eMedicine Specialties > Dermatology > Diseases of the Adnexa
Fox-Fordyce Disease: Treatment & Medication
Updated: Oct 30, 2009
- Overview
- Differential Diagnoses & Workup
- Treatment & Medication
- Follow-up
Treatment
Medical Care
Many Fox-Fordyce disease patients improve when placed on an oral contraceptive pill. 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.10
Surgical Care
Surgical excision of affected areas in the axilla has been performed in the past, but it is seldom recommended. Chae et al reported treatment of Fox-Fordyce disease with liposuction-assisted curettage.7
Consultations
Consultation with a dermatologist is usually recommended in Fox-Fordyce disease.
Activity
Activity that leads to sweating is counterproductive. Swimming is the preferred form of exercise for Fox-Fordyce disease patients.
Medication
Medical therapy for Fox-Fordyce disease 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.11
Hormonal therapy for Fox-Fordyce disease with high-estrogen oral contraceptives, estrogen creams, and testosterone creams has been reported.
In 2006, Pock et al reported effective therapy, with no adverse effects, using pimecrolimus in 3 young female patients.12 The response was deemed "very impressive." Based on this report, the drug of choice could be this class of drug, which includes tacrolimus.
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.
Tretinoin (Avita, Retin-A)
Since 1972, therapy with topical retinoids has the most support in the literature. Several reports exist on the efficacy of topical tretinoin. Severe irritation may occur when used in the axillae. The 0.025% cream, or even a dilution to a milder form or short contact therapy, would be prudent to begin therapy.
Increasing both the time and the amount gradually as tolerated is a safe way to avoid irritation.
Adult
Begin with lowest tretinoin formulation and increase as tolerated; apply hs or qod; lower frequency of application if irritation develops
Pediatric
<12 years: Not established
>12 years: Apply as in adults
Toxicity increases with coadministration of benzoyl peroxide, salicylic acid, and resorcinol; avoid topical sulfur, resorcinol, salicylic acid, other keratolytics, abrasives, astringents, spices, and lime
Documented hypersensitivity; open wounds; lacerations
Pregnancy
C - Fetal risk revealed in studies in animals but not established or not studied in humans; may use if benefits outweigh risk to fetus
Precautions
May take several wk for skin to adapt to irritative effect; by starting application qwk and slowly increasing to qhs, noncompliance from warmth and redness is decreased; avoid contact with eyes and mucous membranes; minimize exposure to sun and UV light
Isotretinoin (Accutane)
By analogy, because isotretinoin worked topically, it was predicted that oral retinoids would be effective. Low doses of isotretinoin have been efficacious. Although symptoms were relieved at relatively low doses, the condition returned in a few months after cessation of therapy.
A US Food and Drug Administration–mandated registry is now in place for all individuals prescribing, dispensing, or taking isotretinoin. For more information on this registry, see iPLEDGE. This registry aims to further decrease the risk of pregnancy and other unwanted and potentially dangerous adverse effects during a course of isotretinoin therapy.
Adult
10-30 mg/d PO; lower doses may be effective (therapy may need to be continued for long periods)
Pediatric
Not established
Toxicity may occur with vitamin A coadministration; pseudotumor cerebri or papilledema may occur when coadministered with tetracyclines; acitretin may reduce plasma levels of carbamazepine
Documented hypersensitivity; possibility of pregnancy; pregnancy
Pregnancy
X - Contraindicated; benefit does not outweigh risk
Precautions
May decrease night vision; inflammatory bowel disease may occur; may be associated with development of hepatitis; occasional exaggerated healing response of acne lesions (excessive granulation with crusting) may occur; patients with diabetes may experience problems in controlling their blood sugar level while on isotretinoin; avoid exposure to UV light or sunlight until tolerance achieved; discontinue treatment if rectal bleeding, abdominal pain, or severe diarrhea occur
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 1995.11 Topical erythromycin should also be helpful.
Clindamycin (Cleocin-T)
Lincosamide for treatment of serious skin and soft tissue staphylococcal infections. Also effective against aerobic and anaerobic streptococci (except enterococci). Inhibits bacterial growth, possibly by blocking dissociation of peptidyl t-RNA from ribosomes causing RNA-dependent protein synthesis to arrest.
Adult
Apply topically bid
Pediatric
Apply as in adults
None reported
Documented hypersensitivity; regional enteritis; ulcerative colitis; hepatic impairment; antibiotic-associated colitis
Pregnancy
B - Fetal risk not confirmed in studies in humans but has been shown in some studies in animals
Precautions
Superinfections may occur with prolonged or repeated antibiotic therapy
Erythromycin (A/T/S, Erycette, Staticin, T-Stat)
Inhibits bacterial growth, possibly by blocking dissociation of peptidyl t-RNA from ribosomes, causing RNA-dependent protein synthesis to arrest. Used in the treatment of staphylococcal and streptococcal infections.
Adult
Apply topically bid
Pediatric
Apply as in adults
Topical erythromycin is inactivated in the presence of acids due to hydrolysis; activity of erythromycin is also reduced in the presence of sodium alginate, pectin, bentonite, calamine, silica, and polysorbate 80
Documented hypersensitivity
Pregnancy
B - Fetal risk not confirmed in studies in humans but has been shown in some studies in animals
Precautions
For external use only; avoid eyes, mouth, and other mucous membranes; adverse reactions include dryness, tenderness, pruritus, desquamation, erythema, and burning sensation; concomitant topical therapy should be used with caution because cumulative irritancy may occur; prolonged use may be associated with overgrowth of antibiotic-resistant organisms
Immunosuppressants
Used because of inflammatory and hyperkeratinization character of the disease.
Pimecrolimus (Elidel) cream or tacrolimus (Protopic) ointment
Because of the rapidity of response, effectiveness of therapy, and lack of adverse effects, this could be current DOC. Both are in immunomodulating macrolactam (neuraminidase inhibitors) class of drugs and have significant anti-inflammatory activity and a highly favorable adverse effect profile in at least the short range. Both are especially safe to use in the axilla, periareolar, and groin areas.
Adult
Pimecrolimus: 1% cream topically bid until relief, then 1-2 times/wk over prolonged period
Tacrolimus: 0.1% ointment topically bid until relief, then 1-2 times/wk over prolonged period
Pediatric
>2 to <12 years: 0.03% tacrolimus; administer as in adults
Topical tacrolimus is minimally absorbed; however, levels may increase with diltiazem, nicardipine, clotrimazole, verapamil, erythromycin, ketoconazole, itraconazole, fluconazole, bromocriptine, grapefruit juice, metoclopramide, methylprednisolone, danazol, cyclosporine, cimetidine, or clarithromycin; levels may reduce with rifabutin, rifampin, phenobarbital, phenytoin, and carbamazepine
Documented hypersensitivity
Pregnancy
C - Fetal risk revealed in studies in animals but not established or not studied in humans; may use if benefits outweigh risk to fetus
Precautions
Do not use with occlusive dressings; may be associated with an increased risk of varicella-zoster virus infection, HSV infection, or eczema herpeticum; long-term safety of topical calcineurin inhibitors not established; although causal relationship has not been established, rare cases of malignancy (eg, skin, lymphoma) reported in patients treated with topical calcineurin inhibitors and thus continuous long-term use should be avoided application should be limited to areas of involvement
More on Fox-Fordyce Disease |
| Overview: Fox-Fordyce Disease |
| Differential Diagnoses & Workup: Fox-Fordyce Disease |
 Treatment & Medication: Fox-Fordyce Disease |
| Follow-up: Fox-Fordyce Disease |
| References |
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References
Fox G, Fordyce J. Two cases of a rare papular disease affecting the axillary region. J Cutan Genito-Urinary Dis. 1902;20:1-5.
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].
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].
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].
Sandhu K, Gupta S, Kanwar AJ. Fox fordyce disease in a prepubertal girl. Pediatr Dermatol. Jan-Feb 2005;22(1):89-90. [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].
Chae KM, Marschall MA, Marschall SF. Axillary Fox-Fordyce disease treated with liposuction-assisted curettage. Arch Dermatol. Apr 2002;138(4):452-4. [Medline].
Bormate AB Jr, Leboit PE, McCalmont TH. Perifollicular xanthomatosis as the hallmark of axillary Fox-Fordyce disease: an evaluation of histopathologic features of 7 cases. Arch Dermatol. Aug 2008;144(8):1020-4. [Medline].
Macarenco RS, Garces S JC. Dilation of apocrine glands. A forgotten but helpful histopathological clue to the diagnosis of axillary Fox-Fordyce disease. Am J Dermatopathol. Jun 2009;31(4):393-7. [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].
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].
Further Reading
Keywords
Fox-Fordyce disease, Fox-Fordyce syndrome, apocrine miliaria, chronic pruritic papular eruption, follicular infundibular occlusion
