Chronic pelvic pain associated with autoimmunity and systemic and peritoneal inflammation and treatment with immune modification

OBJECTIVE: To determine the prevalence of chronic inflammation of the pelvic peritoneum, systemic inflammation and autoimmunity in chronic pelvic pain and to explore the significance of these findings and assess the response to treatment with immune modification. STUDY DESIGN: Prospective, observational clinical studies from 2 centers were performed on 3,238 women presenting with pelvic pain to determine the prevalence of chronic inflammation by biopsy when endometriosis was absent. A second study included 40 women with chronic pelvic pain not resulting from endometriosis; immunologic investigations were carried out and therapy instituted. RESULTS: Chronic inflammation of the peritoneum, while not evident in the absence of pelvic pain, was present in 15.7% of women with chronic pelvic pain. In the second group, 10% had histologic evidence of chronic inflammation, 55% demonstrated evidence of systemic inflammation, and 37.5% were found to have autoimmune disorders. Chronic inflammation of the vagina was found in 42.5% and polycystic ovary syndrome in 22% of those with systemic inflammation. Twelve of the 40 were subsequently treated, with considerable success, with immune-modifying drugs, hydroxychloroquine and methotrexate. CONCLUSION: Chronic pelvic pain is frequently associated with systemic inflammation, including autoimmune diseases. Peritoneal chronic inflammation is sometimes also associated. It is often successfully treated with immune-modifying drugs.     

The expression of cyclooxygenase 2 and inducible nitric oxide synthase indicates no active inflammation in vulvar vestibulitis.

BACKGROUND: Although women with vulvar vestibulitis syndrome have principal symptoms of inflammation such as local erythema and pain in the mucosa around the vaginal introitus, it is not clear if vestibulitis is an inflammatory condition. Cyclooxygenase 2 and inducible nitric oxide synthase are known to be upregulated during inflammation. The aim of the present study was to analyze the expression of these enzymes in the vestibular mucosa in order to evaluate the inflammatory activity in the tissue. METHODS: Ten women fulfilling Friedrich's criteria of vulvar vestibulitis syndrome and ten control subjects were included in the study. Punch biopsies were obtained from the vestibular mucosa for analysis of cyclooxygenas 2 and inducible nitric oxide synthase, using indirect immunohistochemistry and Western dot-blot analyses. RESULTS: Both methods used showed low expression of cyclooxygenas 2 and inducible nitric oxide synthase in the vestibular mucosa of all women. There was no difference observed between the groups. CONCLUSIONS: There is a low expression of the inflammatory markers cyclooxygenas 2 and inducible nitric oxide synthase in the vestibular mucosa of women with vulvar vestibulitis syndrome as well as in healthy control subjects. The results indicate no active inflammation present and imply that topical corticosteroids in the treatment of vulvar vestibulitis are unfounded.     

Medical and surgical management of chronic pelvic pain

Chronic pelvic pain (CPP) affects over 1 million women in the UK, with subsequent impact on ability to work and the economy. It is often debilitating and can be difficult to treat. Gynaecologists have traditionally focussed on the organ-specific approach to the diagnosis of pain. Endometriosis is common as is chronic pelvic inflammatory disease and adenomyosis. Some causes are non-gynaecological such as irritable bowel syndrome and interstitial cystitis. However, as many as 55% of women presenting with CPP will have no obvious underlying pathology following completion of all investigations.This review focuses on the appropriate investigations, diagnosis and management of women with identified pathological causes of pelvic pain. It also considers the holistic approach to the management of the woman with chronic pelvic pain syndrome. Careful prescribing, assessment, interaction and support from a multidisciplinary team are required.     

Chronic inflammation of the vagina: treatment and relationship to autoimmunity

OBJECTIVE: To investigate noninfective, symptomatic, chronic inflammation (CI) of the vaginal mucosa to determine its prevalence and immunologic basis and to initiate an immunologic approach to treatment and assess the response. STUDY DESIGN: A prospective, observational, clinical study of 55 women with dyspareunia and/or discharge of vaginal mucosal origin. Vaginal biopsies and immune investigations were carried out. Treatment was instituted utilizing immune-modifying agents. RESULTS: The prevalence of CI of the vagina in symptom-free women was 0-4.3% and in the symptomatic group, 89%. Systemic immune activation was demonstrated in 43 of the 55, with 21 suffering from an autoimmune disease or a condition in which immune activation plays a part, including endometriosis in 20. Thirty-one were treated; intravaginal hydrocortisone acetate 10% foam was given in 24, giving full relief in 14 and inadequate relief in 10. Hydroxychloroquine, an immune-modifying, antirheumatic drug, was added and largely gave relief in these 10. Hydroxychloroquine alone was given in 4 and was effective in 3. Overall, immune-modifying drugs were successful in 97%. CONCLUSION: CI of the vaginal mucosa stems from local immune activation and is generally associated with evidence of other immune abnormalities, including autoimmune diseases and disorders in which immune activation play a part, including endometriosis. It can be successfully treated by immune modification.     

Laparoscopic findings, management, histopathology, and outcome of 25 women with cyclic leg pain

STUDY OBJECTIVE: To determine pelvic findings, histopathology, and clinical outcome in women with chronic pelvic pain and cyclic sciatica-like pain after laparoscopic surgery. DESIGN: Retrospective cohort study (Canadian Task Force classification II-2). SETTING: University-affiliated teaching hospital. PATIENTS: Of 2115 women with chronic pelvic pain, 25 also complained of cyclic pain radiating to the leg (right 15, left 9, both 1), pain over buttocks, and paresthesia of the thighs and/or knees, exacerbated during menses. INTERVENTION: Laparoscopy. MEASUREMENTS AND MAIN RESULTS: Laparoscopic findings were endometriosis nodules (5 patients), peritoneal pockets and/or peritoneal endometriosis (19), and inflammatory peritoneum (1). Associated pelvic endometriosis was identified and confirmed in 17 women (68%). No additional lesions other than peritoneal pockets were found in eight (32%). All nodules, peritoneal pockets, and abnormal peritoneum were excised with a combination of hydrodissection and carbon dioxide laser. Peritoneum over resultant deep defects was sutured with one to three 2-0 nonabsorbable sutures in accordance with the surgeon's practice and experience. Endometriosis was confirmed in all five nodules, and histology of excised pockets showed endometriosis in nine (60.0%), endosalpingiosis in two (13.3%), chronic inflammation in one (6.7%), and normal tissue in three (20.0%). After laparoscopic excision sciatic symptoms were eliminated in 19, markedly improved in 4, remained the same in 2, and recurred in 3 patients after 2 years. CONCLUSION: Cyclic leg signs and symptoms were associated with pelvic peritoneal pockets, endometriosis nodules, or surface endometriosis of the posterolateral pelvic peritoneum. We hypothesize that the pain associated with these lesions is more likely referred pain originating from pelvic peritoneum than direct irritation of the lumbosacral plexus of the sciatic nerve.     

Mast cells in chronic inflammation,pelvic pain and depression in women

Inflammatory and neuroinflammatory processes are increasingly recognized as critical pathophysiologic steps in the development of multiple chronic diseases and in the etiology of persistent pain and depression. Mast cells are immune cells now viewed as cellular sensors in inflammation and immunity. When stimulated, mast cells release an array of mediators to orchestrate an inflammatory response. These mediators can directly initiate tissue responses on resident cells, and may also regulate the activity of other immune cells, including central microglia. New evidence supports the involvement of peripheral and central mast cells in the development of pain processes as well as in the transition from acute, to chronic and neuropathic pain. That behavioral and endocrine states can increase the number and activation of peripheral and brain mast cells suggests that mast cells represent the immune cells that peripherally and centrally coordinate inflammatory processes in neuropsychiatric diseases such as depression and anxiety which are associated with chronic pelvic pain. Given that increasing evidence supports the activated mast cell as a director of common inflammatory pathways/mechanisms contributing to chronic and neuropathic pelvic pain and comorbid neuropsychiatric diseases, mast cells may be considered a viable target for the multifactorial management of both pain and depression.     

The role of laparoscopy in the management of pelvic pain in women of reproductive age

Objective: To review the diagnostic and therapeutic roles of laparoscopy in women of reproductive age with acute and chronic pelvic pain.Data Identification: Studies relating to the use of laparoscopy in women with acute and chronic pelvic pain were identified through the literature and MEDLINE searches.Conclusion(s): Laparoscopy has an important place in the management of conditions that cause acute pelvic pain in women of reproductive age, including ectopic pregnancy, pelvic inflammatory disease, tubo-ovarian abscess, and adnexal torsion. The procedure frequently facilitates the diagnosis and provides the necessary access for surgical treatment. Prompt diagnosis and effective management prevent complications and help preserve fertility. The role of laparoscopy in women with chronic pelvic pain is more controversial and limited, but abnormal laparoscopic findings are detected in approximately 60% of those who have undergone a multidisciplinary investigation and received a tentative clinical diagnosis. The access provided by laparoscopy permits the effective surgical treatment of many of the conditions encountered, including endometriosis, pelvic adhesions, ovarian lesions, and symptomatic uterine retroversion.     

Comparative measurement of pelvic floor pain sensitivity in chronic pelvic pain

OBJECTIVE: Women with pelvic pain conditions exhibit enhanced somatic pain sensitivity at extragenital sites. Whether comparable differences exist for pelvic floor or vaginal pain sensitivity is unknown. The present study was undertaken to estimate pelvic floor and vaginal pressure-pain detection thresholds both in women with pelvic pain and healthy women. METHODS: We conducted a cross-sectional study of pelvic floor and vaginal pain detection thresholds comparing 14 women with chronic pelvic pain to 30 healthy women without this condition. Using a prototype vaginal pressure algometer, we recorded continuous ascending pressure and determined each subject's pressure-pain threshold at each of eight paired pelvic floor sites and two adjacent vaginal sites. RESULTS: Mean pain detection thresholds for all 10 sites were significantly lower in women with pelvic pain compared with healthy controls (at right iliococcygeus, controls 1.73+/-0.60 kg/cm(2) compared with women 0.96+/-0.38 kg/cm(2), P<.001, other sites similar), and remained so after controlling for differences in patient age and menopausal status. Pelvic floor and vaginal site pain detection thresholds had moderate-to-strong correlations with each other (r=0.62-0.91). CONCLUSION: Chronic pelvic pain is associated with enhanced pelvic floor and vaginal pressure-pain sensitivity. LEVEL OF EVIDENCE: II.     

盆腔炎性疾病与盆腔痛

盆腔炎性疾病严重影响广大女性的生殖健康,若不能及时治疗,易引起后遗病变。慢性盆腔痛是盆腔炎性疾病所引起的后遗病变之一。诊断性腹腔镜是目前评价慢性盆腔痛原因的有效方法,可在进行诊断同时对盆腔病变进行手术治疗。此外,口服药物、理疗等方法也可有效缓解盆腔疼痛。     

Medical and surgical management of chronic pelvic pain

Chronic pelvic pain is common and is estimated to affect over one million women in the UK. It may be a symptom of a number of different conditions and is often multifactorial in nature, caused by a combination of physical, psychological and social factors. For many women, a primary cause cannot be identified. This can make both diagnosis and management difficult. Gynaecological causes of chronic pelvic pain include endometriosis, chronic pelvic inflammatory disease and adhesions. The gynaecologist must also consider non-gynaecological causes of pain related to the gastrointestinal, urinary, neurological, musculoskeletal and psychological systems if satisfactory management of the woman's pain is to be achieved.This review addresses the approach to diagnosis and management of women presenting with chronic pelvic pain. It details specific disease management but also seeks to encourage a holistic approach to all women with chronic pelvic pain, whether or not a primary diagnosis is established.     

Medical and surgical management of chronic pelvic pain

Chronic pelvic pain is common and is estimated to affect over one million women in the UK. It may be a symptom of a number of different conditions and is often multifactorial in nature, caused by a combination of physical, psychological and social factors. For many women, a primary cause cannot be identified. This can make both diagnosis and management difficult. Gynaecological causes of chronic pelvic pain include endometriosis, chronic pelvic inflammatory disease and adhesions. The gynaecologist must also consider non-gynaecological causes of pain related to the gastrointestinal, urinary, neurological, musculoskeletal and psychological systems if satisfactory management of the woman's pain is to be achieved.This review addresses the approach to diagnosis and management of women presenting with chronic pelvic pain. It details specific disease management but also seeks to encourage a holistic approach to all women with chronic pelvic pain, whether or not a primary diagnosis is established.     

Cesarean section as a cause of chronic pelvic pain.

OBJECTIVE: To determine if the history of cesarean section was associated with chronic pelvic pain, independent of the presence of other conditions such as pelvic adhesions, endometriosis, sequelae of pelvic inflammatory disease, leiomyoma and pelvic varices. METHODS: Retrospective case-control study conducted on 199 patients consecutively admitted from January 1998 to January 2000, 116 of them submitted to laparoscopy for the diagnosis of chronic pelvic pain and 83 asymptomatic patients submitted to tubal ligation by laparoscopy. A logistic regression analysis was used to verify the association between chronic pelvic pain and the history of previous cesarean section. RESULTS: In women with chronic pelvic pain, a history of cesarean section was observed in 67.2% of cases, adhesions in 51.7%, endometriosis in 33.6%, sequelae of pelvic inflammatory disease in 31.9%, leiomyoma in 6.9% and pelvic varices in 11.2%. In asymptomatic women, a history of cesarean section was observed in 38.5%, adhesions in 24.1%, endometriosis in 9.6%, sequelae of pelvic inflammatory disease in 4.8%, leiomyoma in 7.2% and pelvic varices in 3.6%. In a logistic model, chronic pelvic pain was associated with a history of cesarean section (O.R.=3.7), as well as with endometriosis (O.R.=8.5), sequelae of pelvic inflammatory disease (O.R.=10.5). CONCLUSIONS: In the present study cesarean section was associated with chronic pelvic pain. This fact may be the cause of a public health problem in the coming years, due to the raised rates of cesarean section in Brazilian women.     

Vaginal apex resection: a treatment option for vaginal apex pain

OBJECTIVE: Vaginal apex pain is a subset of chronic pelvic pain commonly treated with surgical excision of the vaginal apex. Our objective was to estimate long-term postoperative pain levels, recovery time, and return to sexual function in women who have undergone vaginal apex repair for chronic vaginal apex pain. METHODS: Since 1995, 45 women have undergone vaginal apex repair at our institution. All were asked to complete a questionnaire describing pain levels, sexual function, daily activities, ability to work, and medical therapy before and after surgical repair of the vaginal apex. Demographic background, previous medical history, and surgical history were abstracted from the medical records. Fisher exact and Wilcoxon rank sum tests were used to determine associations among baseline characteristics and various outcomes. McNemar chi(2) testing was use to compare before and after pain levels. RESULTS: Twenty-seven women constituted the study sample and were available for evaluation before and after vaginal apex repair. Sixty-seven percent of respondents experienced resolution of pelvic pain after vaginal apex repair for a median of 20 months. The number of women experiencing pain with daily activities decreased from 92% before vaginal apex repair to 41% after vaginal apex repair, and 30% reported sexual activity without dyspareunia after vaginal apex repair (P = .004). Sixty-one percent of women returned to work after vaginal apex repair. Most patients required continued medical therapy after vaginal apex repair. CONCLUSION: Vaginal apex repair improves general levels of pelvic pain in some patients diagnosed with vaginal apex pain. Pain relief after vaginal apex repair is temporary, and women are likely to need continued medical therapy.     

Endometriosis and Mechanisms of Pelvic Pain

Endometriosis remains an enigmatic disorder in that the cause, the natural history, and the precise mechanisms by which it causes pain are not completely understood. The pain symptoms most commonly attributed to endometriosis are dysmenorrhea, dyspareunia, and chronic pelvic pain. Pain may be due to nociceptive, inflammatory, or neuropathic mechanisms, and there is evidence that all 3 of these mechanisms are relevant to endometriosis-associated pelvic pain. It is proposed that the clinically observed inconsistencies of the relationships of endometriosis severity and the presence or severity of pain are likely due to variable roles of different pain mechanisms in endometriosis. A better understanding of the roles of nociceptive, inflammatory, and neuropathic pain in endometriosis is likely to improve the treatment of women with endometriosis-associated pelvic pain.     

子宫切除术后15年并发阴道残端子宫内膜异位症一例

子宫内膜异位症（endometriosis,EMs）是女性常见的慢性炎症性疾病,指子宫内膜的腺体和间质出现在子宫腔以外的部位,常见于卵巢、盆腔腹膜表面或其他盆腔组织。报告1例子宫肌瘤行子宫切除术后15年发生阴道残端子宫内膜异位症的病例,患者48岁,因不规则阴道出血伴腹痛3年、加重2个月就诊,全腹增强CT发现左侧髂血管旁不规则软组织,多学科会诊后拟诊断为阴道残端病变行腹腔镜探查术,根据术中所见行左侧阴道残端肿物切除术,切除组织经石蜡切片病理检查证实为阴道残端EMs。结合此病例讨论并复习相关文献,为临床上子宫切除术后出现阴道出血病例提供了诊疗思路,旨在提高临床医生对手术后并发阴道残端EMs的认识。     

Bladder pain syndrome/interstitial cystitis: a reappraisal for the clinician

Bladder pain syndrome--formally known as interstitial cystitis--is a chronic bladder disorder characterized by pelvic pain and urinary irritability symptoms. The physiopathology is still unclear but is thought to involve bladder mucosal injury, inflammation and neurologic dysfunction. It is hard to diagnose this entity due to symptoms that are common to several other pathologies such as chronic pelvic pain, endometriosis, overactive bladder, urinary tract infection, and vulvodynia, and due to the lack of specific findings. A combination of history, physical examination, and diagnostic tools helps the establishment of the diagnosis by ruling out other similar pathologies. Treatment is multimodal and combines behavioral changes, drugs administered orally or intravesically and even surgery for refractory cases.     

Acute chlamydial salpingitis with ascites and adnexal mass simulating a malignant neoplasm.

Chlamydia trachomatis is a well-known cause of acute and chronic salpingitis, accounting for approximately half of all cases of pelvic inflammatory disease. Typically, patients with acute chlamydial salpingitis present with acute lower abdominal pain, tenderness on bimanual pelvic examination, or vaginal discharge. We describe a case of acute chlamydial salpingitis with marked ascites and an adnexal mass that simulated a malignant neoplasm. Microscopically, a severe lymphofollicular salpingitis and a marked lymphofollicular hyperplasia of the omentum and retroperitoneal lymph nodes were found. Chlamydial inclusions in the fallopian tube epithelium were demonstrated by immunohistochemistry using a mouse monoclonal antibody to a genus-specific outer membrane lipoprotein. Chlamydial infection may cause marked ascites and a palpable adenexal mass and should be considered whenever marked chronic inflammation with a lymphofollicular hyperplasia involves the fallopian tube or other female genital tract sites.     

脑源性神经营养因子在子宫内膜异位症及其相关疼痛中的研究进展

子宫内膜异位症(EMs)是一种常见且影响广大育龄期女性的妇科良性疾病,该病的早期诊断和治疗是目前临床工作中亟需解决的难题.EMs有3种公认的病理类型,分别是腹膜型、卵巢型及深部浸润型.然而不论哪种病理类型,疼痛都是EMs患者最为突出的临床表现,包括经期腹痛、慢性盆腔痛及性交痛等不适,严重影响女性的身心健康,并增加经济负...     

Effectiveness of inpatient and outpatient treatment strategies for women with pelvic inflammatory disease: results from the Pelvic Inflammatory Disease Evaluation and Clinical Health (PEACH) Randomized Trial

OBJECTIVE: Pelvic inflammatory disease (PID) is a common and morbid intraperitoneal infection. Although most women with pelvic inflammatory disease are treated as outpatients, the effectiveness of this strategy remains unproven. STUDY DESIGN: We enrolled 831 women with clinical signs and symptoms of mild-to-moderate pelvic inflammatory disease into a multicenter randomized clinical trial of inpatient treatment initiated by intravenous cefoxitin and doxycycline versus outpatient treatment that consisted of a single intramuscular injection of cefoxitin and oral doxycycline. Long-term outcomes were pregnancy rate, time to pregnancy, recurrence of pelvic inflammatory disease, chronic pelvic pain, and ectopic pregnancy. RESULTS: Short-term clinical and microbiologic improvement were similar between women randomized to the inpatient and outpatient groups. After a mean follow-up period of 35 months, pregnancy rates were nearly equal (42.0% for outpatients and 41.7% for inpatients). There were also no statistically significant differences between outpatient and inpatient groups in the outcome of time to pregnancy or in the proportion of women with pelvic inflammatory disease recurrence, chronic pelvic pain, or ectopic pregnancy. CONCLUSION: Among women with mild-to-moderate pelvic inflammatory disease, there was no difference in reproductive outcomes between women randomized to inpatient treatment and those randomized to outpatient treatment.     

Laparoscopic Posthysterectomy Vaginal Vault Excision for Chronic Pelvic Pain and Deep Dyspareunia

Study ObjectiveTo evaluate the outcome of posthysterectomy laparoscopic vaginal vault excision and its long-term effects on chronic pelvic pain, dyspareunia, quality of life, and patient satisfaction.Materials and MethodsThis is a retrospective cohort study (Canadian task force classification II–3) incorporating case note review and a postal questionnaire. It describes 22 consecutive patients who underwent laparoscopic vaginal vault excision for posthysterectomy dyspareunia and chronic pelvic pain. At laparoscopy, full thickness vaginal vault was excised along with scar tissue or any cyst. The vaginal cuff was closed laparoscopically. The patients were sent a validated questionnaire to assess their pain scores, general health, quality of life, and satisfaction with the surgery. The mean interval from vaginal vault excision and to questionnaire distribution was 1.8 years. The statistical analysis was performed with SPSS 15.ResultsThe mean age of the women was 40 years. All women had vaginal vault tenderness on examination and underwent laparoscopic vaginal vault excision. The only intraoperative complication was 1 puncture injury of the bladder, which was produced by 10-Veres needle during manipulation. A single or a combination of additional procedures was performed at the same time. The patient satisfaction questionnaires were received from 16 (72.7%) women. Of the 16 (72.7%) respondents, 13 (81.25%) confirmed improvement in dyspareunia. The mean pain scores decreased, and quality of life and general health improved significantly after vaginal vault excision (p <.05, t test).ConclusionLaparoscopic vaginal apex excision is a safe and effective management option after carefully excluding other causes of deep dyspareunia and chronic pelvic pain. It also provides an opportunity to detect and surgically excise previously undiagnosed endometriosis and other disease.