Behçet’s disease in pregnancy: a case report and literature review

Abstract

Background

Behçet’s disease (BD) during pregnancy is a relatively rare condition, and there are currently no established guidelines for its management. The effects of BD on both mothers and children remain unclear. In this paper, we present the diagnostic and treatment processes for a patient with BD during pregnancy.

Case presentation

A 20-year-old woman, gravida 2, para 1, presented to our inpatient department with recurrent oral and genital ulcers at 28 weeks and 3 days of gestation. Given the complexity of the patient’s condition, we initiated the first multidisciplinary consultation to establish appropriate treatment regimens. However, the initial treatment was ineffective, and the patient experienced a fever for four days. Consequently, we conducted a second multidisciplinary consultation. The final treatment regimen included azithromycin, hydroxychloroquine, prednisone, and low-molecular-weight heparin calcium. The clinical symptoms resolved, and the female neonate was delivered successfully. No relapse was observed during the four-month follow-up.

Conclusions

The critical issues in treatment involve ensuring medication safety for pregnant women and preventing adverse pregnancy outcomes. Notably, one potential cause of adverse pregnancy outcomes in individuals with BD is vasculopathy, which necessitates prompt treatment with anticoagulant therapy. Obstetricians should closely monitor disease progression and remain vigilant for complications in order to minimize adverse outcomes during pregnancy.

Background

Behçet’s disease (BD) is a chronic multisystem vasculitis characterized by recurrent oral and genital ulcers, uveitis and skin lesions, and it may also involve the heart, gastrointestinal system, nervous system, kidneys, and joints. Epidemiological studies indicate significant geographical differences in the prevalence of BD, which is highest in countries along the ancient Silk Road, stretching from the Mediterranean basin to East Asia [1]. A comprehensive global review reported a prevalence of 10.3 per 100,000 individuals, while the incidence rate in China was estimated at 14 per 100,000 individuals [2].

BD often manifests in young women of childbearing age, with the primary symptoms during pregnancy being oral and genital ulcers, reported at rates of 17.8% and 8.9%, respectively. Other manifestations, though less common, include arthritis (4.4%), uveitis (2.2%), and neurologic symptoms (6.7%) [3]. The existing literature on BD in pregnancy remains limited and presents conflicting findings. Some studies indicate that BD does not increase the risk of adverse pregnancy outcomes [4, 5], while others report a higher incidence of preterm labor, cesarean sections, and gestational diabetes mellitus [3, 6]. Tânia Barros et al. propose that these adverse outcomes may be associated with vascular lesions [3].

In this article, we present a case of BD in pregnancy characterized by recurrent oral and genital ulcers. We also discuss the risk factors for BD that may contribute to adverse pregnancy outcomes and outline management strategies for patients with BD during pregnancy by reviewing the relevant literature.

Case presentation

A 20-year-old woman, gravida 2, para 1, has experienced recurrent oral ulcers since the first trimester without receiving treatment. Due to the presence of genital ulcers accompanied by swelling and pain, she underwent treatment with potassium permanganate (1:5000) in water during a sitz bath, as well as topical anti-inflammatory medications, three days prior at another hospital; however, there was no significant improvement. Consequently, she presented to our inpatient department with recurrent oral and genital ulcers at 28 weeks and 3 days of gestation. She reported no history of rheumatic, genetic, infectious, or psychiatric disorders. Additionally, there was no history of mental or genetic disorders.

Upon admission, physical examinations revealed scattered, round ulcers of varying sizes and depths on the mucosa of the lower lip and the margin of the tongue, with a yellowish coating covering the base. There was congestion of the uvula, and round-like ulcers were also visible on the uvula (Fig. 1). The vulvar clitoris was swollen, and scattered ulcers of varying depths were observed on both the labia majora and labia minora, with notable adhesions on the right labium and a significant amount of yellowish-white discharge present, which was associated with evident tenderness (Fig. 1).

Fig. 1.

The Patient’s oral ulcers and genital ulcers

The blood and urine tests indicated the presence of inflammation, with hypersensitive C-reactive protein (hs-CRP) measured at 37.23 mg/L and an erythrocyte sedimentation rate (ESR) of 34 mm/H. Positive results were observed for the herpes simplex virus (HSV) type I antibody-IgG, anti-Streptolysin “O” test (ASO), anti-cytomegalovirus IgG, complement C3, and complement C4.

Based on the diagnostic criteria established by The International Criteria for Behcet’s Disease (ICBD) and in conjunction with clinical symptoms and laboratory findings, a diagnosis of BD was confirmed at 28 weeks and 3 days of gestation. Initially, treatment involved the administration of dexamethasone (6 mg i.m. every 12 h) to facilitate fetal lung maturation. Given the rarity of the disease, we initiated a multidisciplinary consultation. Following recommendations from dermatologists and clinical pharmacists, the treatment regimen was adjusted to include povidone iodine (200 ml ad us.ext daily) and polymyxin B ointment (100 mg ad us.ext daily) for the treatment of vulvar ulcerated surfaces, tin scatter (100 mg ad us.ext daily) for uvulopalatine ulcerated surfaces, along with aciclovir (450 mg i.m. every 8 h) and continued dexamethasone (6 mg i.m. every 12 h).

Five days after admission, the patient developed a fever that persisted for four days, with a maximum temperature of 38.6℃. Biopsies taken from the margins of the vulvar ulcer lesions revealed suppurative inflammation. A direct laryngoscopy indicated congestion of the mucosa in the palatoglossal arch, palatopharyngeal arch, and larynx, along with first-degree enlargement of the tonsils. Additionally, the surface of the uvula and the posterior pharyngeal wall exhibited white ulcers, while the middle and upper parts of the posterior pharyngeal wall, the root of the tongue, and the lower part of the posterior pharyngeal wall displayed hyperplastic lymphatic follicles. Based on the examination results and symptoms, we added cefoxitin sodium (2 g IV once) to our treatment regimen and replaced polymyxin B ointment with acyclovir ointment.

The second multidisciplinary consultation was initiated due to the patient’s lack of significant improvement. The treatment regimen was modified to include hydroxychloroquine (200 mg orally twice daily), prednisone (40 mg orally once daily), and low-molecular-weight heparin calcium (2050 IU subcutaneously once daily). Six days later, physical examinations revealed no obvious ulcers on the surface of the right labia majora, vaginal wall, and cervix, while the ulcers on the right labia minora showed improvement. A small amount of grayish-white purulent discharge was noted at the vaginal opening (Fig. 2).

Fig. 2.

The Patient’s situation at discharge

Subsequently, she was discharged from the hospital. Hydroxychloroquine (200 mg orally twice daily), prednisone (40 mg orally once daily), and low-molecular-weight heparin calcium (2050 IU subcutaneously once daily) were continued for two weeks, with no recurrence observed before delivery. The patient delivered a live-born female infant at 38 weeks and 5 days of gestation, with Apgar scores of 10 at both 1 and 5 min. The female neonate exhibited no abnormalities. At six weeks postpartum, the patient showed no signs of recurrence.

Discussion and literature review

BD is a rare disorder, and its etiology and pathogenesis remain unclear. However, growing evidence suggests that genetics, environmental factors, infections, and immune status all contribute to the development of BD [2]. In 1990, a collaboration of scientists from seven countries published the International Study Group (ISG) criteria for BD (Table 1) to establish a unified set of diagnostic criteria [4]. Despite this effort, the sensitivity of the ISG criteria for diagnosing BD was found to be low. To enhance sensitivity, the team developed a new set of criteria in 2014, known as ICBD (Table 2) [5]. The diagnostic point score system for BD requires a score of ≥ 4. In 2021, China introduced its own criteria based on the ICBD, and its diagnostic point score system is consistent with that of the ICBD [2].

Table 1.

International criteria for Behçet’s disease for the diagnosis

Manifestation	Definition
Recurrent oral ulceration	Minor aphthous, major aphthous, or herpetiform ulcers observed by the physician or patient, which have recurred at least 3 times over a 12-month period
Plus any two of the following findings:
Recurrent genital ulceration	Recurrent genital aphthous ulceration or scarring, observed by a physician or reported reliably by patient
Eye lesions	Anterior uveitis, posterior uveitis, or cells in vitreous on slit lamp examination; or retinal vasculitis observed by qualified physician (ophthalmologist)
Skin lesions	Erythema nodosum-like lesions, observed by a physician or reported reliably by patient; Pseudofolliculitis or papulopustular lesions; or acneiform nodules observed by a physician in post adolescent patients not receiving glucocorticoids
Positive pathergy test	Test interpreted as positive by a physician at 24–48 h, performed with oblique insertion of a 20-gauge needle or smaller under sterile conditions

Table 2.

International criteria for Behçet’s disease-point score system: scoring ≥ 4 indicates Behçet’s diagnosis

Sign/symptom	Points
Ocular lesions	2
Genital aphthosis	2
Oral aphthosis	2
Skin lesions	1
Neurological manifestations	1
Vascular manifestations	1
Positive pathergy test*	1

*Pathergy test is optional and the primary scoring system does not include pathergy testing. However, where pathergy testing is conducted one extra point may be assigned for a positive result

The primary symptoms of BD during pregnancy include oral ulcers, genital ulcers, skin lesions, and ocular inflammation [3]. Existing literature on the relationship between BD and pregnancy outcomes is limited and often contradictory [6–8]. A study conducted by Tien-Ming Chan et al. indicated that, aside from puerperal cerebrovascular disease and gestational diabetes mellitus, patients with BD do not face a significantly increased risk of complications, and neonatal outcomes appear unaffected by BD [4]. Conversely, research by Seohyuk Lee et al. reported that women with BD are at a higher risk for preterm labor and postpartum venous thromboembolism, with their newborns being more likely to be born prematurely [8]. Additionally, BD during pregnancy is associated with a greater likelihood of cesarean delivery, and this study also found that women with BD were more likely to require prenatal hospitalization compared to those without the condition [8].

We conducted a review of cases of BD during pregnancy. Our literature review identified 18 reports of BD in this context [9–26]. Among these cases, 7 were diagnosed during pregnancy [9–15] (Table 3), while 11 were diagnosed prior to pregnancy [16–26] (Table 4). Two neonates exhibited symptoms of BD syndrome, as reported by O. Fain et al. [19] and A.G. Fam et al. [17]. In the case reported by O. Fain et al. [19], the infant presented with transient orogenital ulcerations and pustular cutaneous lesions. In contrast, the infant in the case by A.G. Fam et al. [17] exhibited fever, stomatitis, and ulcerated pustular lesions on the face, scalp, penis, and buttocks. Additionally, a neonate in another case presented by S. Jog et al. [20] was reported to be deceased. Basak Cakal et al. described a case in which the fetus was aborted, and the patient subsequently died due to extensive pyogenic suppuration throughout the abdominal cavity [23]. Furthermore, three cases reported by Zahra Mirfeizi et al. [26], G. Guzelian et al. [10], and Keita Fujikawa et al. [25] resulted in premature delivery. Fortunately, in the case we presented, BD during pregnancy did not appear to affect the neonate.

Table 3.

BD diagnosed during pregnancy

References	Year	Gestational week	Organ involvement	Symptoms	The treatment	Outcome	Follow-up
J M Casanova et al.	1987	the third trimester	Skin and mucous membrane	genital ulcers	systemic steroids,steroid ointments	caesarean section	no recurrence
G Guzelian et al.	1997	the first trimester	Skin and mucous membrane,gastrointestinal tract	genital and oral ulcers ,abdominal pain	steroids	premature delivery	no recurrence
Kei Takayama et al.	2013	12 weeks	Skin and mucous membrane,eye	blurred vision in right eye,oral and genital ulcers,erythema nodosum	steroid eyedrops,infliximab	viginal delivery	no recurrence
Maria Papadakiet al.	2015	25 weeks	Skin and mucous membrane,eye	bilateral visual loss, oral ulcers	methylprednisolone	viginal delivery	no recurrence
Abiraj Kumar et al.	2015	33 weeks	eye	diminution of vision in her right eye	methylprednisolone,prednisolone,steroids	caesarean section	recurrence
Saori Kiyoharaet al.	2020	25 weeks	Skin and mucous membrane	oral and genital, ulcers, acneiform eruptions, erythema nodosum	prednisolone,methylprednisolone	viginal delivery	no recurrence
Ciara O’Gradyet al.	2020	the first trimester	Skin and mucous membrane,joint,eye	mucosal ulcerations, uveitis, and synovitis	etanercept,prednisolone	caesarean section	no recurrence

Table 4.

BD diagnosed before pregnancy

References	year	The history of BD	Organ involvement	Symptoms	The treatment	Outcome	Follow-up
E M Nóvak et al.	1977	1 years	Neurological manifestations	cranial nerves palsies and pyramidal tract involvement	sistemic dexamethasone ,eye drops of atropine, fluorometolone	caesarean section	visual loss
A G Fam et al.	1981	21 years	Skin and mucous membrane,joint,gastrointestinal tract,heart and great vessels	oral ulcers, inflammatory arthritis, superficial thrombophlebitis, colonic ulcers	corticosteroids, ACTH, azathioprine, methotrexate,levamisole,colchicine	Female neonate-healthy,Male neonate-affected	recurrence
R M Suchenwirth et al.	1984	10 years	Skin and mucous membrane,neurological manifestations	oral and genital ulcers, acute encephalitis	corticosteroids	viginal delivery	recurrence
O Fain et al.	1995	6 years	Skin and mucous membrane,heart and great vessels	superficial thrombophlebitis,pseudofolliculitis,oral and genital ulcers	colchicine	Neonate-affeted	no recurrence
S Jog et al.	2001	7 years	Skin and mucous membrane, joint,gastrointestinal tract,heart and great vessels	oral and genital ulcers, arthritis, colitis, erythema nodosum,thrombophlebitis of lower limbs	steroids	neonatal death	no recurrence
P Fotaki et al.	2002	11 years	Skin and mucous membrane, neurological manifestations	Oral and genital ulcers,erythema nodosum,headaches	analgetic therapy	viginal delivery	no recurrence
Ilseon Hwang et al.	2009	4 years	Skin and mucous membrane, joint	oral ulcers, erythema nodosum, arthralgia	prednisolone	caesarean section	no recurrence
Basak Cakal et al.	2011	4 years	Gastrointestinal tract	extensive pyogenic suppuration in the whole abdominal cavity	subtotal colectomy and end ileostomy	abortion	dead
Yuko Higashi et al.	2013	8 years	Skin and mucous membrane,eye	oral and genital ulcers, uveitis and folliculitis	Granulocyte and monocyte adsorption apheresis	viginal delivery	no recurrence
Keita Fujikawa et al.	2016	6 years	Skin and mucous membrane,gastrointestinal tract	fever, oral and genital ulcers,abdominal pain,hemorrhagic stool	Prednisolone,mesalazine	premature delivery	Recurrence
Zahra Mirfeiziet al.	2018	6 months	Skin and mucous membrane,heart and great vessels	oral ulcers, erythema nodosum,right heart failure progresse	Prednisolone,ceftriaxone ,vancomycin,heparin	premature delivery	no recurrence

The primary objective of treating BD during pregnancy is to swiftly suppress inflammatory exacerbations, minimize adverse pregnancy outcomes, and prevent recurrences that could lead to irreversible organ damage. Given the absence of specific criteria for BD in pregnancy, treatment regimens must be formulated based on existing guidelines for BD. Glucocorticoids serve as the cornerstone of treatment for BD, while additional medications are utilized depending on the site of involvement and the severity of the condition [5]. Medications such as methotrexate, mycophenolate mofetil, cyclophosphamide, and thalidomide, which have been associated with fetal malformations, are contraindicated during treatment [27]. Moreover, the use of other immunotherapeutic agents, such as colchicine, should be carefully regulated in terms of dosage.

It is estimated that 10–37% of patients with BD experience arterial or venous thrombosis [28]. Notably, venous involvement is more prevalent than arterial involvement; however, the hypercoagulable state during pregnancy heightens the risk of adverse obstetric outcomes. The literature reports three cases of phlebitis: two cases of superficial phlebitis [17, 19] and one case of thrombophlebitis in the lower extremities [20]. Additionally, three neonates have been reported with BD syndrome, including one case that resulted in death, as presented by S. Jog et al. It is hypothesized that vasculitis contributes to adverse pregnancy outcomes in patients with BD, making neonatal outcomes particularly vulnerable. This aligns with the findings of Jadaon J et al., who propose that vascular hypercoagulability during pregnancy is a significant factor in miscarriage among their patients with BD [28].

Anticoagulation or thromboprophylaxis is a suitable strategy for preventing adverse obstetric outcomes. Some studies indicate that the risk of venous thromboembolism in the first three months postpartum is 50 times higher than that in non-pregnant women [8]. In our case, we utilized low molecular weight heparin, which may have played a role in preventing relapse and deterioration of the patient’s condition during pregnancy and after delivery. Additionally, cesarean section is recognized as a risk factor for postpartum venous thrombosis [29]. Therefore, meticulous postpartum follow-up is essential for pregnant women with BD, particularly those who have undergone cesarean delivery. Obstetricians must remain vigilant regarding this coexisting complication and provide prompt treatment to avert adverse outcomes.

Conclusion

Obstetricians should be aware of this type of pregnancy and focus on vasculitis as a complication that can increase adverse pregnancy outcomes. Early anticoagulation is indicated to prevent such outcomes. Prompt initiation of anticoagulation and management of thrombosis are essential. After delivery, careful follow-up of both patients and infants is necessary to prevent recurrences.

Abbreviations

BD

Behçet’s disease

hs-CRP

Hypersensitive C-reactive protein

ESR

Erythrocyte sedimentation rate

HSV

Herpes simplex virus

ASO

Anti-Streptolysin “O” test

UU

Ureaplasma urealyticum

ANCA

Anti-neutrophil cytoplasmic antibodies

ANA

Antinuclear antibody

GBS

Group B streptococcus

HPV

Human papilloma virus

TCT

Thinprep cytologic test

ICBD

International Criteria for Behçet’s disease

WBC

White blood cells

ISG

International Study Group

MDT

Multidisciplinary treatment

Author contributions

X.Y. provided the patient’s information and pictures. X.L. wrote the manuscript. All authors have reviewed and approved the final manuscript.

Funding

Not applicable.

Data availability

Data is provided within the manuscript or supplementary information files.

Declarations

Ethics approval and consent to participate

Not applicable.

Consent for publication

Written informed consent was obtained from the patient for publication of clinical details and clinical images. A copy of the written consent is available for review by the editor of the journal.

Competing interests

The authors declare no competing interests.