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Salpingitis Isthmica Nodosa
Introduction
Salpingitis isthmica nodosa, occasionally referred to as diverticulosis of the fallopian tube, has an incidence of 0.6% to 11% in healthy, fertile women and is strongly associated with both infertility and ectopic pregnancies.[1] The etiology of salpingitis isthmica nodosa is still debated; however, the cause is likely due to an acquired process. The management of salpingitis isthmica nodosa is aimed at restoring and maintaining fertility.[2]
Anatomy
Fallopian tubes typically range from 10 to 14 cm in length and have an external diameter of approximately 1 cm.[3] They are described as having 4 different parts: the fimbriae, infundibulum, ampulla, and isthmus, which connect the fallopian tubes to the uterus.[4] The lumen at the isthmus is relatively small (1-2 mm) and is surrounded by a 3-layered muscular wall. This consists of a middle circular layer sandwiched between inner and outer longitudinal layers.[5] Salpingitis isthmica nodosa causes nodular swelling (up to a few centimeters in diameter) predominantly at the isthmus; however, it can involve all other portions of the fallopian tube.[6] The outer serosa of the nodules are smooth and yellow, grey, or brown in color.[7]
Etiology
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Etiology
Though this condition was first described long ago in 1887 by Chiari, the underlying etiology of salpingitis isthmica nodosa frequently remains unknown. Currently, 3 primary etiologies have been proposed: infection, cellular invasion, and congenital malformations.[8]
The most widely accepted of these states that infection during a woman’s reproductive years triggers a chronic inflammatory process within the fallopian tube. Researchers have demonstrated that females with previous histological signs of salpingitis often have the outer membrane protein of C. trachomatis in the affected fallopian tube and high serum antibody titers, suggesting an association between previous Chlamydia infection and salpingitis isthmica nodosa.[9] Another study demonstrated that 89% of women with salpingitis isthmica nodosa had evidence of inflammation in the affected tube. They concluded that salpingitis isthmica nodosa was either a direct complication of infection during reproductive years or that early infection increases the likelihood of future infections, ultimately leading to salpingitis isthmica nodosa.[10]
The noninflammatory theory states that salpingitis isthmica nodosa results from an overgrowth of the inner layer of the fallopian tube, which eventually invades the mucosal wall.[6] This then results in cyst formation, fibrosis, and hypertrophy of the muscular wall. Some experts have hypothesized that the disease process may be similar to that of adenomyosis, which involves abnormal growth of the endometrium into the myometrial portions of the uterus.[2]
Finally, the congenital theory, originally formulated by von Recklinghausen in 1896, states that the tube-like glands are, in fact, Wolffian rests. This is explained by the fact that the isthmus is the location where the Wolffian and Mullerian ducts cross during development. Other previously suggested etiologies include chronic tubal spasm and neoplasia.[8] However, on balance, the majority of evidence appears to lean towards an acquired cause.[11][12]
Epidemiology
Studies indicate that salpingitis isthmica nodosa's prevalence in healthy, fertile women ranges from 0.6% to 11% [2], with an incidence of 8.7% in women undergoing hysterosalpingography (HSG) for infertility.[13] However, salpingitis isthmica nodosa is considerably more common in the presence of infertility and ectopic pregnancies (2.8% to 57%) and is 9 times more likely to affect females of Jamaican origin than the White race.[14] Salpingitis isthmica nodosa is almost twice as likely to occur in the right fallopian tube compared to the left and presents bilaterally in only 4% of cases.[7]
Histopathology
Macroscopically, salpingitis isthmica nodosa causes nodular thickening of the tunica muscularis. However, diagnosis can only be histologically confirmed by diverticula within a hypertrophic, irregular myosalpinx.[7] Other common histological features include regularly spaced glands lined by normal tubal epithelium. These glands are diverticula, which communicate with the lumen and will likely be dilated.
Often, surrounding fibrous tissue or hypertrophy of smooth muscle is present, and endometrial-type stroma may be noted around the glands. The stromal response is typically minimal, and no significant atypia is usually present. These changes commonly occur in the proximal two-thirds of the fallopian tube. Majmudar suggested a histological classification system grade 1 to 3 based on the depth of the lumen within the myosalpinx.[1]
History and Physical
Unfortunately, no pathognomic symptoms of salpingitis isthmica nodosa have been established, and patients can be completely asymptomatic.[7] Salpingitis isthmica nodosa is most commonly diagnosed in patients with a history of ectopic pregnancies or infertility. However, the presence of this condition does not appear to reduce the number of births compared to females in a control group.[15] The mean age of presentation is 30 to 35 years and is commonly an incidental finding in patients undergoing investigation for infertility or pelvic pain.[2]
Evaluation
HSG is the first-line investigation for infertility and a reliable diagnostic technique for salpingitis isthmica nodosa.[16][17] Salpingitis isthmica nodosa cannot be excluded unless HSG has been performed within the last 12 months.[18] However, advances in imaging, eg, high-resolution ultrasound and 3-dimensional magnetic resonance imaging (MRI), are improving diagnostic accuracy in some cases.[13] Radiologically, salpingitis isthmica nodosa usually produces periluminar globular collections of contrast (diverticula), typically around the isthmic fallopian tube.[19] These collections are usually grouped together over a 1- to 2-cm section of the tube and are rarely deeper than 2 mm but can form an uninterrupted connection with the tubular lumen. When this occurs, flecks of contrast can be seen above and below the lumen.[20] In some cases, salpingitis isthmica nodosa can lead to hydrosalpinx, tubular occlusion, or involve the uterine cornu interstitium.[7]
Laparoscopy of a patient with salpingitis isthmica nodosa will inevitably identify nodular swelling and thickening of the isthmus.[21] This is caused by the hypertrophy and hyperplasia of the mesosalpinx around the diverticula pouches. However, diagnosis can only be made following histological assessment. Simultaneous chromopertubation during laparoscopy will identify the diverticular defects along the tube. In severe cases, the anatomy of the tubes will appear grossly abnormal. However, with diluted methylene blue, subtle repetitive notching within the fallopian tube is seen underneath the serosal layer.
Although laparoscopy remains the gold standard for direct visualization of salpingitis isthmica nodosa, it allows for the assessment of severity and potential surgical intervention. However, with the advancement of AI-assisted imaging in radiology, research is underway to determine whether less invasive imaging modalities could provide similar diagnostic accuracy.
Treatment / Management
Assistive Reproductive Technology
Assistive reproductive technology, mainly in the form of in vitro fertilization (IVF), has become the mainstay of management for salpingitis isthmica nodosa due to its immediacy and minimally invasive nature. The success rates have also improved dramatically over the past decade, with Wade et al demonstrating that by the fifth cycle of IVF, the chance of live birth is 80.1%.[22]
Surgery
Reconstructive proximal surgery, originally described in the 1890s, was the standard treatment for decades and has been shown to yield relatively high pregnancy rates of 34%.[23] It has gradually been superseded with the introduction of microsurgical procedures, which carry fewer surgical risks and have been shown to lead to pregnancy rates as high as 68% within the first 2 years following the procedure.[24] These procedures appear to deliver the best outcomes in females under 37 who undergo bilateral anastomosis. Proximal tubal patency can also be restored using transcervical catheterization, an even less invasive procedure. Although this is associated with lower pregnancy rates, transcervical catheterization is occasionally preferred due to its decreased morbidity, reduced cost, and ability to maintain tubular length.[25] Finally, a salpingectomy is recommended for symptomatic patients where fertility is not an issue.[26](A1)
Gonadotropin-Releasing Hormone Analogues
Gonadotropin-releasing hormone analogs (GnRH-a) have been used as a medical treatment for salpingitis isthmica nodosa. Experts believe that these cause tubular patency by creating a hypoestrogenic environment, which shrinks the underlying pathology, similar to the management of adenomyosis.[27] GnRH-a’s have been suggested as the most appropriate nonsurgical treatment for females with occlusive salpingitis isthmica nodosa with endometriosis.[28]
Differential Diagnosis
Carcinoma
Carcinoma can mimic salpingitis isthmica nodosa due to similar gland placement.[29] However, salpingitis isthmica nodosa has far less of a stromal response and no atypia.
Tubular Endometriosis
Differentiating tubular endometriosis and salpingitis isthmica nodosa with hysterosalpingography can be difficult. However, this can be confirmed histologically by the presence of tubal epithelium lining glands in salpingitis isthmica nodosa.[30]
Prognosis
While salpingitis isthmica nodosa itself does not directly cause mortality, and it dramatically increases a patient’s risk of having an ectopic pregnancy, which has a mortality rate of 2% in the developing world and 0.2% in developed countries.[31] As previously described, the treatment of salpingitis isthmica nodosa is focused on restoring and maintaining fertility (IVF, GnRH-a’s, TCA, and interventional radiology interventions) and has improved significantly over the past couple of decades.[22]
Complications
Ectopic Pregnancies
Salpingitis isthmica nodosa has a 10% incidence in females with ectopic tubular pregnancies.[32] However, this increases to 45.9% when looking specifically at isthmic ectopic pregnancies.[33]
Infertility
Salpingitis isthmica nodosa may be identified during evaluation for tubal etiologies of infertility.[34] Karasick et al found that 8.7% of females undergoing hysterosalpingograms for infertility had salpingitis isthmica nodosa, while Saracoglu et al showed that salpingitis isthmica nodosa was present in 7.4% of infertile women with tubular obstruction.[32][30][32] In women with proximal tubal blockages due to salpingitis isthmica nodosa, tubal cannulation has a failure rate of 93%. Therefore, in vitro fertilization is recommended over tubal cannulation for these patients.[35]
Hydrosalpinx
Hydrosalpinx, dilation of the fallopian tube in the presence of distal obstruction, is a recognized complication of salpingitis isthmica nodosa.[32][26]
Hemoperituneum
A recent case report highlighted a rare instance of spontaneous hemoperitoneum due to ruptured salpingitis isthmica nodosa, emphasizing the importance of considering salpingitis isthmica nodosa in differential diagnoses of acute abdomen in women.[36]
Consultations
Salpingitis isthmica nodosa is most likely to be identified during an HSG or diagnostic laparoscopy with chromopertubation. If salpingitis isthmica nodosa is identified, referral to a reproductive endocrinologist capable of providing IVF or an appropriately skilled surgeon if fallopian tube reconstruction is desired.
Deterrence and Patient Education
Due to the potential inflammatory or postinfection causes of salpingitis isthmica nodosa, early identification and initiation of treatment, or ideally prevention of sexually transmitted diseases, may reduce the risk of developing salpingitis isthmica nodosa and its subsequent complications. This is best achieved through comprehensive education.[37] As Chlamydia is suspected to be the most prevalent cause of salpingitis isthmica nodosa, routine screening in high-risk populations at the time of a Papanicolaou test is warranted.[38][10]
Enhancing Healthcare Team Outcomes
A knowledgeable interdisciplinary team with effective communication is essential for optimizing care for patients with salpingitis isthmica nodosa. Physicians in both primary and secondary care must be well-versed in recognizing this condition to include it in differential diagnoses for infertility and ectopic pregnancy. Radiologists play a crucial role in identifying characteristic findings on hysterosalpingography, while pathologists must be adept at confirming the diagnosis through histological analysis. Accurate identification and early diagnosis depend on seamless collaboration between these specialists, ensuring that patients receive timely and appropriate interventions.
Beyond diagnosis, comprehensive patient care requires strong support from nursing staff and pharmacists. Nurses play a vital role in providing emotional and psychosocial support, helping patients cope with the challenges of infertility and ectopic pregnancies. Meanwhile, pharmacists assist in guiding physicians on appropriate medical management, particularly for nonsurgical candidates, ensuring symptom control and optimizing treatment plans. By fostering interprofessional collaboration, healthcare teams can improve patient-centered care, enhance outcomes, and ensure patient safety through a well-coordinated approach to managing salpingitis isthmica nodosa.
References
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