|CASE BASED REVIEW
|Ahead of print publication
Aortitis in systemic lupus erythematosus: A report of two cases and review of literature
Kasturi Hazarika1, Latika Gupta2, Juhi Dixit1, Rasmi Ranjan Sahoo1, Durga Prasanna Misra2, Anupam Wakhlu1
1 Department of Clinical Immunology and Rheumatology, King George's Medical University, Lucknow, Uttar Pradesh, India
2 Department of Clinical Immunology and Rheumatology, Sanjay Gandhi Postgraduate Institute of Medical Sciences, Lucknow, Uttar Pradesh, India
|Date of Submission||24-Apr-2020|
|Date of Acceptance||29-Jul-2020|
Department of Clinical Immunology and Rheumatology, King George's Medical University, Lucknow - 226 003, Uttar Pradesh
Source of Support: None, Conflict of Interest: None
Aortitis is not typically described in systemic lupus erythematosus (SLE).We describe two cases where aortitis was seen to occur concurrently with SLE or in its temporality. The possibility of an uncommon Takayasu-SLE overlap cannot be ruled out.
Keywords: Large vessel, overlap, systemic lupus erythematosus, Takayasu arteritis, vasculitis
|How to cite this URL:|
Hazarika K, Gupta L, Dixit J, Sahoo RR, Misra DP, Wakhlu A. Aortitis in systemic lupus erythematosus: A report of two cases and review of literature. Indian J Rheumatol [Epub ahead of print] [cited 2021 Mar 1]. Available from: https://www.indianjrheumatol.com/preprintarticle.asp?id=298852
| Introduction|| |
Systemic lupus erythematosus (SLE) is an autoimmune disorder, which by its definition can involve multiple organ systems including blood vessels, of which small vessels and coronary arteries are more commonly described. Few cases reported aortic dissection, aneurysm, and aortitis occurring in SLE.,,, Besides chronic inflammation, prolonged steroid use may be a possible contributing factor for aortic dissection and aneurysm, especially in patients with long standing disease. Other than that there were instances where it was contemplated that SLE and Takayasu arteritis (TA) occurred in the same individual., Both diseases occur in the same age group and with a similar gender predisposition. SLE was ascribed as one of the causative factors in the initial few descriptions of TA.,, The autoimmune nature of TA has also been considered from its association with other autoimmune disorders such as sarcoidosis and Crohn's disease.
We describe two clinical scenarios where we encountered aortoarteritis in patients with SLE. The first patient was a diagnosed case of TA, who developed features suggestive of SLE 13 years later. The second case was a young man, who manifested with symptoms suggestive of aortitis but was later found to have nephritis and other defining features of SLE.
| Case Reports|| |
A 42-year-old female was diagnosed with TA in 1996, based on her systemic features, renovascular hypertension, raised inflammatory markers and confirmed by computerized tomography (CT) angiography. She had a solitary right kidney with renal artery stenosis for which renal angioplasty with stenting had been performed (April 1996). The left kidney was not detected or atrophied probably due to severe left renal artery stenosis. She was on treatment with antihypertensives, low-dose glucocorticoids, and methotrexate with default in between.
The patient presented to the rheumatology clinic on July 2019 for malar rash. The photosensitive rash was recurring for the past 7 years. She also reported Raynaud's phenomenon on the tip of nose (only in winters) and polyarthritis, mainly involving the proximal interphalangeal (PIP) joints for the past 6 years, with worsening in the winters. She reported undergoing a repeat CT angiography in December 2017, 21 years after the initial diagnosis of TA, which was suggestive of circumferential mural thickening and significant narrowing in the renal and infrarenal part of aorta with narrowing of the left renal artery. The large vessel vasculitis (LVV) seemed to be stable with no new vascular bed involvement. She had also undergone a hip arthroplasty for avascular necrosis of the left femoral head in September 2018. She denied symptoms suggestive of sicca, skin thickening, or esophageal dysmotility.
On examination, she had a violaceous rash over the malar area and bridge of the nose and all PIPs were swollen and tender [Figure 1]. Pulses were symmetrical and equal over all limbs with no appreciable bruit. Blood pressure in the right upper limb was 130/80 mm Hg, left upper limb was 120/80 mm Hg, right lower limb was 130/90 mm Hg, and left lower limb was 140/90 mm Hg. Rest of the systemic examination was unremarkable. She was investigated for a suspected connective tissue disease. Her hemogram, liver function, and kidney function tests were within normal limits [Table 1]. Urine examination was normal. Anti-nuclear antibody (ANA) was positive (4+) with a fine-speckled pattern and extractable nuclear antigen (ENA) panel revealed anti-Ro-52 antibodies. Anti-double stranded DNA antibody was negative and complements were normal. Antiphospholipid antibodies anti-beta 2 GP1 immunoglobulin G (IgG) (anti beta-2-glycoprotein 1), IgM, and IgG anticardiolipin were negative and direct Coomb's test (DCT) was 1+ (positive).
|Figure 1: Typical malar rash sparing the nasolabial folds (a) and swollen proximal interphalangeal joints (b) in case 1|
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With a positive ANA, the patient fulfilled the entry criteria for SLE as per the new American College of Rheumatology-European League against Rheumatism (ACR-EULAR) classification criteria for SLE. With the facial rash as subacute cutaneous lupus and arthritis, she had a score of 10, thus satisfying the classification criteria for SLE. Although DCT was 1+, there was no evidence of hemolysis. The patient was asymptomatic and stable from the point of view of LVV for the past 13 years, which was diagnosed as TA. In hindsight, however, LVV could be a rare manifestation of lupus per se.
A 22-year-old male presented with Raynaud's phenomenon, intermittent left upper abdominal pain for the past 2 years and claudication of bilateral lower limbs for the past 3 years. The pain in abdomen was intermittent, periumbilical, and aggravated after food intake. The Raynaud's phenomenon was complete, involving all fingers of hands, though it was not associated with digital pitting, ulcers, or gangrenous changes. The claudication in both lower limbs was progressively worsening over the past 5 months. The past history was significant for a single episode of syncope lasting for a few minutes, which occurred 2 years back and without involuntary movements, bowel or bladder incontinence, headache, focal neurological deficit, chest pain, or visual complaints. The past history revealed a single episode of jaundice 15 months back with indirect hyperbilirubinemia, without features of obstruction or hepatic decompensation and he received four units of packed red blood cells transfusion during this period for severe normocytic normochromic anemia. The patient was a known hypertensive for the past 1 year on irregular anti-hypertensive medications. He lacked any other features of a connective tissue disorder.
In September 2019, he presented to emergency with complaints of pain in the left upper abdomen, anasarca, and generalized weakness of 20 days' duration. On examination, he had pallor, a single left axillary lymph node (1 cm × 1 cm). Hypertension was documented in both upper limbs with a systolic BP difference of 10 mm Hg; absent femoral, popliteal pulses, and a left renal bruit.
Investigations revealed normocytic normochromic anemia, leukopenia with raised inflammatory markers [Table 1]. DCT was negative. He also had hypoalbuminemia and urine examination revealed proteinuria of 1000 mg/dl without any active sediments, with a 24-h urinary protein of 7.3 g. His renal and liver function tests were normal. ANA was 4 + fine speckled with ENA revealing anti-Sm, anti-Ro and anti-La [Table 2]. Complements and anti-dsDNA levels were within normal limit. Ultrasonography (USG) was suggestive of mild hepatomegaly with coarsened liver echotexture, dilated portal vein of 13 mm, and moderate splenomegaly. Two-dimensional echocardiography showed coarctation of the abdominal aorta with the narrowest portion at the level of superior mesenteric artery. CT aortogram showed diffuse circumferential mural thickening with multiple foci of atheromatous mural calcification involving descending thoracic aorta and abdominal aorta. Few areas of focal narrowing with poststenotic dilatation in suprarenal abdominal aorta at the level of D12 vertebral level, just above the origin of coeliac trunk and also narrowing in infrarenal abdominal aorta at L2 and L3 vertebral levels for a segment length of approximately 5 cm, were also described. There was focal stenosis at the origin of coeliac trunk with post-stenotic dilatation while rest of the aorta, bilateral subclavian arteries, bilateral carotids, and vertebral arteries were normal [Figure 2]. In addition, the CT revealed an enhancing, circumferential mural thickening involving the terminal ileum, ileocecal junction, caecum, proximal part of ascending colon with necrotic abdominal and mesenteric lymph nodes. Colonoscopy done revealed no abnormality and subsequent USG of the abdomen showed regressed lymph nodes and no bowel thickening. Chest radiograph was normal and Mantoux test was negative.
|Table 2: Comparison of the demographic and clinical features of the two cases|
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|Figure 2: Computerized tomography angiography showing diffuse mural thickening involving descending aorta with stenosis (orange arrow) and poststenotic dilatation (green arrow) at multiple levels of abdominal aorta|
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Renal biopsy done showed endocapillary proliferation with subepithelial humps and immune complex deposition suggestive of Class V lupus nephritis [Figure 3]. As per the ACR-EULAR 2019 classification criteria, he fulfilled the entry criteria and with features of leukopenia, possible autoimmune hemolysis in the past and class V nephritis, he classified as SLE with a total score of 15. With the history of claudication and pain in extremities, blood pressure inequality, absent lower limb pulses, age of onset <40 years, angiographic abnormality, he satisfied the ACR classification criteria for TA (1990) as well. Thus, a diagnosis of SLE with nephritis and Aortitis, possibly Takayasu type 3 was made. He was started on prednisolone 1 mg/kg along with monthly cyclophosphamide pulses and antihypertensives. At follow-up, he became symptomatically better along with improvement in his anemia and leukopenia. His proteinuria is currently under follow-up.
|Figure 3: Histopathological examination of renal biopsy specimen (×20) showing (a) capillary wall thickening and endocapillary proliferation (orange arrow) and subepithelial spikes (green arrow) on periodic acid-Schiff stained sections and (b-d) showing immunoglobulin G, C1q and immunoglobulin A deposition respectively on immunofluorescence|
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| Review of Literature|| |
We conducted a literature search in PUBMED using the key words “lupus” AND “aortitis” as per the published guidelines for narrative reviews. Eighteen case reports and case series of patients with lupus associated with aortitis published in English language year 2000 onward were selected. After screening the titles and abstracts, we found 5 relevant case reports. Cross referencing was also done using Google scholar to include additional relevant literature.
The salient features of these patients compared with our cases are shown in [Table 3].
| Discussion|| |
Aortitis in SLE, albeit rare, has been described in a number of case reports world over.,,,,,,,,
Of the 7 cases [as described in [Table 3], 5 had features of aortitis prior to the appearance of SLE and in 2 of them, SLE was diagnosed at the same time as aortitis. The manifestations of SLE varied from mucocutaneous, musculoskeletal to leukopenia, and severe organ-threatening nephritis (three patients). Co-existent antiphospholipid antibody syndrome was present in a single patient. All patients were on steroids and hydroxychloroquine was given in five cases. Cyclophosphamide was administered in patients with renal involvement. Aortitis was symptomatic with features ranging from limb claudication, unequal blood pressure, and syncope with gangrene of toes occurring in a single case. Aortographic findings were recorded in all the patients. Granulomatous panarteritis was demonstrated on biopsy of the aorta in one patient. In another patient, there were attacks of recurrent aortoarteritis manifesting as constitutional symptoms with raised inflammatory markers which on 18-fluorodeoxyglucose positron emission tomography showed the involvement of aorta and its major branches on multiple occasions.
Worth mentioning here is a case based review of 19 patients done by Saxe and Altman in 1992 on co-existence of SLE and TA. Females were predominant with majority of them having aortitis diagnosed before SLE. One patient had co-existent anti-phospholipid syndrome. The findings of the 19 cases are summarized in [Table 4].
Of our two cases, features of SLE appeared in a known patient of Takayasu's and in one, nephritis and aortitis occurred concurrently. Whether it is SLE and TA occurring concomitantly in the same patient or aortitis occurring as a feature of SLE; can only be differentiated by tissue diagnosis, accessible only at autopsy or during a surgical procedure. Both diseases occur in young females, with differing human leukocyte antigen associations, autoantibody positivity, type of vessel involvement, and variable systemic features. SLE classically affects small arteries whereas TA mainly involves aorta and its major branches. Hematological involvement, serositis, mucocutaneous involvement, and arthritis typically occur in SLE.
Vasculopathy, accelerated atherosclerosis, and vasculitis are the varied vascular manifestations of SLE. Aortic dissection, a severe form of aortitis has also been described in a few instances in SLE. Accelerated atherosclerosis consequent to steroid use and prolonged inflammation was postulated to be one of the contributing causes. Vasculitis due to immune-complex deposition resulting in fibrinoid degeneration, intimal thickening, thrombosis, and sclerosis have been identified in SLE, but occurs primarily in small-sized arteries and arterioles. Medium-sized artery involvement presents more with thrombotic events and lesions of aorta are very rare. Therefore, aortitis occurring prior to the other features or as a presenting feature would be a rare exception in SLE. Whether SLE and TA co-exist can possibly be proved only by biopsy, which would reveal mononuclear infiltration, granulomatous change and fibrosis in the media with intimal thickening and obliterative lesions in case of TA. From a therapeutic standpoint, in the first case, there would not be much of a change in terms of treatment, as her aortitis seemed inactive at present. Her SLE manifestations were primarily mucocutaneous and arthritis, which could be adequately controlled with methotrexate and hydroxychloroquine. In the second case, the patient was symptomatic for the aortitis with raised inflammatory markers and the SLE nephritis demanded urgent treatment. Aortitis could have been controlled with steroids and methotrexate/azathioprine. The standard management of Class V lupus nephritis is usually high-dose steroids and mycophenolate mofetil along with angiotensin converting enzyme inhibitor. However, there is enough evidence to show that intravenous cyclophosphamide is as effective as mycophenolate mofetil for the induction therapy of Class V lupus nephritis, with no significant difference in partial remission or resolution of proteinuria. Cyclophosphamide has been used with success in the treatment of severe, refractory, relapsing TA and also when specific organs/structures such as the retina, pulmonary artery, aortic valve, or myocardium have been involved., Financially, cyclophosphamide made economic sense to the patient. We plan to follow-up with azathioprine after completing doses of cyclophosphamide, which should take care of both aortitis and nephritis.
| Conclusion|| |
Aortitis may be seen as a rare disease manifestation in SLE. In addition, SLE and TA occur together in conjunction. A definitive distinction between the two situations is often impossible clinically and may only be possible through a tissue diagnosis. Selection of an affordable immunosuppressive agent that covers aortic involvement and manifestations of SLE, for example, nephritis, constitutes a pragmatic, and valid therapeutic intervention.
Declaration of patient consent
The authors certify that they have obtained all appropriate patient consent forms. In the form the patient(s) has/have given his/her/their consent for his/her/their images and other clinical information to be reported in the journal. The patients understand that their names and initials will not be published and due efforts will be made to conceal their identity, but anonymity cannot be guaranteed.
We are thankful to Dr. Kiranpreet Malhotra for providing the histopathology images of renal biopsy sample of case 2.
Financial support and sponsorship
Conflicts of interest
There are no conflicts of interest.
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[Figure 1], [Figure 2], [Figure 3]
[Table 1], [Table 2], [Table 3], [Table 4]