fox fordyce disease

Fox Fordyce disease

Fox-Fordyce disease also known as “apocrine duct occlusion”, “sweat retention disease”, “apocrine miliaria” or chronic pruritic papular eruption of the pubis and armpits, is a rare skin disorder that occurs mainly in women between the ages of 13 and 35 years. However, in rare cases, it can affect males and children. Some reports place the ration of affected women to men at 9:1. Fox-Fordyce disease is characterized by the development of itchy bumps around the hair follicles of the underarm area, pubic region, and around the nipples. Fox-Fordyce disease results from inflammation of the apocrine sweat glands, which are found only in these areas 1). Fox-Fordyce disease may result in very intense itch that disturbs sleep, but in some cases does not result in any symptoms. The lesions tend to display chronic evolution, described as lasting weeks to years 2).

Clinically, Fox-Fordyce disease is characterized by the presence of multiple skin-colored follicular papules, slightly yellowish or brown, dome-shaped, with a smooth surface, which may be accompanied by mild to moderate pruritus or even be asymptomatic. Exacerbating symptoms include stress, heat, moisture, physical activity, friction with clothing, and excessive sweating 3). Laser hair removal and intense pulsed light have also been described as triggers 4).

Fox-Fordyce disease common features include:

  • Dome-shaped flesh-colored to small reddish papules affecting almost every hair follicle in the area
  • Darkened, thickened and dry skin as a consequence of scratching (lichenification)
  • Reduced or absent sweating in the affected area.

Fox-Fordyce disease was first described in 1902 by American authors George Henry Fox and John Addison Fordyce 5). The pathogenesis of Fox-Fordyce disease remains unknown, although proposed theories suggest that hormonal factors, hair removal, and inheritance may be involved in the apocrine duct obstruction, sweat retention, and inflammation 6). The incidence of Fox-Fordyce disease is unknown. Heat, humidity, stress and exercise have been noted as exacerbating factors. Fox-Fordyce disease may persist for many years.

In some instances, Fox-Fordyce disease may be more severe during menstruation and tends to disappear (spontaneously resolve) during pregnancy for unknown reasons. In others, it may resolve at the menopause (but it may also persist afterwards).

Individuals with Fox-Fordyce disease should consult with a dermatologist regarding treatment. There is no definitive treatment for Fox-Fordyce disease. The treatment of Fox-Fordyce disease is directed toward the specific symptoms that are apparent in each individual. Some of the recent treatments for the Fox-Fordyce disease include: interlesional glucocorticoids, topical steroids, oral and topical retinoids, topical antibiotics, topical clindamycin, topical pimecrolimus cream, benzoyl peroxide, oral antibiotics and oral contraceptives or antiandrogenic hormonal therapy 7). Estrogen hormones, usually given as part of estrogen-based oral contraceptives, have been most effective in treating women with Fox-Fordyce disease. Less effective therapies include oral retinoids (such as tretinoin), corticosteroid creams and topical antibiotics (such as clindamycin) have been beneficial in some cases while ineffective in others. Some of these therapies may be associated with irritation, limiting their ability to be used a long-term therapy. Pimecrolimus and tacrolimus, both with significant anti-inflammatory activity and low side-effects, have provided rapid improvement in a limited number of cases 8). Other forms of treatment used are ultraviolet radiation (phototherapy), dermabrasion, liposuction and surgical excision 9). Immunosuppressants have been utilized with modest success. For individuals who do not respond to medications, destruction or removal of the apocrine sweat glands (glands that surround hair follicles) has been effective in some cases 10).

Figure 1. Apocrine sweat gland

Apocrine sweat gland

Figure 2. Fox-Fordyce disease

Fox-Fordyce disease

Footnote: Clinical appearance of Fox-Fordyce disease. Multiple skin-colored or reddish, hair follicle-centered papules (2-4mm) in the armpits. The patient is a 26-year-old woman with complaints of skin lesions in the bilateral axillae and vulva areas for 7 years. Seven years ago, some pruritic skin-colored papules began to appear in the bilateral axillae and vulva areas. The number of skin lesions increased gradually from then on. The lesions were intermittently pruritic, particularly in higher temperature during mental strain. She was well before, and both medical history and family history of the patient were unremarkable. The physical examination revealed numerous round (2-4mm), skin-colored to reddish papules. The hair in both axillae were sparse, and there was hair growth throughout from the center of some papules. The surrounding skin was normal.

[Source 11) ]

Figure 3. Fox Fordyce disease

fox fordyce disease

Footnote: Punctate papules with follicular distribution in the armpits and hemorrhagic crusts due to scratching.

[Source 12) ]

How can Fox-Fordyce disease be managed in the long-term?

Fox-Fordyce disease is a chronic condition. Once relief has been achieved, long-term, low-dose therapy is recommended. Individuals with Fox-Fordyce disease should avoid activities that can lead to sweating 13).

Are there over-the-counter medications which can help manage Fox-Fordyce disease?

After an extensive search of the resources currently available, there are no reports of over-the-counter medications which have been used to manage this condition. We recommend that you consult with a dermatologist for further information regarding treatment of Fox-Fordyce disease.

Fox Fordyce disease causes

The cause of Fox-Fordyce disease is currently unknown. Researchers have speculated that obstruction of the apocrine gland ducts is necessary for the development of Fox-Fordyce disease, but studies have not been able to definitely confirm this theory. Researchers speculate that apocrine sweat becomes trapped as a scaly plug forms in the hair follicle and the blocked apocrine sweat ducts rupture causing inflammation where the duct comes close to the hair follicle, resulting in intense itching. The inflammatory reaction around hair follicles includes specialized leukocytes (white blood cells) that engulf extruded secretory debris.

Factors identified as playing a part in the development of the condition include:

  • Emotional and hormonal influences
  • Alterations in sweat components

Researchers have also speculated that additional factors such as hormonal or genetic ones may play a role in the development of Fox-Fordyce disease. However, research into the cause(s) of Fox-Fordyce disease has not yielded any definitive answers as yet. More research is necessary to determine the exact cause of Fox-Fordyce disease.

Fox Fordyce disease differential diagnoses

Differential diagnoses include Graham-Little-Piccardi-Lasseur syndrome, trichostasis spinulosa, Darier’s disease, syringomas, lichen nitidus, lichen amyloid, and papular mucinosis 14), 15).

Fox Fordyce disease symptoms

The symptoms of Fox-Fordyce disease may appear suddenly usually following conditions of heat, humidity or friction. The disease is characterized by an eruption of multiple, small, raised bumps on the skin near the apocrine glands.

The apocrine glands are specialized sweat glands that play a pheromonic role in animals; a similar role has been postulated in humans. Pheromones are chemicals secreted by animals that influence social or sexual behavior of other animals of that species. Apocrine glands respond to sex and stress stimuli. Apocrine glands become extremely active during puberty. Most apocrine glands are found in the armpits or the groin. They may also be found by the nipples, external ear canal, eyelids, and around the bellybutton.

The papules are usually skin-colored, but may be yellowish or reddish in color. They are usually dome-shaped and smooth. Affected areas usually have many small papules. Papules are most often found in the armpits (axillae). The affected areas are often extremely itchy (pruritus) and sweating in these areas may also be absent (anhidrosis). Itching may be mild or may be severe enough to disturb sleep. Hairs within follicles in the affected area may fall out.

Fox Fordyce disease diagnosis

A diagnosis of Fox-Fordyce disease is made based upon identification of characteristic symptoms (i.e., papular eruptions on apocrine gland areas), a detailed patient history, and a thorough clinical evaluation. Surgical removal and microscopic evaluation (biopsy) of affected tissue may be useful in obtaining a diagnosis. An experienced dermatopathologist will be necessary to correctly diagnose the disease from a biopsy.

Histopathological examination may show nonspecific findings such as intrafollicular corneal plug, hyperkeratosis, spongiosis, retention vesicles, glandular dilation with mucin deposits, and perifollicular lymphohistiocytic inflammatory infiltrate 16). The presence of infundibular dyskeratotic cells, vacuolar changes, and parakeratosis similar to cornoid lamella have also been described 17). However, Bormate et al. 18) recently described the presence of foamy or xanthomatous histiocytes (perifollicular xanthomatosis) as a distinctive, consistent, and more specific feature of this pathology.

Fox Fordyce disease treatment

There is no cure for Fox-Fordyce disease. Consultation with a dermatologist is recommended. Medical treatments that have been used with varying degrees of success, the lesions and symptoms may recur or persist.

Fox Fordyce disease treatment options include:

  • Topical retinoids
  • Topical steroids
  • Oral antibiotics
  • Clindamycin solution
  • Antiandrogenic hormonal therapy

First-line treatments include topical and oral retinoids, benzoyl peroxide, topical calcineurin inhibitors, clindamycin, intralesional or topical steroids, and oral contraceptives, the latter reported with complete resolution of lesions 19).

Alternative therapies as second-line treatment or in severe cases, such as botulinum toxin, ultraviolet radiation (phototherapy), electrocoagulation, copper vapor and CO2 laser, dermabrasion, liposuction, curettage, surgical excision and microwave have been described with favorable results 20).

Fox Fordyce disease prognosis

Management with topical retinoids and antibiotics has brought some hope to patients with Fox-Fordyce disease for decades. Long-term follow-up studies are not available; therapy may need to be prolonged for a very long time. Acceptable therapy should be safe and relatively inexpensive. In 1994, Effendy et al reported the short-term success of isotretinoin when given for 4 months in a daily oral dose of 15-30 mg; the condition returned 3 months after cessation of therapy.

Fox-Fordyce disease has no risk of loss of life or limb. Patients often experience severe itch (pruritus). Therefore, the patient’s quality of life may be adversely affected.

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