Chapter 24

Gynecological and Reproductive Complications

in Primary Sjögren’s Syndrome

Andreas V. Goules and Athanasios G. Tzioufas

Contents

24.1Introduction

Primary Sjögren’s syndrome (SS) almost exclusively afflicts women. The external genitalia are commonly affected and as a result, vaginal dryness and dypareunia may occur. Other less common gynecological problems have also been described.

The mean age at diagnosis for patients with SS occurs around menopause. Thus, the disease does not usually become clinically apparent until the fourth decade of life. Although a considerable number of patients are affected during reproductive age, SS does not appear to affect the fertility of patients. However, the presence of anti-Ro/SSA and/or anti-La/SSB autoantibodies posses a significant concern, because these autoantibodies can enter the embryonic circulation and lead in a subset of patients to the neonatal lupus syndrome (NLS).

A.V. Goules • A.G. Tzioufas (*)

Department of Pathophysiology, School of Medicine, University of Athens, Athens, Greece

24.2Gynecological Manifestations in Sjögren’s Syndrome

Capriello et al. first described the common symptoms of dyspareunia and pruritus caused by vaginal dryness among women with SS [1]. In a systematic study that included 51 female SS patients (mean age 51 years) and 57 healthy, age-matched controls, Skopouli et al. described the disease effects on parity, fertility, and sexual activity [2]. Thirty-one (61%) of the 51 SS patients and 22 (39%) of the controls were postmenopausal. The reported age at the beginning of menopause was similar in the two groups. Sicca symptoms appeared in 34 (67%) of the SS patients before the menopause and in 17 (33%) after the menopause.

Fertility and parity rates, as well as the reproductive success rate were similar in both groups. Forty-eight of 51 patients with SS reported a total of 207 pregnancies and 50 of 57 healthy women had 187 pregnancies. The first sexual activity, frequency of intercourse, and libido were also similar in patients and controls. Twentyfive of 49 (51%) SS patients reported of dyspareunia, compared to only 3% of the controls. Eight of 20 (40%) SS patients were premenopausal and 17 of 29 (58.6%) were postmenopausal. Of the eight premenopausal patients, four had an obvious aetiology of dyspareunia (two had a perineal operation and two had vaginitis) and after appropriate treatment the dyspareunia disappeared. In the remaining four patients, the physical examination was normal and the cytological examination did not show signs of atrophy or inflammation. Vaginal biopsies from symptomatic patients disclosed nonkeratinised stratified squamous epithelia and a mild to moderate perivascular inflammatory lymphocytic infiltration in the underlying stroma.

Mulherin et al. assessed 11 patients with SS and also found that chronic dyspareunia could be the presenting symptom in these patients, preceding sicca symptoms in the eyes or mouth by many years [3]. These findings have been confirmed by other investigators despite the fact that their frequency did not always reach a statistically significant difference with an age-matched control population [4, 5]. Cirpan et al. evaluated 33 women with SS and 67 healthy controls who underwent cytology and colposcopic examination as well as DNA testing for the human papilloma virus [4]. No significant differences were observed between the two groups except for a higher prevalence of dyspareunia and vaginal dryness among patients with SS.

In a study of 58 patients with pSS and 157 controls, gynecological problems and relevant interventions were evaluated using a self-administered questionnaire [6]. Amenorrhea lasting for more than 3 months, menorrhagia/metrorrhagia (54.5% vs. 35.7%, p=0.012), vaginal dryness (52.9% vs. 28.3%, p=0.005), endometriosis (8.5% vs. 2.1%, p=0.03), and surgical intervention for endometriosis (6.3% vs. 0.7%, p=0.009) were found to occur more frequently in patients with SS compared to healthy individuals. In conclusion, women with SS have more gynecological problems compared to the general female population, with dyspareunia and vaginal dryness being the leading symptoms. Amenorrhoea, menorrhagia/metrorrhagia, and endometriosis are also reported to occur in younger patients with SS, but further research is needed in order to confirm these data and establish their underlying mechanisms. Table 24.1 shows the major gynecological problems affecting women with SS.

Fig. 24.1 The classic periorbital rash consistent with neonatal lupus (This figure was kindly provided by Dr. Jill Buyon)

Because the neonatal rash is self-limited, no treatment is required, but topical steroids can be used with caution. In general, the long-term prognosis of children with skin disease is excellent.

The hematologic abnormalities reported in the literature include thrombocytopenia in 10–20% of patients [17] and neutropenia [18]. However, these abnormalities are transient and follow a benign course. Approximately 20–40% of the affected children present with hepatomegaly as a result of congestive heart failure [7, 19]. Asymptomatic elevation of liver enzymes has been observed in 26% [20]. Other rare extracutaneous manifestations reported in children with NLS include learning disabilities [21], anemia [7], and hydrocephalus [22].

Heart involvement is generally the most serious complication of NLS. Fetal clinical manifestations include heart block of various degrees, valve disease, myocarditis, and hydropic changes of the heart. CHB may have the form of first-, second-, or third-degree atrioventricular (AV) block. In complete CHB, the ventricular rate ranges from 30 to 110 beats/min [23]. Fetal heart rates less than 50 beats/min have been associated with fetal hydrops, heart failure, and neonatal death [23, 24]. Progression of CHB has been reported rarely to occur in the postpartum period, despite clearance of the maternal antibodies. This fact confirms that in utero injury to the fetal conduction system is the key pathophsyiological event. However, even if a partial heart block appears to regress after birth, the infant should be followed well into childhood to ensure that conduction disturbances do not emerge from subclinical damage (Fig. 24.2).

Approximately 6% of newborns with CHB may develop dilated cardiomyopathy and congestive heart failure [25, 26]. Most of these patients require cardiac transplantation. CHB has been also reported to be associated with endocardial fibroelastosis [27]. Unconfirmed cardiac manifestations possibly associated with NLS are sinus bradycardia and QT prolongation [28–31]. Rare complications of