Introduction
Incontinentia pigmenti (IP) is a rare X-linked disorder caused by a mutation in the nuclear factor-κB essential modulator (NEMO) gene that affects ectodermal tissues, including the skin, hair, eyes, teeth, and the central nervous system. IP can be associated with alopecia, often on the vertex scalp, presenting in a diffuse or whorled pattern, or involving eyebrows and eyelashes, in up to 67% of patients.1,2 IP-associated alopecia has been suggested as scarring in nature, although the specifics of the alopecia seen in this setting are poorly addressed in the literature. One review of 11 patients with IP reported that vertex alopecia usually occurred after blistering in the region; however, other studies (and our clinical observations) suggest that alopecia often occurs without preceding inflammatory activity.3 IP-associated alopecia tends to be permanent and may be the only manifestation of IP in adolescents and adults, once the other cutaneous manifestations resolve.2 There is no established therapy for IP-associated alopecia, although hair transplantation has been reported as 1 option.4 Here, we describe a patient with IP-associated alopecia who experienced marked rapid regrowth while being treated with dupilumab for her concomitant atopic dermatitis (AD).
Case report
A 6-year-old girl with poorly controlled AD for 2 months of life, who failed therapy with mid- and high-potency topical corticosteroids, topical calcineurin inhibitors, antihistamines, bleach baths, and wet wrap therapy, was started on subcutaneous dupilumab injections. She was diagnosed with IP as a newborn, based on characteristic skin findings (Fig 1, A and B) and a history of known IP in her mother (Fig 1, C). One of her IP cutaneous stigmata was curvilinear scalp alopecia (Fig 2, A), which was initially noted at the age of 4 years. After 10 weeks of dupilumab therapy, marked regrowth of coarse terminal hairs in the affected area of the scalp was noted (Fig 2, B), in addition to a marked improvement in her AD (Patient-Oriented Eczema Measure score improved from 26/28 to 9/28). She is currently continued on dupilumab therapy and tolerating it well, aside from mild conjunctivitis responsive to artificial tears.
Fig 1.
Incontinentia pigmenti in the patient and her mother. A, Vesicles, verrucous papules, and hyperpigmentation following a curvilinear pattern along lines of Blaschko on the trunk. B, Similar lesions following a linear distribution on the upper extremity. C, Atrophic, linear hypopigmented streaks with alopecia on the lower portion of the leg of the patient’s mother.
Fig 2.
A, Well-demarcated patch of whorled alopecia on the vertex scalp. B, Hair regrowth after 10 weeks of treatment with dupilumab.
Discussion
Dupilumab is a human monoclonal antibody that targets the interleukin 4 receptor α, blocking interleukin 4, and interleukin 13 signaling. It is US Food and Drug Administration-approved for the treatment of moderate-to-severe AD in patients aged ≥6 months. Dupilumab has been used off-label in patients with alopecia areata, including ophiasis pattern, patchy type, totalis, and universalis, with reports of treatment success.5 The mechanism of hair regrowth in patients with alopecia areata treated with dupilumab may be related to the downregulation of the Th2 (T helper 2 cell) pathway, given the probable involvement of this pathway in disease pathogenesis, in addition to the traditionally-implicated Th1 (T helper 1 cell) pathway.6 To our knowledge, there is no existing literature on the effectiveness of dupilumab therapy (or its mechanism of action) in IP-related alopecia. Our observation of successful hair regrowth with dupilumab in a patient with IP-associated alopecia suggests a possible role of the Th2 inflammatory pathway in the pathogenesis of alopecia seen in the setting of IP and supports further research into the potential use of this biologic agent for other hair loss disorders. It also calls into question the traditional suggestion that IP-associated alopecia is a permanent, scarring process.
Conflicts of interest
None disclosed.
Footnotes
Funding sources: None.
IRB approval status: Not applicable.
References
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