Vulvar inflammatory disorders: A review

INTRODUCTION

Vulvar inflammatory disorders (VID) are a miscellaneous group of non-infectious conditions affecting the vulvar area that are characterized predominantly by inflammation.

CLASSIFICATION

VID can be broadly classified based on etiology or pathology though there is no universally used single classification. The International Society for the Study of Vulvovaginal Disease (ISSVD) has classified VID based on histological reaction patterns [Table 1].^[1]

This review will focus only on common VID, and a few rare conditions with characteristic features. Autoimmune vesiculobullous conditions, drug-induced vulvar dermatoses and many such, which occur as part of generalized disease, are not discussed here.

Commonly encountered VID are vulvar contact dermatitis, vulvar psoriasis, lichen planus, lichen sclerosus (LS), hidradenitis suppurativa, and lichen simplex chronicus (LSC).^[2] Vulvar pyoderma gangrenosum, plasma cell vulvitis, and desquamative vaginitis are relatively rare.^[3] Vulvar Crohn’s disease and acantholytic dermatoses of the vulvocrural area are often misdiagnosed.

VULVAR DERMATITIS

Vulvar area is prone to barrier disruption and dermatitis due to varying factors such as anatomical position, occlusion, frequent contact with bodily secretions, estrogen deficiency, friction, and heat.^[4] Vulvar dermatitis manifests as erythema, epithelial disruption, erosions, and lichenification associated with pruritus. Common endogenous causes include atopic dermatitis, seborrheic dermatitis, and LSC, whereas exogenous dermatitis comprises allergic and irritant contact dermatitis. These two entities may overlap.^[5]

Diagnosis is usually clinical; histopathological examination, which reveals prominent spongiosis with lymphohistiocytic infiltrate can differentiate dermatitis from specific causes. Intraepidermal vesiculation is characteristic of acute cases, whereas hyperkeratosis and acanthosis are present in chronic cases.

VULVAR PSORIASIS

Up to 5% of women with persistent vulvar symptoms are subsequently diagnosed as vulvar psoriasis.^[6,7] In the vulvar area, friction can act as a Koebner phenomenon leading to formation of psoriatic lesions.

Classic plaque-type psoriasis and inverse psoriasis are common, though pustular psoriasis also may occur. The well demarcated, erythematous plaques with silvery white scales of classic psoriasis have a predilection for hair-bearing areas such as mons pubis and labia majora.^[8] Inverse psoriasis is seen in intertriginous areas and folds as shiny, erythematous plaques with minimal scaling and at times, as fissuring.^[5,6,9] Common symptoms include pruritus and burning (65% cases), pain (45%), and dyspareunia (30%).^[10] The presence of typical psoriatic lesions (in other areas) and nail changes provides a clue in up to 30% cases.^[10-12] Lichenoid dermatoses, LSC, vulvovaginal candidiasis, or contact dermatitis may be confused with psoriasis.^[10]

Vulvar psoriasis reflects the characteristic histopathology of psoriasis. Occasionally superadded dermatitis or infections may necessitate a clinicopathological correlation. Dermoscopy reveals typical, red dot capillaries on an erythematous background.

Treatment: The mainstay is potent TCS, followed by less potent steroids and psoriasis-specific treatments, such as coal tar cream, topical calcipotriol, topical retinoids, and topical tacrolimus.^[12] Systemic methotrexate and dapsone are reserved for severe, resistant, or generalized disease.^[7,12,13]

VULVOVAGINAL LICHEN PLANUS (VVLP)

VVLP can occur in isolation, or as part of a generalized disease in up to 50% of patients.^[14,15] Vulvovaginal-gingival syndrome is seen in up to 65% of patients with generalized disease.^[16]

Clinical subtypes include classical papulosquamous, hypertrophic, and erosive types.

Classical papulosquamous variant has papules and plaques with whitish lacy striae on vulvar and periclitoral areas. It is responsive to TCS and may spontaneously resolve.^[14]

Hypertrophic variant is extremely itchy and is resistant to treatment.^[14]

Erosive VVLP (EVVLP) is the most common form, characteristically affecting the introitus and labia minora in perimenopausal women and may be associated with oral LP.^[14]

Pain, burning sensation and irritation (92%) are more predominant than itch (50%).^[8] Erosions may be non-specific or glazed/glossy in appearance with reticulated white borders. Complications include vaginal scarring, synechiae, obstruction, bleeding, and copious yellow discharge.^[17,18]

In severe cases, strictures with loss of vulvar architecture, vaginal shortening, marked narrowing or agglutination of introitus, and phimosis of the clitoral hood can occur and may often go unnoticed.^[19-21] There may be difficulty in micturition, per vaginal examination, and normal intercourse. EVVLP is associated with significant dyspareunia and emotional distress.^[22] There is a 2.3% estimated risk of malignant transformation, with sporadic reports of vulvar neoplasia.^[23-25]

The Delphi diagnostic criteria for erosive vulvar LP is given in Table 2.^[26]

Diagnosis can be confirmed by dermoscopy showing Wickham’s striae and histopathology revealing typical lichenoid interface dermatitis.

Hypertrophic LP shows pronounced irregular acanthosis. Erosive LP shows epidermal erosion with underlying inflammation and typical LP changes in the edge of the lesion.^[27] It is imperative to include the edge of the lesion in the biopsy.

Differential diagnoses include LS, drug eruption, cicatricial pemphigoid, vaginal intraepithelial neoplasia, and graft versus host disease (conditions that manifest with erosion, sclerotic changes, or whitish discoloration).

Treatment aims at alleviating the suffering and preventing the progression of the disease.

Ultrapotent TCS is the first-line therapy with up to 71% response rate, which may be accordingly tapered once the active lesions resolve.^[20]

Second-line treatment includes topical calcineurin inhibitors.^[21,28]

For severe disease, systemic treatment is required.^[2,29] Oral prednisolone (0.5 mg/kg body weight) or monthly intralesional infiltration of triamcinolone acetonide (10 mg/ml) is used for rapid control of symptoms. Corticosteroid-sparing agents found useful are azathioprine, cyclophosphamide, cyclosporine, dapsone, griseofulvin, hydroxychloroquine, minocycline combined with nicotinamide, mycophenolate mofetil, methotrexate, systemic retinoids, thalidomide, and biological agents such as adalimumab and etanercept. These are useful in long-term management, though often the results are disappointing, and adverse effects limit their prolonged use.^[30,31]

Hydrocortisone cream or suppositories in tapering frequency, and periodic insertion of vaginal dilators smeared with corticosteroid ointment maintains vaginal patency in patients with vaginal strictures.^[32] 150 mg fluconazole once a week is used as prophylaxis against candidal superinfection.^[33]

Labial fusion, vaginal stenosis, and clitoral phimosis may require surgical intervention after the control of the active disease, for relief of symptoms, and for restoration of urinary and sexual functions.^[34,35]

PLASMA CELL VULVITIS

Also called as vulvitis circumscripta plasmacellularis or Zoon’s vulvitis, this is a distinctive, chronic, idiopathic condition exhibiting well-demarcated shiny, erythematous, orange-red plaques, occasionally with punctate petechiae, in the vestibule and around the meatus, which may extend up to labia minora, causing itching, and burning sensation.^[2]

It must be differentiated from erosive vulvar LP and vulvar intraepithelial neoplasia (VIN). Histopathology shows atrophic epidermis with flattened, “lozenge shaped” epithelial cells, and a dermal infiltrate predominantly composed of plasma cells (>20%).

Treatment involves use of potent TCS such as clobetasol propionate 0.05% twice daily, imiquimod 5%, topical cyclosporine, topical tacrolimus 0.1%, and topical pimecrolimus 1%. For resistant lesions, intralesional infiltration with triamcinolone acetonide 10 mg/ml and ablative CO₂ laser may be tried.^[55]

DESQUAMATIVE INFLAMMATORY VAGINITIS

It is a lesser known, idiopathic, inflammatory mucositis pertaining to vagina, manifesting as excessive purulent discharge associated with itching, burning sensation, and dyspareunia. Erythema and edema of introitus and labia minora may be seen. It is a diagnosis of exclusion.^[2]

Differentials include all causes of vaginitis/cervicitis such as candidiasis, trichomoniasis, bacterial vaginosis, gonococcal, non-gonococcal, and atrophic vulvovaginitis and erosive conditions such as EVVLP, Zoon’s vulvitis, and atrophic vulvitis.

Diagnosis: Wet mount shows increased polymorphonuclear lymphocytes and squamous cells with absence of lactobacilli. Vaginal pH is more than 5.

Infectious causes should be ruled out by appropriate tests. In menopausal women, a trial with estrogen cream should be done.

Treatment includes vulvovaginal low potent steroid such as hydrocortisone and clindamycin vaginal pessaries for 1 month, later to be tapered to the least frequency required.^[2]

Low dose doxycycline, low dose naltrexone, and even oral immunosuppressives are tried in resistant cases.

PAPULAR ACANTHOLYTIC DERMATOSES OF THE VULVOCRURAL AREA

This is a rare, focal acantholytic disorder. Some consider this as a variant of Hailey-Hailey disease or Darier’s disease localized to the genitalia.^[56] Painful or pruritic, hypo-pigmented to slightly erythematous, papules, and plaques appear over the vulva which may extend to the perineum and the medial aspect of thighs.^[57] Clinical differentials include Hailey-Hailey disease, Darier’s disease, warty dyskeratoma, pemphigus vegetans, and condyloma acuminata.

Histopathology reveals hyperkeratosis, focal parakeratosis, full thickness acantholysis, and dyskeratosis visible as “corps ronds” and grains.

Treatment: Unlike Hailey-Hailey and Darier’s disease, lesions are very resistant to any form of therapy including topical steroids, tacrolimus, and tretinoin. CO₂ laser, radiofrequency ablation as well as cryotherapy have been tried. Solitary or a few nodules can be surgically excised.

VULVAR CROHN’S DISEASE

Mucocutaneous involvement is seen in approximately 15% cases of Crohn’s disease, and skin involvement precedes intestinal disease in one-fourth cases. Contiguous disease from the colon produces perianal fistulas, whereas metastatic Crohn’s has varying presentations.

Distinctive clinical features include non-pitting vulvar edema and knife cut ulcers at skin creases. Other features include perianal fistula, violaceous nodules, and firm or verrucoid tags. Chronicity leads to lymphedema, lymphangiectasia, verrucosa nostras, and vulvar ulcers.^[58] Young girls typically present with indurated labial edema.^[59]

Diagnosis is by correlation with other organ involvement; granulomatous inflammation is characteristic on histopathology.

Elevated fecal calprotectin level (>250 microgram/mg) is 87% specific and 99% sensitive for diagnosis.^[60]

Systemic treatment of Crohn’s disease will improve the vulvar lesions too.

ATROPHIC VULVOVAGINITIS

The current term is “genitourinary syndrome of menopause” (GSM).^[61] It occurs in an estrogen depleted (after natural or surgical menopause, or even during prolonged breast feeding) vulva and vagina. There is atrophy, decreased moisture and elasticity predisposing to barrier dysfunction, erythema, erosions, and mucopurulent discharge. Symptoms include dry, itchy irritated skin with burning sensation, and dyspareunia. Occasionally urinary symptoms such as increased frequency, dysuria, and recurrent urinary tract infections are seen.^[2] Diagnosis is confirmed by microscopy which shows immature parabasal squamous cells with normal or increased polymorphonuclear leukocytes on saline wet mount.

Management: First-line treatment is topical estrogen cream 0.5–4 g at night for 2 weeks, alternate nights for 2 weeks, then maintenance therapy of 1–2 times/week. Adjuvants include moisturizers and lubricants, and short term or intermittent use of low potent steroid such as hydrocortisone 1% cream. Oral ospemifene, an estrogen agonist has been tried, but is not widely used. Counseling the patient (regarding the condition, use of topical estrogen and its side effects and the need for sustained treatment) is of paramount importance. Superadded candidiasis should be treated.^[2]

GRANULOMATOUS VULVITIS

This is a lesser known entity also known as hypertrophic vulvitis, chronic edema of the vulva and Melkersson-Rosenthal vulvitis.^[39] It is considered to be a counterpart of orofacial granulomatosis, though some consider it to be an early spectrum of Crohn’s disease. It may be associated with granulomatous cheilitis. Progressive fibrosis and lymphedema may complicate the course.

Histopathologically, it is characterized by dermal edema, lymphocytic infiltrate, and non-necrotizing epitheloid cell granulomas in the deep dermis. Crohn’s disease and sarcoidosis, which also present with vulvar edema and granulomatosis, must be ruled out.^[39]

Treatment involves intralesional or systemic steroids for acute and severe cases. Oral metronidazole, clofazimine, hydroxychloroquine, and danazol can be used as maintenance treatment.^[39]

DERMATITIS ARTEFACTA

This has to be considered in any vulvar condition which appears atypical and induced. The means of production and appearance of lesions vary considerably, though common methods include application of irritants, chemicals, marking nut and intravaginal insertion of foreign bodies which can lead to erythema, edema, blistering, erosion, and vaginal discharge. A high index of suspicion is needed to make the diagnosis. Symptomatic treatment with psychiatric and clinical psychology consultations forms the crux of the management.

MANAGEMENT OF VULVAR DERMATOSES

All vulvar dermatoses present almost alike with erythema, edema, itching, burning, and dyspareunia. Erosions or ulcers may be primary to the pathology or induced by scratching. Infection induced and neoplastic vulvar dermatoses may mimic inflammatory conditions. Hence, a thorough physical and laboratory examination with a careful eye to any subtle clue should be the norm.

History taking should be thorough and focus on the chronicity, precipitating factors, menstrual history, type and amount of discharge or lesions, and any associated systemic complaints.

A detailed, careful inspection of the vulva including mons, crural folds, and perianal region, and then focusing centripetally should be performed. A general examination and dermatological examination should complement the genital examination.

Other causes for vulvar edema and erosions should be ruled out, a detailed description of which is beyond the realm of this article [Table 3].^[39]

Corroborative investigations include wet mount or Gram stain of the vaginal discharge, potassium hydroxide (KOH) mount to rule out fungal infections, or even acetowhitening, tests for other sexually transmitted infections and biopsy wherever indicated. Dermoscopy of vulvar area is now widely practiced and can help in the diagnosis of conditions such as psoriasis, lichen planus, and various malignancies.

Occasionally, more than one pathology may co-exist (e.g., LS with LSC or psoriasis with allergic contact dermatitis); hence, it is prudent to keep a discerning eye.

TCS are the treatment of choice in most inflammatory conditions. Topical steroid sparing agents, systemic steroids, and other immunosuppressives may be added in severe, non-responsive cases.

Fungal superinfection should be prevented by prophylactic antifungal therapy whenever prolonged treatment is anticipated.

Associated factors such as malnutrition, anemia, and psychosexual distress should be dealt with. Proper genital hygiene measures should be discussed with the patient. The need for prompt and timely follow-up should be overemphasized.

CONCLUSION

Vulvar inflammatory disorders are more common than encountered, due to reticence of females to seek professional help. A thorough knowledge of the nuances of presentation of various inflammatory conditions, along with judicious investigation and apt management will go a long way in providing physical and psychological comfort to the patient.