and Filippo Murina2
(1)
Center of Gynecology and Medical Sexology, San Raffaele Resnati Hospital, Milan, Italy
(2)
Lower Genital Tract Disease Unit V. Buzzi Hospital, University of Milan, Milan, Italy
Case histories may help students and learning physicians to focus on the real complaint of vulvar pain and associated comorbidities, sexual and urogenital, with their impact on the real life of patients. They will illustrate how sexual pain can affect a woman’s life and how an early diagnosis can definitely change the woman’s and couple’s sexual experience for the better while curing a disturbing vulvar pain and associated symptoms. All names in the following case stories have been changed. Readers should focus on what should be listened to and selected as critical info from the narrative of the problem. Symptoms should be evaluated with a pathophysiologic reading of predisposing, precipitating, and perpetuating factors, to get the proper diagnosis and a well-tailored effective treatment (Graziottin and Murina 2011; Graziottin and Gambini 2016).
Case 1
I’ve always been shy and reserved, so different from my schoolmates. I had pain from the very first intercourse. Sex has always caused problems to me. I hoped it would have gone better over time. I tried many times, but pain became more and more excruciating. I had tears every time we tried. When I tried to make love, I felt that my vagina was tight and dry. I tried but my body did not respond. Sometimes I also had a sense of burning pain at the entrance of the vagina. He immediately stopped making love for fear of hurting me. No, I do not think we ever had a complete intercourse. Maybe I’m still virgin, I do not know. Now I cannot get aroused any more, not even a little bit, because I’m afraid of pain. Even my sexual desire has gone away. My family physician prescribed the contraceptive pill for me, suggesting that perhaps I was afraid of getting pregnant and did not relax. The pain didn’t change. It’s 3 years now that we do nothing. We have lost any type of intimacy, for fear that he gets aroused and we try again to have sex. We are very close, and he is so patient with me! I feel guilty for disappointing him and being unable to do what is so easy and funny for the majority of women. Now I’m here because we would love to have a child….
Alicia, 33 years of age
12.1 Clinical Evaluation
Alicia’s wording suggests a lifelong vaginismus with an unconsummated marriage, acquired loss of desire, arousal difficulties, and significant distress. The burning pain suggests comorbidity with lifelong vulvar vestibulitis/provoked vestibulodynia (VVS/PVD).
When asked, Alicia reports that:
- (a)
Since her first period, she could not use tampons during menstruation, because she could not insert them: “I felt I had a wall there.”
- (b)
Since she was a girl, she was afraid of feeling pain at intercourse, in spite of longing for a closer intimacy with her boyfriend. Probably something she heard about “how painful is to stay with a man,” in a conversation between her mother and her aunt, could have increased her fears. Interestingly, the mother said she had the same problem, when Laura dares to ask her about “problems with dad” after the first therapeutic sessions.
- (c)
She was not abused or harassed.
- (d)
She received a strict catholic education, where sex was not considered appropriate for a girl until marriage.
These observations suggest that she could have lifelong vaginismus, severe enough to prevent intercourse, leading to the non-consummation of her marriage and a hyperactive pelvic floor. Attempts of penetration may have caused microabrasions of the mucosa at the entrance of the vagina leading to VVS/PVD, sufficient to worsen the vaginismic attitude and further predispose her to lifelong introital dyspareunia, so frightening that she gave up any intimacy (Graziottin 2006; Graziottin and Murina 2011; Graziottin and Gambini 2016).
12.2 Clinical Examination
Her body language indicated a systemic anxiety and fear of being examined. She could not relax in spite of her physician’s reassuring manner. A third-degree vaginismus (according to John Lamont classification) was diagnosed. Exquisite pain was elicited at 5 and 7 o’clock (when viewing the vaginal opening as a clock face with the anus at 6 o’clock), between the hymen remnants and the introitus vaginae (the opening of the vagina), when using gently a swab to design the “pain map” in the vestibular area. With the gentle examining gloved hand, tender points were elicited where the muscle levator ani inserts at the spine on both sides, with more intense pain on the left side. This “asymmetry” is frequent (72 % in the personal series – unpublished data). It may reflect postural problems and be worsened by the habit of keeping the legs tightly crossed most of the time. Postural issues and correct position of legs in the seated position should be addressed in the therapeutic plan.
12.3 Diagnosis
Lifelong vaginismus and dyspareunia, with unconsummated marriage, comorbid with vulvar vestibulitis/provoked vestibulodynia and a tightened, myalgic pelvic floor (Graziottin 2006; Graziottin and Murina 2011). Lifelong vaginismus could be the predisposing factor to dyspareunia. Both vaginismus and VVS/PVD have been discussed in the chapter on the pathophysiology of vulvar pain. Acquired genital arousal disorder and acquired loss of sexual desire were the comorbid female sexual disorders (FSD). According to the DSM V, currently the diagnosis would be genito-pelvic pain penetration disorder (GPPPD), comorbid with other FSD (Graziottin and Gambini 2016).
12.4 Comment
Comorbidity between different FSDs and between FSD and medical conditions is frequent in women. A careful clinical history is essential to identify predisposing, precipitating, and maintaining/perpetuating factors, which may be biological, psychosexual, and/or relational. In this case, the natural history of the current complaint had vaginismus as a likely predisposing factor, while intercourse was the precipitating one. Maintaining factors were biological (vulvar vestibulitis/provoked vestibulodynia), psychosexual (systemic fear and anxiety about pain), and relational: a shared fear of the natural “aggressiveness” intrinsic to penetration (Graziottin 2006; Graziottin and Murina 2011; Graziottin and Gambini 2016). Acquired desire and arousal disorders increased the vulnerability of the introital mucosa to the mechanical trauma, due to the lack of lubrication in response to sexual stimulation. The partner respectful attitude was positive in maintaining the emotional intimacy between the partners. However, this a bit “passive” behavior contributed to the acceptance of a nonsexual relationship for years, until the desire of children becomes prominent.
Case 2
The first problem was a cystitis, with blood in the urine, 4 years ago, after my first intercourse at 19. I was treated with antibiotics. Things seemed to go better but then I had new cystitis, three-four times a year, always 1 or 2 days after the intercourse, and recurrent Candida vaginitis. Now I have continuous pain in the bladder, that gets worse after intercourse, and burning pain at the entrance of the vagina. Urine exams showed Escherichia coli in the first episodes. Now most of the time the urine exam is negative and I still have bladder symptoms! I consulted seven physicians: urologists keep on prescribing antibiotics, gynaecologists give me vaginal creams and antimycotic, but none seems to understand what’s going wrong… I feel helpless.
Paula, 23 years of age
12.5 Clinical Evaluation
Paula’s history is typical: her symptoms started with recurrent cystitis, with antibiotics triggering Candida infections, leading to inflammation of the vestibular region, consequent introital dyspareunia, and symptoms of urinary urgency/frequency, pelvic pain, and nocturia, currently in the absence of bacterial infection or any other identifiable pathology.
12.6 Clinical Examination
Relevant examination findings are tenderness of the urethra and bladder base and tenderness to pressure with a cotton swab at the vestibule. Hypertonic/hyperactive pelvic floor dysfunction with muscle tenderness, myofascial pain, and tender points is also present.
12.7 Diagnosis
Painful bladder syndrome, with a history of recurrent (postcoital) cystitis, comorbid with vestibulodynia and recurrent Candida vaginitis, introital dyspareunia, and hyperactive myalgic pelvic floor.
12.8 Comment
Interstitial cystitis/painful bladder syndrome (IC/PBS) is a chronic bladder disorder characterized by inflammation of the bladder wall, pelvic pain, and irritative voiding symptoms. The symptoms of IC/PBS can overlap with such conditions as vestibulodynia, recurrent urinary tract infection, and chronic pelvic pain. IC/BPS and vulvodynia are frequently seen as comorbid to each other (in about 25 % of patients according to Reed et al. 2012 up to 60 % according to Salonia et al. 2013). Hypertonic/hyperactive pelvic floor dysfunction (HTPFD) is commonly seen in both conditions. It is still unclear if HTPFD results from chronic pain of IC/BPS and vulvodynia or if it is a precipitating factor or both.
An interesting survey on women affected with IC/PBS and controls (Peters et al. 2007) well indicates that affected women are significantly more likely to have suffered from lifelong vaginismus, lifelong fear of pain at intercourse, and lifelong introital dyspareunia than controls. This supports the hypothesis that a lifelong hyperactive pelvic floor, associated with vaginismus and/or lifelong dyspareunia, can be a “biomechanical” predisposing factor to recurrent postcoital cystitis (which are complained of 24–72 h after intercourse). When unaddressed, the persistent bladder inflammation caused by the intercourse and associated pathogenic biofilms of Escherichia coli (or other pathogens) contributes to PBS (Graziottin and Zanello 2015). If unaddressed, it can become as well a perpetuating factor for both the bladder and vestibular symptoms. This contributes to maintain the pelvic chronic inflammations while increasing the neuroinflammation and the shifting of pain from nociceptive to neuropathic, a real disease per se.
Neuropathic vestibular pain can include peripheral and central nervous system components. In the vestibulum, noxious insults trigger inflammatory mediators, neurotransmitters, and nerve growth factor activity, which can result in nociceptor sensitization or ectopic excitability of afferent neurons. This results in innocuous stimuli at the site of inflammation, such as light touch, warm, or cool temperatures, being perceived as painful (allodynia), and stimuli that usually are felt as uncomfortable or slightly painful, such as a pinprick, becoming extremely painful (hyperalgesia) central neurons.
Peripheral vestibular sensitization characteristically occurs after peripheral inflammation and comprises a reduction in threshold and an increase in the excitability of the peripheral terminals of nociceptors in response to sensitizing inflammatory mediators.
Nerve grow factor (NGF) appears to be a key molecule in the orchestration (also) of vestibular/vulvar peripheral inflammation. Inflammation-driven release of cytokines from immune cells provokes hyperalgesia through stimulation and production of other proinflammatory agents (Schaible 2015). Peripheral mast cell activation at vestibular level is generally considered proinflammatory and pro-nociceptive.
Physical, chemical, and mechanical stimuli activate local mast cells, causing degranulation and secretion of mediators that have been found to sensitize and induce the proliferation of C-afferent nerve fibers. These nerve fibers release inflammatory mediators, including NGF, which increase the proliferation and degranulation of mast cells, causing hyperesthesia, and enhance the inflammatory response. Mast cells show particular complexity in relation to the inflammatory response, and their density in inflamed tissue changes over time. In tissue where there is an acute inflammatory response, the concentration of mast cells is high (Graziottin 2009; Graziottin et al. 2013, 2014; Chatterjea and Martinov 2015). As the inflammation becomes more chronic, the number of mast cells decreases, and there is a parallel increase in neuronal proliferation. At this stage of the inflammatory process, neuropathic symptoms became prominent, but mast cell reactivation can occur at any time, with an exacerbation of symptoms or acceleration of neurogenic inflammatory processes (Xanthos et al. 2011).
HTPFD can exacerbate symptoms and can itself worsen in response to IC/BPS or vulvodynia flares. A multidisciplinary approach, including referrals to a well-trained physiotherapist or midwife to retraining the pelvic floor, is essential (Graziottin and Gambini 2016). A well-tuned teamwork is vital to address the biological, sexual, and psychosocial factors that contribute to the persistence of vulvar and bladder inflammation that keep on worsening pain in vulvodynia and PBS/IC.
Key Points
Every healthcare provider involved in the diagnosis and cure of vulvar pain in the lifespan should be familiar with the concepts that:
- 1.
Acute vulvar pain can evolve to chronic and neuropathic if etiological factors are not timely addressed, particularly in the subset of women with immune-allergic inadequacies/vulnerabilities.
- 2.
Chronic tissue inflammation mediated by the hyperactivated mast cells and other inflammatory cells is the first etiologic factor in vulvar pain.
- 3.
It triggers neuroinflammation with progressive central sensitization and neurogenic neuroinflammation.
- 4.
This changes over time the characteristics of pain perception and reporting by women complaining of vestibular/vulvar pain; of associated introital dyspareunia, either acquired or lifelong; and of medical and sexual comorbidities.
- 5.
Attention to the hyperactivity of the pelvic floor, so frequently associated with vulvar pain, is a mandatory part of the clinical examination and treatment plan.
Cases 3 and 4
I loved making love. I had a satisfying sexual life since my first intercourse, at age 16. I do not want to catch diseases, so I had always used condoms as a protection against sexually transmitted infections (STI) and as contraceptive. I never had STI. My last gynaecological examination was performed 3 years ago, with a normal record and normal pap-smear. Everything was perfect. Then, 2 years ago something started to change. Sometimes I had pain in some positions when penetration was deeper. So I avoided them. Pain got really worse in the last year. Now I have a worsening acute pain during intercourse at deep penetration in every position. Sometimes it is like a stabbing pain. I have to stop in tears. It’s a nightmare! Yes, periods were progressively more painful since my adolescence. They are now so debilitating, that I have to take 2 days off work to stay home because of my ‘cramping’ periods. And my boy-friend cannot understand why I turned to be ‘sex-avoidant,’ whilst I was so fond of making love with him before!.
Diana, 26 years of age
I detest having periods! They are a curse! Every months I have 2 days of pain, I cannot go to school, meet my friends, do anything. I’m just lying in the bed ingurgitating pain killers until pain goes down a bit. Last year I had my first intercourse. At that time I had little pain at the entrance of the vagina and an horrible pain deep in the vagina. Now I have pain everywhere: at the entrance and deep! My gynaecologist says that I have both vulvodynia and endometriosis, located in the vaginal wall between the vagina and the rectum. He showed me the picture on the atlas and showed that endometriosis invades the “utero-sacral” ligaments that connect the uterus to the sacrum. This is why intercourse is so painful. He says I should do a complex treatment for vulvodynia and be operated for the endometriosis, but I’m very afraid… Why am I so unfortunate?!.
Claudia, 21 years of age
12.9 Clinical Evaluation
Diana’s and Claudia’s wording suggests endometriosis. Two leading suggestive symptoms are the invalidating and worsening pain during periods and coital pain deep in the vagina, suggesting endometriosis of the uterosacral ligaments and/or in the Douglas pouch, in the posterior fornix, or in the rectovaginal septum. Claudia developed vestibulodynia as well: the comorbidity between the two pathologies induces clinicians to talk about “the evil twins.”
12.10 Clinical Examination
At examination, Diana has a specific tenderness at the location of the uterosacral ligaments, with acutely elicited pain when these ligaments are palpated. An ovarian cyst of apricot size is objectively present on the right side. Claudia reports an acute pain and a stabbing pain, at the gynecological examination, when the uterosacral ligament is investigated. She says she has the very same pain when she has intercourse and when she underwent vaginal ecographic evaluation.
Key Practical Point
To explore well the pelvic area, the gynecologist should put the examining index finger between the cervix and the posterior vaginal wall, in the vaginal posterior fornix, to “put in tension” the uterosacral ligaments. If deep endometriosis is present, this maneuver elicits acute pain, exactly the same the woman experiences during intercourse. Every clinician should gently perform this maneuver when patients complain of deep dyspareunia. This provoked pain can be the first sign of a deep endometriosis – when the islands of ectopic endometrium are still too little (<2 mm of diameter) to be “seen” with ultrasound, MRI, or even laparoscopy. Yet they contain already some 10–20.000 cells which undergo the typical changes across the menstrual cycle and bleed within the tissue during periods, thus causing a very intense tissue inflammatory response and pain (Graziottin and Gambini 2016).
Therefore, women complaining of severe dysmenorrhea and deep dyspareunia should not be told “you have nothing” when exams are not informative, but “the endometriotic spots that cause your pain are still too little to be seen with the current instrumental methods. Yet they are active enough to cause deep inflammation of your pelvic tissues, causing the severe pain you are complaining of. I trust your pain and I’ll do my best to relieve it!”. This is an example of a good and respectful communication aiming at creating a solid trust between the patient and her physician. Then an appropriate medical treatment should be started immediately after the diagnosis: either with a continuous pill (Graziottin 2015a) or a progestogen.
Every specialist in vulvar pain clinics should be aware of the frequent comorbidity between endometriosis, leading to deep dyspareunia, and vulvodynia, causing introital dyspareunia. He/she should look carefully for both conditions as they contribute to increase the “river of inflammation” and the probability of a progressive neuroinflammation (Graziottin et al. 2013, 2014). The brain involvement then translates into a progressive shift to neuropathic pain, sickness behavior, depression, and progressive neurogenic neuroinflammation that can further potentiate the neuropathic pain associated with both conditions (Graziottin et al. 2014).
12.11 Exams
In Diana, the blood sample of the specific marker CA-125 is elevated (56 mU/ml). The ultrasound confirms an ovarian cyst of 5.2 cm in diameter, on the right, suggestive of endometriosis. RM confirms these findings and tiny endometriotic spots deep at the level of the uterosacral ligament. In Claudia, exams are not yet informative.
Key Point
The different exam findings in spite of similar symptoms point out to the need of looking at the “narrative” of a disease, say, its evolution over time that can be different in different people. The moment of the diagnosis is just a photogram in the movie of that disease. This stresses as well the importance of listening carefully to the symptoms’ wording (severe dysmenorrhea and deep dyspareunia), as they are very informative about endometriosis as a leading etiological factor. With a rule of thumb, between symptoms and exams, always trust symptoms first. And try to give a clinical “meaning” to them with a solid pathophysiologic reading of symptoms and comorbidities.
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