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
Vulvar pain is often multifactorial in origin. Therefore, a multimodal approach to treatment should be considered. Multimodal interventions include the use of more than one type of therapy for the care of patients with acute, chronic, or pathologic/neuropathic pain (Graziottin 2006; Graziottin and Murina 2011; Graziottin and Gambini 2015a; Graziottin et al. 2016).
A committed trustworthy relationship with the patient is essential: the woman affected with the challenging vulvar pain needs to know, see, and feel, at any age, that the healthcare provider (HCP) trusts the biological truth of her pain and will do his/her best to diagnose the cause(s) of it and treat them in the most effective ways. Avoiding a minimalist approach is the first challenge (Box 11.1) (Graziottin et al. 2016).
Box 11.1: The Vulvar Scenario First: The Challenge of Avoiding a Minimalistic Approach
The missing listening or the collusion of silence:
Women feel often ashamed and embarrassed to speak about vulvar pain and sexual issues with the physician. The majority of women think that vulvar pain is “too intimate to be spoken of” until it becomes invalidating. This is why HCPs should routinely ask about vulvar and sexual pain as a normal part of the clinical history. Otherwise it is difficult to provide an effective intervention if there is no mention of a problem
One third of women would not even speak about their vulvar pain, and/or vulvovaginal atrophy (VVA), with their partner. It is even more the physician’s responsibility to raise the problem and, if present, ask the proper questions (Box 11.2) and analyze vulvar complaints with an investigative mindset and a pathophysiologic reading of the woman’s narrative of symptoms.
The missing diagnosis:
The physician superficially examines the woman and concludes: “You have nothing, pain is all in your head,” or ”It is psychogenic.” To improve the examining skills is mandatory! (Box 11.3)
Minimalistic treatments:
What happens when vulvar and/or sexual pain are overtly reported? The majority of women facing vulvar and sexual pain, and associated comorbidities, receive a lubricant as an answer for their sexual concerns. This is frequently perceived as humiliating by the woman, as a deception by the man, as a fiction of arousal by the couple.
To address vulvar symptoms in a comprehensive multimodal approach is essential if vulvar pain is to be effectively and definitely cured.
Modified from Graziottin et al. (2016)
The second challenge is to distil an essential history taking, useful for every physician in his/her practice (please see the Chap. 10 on diagnosis of vulvar pain). Here the key questions and examining issues are summarized to ease the younger readers to systematize their vision of vulvar pain diagnostic basis, essential to design an effective treatment, and/or readers interested just on this chapter.
Box 11.2: Vulvar Pain: The Basic Mindset in the History Taking
Careful listening of spontaneous woman’s wording, rich of critical informations to design a personalized protocol and to prevent recurrences
Mandatory questions:
- 1.
When did your vulvar pain initiate? Is it recent (lasting 3 months or less) or not?
- 2.
Do you recall any specific event triggering it (vulvar trauma, vaginitis, cystitis, antibiotics, intercourse, childbirth, sexual abuse, surgical operations, etc.)?
- 3.
How would you describe your vulvar pain: pain, burning, itching, irritation, dryness, or soreness? Is it continuous or intermittent, localized, or extended to the whole vulva (“generalized”)? Is it worse at night or not? Please indicate as many key words as you feel appropriate.
- 4.
Do you specifically suffer from burning vulvar pain?
- 5.
Is it spontaneous or provoked (by the use on tampons, or the intercourse, or the clinical examination, or stress, or what else)?
- 6.
Does intercourse hurt at the entrance of the vagina (“introital dyspareunia”)?
- 7.
Is there any pattern of recurrence: after intercourse or not?
- 8.
Does it worsen during the menstrual period?
- 9.
Do you suffer from recurrent vaginitis (particularly from Candida), recurrent or postcoital cystitis, irritable bowel syndrome (i.e., diarrhea/constipation), obstructive constipation, endometriosis, fibromyalgia, or headache?
- 10.
Are you taking hormonal contraceptives (pill, patch, vaginal ring)?
- 11.
Are your periods regular or are you without periods (amenorrhea: hypothalamic, postpartum, menopausal)?
- 12.
Are you diabetic? How is your glycemic control? Do you have relatives with diabetes?
- 13.
Since your vulvar pain has become chronic, did you have other symptoms such as fatigue, mood swings/depression, sleep difficulties, concentration, and memory problems?
- 1.
Modified from Graziottin (2014)
Box 11.3: Vulvar Pain: The Mandatory Gynecological Examination
- 1.
Examine the vulva and the perineum: is there any vestibular/vulvar erythema? Scratching signs? Scars? Dermatosis? Any discharge? Is there any sign of retracted/hyperactive pelvic floor (usually so in nulliparous women reporting positive answer to questions 1–6 (Box 11.2)) Hemorrhoids (suggestive of an hyperactive pelvic floor and/or chronic constipation)?
- 2.
Perform the swab test, at five and seven, looking at the entrance of the vagina like a clockface and then random all over the vulva. The test is usually positive when the woman answers yes to two out of three questions 4–6 (Box 11.2). Is the clitoris painful?
- 3.
Examine the pelvic floor: is it tense? Are there tender and/or trigger points at the insertion of the levator ani on the ischiatic spine bilaterally? How’s the perineal command (absent, correct, inverted, i.e., when the woman is requested to push and relax the levator ani/perineal floor, she automatically pulls and retract it even further)? A hyperactive pelvic floor is usually present in case of at least four positive answers to questions 1–6 (Box 11.2). Examine the obturator muscle and the Alcock canal, bilaterally.
- 4.
Perform an accurate gynecological examination: are there other areas of pain (along the anterior vaginal wall, in case of comorbid urethritis; deep in the posterior fornix and along the uterosacral ligaments in case of comorbid endometriosis; laterally, in the adnexal area in case of pelvic inflammatory disease [PID], etc.)?
- 5.
Evaluate the vaginal pH: a pH of 4 is physiologic, but associated with recurrent Candida; pH of 4.6–5 or more is associated with bacterial vaginosis and increased vulnerability to invasion/infection from colonic germs, uropathogenic Escherichia Coli (UPEC) most. Usually the vaginal pH is elevated in case of positive responses to question 11 (Box 11.2) (i.e., in case of prolonged amenorrhea).
Modified from Graziottin (2014)
When women affected with chronic or pathologic/neuropathic vulvar pain finally meet a dedicated and committed HCP, they (and their families!) are usually devastated by years of unaddressed inflammation and vulvar pain, of diagnostic neglect, and the frequent appearance of other painful comorbidities (Graziottin and Murina 2011).
Moreover, the inflammation peripherally modulated by mast cells (Graziottin 2009) has reached the brain (please see the Chap. 3 on pathophysiology of vulvar pain). Chronic neuroinflammation induces:
Neurogenic neuroinflammation, with massive upregulation of the microglia, whose role shifts from neuroplastic to neurotoxic (Graziottin et al. 2013, 2014a, b, 2015; Xanthos et al. 2011; Walker et al. 2013; Skaper et al. 2015). Behavioral correlates include maladaptive sickness behavior, depression (which is first of all the epiphenomenon of a massive neuroinflammation (Derry et al. 2015), not just a “black cloud over the head”), fatigue, sleep disorders, memory difficulties, and concentration problems. These symptoms are frequently reported to the listening physician. The treatment should address them and their pathophysiologic basis as well.
Neurogenic peripheral inflammation, with persisting vulvar pain (and increasing comorbidities, worsening over time).
Key Point
When vulvar pain becomes neuropathic, it is just the tip of the iceberg of a massive systemic and brain inflammation. Treatment cannot be minimalistic, focused only on the vulva, but must address the neuropathic complexity with a strategic, pathophysiologically based vision.
A careful evaluation of lifestyles and behaviors potentially contributing to vulvar pain is a vital part of the diagnosis and treatment. Unfortunately it is often omitted, thus impairing the potential for a full recovery. A well-designed treatment should therefore address first of all the modification(s) of inadequate lifestyles to maximize the benefits in a well-designed therapeutic plan (Box 11.4).
The simple example that works to motivate many patients in improving their lifestyles is that the river of pain originates from the river of inflammation (that means to set a biochemical fire), like the intensity of smoke depends on the intensity of fire in the real world.
The river of inflammation has many tributaries, including but not limited to:
Overweight/obesity, as the adipose tissue produces massive amounts of cytokines and other inflammatory molecules that flood the body and the brain (Pedersen 2009).
Physical inactivity that is a major contributor of systemic diseases. The majority of them have inflammation and pain as leading characteristics (Booth et al. 2012).
Unhealthy diet: women with unhealthy diet have more than twice the risk of widespread chronic pain (Vandenkerkhof et al. 2011), through different pathophysiologic pathways.
Reduced quality of sleep, a major biological stress and cause of neuro and systemic inflammation when chronic, through the hyperactivation of the corticotrophin releasing pathway (CRP) (Finan et al. 2013).
Chronic stress: biological, psychological, and/or context dependent (Derry et al. 2015).
Key Point
Neuroinflammation should first be addressed through the improvement of lifestyles, when inadequate, or altered by pain itself and associated behavioral changes.
Box 11.4: Vulvar Pain: Improve Lifestyles to Reduce Systemic and Brain Inflammation
Weight reduction may improve the treatment outcome of vulvar (and any other) pain. Reducing adipose tissue:
Reduces in parallel the associated systemic and neuroinflammation, decreasing the risk of maladaptive sickness behavior, typical of neuropathic pain, of fatigue and depression (Pedersen 2009; Derry et al. 2015)
Improves body image, self-perception, vital energy, mood, and sex drive, especially if combined with daily physical activity. All these positive changes may contribute to the “healing project” in a comprehensive and rewarding way. As a patient said: “I’m so glad, doctor, that you are looking at me and curing me as a woman, not just as a painful walking vulva”
Physical exercise: the anti-inflammatory effect of regular exercise can be mediated via:
An induction of an anti-inflammatory environment with each bout of exercise.
A reduction in visceral fat mass. The finding that muscles produce and release myokines provides a conceptual basis to understand the mechanisms whereby exercise influences metabolism and exerts anti-inflammatory effects (Pedersen 2009).
A reduction of the consequences of psychosocial and physical stress, a major contributor of depression (Slavich and Irwin 2014) and worsening of pain perception.
A reduction of systemic inflammation, neuroinflammation, and depression, and a better immune functioning and a better sleep, the great and underappreciated guardian of health and sexuality, reduced fatigue and distress.
A mental and psychological redesign of the woman’s body map, giving the correct importance to all the body parts and not focusing only on the sick vulva.
A modulation of the dopaminergic system, increasing dopamine secretion. It is likely that all these factors positively impact the recovery of sexuality as well.
Healthy diet: increasing evidence supports the role of a healthy diet as a substantial health promoter and specifically as a pain reducer/controller, through the reduction of the inflammation induced by inadequate quality of food intake (Vandenkerkhof et al. 2011). Recommendations include limit alcohol to no more than one drink/day and avoid smoking. Alcohol and smoke may exacerbate inflammatory condition and have a detrimental mental effect.
Sleep quality and duration: to maintain low levels of systemic inflammation, human being (with few exceptions) should sleep 1 h every 2 h wake. To improve quality and duration of sleep reduces inflammation, pain, and pain perception. Even napping may significantly reduce pain (Faraut et al. 2015). Protecting/improving the quality of sleep may significantly reduce pain (Finan et al. 2013). This can be achieved also with the help of melatonin, a natural circadian sleep hormone which has an anti-inflammatory effect.
11.1 The Start-Up: Explain the Diagnosis of Vulvar Pain and Realistic Treatment Goals
Any treatment approach should begin with a discussion including an explanation of the diagnosis and realistic treatment goals. A general guiding principle is to begin with those treatment options with the fewest side effects or potential complications.
Discussion of lifestyles must be included.
The patient should be counselled that follow-up is needed to evaluate treatment responses and adjust the therapeutic plan as needed to maximize pain reduction. A multidisciplinary intervention should be part of a treatment strategy for patients with vulvar pain. Multidisciplinary interventions are multimodality approaches in the context of a treatment program that includes more than one discipline.
The team of HCPs may involve gynecologist, dermatologist, psychosexual counselors, urologist, and physical therapists, plus other specialists when indicated. It is crucial to maintain communication among all the involved treating providers to avoid duplication of therapy and optimize a cohesive treatment plan.
Key Point
The three golden steps for a well-designed and effective treatment of vulvar pain are:
To listen openly to health and sexual concerns focused on the vulva
To encourage the dialogue on vulvar pain and associated sexual issues and comorbidities
To address them with structured, comprehensive, and effective pharmacologic/rehabilitative therapeutic strategies, including improvement of inadequate lifestyles, directed at curing the underlying vulvar and systemic pathophysiology.
11.1.1 Vulvar Care Guidelines
Multiple studies have been conducted to show that there are important differences between vulvar tissue and other skin surfaces. Such characteristics as tissue structure itself, hydration status, occlusion, friction, and permeability make vulvar tissue more susceptible to inflammation as well as friction-related injuries (Podorozhansky et al. 2012).
We recommend that the patient should initially be encouraged to follow a few general advices for minimizing vulvar irritation. This is the first specific level of treatment that each physician must recommend to any patient with acute vulvar pain, chronic vulvar pain, and, even more so, provoked or spontaneous vestibulodynia/vulvodynia. By following vulvar care guidelines with regard to personal hygiene and product use, patients in whom contact dermatitis potentially contribute to vulvar pain should be able to see improvement in their symptoms.
Although vulvar care guidelines are not enough to constitute the entire scope of treatment of various vulvar disorders, they can serve as an important adjunct to conventional treatment (Box 11.5).
Box 11.5: Vulvar Care Measures to Minimize Vulvar Irritation
Avoid vulvar irritants (perfumes, dyes, shampoos, detergents) and douching.
Use adequate lubrication for intercourse.
Wear all-white cotton or medicated silk fibroin underwear.
Wear loose-fitting pants or skirts; do not wear pantyhose or jeans.
Use dermatologically/gynecologically approved intimate detergents.
Use soft, white, unscented toilet paper.
Avoid getting shampoo on the vulvar area.
Do not use bubble bath, feminine hygiene products, or perfumed creams or soaps.
Avoid penetration until vestibular inflammation and pain are resolved (Box 11.6).
Do not use anesthetic cream to ease intercourse, as this will perpetuate the vestibular trauma and inflammation.
Apply ice, or a frozen blue gel pack (lunchbox size), wrapped in a single layer of towel to relieve burning after intercourse (if accepted in spite of pain).
After sexual intercourses, urinate to prevent infection and rinse vulva with cool water.
Avoid exercises that put direct pressure on the vulva, such as bicycle riding and horseback riding.
Limit intense exercise that creates a lot of friction in the vulvar area (try lower-intensity exercises such as brisk daily walking).
Adapted from “Self-Help Tips for Vulvar Skin Care”, National Vulvodynia Association, http://www.nva.org/
Box 11.6: The Amletic Dilemma: To Have Intercourse or Not to Have it?
A special note is to be made about having intercourse while vestibular pain is complained of:
Many women accept intercourse, in spite of the burning pain persisting for days after penetration and worsening over time because of the repeated intercourse, for fear of losing the partner.
Many partners insist that having intercourse is a normal part of the couple relationship.
Many physicians recommend the use of an anesthetic cream to reduce coital pain and allow intercourse, “to help the couple to have a normal sexual life.”
This is absolutely wrong from the pathophysiologic point of view. Which physician would recommend/prescribe an anesthetic to a man or a woman with a broken leg (or whatever other fracture), ”so that you can use it”?!
With a broken leg, everybody would agree that the first goal is to heal the fracture, do the proper rehabilitative therapy, and then start walking and doing sport again.
Why the vulva and the vagina should be treated differently? A woman is more than a vulva to be enjoyed and a vagina to be “used” while being penetrated.
Women and partner should be informed that pain (vestibular and sexual) is not just a disturbing symptom. It is the tip of the iceberg of a real, severe inflammatory disease of the vulva, with increased proliferation of pain fibers that multiply pain and make it chronic and pathologic/neuropathic, if the microtraumas of the vestibular mucosa are further repeatedly caused by insisting on having intercourse. Inflammation often extends to neighbor organs such as the bladder, causing cystitis 24–72 h after the intercourse in 60 % of cases (Salonia et al. 2013). A process called “comorbidity” that causes pain of progressive severity.
11.2 Therapy of Specific Disorders Causing Vulvar Pain in the Lifespan
11.2.1 Labial Adhesion
This term is used when the labia minora fuse together in prepubescent girls. Other nomenclature used to describe the condition includes labial agglutination, labial fusion, and vulvar synechiae. It is not a rare condition and has been reported to occur in up to 1.8 % of female prepubertal patients. It mainly affects girls 5 years of age, with a peak incidence around the age of 13–23 months (Simpson and Murphy 2014).
The etiology of the condition is unknown but it is believed to be associated with the low estrogenic state in prepubertal girls (Davis 2003). Less commonly, it occurs secondary to vulvar inflammation and irritation in which the skin becomes excoriated and denuded leading to fusion of the labial edges during the healing process. This condition can be distinguished from imperforate hymen or labioscrotal fusion (androgen associated, midline fusion of external genitals) by the inability to visualize the urethra (Davis 2003).
11.2.1.1 Management
Explaining how the fusion has arisen, reassurance that it is a self-limiting condition and that the internal anatomy is normal is helpful for most parents.
If more than 75 % of the labia are closed, and/or if the child complains of burning pain, and/or dysuria, urinary tract infection, and obstruction, it is appropriate to treat this with topical estrogen applied sparingly to the line of adhesion, twice daily, until separation occurs. Estrogen treatment should be continued until the urethra is visualized, as long as there is no evidence of systemic estrogenization (breast bud). Therapy may take up to 6 weeks (Davis 2003). Treatment can be repeated in case of recurrence.
There is no consensus about the type of estrogen, the preferable frequency and duration of the application. In our experience, treatment may be required for several weeks to achieve separation of the labia minora, and the application of estriol gel 0.05 % once a day can prove to be very effective.
Adhesions tend to recur if preventive measures are not taken (i.e., gentle labial separation to visualize the urethra with the application of petroleum jelly or barrier cream to reduce labial adherence). Additional management includes daily baths, avoidance of irritants such as soapy water or bubble baths, and vulvar “airing” (a daily period of time when the diaper is removed or not wearing underwear during the night). The surgical release of labial adhesions is rarely required.
Underwear made of medicated silk fibroin, indicated for different atopic dermatoses in children, can complement the effectiveness of treatment, as it reduces dermatitis and associated bacteric infections.
Surgical intervention should be reserved for severe cases resistant to conservative management in girls presenting with urinary retention and/or voiding difficulties and/or recurrent cystitis due to the stenosis induced by the tight central labial fusion.
11.2.2 Vulvovaginal Infections
- 1.
Childhood vulvovaginitis
It is one of the most common gynecological conditions encountered in pediatric outpatient clinics, in both prepubertal and pubertal children.
Group A beta-hemolytic streptococcus (ABHS) is the most common cause of prepubertal vulvovaginitis. ABHS can cause a burning red rash in the vulva, and/or perineum, and/or perianal area, with or without fissures.
11.2.2.1 Management
Treatment is with oral penicillin in adequate pro/kg doses (to be prescribed by the pediatrician) for 10–14 days, or clindamycin cream 2 % per vagina for 7–10 days. Nevertheless a recent randomized controlled trial compared oral penicillin against cefuroxime for Group A beta-hemolytic Streptococcus pyogenes perianal dermatitis in children under 16 years of age. Successful eradication of infection, as determined by a posttreatment swab, was greater in the cefuroxime group compared with the penicillin group (93 % vs. 47 %, p < 0.01).
The authors therefore concluded that 7 days of cefuroxime was more efficacious than 10 days of penicillin and should therefore be considered the treatment of choice for this condition (Meury et al. 2008).
The opportunity to integrate the antibiotic treatment with probiotics should be discussed with the pediatrician who looks after the child. Probiotics are increasingly utilized in the lifespan to restore the normal intestinal microbiota, usually devastated by high-dose antibiotic treatments.
- 2.
Vulvovaginal candidiasis
Candida albicans is rare in childhood and is usually diagnosed only in severely immunodepressed children. Candida vaginitis is increasingly frequent in postpubertal girls, when estrogens play a critical role as “permitting” factors in the transition of Candida from the “sleeping” phase of spore to the vegetative phase of hypha. Cardinal symptoms of vulvovaginal candidiasis include vulvovaginal pruritus, irritation, soreness, dyspareunia, and vaginal “cheese-like” white discharge.
Clinical signs are best exemplified by vulva erythema, edema, excoriation, and fissure formation together with introital and vaginal erythema.
It is essential to treat adequately the recurrent vulvovaginal candidiasis because infection or a hypersensitivity reaction to subclinical candidiasis is believed to play a prominent role in the development of vulvar pain and vestibulodynia (please see Chap. 6 on vulvar pain in adolescents).
11.2.2.2 Management
It is not necessary to treat an asymptomatic colonization, because Candida is a commensal of human vagina.
Topical treatment of acute vulvovaginal candidiasis can be performed for a period of 3 to 5 days using imidazoles with different preparations such as creams or vaginal tablets or suppositories, if the girl has already had intercourse; oral triazoles (3-day treatment) and antimycotic creams for the vulva may also be used. All of the different treatment regimens produced similarly good clinical and mycological results.
Management of recurrent vulvovaginal candidiasis can be problematic, and current guidelines clearly indicate both the relative high incidence of relapse in the follow-up and poor compliance of the patients. Different regimens are summarized in Table 11.1.
Table 11.1
Proposal of therapy for vulvovaginal candidiasis
Drug
Formulation
Dose
Acute
Clotrimazole
1–2 % cream
3–5 g daily for 5–7 days
Miconazole
2–4 % cream
4 g daily for 5–7 days
Fenticonazole
600 mg vaginal suppository
q 72 h for 3 doses
Fluconazole
150–200 mg oral pills
q 72 h for 3 doses
Recurrent
Fluconazole
150–200 mg
Induction, 150–200 mg q 72 h for 3 doses
Maintenance regimen, 150 mg q weekly for 6 months
or
200 mg weekly for 2 months, followed by 200 mg biweekly for 4 months, and 200 mg monthly for 6 months
or
200 mg weekly for 4 weeks, then 1 after 10–15 to 20–30 days
Itraconazole
100–200 mg
Induction, 200 mg bid × 3 doses
Maintenance, 100–200 mg/d for 6 months
Attention to adequate lifestyle, including improving the diet by reducing yeast-containing foods (bread, pizza, biscuits, etc.), glucose, and excess calories, increasing fresh food, and having daily aerobic exercise (1 h brisk walking or any other sport of preference) to optimize the peripheral use of insulin, is part of a strategic management.
The oral weekly administration of a single dose of 150 mg of fluconazole for a period of 6 months proved to be successful in 91 % of the cases, but decreased to 43 % during the observation period 6 months after the cessation of the therapy (Sobel et al. 2004).
Other regimen with a personalized and decreasing administration of 200 mg fluconazole doses, often for rather long periods (4 months on average), has been proposed. This therapeutic scheme has shown no evidence of clinical recurrence in 75–90 % of women and reduced to 70–75 % after 1 year (Donders et al. 2008).
Probiotic bacteria have been targeted as potential therapeutic agents of recurrent vulvovaginal candidiasis. Possible mechanisms of this protection include inactivation of pathogens by different Lactobacillus products (lactic acid, H2O2, and bacteriocins), competition for epithelial cell attachment sites, and creation and maintenance of a vaginal biofilm that hinders the persistence of an infection caused by Candida.
It is crucial to interfere with biofilm formation early after the drastic reduction of the Candida concentration (e.g., induction phase with fluconazole) and then to maintain the “positive” biofilm with a greater interval of use of the lactobacilli. It was demonstrated that a product formulated in slow-release, slightly effervescent vaginal tablets containing live cells of Lactobacillus fermentum LF10 and Lactobacillus acidophilus LA02 is effective in the treatment of recurrent vulvovaginal candidiasis: 72 % of patients experienced no clinical recurrence throughout the 7-month follow-up period (Murina et al. 2014).
11.2.3 Herpes Simplex Virus Infection
It is a very common cause of vulvar pain, particularly recurrent pain. It may become a challenging infection when recurrences are frequent and/or trigger neuropathic pain (Graziottin et al. 2015).
Women usually present with recurrent disease, often with unilateral episodic burning and discomfort. Standard treatment regimens for initial either primary or non-primary genital HSV include acyclovir, valacyclovir 1 g bd, and famciclovir (Box 11.7).
Box 11.7: Treatment Regimens for Herpes Simplex Virus Genital Infections
First Clinical Episode of Genital Herpes
Acyclovir 400 mg orally three times a day for 7–10 days
Acyclovir 200 mg orally five times a day for 7–10 days
Famciclovir 250 mg orally three times a day for 7–10 days
Valacyclovir 1 g orally twice a day for 7–10 days
The treatment may be extended if healing is incomplete after 10 days of therapy.
Episodic Therapy for Recurrent Genital Herpes
Acyclovir 400 mg orally three times a day for 5 days or 800 mg orally twice a day for 5 days
Acyclovir 800 mg orally three times a day for 2 days
Famciclovir 125 mg orally twice a day for 5 days or 1000 mg orally twice daily for 1 day
Valacyclovir 500 mg orally twice a day for 3 days or 1.0 g orally once a day for 5 days
Recommended Regimens for Suppressive Therapy (Immune-Competent Patients)
Acyclovir 400 mg orally twice a day
Famciclovir 250 mg orally twice a day
Valacyclovir 500 mg orally once a day or 1.0 g orally once a day
Romero and Nygaard (2015)
11.2.4 Vulvar Dermatosis
They are inflammatory conditions responsible for chronic or recurrent itching and pain. Pain and itch are thought to be closely related in that weak activation of nociceptors mediates itch, while strong activation of the same receptors results in weak pain. Moreover, there is a broad overlap in neuromediators of pain and itch signal processing. Interestingly, scratch-induced pain can abolish itching, suggesting reciprocal control of pain and itch (Lee et al. 2013). The lesions are either circumscribed to the vulva or associated with extragenital localizations which may help to assess the diagnosis. The most frequent vulvar dermatoses are lichen sclerosus, lichen simplex chronicus, and lichen planus.
- 1.
Vulvar lichen sclerosus (VLS)
It is a chronic inflammatory disease with considerable impact on health-related quality of life (Simonetta et al. 2015). Patients with VLS complain mainly of itching, burning, pain, dyspareunia, and sexual dysfunction.
11.2.4.1 Management
A definitive cure does not currently exist. The ideal treatment for VLS should aim at inducing relief of symptoms, reversing signs, and preventing further anatomical changes.
Topical potent and ultrapotent corticosteroids represent the recommended first-line treatment for vulvar lichen sclerosus, both in the active phase and in maintenance treatment (Fistarol and Itin 2013).
No trials comparing different treatment regimens are available. Clobetasol propionate 0.05 % ointment or cream for 12 weeks is the most used. Recent studies have shown that the less potent corticosteroid mometasone furoate 0.1 % (MMF) is effective in treating VLS as well. MMF is a potent glucocorticoid with greater anti-inflammatory activity and duration of action than other steroids of similar potency, characterized by a low potential to cause side effects and the convenience of once-daily administration (Virgili et al. 2014; Murina et al. 2015).
Box 11.8: Lichen Sclerosus Practice Points
Topical steroid regimens:
Clobetasol propionate 0.05 % ointment applied once daily, at night, for 4 weeks, then on alternate nights for 4 weeks, and then twice weekly for further 4 weeks.
MMF 0.1 % ointment initially once daily for 5 days a week for 4 weeks, then on alternate days for 4 weeks, and, for the final third month, twice weekly.
MMF 0.1 % ointment daily for 4 weeks and then twice weekly for another 4 weeks in combination with a moisturizing cream.
The use of an emollient, in addition to the topical steroid during the initial treatment phase, and then as maintenance therapy, is very beneficial.
For the very rare cases of resistance to topical steroids of VLS, therapeutical alternatives should be investigated (topical calcineurin inhibitors, topical and systemic retinoids, and photodynamic therapy).
Prevention of squamous cell carcinoma associated with VLS relies on detection of precursors which should be suspected in the case of a circumscribed white raised lesions or pink patches.
The 5 % risk of neoplastic progression makes mandatory a regular follow-up, yearly or more frequently when clinically indicated in individual cases.
- 2.
Lichen simplex chronicus
It is usually treated with the therapeutic strategy used for lichen sclerosus.
- 3.
Lichen planus (LP)
It is far less common than LS and commonly causes vulvar pain. Classically, painful LP is scarring and erosive with a glazed erythema, usually on the vulvar vestibule and posterior fourchette.
LP, unlike LS, can involve the vagina (with or without vulvar involvement) with erosions and/or desquamative vaginitis resulting in a vaginal discharge.
Evidence-based data on the treatment of LP are limited, and management choices mainly rely on clinical experience (Box 11.9).
Box 11.9: Treatment of Lichen Planus
Clobetasol or mometasone ointment
Triamcinolone acetonide intramuscular
Prednisone 40–60 mg orally once a day, taper as clinically indicated
Topical tacrolimus 0.03, 0.1 % ointment
Other systemic treatment for very severe LP
Methotrexate 5–10 mg/week orally
Cyclosporine 4–5 mg/kg/day orally for 3–4 months
Intravaginal hydrocortisone acetate suppository 25 mg (available) or 100 mg (compounded) 10 % compounded vaginal cream
Zendell (2015)
11.3 Management of Vulvovaginal Atrophy (VVA)/Genitourinary Syndrome of Menopause (GSM)
GSM is a more descriptive term than VVA, which is part of it. It is defined as a collection of symptoms and signs associated with a decrease in estrogen and other sex steroids involving changes to the labia majora/minora, clitoris, vestibule, vagina, urethra, and bladder.
The syndrome may include, but is not limited to, genital symptoms of dryness, burning, and irritation and sexual symptoms of lack of lubrication, discomfort or pain, and impaired sexual function (please see the Chap. 8 on vulvar pain after the menopause for a detailed discussion of different treatment options).
The characteristic vulvovaginal changes that occur during and after the menopause are due to the combination of pathophysiologic aging, hypoestrogenism, and hypoandrogenism (Graziottin and Gambini 2016).
Estradiol, the primary form of estrogen produced by a woman’s ovary during her reproductive years, plays an essential role in maintaining the elasticity and health of her genital tissues, including an appropriate vaginal ad vulvar microbiota and adequate low vaginal pH (Graziottin and Zanello 2015).
The genital involution is more rapid and anticipated in women affected by a premature ovarian insufficiency (Graziottin and Lukasiewicz 2016). A iatrogenic menopause after gynecologic cancers may have an even more dramatic impact on anatomy and function of genital organs, when the premature or anticipated menopause is complicated with the side effect of vaginal/pelvic radiotherapy (Lukasiewicz and Graziottin 2015; Graziottin et al. 2016; Graziottin and Gambini 2016).
Testosterone loss is responsible for the hormone-dependent involution of the cavernosal bodies (clitoral, bulbocavernous, and part of the equivalent of the male corpus spongiosum, around the urethra), of the androgen-dependent cells of the skin, of the connective tissue (fibroblasts and myocells), and of the androgen-dependent nitrergic nerve fibers, present at vaginal (1/3 is nitrergic, 2/3 are vipergic) and vulvar level (Graziottin et al. 2015b). This is the pathophysiologically based reason why topical estrogen and testosterone are the leading treatments for the VVA and GSM, with special focus on vulvar dystrophy and associated symptoms (Box 11.10).
GSM is a chronic condition and therefore requires long-term therapy as symptoms tend to return when treatment is stopped.
Box 11.10: Management of GSM/VVA
Topical Treatments
Topical estrogens include estradiol-containing tablets and rings; estriol pessaries, creams, and ovules; and promestriene and conjugated estrogens. Compared with placebo, vaginal estrogens improved dryness, dyspareunia, urinary urgency, frequency, and stress urinary incontinence (SUI) and urgency urinary incontinence (UUI). Urinary tract infection rates decreased. The various estrogen preparations had similar efficacy and safety; serum estradiol levels remained within postmenopausal norms for all except high-dose conjugated equine estrogen cream (Rahn et al. 2014). The literature supports the efficacy of lower doses while minimizing adverse effects.
The efficacy of vestibular use of 0.005 % estriol for the treatment of postmenopausal dyspareunia has recently been demonstrated. The tenfold reduction in dose of estrogen currently administered was effective in significantly normalizing vestibular innervation sensitivity. Its formulation as a highly mucoadhesive hydrating gel provides a reservoir effect for lengthy maintenance of active estriol on the vestibular surface (Murina et al. 2016a).
Topical testosterone (testosterone propionate 2 % or, in alternative, testosterone of vegetal origin) is very effective for the treatment of VVA and GMS in the Author’s experience in otherwise healthy postmenopausal women. Topical testosterone applied daily for 3 months improves vulvovaginal trophism and relieves symptoms of VVA and GSM. It definitely improves the genital sexual response, both in the arousal and orgasm dimension, with great satisfaction of the woman and of her partner.
Topical testosterone has been used in patients with breast cancer under aromatase inhibitor treatment. Preliminary data are encouraging (Witherby et al. 2011). More recent data indicate that 300 microgram of testosterone applied in the vagina has a very significant impact on women’s sexuality: when compared with baseline FSFI scores, there was a statistically significant improvement for individual domain scores of desire (P = 0.000), arousal (P = 0.002), lubrication (P = 0.018), orgasm (P = 0.005), satisfaction (P = 0.001), and pain (P = 0.000). Total domain scores reflecting sexual health quality of life also improved when compared with baseline (P = 0.000). Long-term controlled studies on the safety profile are needed (Dahir and Travers-Gustafson 2014).
Vaginal dehydroepiandrosterone (DHEA). Daily intravaginal administration of 0.5 % (6.5 mg) DHEA for 52 weeks significantly improves dyspareunia, vaginal dryness, and irritation/itching. Cream applied in the vagina is another useful tool to be explored in treatment of VVA and GSM. Preliminary data are very positive in terms of vaginal lubrication, with no changes in the systemic levels of prasterone (Bouchard et al. 2016; Davis et al. 2016; Labrie et al. 2016). Daily dosing is necessary as reduced efficacy has been shown when the treatment is reduced to two doses/week (Bouchard et al. 2016). However, the pharmacology and mechanism of action suggest that the effect on vestibular pain could be positive, on daily dosing, as shown by Author’s experience (still preliminary results).
Nonhormonal vaginal lubricants and moisturizers. Lubricants, in general, give only temporary relief of symptoms. They must be applied frequently for more continuous relief and require reapplication before intercourse.
Fractional laser. Laser therapy may result in remodeling and thickening of vaginal connective tissue. It improves glycogen storage of the vaginal epithelium in women with vaginal atrophy. Improvement in VVA symptoms (vaginal dryness, burning, itching, and dyspareunia) and vaginal health index scores have been reported. Pulsed CO2 lasers (Monnalisa) (Pieralli et al. 2016) and erbium laser treatment (Gambacciani et al. 2015) are increasingly used in the treatment of VVA after the menopause, particularly in women after breast cancer.
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