The Impact of High Dose Glucocorticoids on Bone Health and Fracture Risk in Systemic Vasculitides.

Systemic vasculitides are a range of conditions characterized by inflammation of blood vessels which may manifest as single organ or life-threatening multisystem disease. The treatment of systemic vasculitis varies depending on the specific disease but historically has involved initial treatment with high dose glucocorticoids alone or in conjunction with other immunosuppressive agents. Prolonged glucocorticoid treatment is frequently required as maintenance treatment. Patients with small and large vessel vasculitis are at increased risk of fracture. Osteoporosis may occur due to intrinsic factors such as chronic inflammation, impaired renal function and to a large extent due to pharmacological therapy with high dose glucocorticoid or combination treatments. This review will outline the known mechanism of bone loss in vasculitis and will summarize factors attributing to fracture risk in different types of vasculitis. Osteoporosis treatment with specific consideration for patients with vasculitis will be discussed. The use of glucocorticoid sparing immunosuppressive agents in the treatment of systemic vasculitis is a significant area of ongoing research. Adjunctive treatments are used to reduce cumulative doses of glucocorticoids and therefore may significantly decrease the associated fracture risk in patients with vasculitis. Lastly, we will highlight the many unknowns in the relation between systemic vasculitis, its treatment and bone health and will outline key research priorities for this field.

Biologic therapy in ANCA-negative vasculitis.

Standard therapeutic schemes for vasculitis are usually associated with numerous side effects and uneven clinical response. However, recent advances in understanding of the pathogenesis of these systemic diseases have resulted in the development of a group of biologic agents potentially useful in patients with vasculitis. Thus, anti-tumor necrosis factor-α drugs may be effective in patients with refractory Kawasaki disease but have failed to do so in giant cell arteritis, and their role in Takayasu arteritis is yet unclear. Preliminary reports on the use of the anti-IL6-receptor antibody, tocilizumab, in large-vessel vasculitis have been encouraging. Interferon alpha has showed positive results in hepatitis B virus-associated polyarteritis nodosa, and hepatitis C virus-induced cryoglobulinemia. Early experience with rituximab in several types of vasculitis has been quite promising, but must be confirmed in ongoing randomized clinical trials. The development of new biologic targeted therapies will probably open a hopeful future for patients with vasculitis.

Acute dilated cardiomyopathy in a patient with beriberi and cryoglobulinaemic vasculitis: an unusual potential complication of two rare disorders.

We report the case of a 45-year-old patient who presented with acute dilated cardiomyopathy. During admission the patient was consecutively diagnosed with cryoglobulinaemic vasculitis and beriberi. In both diseases, cardiac involvement may occur as dilated cardiomyopathy. Thiamin deficiency was the final cause for the severe cardiac manifestations (cardiac acute beriberi or Shoshin syndrome), which returned to normal after thiamin supplementation.

Renal vasculitis in 2012: reclassification and the introduction of biologicals.

2012 saw the classification of the systemic vasculitides revised. Genetic studies showed that granulomatosis with polyangiitis (GPA) and microscopic polyangiitis (MPA) are different diseases with aberrant immune responses to different autoantigens. B-cell depletion with rituximab also acquired a primary role in the treatment of GPA and MPA, as well as in cryoglobulinaemic vasculitis.

[Biologic therapies in the systemic vasculitides]. / Terapia biológica en las vasculitis sistémicas.

Several biological therapies have been evaluated in systemic vasculitis. Anti TNF-α agents may have a role in the treatment of Takayasu's arteritis and probably in giant cell arteritis. In Kawasaki's disease, infliximab is an option in subjects with intravenous immunoglobulin-resistant disease. Anti TNF-α cannot be recommended to treat ANCA-associated vasculitis. Anti-T lymphocyte globulin and alemtuzumab could have a role in the treatment of ANCA associated vasculitis, although current information about these two biological treatments comes from conventional resistant treatment cases, so the high incidence of complications and relapses observed with these treatment may be intrinsic to the severity of the disease and not related to the biological agents.

Manifestaciones oculares de las vasculitis primarias sistémicas / Ocular manifestations of primary systemic vasculitis

Las vasculitis primarias (VP) pueden cursar con diversas manifestaciones oculares y estas pueden ser las únicas al inicio de la enfermedad. La afección ocular es común en las VP y potencialmente conduce a morbilidad significativa, incluyendo pérdida de la visión. El diagnóstico y tratamiento tempranos mejoran el pronóstico visual. El abordaje terapéutico constituye un reto y debe ser multidisciplinario. El tratamiento de las manifestaciones oculares corresponde al de la enfermedad de base. La primera línea de tratamiento son los corticoesteroides sistémicos, generalmente combinados con fármacos inmunomoduladores, que fungen también como ahorradores de glucocorticoides. Existen nuevos tratamientos, como los agentes biológicos, que parecen prometedores para las alteraciones oculares de las VP (AU)

A variety of ophthalmic manifestations can occur in patients who have systemic vasculitides and may be the presenting feature. Ocular involvement is frequently found and can result in significant morbidity, even in blindness. Early diagnosis and treatment may improve visual outcome. The management is challenging and requires a multidisciplinary approach. Treatment of ocular manifestations and systemic disease usually follows the same path. The mainstay of treatment is the use of systemic corticosteroids, usually combined with steroid-sparing immunosuppressive drugs. New, promising, emerging therapies rely on the development of biologic agents, which seem useful in the ocular manifestations of systemic vasculitides (AU)

Terapia biológica en las vasculitis sistémicas / Biologic therapies in the systemic vasculitides

Varias terapias biológicas se han probado en las vasculitis sistémicas. Los anti-TNF- pudieran tener un papel en el tratamiento de la arteritis de Takayasu y probablemente en la arteritis de células gigantes. En el caso de la enfermedad de Kawasaki, existe información de que el infliximab puede ser usado como una alternativa a la gammaglobulina por vía intravenosa en pacientes sin respuesta a una primera dosis de ésta. No se puede recomendar el uso de anti TNF- en las vasculitis asociadas a ANCA. La gammaglobulina antitimocito y el alemtuzumab pudieran tener algún papel en el tratamiento de las vasculitis asociadas a ANCA. La información existente acerca de la utilidad de estos dos fármacos proviene de casos refractarios al tratamiento convencional, por lo que la alta incidencia de complicaciones y recaídas observadas en los casos tratados con estos fármacos pudiera ser más bien intrínseca a la gravedad de la enfermedad y no debida a los agentes biológicos (AU)

Several biological therapies have been evaluated in systemic vasculitis. Anti TNF- agents may have a role in the treatment of Takayasu’s arteritis and probably in giant cell arteritis. In Kawasaki’s disease, infliximab is an option in subjects with intravenous immunoglobulin-resistant disease. Anti TNF- cannot be recommended to treat ANCA-associated vasculitis. Anti-T lymphocyte globulin and alemtuzumab could have a role in the treatment of ANCA associated vasculitis, although current information about these two biological treatments comes from conventional resistant treatment cases, so the high incidence of complications and relapses observed with these treatment may be intrinsic to the severity of the disease and not related to the biological agents (AU)

[Ocular manifestations of primary systemic vasculitis]. / Manifestaciones oculares de las vasculitis primarias sistémicas.

A variety of ophthalmic manifestations can occur in patients who have systemic vasculitides and may be the presenting feature. Ocular involvement is frequently found and can result in significant morbidity, even in blindness. Early diagnosis and treatment may improve visual outcome. The management is challenging and requires a multidisciplinary approach. Treatment of ocular manifestations and systemic disease usually follows the same path. The mainstay of treatment is the use of systemic corticosteroids, usually combined with steroid-sparing immunosuppressive drugs. New, promising, emerging therapies rely on the development of biologic agents, which seem useful in the ocular manifestations of systemic vasculitides.

Manejo de la inmunosupresión en enfermedades sistémicas que afectan al riñón / No disponible

Hemos revisado la literatura 2007 en relación con 3 grupos de enfermedades sistémicas que afectan al riñón: nefropatíalúpica (NL), vasculitis de pequeño vaso (VPV) y amiloidosis renal. En una revisión sistemática que incluye 268pacientes con NL reunidos en 4 estudios, el ácido micofenólico(AMF) durante la fase de inducción provoca más remisiones y consigue una mayor supervivencia renal que la ciclofosfamida (CF), en consecuencia se confirma como alternativa válida a la CF. Con un protocolo que incluye rituximaby AMF en la fase de inducción (14 días) el AMF solo, sin corticoides, en la fase de mantenimiento es eficaz y seguro. El rituximab también se ha utilizado con éxito en las formas de NL resistentes a la CF, disminuye la actividad clínica y la proliferación mesangial. Los intercambios plasmáticos consiguen mejores resultados que los bolus de corticoides en las VPV con insuficiencia renal grave. Las complicaciones son severas. Los antiTNFa no aportan beneficio en esta indicación. Los corticoidesa dosis bajas, administrados de forma prolongada, disminuyen la incidencia de recidivas. El AMF es una alternativa a la CF en caso de no poderse administrar el fármaco. Con el rituximab se consiguen buenos resultados en las formas resistentes a la CF. Según un ensayo controlado, el tratamiento de la amiloidosis AL con dexametasona y melfalan tiene unos resultado sequivalentes a las dosis altas de melfalan y rescate con trasplante con progenitores hematopoyéticos. En la amiloidosis AA, el eprosidate disminuye la velocidad de progresión de la insuficiencia renal (AU)

We reviewed the literature in 2007 on 3 groups of systemic diseases affecting the kidney: lupic nephropathy (LN), small vessel vasculitis (SVV) and renal amyloidosis. A systematic review of268 patients with LN pooled from 4 studies found that mycophenolicacid (MPA) in the induction phase caused more remissions and achieved greater renal survival than cyclophosphamide(CP), confirming it as a valid alternative to CP. Using a protocol including rituximab and MPA in the induction phase (14 days),MPA alone without corticoids is effective and safe in the maintenance phase. Rituximab has also been successfully used in CP-resistant forms of LN, where it reduces clinical activity and mesangial proliferation. Plasma exchanges achieve better results than bolus corticoids in SVS with severe renal failure. Complications are severe. Anti-TNF-a agents provide no benefit in this indication. Prolonged administration of low-dose corticoids reduces the incidence of relapses.MPA is an alternative to CP if this drug cannot be administered. Good results are achieved with rituximab in CP-resistant forms. According to a controlled trial, treatment of AL amyloidosis with dexamethasone and melphalan has equivalent results to highdosemelphalan and rescue with hematopoietic stem cell transplant .In AA amyloidosis, eprosidate slows the rate of progression of renal failure (AU)