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Fox-Fordyce disease

  • Author(s): Yost, John
  • Robinson, Maria
  • Meehan, Shane A
  • et al.
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Fox-Fordyce disease
John Yost MD, Maria Robinson MD, Shane A Meehan MD
Dermatology Online Journal 18 (12): 28

The Ronald O. Perelman Department of Dermatology, New York University School of Medicine, New York, New York

Abstract

Fox-Fordyce disease (FFD) is a rare inflammatory disorder that affects the apocrine sweat glands. Clinically, lesions are equidistant, smooth, uniform, firm, folliculocentric papules, which can range in color from flesh-colored to red-brown to slightly yellow. Whereas the axillae are most commonly involved, FFD also can involve the anogenital and periareolar areas, lips, umbilicus, sternum, perineum, and upper medial aspects of the thighs. The underlying etiology of FFD remains unclear although epidemiologic data support a hormonal component because women are more commonly affected than men. Moreover, symptoms initially present after the onset of puberty, flare perimenstrually, and often resolve during pregnancy and after menopause. Histopathologic findings include the obstruction of the apocrine duct by a hyperkeratotic plug in the follicular infundibulum, which is believed to represent the primary pathophysiologic process; subsequent ductal rupture and resulting inflammatory response produce the typical clinical picture. Treatment of FFD is difficult because no one agent has proven particularly effective. Topical and interlesional glucocorticoids are often considered the first-line pharmacologic agents, although use is often limited by concerns for atrophy. Other agents that have shown some success include topical and systemic retinoids, topical clindamycin, topical pimecrolimus cream, benzoyl peroxide, and oral contraceptives. For medication-refractory cases, mechanical destruction or removal of the apocrine glands has been efficacious in small case series.



History


Figure 1Figure 2

A 24-year-old woman originally from Sierra Leone presented to the Dermatology Clinic of Bellevue Hospital Center with a ten-year history of multiple, pruritic papules in her axillae and on her vulva. She also noted similar appearing papules near her nipples that were asymptomatic. The symptoms were worse during the summer and also were exacerbated by sweating. Over the same time period, she also noted a gradual thinning of the axillary hair. She denied any improvement during pregnancy or while taking oral contraceptives. Previously, betamethasone cream had been prescribed for the axillae by an outside dermatologist, which was only marginally successful in controlling the pruritus.

Past medical history inlcuded one normal pregnancy with a vaginal delivery. Medications included oral contraceptives.

A punch biopsy specimen was obtained from a representative lesion in her right axilla. She is currently applying tacrolimus 0.1 percent ointment to the lesions in the axillae and around the areolae and fluocinolone 0.025 percent ointment to the lesions on the vulva.


Physical examination

Multiple, monomorphic, flesh-colored, follicular papules were present in the axillae and on the upper mons pubis. Similar, small, flesh-colored papules also were noted in a periareolar distribution. Axillary hair was almost entirely absent, with only a few terminal hairs present.


Laboratory data

None.


Histopathology

There is a perivascular and perifollicular, lymphocytic infiltrate that is associated with peri-infundibular fibrosis, follicular spongiosis, and slight dilation of an apocrine duct beneath a hair follicle.


Discussion

Originally described by George Henry Fox and John Addison Fordyce in 1902, Fox-Fordyce disease (FFD) is a rare inflammatory disorder of the apocrine sweat glands [1]. Lesions are classically smooth, uniform, equidistant, firm, folliculocentric papules that range in color from flesh-colored to red-brown to slightly yellow and often lack an associated hair shaft [2]. Most commonly, FFD affects the axillae followed by the anogenital and periareolar areas. However, it also has been reported to involve the lips, umbilicus, sternum, perineum, and upper medial aspects of the thighs [3]. The associated pruritus is often very intense and can paroxysmally worsen with stress, excitement, exercise, hot weather, emotional crises, sexual activity, and in response to certain physical and pharmacologic stimuli [3, 4, 5, 6].

Although the etiology of FFD remains unclear, much of the epidemiologic data support a strong hormonal component, with 90 percent of cases occurring in women between the ages of 13 and 35 years; symptoms usually first present after the onset of puberty [3]. The observations that symptoms can worsen perimenstrually and improve during pregnancy, after menopause, and with oral contraceptive use lend further weight to a hormonal role in disease pathophysiology [7, 8]. However, despite this clear clinical correlation between disease activity and sex hormone levels, multiple studies have failed to identify patterns of laboratory abnormalities among affected individuals [9]. Several recent reports of FFD in pre-pubertal girls suggest that the underlying etiologic process is likely multi-factorial [10, 11, 12].

Termed apocrine miliaria by Shelly and Levy in 1956, FFD is difficult to diagnose by histopathologic features alone because the associated findings vary greatly [13]. A hyperkeratotic plug of the follicular infundibulum that also obstructs the apocrine duct is believed to be the critical early event in pathophysiology [5]. This process then produces an apocrine anhydrosis and eventually causes ductal rupture. The subsequent sweat extravasation and resulting inflammatory response are believed to trigger the extreme pruritus that is characteristic of FFD. Whereas historically FFD was only believed to affect follicular apocrine glands, new evidence suggests that eccrine and non-follicular variants also may exist [5, 12].

Treatment of FFD is difficult, with all treatment data derived from case reports and small case series [6]. Almost all evidence regarding the treatment of FFD focuses exclusively on axillary disease, with no mention of other sites of involvement. Topical and intralesional glucocorticoids are considered first-line agents although their use is limited by concerns for skin atrophy. Because hyperkeratosis plays a critical role in disease pathophysiology, topical retinoids have been used with some success. In one study, daily use of 0.1 percent tretinoin reduced pruritic symptoms and produced a mild regression of the axillary papules [14]. However, local irritation and retinoid dermatitis often limit long-term use. Systemic isotretinoin is even more efficacious in the short term. In one study, a near complete resolution of all axillary papules was achieved after two months at a dose of 30 mg/day although lesions recurred within three months after discontinuing the medication [15]. Clindamycin solution, pimecrolimus cream 1 percent, and benzoyl peroxide 5 percent also have been anecdotally effective in mitigating symptoms [7, 16, 17]. Owing to the profound symptom improvement that is associated with pregnancy and menopause, combined oral contraceptives (with both progesterone and estrogen analogs) represent another therapeutic option and are used frequently adjunctively with other topical agents [18].

In medication-refractory cases, several surgical interventions have proven to be successful in case reports, which include mechanical destruction of the apocrine glands via liposuction-assisted curettage, electrocautery, and surgical excision [19, 20, 21].

References

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