When your sweat glands decide to play hard-to-get, but the itch insists on staying close! Fox-fordyce, also known as apocrine miliaria, is a condition that presents itself as inflamed, itchy regions on the armpits, mainly seen in women. They result from trapped sweat within the apocrine glands.¹ In this article, we delve into the characteristics of this condition by covering the symptoms, causes, management, as well as diagnosis of Fox-Fordyce disease. 

Introduction

Fox-Fordyce, coined after the names of its discoverers, George Henry Fox and John Addison Fordyce,² is a rare chronic, inflammatory disease that is characterised by the presence of itchy, non-pus-like bumps in the anogenital areas. These bumps are commonly seen in the armpits of individuals affected. The exact cause of this remains elusive, although some theories point toward an increase in hormonal levels since it usually occurs in females.³ Fox-Fordyce can cause extremely debilitating itchiness that can persist even during one’s slumber, keeping you up all night, although presenting as asymptomatic in most cases.

What causes Fox-Fordyce disease?

Although the exact cause of Fox-Fordyce disease is unknown, it is speculated that it can arise due to hot and humid temperatures that irritate the anogenital areas and armpits. 

It is primarily due to an alteration of the sweat glands that cause a reduction in sweating because of the formation of keratinous plugs as a result of pore occlusion, which results in the mechanical blockage of sweat glands from producing sweat. The cause is quite ironic, with it being due to excessive sweating, profusely on a hot or humid day over a prolonged period.⁴

There are three main kinds of sweat glands in the body, namely: the eccrine, apocrine, and apoeccrine glands.⁵ Focusing on the apocrine glands for this article, these glands are present in the body since birth, but are only really activated when the individual undergoes puberty. These glands are found mainly concentrated in the face, scalp, perineum, breasts, specifically the areolar region, axilla, and anogenital area.⁶

When there is an accumulation of keratin in the follicular infundibulum. The infundibulum is the topmost layer of the epidermis in the skin, connecting the skin to the sebaceous gland. Upon this structure becoming clogged, the development of pruritic papules takes place. The sweat glands could also get detached from the sebaceous glands in some cases, leading to Fox-Fordyce. 

Increased sweating, hot and humid temperatures, tight clothing, emotional stress, and anxiety are some causes that can be correlated with Fox-Fordyce disease. 

Symptoms and Signs of Fox-Fordyce disease

Before the onset of Fox-Fordyce disease, one can witness:

• Localised hyperhidrosis
• Localised alopecia, in the regions afflicted. 
• Discolouration of skin
• Changes in the texture of the skin, where the skin becomes more leathery and rough
• Thickening of skin due to constant itching - lichenification of skin
• Asymptomatic lesions that appear at first and are not itchy do not alarm the individual immediately (Perifollicular Xanthomatosis)
• Persistent drying and scaling of the skin in the affected regions

Diagnosis of Fox-Fordyce disease

In order to diagnose Fox-Fordyce disease accurately, an extensive history and physical examination are conducted to differentiate it from other similar conditions, such as arthropod bites, scabies, lichen planus, lichen nitidus, and chronic dermatitis.⁶

The period of the itches is taken into consideration as well as how rapidly they appeared. 

The intensity and times at which the itch is extreme are noted to see if it increases specifically at night or at certain temperatures. 

If the papules are all discoloured the same way, and if they are all a uniform size, or if there is any difference in them. As well as check for any signs of discharge or pus that could differentiate them. 

Check the family history and note any potential triggers that could cause the onset of Fox-Fordyce. This is done to differentiate it from other conditions that arise due to allergies, i.e., contact dermatitis or even early stages of psoriasis. 

There are chances that Fordyce spots could be confused with Fox-Fordyce disease. Fordyce spots are tiny (1 to 5 mm), slightly elevated yellowish or white papules representing a variant of sebaceous glands. They are visible without hair follicles and commonly involve the vermilion border of the lips, buccal mucosa, glans or shaft of the penis, and the vulva in females. While they are of no medical consequence, patients often seek consultation due to cosmetic concerns.

Laboratory testing is ordered to diagnose Fox-Fordyce 

Fox-Fordyce disease is usually diagnosed clinically, but certain tests can also be utilised to narrow down the differentials. 

Hormonal tests

When suspected of certain endocrine disorders, that could in a few instances exacerbate or even at times trigger Fox-Fordyce disease. In cases of hirsutism or hormonal imbalances, via irregular menstrual cycles. These studies enable the medical professional to gain a better evaluation of the patient’s hormonal status. 

Other tests to check for levels of thyroid, oestrogen, progesterone, and androgens in the body could also be conducted. These aid in determining if there is any factor that determines why there is an excessive deposit of sweat or keratin in the apocrine glands. 

Tests to rule out other infectious diseases

There are certain other infectious skin conditions, like folliculitis, that occur due to viral, fungal, or bacterial infections. Cultures in microbiology or PCR tests can be performed in the affected areas to exclude certain infectious diseases. When tested negative for all other conditions, Fox-Fordyce can be concluded. For further confirmation, in rare cases, imaging techniques could also be used to narrow it down from other deep-seated abscesses.

Dermoscopy

Mainly used during skin cancer to check for melanoma cells, this technique can also be utilised to reveal hair follicle-centred papules, blackheads that block the sweat glands, as well as traumatised terminal hair. 

Treatment and management of Fox-Fordyce

Initially, via the use of topical retinoids, which normalise keratin levels, and topical steroids, to reduce inflammation, can be applied on the infected regions to reduce bumps and itching. If itching continues, antibiotics prescribed by your local healthcare provider can also be used. 

Trying to reduce stress and wearing less tight-fitting clothing can aid in reducing the occurrence of Fox-Fordyce.

However, Fox-Fordyce follows a relapsing-remitting course; hence, in extreme conditions of itchiness, anti-androgen medications or laser therapy can be used to target and destroy the afflicted apocrine glands to provide symptoms of relief. 

Regular follow-up checks and adjusting therapy based on the outcome of the individual’s conditions are recommended. Always make sure to consult with your healthcare provider for their professional opinion and guidance before taking matters into your own (itchy) arms. 

FAQs

What are the symptoms of Fox-Fordyce disease? 

Fox-Fordyce disease is usually identified upon the presentation of minute but firm bumps, also called papules, around the regions of the skin where the presence of the apocrine glands is seen - such as the anogenital areas (anus and genitalia) as well as the armpits, nipples, and pubic region. These papules or bumps, in general resemble the skin of the individual with slight pigmentation being present. They often tend to be associated with sensations of extreme itchiness, mainly during humidity and heat. They can arise during periods of stress or when using a blunt razor, which can irritate. Once formed, they can lead to serious, debilitating impacts on the individual's life, termed as a chronic infection, which can also lead to disrupted sleep due to constant itching. The symptoms of Fox-Fordyce are rudimentary and asymptomatic.

Can Fox-Fordyce Disease go away?

In most cases, Fox-Fordyce is a persistent condition, being chronic, it can last for numerous years. Whilst the symptoms may be non-periodic, at certain times the papules are extremely itchy, and at other times there are periods of relief and some signs of healing. There seems to be a noticeable decline in the condition when females enter menopause. Although there is no exact evidence-based connection between the two, there does seem to be a slight role involving hormones. Especially since it occurs in females, commonly aged between 13 to 35 years of age. 

What is the best treatment for Fox-Fordyce disease? 

To treat Fox-Fordyce disease, a focus is placed on managing the symptoms since there is no definitive cure that aids in the eradication of the disease in its entirety as of yet. Topical corticosteroids may be administered to reduce the regional inflammation caused by the disease, which in turn aids in reducing the feeling of itchiness. Some other treatments can be utilised, such as the use of hormone therapy or retinoids to promote the turnover of the older skin cells to generate new ones as a replacement to maintain healthy skin. Laser therapy, such as carbon dioxide laser therapy or light-based laser therapy, is used to target the damaged and inflamed cells and replace them in cases of severe damage. It is crucial to contact and work with your dermatologist about your condition to come up with the best possible treatment to address and treat your specific needs and symptoms.

What is the pathology of Fox-Fordyce spots? 

The pathology of Fox-Fordyce entails the obstruction of the sweat glands in the body, specifically known as the apocrine sweat glands. This leads to the formation of minuscule, itchy papules that are slightly pigmented. When tested histologically, they are characterised by the thickening of the outer layer of one’s skin (hyperkeratosis) followed by the thickening of the middle layer of the skin (acanthosis). This is the result of the sweat glands becoming blocked and swelling up due to the buildup of sweat, causing inflammation. Medically, one of the ways of differentiating it from other similar conditions is the lack of inflammatory cell infiltration.

Summary

Fox-Fordyce Disease, also known as apocrine miliaria, is a rare, chronic inflammatory skin condition characterised by itchy, skin-coloured or slightly pigmented papules that primarily affect areas rich in apocrine sweat glands, such as the armpits, anogenital region, and under the breasts. The condition arises from the blockage of apocrine sweat glands, often exacerbated by factors like heat, humidity, and hormonal changes. While the exact cause remains unclear, it is commonly seen in women and can significantly impact the quality of life due to persistent itching, particularly at night. Diagnosis involves differentiating Fox-Fordyce from other skin conditions with similar symptoms, using patient history, physical examination, and sometimes laboratory tests. Treatment focuses on symptom management through topical corticosteroids, retinoids, and, in more severe cases, hormonal therapies or laser treatments. Regular follow-ups are essential to adjust therapies based on the individual's response.