Rare paediatric cardiopulmonary presentation of Behcet’s disease

Abstract

This case discusses a 10-year-old boy who presented in significant respiratory distress with cardiac tamponade with associated gross ascites and hepatomegaly, requiring urgent transfer for pericardiocentesis. On further investigation, he was found to have multiple pulmonary emboli and evidence of panserositis. An underlying rheumatological cause was suspected in the absence of any evidence of infection or malignancy, and blood tests were positive for anti-double stranded DNA, anticardiolipin and antiglycoprotein antibodies as well as HLA B51. In his medical history, he has previously had mouth ulcers, chronic anaemia of undetermined cause and erythema multiforme. These symptoms, along with clinical presentation, mean a diagnosis of Behcet’s disease and associated antiphospholipid syndrome was felt to be most likely. Anticoagulation therapy was commenced for treatment of the emboli, and colchicine was started for management of Behcet’s disease. The patient was discharged clinically well from the hospital and continues under specialist rheumatological and haematological follow-up.

Background

Behcet’s disease is a vasculitis affecting all vessel sizes, with up to 20% of cases occurring in children. It is a systemic disease which can affect various organs, and the aetiology is unknown.¹ There is no single diagnostic test, and diagnosis is reliant on clinical features. A number of classification criteria have been published, including the International Classification Criteria and the Paediatric Behcet’s Disease (PEBDB) classification criteria for children in 2015.² The most common presenting feature in children appears to be oral and genital ulcerations, along with fever of unknown origin.

Childhood cardiopulmonary complications are extremely rare, occurring in only around 3%–7% of young patients, and are slightly more common in male patients, and these complications have a high morbidity and mortality rate.³ Some of the cardiopulmonary complications documented in the literature include intracardiac thrombi, pulmonary artery aneurysm, pulmonary embolism and ruptured aneurysms, which can lead to cardiac tamponade. Venous involvement is more common (12%) than arterial involvement (7%).⁴ Mortality rate is about 20% in severe cases.⁴

Behcet’s disease has a strong genetic component and HLA-B51 is associated, usually in men, with a higher prevalence of genital ulcers, ocular and skin manifestations, and less gastrointestinal involvement.⁵

The mainstay of treatment for Behcet’s disease includes steroids, anti-inflammatories and, in some cases, immunosuppressants including biological agents.

We present a case of a child diagnosed with Behcet’s disease after an extremely rare presentation with cardiac tamponade, which had a significant mortality risk.

Case presentation

A 10-year-old boy presented to the emergency department with acute breathlessness, on a background of 4 weeks of worsening abdominal pain, distention and a dry cough. He had recently completed a course of oral antibiotics after presenting with a cough and having a slightly raised C reactive protein (CRP). On presentation, he had a clear chest but gasping pattern of respiration, with normal oxygen saturations. He was tachycardic, with a slightly prolonged capillary refill time, and therefore received a fluid bolus. On examination, he was found to have gross abdominal distention with ascites.

His chest X-ray showed globular cardiomegaly (figure 1), and a bedside echocardiogram revealed gross pericardial effusion (figure 2) with cardiac tamponade (video 1). He required retrieval and immediate drainage of the effusion. On arrival to the cardiac centre, he had pulsus paradoxus and a narrow pulse pressure. Heavily blood-stained fluid of 970 mL was aspirated, and a drain was left in situ. He was also found to have a right-sided pleural effusion for which a pleural drain was required (figures 1 and 3).

Figure 1.

CXR showing gross cardiomegaly and pleural effusions.

Figure 2.

Echocardiogram showing the heart being compressed by a pericardial effusion.

Video 1.

bcr-2021-248134supp001.mp4 ^{(668.9KB, mp4)}

DOI: 10.1136/bcr-2021-248134.video01

Figure 3.

Echocardiogram showing slit-like ventricles due to compression from the effusion.

During admission, he underwent further investigations and was reviewed by the paediatric rheumatology, haematology and ophthalmology teams alongside his cardiac care.

His medical history included a previous hospital admission for swollen joints and erythema multiforme rash, chronic refractory anaemia of unknown cause, chronic mildly raised CRP and Erythrocyte Sedimentation Rate (ESR) and a history of oral mouth ulcers and gingivitis. All of these presentations, retrospectively, could have been relevant to his current working diagnosis.

Investigations

On admission to the tertiary centre, pleural and pericardial fluid samples were obtained from our patient at the time of drain insertion. Both samples were negative for malignant cells and acid–fast bacilli, and negative on microscopy and culture. The pericardial fluid showed a mix of acute and chronic inflammations (video 2).

Video 2.

bcr-2021-248134supp002.mp4 ^{(668.9KB, mp4)}

DOI: 10.1136/bcr-2021-248134.video02

On the following day, a CT of his chest, abdomen and pelvis showed the chest had prominent lymph nodes, an enlarged heart, pericardial effusion, multiple segmental pulmonary emboli (PEs) bilaterally, ground-glass changes and oedema in dependent regions. There were also widespread vertebral serpentine lesions, which could be consistent with long-standing microvascular occlusions. There were no obvious aneurysms seen on CT (figure 4). This began to raise the suspicion of a rheumatological disease with pan serositis. Further blood samples were therefore taken for investigation.

Figure 4.

CT of the chest after drain insertion showing multiple small pulmonary emboli, cardiomegaly and a small pericardial effusion.

His virology samples were negative for acute infection of Herpes simplex virus, Hepatitis C, Hepatitis B, Cytomegalovirus, Epstein-Barr virus and HIV. He also had a negative T spot. His inherited thrombophilia screens were also normal.

Anti DSDNA was positive on initial rheumatological testing, as well as IgG anticardiolipin antibodies and IgG antibeta 2 glycoprotein I antibodies. IgM for both of these antibodies was negative. This is suggestive of antiphospholipid syndrome (APS).

Human Leuckocyte Antigen (HLA) screening was HLA Baa51 positive, which is associated with his working diagnosis of Behcet’s disease. He also had a raised faecal calprotectin at 529, suggesting gut inflammation was also present, which is in keeping with panserositis.

Differential diagnosis

Initial differentials for findings of significant effusions included infection (viral, bacterial or tuberculosis) and malignancy such as lymphoma/leukaemia, cardiac causes and lupus.

The finding of a high faecal calprotectin also raised suspicion for inflammatory bowel disease with systemic symptoms. Crohn’s disease can cause oral ulceration, joint pain and swelling, rashes and uveitis. However, this does not usually cause panserositis or widespread vasculitis.

Echocardiogram findings once the effusions were drained was unremarkable with a structurally normal heart, and biopsies taken on endoscopy were also reported as normal. The discharge echocardiogram showed a small residual pericardial effusion but normal biventricular systolic function. Therefore, underlying cardiac disease was unlikely.

As mentioned previously, no evidence of infection or malignancy could be found on testing samples. This, along with the CT findings, particularly the pulmonary embolisms and microvascular occlusions, led to a focus on rheumatological diagnostic testing.

One differential diagnosis is systemic lupus erythematous (SLE) as antiphospholipid was positive, but Anti-nuclear Antibodies were negative. SLE usually occurs more in women, and our patient did not have any classical skin lesions. However, SLE can cause erythema multiforme, which he had previously been diagnosed with.

A20 haploinsufficiency (HA20) is a more recently described autoinflammatory condition associated with a mutation in the TNFAIP3 gene, with clinical features similar to Behcet’s disease and Crohn’s disease. It can cause oral ulceration, joint pain and swelling, rashes and uveitis and so is a differential diagnosis to keep in mind.⁶ HA20 usually presents with symptoms early in childhood, with recurrent fever as a common feature, and it may not respond well to colchicine treatment. HLA B51 antigen is uncommon in HA20.⁷

Our patient was HLA B51 positive, with previous history of oral ulcers, chronic anaemia and a presentation showing panserositis, and therefore the most likely diagnosis is Bechet’s disease. APS is thought to be a secondary phenomenon.

Treatment

This patient was initially admitted to paediatric intensive care unit and underwent emergency treatment for the effusions with pericardial and pleural drain insertion. He required intubation due to instability at the time of drain insertion but only for a short time. Broad-spectrum antibiotics and diuretics were commenced (figure 5).

Figure 5.

Chest X-ray after drain insertion.

Following the CT findings of significant bilateral PEs, haematology opinion was sought for anticoagulation management. He was commenced on a heparin infusion which was later converted to subcutaneous dalteparin during his inpatient stay. This was subsequently converted to warfarin for long-term outpatient therapy and he is continuing this postdischarge.

There was discussion with the haematology team surrounding possible rivaroxaban use to reduce the need for blood test monitoring, but this is contraindicated in patients who are anticardiolipin antibody positive and therefore was decided against.

He was commenced on colchicine orally and was also discharged on this medication. Since discharge, his colchicine dose has been increased. Diuretics have been discontinued.

He saw the ophthalmology team during his inpatient stay and had a normal eye examination.

His general paediatric team commenced Anbesol and betamethasone mouthwash for 14 days for recurrence of oral ulcers during his admission.

Outcome and follow-up

This child has been discharged home and remains clinically well. He did have one further attendance to his local emergency department after discharge for abdominal pain, but all investigations were normal and he did not require admission.

A week prior to discharge, an MRI scan of his chest showed there was a small pericardial lesion, which could be in keeping with pus or a clot related to the drain insertion (figure 6). The pericardial effusion had significantly reduced in size; the pleural effusion had significantly improved; and the imaged vessels were structurally normal. The heart was of normal structure, and after a further outpatient echocardiogram postdischarge, which was entirely normal, he was discharged by the cardiology team.

Figure 6.

MRI of the chest showing improved pericardial effusion and resolved left lower lobe consolidation.

He will continue to be followed up by the rheumatology and haematology teams. He has regular contact with the community anticoagulation team for monitoring of his warfarin therapy, and ophthalmology will offer him a further outpatient appointment.

Discussion

It is rare for children to present with significant cardiopulmonary complications as a result of Behcet’s disease, but they have a significant mortality risk. The other case reports of children with these rare complications have mostly been reported to have a pulmonary artery embolism causing their cardiac complications.

One case reports a 12-year-old boy with a history of recurrent oral ulcers and extensive thrombosis, but he had bilateral inferior pulmonary artery embolisms subsequently requiring resection. In this case, Behcet’s disease was treated with steroids, anticoagulant therapy and immunosuppressants.⁸ Interestingly, our patient was not treated with steroids throughout his admission. Another study of 26 adolescents with Behcet’s disease found that 3 of their patients had cardiopulmonary complications with intracardiac thrombi and pulmonary artery aneurysms. All patients had a good response to anti-inflammatory agents.⁹ A further case report is that of a 14-year-old patient with Behcet’s disease and recurrent haemoptysis who had an underlying right ventricular thrombus and pulmonary artery aneurysm, and responded well to infliximab treatment.¹⁰

It appears that most reported cardiopulmonary complications involve a pulmonary artery aneurysm. This was not the case for our patient. He had a significant effusion with cardiac tamponade and multiple small emboli, but imaging did not show a large thrombus (figure 4). There is a reported case of a 30-year-old woman with recurrent pleuropericardial effusions and underlying Behcet’s disease.¹¹ It is likely in this case and with our patient that the underlying panserositis was the cause of effusions and not a single significant thrombus.

As discussed, there are many paediatric scoring systems used for Behcet’s disease, and currently, there is no single guideline suggesting how to use them. There have been 18 diagnostic classification/criteria published thus far. One study analysing the criteria suggests that PEDBD criteria focuses on paediatric patients and the rest of the criteria are mostly for adult use. Therefore, we considered these criteria for our patient. Three out of six criteria should be fulfilled to make a diagnosis of Behcet’s disease (see table 1). It is unclear in his case whether he had a history of ulcers at least three times per year, and this was not documented in the history. So he fulfilled two criteria and possibly the third.

Table 1.

PEDBD diagnostic criteria versus child C’s presentations

Recurrent oral ulceration (at least three times per year)	Yes but unclear if three times/year
Genital ulceration	Not documented
Skin involvement	Yes—previous erythema multiforme
Ocular involvement	Not documented
Neurological signs	Not documented
Vascular signs	Yes

However, with his clinical history, imaging and HLA result, Bechet’s disease is the most likely diagnosis for this patient, but as discussed, it is still important to bear in mind other rheumatological diagnoses with overlapping symptoms. Our patient is being managed with colchicine as an anti-inflammatory agent, along with anticoagulation currently. Colchicine works as an anti-inflammatory agent by inhibiting the enhanced chemotactic activities of neutrophils. In a large randomised double-blind controlled crossover trial, the overall disease activity index for Behcet’s disease improved significantly with colchicine.¹²

Our patient was anticardiolipin and antiglycoprotein positive and therefore was also diagnosed with APS. One recently published systematic review and meta-analysis established that there is a significantly higher prevalence of antiphospholipid antibodies in patients with Behcet’s disease as compared with controls, which contributes to thrombosis.¹³ APS is thought to be a secondary diagnosis, in addition to Behcet’s disease, in this case.

Learning points.

• A patient presenting with panserositits should be investigated for rheumatological conditions after ruling out infection and malignancy. Rheumatological conditions are chronic, and early identification and specialist input lead to a better outcome for the patient.

• There is no diagnostic test for Behcet’s disease, and diagnosis is guided by typical clinical features and HLA testing. If suspected, discussion with and guidance from a paediatric rheumatologist are vital.

• Antiphospholipid syndrome (APS) and acute thrombosis are life-threatening complications of Behcet’s disease and, if diagnosed, require prompt and long-term treatment; therefore, any patient with a diagnosis of Behcet’s disease should be investigated for these associated conditions.

• It is important to confirm or rule out APS in patients with Behcet’s disease as long-term anticoagulation with rivoroxiban is contraindicated in this syndrome.

Ethics statements

Patient consent for publication

Consent obtained from parent(s)/guardian(s).