibodies (ANCA) are associated with small vessel vasculitides (AASV) affecting the lungs and kidneys. Structured clinical assessment using the Birmingham Vasculitis Activity Score and Vasculitis Damage Index should form the basis of a treatment plan and be used to document progress, including relapse. Severe disease with organ or life threatening manifestations needs cyclophosphamide or rituximab, plus high dose glucocorticoids, followed by lower dose steroid plus azathioprine, or methotrexate. Additional plasmapheresis is effective for very severe disease, reducing dialysis dependence from 60 to 40% in the first year, but with no effect on mortality or long-term renal function, probably due to established renal damage. In milder forms of ANCA-associated vasculitis, methotrexate, leflunomide, or mycophenolate mofetil are effective. Mortality depends on initial severity: 25% in patients with renal failure or severe lung hemorrhage; 6% for generalized non-life threatening AASV but rising to 30-40% at 5 years. Mortality from GPA is four times higher than the background population. Early deaths are due to active vasculitis and infection. Subsequent deaths are more often due to cardiovascular events, infection, and cancer. We need to improve the long-term outcome, by controlling disease activity but also preventing damage and drug toxicity. By contrast, in large vessel vasculitis where mortality is much less but morbidity potentially greater, such as giant cell arteritis (GCA) and Takayasu arteritis, therapeutic options are limited. High dose glucocorticoid results in significant toxicity in over 80%. Advances in understanding the biology of the vasculitides are improving therapies. Novel, mechanism based therapies such as rituximab in AASV, mepolizumab in eosinophilic granulomatosis with polyangiitis, and tocilizumab in GCA, but the lack of reliable biomarkers remains a challenge to progress in these chronic relapsing diseases.

Serum ferritin as an activity marker for granulamotosis with polyangiitis

“…Lack of markers that predict activity and relapses make management of GPA challenging and there is no clear consensus on the duration of maintenance treatment. Hence, reliable biomarkers are needed to guide the treatment [20]. Several studies have shown association between serum ferritin and disease severity in various inflammatory disorders including renal involvement in SLE and interstitial lung disease in dermatomyositis [13,14].…”

Vasculitis ANCA and Systemic Scleroderma

“…Teniendo en cuenta la epidemiología de la enfermedad y la forma de presentación clínica, se descartó crisis renal esclerodérmica, paso fundamental, dado que el uso de esteroides en esos casos puede ser deletéreo 6 , contrario a lo que sucede con las vasculitis, donde es la piedra angular del tratamiento de inducción y mantenimiento. El inicio temprano influye en la evolución y el pronóstico de la enfermedad 19 . La utilización de la escala BVAS para el seguimiento es de gran utilidad, la meta con el tratamiento es obtener un puntaje de 0.…”

Adulter Morbus Still mit Kleingefäßvaskulitis

“…Bei der Behandlung der Riesenzellvaskulitis zeigt Tocilizumab in kleinen Fallsammlungen vielversprechende Ergebnisse [5,8]. Bei nicht-ANCA-assoziierten Kleingefäßvas-kulitiden gibt es jedoch sonst deutlich weniger Erfahrungen mit dem Einsatz von Biologika [3]. Wir behandelten unseren Patienten mit Tocilizumab, denn die IL-6-Rezeptorhemmung wird effektiv zur Behandlung des adulten Morbus Still eingesetzt [1].…”