AUTHOR AND EDITOR INFORMATION

Section 1 of 9  

• Authors and Editors
• Introduction
• Clinical
• Differentials
• Workup
• Treatment
• Medication
• Follow-up
• References

INTRODUCTION

Section 2 of 9  

• Authors and Editors
• Introduction
• Clinical
• Differentials
• Workup
• Treatment
• Medication
• Follow-up
• References

Background

Fox-Fordyce disease is an infrequently occurring chronic pruritic papular eruption that localizes to areas where apocrine glands are found. The etiology is currently unknown. The eponym is based on the 1902 report by G. Fox and J. Fordyce.

Pathophysiology

Fox-Fordyce disease is a disease of the skin alone. In 1956, Shelley and Levy proposed apocrine miliaria as the cause. The observed pathophysiology is a keratin plug in the hair follicle infundibulum obstructing the apocrine acrosyringium and producing an apocrine anhidrosis. Histologically, a rupture of the apocrine excretory duct occurs, and spongiotic inflammation results. Extravasation of sweat and inflammation is postulated to cause the intense itching. Ranalletta et al found that the acrosyringium of the eccrine glands was similarly involved.

In 2003, Kamada et al published a histopathologic analysis from which they concluded that the 2 types of this disease are (1) an apocrine (follicular) type and (2) an apocrine (nonfollicular) type.

Frequency

United States

Fox-Fordyce disease is an infrequent condition. Geographic influence is not evident. Many case reports mention heat, humidity, and stress as exacerbating factors.

International

Reports from the United States are the most common; however, a geographic limitation is not evident.

Mortality/Morbidity

This disease has no risk of loss of life or limb. Patients often experience severe pruritus. Therefore, the patient's quality of life may be adversely affected.

Race

No racial predilection is evident.

Sex

A distinct predilection for women exists; the female-to-male ratio is 9:1.

Age

Fox-Fordyce disease is most common in women aged 13-35 years; it is rare before or after this age.

CLINICAL

Section 3 of 9  

• Authors and Editors
• Introduction
• Clinical
• Differentials
• Workup
• Treatment
• Medication
• Follow-up
• References

History

• This condition frequently appears under conditions of heat, humidity, and friction, often appearing suddenly.
• Many patients present after decades of symptoms.
• Few patients are asymptomatic.
• Most patients relate pruritus that disturbs sleep.
• Changing antiperspirants has not been reported to help.
• Some patients report diminution of sweating after the onset of symptoms.

Physical

• The apocrine glands are the site of Fox-Fordyce disease.
• Lesions are most often found in the axillae, where they tend to be bilateral.
• Lesions may also affect the periareolar, inframammary, and pubic areas.
• The primary lesion is a flesh-colored to reddish, smooth, dome-shaped, discrete, and follicular or perifollicular papule.
• Affected areas usually have many papules. The papules usually appear to affect every follicle in a given area.
• Excoriations and lichenification may be seen as a consequence of scratching.
• Sweating is often absent in the affected area.

Causes

• The definite increased prevalence in women has led to an unproved theory of hormonal influences. Reports of cases in prepubertal girls are evidence against the hormonal theory. The exact pathophysiology is still unknown.
• A number of factors, including (1) emotional and/or hormonal influences and (2) alterations in sweat components, have been implicated.

DIFFERENTIALS

Section 4 of 9  

• Authors and Editors
• Introduction
• Clinical
• Differentials
• Workup
• Treatment
• Medication
• Follow-up
• References

Other Problems to be Considered

Pseudofolliculitis of the axillae

WORKUP

Section 5 of 9  

• Authors and Editors
• Introduction
• Clinical
• Differentials
• Workup
• Treatment
• Medication
• Follow-up
• References

Lab Studies

• Histopathologic diagnosis may be very difficult with conventional sectioning. Stashower et al proposed transverse histologic sectioning as the most effective way to demonstrate diagnostic features.
• Diagnosis is usually made on clinical/historical grounds. Laboratory or even histopathologic tests are seldom necessary for clinicians familiar with this condition.

Procedures

• In 2002, Chae et al described axillary Fox-Fordyce disease treated with liposuction-assisted curettage.

Histologic Findings

The proposed apocrine origin was based on the finding of a keratin plug in the follicular infundibulum that occluded the apocrine acrosyringium. Reports also include a rupture of the apocrine duct and a resulting spongiotic inflammation. Plasma cells may be noted, and the deeper apocrine duct may be dilated with sialomucin. The dermis may show fibrosis and chronic inflammation. These latter findings depend on the condition's chronicity.

TREATMENT

Section 6 of 9  

• Authors and Editors
• Introduction
• Clinical
• Differentials
• Workup
• Treatment
• Medication
• Follow-up
• References

Medical Care

Based on the observations of follicular occlusion, Shelley proposed topical tretinoin cream as therapy in 1972. Reports of success with topical retinoids followed, along with reports of success with topical steroids, antibiotics, clindamycin in alcoholic propylene glycol solution, hormonal therapy in women, ultraviolet light, dermabrasion, and surgical excision. Usually, these therapies were not curative and were often complicated by intolerable irritation. 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.

Surgical Care

Surgical excision of affected areas in the axilla has been performed in the past, but it is seldom recommended.

Consultations

Consultation with a dermatologist is usually recommended.

Activity

Activity that leads to sweating is counterproductive. Swimming is the preferred form of exercise.

MEDICATION

Section 7 of 9  

• Authors and Editors
• Introduction
• Clinical
• Differentials
• Workup
• Treatment
• Medication
• Follow-up
• References

Medical therapy has been complicated by the irritant potential of the topical medications. Topical steroids have not been useful. Topical retinoids have been irritating, which has limited their long-term use. In 1979, Giacobeti reported success with topical 0.1% tretinoin cream. In 1990, Casani reported treatment with topical 0.5% tretinoin cream. In 1995, Miller et al reported treatment of Fox-Fordyce disease with topical clindamycin solution.

Hormonal therapy with high-estrogen oral contraceptives, estrogen creams, and testosterone creams has been reported, sometimes with success but often with failure.

In 2006, Pock et al reported effective therapy, with no adverse effects, using pimecrolimus in 3 young female patients. The response was deemed "very impressive." Based on this report, the DOC could be this class of drug, which includes tacrolimus.

Drug Category: Retinoids

Based on follicular infundibular occlusion, the retinoids (first tretinoin, later isotretinoin) have been used with reported short-term success. Consider therapy with alternative retinoids as they become available. Based on the success of tretinoin, oral retinoids have also been used with reported success.

Drug Category: Antibiotics

Topical clindamycin in propylene glycol was first reported to help patients with Fox-Fordyce disease in 1992. Confirmation of this study was reported in 1995. Topical erythromycin should also be helpful.

Drug Category: Immunosuppressants

Used because of inflammatory and hyperkeratinization character of the disease.

FOLLOW-UP

Section 8 of 9  

• Authors and Editors
• Introduction
• Clinical
• Differentials
• Workup
• Treatment
• Medication
• Follow-up
• References

Further Outpatient Care

• Advise patients of the chronicity and the possible need for long-term therapy because this condition is often controlled but not cured.

Deterrence/Prevention

• Environmental modification and hormonal therapy have not always proven to affect the course of Fox-Fordyce disease.

Complications

• Manage complications (eg, local superinfection) in the standard ways.

Prognosis

• Management with topical retinoids and antibiotics has brought some hope to patients with this condition 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.

REFERENCES

Section 9 of 9

• Authors and Editors
• Introduction
• Clinical
• Differentials
• Workup
• Treatment
• Medication
• Follow-up
• References

• Chae KM, Marschall MA, Marschall SF. Axillary Fox-Fordyce disease treated with liposuction-assisted curettage. Arch Dermatol. Apr 2002;138(4):452-4. [Medline].
• Effendy I, Ossowski B, Happle R. Fox-Fordyce disease in a male patient--response to oral retinoid treatment. Clin Exp Dermatol. Jan 1994;19(1):67-9. [Medline].
• Fox G, Fordyce J. Two cases of a rare papular disease affecting the axillary region. J Cutan Genito-Urinary Dis. 1902;20:1-5.
• Kamada A, Saga K, Jimbow K. Apoeccrine sweat duct obstruction as a cause for Fox-Fordyce disease. J Am Acad Dermatol. Mar 2003;48(3):453-5. [Medline].
• Miller ML, Harford RR, Yeager JK. Fox-Fordyce disease treated with topical clindamycin solution. Arch Dermatol. Oct 1995;131(10):1112-3. [Medline].
• Pock L, Svrckova M, Machackova R, Hercogova J. Pimecrolimus is effective in Fox-Fordyce disease. Int J Dermatol. Sep 2006;45(9):1134-5. [Medline].
• Ranalletta M, Rositto A, Drut R. Fox-Fordyce disease in two prepubertal girls: histopathologic demonstration of eccrine sweat gland involvement. Pediatr Dermatol. Jul-Aug 1996;13(4):294-7. [Medline].
• Sandhu K, Gupta S, Kanwar AJ. Fox fordyce disease in a prepubertal girl. Pediatr Dermatol. Jan-Feb 2005;22(1):89-90. [Medline].
• Shelley WB, Levy EJ. Apocrine sweat retention in man. II. Fox-Fordyce disease (apocrine miliaria). AMA Arch Derm. Jan 1956;73(1):38-49. [Medline].
• Stashower ME, Krivda SJ, Turiansky GW. Fox-Fordyce disease: diagnosis with transverse histologic sections. J Am Acad Dermatol. Jan 2000;42(1 Pt 1):89-91. [Medline].

Article Last Updated: Jan 12, 2007