Symptoms of Fox-Fordyce Disease

Introduction

What is Fox-Fordyce disease?

Fox-Fordyce disease, known as FFD or apocrine miliaria, is a chronic, inflammatory skin disorder.^1,2,3 It is caused by the accumulation of keratin at the root of the hair follicles, which blocks the duct of the sweat/apocrine glands and accumulates sweat underneath. The inflammation leads to a so-called pruritic papular eruption, a rash consisting of small, itchy bumps on the skin. 

Influencing factors 

Interestingly, the exact cause is unknown, but it is generally thought to occur due to sporadic causes. Some argue that familial cases may be present, though they are rare. Hormonal composition, environmental factors like humidity or temperature, and events like laser hair removal can all trigger the onset of FFD.^1,3 

Who does it affect? 

The condition primarily affects adolescent females who are already past puberty, however, cases can also occur in males and during adulthood as well. Interestingly, the higher predisposition in people assigned female at birth (AFAB) is not directly linked to genetic factors, but rather the intense hormonal changes that occur mainly at the start of menstruation. 

The other main reason why people AFAB are more associated with FFD is the fact that they often go through laser hair removal, an activity quite uncommon for men. The development of FFD usually requires multiple laser removal sessions and can arise due to the thermal damage hair follicles experience during the process.^1,3

Symptoms associated with Fox-Fordyce disease

Symptom development 

As mentioned, Fox-Fordyce disease is caused by the blockage of apocrine gland ducts due to keratin accumulation, likely triggered by physical influence or hormonal changes.¹ Since apocrine glands are most densely located in the armpits, breasts, and genital area, FDD symptoms are mainly confined to these body parts and can simultaneously affect one or more of these areas.⁴

It is also important to mention that FFD might not lead to any physical signs. Indeed, the condition can remain asymptomatic in up to 75% of patients.³

Symptoms experienced by the patients

• Pruritus (Itching)
• Papular eruptions
• Hyperpigmentation

Patients with Fox-Fordyce disease typically experience intense pruritus, or itching, which can be exacerbated by heat, stress, or friction. Alongside itching, the condition is characterised by small, dome-shaped papular eruptions that are skin-coloured or yellow and primarily appear in areas where apocrine glands are concentrated, such as the underarms, pubic region, and areolas. Over time, these affected areas may undergo hyperpigmentation, resulting in a darker, brown-yellow appearance of the skin.^2,4 

The diagnosis of Fox-Fordyce disease is usually clinical, based on the presence of these pruritic papules. However, it is important to consider other possible conditions with similar symptoms. A thorough evaluation is needed to rule out alternatives like pseudofolliculitis or granular parakeratosis. This is typically achieved through a biopsy, after which the diagnosis can be confirmed by performing histological staining and analysis of the pathology. 

Histopathology

For appropriate diagnosis, to differentiate from other conditions that present with symptoms similar to FFD to the naked eye, a biopsy is performed, where a small fragment of epithelial tissue is removed from the affected area. To achieve this, doctors usually take a small skin sample and a 4 mm punch biopsy is often used with transverse sectioning. This sample is examined under a microscope, where different staining techniques help highlight specific tissue features. One method, called immunohistochemistry (IHC), helps identify certain proteins, while another, haematoxylin and eosin (H&E) staining, provides a general view of the skin’s structure.

The histological findings associated with Fox-Fordyce disease include intrafollicular plugs (blockages within hair follicles), keratin accumulation, intracellular oedema called spongiosis (swelling of skin cells), trapped fluid-filled vesicles/sacs, glandular dilation (enlarged sweat glands), and the presence of immune cells causing inflammation.³ 

Symptom management

First-line treatment options include topical/oral retinoids, calcineurin inhibitors, topical corticosteroids, clindamycin, and benzoyl peroxide.^1,3 

Out of these first-line options, corticosteroids and topical clindamycin are the most popular choices, thanks to their easy application (twice daily on the affected area) and minimal risk of side effects. Calcineurin inhibitors are also found to result in almost complete clearance, while, although effective, topical retinoids often cause skin irritation in patients.¹

Severe and recurrent cases, however, often do not respond to first-line treatment. In these cases, more aggressive interventions are available. These second-line treatment options include surgical removal, laser treatment, phototherapy, and botulinum toxin (Botox) injections^. 

Summary

Fox-Fordyce disease (FFD) is a chronic, inflammatory skin condition primarily affecting adolescent females, characterised by intense itching, papular eruptions, and hyperpigmentation in areas with dense apocrine glands. The exact cause remains unclear, but hormonal changes, environmental factors, and physical triggers like laser hair removal may contribute to its onset.

Diagnosis is usually clinical, with biopsy and histopathological analysis used to confirm the condition and rule out similar disorders. Treatment options range from first-line therapies, such as topical corticosteroids and retinoids, to more aggressive second-line interventions like surgical removal and laser treatments for severe cases. 

While management strategies can alleviate symptoms, recurrence is common, and no definitive cure has been established. Ongoing research is essential to improve understanding and develop more effective treatment protocols for this challenging condition.