3.3.1: Inflammatory Disorders of the Vulva

Note

Inflammatory disorders of the Vulva are a miscellaneous group of non-infectious conditions affecting the vulvar area and are characterized mainly by inflammation.¹ This section will cover Vulva lichen sclerosis (VLS) since it is one of the most common pathologies present in clinics.

For details on other inflammatory conditions affecting the vulva, including atopic dermatitis, contact dermatitis, lichen simplex chronicus (LSC; squamous cell hyperplasia) and vulvar psoriasis, please refer to Prabhu, Smitha and Swathy Krishna. "Vulvar inflammatory disorders: A review". Journal of Skin and Sexually Transmitted Diseases. 4 No. 2 (July-December 2022). 189-195. DOI. 10.25259/SSTD_11_2021 This open-access article distributed under the terms of the Creative Commons Attribution-Non Commercial-Share Alike 4.0 License. https://jsstd.org/view-pdf/?article=ddef97141e2f1afa86fb2029d051544fvPLQsgFIo5Q=.

3.3.1.1 Vulvar Lichen Sclerosus

• Overview and Definition

Lichen sclerosis is a chronic progressive inflammatory auto-immune, non-contagious, and non-neoplastic dermatosis of the genital skin. It presents with white, atrophic plaques often forming a “figure-of-eight” configuration around the vulva and perianal region, and can lead to scarring and functional impairment. The current International Society for the Study of Vulvovaginal Disease (ISSVD) classification includes this disease entity with vulvar dermatoses, which are nonneoplastic and non-infectious. There is a potential for lichen Sclerosis to transform into vulvar intraepithelial neoplasia (VIN) and keratinizing vulvar carcinoma. Also, VIN associated with LS is differentiated (dVIN); cancer seems always to be preceded by dVIN in the context of LS.²

• Epidemiology, Etiology, Risk Factors, and Pathogenesis

VLS has a bimodal age distribution, primarily affecting prepubertal girls and postmenopausal women, with an estimated prevalence of 1:30 in the latter. Incidence has doubled over two decades, possibly due to increased awareness. The etiology of LS remains unknown, but several mechanisms have been studied for this noncontagious disease. Studies suggest multiple etiologies, including a genetic (Up to 12% report a first-degree relative with VLS; HLA-DQ7, -DQ8, -DQ9, and -DR12 associated with increased susceptibility; HLA-DR17 may be protective​), autoimmune (High co-occurrence with autoimmune disorders such as thyroiditis, type 1 diabetes, and systemic sclerosis and presence of activated T cells in the subepithelial infiltrate), hormonal (More common in hypoestrogenic states; theories on local androgen deficiency), local trauma (Koebner phenomenon—lesions arising at sites of chronic irritation), and infectious (Borrelia burgdorferi, HPV, and HCV) background.³

• Pathogenesis

Autoimmune-driven inflammation involves T-cell infiltration and basal keratinocyte damage leading to collagen hyalinization and tissue sclerosis. Overexpression of miR-155 inhibits Treg function and promotes autoimmunity. Th1 cytokines and oxidative stress promote chronic inflammation. Details on the pathogenic mechanisms are outlined in Figure 3.3.1.⁴

Figure 3.3.1. Schematic overview of lichen sclerosus pathogenesis. (1) Risk factors for LS; (2) The inflammatory early stage of LS is unspecific and shows a dermoepidermal interface band of mostly T-cells. (3) miR-155 is overexpressed in LS, stimulates the Th1 profile and the dermal sclerosis. (4) Th1 cytokines implicated in the pathogenesis of LS. (5) Lichenoid infiltrate of TCD4+, TCD8+, and Tregs cells in the upper dermis. (6) Abnormal expression of CD44 in the epidermis and lichenoid infiltrate. (7) The sclerotic late stage of LS presents an atrophic epidermis, with comedo-like plugs and a cleft in the stratum corneum, dermal sclerosis, reduction and dilation of dermal vessels and the appendages disappear. (8) The autoantibodies against EMC1 may activate MMP9, which subsequently activates TGF-β. (9) TGF-β and BMP2 induce the synthesis of collagen I and III in fibroblasts. (10) Galectin-7 induces the synthesis of collagen I and III. (11) Along with inflammation, the vessel sclerosis contributes to the oxidative stress in LS, leading to downregulation of tumor suppressors genes and overexpression of p53 in the skin, factors related with the development of skin carcinomas. The precise sequence of events and their interactions are only incompletely understood. References: BMP2: bone morphogenetic protein 2; EMC1: extracellular matrix protein 1; LS: lichen sclerosus; MMP9: metalloproteinase 9; TGF-β: tumor growth factor beta. TNF-α: Tumor necrosis factor alpha.
Source: De Luca DA, Papara C, Vorobyev A, et al. "Lichen sclerosus: The 2023 update." Front Med (Lausanne). 10 (Feb 16 2023) doi:10.3389/fmed.2023.1106318. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY).

• Morphology

Grossly, lesions are smooth, porcelain-white plaques. There is marked hyperkeratosis (excessive keratinization), thinning of the epidermis (epidermal atrophy), degeneration of the basal layer, loss of rete pegs (finger-like extensions of the epidermis into the dermis), papillary dermal edema and sclerotic changes, hyalinization and homogenization of collagen in the upper dermis, and chronic inflammatory infiltrate in the dermis around blood vessels (lichenoid or band like) (Figure 3.3.2). Early LS may be histologically misdiagnosed as eczema or “nonspecific vulvitis.” ⁵

Figure 3.3.2. Classic histology of vulvar LS includes hyperkeratosis of the epidermis (A), epidermal atrophy with loss of rete ridges (B), homogenization of the collagen below the dermal-epidural junction (C), and lichenoid T-lymphocyte infiltrate near the basement membrane (D). This work is published and licensed by Dove Medical Press Limited.
Source: Krapf, Jill M., Leia Mitchell, Michelle A. Holton, and Andrew T. Goldstein. “Vulvar Lichen Sclerosus: Current Perspectives.” International Journal of Women’s Health, 2020. https://doi.org/10.2147/IJWH.S191200.This work is published and licensed by Dove Medical Press Limited. The full terms of this license are available at https://www.dovepress.com/terms.php and incorporate the Creative Commons Attribution – Non-Commercial (unported, v3.0) License http://creativecommons.org/licenses/by-nc/3.0/.

• Clinical Picture and Diagnosis

The diagnosis of LS is usually clinical. Careful history-taking and clinical examination are essential for diagnosis. The condition presents with patchy, thin, glistening, smooth, white areas affecting the labia and perineum with subsequent atrophy of the labia, and vulvar skin and constriction of the vaginal orifice leading to significant pain and sexual dysfunction. Diagnosis is mainly based on clinical features, and biopsy is reserved for cases if there is a doubt in diagnosis, a suspicion for preneoplastic and neoplastic change such as vulvar intraepithelial neoplasia and vulvar cancer, resistance to adequate treatment, or atypical extragenital presentations. Biopsy should be performed from the interface between normal and abnormal areas. A biopsy should also be performed on the hyperkeratotic areas and erosions that do not improve with treatment or sites with altered pigmentation. Assessment should also include workup for autoimmune diseases such as type 1 diabetes mellitus, thyroid disease, scleroderma, and rheumatoid arthritis, as there is an association between VLS and autoimmune diseases.⁶

• Differential Diagnosis

VLS is commonly misdiagnosed as Candida albicans vulvitis, thrush, or postmenopausal atrophy. The differentials also include lichen planus, localized scleroderma, leukoplakia, and vitiligo, and immunobullous disorders such as cicatricial pemphigoid, cutaneous patch of Lyme disease and vulvar intraepithelial neoplasia (VIN).⁷

• Treatment

Early and adequate treatment, ensuring restoration of normal skin color and texture, is essential for lowering the risk of malignant transformation. The first line of treatment is topical corticosteroids. Second-line treatment includes topical calcineurin inhibitors. Systemic immunosuppressives (cyclosporine and methotrexate) and oral acitretin can be used in resistant cases. Other therapies include fractional CO2 laser therapy, platelet-rich plasma, and high-intensity focused ultrasound. However, no evidence supports the role of these emerging therapies in preventing malignant transformation. Surgical techniques for restoring vulvar anatomy and treating clitoral phimosis, introital stenosis, and vulvar granuloma fissuratum lead to improved sexual dysfunction and satisfactory outcomes.⁸

3.3.1.2 Juvenile Vulvar Lichen Sclerosus (JVLS)

• Definition and Epidemiology

JVLS is a chronic inflammatory, autoimmune dermatosis of the anogenital region occurring in girls in childhood and adolescence. Affects approximately 1 in 900 girls aged 2–16. It is clinically similar to adult VLS, but with additional psychosocial and diagnostic challenges​, including being underreported (misattribution to abuse or infection) and often persisting beyond puberty (complete remission is rare​).⁹

• Etiology and Pathogenesis

Similar to adult VLS, with an autoimmune basis. Histological features (Th1-dominant inflammation with features of autoimmune attack) are consistent across age groups, suggesting immune-mediated mechanisms. Early-onset JVLS has not been associated with neoplastic progression but necessitates long-term surveillance. No reported cases of differentiated valvular intraepithelial neoplasia or valvular squamous cell carcinoma in juveniles, but adult sequelae are possible; hence, long-term surveillance is recommended.¹⁰

• Clinical Features and Morphology

Symptoms include pruritus, pain, constipation, and perineal involvement. Histologically, JVLS demonstrates general features of VLS, including epidermal thinning, loss of rete ridges, hyperkeratosis, dermal sclerosis, papillary edema, melanophages, and lymphocytic infiltrate. Some features (e.g., basal vacuolar change) are more prevalent in younger children​.¹¹

• Treatment and Prognosis

Management parallels adult protocols. Regular follow-up is critical due to the risk of architectural distortion and chronicity.¹²

3.3.1.3 Other Vulvar Inflammatory Dermatoses

• Valvular Dermatitis

Vulvar dermatitis typically presents with redness, skin breakdown, erosions, and thickened skin (lichenification), often accompanied by itching. It may arise from internal (endogenous) conditions such as atopic dermatitis, seborrheic dermatitis, or lichen simplex chronicus (LSC), or from external (exogenous) triggers like irritant and allergic contact dermatitis. These forms can coexist or overlap. Diagnosis is primarily clinical. Histopathology helps distinguish dermatitis from other conditions, as well as confirming atypical cases or those unresponsive to treatment. Key microscopic features include marked spongiosis with a lymphohistiocytic infiltrate. Acute dermatitis may show intraepidermal vesicles, while chronic cases often exhibit hyperkeratosis and epidermal thickening (acanthosis). A comprehensive clinical history is warranted for accurate diagnosis. Therapy aims to reduce the inflammatory process to culminate symptoms like itching and help restore the skin barrier. Treatment aims to control inflammation, stop the itch-scratch cycle, and restore the skin barrier. Avoiding known irritants and allergens is essential. First-line therapy includes topical corticosteroids (TCS) twice daily for a week and then gradually reduced to once weekly. The regular use of emollients supports skin barrier repair and relieves itching. Sedating antihistamines may be beneficial for nocturnal itch control. For cases unresponsive to corticosteroids, topical calcineurin inhibitors (such as tacrolimus 0.03% or 0.1% or pimecrolimus 0.1%) serve as second-line options. Addressing underlying factors such as stress, tight clothing, obesity, and excessive cleansing practices can improve outcomes. Patients should be advised against overzealous genital hygiene routines.¹³

• Atopic Dermatitis

Usually presents with a picture similar to eczema during childhood and is associated with a family history of atopy.¹⁴

• Lichen Simplex Chronicus (LCS)

Occurs either as a primary disease or secondary to other valvular conditions. Chronic scratching secondary to chronic pruritus aggravated by heat, moisture, menstruation, and tight clothing results in breaking skin barriers with subsequent susceptibility to infections. Mainly affects hair-bearing areas, leading to hair loss in chronic cases, and may affect the perineum and mucous surfaces. Lesions are thickened and lichenified. Histology reveals acanthosis, hyperkeratosis, hypergarnulosis, papillomatosis, inflammatory infiltrate, and lamellar dermal thickening. Neural fibrosis may be seen.¹⁵

• Contact Dermatitis

Triggered by direct injury caused by irritants or allergens (menstrual pads, excessive washing, and hair removal). Irritant contact dermatitis is more frequent than allergic forms and results from disruption of the skin barrier by substances like urine, feces, vaginal discharge, sweat, semen, topical medications, soaps, and depilatory creams. It commonly affects older women with urinary incontinence and those who practice excessive genital cleansing. Allergic contact dermatitis arises from sensitization to allergens such as fragrances, preservatives, local anesthetics, antiseptics, wet wipes, condoms, nail polish, and nickel. Clinical features of both types include erythema, scaling, vesiculation, oozing, and crusting. Irritant dermatitis typically presents with more pronounced rawness and weeping.Chronic inflammation may lead to secondary lichen simplex chronicus due to persistent scratching and skin thickening. Diagnosis is clinical or via patch testing.¹⁶

• Lichen Planus (LP)

LP is an immune-mediated condition affecting mucocutaneous surfaces. It may present as an isolated disease or part of a generalized syndrome (e.g., vulvovaginal-gingival). Clinical variants include the classical papulosquamous, hypertrophic, and erosive subtypes. Classical papulosquamous VVLP appears as papules or plaques with characteristic white, lacy striae over the vulva and periclitoral skin. This form is generally responsive to topical corticosteroids and may even resolve spontaneously. Erosive LP (most common) primarily affecting the introitus and labia minora, particularly in perimenopausal women. It may coexist with oral lichen planus. Presents as glazed erosions with white reticulated borders, leading to vaginal stenosis and scarring. Complications may include abnormal vaginal discharge, bleeding, tissue adhesions (synechiae), and progressive scarring, potentially resulting in significant anatomical changes. These changes include introital narrowing or agglutination, vaginal shortening, and clitoral hood phimosis, resulting in dyspareunia and distress. There is a risk of malignant transformation. Patients often report pain, burning, and irritation symptoms more prevalent than itching and experienced by up to 92% of those affected. Diagnosis is largely clinical and supported by dermoscopy (showing Wickham’s striae). Hypertrophic VVLP is intensely pruritic and often resistant to standard therapies. ¹⁷

• Histologically

Hypertrophic lichen planus is characterized by marked and irregular thickening of the epidermis (acanthosis). In contrast, erosive lichen planus is defined by areas of surface erosion accompanied by a dense inflammatory infiltrate, with hallmark features of lichen planus most prominently seen at the periphery of the lesion. For accurate diagnosis, it is essential that biopsies include the edge of the affected area.

The differential diagnosis for these forms includes other erosive or sclerotic vulvar conditions such as lichen sclerosus, drug-induced eruptions, cicatricial pemphigoid, vaginal intraepithelial neoplasia, and graft-versus-host disease.

The primary goals of treatment are to reduce symptoms and prevent disease progression. Ultrapotent topical corticosteroids are considered the first-line therapy and have shown clinical improvement in up to 71% of cases. Once the active disease is under control, the dosage is typically tapered. Systemic treatment options for severe VVLP include oral corticosteroids (e.g., prednisolone at 0.5 mg/kg/day) and intralesional corticosteroid injections (e.g., triamcinolone acetonide 10 mg/mL). For patients with vaginal stenosis, maintenance strategies such as tapering doses of hydrocortisone cream or suppositories and the regular use of corticosteroid-coated vaginal dilators help preserve vaginal patency. Weekly fluconazole (150 mg) is sometimes used to prevent secondary candidal infections. In advanced cases presenting with labial fusion, clitoral phimosis, or vaginal stenosis, surgical intervention may be necessary to relieve symptoms and restore urinary or sexual function.¹⁸

• Psoriasis

Lesions can be induced by mechanical friction in the vulvar region through the Koebner phenomenon. Common presentations include plaque-type and inverse psoriasis, though pustular forms may also occur. Classic plaque psoriasis typically affects hair-bearing areas such as the labia majora and mons pubis, appearing as well-defined, red plaques covered with silvery scales. In contrast, inverse psoriasis affects skin folds, presenting as smooth, shiny, red plaques with little to no scaling and occasional fissuring. Frequently reported symptoms include itching and burning in the majority of patients, pain, and dyspareunia. Psoriasis in other body areas or associated nail changes can aid diagnosis. Due to overlapping features, it can be mistaken for other dermatoses such as lichen simplex chronicus, lichenoid disorders, candidiasis, or contact dermatitis.

Histopathological examination usually shows characteristic features of psoriasis; concurrent dermatitis or secondary infections necessitate correlation with clinical findings. Dermoscopic examination often reveals red dot capillaries against an erythematous background.

Treatment is centered on the use of high-potency topical corticosteroids. Other options include coal tar preparations, topical calcipotriol, retinoids, and tacrolimus. In cases that are widespread, severe, or resistant to topical therapy, systemic medications such as methotrexate or dapsone may be considered.¹⁹

Footnotes

1. Prabhu, Smitha, Swathy Krishna, “Vulvar Inflammatory Disorders: A Review.” Journal of Skin and Sexually Transmitted Diseases 4, no. 2 (October 14, 2022): 188–95. https://doi.org/10.25259/JSSTD_11_2021. This open-access article distributed under the terms of the Creative Commons Attribution-Non Commercial-Share Alike 4.0 License.
2. Singh, Nilanchali, and Prafull Ghatage. “Etiology, Clinical Features, and Diagnosis of Vulvar Lichen Sclerosus: A Scoping Review.” Obstetrics and Gynecology International 2020 (2020). https://doi.org/10.1155/2020/7480754; Prabhu and Krishna, 2022; Prabhu and Krishna, 2022.
3. Singh and Ghatage, 2020; Krapf, Jill M., Leia Mitchell, Michelle A. Holton, and Andrew T. Goldstein. “Vulvar Lichen Sclerosus: Current Perspectives.” International Journal of Women’s Health, 2020. https://doi.org/10.2147/IJWH.S191200.
4. De Luca DA, Papara C, Vorobyev A, et al. "Lichen sclerosus: The 2023 update." Front Med (Lausanne). 10 (Feb 16 2023) doi:10.3389/fmed.2023.1106318. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY).
5. De Luca et al, 2023.
6. Singh and Ghatage, 2020.
7. Singh and Ghatage, 2020.
8. Prabhu and Krishna, 2022.
9. Morrel, Beth, Patricia C. Ewing-Graham, Irene A.M. van der Avoort, Suzanne G.M.A. Pasmans, and Jeffrey Damman. “Structured Analysis of Histopathological Characteristics of Vulvar Lichen Sclerosus in a Juvenile Population.” Human Pathology 106 (2020). https://doi.org/10.1016/j.humpath.2020.09.003.
10. Morrel et al, 2020.
11. Morrel et al, 2020.
12. Morrel et al, 2020.
13. Prabhu and Krishna, 2022.
14. Prabhu and Krishna, 2022.
15. Prabhu and Krishna, 2022.
16. Prabhu and Krishna, 2022.
17. Prabhu and Krishna, 2022.
18. Prabhu and Krishna, 2022.
19. Prabhu and Krishna, 2022.

Image Acknowledgements

• De Luca DA, Papara C, Vorobyev A, et al. "Lichen sclerosus: The 2023 update." Front Med (Lausanne). 10 (Feb 16 2023) doi:10.3389/fmed.2023.1106318. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY).
• Krapf, Jill M., Leia Mitchell, Michelle A. Holton, and Andrew T. Goldstein. “Vulvar Lichen Sclerosus: Current Perspectives.” International Journal of Women’s Health, 2020. https://doi.org/10.2147/IJWH.S191200.This work is published and licensed by Dove Medical Press Limited. The full terms of this license are available at https://www.dovepress.com/terms.php and incorporate the Creative Commons Attribution – Non-Commercial (unported, v3.0) License http://creativecommons.org/licenses/by-nc/3.0/.