15 - 83 - FOX-FORDYCE DISEASE

Question 1

A rare, itchy, chronic papular eruption localized to apocrine gland–bearing areas of the body with unclear etiology.

Answer 1

Fox-Fordyce Disease

• Females are disproportionately affected compared to males (9:1), with age of onset most commonly between 13-35 years of age.
• Lesions are characterized by numerous firm, flesh-colored, follicular-based papules arranged in a grouped configuration
• typically manifests after the onset of puberty, most commonly in the axillae
• Pruritus is intermittent and intense.
• Diminished sweat production is frequently observed in affected areas

Question 2

thought to be the primary pathophysiologic event, leading to duct dilation, rupture, inflammation, and pruritus of fox-fordyce disease

Answer 2

Hyperkeratotic obstruction of the follicular infundibulum at the apocrine gland duct insertion site

• The intraluminal obstruction leads to glandular distension and eventual ductal rupture
• The subsequent expulsion of glandular contents into the surrounding dermis then causes an inflammatory response that manifests clinically as the intensely pruritic, dome-shaped, perifollicular papules.

Question 3

most consistent histopath finding in fox fordyce disease

Answer 3

hyperkeratosis of the infundibular epithelium and dilation of the follicular infundibulum

• Perifollicular and periductal xanthomatosis cells are frequently seen
• Focal spongiosis of the upper infundibulum along with perifollicular adventitial fibrosis and lymphohistiocytic infiltrate also were consistently observed
• Other findings include **vacuolar alterations at the dermato–epithelial junction **of the infundibula; smatterings of dyskeratotic cells throughout the infundibula; and tiny columns of cornoid lamella-like parakeratosis in close proximity to the acrosyringium of the apocrine duct, with eosinophilic keratinocytes found underneath
• existence of pathognomonic “sweat retention” vesicles described by Shelly and Levy 6 is controversial, as these vesicles are rarely demonstrated in histologic specimens

Question 4

Therapeutic Strategies for Fox-Fordyce

Answer 4

• Stress reduction and heat avoidance may help minimize pruritus.
• First-generation oral antihistamines can be useful for alleviating itch, especially during the night.
• Low doses of doxepin (<10 mg), up to 3 times a day, can be used as an alternative to oral antihistamines.
• There is no evidence to suggest that shaving or deodorant use worsen symptoms; however, thick creams and lotions, which can exacerbate follicular obstruction, should be avoided.
• Topical steroid creams are first-line therapies and can temporarily relieve itching; however, continuous application for more than 10 to 14 days is discouraged because of the risk of skin thinning and formation of striae
• **Intradermal triamcinolone **may help alleviate itching during acute flares, but can also cause cutaneous atrophy with repeated administrations.
• **Topical calcineurin inhibitors (1% pimecrolimus cream, 0.1% tacrolimus) **can be used as alternatives to steroids and will not thin the skin.
• **Pimecrolimus 1% cream **applied twice daily over 8 weeks induced complete remission in 1 patient and partial remissions in 2 patients.
• ** Topical tretinoin **can be effective but is often abandoned because of excessive irritation of the skin.
• Topical 0.1% adapalene gel, which is better tolerated than tretinoin, produced mild-to-moderate improvements in itch and number of papules in 1 case when applied every other day for 2 months
• In 2 cases,** topical clindamycin in propylene glycol solution** led to rapid resolution of papules after 1 month of treatment without recurrence at 6 to 9 months.
• Other medical therapies include diethylstilbestrol, oral contraceptives, testosterone, corticotropin, ultraviolet light therapy, and X-ray therapy. 2
• Oral isotretinoin dosed at **15 to 30 mg daily **for 16 weeks induced near-complete remission of lesions and pruritus in 1 case ; however, lesions recurred 3 months after discontinuing therapy, accompanied by a more intense pruritus than before.
• A one-time injection of botulinum toxin type A (2 units diluted into 2.5 mL of 0.9% saline at multiple points 2-cm apart in axillae) produced complete remission 15 days after injections without recurrence at 8 months of followup.
• procedural therapies: electrocautery, excision-liposuction with curettage, microwave thermal ablation, and laser-based excisions, can be curative, but are generally late-line options because of concern about infection, hypertrophic scarring, and/or disfiguration.