Case Report

Takayasu Arteritis and Pregnancy in a Black Patients in Zambia: A Case Based Review

John Kasanga¹, Achieve Denhere Chinyathi^2,3* & Ian Chikanza C⁴

¹Registrar, Department of Internal Medicine, Livingstone University Teaching Hospital, Akapelwa St, Livingstone, Republic of Zambia

²Department of Internal Medicine, Former [Senior Clinical Lecturer, Cavendish University Zambia-School of Medicine/Honorary Consultant Physician], Livingstone University Teaching Hospital, Akapelwa St, Livingstone, Republic of Zambia

³Department of Internal Medicine, Consultant Physician, Division of Geriatrics, Tipperary University Hospital, Western Road, Clonmel, Tipperary, E91 VY40, Republic of Ireland

⁴International Arthritis & Hypermobility Centre, @Harley Street Clinic, London W1G 7AF, UK; & Faculty of Medicine, Catholic University, Harare; and Department of Paediatrics & child Health, Medical School, Univ of Zimbabwe, Harare, Zimbabwe

Submission: August 29, 2024; Published: September 18, 2024

*Corresponding author: Achieve Denhere Chinyathi, Department of Internal Medicine, Former [Senior Clinical Lecturer, Cavendish University Zambia-School of Medicine/Honorary Consultant Physician], Livingstone University Teaching Hospital, Akapelwa St, Livingstone, Republic of Zambia and Internal Medicine, Consultant Physician, Division of Geriatrics, Tipperary University Hospital, Western Road, Clonmel, Tipperary, E91 VY40, Republic of Ireland, Email: denhere.ca@gmail.com

How to cite this article: John Kasanga, Achieve Denhere Chinyathi* & Ian Chikanza C. Takayasu Arteritis and Pregnancy in a Black Patients in Zambia: A Case Based Review. Ortho & Rheum Open Access J. 2024; 23(5): 556124. DOI: 10.19080/OROAJ.2024.23.556124

Abstract

Takayasu arteritis is a rare large vessel vasculitis. Clinical assessment of the peripheral vascular system is equally essential for diagnosis. Angiography is the imaging modality of choice; a Doppler ultrasound study is an alternative with limited resources. Steroids and anti-hypertensives are the mainstays of treatment. Treatment is individualized, especially in pregnancy, as some immunosuppressants and anti-hypertensives can cause fetal harm. Angioplasty or vascular surgery is reserved for critical organ vascular stenosis.

Case: A 29-year-old black African woman presented with severe hypertension in the left arm and unrecordable right arm blood pressure. She had right upper limb claudication. Her peripheral vascular examination was significant for absent pulses at and distal to the right brachial artery. A diagnosis of Takayasu arteritis with possible renovascular involvement was postulated. A Doppler study demonstrated right diminished blood flow at and distal to the right axillary artery, later confirmed by Computed Tomography angiography. Left renal artery stenosis was diagnosed on CT angiography. She was treated with immunosuppressants and antihypertensives with good effect. A month later, she conceived, and medications were changed to pregnancy-friendly alternatives. The pregnancy reached full term, and delivery was uneventful.

Conclusion: Takayasu arteritis is rare; angiography is the gold standard investigation tool. Doppler studies are an alternative imaging modality and should be used instead of inappropriate radiography. Treatment can be individualized and adjusted in pregnancy with good outcomes. Surgery or angioplasty does play a role in critical organ vascular stenosis.

Keywords: Takayasu arteritis; Young; Black African; Woman; Angiography; Pregnancy; Immunosuppression; Case report

Abbreviations: ACR: American College of Rheumatology; EULAR: European League Against Rheumatism; FMD: Fibromuscular Dysplasia; TAK :Takayasu arteritis; CYC: Cyclophosphamide

Introduction

Takayasu arteritis (TAK) is a rare vasculitis of unknown etiology. It is worldwide but is more common in young Asian women [1]. The data on the epidemiology of TAK is limited, probably because of its rarity [1] Our case report, which adds to the global data on the epidemiology of TAK, highlights the diagnostic challenges, therapeutic options, and the influence of pregnancy on TAK management. The experiences encountered in our resource-limited setting contribute to the global knowledge of TAK management in pregnancy in Africa and beyond. A few cases of TAK have been documented in a handful of African countries. Tunisia has the most publications on TAK, with 29 patients confirmed with TAK in one ten-year retrospective study between 1996 and 2006 in Southern Tunisia [2] and 27 cases in another retrospective study in Central Tunisia [3]. Morocco had 47 confirmed cases of TAK in a retrospective study by El Asri et al. between 1988 and 1999 [4]. Most cases of TAK in Sub-Saharan Africa were documented in South Africa [5].

In Africa’s most extensive retrospective study on TAK, spanning over 50 years (1952-2002), Mwipatayi et al. reviewed 272 cases of TAK in South Africa, and only 8% were Caucasians [6]. Occasional case reports of TAK have been published in other countries but are not limited to Gabon, Ivory Coast, Niger, Senegal, Cameroon [West Africa], Kenya [East Africa] and South Africa [Southern Africa]. In Zambia (South-Central Africa), no case of TAK has been documented to date; this could be due to a lack of recognition or awareness of the disease or just that it is rare in a predominantly black population.

These African studies and this case report highlight the geographical variability in TAK distribution in Africa, with most cases recorded in Northern Africa and the Republic of South Africa [5]. This case report also underscores the unique clinical course of TAK in pregnancy and the associated therapeutic challenges. The need to review therapeutic agents to minimize fetal harm and maximize maternal health presents a significant challenge, particularly when safer treatment options are unavailable or expensive. Treatment aims to minimize the morbidity and mortality arising from end-organ damage of critical organs due to vascular stenosis. The brain, heart, and kidneys are the primary culprit organs affected [7].

Case

A 29-year-old, black African, Zambian woman presented to our emergency department with a hypertensive urgency. She had a severe headache, right upper limb intermittent claudication, and no neurological deficits. She had severe hypertension (184/129mmHg )in the left arm and unrecordable right arm blood pressure. She was started on enalapril and admitted for further work-up and management (Table 1).

This presentation was her second visit to an emergency department with a similar presentation. Two years before this presentation, she had presented at a different facility and had a radiographic (roentgenogram) evaluation of her right arm as part of her work-up for pulselessness. She was discharged then and was not referred to a tertiary institution for specialist assessment.

In this current presentation, her peripheral vascular examination was significant for absent pulses at and distal to the right brachial artery. Despite the absence of pulses distal to the right brachial artery, there was no ipsilateral limb atrophy or features of previous vascular surgery or thromboangitis obliterans. There was no carotidynia or temporal artery tenderness. The rest of the physical exam was normal, and there were no features of target organ disease on ECG(electrocardiogram), but an elevated Creatinine of 159.6μmol/l at presentation. Her profile: 29 years of age(<40 years), female gender, pulseless right upper limb, left upper arm hypertension, lack of previous vascular surgery and no alternative probable cause of secondary hypertension, a clinical diagnosis of Takayasu’s arteritis with possible renovascular involvement was postulated based on the 2022 EULAR/ACR classification criteria for TAK.

Findings

A Doppler study demonstrated that the axillary, brachial, radial, and ulnar arteries had reduced blood flow. A CT angiogram (Figure 1 & Table 3) confirmed multivessel stenosis, namely the right (axillary, brachial, radial, ulnar) arteries and left renal artery stenosis. The right hand had significant collateral blood flow. Post admission, enalapril was discontinued because she had an elevated creatinine at presentation, renal artery stenosis, and she was of childbearing age(enalapril is not advised in pregnancy) and substituted with amlodipine. Other laboratory findings were elevated inflammatory markers, CRP, and ESR of 20.64mg/L and 70mm/hr, respectively (Table 2). Her clinical presentation and vascular imaging results scored 9, thus fulfilling the 2022 ACR/ EULAR classification criteria for TAK (Figure 2). A score of ≥ 5 points is needed for classification of Takayasu arteritis [8].

Treatment

For TAK treatment, she was started on a high dose of prednisolone(60 mg daily) for one month with a subsequent taper. The inflammatory markers CRP and ESR normalized within three months of treatment. To avert potential steroid side effects due to prolonged use, she was switched to azathioprine ahead of methotrexate. Azathioprine was preferred to methotrexate because she conceived during the first month of treatment. She was referred to the antenatal department for early booking and obstetrics input. Physicians continued to manage her TAK and hypertension. Amlodipine was replaced with nifedipine to comply with best clinical practice and local guidelines on the treatment of hypertension in pregnancy in Zambia, as the first choice, labetalol, is not readily available. The pregnancy was uneventful, as she remained normotensive throughout the pregnancy. She delivered a healthy baby girl at full term at UTH(University Teaching Hospital) in Lusaka without any complications. She did not require renal angioplasty or renal artery by-pass grafting.

Discussion

Takayasu arteritis (TAK) is a rare granulomatous disease of unknown etiology. It is worldwide in distribution but more common in young women in Asia [1]. There are few reported cases of TAK in Africa [5]. The implications for diagnosis are that immunosuppressive and antihypertensive medications are readily available.

Takayasu arteritis is an important differential diagnosis in any young person who presents with hypertension and pulseless limbs. The diagnosis is often missed or delayed. Fibromuscular dysplasia (FMD) causes renovascular hypertension. Still, in FMD, there are normal limb pulses, and on angiogram, there is a characteristic string of beads appearance resulting from multifocal stenosis and dilatations of the renal artery [9]. FMD is non-inflammatory compared to TAK and does not fit the TAK ACR/ EULAR criteria [10]. Peripheral vascular examination is essential, looking in particular for the absence of superficial temporal artery tenderness (may be seen in Giant Cell Arteritis), presence of (carotidynia, carotid, and renal bruits), reduced or absent pulses of large arteries as well as blood pressure discrepancies of at least 20mm Hg between the arms and or legs may be seen [8]. This patient had characteristic absent pulses at the right brachial artery and distally. She did not have superficial temporal artery tenderness, carotidynia, or carotid and renal bruit.

TAK has a triphasic presentation and eventually “burns out.” Phase I: Systemic/pre-pulseless: There are constitutional features(e.g., fever, night sweats); Phase II: There is vascular inflammation, including tenderness over arteries(e.g., carotidynia) and Phase III: vascular damage or fibrosis stage, where features related to renal stenosis occur. Not all patients have a triphasic phase [11]. Our patient presented at Phase III with hypertension, elevated Creatinine, and angiographic evidence of left renal artery stenosis. ESR and CRP are not always reliable in reflecting disease activity. These inflammatory markers may be normal and misleading in 20% of the patients with active disease [12]. Biochemically, she exhibited an inflammatory phase, as evidenced by high CRP and ESR levels, but clinically and radiologically, she was in the vascular fibrosis stage (Phase III), as evidenced by hypertension and angiographic left renal artery stenosis.

Various criteria are available to aid the diagnosis of TAK. The ACR (1990) and now the revised ACR/EULAR (2022) criteria are widely used in the disease classification of TAK [8]. The hallmark of Takayasu arteritis is inflammation of large vessels [13]. The inflammatory nature (large vessel vasculitis) makes TAK amenable to steroids, DMARDs (methotrexate, mycophenolate mofetil, and azathioprine ), biologics, and cyclophosphamide.

The current treatment modalities include glucocorticoids, other immunosuppressive therapy, and non-medical intervention: surgery or angioplasty [7,14]. All these treatment modalities and expertise are available in Zambia. Recognition of the diagnosis is the first step. The choice of immunosuppressive therapy is individualized on a case-by-case basis. In this case report, the patient’s pregnancy state influenced the treatment choices (Figure 3).

Glucocorticoids are the mainstay of medical treatment. Improvement or resolution of systemic symptoms has been reported in 25-100% of glucocorticoid-treated patients. An initial dose of prednisone 1 mg/Kg/day (maximum 60 mg/day) is recommended in all newly diagnosed patients. Takayasu’s arteritis is a chronic inflammatory condition; hence, there is an increased risk of developing premature atherosclerosis [7]. Cardiovascular risk assessment should be made with careful attention to the treatment of hypertension. Antiplatelet therapy is no longer routinely recommended for primary prevention unless there is a compelling indication, like cerebrovascular or cardiovascular disease [7]. In our case, it was considered for the prevention of preeclampsia. Consideration of surgical intervention into renal artery stenosis should be made in hypertension refractory to medical treatment, as well as selected cases with stenosed segments of arteries, aortic valve insufficiency, and aneurysms [7]. Angioplasty /and stenting are used to treat coronary atherosclerosis and renal artery stenosis [14-17]. Restenosis is less likely following bypass grafting than angioplasty [17].

Prognosis

Early diagnosis and initiation of immunosuppressive treatment improves the outcome in patients with TAK. TAK presentation varies greatly, and mortality is mainly due to congestive cardiac failure, cerebrovascular events, myocardial infarction, aneurysm rupture, and renal disease [18]. Predictors of poor outcomes are progressive disease, TAK retinopathy, secondary hypertension, aortic valve insufficiency, or aneurysms [19]. Our patient had none of the above features.

TAK and Pregnancy

Partalidou et al. showed that there were significantly higher rates of maternal complications, namely hypertension, miscarriage, and pre-eclampsia, occurring in 37%, 16%, and 14% of pregnancies in TAK women, respectively, compared to the general population [20]. The French Takayasu Network has also reported similar unfavorable outcomes. Maternal complications of TAK are mainly new-onset or worsening hypertension [21]. The risk factors for unfavorable outcomes of pregnancy in TAK are high disease activity during pregnancy, followed by renal artery involvement, and a history of hypertension [22]. Despite renal involvement, our patient had a favorable outcome(uneventful pregnancy). She had low disease activity (ESR/CRP -were normal) post steroid therapy. TAK tends to be stable, and disease activity decreases once conception has been achieved during a period of low disease activity [23]. Other factors that may have contributed to a good outcome are well-controlled hypertension, the use of aspirin, early provision of antenatal care services, and obstetric follow-up.

Conclusion

Our case report seeks to raise awareness of TAK in Zambia. To our knowledge, this is the first documented case of TAK. Although TAK is rare, the diagnostic criteria are simple, and treatment is widely available too. Clinicians should consider TAK in patients who present similarly, although it is rare in blacks. Recognition and early referral to specialist centers equipped with appropriate imaging are essential. Radiographic imaging is unable to detect vascular involvement. Doppler flow studies are helpful where advanced imaging techniques are unavailable. Treatment will limit vascular damage. Immunosuppressive and anti-hypertensive therapy should be individualized in pregnancy; the goals are safe immunosuppression, low disease activity, and pre-eclampsia prevention with aspirin to ensure good maternal and fetal outcomes.

Acknowledgment

i. The doctors and other healthcare staff were involved in the patient’s clinical management.

ii. Special thanks to the patient, who gave informed consent for this write-up.

iii. Special thanks to Dr Oscar Ngongo, who admitted the patient for further investigations and management.

iv. We want to thank Dr. John Kasanga, a Department of Internal Medicine registrar, who helped manage the patient after diagnosis and during her pregnancy.

v. Our radiology department, Dr. Sandeep Ballal, and the team for the Doppler studies, CT angiography, and report deserve special thanks.

vi. Special thanks to the obstetric and midwifery teams at Livingstone University Teaching Hospital and UTH for successfully managing the pregnancy and delivery and monitoring potential complications.

All authors contributed, read, reviewed, and approved the final manuscript.

Funding

No funding sources. The authors declare that funding was not utilized to prepare this manuscript.

Availability of Data and Materials: All the data presented in the manuscript have been de-identified, and further inquiries can be directed to the corresponding author.

Declarations Ethics Approval and Consent to Participate: Not applicable.

Consent for Publication: Written informed consent was obtained from the patient before submission of this manuscript.

Competing Interests

The authors declare that they have no competing interests. Sum the scores for ten items, if present. A score of ≥ 5 points is needed to classify Takayasu arteritis (Table 4).

i. Evidence of vasculitis in the aorta or branch arteries must be confirmed by vascular imaging (e.g., computed tomographic / catheter-based/magnetic resonance angiography, ultrasound, positron emission tomography).

ii. Bruit detected by auscultation of a large artery, including the aorta, carotid, subclavian, axillary, brachial, renal, or iliofemoral arteries.

iii. Reduction or absence of pulse by physical examination of the axillary, brachial, or radial arteries.

iv. Reduction or absence of pulse of the carotid artery or tenderness of the carotid artery.

v. Number of arteries with luminal damage (e.g., stenosis, occlusion, or aneurysmal) detected by angiography or ultrasonography from the following nine territories: thoracic aorta, abdominal aorta, mesenteric, left or right carotid, left or right subclavian, left or right renal arteries.

vi. Bilateral luminal damage (e.g., stenosis, occlusion, or aneurysmal) detected by angiography or ultrasonography) from the following paired vascular territories: carotid, subclavian, or renal arteries.

Luminal damage (e.g., stenosis, occlusion, or aneurysmal) detected by angiography or ultrasonography) involving the abdominal aorta and either renal or mesenteric arteries [8].

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