Management of Buerger’s disease during pregnancy

Abstract

Buerger’s disease (BD), also known as thromboangiitis obliterans, is a non-atherosclerotic inflammatory disorder of unknown aetiology that affects small-sized and medium-sized vessels of the extremities. It is usually observed in middle-aged adults, especially those who smoke or use tobacco products. This condition is more frequently observed in men, although recent findings indicate an increasing prevalence among women, potentially due to increased cigarette use. The association between pregnancy and BD is rare, with only a few published cases. Previous reports have indicated that BD may worsen during gestation due to the characteristic hypercoagulable state of pregnancy. In addition, it seems to be associated with intrauterine growth restriction secondary to infarction of placental vessels. Careful obstetric management of maternal and fetal status is mandatory in pregnancies complicated with BD. We report a successful case of a pregnancy in a patient with BD treated with low-molecular-weight heparin.

Background

The association between pregnancy and Buerger’s disease (BD) is rare, and previous reports have indicated that BD may worsen during gestation. Multidisciplinary care with close monitoring is the key to a well-succeeded pregnancy.

Case presentation

We describe a case of a woman in her early 30s, primigravida, with a body mass index of 29, who was referred to a tertiary centre for pregnancy surveillance at the 20th week of gestation. The patient had been diagnosed with BD 5 years earlier. Preceding the diagnosis, she experienced coldness, pain, paraesthesia and delayed wound healing of the right leg, and she had smoked 20 cigarettes per day in the past 6 years. The patient’s blood pressure and heart rate were normal. An angiographic examination (figure 1) revealed ‘occlusion of the tibioperoneal trunk, and the posterior tibial and peroneal arteries; stenosis of the initial segment of the anterior tibial artery; observation of corkscrew collaterals’, which helped with the diagnosis. Alternative diagnoses were excluded, with investigations including a normal echocardiogram and negative antiphospholipid, antinuclear, anticentromere and Scl-70 antibodies. The patient had no family history of similar symptoms.

Figure 1.

Angiography: Corkscrew collateral vessels (red arrows), tibioperoneal trunk not observed—occlusion (blue arrow).

After diagnosis, the patient quit smoking, started treatment with iloprost infusions and was submitted to surgical sympathectomy with significant clinical improvement. She was then given low-dose aspirin (100 mg) as a maintenance treatment.

The pregnancy was achieved spontaneously and uneventfully before referral to a tertiary centre. Maternal-fetal monitoring was carried out every 2 weeks. The presence or absence of a flare, pre-eclampsia symptoms, blood pressure and fetal heart rate were documented at each visit. Ultrasound scans to assess fetal growth and well-being (amniotic fluid assessment, Doppler measurements of fetal blood flow) were made every 2 weeks beginning in the third trimester.

Considering the hypercoagulable status of pregnancy added to the BD’s increased risk of clot formation, she started taking low-molecular-weight heparin (LMWH) 40 mg/day at 20 weeks of gestation. At the end of the second trimester, the ischaemic symptoms in the right leg worsened, which prompted an increase in LMWH dose to 80 mg/day. Fetal growth evaluation was normal until the 36th week of gestation with normal fetal and uterine Doppler fluxometry evaluation when a fetal growth restriction (FGR) was diagnosed (third percentile) with abnormal Doppler blood flow in the middle cerebral artery and umbilical artery (cerebral-placental ratio below 2, fifth percentile). Alternative diagnoses for FGR were discarded, such as pre-eclampsia. Labour induction was decided a week later, and a 2460 g male infant with an Apgar Score of 9/10 was delivered by caesarean section due to failed induction of labour.

Outcome and follow-up

The postpartum period was uneventful, without further flares, and the LMWH was kept for 6 weeks post partum. Pathological examination revealed a low-weight placenta for gestational age (below the third percentile), with hypoxic changes.

Discussion

BD is a non-atherosclerotic, occlusive, thrombotic, segmental inflammatory pathology that most commonly affects the small-sized and medium-sized arteries, veins and nerves in the upper and lower extremities.¹ The most potent risk factor in developing BD is tobacco smoking.² Additional risk factors are mentioned in box 1.^{1 3 4}

Box 1. Risk factors for Buerger’s Disease.

• Tobacco smoking

• Male sex

• Age between 20 and 45 years

• Region of origin: southeast Mediterranean, Middle East and Far East

• Medical history of Raynaud’s disease or autoimmune disease

Despite its strong association with tobacco exposure, the general pathophysiology of this disease is still unknown, but some scientists believe that BD may be an autoimmune disorder.⁵ BD mainly affects young patients who usually present with ischaemic ulcers, rest pain, claudication, coldness of extremities, migratory thrombophlebitis and Raynaud phenomenon. Distal arterial occlusions can ultimately lead to limb amputation.¹

The traditional diagnosis of BD is based on five criteria: smoking history, onset before the age of 50 years, infrapopliteal arterial occlusive disease, either upper limb involvement or phlebitis migrans, and absence of atherosclerotic risk factors other than smoking.⁶ There is no specific diagnostic test and a lack of positive serological markers. Although not universally accepted, a confident clinical diagnosis should be made only when all these five criteria have been fulfilled.⁷ The angiographic findings in BD like ‘corkscrew’, ‘spider legs’ or ‘tree roots’ are helpful but not pathognomonic.⁸

Although there is no cure for BD, the cornerstone of management is smoking cessation. Even smoking one or two cigarettes per day can perpetuate the disease.¹ Other treatment options include vasodilators, such as intravenous prostaglandins and calcium channel blockers, anticoagulation, revascularisation and sympathectomy.^{1 6}

There are few reports describing BD and pregnancy (table 1), and in most of them, it was verified that the disease worsened during pregnancy,^{2 9} such as observed in the present case report, which can be easily explained considering that pregnancy itself is a hypercoagulability state.

Table 1.

Maternal and neonatal outcomes for published cases of Thromoboagiitis obliterans in pregnancy

Author	Smoking	Treatment during pregnancy	Course of Buerger’s disease during pregnancy	Fetal growth restriction	Gestation at delivery	Neonate	Pathological findings of the placenta	Post partum
Zelikovsky et al11	20/day a few years	Symptomatic treatment	Worsening of lower limb ischaemic symptoms and gangrene of left first to third toes post partum	ND	ND	ND	ND	Left sympathectomy Good course after operation
Young et al12	40/day 5 years	None	Worsening lower limb ischaemic symptoms and gangrene of right great toe	No	37 weeks	3320 g, AP 7/9	ND	Good course
		None	Worsening lower limb ischaemic symptoms	No	40 weeks	3350 g, AP 8/9	ND	Good course
Casellas et al13	Over 30/day 3 years	None	Necrosis of finger	Yes	32 weeks	1000 g, AP 6/8	Multiple infarctions, calcifications	ND
Kikuchi et al2	20/day 8 years	Heparin 10 000 IU/day from 12 weeks	Lower limb ischaemic symptoms; ulceration and necrosis of left lower limb	Yes	36 weeks	1814 g, AP 8/9	Small infarction	Good course, continued anticoagulant therapy for 1 month.
Ohwada et al9	20 /day 3 years	None	Stable	No	39 weeks	2828 g, AP 8/9	Areas of infarction	Worsening ischaemic episodes in her lower extremities
		Heparin 5000 IU two times per day from 27 weeks	Stable	No	38 weeks	2634 g, AP 10/10	Areas of infarction	Good course
Farquhar and Lamprecht14	Five packsse of LMWH due to per year Occasional marijuana	Enoxaparin 40 mg/day from 12 weeks Aspirin 100 mg/day	Stable	Yes	38 weeks	3460 g	Syncytial knots, infarctions and membranous haemosiderin	ND
Karena et al10	No history of smoking	Aspirin 75 mg/day Prednisolone 5 mg/day Azathioprine 50 mg/day Nifedipine 10 mg/day	Necrosis of finger, non-healing ulcer	Yes	37 weeks	ND	ND	Good course
Current case	20/day 6 years	Aspirin 100 mg/day Enoxaparin 40 mg/day from 20 weeks	Worsening lower limb ischaemic symptoms	Yes	37 weeks	2460 g, AP 9/10	Low-weight placenta for gestational age and hypoxic changes	Good course

AP, Apgar Score.

LMWH and aspirin remain the basis of antithrombotic treatment and prophylaxis during pregnancy.¹⁰ In our case, there was a need to increase the dose of LMWH due to the worsening of symptoms, and it was shown to be effective in preventing the progression of the disease.

In addition, there is growing evidence that BD may predispose to adverse pregnancy outcomes like FGR, which may be associated with pathological placental vascularisation, leading to inadequate fetomaternal circulation.²

The presented case report describes the management of a pregnancy complicated by BD. The treatment plan included the administration of aspirin and LMWH. Despite the worsening of ischaemic symptoms during pregnancy, as well as placental malperfusion and FGR, the overall outcome was positive. The key to success in such patients lies in multidisciplinary care with close monitoring: early detection of maternal and fetal well-being threats, with judicious use of appropriate medications.

Learning points.

• According to the literature, and as in our case, Buerger’s disease may worsen during pregnancy.

• Buerger’s disease may predispose to adverse pregnancy outcomes such as fetal growth restriction.

• Low-molecular-weight heparin and aspirin remain the basis of antithrombotic treatment and prophylaxis during pregnancy.

Ethics statements

Patient consent for publication

Consent obtained directly from patient(s).