Update in Vulvodynia: current classification, etiology, diagnosis and management Review article
- Introduction
- Materials and methods
- Results
- Epidemiology
- Etiology
- Clinical history
- Pain Measurement
- Physical examination
- Electrophysiological studies
- Differential Diagnosis
- Medical treatment
- Hygienic measures
- Physiotherapy
- Psychological treatment
- Surgical treatment
- Discussion
- Conclusion
- References
Introduction: Vulvodynia is a complex multifactorial disorder that belongs to the identified like chronic pelvic pain syndrome. It is defined as a chronic vulvar discomfort characterized by burning, stinging or irritation, with the typical characteristics of neuropathic pain. As is known, the management of this condition usually is very difficult.
Objectives: We would like to clarify and update vulvar pain syndromes, their current classification, etiology, diagnosis and the different therapeutic approaches.
Materials and methods: We performed a literature search through the data base "Medline/Pubmed" using the term "vulvodynia", to which we add the terms "etiology", "epidemiology", "diagnosis", "neurophysiological test" and "treatment".
Results: We develop the highlights of vulvodynia: current classification, epidemiology, etiology, diagnosis, electrophysiological studies and the different therapeutic options are commented and analyzed: hygienic measures, local anesthetics in ointment form, topical gabapentin, antidepressants, anticonvulsants, local anesthetics and corticoid infiltrations, physiotherapy and biofeedback, Botox infiltrations, vaginal dilators, psychological and surgical treatment.
Conclusion: First, it must be clear that this is a complex syndrome, which requires an interdisciplinary approach in most cases. Nowadays, we have diagnostic and therapeutic tools that allow us to treat this disabling syndrome in majority of cases; however, more studies are needed to improve de quality of life of these patients.
Key words: Vulvodynia, neuropathic pain, chronic pelvic pain.
Vulvodynia or vulvar pain is a complex entity which is difficult to deal with both for patients, who suffer from it painfully, as well as for professionals, who have to manage it as a real challenge [1]. We are faced with a nosological entity of great clinical importance within chronic pelvic pain syndromes.
In 1976, members of the ISSVD (International Society for the Study of Vulvovaginal Disease) recognized vulvar pain as a unique entity, and called it burning vulvar syndrome. In 1985, the ISSVD renamed this disorder vulvodynia and classified it into two clinically distinctive subsets: dysesthetic vulvodynia and vulvar vestibulitis.
Later, in 1991 the ISSVD defined vulvodynia as "chronic vulvar discomfort characterized by burning, stinging or irritation", along with the typical features of neuropathic pain.
Objective
We would like to clarify and to update vulvar pain syndromes, their classification, etiology, diagnosis and the different therapeutic approaches. It also aims at serving as a guideline to assist professionals involved in the improvement of the quality of life of women suffering from it.
We performed a literature search through the data base "Medline/Pubmed" using the term "vulvodynia", to which we add the terms "etiology", "epidemiology", "diagnosis", "neurophysiological test" and "treatment".
We have found 289 papers. It is a surprise the very few number of articles published talking about vulvodynia in the relation with its high prevalence [6].
A systematic review of one of the different topics about this condition could not be possible because there are so few publications related with one topic, for example, we have just got two relative to the use of gabapentin in vulvar pain.
Then, our idea have been to choose the more representatives papers to get the best profile for better understanding of this condition. In addition, we as well have chose some classic studies in pain for supporting our line of work.
We develop the highlights of the vulvodynia: current classification, epidemiology, etiology, diagnosis, electrophysiological studies and the different therapeutic options are commented and analyzed: hygienic measures, local anesthetics in ointment form, topical gabapentin, antidepressants, anticonvulsants, local anesthetics and corticoid infiltrations, physiotherapy and biofeedback, Botox infiltrations, vaginal dilators, psychological and surgical treatment.
Current Classification (2003) [2]
ISSVD Terminology and Classification of Vulvar Pain A) Vulvar Pain Related to a Specific Disorder 1) Infectious (e.g. candidiasis, herpes, etc.).2) Inflammatory (e.g. lichen planus, etc.). 3) Neoplastic (e.g. Paget's disease, squamous cell carcinoma, etc.).4) Neurological (e.g. postherpetic neuralgia, spinal nerve compression, complications following an episiotomy, elongation of the pudendal nerve after delivery, etc.).B) Vulvodynia 1) Generalized a) Provoked by stimuli (sexual, nonsexual, or both). b) Unprovoked. c) Mixed (provoked and unprovoked). 2) Localized (vestibulodynia, clitorodynia, hemivulvodynia, etc.). a) Provoked by stimuli (sexual, nonsexual or both). b) Unprovoked. c) Mixed (provoked and unprovoked).
In Spain there is no record of the prevalence and incidence of this problem. However, it is a frequent cause for consultation. Patients who suffer from it often turn to family doctors first, then seek help from gynecologists, urologists, dermatologists, neurologists etc. to very often end up at psychiatrists or psychologists. The difficulties of their treatment turn these women into real pilgrims in search of a solution that is rarely found. Therefore, it is understandable that anxiety, depression and sexual dysfunction are entities that are frequently related to this pathology, extremely complicating its management [3,4,5].
In the United States its prevalence has been estimated to reach 15% [6]. In 2003 the results of a study in 4,915 women were published: 16% of respondents had had vulvar pain on contact for at least three months or longer. The pain decreased with increasing age, but the frequency was similar across all age groups. Moreover, a similar prevalence has been reported among white and African American women, but Hispanic women were 80% more likely to experience chronic vulvar pain. Nearly 40% of women chose not to seek treatment and 60% of those who did saw 3 or more doctors. The authors concluded that at least 14 million women in the U.S. may have experienced chronic vulvar pain at some point in their lives [7].
• Candidiasis. Ramírez et al. found that a history of vulvovaginal candidiasis is frequently mentioned by women with vulvodynia, although rates of colonization by Candida in these women are not higher compared with control figures. It seems that sensitization occurs due to contact allergens of yeast [8].
• Dietary factors. Calcium oxalate crystals in the urine cause vulvar burning [9]. • Iatrogenic factors. The multiple use of topical agents: prescriptions, magistral formulas, bubble bath soaps or scented sanitary sprays. Irritation caused by topical medications is more common in the vulva compared with the skin since the stratus corneum of the vulvar mucosa is not as effective as skin acting as a protective barrier [10].
• HPV infection. There is controversy about the role of human papillomavirus. Some studies found histological evidence of its existence [11]. However, other studies have failed to establish a possible etiology. [12]. Prayson et al. found no lesions suggesting HPV infection in samples from women with chronic vulvar pain in their series [13]. Likewise, Morin et al. found no statistically significant association between HPV and vulvodynia [14].
• Psychosexual morbidity. Stress and anxiety affect the perception of pain and its symptoms [15]. There are publications which suggest that vulvodynia is the result of psychological and / or sexual dysfunction, but so far there is no clear evidence which supports it. In a review article, Mascherpa et al. suggest that it is a psychological disorder and recommend a sexual evaluation and psychotherapy to alleviate vulvodynia. [16].
• Central and peripheral sensitization and neurogenic inflammation: sensitization of the CNS and PNS leads to hyperesthesia due to previous trauma and an intraepithelial increase of nerve fiber density among women with vulvodynia occurs [25]. Also, the significant decrease in the expression of estrogen receptors in the vestibular mucosa of women suffering vulvodynia [17] and the relationship with autoimmune diseases such as contact dermatitis, lichen planus, Behcet's syndrome, lupus erythematosus and Sjögren syndrome may be associated with an abnormal inflammatory response due to a decrease in natural killer cells, a reduction in the production of interleukin-1 and low production of IFN a [18]. Likewise, substance P is released. All these are signs of neurogenic inflammation. Furthermore, some experts such as Omoigui [19] propose the hypothesis that vulvodynia could be included in the complex regional pain syndrome (CRPS) since it is similar to other disorders such as interstitial cystitis and fibromyalgia. There is a process called central nervous system sensitization (wind-up) within those CRPS, which leads to increased systemic pain perception and in which there is a gradual increase in the activity of bone marrow cells in the dorsal horn after repetitive activation of afferent C fibers [20]. High frequency of coexistence of vulvodynia and other CRPS has been reported, especially interstitial cystitis [21, 22].
Clinical diagnosis of vulvodynia patients typically presents the following symptoms: It has a similar frequency across all population age groups. The prevalence in white and African American women is equal, but Hispanic women are more likely to experience chronic vulvar pain. They frequently present pain due to superficial dyspareunia and tampon intolerance. The patient may have experienced pain in her first sexual encounter or may have had a period of normal sexual activity before the pain first occurred. There is usually a period of more than 6 months between the onset of symptoms and diagnosis. We will be facing an anxious woman, who is also frightened and frustrated. These women either have sexual phobia or at least reject sex somehow, which turn them into risk factors for sexual dysfunction as well as for vaginismus and vulvar pain syndromes. There may occasionally be constant neuropathic pain in the region of the vulva or in the perineal region. The nature of pain is burning or disturbing and has a great analogy with nerve pain syndromes such as postherpetic neuralgia. Allodynia is not usually present, but could be found. Peri or postmenopausal women with multiple inappropriate use of topical agents prior to diagnosis can be detected using the clinical history. Patients may experience perineal, rectal and urethral discomfort like in pelvic floor myofascial pain syndrome.Clinical history
Pain Measurement
We can measure it with the visual analog scale (VAS), often used just as the DN4 for neuropathic pain. Both are extremely easy to use and very effective to monitor patients" evolution. McGill"s questionnaire is reliable and valid to measure pain as a multidimensional experience, as it measures sensitive, emotional and pain intensity aspects. Filling it out is somewhat cumbersome and lengthy.
The cotton swab test is also a useful and simple way to show tenderness inside the vestibule. A cotton swab is gently applied as a control to normal skin, as well as around the different areas of the external genitalia. In vestibulodynia, pain in response to a light touch is typically felt in the vestibular area – called "allodynia" -, where there is no pain under normal conditions. This hyperesthesia can be generalized throughout the vestibule or it may be more localized.
The cotton swab test quantifies tenderness, but it is not a reproducible action. Another objective method for assessing hyperesthesia is the use of a handheld probe applied to the mucosa, which allows a variable degree of pressure that we can measure and compare with the level of produced discomfort. This device is known as a vaginal algometer.
Clinical examination of the vulva is often normal. Vulvar erythema may exist, but can also be an anatomic variant. According to Pagano, vulvar colposcopy is a useful tool to detect changes that may be suggestive of chronic vulvar candidiasis [26]. • Superficial and deep palpation: When pain becomes chronic in vulvodynia, trigger points (TP) appear. They are identified by palpation, first superficially and then deeply. In addition to the TP evaluation, the basal tone of the chest diaphragm, of the subumbilical abdominal girth, and of the pelvic floor should also be ckecked, as well as mobility and connective tissue consistency in all these areas. Exploring the area to find the TP and the taut band that comprises it, you can find: hyperirritability, immobility, painful sensitivity, edema, tension and muscular contracture. The "jump sign" is characteristic and gives us an invaluable clue that this is a TP. • Administration of a muscle relaxant two hours before will allow a better exploration and a more accurate detection of active TP because it temporarily reduces the pain of secondary and satellite TP. • Dry needling as a diagnostic tool. A needle is inserted in the TP causing local twitch response (shaking). • Local anesthetic block. Local and referred pain disappear. • Pressure using the algometer. To measure the pressure-pain threshold on the muscles that have TP. Electrophysiological studies Electrophysiological studies are essential in the diagnosis of vulvodynia, since the pudendal nerve entrapment is one of the possible etiologies [27,28]. However, trigger points and an increase in the tone of the pelvic floor muscles are often found in these patients and we are also obliged to objectify their existence for a better therapeutic approach. Accordingly, Glazer et al. carried out two interesting neurophysiological studies which clearly show that women with vulvodynia have high muscle tone, twitching and poor balance between contraction and relaxation exercises [29]. Electrodiagnostic features of trigger points were stated for the first time by Weeks and Travell in 1957. Hubbard and Berkoff reported similar electrical activity in myofascial TP and concluded that only high frequency spike potentials would be characteristic [30]. Later, Simons and Hong detected another component as a low amplitude noise which was always present. This noise was called spontaneous electrical activity [31, 32].Physical examination
This tool could be useful in assessing the outcome of patients after different therapeutic interventions [33, 34, 35].
Vulvar pains associated with specific disorders: 1. Lichen sclerosus. 2. Eczema. 3. Fissuring vulva syndrome. 4. Symptomatic dermographism. 5. Aphthous ulceration. 6. Erosive lichen planus. 7. Blistering disease. 8. Herpes simplex infections. 9. Sacral meningeal cysts. 10. Alcock's canal syndrome [28]. Likewise, we should rule out other diseases that also cause vulvar pain: – Infections. – Physical problems resulting from accidents or sexual abuse. – Systemic diseases such as Behcet's disease, Sjögren"s syndrome, lupus and Crohn's disease. – Precancerous conditions and cancer. – Irritants such as detergents, underwear which is colored and not made of cotton, creams, suppositories, feminine hygiene products, etc. – Skin conditions like contact dermatitis, psoriasis, pemphigoid and pemphigus.
Some dietary guidelines such as eating foods low in oxalate and calcium citrate supplements are recommended. In their studies Metts and Baggish et al. relate the excretion of oxalate in the urine with vulvar irritation and burning sensation [66, 67]. Solomons et al. recommend the use of calcium citrate, since it competes with oxalate because of their similar chemical structure [36.].Medical treatment
Hygienic measures
Symptoms resolve without treatment in 30% of women, of which 50% will resolve within the first year. Patients should be advised strict vulval hygiene to reduce local irritation [10]. In a clinical practice guideline, Haefner discourages the use of underwear or menstrual pads that are not 100% cotton. Additional lubrication should be used for sexual intercourse, for example lidocaine ointment 5%, or prilocaine 2.5% and lidocaine 2.5% (EMLA) should be used three times a day to desensitize the area. Natural oils that have no excipients or petroleum jelly may also be used. Improvement with continued use of petroleum jelly may be linked to the reduction of friction. He does not recommend douches, but only clean gently with water and pat dry the area with a soft cloth and use mild soaps for general bathing [37]. The American College of Obstetricians and Gynecologists [38] recommends a number of hygienic measures for the care of the vulva, which can help relieve the pain of vulvodynia:
• Wear 100% cotton underwear (no use of underwear at night) • Avoid tight-fitting underwear and pantyhose
• Avoid douching • Use mild soap to bathe and wash the vulva with water only
• Do not use vaginal wipes or deodorants or bubble bath soap
• Do not use pads or tampons with deodorant
• Use a lubricant for sexual intercourse
• Apply cool gel packs to the vulva area to reduce pain and itching
• Avoid exercises that put pressure directly on the vulva, such as cycling.
Local anesthetics in ointment form
They have some specific advantages: they allow penetration and act as a lubricant. Lidocaine ointment 5% is the most common. The reason for its use is that it has the lowest incidence of sensitization. Apply 15 to 20 minutes before sexual activity [39].
Topical Gabapentin
Topical gabapentin helps desensitize vulvar tissues, which are always very sensitive to any irritation that may lead to a neurogenic inflammation. In an interesting study, Boardman et al. concluded that topical gabapentin 2% to 6%, which is usually well tolerated, is associated with significant vulvar pain relief after a minimum of eight weeks treatment [40].
Antidepressants
Antidepressants have been used in both localized and generalized vulvodynia, especially tricyclics, at lower doses than those used for depression. Amitriptyline is the most widely used antidepressant, given its good results for pain control. The mechanism of action occurs due to the increase of activity of the descending inhibitory tract in the CNS and modifying the activity within the dorsal horn of the spinal cord. A dose of 10 mg daily will be prescribed at the beginning, increasing weekly until target is reached.
The average dose will be 60 mg/day not exceeding 150 mg/day. Patients should be informed about side effects and warned not to stop them abruptly but gradually. In case of using serotonin reuptake inhibitors concomitantly, it is important to indicate that they may cause sexual dysfunction and weight gain. In a study by Munday [41] and in another one by Reed et al. [42] good results were obtained with amitriptyline in this type of neuropathic pain. Other antidepressive agents such as imipramine or nortriptyline are of less use. Their most common side effects would include: dry mouth, weight gain, sedation and hangover effect. The average duration of treatment is 6 months depending on progression.
Anticonvulsants
A series of studies reported the benefit of gabapentin in the treatment of vulvodynia [43, 44]. Harris et al. reported an improvement of at least 80% in 64% of patients, of a total of 152, in the use of this anticonvulsant with a low profile of side effects.
In recent literature we find the description of a case successfully treated with pregabalin which was previously refractory to standard treatments [45].
Local infiltration
Submucous infiltrations of lidocaine and betamethasone have been used successfully in the treatment of vulvodynia located in the mucosa [46, 47].
Physiotherapy • Physical therapy and biofeedback
According to a survey study by Hartman et al., physical therapy in patients with vulvodynia is common practice in the U.S.: 63% of physiotherapists treat this type of ailment. And they treat women one hour a week for 7-15 weeks. Gynecologists and obstetricians are the main referrals for these professionals [49]. Likewise, we found a study reporting the effectiveness of physical therapy in vulvodynia [50], and another one which mentions its utility in vestibulodynia for dyspareunia [51].
Biofeedback therapy intending to regain pelvic floor muscle tone is used for the treatment of sexual intercourse that causes discomfort and / or vulvar pain [23]. Thus, McKay et al. reported a significant improvement in more than half (51.7%) of the women treated with this technique [52]. With biofeedback equipment patients can view the evaluation of muscle tension (colored lights or scales) and thus develop voluntary control [50].
• TP methods of release
Immediate muscle elongation promotes balance to the sarcomere length and, when done slowly, it helps reconfiguring the new sarcomere length, which thus tends to stabilize. In any case, full relaxation of the patient is a prerequisite for effective release. TP pressure release It consists of applying gentle pressure and gradually increasing it over the TP until the finger encounters increased tissue resistance. Normally, when performing this maneuver bearable pain occurs. Pressure will be maintained until the clinician detects a decrease in tension under the palpating finger. At this point, the finger increases pressure just enough to reach the new barrier, the finger "follows the tissues that are relaxing." Again, the clinician maintains only a slight pressure until more tension diminishes and is released under the finger [53]. Weiss has reported successful results in 52 patients with interstitial cystitis syndrome, which is related to vulvodynia as we have seen above. Decreased muscle tone was proven electromyographically. The symptomatology was present between 6 and 14 years [54]. Dry needling
It is a TP release method which is increasingly becoming popular among physiotherapists, although it is also practiced by physicians. Its therapeutic utility has been recognized by such prestigious institutions as the Cochrane Collaboration [55].
However, the false popular and professional belief to think that Chinese acupuncture and medical acupuncture or dry needling is the same leads to error and creates confusion. Nevertheless, there is a high location correspondence of 71% between the points of traditional acupuncture and dry needling [56]. Gunn et al. have developed a method for deactivation of TP called intramuscular stimulation, which involves inserting a needle into the TP as performed in the dry needling technique. This can be combined with electrical stimulation through the inserted needle.
Botox infiltrations
Formerly, when dealing with this type of chronic pelvic pain, we seemed to find ourselves before an entity of psychological origin, since no clinical findings were detected either on examination or on additional diagnostic tests. Today, with new diagnostic tools, the psychological component would simply be one among others.
This does not mean that psychological support is not necessary. On the contrary, it is known that these women often have relationship, social, professional and / or family problems that can aggravate vulvodynia. It is believed that most psychological problems are the consequence rather than the cause of pain. Thus, Lotery et al. and Aikens et al. abound in their respective studies on the importance of the increase of depressive symptoms in women suffering from vulvodynia [3, 18]. Patients are usually reluctant to accept psychological help, even when they themselves perceive evidence of emotional lability, thus suggesting psychological support should be provided prudently. We must make them understand that psychological support can help improve their sex life, often altered by dyspareunia [58].
Much of the therapeutic success relies on proper communication with the woman, making it clear to her that we know the pain that she has is not a product of her imagination. It is important to emphasize that vulvodynia is a well-known syndrome that affects many women in the world, that it is not a sexually transmitted infection and that it is not a malignant disease. Likewise, they should be aware of the fact that a 100% cure is very difficult to obtain and that improvement is usually slow [37, 59, 60].
Melzak and Wall"s gate control theory has been widely used in the management of ongoing pain in affected women. The theory states that the spinal cord has a number of doors inside that allow pain signals from all over the body to go through. The type of nerve signal which goes through the gate to reach the cortex depends on psychological factors in women with emotional stress and anxiety. Therefore, the more gates are opened, the more signals will be carried to the cortex and the higher the levels of pain that will be experienced. The factors that close the gate and prevent signals at segmental and suprasegmental areas from going through include relaxation, exercise, stretching and therapeutic massage [61)
It is the last resort for women with vulvodynia refractory to conservative treatment. The aim is to remove the vulvar mucosa. The best results are obtained with modified vestibulectomy. Post-surgical complications are rare. Women who respond to lidocaine before having intercourse are more responsive to treatment. In a series of 57 patients carried out by Kehoe et al. 61% achieved complete response, while 28% and 11% achieved partial response or no response, respectively. The success rate can be improved with complementary therapy to help rehabilitate the patient after surgery, both physically and psychologically [62]. More recently, other authors include modified vestibulectomy, a simple and effective option for symptomatic control of vulvodynia [63, 64]. Other complementary therapies Sometimes we can use other therapies such as hypnosis [4] or acupuncture [65] -which have no definitive scientific evidence, but are not aggressive at all- that can help us improve the quality of life of these refractory patients to conventional treatments.Surgical treatment
Discussion
For an accurate diagnosis we will build on a careful clinical history, with special attention to the characteristics of neuropathic pain. We can measure it with the visual analog scale (VAS), often used just like the DN4 for neuropathic pain. Both are extremely easy to use and very effective to track the evolution of patients. Electrophysiological studies are essential in the diagnosis of vulvodynia, since the pudendal nerve entrapment is one of its possible etiologies. Moreover, trigger points and increased tone of the pelvic floor muscles, typical in the myofascial pain syndrome, are very often found in these patients and we are also obliged to objectify their existence for a better therapeutic approach.Our experience shows that we almost always find increased basal muscle activity at rest in relation to etiopathogenical process. This fact is quantifiable with the averaging of the turns/amplitude rate using the electromyographic equipment. In essence, the number of turns of the EMG signal during a time unit and the mean amplitude of the turns obtained during that time are measured, and the results will be compared with healthy subjects. Basically, the test consists of recording EMG activity in several muscle sites (between 6 and 10) preferably in the area halfway between the motor point and the tendon. Each point represents the automatic analysis of a period or "epoch." Between 20 (minimum) and 30 tests are conducted. Under normal conditions, the points are distributed in a "cloud", where 95% of them fall into it. It is considered pathological when at least 10% of the points fall outside a cloud (Figure 1).
Figure 1: Turns/ amplitude rate in levator ani muscle
The treatment will be staged, starting with the hygienic measures discussed above. At the same time, we will prescribe a lidocaine ointment 5% or 3-5% topical gabapentin. We could then use tricyclic antidepressants- amitriptyline and duloxetine. Anticonvulsants -gabapentin and pregabalin- have also been successfully tested.
Local infiltration and regional blocks of pudendal nerve are useful in combination with physical therapy to achieve faster and sustained relief, through desensitization both at peripheral and central levels.
Physiotherapy treatment together with trigger point infiltrations seem to be necessary when we find myofascial pelvic pain syndrome accompanying the long-lasting cases of vulvodynia.
In some cases, especially difficult, we can try Botox infiltrations in the perineal and vaginal muscles.Some cases of vulvodynia evolve torpidly and unpredictably making its management very difficult. Then, we can consider surgery, as a last resort, in patients with vestibulodynia and patients who probably suffer from pudendal nerve entrapment.
First, it must be clear that this is a complex syndrome, which requires an interdisciplinary approach in most cases. Primary care physicians and gynecologists will be the first necessary professionals, but urologists, dermatologists, psychiatrists, sex therapists, physiotherapists and algologists have an important role in alleviating these women"s suffering. When diagnosis is made earlier, the approach will be better, due to the lack of sensitization of the peripheral and central nervous systems. We should never create false expectations about the success of surgery because there is no panacea for these pathologies.
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