Our case highlights an unfortunate occurrence where the patient had already developed a cerebrovascular event at diagnosis, seen in up to 6-8% of patients at presentation and up to 20% in the course of the illness.(7,8)
Also, important to note is the pattern of vascular involvement which can be identified both clinically but more accurately radiologically (9). Takayasu arteritis can affect several large arteries. The pattern of vascular involvement appears to vary with geographical region; patients in Japan and India have predominant aortic arch and abdominal aorta lesions respectively on imaging. (10). Whereas patients with Takayasu arteritis in Tunisia and Morocco in North Africa, tend to present with mostly aortic arch and/or subclavian artery involvement as described by several authors. (11–13) Conversely, in South Africa, two case series including the largest case series in Africa on Takayasu arteritis with two hundred and seventy two patients by Mwipatayi et al describe more patients with hypertension as the presenting feature and predominant abdominal aorta involvement compared to the aortic arch and its branches.(14,15)
The cases in literature describing patients from East Africa show a mixed pattern at initial presentation with diffuse aortic and retinal involvement respectively in two cases in Tanzania. (16,17) Elsewhere in Uganda, a case report describes autopsy findings of fibrosis in several branches of the arch of aorta. (18) In Kenya, two cases have been reported, one presenting as chronic headache with carotid artery stenosis and thoracic aorta involvement with another describing femoral involvement from biopsy of amputated limb in a set up with limited angiography capabilities at the time. (19,20) Our patient had predominantly subclavian and carotid artery involvement and no clear aortic localization which is similar to a case series description in Tunisia. (13) Inflammatory markers such as erythrocyte sedimentation rate and C reactive protein are frequently elevated as was the case in our patient but there are non-specific.
Generally, treatment is multidisciplinary with both medical and surgical interventions needed. Systemic glucocorticoids form the backbone of medical treatment of Takayasu arteritis patients. Additionally, disease modifying antirheumatic drugs (DMARDS) such as azathioprine and methotrexate are concomitantly used to allow for tapering of steroids and minimize glucocorticoid associated side effects. Lastly, biologic agents such as Tocilizumab and ant—Tumor Necrosis Factor inhibitors can be used. Surgery on the other hand is usually indicated in critical vessel stenosis or to repair arterial aneurysms.
Two major rheumatology organizations namely EULAR and ACR have published guidelines on management of Takayasu arteritis. However, the quality of evidence available to support these recommendations has remained low. (21,22)
The European League Against Rheumatism (EULAR) 2018 guidelines offer several recommendations to guide management of patients with Takayasu Arteritis. Acutely, EULAR supports initiation of glucocorticoids plus disease modifying antirheumatic drug as initial treatment with tapering off of steroids as tolerated. In refractory disease or major relapse, adjunctive therapy with Anti-IL6 agent tocilizumab and Anti- TNF agents are recommended. More specifically, for minor relapses, a trial of re-institution of higher glucocorticoid doses is advised before initiating Tocilizumab or anti-TNF agents. Additionally, for recurrent relapses adjunctive therapy with biologic agents is advised. Antiplatelet agents are also not routinely recommended and should only be considered on a case-by-case basis based on degree of stenosis and other risk factors. Further, the EULAR guidelines recommend for vascular surgical interventions to be done electively during stable remission since interventions during flares are associated with poor patency rates of repaired vessels. However, whenever critical stenosis causing ischemia or dissecting aneurysms is present surgical intervention should be pursued emergently. Finally, despite there being no research evidence to support follow up process, initial close follow up of 1-3 monthly visits in the first year followed by 3-6 monthly visits afterwards is advised due to high relapse rates. If relapse-free remission is achieved, then annual follow-ups can be scheduled thereafter. During follow ups, clinical assessment including ESR and CRP measurements are advised with imaging being ordered on a case-by-case basis. (21)
On the other hand, the American College of Rheumatology (ACR) guidelines are largely similar to the EULAR guidelines except for a few subtle differences. Some of the most notable ones are recommendation for use of ant-TNF inhibitors over Tocilizumab as initial addition in refractory disease and addition of aspirin therapy in patients with active disease and critical cranial or vertebrobasilar involvement. Additionally, despite recommending oral over intravenous glucocorticoids, the ACR guidelines give leeway for use of intravenous pulse steroids in cases of organ or life threatening disease like in our patient’s case. (22)
Despite advances in diagnostic and treatment of Takayasu arteritis, the rate of complications prevails with reported rates as high as 50%. Some of these complications include ischemic cerebrovascular incidences as experienced by our patient, as well as aortic regurgitation and associated heart failure, end stage renal disease in cases where renal vasculature has been involved. As expected, patients with more extensive disease at the time of diagnosis have higher complication rates. (23,24) Similarly, patients with a more progressive course, i.e., with few or no event free periods also experience higher rates of complications.(25)
Takayasu Arteritis has been described as a chronic condition with a relapsing pattern and this contributes significantly to the morbidity of the patients.(26) Recent studies have found that the male sex, presence of ongoing inflammation with elevated CRP levels and those carotidynia are more likely to experience relapses.(27,28)
Although limited data is available, it should be noted that Takayasu Arteritis is associated with reduced patient reported quality of life with patients with the disease also reported to have higher rates of clinical depression and anxiety compared to the general population particularly during active disease.(29) It is therefore important to ensure the evaluation of patients includes these aspects to ensure all concurrent morbidities are appropriately evaluated and managed.