Introduction

First described in 1902, Fox-Fordyce disease is a rare inflammatory skin disorder that mainly affects the sweat glands, more formally known as apocrine glands.¹ The disease predominantly affects people assigned female at birth, with a ratio of 13:1.² Fox-Fordyce disease is characterised by the formation of small raised bumps on the skin, known as papules, particularly in areas where sweat glands are abundant (armpits, pubic area, around the nipples).³ 

Although not lethal, the pain and discomfort brought on by these papules can have a grave impact on the patients’ quality of life. At the moment, there is no definitive cure for the disease, and existing treatment methods focus on alleviating the symptoms.⁴ As such, it is important that we understand the contributing factors to the development of Fox-Fordyce disease in order to appropriately manage and treat it. 

Causes of Fox-Fordyce disease

The pathogenesis of Fox-Fordyce disease – the process by which the disease develops – is currently still unclear. However, research has given us a few theories as to what causes the disease. 

Blocking of apocrine sweat glands

The obstruction of apocrine sweat glands is considered to be the most widely accepted explanation as to what causes Fox-Fordyce disease. 

The apocrine sweat glands are known for producing perspiration – it's what makes you sweat, hence its name. They’re most abundant in the armpits, the nipples, as well as the perianal area – the labia majora in the female reproductive external organs and the scrotum in male reproductive external organs.⁵ 

Obstruction of the apocrine glands at the point of entry to the epidermis is said to block sweat secretion.⁶ It is believed that this is caused by what is called a ‘keratin plug’, whereby keratin – a key component of our skin, nails, and hair – accumulates and forms plugs within the apocrine sweat ducts.⁸ Over time, this causes the apocrine duct and gland to become enlarged, and the pressure within the glands continues to build, ultimately causing leakage into the surrounding areas. This induces an inflammatory reaction, rupture of the ducts, and the formation of the characteristic papules.⁷ 

Role of hormonal changes

Fluctuations in hormonal levels are another contributing factor to the development of Fox-Fordyce disease. This theory is supported by the epidemiological data, with the disease predominantly occurring in people assigned female at birth between the ages of 13 and 35.¹² 

Fox-Fordyce disease is rare not only in people assigned male at birth, but also in people assigned female at birth before they reach puberty or after menopause.¹³ The predominance of the disease in people assigned female at birth in the 13 to 35 age range indicates a relationship between hormonal changes and Fox-Fordyce disease, as this period of life is characterised by important hormonal activity. This is further supported by reports of disease remission after menopause, use of oral contraceptives (birth control pills), or during pregnancy.¹⁴ 

Androgens are steroid hormones present in the human body, regardless of gender. In particular, it is believed that changes in androgen levels alter the activity of the apocrine ducts, blocking sweat from being secreted, ultimately causing rupture of the apocrine glands and inflammation.⁸ Another hormone that has been implicated in the development of Fox-Fordyce disease is the Follicle Stimulating Hormone (FSH), with elevations in its levels being noted in cases of the disease.²

Genetic predisposition

For the most part, Fox-Fordyce disease appears to occur randomly. Of course, given that its exact cause and mechanism is not yet known, this is not a sure fact. There have been reports of Fox-Fordyce disease occurring in families where the male parent and female child were affected, or both twins – assigned male and assigned female at birth, or sister duos, indicating that genetic predisposition may play a role in the development of the disease.^7,9-11 However, the specific genes involved have yet to be identified, and further research is still needed to uncover the genetic basis of this disease. 

Risk factors associated with Fox-Fordyce disease

The following risk factors play a significant role:^1-14

• Gender: Fox-Fordyce disease occurs with an overwhelming predominance in people assigned female at birth, with a ratio of 13:1 of female:male cases
• Physiological or medical events that may cause hormonal fluctuations: this includes puberty, menstruation, pregnancy, hormonal replacement therapy, and the use of medication that may cause hormonal imbalances
  • Examples of medication that may influence hormone levels include antidepressants and hormonal contraceptives
• Laser hair removal
• Emotional or physical stress
• Environmental factors such as heat and humidity
• Personal hygiene and care
  • Use of skin products that block pores: examples include antiperspirants and heavy creams
  • Shaving and waxing: excessive irritation of the affected areas may exacerbate the disease
• Tight clothing: may cause excessive friction and irritation in the affected areas
• Family history: while not established, genetic predisposition could be contributing risk factor

Summary

Fox-Fordyce disease is a chronic inflammatory disorder that primarily affects people assigned female at birth in their reproductive years. This disease is characterised by the formation of small, raised bumps known as papules in areas rich in apocrine sweat glands, such as the armpits, nipples, and genitals. These papules result in intense itching in these areas. 

The exact cause of Fox-Fordyce disease is still unknown, but several theories have been proposed. The most widely accepted theory mainly involves the blockage of the apocrine sweat glands, which are responsible for producing and secreting sweat. It goes like this: the apocrine sweat ducts are obstructed by keratin accumulation, and sweat secretion is blocked. Overtime, the apocrine glands become enlarged, and the pressure within the glands increases. Eventually, the sweat built up within the ducts leaks into the surrounding tissue. This induces an inflammatory reaction and the ducts are ruptured, thus causing the formation of characteristic papules. 

Other factors that have been implicated in the development of Fox-Fordyce disease include genetic predisposition as well as changes in hormonal levels. 

Several risk factors have been associated with the development of Fox-Fordyce disease. These include (i) gender, with strong predominance in people assigned female at birth; (ii) hormonal fluctuations caused by puberty, the menstruation cycle, pregnancy, hormonal replacement therapy, or hormonal medication; (iii) laser hair removal; (iv) family history of the disease; and (v) personal hygiene practices such as pore-blocking skin products and shaving/waxing in affected areas. Environmental and lifestyle factors – heat, humidity, tight clothing, and stress – that increase sweating apparently worsen the symptoms of the disease. 

While Fox-Fordyce disease is not a life-threatening condition, the intense itching and discomfort the disease causes can significantly impact one’s quality of life. Although there is yet to be a definitive cure for the disease, understanding the factors contributing to its development plays a big part in effective treatment methods and improving patient care for those affected by Fox-Fordyce disease.