Fox-Fordyce disease treated with fractional CO2 laser: A case report

Fox-Fordyce disease (FFD) is a rare inflammatory condition affecting apocrine sweat glands.1Salloum A. Bouferraa Y. Bazzi N. et al.Pathophysiology, clinical findings, and management of Fox-Fordyce disease: a systematic review.J Cosmet Dermatol. 2022; 21: 482-500Crossref PubMed Scopus (2) Google Scholar Patients with FFD typically present with folliculocentric papules that are often pruritic and lack an associated hair shaft. Lesions are smooth, uniform, firm, and range from yellow to reddish-brown in color.2Yost J. Robinson M. Meehan S.A. Fox-Fordyce disease.Dermatol Online J. 2012; 18: 28Crossref PubMed Google Scholar An evidence-based approach to management has yet to be established. A 23-year-old female with no significant medical history presented to clinic with well-defined skin-colored papules in the axillae bilaterally (Fig 1). The lesions were misdiagnosed as warts by the patient’s family physician and had previously been treated with liquid nitrogen with no improvement. The patient complained of subsequent hyperpigmentation after cryotherapy, which had partially faded over time with topical lightening agents. To clarify the diagnosis, 4 mm punch biopsies were taken from the axillae bilaterally. Histopathology was consistent with FFD, showing superficial perivascular and perifollicular lymphoid infiltrate extending focally around the opening of apocrine ducts near follicular infundibula (Fig 2). The epidermis was unremarkable and periodic acid-Schiff stain was negative on both biopsies. After reviewing treatment options with the patient, we elected to proceed with fractional carbon dioxide (CO2) laser (Lutronic ECO2) to manage her condition. The patient underwent 3 fractional CO2 laser treatments over a 5-month period with significant improvement (Fig 3). There were no complications throughout the course of therapy and the patient’s results have been maintained for 1 year postinitiation of therapy. FFD occurs more frequently in females with a peak in incidence in young adulthood. Previously referred to as apocrine miliaria, FFD most commonly affects the axillae with rarer occurrences in the anogenital areas, periareolar areas, lips, upper thighs, and chest.1Salloum A. Bouferraa Y. Bazzi N. et al.Pathophysiology, clinical findings, and management of Fox-Fordyce disease: a systematic review.J Cosmet Dermatol. 2022; 21: 482-500Crossref PubMed Scopus (2) Google Scholar,2Yost J. Robinson M. Meehan S.A. Fox-Fordyce disease.Dermatol Online J. 2012; 18: 28Crossref PubMed Google Scholar A 2021 systematic review performed by Salloum et al found that 71% of patients experienced pruritus and that 90% of FFD lesions were bilateral.1Salloum A. Bouferraa Y. Bazzi N. et al.Pathophysiology, clinical findings, and management of Fox-Fordyce disease: a systematic review.J Cosmet Dermatol. 2022; 21: 482-500Crossref PubMed Scopus (2) Google Scholar The pathophysiology of FFD is not yet fully understood. Given that the typical case of FFD is a postpubertal and premenopausal female, hormonal changes are thought to play a role.1Salloum A. Bouferraa Y. Bazzi N. et al.Pathophysiology, clinical findings, and management of Fox-Fordyce disease: a systematic review.J Cosmet Dermatol. 2022; 21: 482-500Crossref PubMed Scopus (2) Google Scholar Symptoms in previous FFD cases have improved with the onset of menopause or oral contraceptives.3Kronthal H.L. Pomeranz J.R. Sitomer G. Fox-Fordyce disease: treatment with an oral contraceptive.Arch Dermatol. 1965; 91: 243-245Crossref PubMed Scopus (18) Google Scholar,4Montes L.F. Caplan R.M. Riley G.M. Curtis A.C. Fox-Fordyce disease: an endocrinological study.Arch Dermatol. 1961; 84: 452-458Crossref PubMed Scopus (7) Google Scholar Keratotic obstruction leads to destruction of the duct and secretory portions of apocrine sweat glands, causing a downstream inflammatory response, in which lymphocytes and histiocytes are recruited to the site of epithelial injury.2Yost J. Robinson M. Meehan S.A. Fox-Fordyce disease.Dermatol Online J. 2012; 18: 28Crossref PubMed Google Scholar,5Kamada A. Saga K. Jimbow K. Apoeccrine sweat duct obstruction as a cause for Fox-Fordyce disease.J Am Acad Dermatol. 2003; 48: 453-455Abstract Full Text Full Text PDF PubMed Scopus (34) Google Scholar The differential diagnoses of FFD include acne vulgaris, milia, folliculitis, Darier disease, and lichen amyloidosis.1Salloum A. Bouferraa Y. Bazzi N. et al.Pathophysiology, clinical findings, and management of Fox-Fordyce disease: a systematic review.J Cosmet Dermatol. 2022; 21: 482-500Crossref PubMed Scopus (2) Google Scholar,6Kao P.H. Hsu C.K. Lee J.Y. Clinicopathological study of Fox–Fordyce disease.J Dermatol. 2009; 36: 485-490Crossref PubMed Scopus (18) Google Scholar Perifollicular foam cell infiltrate, infundibular dilation, hyperkeratosis, plugging, and acanthosis have been shown to be distinctive histopathological attributes of FFD.6Kao P.H. Hsu C.K. Lee J.Y. Clinicopathological study of Fox–Fordyce disease.J Dermatol. 2009; 36: 485-490Crossref PubMed Scopus (18) Google Scholar The low incidence rate and poorly understood pathophysiology of FFD have prevented an evidence-based treatment protocol from being established. Data regarding FFD management have largely come from case reports and small case series.7Bormate A.B. Leboit P.E. McCalmont T.H. Perifollicular xanthomatosis as the hallmark of axillary Fox-Fordyce disease: an evaluation of histopathologic features of 7 cases.Arch Dermatol. 2008; 144: 1020-1024Crossref PubMed Scopus (617) Google Scholar The systematic review published by Salloum et al also summarized treatment regimens for previously reported cases of FFD. Topical retinoids were the most commonly reported treatment, used in 18% of reported cases. Less than 10% of cases treated with topical retinoids alone reached complete resolution, and 64% of patients experienced mild to moderate improvement of their symptoms. Topical clindamycin was shown to have varying results, as half of cases reached significant resolution while the other half showed little to no improvement. Topical calcineurin inhibitors, particularly pimecrolimus, showed strong efficacy, albeit with a limited sample size. Five of 6 patients experienced marked improvement of their symptoms. Most FFD cases treated with topical steroids showed little to no resolution.1Salloum A. Bouferraa Y. Bazzi N. et al.Pathophysiology, clinical findings, and management of Fox-Fordyce disease: a systematic review.J Cosmet Dermatol. 2022; 21: 482-500Crossref PubMed Scopus (2) Google Scholar Oral treatments, such as isotretinoin and contraceptives, and procedural treatment, such as surgical excision and liposuction, were attempted in isolated cases.1Salloum A. Bouferraa Y. Bazzi N. et al.Pathophysiology, clinical findings, and management of Fox-Fordyce disease: a systematic review.J Cosmet Dermatol. 2022; 21: 482-500Crossref PubMed Scopus (2) Google Scholar Two cases of FFD successfully treated with botulinum toxin have also been recently published, presenting another promising therapeutic possibility.8Alhameedy M.M. Tariq M.U. Refractory pruritic Fox-Fordyce disease successfully treated with botulinum toxin type A.Int J Women's Dermatol. 2022; 8: e039Crossref PubMed Google Scholar,9Klager S. Kumar M.G. Treatment of pruritus with botulinum toxin in a pediatric patient with Fox-Fordyce disease.Pediatr Dermatol. 2021; 38: 950-951Crossref PubMed Scopus (4) Google Scholar Fractional lasers have not been extensively used in the treatment of FFD lesions. There has been 1 published case of FFD treated with fractional CO2 laser. The lesions and pruritus improved dramatically over the course of 3 sessions.10Ahmed Al-Qarqaz F. Al-Shannag R. Fox–Fordyce disease treatment with fractional CO2 laser.Int J Dermatol. 2013; 52: 1571-1572Crossref PubMed Scopus (9) Google Scholar The degree of success seen in our patient, as well as in this previous case, suggest that fractional CO2 laser may be an effective option in the management of FFD. Future efficacy and durability studies with larger sample sizes and longitudinal follow-up should be performed to further investigate this promising treatment modality for this condition. None disclosed.

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