Introduction

Fox-Fordyce disease is also referred to as Apocrine miliaria or apocrine duct occlusion, an infrequent chronic inflammatory skin disorder affecting the apocrine glands, characterised by an itchy papular rash in areas such as the axillae and anogenital areas.¹ Most cases of Fox-Fordyce disease occur in the extragenital areas rather than the genitals region.

Prevalence

The disease rate of occurrence is not well-documented because of its rarity. However, it predominantly affects women, especially those between the ages of 13 and 35 years.² Fox-Fordyce disease is less commonly reported in men. Due to the rarity of the disease, specific prevalence rates are not widely available and much of the existing data comes from case reports and small studies.

Aetiology

The exact cause of the disease remains unknown, but a significant in its development appears to be the blockage of the apocrine gland duct which is because of keratin buildup in the follicular infundibulum.3 Some hypothetical factors include the following:

• Genetic predispositions
• Hormonal involvement which is observed in post-pubertal adolescent girls and women, occasionally in prepuberty, postmenopausal women and men. Additionally, it is aided by premenstrual flare-ups and improvement during pregnancy and with the use of oral contraceptives⁴
• Laser hair removal due to exposure to laser irradiation resulting in keratinocyte dysmaturation followed by keratin plugging⁵
• Trigger factors that induce sweating and itching like emotional stress, excitement, and sweats due to exercise. Additionally, tight clothing, sexual activity, humid and hot weather trigger pruritis in this disease condition¹

Signs and symptoms

The following signs and symptoms can help in identifying the disease condition;

• Itchy papules: The most popular symptom is the appearance of small, itchy, skin-coloured red pumps in areas where apocrine glands are present
• Pruritus: Intense itching is the hallmark of the disease which may worsen with sweating, heat or friction
• Affected areas: The disease condition normally affects areas such as the underarms, the anogenital areas around the nipples and occasionally the lower abdomen or chest
• Hyperpigmentation: Over time, the affected areas may develop intense dark pigmentation because of repeated inflammation and scratching
• Papular eruption: The bumps may appear clustered and can sometimes merge into larger patches. The papules may also have a rough or grainy texture as shown in figure 1
• Sweating retention: Some individuals may experience a reduction in sweating in the affected regions because of blocked sweat ducts

Figure 1: showing rashes in the affected regions of the vulva⁶

Clinical evaluation of Fox-Fordyce disease

The prognosis of the disease condition is based on clinical presentations. However, there are more diagnostic methods utilised for the evaluation of the disease which may include:

• Histopathology: employed to ascertain features and characteristic changes, such as perifollicular foam cells
• Dermaoscopy: which is used to unravel the affected terminal hairs, blackheads and hair follicle-centered papules⁷

Treatment options for Fox-Fordyce disease

Clinical presentations of the signs and symptoms of the disease condition aid in therapy to alleviate the causes of the disease. These include:

• Topical steroids: which are usually used as the first line of therapy to reduce inflammation and itching. Though it can be effective in managing symptoms but may not fully resolve the condition
• Topical retinoids: are employed to decrease keratin plug formation in the sweat glands. However, it can cause irritation and cannot be used for sensitive skin areas. It is advisable for patients to apply every other day more tolerably than daily use to reduce the irritation caused by using the topical retinoids^8-9
• Laser hair removal: These are used to target hair follicles and may reduce the occurrence of blocked sweat glands which can provide long-term relief but multiple sessions are usually needed
• Surgical excision: employed in severe cases to remove affected sweat glands and can offer a permanent solution. However, surgery carries risks such as scarring and may not be feasible for all patients
• Antimicrobials: often given to treat secondary infections if present or suspected and limited to cases where infection complicates the disease condition
• Oral contraceptives: employed to treat the hormonal involvement of the disease condition and effectiveness varies but long-term use has associated risks

Reason for treatment of Fox-Fordyce disease with Oral Contraceptives

The rationality behind the use of oral contraceptives in the treatment of the disease is based on their ability to regulate hormone levels, specifically androgens.10 Consequently, this tends to alleviate the problem of the hormonal involvement aspect of the aetiology of the disease which usually affects women during reproductive years. Furthermore, this shows improvement during periods of hormonal stability such as pregnancy and post-menopause. The mechanism of action of oral contraceptives in the treatment of the disease includes;

• Hormonal regulation: they contain synthetic forms of estrogen and progesterone, which help to normalise hormone levels thereby reducing the influence of androgens which causes an increase in the activity of apocrine sweat glands
• Decrease in androgen effects: by reducing the levels of free androgens in the body, oral contraceptives can minimise the stimulation of apocrine glands which are responsible for producing sweat and contributing to the keratin plug production that constitutes Fox-Fordyce disease
• Management of clinical presentation: this is done by stabilising hormone fluctuations, decreasing the occurrence and severity of symptom flare-ups linked to the menstrual cycle

Potential risks and considerations

The use of oral contraceptives in the treatment of Fox-Fordyce disease needs to be monitored because of its side effects such as 

• weight gain
• nausea  
• mood changes

It is pertinent to note disease conditions that are contraindicated with the use of oral contraceptives to avoid life-threatening situations. Additionally, long-term use of oral contraceptives needs to be monitored and regular medical follow-up to prevent any adverse effects.

Future directions in research and treatment

Currently, there are no published reports on new treatments. However, there is a hypothetical theory that recommends fractionated microneedle frequency might be a promising treatment option for Fox-Fordyce disease.¹¹

Summary

The use of oral contraceptives in Fox-Fordyce disease aims to manage the hormonal triggers that worsen the disease condition thereby causing a decrease in symptoms and enhancing the quality of life for the patients. Adequate monitoring and regular medical follow-up are essential for patients on long-term therapy.