Epidermolytic hyperkeratosis of the vulva: Case report and review of the literature

Abstract Epidermolytic hyperkeratosis is a rare histopathological phenomenon which has been reported in a number of dermatological conditions. It is rare but can cause chronic and intractable symptoms which can impede the quality of life of those affected. Treatment options are variable and not enough data exists to provide a definitive protocol for management. We present this case to highlight a simple, efficacious way for dermatologists to treat the condition and provide a literature review.


| INTRODUCTION
Epidermolytic hyperkeratosis (EHK) is a rare histopathological phenomenon which has been reported in a number of dermatological conditions.It is rare but can cause chronic and intractable symptoms which can impede the quality of life of those affected.Treatment options are variable and not enough data exists to provide a definitive protocol for management.We present this case to highlight a simple, efficacious way for dermatologists to treat the condition and provide a literature review.

| CASE SYNOPSIS
A 67-year-old female with no prior dermatological history was referred to gynaecology for a vulvar rash.She had reported longstanding pruritus and genital lesions spanning 2 decades that interfered with her quality of life.Her pruritus was quantified using the verbal rating scale (VRS) at a 4, denoting very severe pruritus.There was no associated vaginal discharge.A shave biopsy, taken instead of a punch biopsy due to the patient's reluctance to have any sutures, from the vulva revealed epidermal hyperplasia demonstrating hypergranulosis and superficial to mid epidermal vacuolar degeneration (Figure 1, top and bottom left).A Periodic acid-Schiff stain was negative for fungal hyphae (Figure 1, bottom right), and there was no evidence of malignancy.These changes were consistent with the EHK reaction pattern.Given the anatomic location and clinical setting, EHK of the vulva was favoured.
The patient was referred to dermatology for further management of her persistent symptoms.Physical examination revealed approximately 30 clustered, grey to white coloured, flat-topped, shiny monomorphic papules with no papulovesicular or scaly component.Differential diagnoses considered included lichen planus, condyloma acuminata, chronic spongiotic dermatitis, and vaginal inclusion cysts, however pathology results did not demonstrate features consistent with these.The patient was prescribed augmented betamethasone 0.05% ointment BID for 2 months.Within 1 month of twice daily application of the steroid, the patient reported complete resolution of her pruritus for the first time in 30 years.On clinical exam there were only a few remaining scattered vulval papules, with the majority of prior lesions having resolved completely.Her pruritus VRS score came down to 0, denoting no itch.The patient currently uses short bursts of the betamethasone ointment for a couple of days at a time to control any recurrence of her symptoms and has remained well controlled on this regimen for 1 year to date.

| CASE DISCUSSION
EHK is now considered to be a histologic reaction pattern. 1 While originally EHK was associated with bullous congenital ichthyosiform erythroderma,2 focal EHK has recently been described within seborrhoeic keratoses, epidermal nevi and verrucae. 3Additionally, solitary lesions demonstrating EHK in the vulval and scrotal regions, termed epidermolytic acanthoma, have also been documented. 4,5EHK of the vulva is exceedingly rare.In one study that aimed to demonstrate the relative frequency of various gynaecological dermatoses, EHK made up just one of 183 total cases. 6rom the literature review we performed, the average age of presentation for EHK of the vulva was 53.4 years old and the average time taken from first presentation to diagnosis was 8.9 years (Table 1).
[3]7 In most cases, the presenting complaint is intense pruritus, though some women are asymptomatic whose lesions are incidentally noted by their healthcare provider during routine clinical examinations.The exact aetiology of these lesions is unclear, although a rare case of epidermolytic acanthoma of the scrotum has been thought to be triggered by chronic traumatisation (i.e., itching and scratching), 4 and there is no documentation in the literature of malignant transformation of either epidermolytic acanthoma or EHK of the vulva.Patients can therefore be reassured of a benign inflammatory process based on the biopsy results.
Treatment options, so far, have focused on a combination of conservative measures such as emollients and mild keratolytic agents including lactic acid, salicylic acid, and glycolic acid. 1,8Occasionally, locally destructive therapies such as liquid nitrogen, curettage, and electrodessication and cautery have been used; however, these are painful, potentially disfiguring treatments that may cause scarring and resultant unwanted complications. 2 The cutaneous eruptions can be refractory to high potency topical steroid and topical oestrogen. 3We can only speculate that oestrogen was prescribed in this case for a presumed atrophic vaginitis related pruritus rather than for targeted treatment of any F I G U R E 1 Top: low power examination reveals hyperkeratosis and mild epidermal hyperplasia with slight epidermal pallor and hypergranulosis (H&E, 40�).Bottom left: higher power inspection reveals both coarse keratohyalin granules (black arrow) and variable vacuolar degeneration of the granular and spinous layers (H&E, 100�).A PAS stain was negative for fungal hyphae (PAS, 100�).PAS, Periodic acid-Schiff.visible hyperkeratotic disease.In one case 7 a patient with a clinical and histopathological diagnosis of EHK had significant improvement with a combination of 0.1% oestriol, 2% miconazole and 1% hydrocortisone creams, though it is hard to delineate exactly which of these provided the beneficial effect.
Topical calcineurin inhibitors are not yet mentioned in the literature as a treatment option.One case report noted complete resolution of scrotal epidermolytic acanthomas following a 4-week course of 5% imiquimod ointment, 12 but the potentially painful, inflammatory, and systemic side effects caused by use of imiquimod on sensitive areas of the body must be taken into consideration.

| CONCLUSION
This is the first case of EHK of the vulva in a patient whose disease was successfully controlled with intermittent use of high potency topical steroids.Attaining the correct diagnosis and using potent topical steroids resulted in a significant improvement to her quality of life.We present this case to remind clinicians to consider this rare diagnosis in a patient presenting with pruritic, papular eruptions of the vulva.Additionally, this case highlights how potent topical steroids can bring about intense relief in a rapid and effective manner in symptomatic patients who have suffered with years of discomfort.
While there have been reports in the literature of EHK becoming quiescent and not progressing even without topical treatment, 2 a significant proportion of patients struggle with debilitating pruritus for up to 30 years. 9Our recommendation in symptomatic individuals is to use high potency topical steroid continuously for a prolonged period (1-2 months), similar to the treatment schedule for vulval lichen sclerosis, and then use the steroid intermittently in shorter burst for maintenance of disease control.
These findings are of heightened importance given the recently recognized dearth of literature surrounding women's health.The condition affects women from menarche to menopause and based on our literature review, a significant proportion of women were misdiagnosed and suffered years of debilitating pruritus prior to biopsies being taken.The appearance of pruritic whitish-grey, sessile, verrucous papules should alert T A B L E 1 Previously described cases of epidermolytic hyperkeratosis of the vulva.

Age at presentation Clinical features Time to diagnosis Treatment
Iglesias-Plaza et al. primary care physicians, gynaecologists, and dermatologists to the possibility of this diagnosis and need for biopsy.
This is an open access article under the terms of the Creative Commons Attribution License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited.© 2023 The Authors.Skin Health and Disease published by John Wiley & Sons Ltd on behalf of British Association of Dermatologists.