Chemen M. Tate
History of present illness
A 42-year-old gravida 2, para 2 woman presents to your office as an urgent consultation from her primary care physician for persistent symptoms of vaginitis not responsive to traditional therapy. The patient reports symptoms of vaginal dryness, burning with intercourse, an excessive amount of yellow dis- charge, and intermittent feelings of vaginal irritation for the past two years. She denies vaginal odor, does not douche, and is in a monogamous relationship with her husband who has had a vasectomy. She reports being tested for “everything” with only negative results. She has been treated multiple times with oralfluconazole, terconazole, and metronidazole by sev- eral providers with minimal or no relief. She has most recently been treated with boric acid suppositories, which only made her symptoms worse for a time. She reports regular menses and has no medical or surgical history. She takes no medications.
She is embarrassed by her symptoms and rarely enjoys intercourse because of the discomfort. She is concerned these issues are damaging her relationship with her husband and reports feeling hopeless and frustrated. She is “willing to try anything.”
Physical examination
General appearance: Well-developed, well-nourished woman in no apparent distress
Vital signs:
Temperature: 37.0°C Pulse: 97 beats/min
Blood pressure: 106/68 mmHg Respiratory rate: 15 breaths/min HEENT:Negative
Chest:Clear to auscultation Cardiac:Regular rate and rhythm
Abdomen:Soft, nontender, no palpable masses External genitalia:Unremarkable
Vagina:Erythematous mucosa, a yellowish discharge is noted, no ulcers or lesions
Cervix:Parous and without abnormality
Uterus:Anteverted, mobile, and nontender, normal size Adnexa:Nontender, no masses palpated
Laboratory studies:
NAATs: Negative for chlamydia and gonorrhea
Candida/bacterial vaginosis/trichomonas DNA probe:
Negative
HSV-1/2 serum IgG: Negative Whifftest: Negative
Vaginal pH: 6
Wet prep: Many WBCs, amidst rounded-appearing epithelial cells with prominent nuclei, and an absence of lactobacilli. Negative for trichomonas, hyphae, or clue cells
How would you manage this patient?
This patient gives a history that is common for many types of vaginitis. She has dyspareunia, abnormal discharge, and vaginal irritation. On examination, she has clinical features of an inflammatory vaginitis but typical laboratory studies for infectious vaginitis (trichomoniasis, bacterial vaginosis, candidiasis, etc.) are all negative. Microscopy confirms an inflammatory process with the increased presence of white blood cells (WBCs) and shows signs of desquamation with the presence of immature epithelial cells or parabasal cells.
While one mightfind many similarities with postmenopausal atrophic vaginitis, this patient is menstruating regularly and does not endorse any other symptoms of estrogen deficiency.
This patient’s combination of physical and microscopicfind- ings are consistent with the diagnosis of desquamative inflam- matory vaginitis or“DIV.”
Desquamative inflammatory vaginitis
As in this patient, the diagnosis of desquamative inflammatory vaginitis (DIV) is clinical. The basic diagnosis involves a triad of dyspareunia, increased vaginal discharge, and inflammation, as evidenced by vaginal erythema and increased WBCs on wet prep [1]. Trichomoniasis, bacterial vaginosis, candidiasis,Neis- seria gonorrhoeae, andChlamydia trachomatisshould also be excluded. The differential diagnosis also includes more rare causes of vaginitis such as erosive vulvar lichen planus, cica- trical pemphigoid, pemphigus vulgaris, and linear immuno- globulin A (IgA) disease. These diseases may show extra genital manifestations, such as oral or integumentary ulcer- ations, bullae, or erosions, and will likely be unresponsive to the therapy outlined in this case. Specific histopathology or immunofluorescence findings can also be seen on biopsy in these rare cases. Common histologicfindings of vulvar erosive lichen planus include a well-defined band, composed primarily Acute Care and Emergency Gynecology, ed. David Chelmow, Christine R. Isaacs and Ashley Carroll. Published by Cambridge University Press.
© Cambridge University Press 2015.
of lymphocytes, at the dermoepidermal junction and liquefac- tion or signs of degeneration of the basal layer [2]. The auto- immune bullous disorders are primarily diagnosed by direct immunofluorescence (DIF) techniques. Deposition of anti- bodies, often IgG, IgA, or C3, are seen along the basement membrane zone in 80–100% of these cases [3].
The evaluation of all women with complaints of recurrent vaginitis should include a speculum examination, vaginal pH testing, and saline microscopy with further infection testing as indicated. Commercial DNA-based tests are available and can significantly improve the detection of bacterial vaginosis (45% vs. 14%) andCandida(11% vs. 7%), when compared to saline microscopy alone. The low sensitivity of microscopy as a diagnostic tool for trichomonas infections make it insufficient for the exclusion of this pathogen. WBCs, which are numerous in patients with DIV, can also make it very difficult to identify trichomonads on saline microscopy.
Nucleic acid-based testing for trichomoniasis is now con- sidered the gold standard and can be performed with testing for N. gonorrhea and C. trachomatis infection from a thin prep vial, endocervical swab, or urine sample. These testing modalities increase the accuracy of the diagnosis in settings where speculum examination and/or microscopy is/are unavailable or unfeasible. When there is suspicion for extragenital disease manifestations, ulcerative lesions, or unresponsiveness to therapy, biopsy for histopathologic evaluation should be considered [4].
It is not known whether DIV represents a sterile inflamma- tory vaginitis or is the result of an infectious agent. Therefore, treatment of DIV is targeted at resolution of inflammation and/or treatment of potential infectious organisms. There are no randomized control trials available to guide treatment and most available studies characterizing DIV involve small numbers of patients. The International Society for the Study of Vulvovaginal Disease (ISSVD) recommends treatment with clindamycin 2% vaginal cream and 10% hydrocortisone cream administered intravaginally [5].
There are several strategies that have been recommended by the ISSVD and have shown to be effective (Table 8.1).
Duration of treatment seems to be an important factor that is common among all described treatment regimens, and should last four to eight weeks. It is generally recommended to treat for four weeks followed by a repeat pelvic examination and repeat microscopy [6]. If physical examination and micro- scopyfindings are normal after four weeks, treatment can be considered complete. If inflammation is still present on phys- ical examination or microscopy, treatment should be con- tinued an additional two to four weeks depending on the clinical response. Some patients will not be able to stop treat- ment without relapsing and may need maintenance therapy with either topical clindamycin or hydrocortisone used once or twice per week. In more severe cases, a higher potency steroid such as clobetasol can be used during the initial treatment phase. A lower potency steroid such as hydrocortisone should be used for maintenance.
Unfortunately, patients may relapse at intervals of months to years later. Treatment should be approached in the same way and routine surveillance via microscopy during symptom- free intervals may be considered. As most women with DIV are nonmenopausal and in their thirties to mid-forties, vaginal estrogen is not part of the treatment and does not seem to improve symptoms. DIV does occur in postmenopausal women and should be considered if estrogen therapy does not resolve atrophic vaginitis, or in patients who have a large amount of purulent vaginal discharge.
To help diminish feelings of frustration and to encourage long-term follow-up and compliance, patients should be counseled that many types of vaginitis are recurrent and can require extended treatment durations or maintenance medica- tions to control symptoms. Patients should also be counseled that a great deal of research still needs to be done regarding the cause of all types of recurrent vaginitis and that treatment regimens will continue to evolve. The patient in this case had significant improvement after a four-week treatment course,
Table 8.1 Desquamative inflammatory vaginitis (DIV) treatment strategies
Medication Instructions
Clindamycin 2% vaginal cream Use nightly × 4 weeks. If incomplete response, continue and evaluate in 2–4 weeks, or switch to 10% hydrocortisone administered vaginally
10% Hydrocortisone vaginal cream or suppository* Use nightly × 4 weeks. If incomplete response, continue and evaluate in 2–4 weeks or switch to clindamycin 2% vaginal cream
2% Clindamycin + 10% hydrocortisone
compounded as a vaginal cream or suppository Use nightly × 4 weeks. If incomplete response, continue and evaluate in 2–4 weeks Maintenance therapy†
(for recurrent or refractory cases) Once or twice weekly 2% clindamycin or 10% hydrocortisone
* 10% Hydrocortisone cream is not commercially manufactured: 25 mg hydrocortisone rectal suppositories (Anusol®) can be more cost effective and can be administered vaginally as a substitute when compounding is not available.
†Maintenance therapy is dictated by patient symptoms. Therefore, patients can self-taper to a dosing frequency that maintains a symptom-free state.
but ultimately required weekly clindamycin to maintain a symptom-free state.
Key teaching points
Desquamative inflammatory vaginitis (DIV) is a form of vaginitis. The diagnosis involves a triad of dyspareunia, increased vaginal discharge, and inflammation as
evidenced by vaginal erythema and increased white blood cells on wet prep.
Other causes of vaginitis including trichomoniasis, bacterial vaginosis, and candidiasis must be ruled out.
It is not known whether DIV represents a sterile inflammatory process, an infectious process, or some combination of both. Treatment is aimed at eliminating inflammation with intravaginal steroids and eliminating infection using intravaginal clindamycin.
Treatment duration of four to eight weeks is usually required. Some patients will require weekly maintenance therapy with intravaginal clindamycin or steroid.
References
1. Sobel JD. Desquamative inflammatory vaginitis: A new subgroup of purulent vaginitis responsive to topical 2%
clindamycin therapy.Am J Obstet Gynecol1994;171(5):1215.
2. Simpson RC, Thomas KS, Leighton, P, Murphy R. Diagnostic criteria for erosive lichen planus affecting the vulva: An international
electronic-Delphi consensus exercise.
Br J Dermatol2013;169(2):337.
3. Yali S, Pelivani N, Beltraminelli H, et al.
Detection of linear IgE deposits in bullous pemphigoid and mucous membrane pemphigoid: A useful clue for diagnosis.
Br J Dermatol2011;165(5):1133.
4. Brown HL. Overview of vaginitis:
office-based DNA testing.The Female Patient2006;31(8 suppl):1–6.
5. International Society for the Study of Vulvovaginal Disease.21st Biennial Conference on Diseases of the Vulva and Vagina. Sept. 6–9, 2012. Available at www.ISSVD.org.
6. Sobel JD, Reichman O, Misra D, Yoo W. Prognosis and treatment of desquamative inflammatory vaginitis.Obstet Gynecol 2011;117;4:850.
Case 8: A 42-year-old woman with recurrent unexplained vaginitis symptoms