Knowledge on rare diseases and orphan drugs

Takayasu arteritis (TAK) prevalence has been estimated to be 13 to 40 per million habitants. Cases have been reported worldwide but TAK seems to be more frequent in asians. A high female-to-male sex ratio is well documented.

TAK generally presents before 40 years, although rare pediatric cases are found. Active periods of inflammation may present with non-specific features such as headache, malaise, palpitations, night sweats, polyarthralgia or arthritis, erythema nodosum-like or ulcerating nodular cutaneous lesions, fever, fatigue, and weight loss. Vascular manifestations depend on the location and extent of vessel involvement and occurrence of complications (vascular stenoses, occlusions, and more rarely aneurysms). Clinical features include claudication, rest pain (limbs), hypertension (renal), headache, blurred or double vision, optic atrophy, transient ischemic attack, stroke and seizures. Cardiovascular manifestations include bruit, murmurs, blood pressure difference of extremities, carotidodynia, congestive heart failure, aortic regurgitation or insufficiency, pulmonary hypertension and aortic or arterial aneurysm. Pulmonary artery involvement may result in pulmonary hypertension and coronary or bronchial-pulmonary shunts.

The etiology of the inflammatory vasculitis in TAK is unknown. An underlying inflammatory mechanism and genetic factors are thought to play a role. Genetic studies have found HLA B-52 to be related to TAK. Recent GWAS studies revealed association of single nucleotide polymorphisms in IL12B and FCGR2A/3A genes to TAK.

The diagnosis is difficult to establish and is frequently delayed (years or even decades). It is based on the clinical features and physical examination. Vascular manifestations could guide morphologic investigations. However, the main change is related to the use of noninvasive imaging techniques (ultrasound, magnetic resonance imaging, CT angiography and positon emission tomography). Such exams could allow early diagnosis by demonstrating arterial wall thickening or inflammation in the pre-stenotic phase.

The differential diagnosis of TAK is very broad and may include other inflammatory diseases (atherosclerosis, giant cell arteritis, IgG4 related aortitis), infectious aortitis and fibromuscular dysplasia.

Treatment and management depend on disease severity and the specific complications. Corticosteroid therapy is the main treatment modality for TAK although it is associated with known long-term adverse effects. Remission following immunosuppressive therapy is achieved in about 60% of cases. Other immunosuppressive agents may be needed to achieve relapse (methotrexate, azathioprine, mycophenolate mofetil, leflunomide, tacrolimus, or cyclophosphamide). Biologic drugs, first of all anti-TNF alpha and probably anti-IL6 could be used in patients resistant or intolerant to conventional treatment. Vascular interventions are used to re-establish vascular patency in stenosed and occluded arteries that cause organ ischemia or hypertension, and for aneurysmal disease.

TAK is associated with significant morbidity, especially when diagnosed late, and may be life-threatening in severe cases. Adverse effects from long-term corticosteroid therapy may reduce quality of life.

Last update: April 2019 - Expert reviewer(s): Pr Marc LAMBERT