Clinically isolated descending thoracic aortitis in a healthy older woman: a diagnostic challenge
- Max Amos Hoffman and
- Adel Ekladious
- Faculty of Health and Medical Sciences, The University of Western Australia, Perth, Western Australia, Australia
- Correspondence to A/Professor Adel Ekladious; ekladiou@hotmail.com
Abstract
A woman travelling to Australia in her early 70s presents to a regional emergency department with chest pain and associated shortness of breath. Her medical history was that of seasonal affective disorder treated with citalopram, and an allergy to ibuprofen. Subsequent CT imaging revealed aortic wall thickening and associated periaortic fluid, and a moderate pleural effusion. This was successfully treated with oral prednisolone, responding within 1 day. Further blood tests revealed a high CD4/CD8 T-cell ratio, which can be seen in autoimmune disease, sarcoidosis and haematological malignancies. Without evidence for other autoimmune processes, the patient was given a provisional diagnosis of descending thoracic aortitis secondary to sarcoidosis, prescribed a weaning regimen of prednisolone, and asked to seek further investigation and management in her home country. This is a case with several learning points; rare disease can cause common presentations/reports, and sometimes empirical therapy is the only therapy.
Background
This case highlights a few key points relating to clinical medicine. It demonstrates that common presentations with common causes could be manifestations of a rare disease, which may require extensive investigation before reaching a definitive or even probable diagnosis.
This case also demonstrates the need for clear communication and heavy safety netting, as this patient was from overseas and would likely require ongoing/further investigation and management. The challenges faced here are that the patient may be lost to follow-up, or their treating doctor in their country of origin may not be provided with sufficient clinical information to manage/refer the patient appropriately.
Finally, this case demonstrates the need to treat empirically on occasion. With no definitive diagnosis but ongoing concerning and bothersome symptoms, symptom management at the very least should be a goal. The best way to do this is to attempt to treat the underlying disease, which is difficult to do without knowledge of what the underlying disease is. Hence, an educated guess is made with the available information on how the disease may respond to certain therapies, and response to such therapies can add diagnostic clarity.
Case presentation
A woman travelling in Australia from the UK in her early 70s presents to a regional emergency department with central/left-sided chest pain radiating to her back between her shoulder blades, and associated mild shortness of breath worsened by exercise. Further history revealed that 1 week earlier, the patient had experienced some low-back pain which progressed to intermittent interscapular thoracic back pain lasting for 2 days prior to presentation before developing into central/left-sided band-like chest pain. The patient did not have shortness of breath until asked specifically, at which point she described mild shortness of breath on exertion, which was unusual for her. She described the chest pain as a combination of dull and sharp, which did not worsen significantly with deep inhalation/exhalation. She denied diaphoresis, nausea/vomiting, claudication, joint/muscle pain or any feature of systemic infective illness. She was previously well. Her medical history included only seasonal affective disorder for which she was being treated with citalopram successfully. She was allergic only to ibuprofen. There was no known significant family history.
On examination, the patient was alert, not in distress and appeared generally well. Vital signs were within normal limits, and there was no significant blood pressure differential between the right and left arms. A borderline tachycardia was present with a heart rate of 98, in normal sinus rhythm. She had a respiratory rate of less than 20, and pulse oximetry reading above 95% on room air. The patient was afebrile. There was reduced air entry to the left lung base with a subtle decrease in vocal resonance, and no crepitations. Heart sounds were dual with no audible murmurs, and the patient was peripherally perfused. Abdomen was soft and non-tender. There was no focal neurology, with normal upper, lower and cranial neurological examinations. There were no rashes, bruises, palpable lymph nodes or signs of local infection. There were no changes to hair, nails or skin. Examination was otherwise unremarkable.
Investigations
A number of bedside tests, blood tests and imaging were performed in the emergency department (figure 1, tables 1 and 2).
CT aortogram on day of presentation demonstrating aortic wall thickening and a small amount of pleural effusion/periaortic fluid visible on this image, indicated by the arrows.
Emergency department blood and bedside tests
| Blood test | Result |
| FBC | Hb: 121, WCC: 12.09, Plt: 389 |
| UEC | Na: 133, Cr: 38 |
| CRP | 200 (<5) |
| Troponin | Negative at both 1 and 8 hours post-onset |
| D-dimer | 2.26 (<0.50) |
| ECG | Normal sinus rhythm, no ischaemic features, predominant right ventricle |
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Cr, creatinine; CRP, C reactive protein; FBC, full blood count; Hb, haemoglobin; Na, sodium; Plt, platelet; UEC, urea, electrolytes and creatinine; WCC, white cell count.
Emergency department radiological investigations
| Imaging | Result |
| Chest X-ray | Small pleural effusion with mild interstitial changes in the left base. Diminished air in the lung field on the left |
| CTPA | No pulmonary arterial thrombosis. Fluid surrounding the descending thoracic aorta with a moderately sized pleural effusion on the left. Origin of the fluid on the left is indeterminate |
| CT aortogram | No evidence of aortic dissection or aneurysmal dilatation. Suggestion of stenosis at the origin of the left renal artery. No stenosis of the origin of subclavian arteries. Descending thoracic aorta wall thickening, associated fluid surrounding aorta |
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CTPA, CT pulmonary angiogram.
The blood results excluded myocardial infarction (negative troponins), showed that a pulmonary embolism could not be excluded (positive D-dimer) and demonstrated that an inflammatory process was occurring (C reactive protein/CRP 200) (table 1).
The imaging demonstrated that there was no pulmonary embolism or aortic dissection, but showed a thickened descending thoracic aortic wall, with a small associated pleural effusion (table 2, figure 1).
Following these investigations, immediate life-threatening causes had been excluded (eg, pulmonary embolism, aortic dissection/aneurysm, myocardial infarction), and a provisional diagnosis of descending aortitis was made, from which a list of differentials was created. The patient was admitted to the general medical ward, and underwent further bloods tests and imaging, which will be discussed in the next section.
Differential diagnosis
Aortitis has many possible causes, which form the list of differential diagnoses. Typically these are separated into infectious and non-infectious causes, as listed below.
Non-infectious causes of aortitis1:
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Temporal arteritis.
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Takayasu arteritis.
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Behcet’s syndrome.
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Cogan’s syndrome.
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Systemic lupus erythematosus.
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Rheumatoid arthritis.
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HLA-B27-associated spondyloarthropathies.
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Antineutrophil cytoplasmic antibodies (ANCA)-associated vasculitis.
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Sarcoidosis.
Infectious causes of aortitis2:
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Gram-positive cocci, particularly Staphylococcus, Enterococcus and Streptococcus pneumonia.
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Salmonella.
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Treponema pallidum (syphilis).
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Mycobacterium tuberculosis.
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Candida.
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Aspergillus.
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Hepatitis B and C.
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Other viral infections have an association (not necessarily causative) with aortitis and vasculitis, including Epstein-Barr virus (EBV), cytomegalovirus (CMV), varicella-zoster virus and herpes simplex virus (HSV).
Infectious causes of aortitis are considerably rarer than non-infectious causes,1 and given this patient showed no signs of systemic or localised infection, suspicion was higher for a non-infectious cause.
Further imaging and blood tests were performed to narrow down the differential list (tables 3 and 4).
The imaging allowed us to conclude that it was unlikely this patient had temporal arteritis, one of the most common causes of aortitis,1 given lack of clinical features and negative findings on ultrasound (table 3). Halo sign has a sensitivity and specificity of 75% and 85%, respectively, for temporal arteritis.3 The echocardiogram excluded cardiomyopathies as a cause of this patient’s symptoms (table 3).
Blood tests performed on the medical ward
| Blood test | Result |
| Liver function tests | All within normal limits |
| Erythrocyte sedimentation rate | 70 (1–35) |
| Complement | C3 and C4 are towards the upper limits of normal, but still within normal range |
| Antinuclear antibodies | 6 (ref range <7) |
| Anti SSA-Ro | Not detected |
| Double-stranded DNA | 1 (ref range <7) |
| Extractable nuclear antigen | Negative |
| Antineutrophil cytoplasmic antibodies | <3 (ref range <4) No pattern observed |
| Epstein-Barr virus serology (EBV) | EBV IgG: positive; EBV IgM: negative |
| Cytomegalovirus serology (CMV) |
CMV IgG: 0.8 (considered positive/detected if above 6.0); CMV IgM: negative |
| Herpes simplex virus serology (HSV) | HSV-1 IgG EIA: positive; HSV-2 IgG EIA: negative |
| Varicella serology | IgG CLIA: positive (consistent with past infection/vaccination) |
| Adenovirus | Adenovirus CFT <10 |
| Urea, electrolytes and creatinine | Normal values throughout admission |
| Thyroid function test | T4 and TSH within normal limits |
| Urine microscopy and culture | No abnormalities seen, no growth in culture |
| Blood cultures | No growth |
| Treponemal serology | Treponema pallidum total antibody: not detected |
| IgG subclasses | All within normal limits |
| Flow cytometry (peripheral blood lymphocyte analysis) | CD4: 69% (30–61) CD8: 8% (12–45) CD4/CD8 ratio: 8.63 (0.72–4.18) |
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CFT, Complement Fixation Test; CLIA, chemiluminescence immunoassay; EIA, enzyme immunoassay; TSH, thyroid stimulating hormone.
Radiological investigations performed on the medical ward
| Imaging | Result |
| Ultrasound scan temporal arteries | No evidence of temporal arteritis, no halo sign |
| Echocardiogram | Concentric left ventricular remodelling with normal systolic function. Normal right ventricular size and systolic function. No haemodynamically significant valvular dysfunction |
With the relatively extensive autoimmune and vasculitic screen completed and returned essentially normal (apart from CD4/CD8 ratio), the differential diagnosis could be narrowed considerably (table 4). Takayasu arteritis was ruled out as the patient is too old to fit clinical criteria for this condition and does not display any features other than aortitis.1 Behcet’s syndrome was excluded as the patient did not meet the diagnostic criteria.4 Cogan’s syndrome was excluded as the patient did not have eye or ear symptoms.5 Systemic lupus erythematosus was considered unlikely based on a combination of lack of clinical features and normal biomarkers (complement, antinuclear antibody, anti-SSA-Ro, double-stranded DNA, extractable nuclear antigen (ENA))6 7 (table 4). ANCA-associated vasculitides were excluded based on lack of clinical features and negative ANCA.8 Although HLA-B27-associated spondyloarthropathies could not be excluded by blood test (HLA typing not performed), the lack of clinical features supportive of this diagnosis was sufficient to consider it unlikely.9 A viral screen also excluded several possible infectious causes such as EBV, CMV, HSV, varicella, adenovirus and syphilis10 11 (table 4). Normal IgG subtyping makes immunodeficiency (and subsequent occult infection) and autoimmune processes less likely12 13 (table 4). The only differential left on the list is now sarcoidosis, which is very difficult to rule in or out. Sarcoidosis as a cause of this patient’s symptoms was possibly supported by the elevated CD4/CD8 ratio found on peripheral blood lymphocyte analysis (table 4). The literature on this point is mixed, and there is controversy surrounding this association as most of the available literature suggests that lymphocyte analysis of affected tissues is a more useful diagnostic tool, such as bronchoalveolar lavage fluid in pulmonary sarcoidosis, or vitreous humour in ocular sarcoidosis.14 15 Despite this, there is limited, mixed evidence that a raised CD4/CD8 ratio in peripheral blood may be supportive of a diagnosis of sarcoidosis,14 16–18 and as such we feel that this is positive finding on peripheral blood, as well as having the other more common causes considered unlikely or excluded, can support a suspicion of sarcoidosis and guide subsequent investigation and management.
Overall, the underlying cause of this patient’s descending thoracic aortitis remains unknown, but the available information suggests sarcoidosis as a possible cause and rejects a diagnosis of one of the more common non-infectious causes of aortitis.
Treatment
The patient was commenced on 50 mg oral prednisolone daily, and within 8 hours of the first dose began to feel symptomatic improvement. This continued for 3 more days, until the patient’s exercise capacity was returned to near normal. The steroids were planned to continue for 1 week followed by a weaning regimen, decreasing the dose by 10 mg per week until stopped.
Repeat imaging prior to discharge showed significant interval improvement in aortic wall thickening and periaortic fluid, as well as improvement of the previously seen left-sided pleural effusion (figure 2). This was accompanied by falling inflammatory markers over the same time, with CRP dropping from 200 to 69. These comparative images, and the trend of inflammatory markers demonstrate the improvement over 3 days of oral prednisolone, 50 mg once daily (figure 2).
Comparison of aortic wall thickening at time of diagnosis (left), versus 3 days of oral prednisolone (right).
Outcome and follow-up
Following successful treatment in hospital, the patient was discharged home with the view of returning to her home country in a few weeks and seeking further diagnostic work-up/treatment as required.
Unfortunately, the patient had an adverse reaction to the steroid treatment (low mood and fatigue), and represented to hospital 7 days later. During this admission, a repeat CT aortogram was performed and showed ongoing improvement/resolution of the aortitis with the steroid treatment. By this time, the CRP had dropped to 2.6 (normal values <5).
As this patient is an international traveller, follow-up had inherent pitfalls. The patient was asked to see a doctor once she returned to the UK for further treatment and investigation as required, with the suggestion of CT-positron emission tomography given the suspicion of sarcoidosis. Copies of the discharge summary were provided to the patient and mailed to her nominated general practitioner (GP) in her home country as well as a GP known to her family in Bunbury. A clear, plain English explanation of the suspected disease entity and follow-up recommendations in both writing and verbally were given to the patient, to further reduce risk of misinformation and poor follow-up.
At the time of writing this report, it was unknown whether the patient had sought further investigation and management as suggested, and whether or not they had received a definitive diagnosis.
Discussion
Chest pain is a common presentation for emergency departments in Australia and around the world, with throat and chest pain accounting for 3.8% of all presentations to Australian emergency departments in 2017/2018.19 This was surpassed only by presentations for pelvic and abdominal pain.19 with an average of 22 000 presentations to the emergency department per day in Australia, the emergency department clinician can expect to manage many patients with chest pain.19 It is usually the case that common presentations are caused by common diseases, however in the case of our patient it is shown how common presentations can be manifestations of rare diseases. Diagnosis of rare disease could be very difficult and may require exclusion of many other diagnoses before arriving at the correct one. For this reason, exclusion criteria and structured guidelines to the approach in managing patients with common presentations that have possible life-threatening pathology are important. These guidelines both prevent missed diagnoses of dangerous pathology, and allow the clinician to explore alternative, rarer diagnoses once the life-threatening or easily treatable condition has been ruled out. In the case of the patient in this case report, timely exclusion of ischaemic heart disease, respiratory disease, aortic dissection and other such serious diseases were ruled out in the emergency department, allowing the physician to safely manage and investigate the patient on the ward.
There have been a small number of published cases of aortitis secondary to sarcoidosis, both with and without chest pain, however there has often been an associated vasculitis diagnosed either before or after the diagnosis of sarcoidosis (sarcoidosis confirmed by tissue biopsy).20–22 As of 2015, there had only been 10 reported cases of aortic sarcoidosis, making it extremely rare.23 This case does not appear to be the first patient to present with chest pain as a manifestation of aortitis, nor aortitis as a manifestation of sarcoidosis, however it does appear to be unique in the sense that the patient had no other pathological findings other than descending aortitis and associated pleural effusion. There have been cases described in the literature that fit this clinical picture, termed clinically isolated aortitis (CIA—aortitis without evidence of systemic vasculitis).24 The possibility remains that CIA is the ultimate diagnosis for this patient, a disease entity which is still not well understood but that has some evidence supporting the use of immunosuppressive therapy and periodic aortic imaging.24 Determination of underlying pathology will guide clinical course and necessary management, and as such it is important that this patient receives adequate follow-up. Such is the challenge of treating overseas travellers with rare and elusive diseases.
Empirical treatment is the provision of therapy/intervention without yet knowing the definitive diagnosis. This is a very important part of our practice as clinicians, as it is often that treatment is initiated before a definitive diagnosis is made. There are obvious challenges associated with this practice, such as possible adverse reactions to the medical therapy provided, and more complex ones such as the likely morbidity associated with failing to initiate empirical therapy. This case highlights the utility of empirical treatment. In cases where a diagnosis is evasive and difficult to make, and where patients are suffering from symptoms caused by the as yet unknown disease entity, it is difficult to justify the delay in treatment of their symptoms. Using the available information, the clinician will make an educated guess about likely underlying causes and their likely responses to different therapies and administer treatment accordingly. With high-risk patients, or high-risk therapies, this is always best to be done under close observation like it was for the patient mentioned in this case, who was admitted to hospital for investigation and management.
Patient’s perspective
Below is a review written by the patient, and posted online in an Australian healthcare opinion-sharing forum:
I was taken in while visiting my adult child and family. My back started to ache, then my ribs did the same. I found it hard to draw breath and began to feel like my chest was being constricted in a clamp. Fearing a heart attack, I went to [Hospital name] Emergency and was received and registered, just using my overseas passport, with great efficiency. Triage attended to me very professionally and I was quickly admitted to an emergency ward.
I was kept advised about what their sundry investigations revealed about my condition. It was decided that I should be admitted to the medical ward immediately.
My experience in the hospital was very positive, all the staff members, with whom I had contact, were lovely, helpful and maintained a cheerful atmosphere. The consultant and his team were charming, reassuring, supportive and informative. I was subjected to every conceivable scan, X-ray, blood test that I can imagine and even ultrasound. The care and attention that I received was exemplary and I cannot imagine that there is anywhere in the world where I might have received better treatment in my opinion.
I was diagnosed as having Aortitis and subsequently Sarcoidosis is suspected, shown the reports, photos and results of all the tests, that were available and my consultant explained, in terms that I could understand, what they all meant. My fears and apprehension were all expelled by the confidence that he and his team inspired. I was advised that the full scans, pictures and tests reports will be forwarded to my overseas general practitioner to support my continuing treatment and that I will receive a copy of my case study, which Professor Adel intends to submit to The British Medical Journal. However, I do understand that there can be some delay before these final documents reach my clinic overseas.
Thank you [Hospital name] for all you have done for me, I love you all.
Learning points
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Common presentations can be caused by rare disease, and those with the common causes excluded should be thoroughly investigated for alternative and rarer diagnoses, as a correct diagnosis allows the best possible management and follow-up.
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Empirical treatment is often required, and is a valuable strategy employed by clinicians, especially when a diagnosis is difficult to make, either due to lack of clinical evidence or lack of specific non-invasive investigations. Empirical therapy in high-risk patients, or of high-risk therapies should be done under close observation.
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Overseas travellers have a high risk of poor follow-up due to inherent difficulties in clinical handover of patients. Risk stratification should be done of patients and their diseases, and appropriate safety netting should be put in place.
Footnotes
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Contributors MAH—the junior medical officer working in Bunbury Hospital on the team that treated the patient who is the subject of the case report—produced and compiled the written article, and acquired images, information and consent. AE—the professor of medicine and senior consultant in general medicine at Bunbury Hospital and the consultant managing the patient who is the subject of the case report during their admission(s) to hospital—provided guidance, direction and critical appraisal of the article, giving suggestions and some citations for the article, thus ultimately deciding that the article is ready for submission.
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Funding The authors have not declared a specific grant for this research from any funding agency in the public, commercial or not-for-profit sectors.
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Competing interests None declared.
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Patient consent for publication Obtained.
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Provenance and peer review Not commissioned; externally peer reviewed.
- © BMJ Publishing Group Limited 2020. No commercial re-use. See rights and permissions. Published by BMJ.
References
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