Case Report of Treatment Resistant Vulvodynia
Vulvodynia is a painful vulvar medical condition with many proposed etiologies and treatments. We describe two compounded pharmaceutical treatments of an elderly female with treatment resistant vulvodynia. The first treatment consisted of 4% cromolyn sodium, 2% Lidocaine USP, 4% Amitriptyline HCl USP, 0.25% Atropine Sulfate USP, and 2% Ketoconazole USP in a polyethylene glycol base. It merely increased the patient's discomfort. The second treatment consisted of 0.25% Atropine Sulfate USP, 10% Ketoconazole USP and 10% Biotin USP as a combination in a cocoa butter base. It resulted in the full remission of the vulvodynia.
Vulvodynia literally means "vulvar pain." Therefore, vulvodynia is a symptom, not a disease. One that indicates a variety of unpleasant chronic vulvar sensations, including burning, rawness, soreness, irritation, sensitivity, formication and sometimes dyspareunia.1 Classical primary "vulvodynia" is without objective physical findings to explain the symptoms. A satisfactory understanding of prevalence, pathogenesis, natural history, and management of this distressing condition continues to be elusive. Prevalence studies suggest one in six women may experience vulvodynia, although such a figure reflects clinic, patient or author reporting bias. Symptoms are as likely to be found in non-white as in white women. Although infection is often blamed, evidence for its role or that of inflammation is minimal. Immunohistochemistry has shown altered density of nerve endings and estrogen receptors. There may be overlap with other pain syndromes.
Several reviews have examined the many therapies available. Pharmacological alteration of nerve conduction (tricyclic antidepressants, gabapentin, local anesthetics), biofeedback and sometimes surgery are helpful, but not always. Therefore, a pressing need exists for case-control studies of potential causes of vulvodynia and for randomized trials of interventions.2,3
With this background, we present a case report on the successful treatment of a treatment-resistant seventy-four year old woman with vulvodynia. On her intake she was clearly in discomfort sitting in her chair. She reported a six year history of "severe vulvodynia" diagnosed by four gynecologists and three primary care physicians who prescribed various treatments that were "not helpful." Her treatments included:
With these unsuccessful preliminary treatments, and an unknown etiology, we considered a vaginal suppository with multiple ingredients with different therapeutic mechanisms. All precursor agents were United States Pharmacopeia pharmaceutical grade quality.
Her first suppository included 4% cromolyn sodium, 2% Lidocaine USP, 4% Amitriptyline HCl USP, 0.25% Atropine Sulfate USP, and 2% Ketoconazole USP in a polyethylene glycol base. The patient used the first suppository and immediately experienced a worsening of her vaginal pain, and was directed to discontinue treatment. It was determined that she had incorrectly reported that she had "no allergies," and actually had an allergy to lidocaine. It was hypothesized this might have been the source of her discomfort.
Another final option was proposed. It contained 0.25% Atropine Sulfate USP, 10% Ketoconazole USP and 10% Biotin USP in a combination prescribed in a cocoa butter base. These components were selected since vulvodynia etiologies include hyperirritability of pelvic floor muscles, chronic yeast infections, human papillomavirus, neuropathic dysfunction and nutritional deficiencies. Therefore, we considered a suppository, which might address these various possible etiologies in a localized delivery treatment.
The use of low-dose local atropine was intended to decrease any possible hyperirritability of pelvic floor muscles, leading to painful spasms. The genital tract is lined with involuntary smooth muscle. The autonomic motor neuron synapses of the smooth muscles have muscarinic receptors to react to neurotransmitter release. Atropine, an antispasmodic, blocks these muscarinic receptors and prevents the signaling cascade of muscle contraction. As a result, atropine may be effective in treating vulvodynia by reducing the pain. 4-11 Ketoconazole is an azole antifungal that has demonstrated anti-inflammatory activity.12,13 Biotin is a water-soluble B vitamin that has been shown to improve neurologic symptoms in patients. The results of clinical studies have provided evidence that marginal biotin deficiency is more common than was previously thought.14 Even oral supplementation in healthy elderly patients, eating well, and taking a single multivitamin, still showed 39% had essential nutrient deficiencies, including deficiencies of biotin.15 In addition, 1 in every 123 individuals may have biotinidase deficiency, so some women with chronic vaginal candidiasis, possibly causing treatment resistant vulvodynia, might respond to biotin administration.16 Cocoa butter was chosen as the base to minimize chemical insult and for its soothing properties.
The patient was instructed to use one suppository vaginally in the morning and evening. After twelve days of treatment, she returned for a consultation. She experienced a dramatic elimination of her vaginal pains and discomfort. Specifically, when asked about the effects of the treatment, she explained "it was not important." She began to talk about family tensions and other social problems. She was redirected twice back to the treatment for vulvodynia. She simply explained that her "pain was entirely gone," she was "very pleased that finally" she had "a treatment that worked," and returned to talking about her relatives. She appeared very comfortable as she conversed, smiled, and moved around the room. In complete contrast to her intake session.
The atropine sulfate, ketoconazole and biotin formula was successful for this elderly woman. However, it would be inappropriate, due to the complexity and uncertainty of this disorder's etiology, to assume that this treatment would be successful in most vulvodynia patients. We do believe a sub-group would benefit, but have no scientific grounds to propose a percentage that might find this treatment useful.
Nevertheless, any suggestion that this patient had a spontaneous resolution during the week she initiated treatment does not seem compelling. We believe this compounded suppository was the agent of pain relief for three reasons. She had six years of continuous suffering, her pain promptly ended with treatment and lasted over ten months, and the treatment is consistent with some of the proposed causes of vulvodynia.
This case demonstrates that compounding is not merely an integral component of the profession of pharmacy, but it is also a useful tool for physicians in obtaining treatment options. Sample options include combination medications and transdermal medications in which oral routes are not functional or optimal due to nausea, diarrhea or iatrogenic irritation of the intestinal lining. Compounders also make an unappealing liquid medication more palatable or convert tablets into liquid delivery systems.17 They also are routinely involved in creating precise hormone replacement preparations.
Pharmaceutical compounding involves additional accredited training or a fellowship, just as subspecialties or certifications in medicine require additional training. The compounding of individualized pharmaceutical agents falls under the authority of the individual state boards of pharmacy, and not the U.S. Food and Drug Administration, since compounding is not considered manufacturing.18 Further, compounders adhere to strict compounding regulations, and use base medications meeting United States Pharmacopeia pharmaceutical quality standards.
Physicians interested in finding a local compounding pharmacist for this preparation or other pharmaceutical goals might seek a referral from:
James Schaller, M.D., M.A.R.
Michael Briggs, Pharm.D.
Ben Briggs, R.Ph., C.N.C.
Dr. Schaller has no disclosures.
Dr Michael Briggs and Ben Briggs are members of Professional Compounding Centers of America. Therefore, as compounding pharmacists they could, along with thousands of other members, produce the suppository in this article.