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Going retro: Reactivation of incontinentia pigmenti

DII small banner By Warren R. Heymann, MD
Oct. 11, 2016

The concept of reactivating incontinentia pigmenti (IP) has always fascinated me — I have only encountered cases in my readings. Of course you will recall the vesicular, verrucous, hyperpigmented, and hypopigmented (atrophic) phases of this X-linked dominant disease. Eighty percent of IP patients carry mutations in the NEMO gene, which codes for the nuclear factor kB (NFkB) essential modulator. NFkB is key in regulating TNF-induced apoptosis. Reactivation, manifested by the reappearance of the vesicular and/or verrucous phases of IP that already resolved, may occur without provocation, but typically appear with when specific triggers (infections, fever, or vaccinations) reactivate pathways in mutant cells (1).

Bodak et al reported 5 cases of children who experienced episodes of late reactivation of IP. In all cases, the recurrences occurred on the previously hyperpigmented streaks several months or years after resolution of the initial eruptions. In most cases, the recurrences were preceded by an infectious episode (2).
Jefferson and Grossberg reported the case of a 7-month-old boy with IP who presented with fever, vesicles, and bullae of the hands and feet and periorally. (Remember, IP is overwhelmingly prevalent in girls; affected boys may have Klinefelter syndrome, or, as is the case here, express IP secondary to a post-zygotic mutation with somatic mosaicism.) The diagnosis of atypical hand-foot-mouth disease (AHFMD) triggering reactivation of IP (“incontinentia pigmenti coxsackium”) was considered because the patient’s older brother had AHFMD acquired from an outbreak in the brother’s preschool class. The presumption of IP reactivation, rather than just AHFMD, was made because of the development of characteristic hyperpigmented patches several months after the resolution of the infection. Confirmatory biopsies and viral studies were not performed (3).

Outbreaks of AHFMD due to Coxsackie A6 have been increasingly reported. Lesions may be vesicular, erosive, papular, desquamative, or purpuric, and may resolve with onychomadesis. Genotypic analysis may be used to confirm the etiology of Coxsackie A6, compared to the usual enteroviral pathogens Coxsackie A16 or enterovirus 71 (4). While I don’t expect to see a flurry of cases of IP being reactivated by AHFMD, there is no question that understanding how going retro clinically with the virus will allow us to move forward in our understanding of apoptotic pathways.

1. Bodak N, et al. Late recurrence of inflammatory first-stage lesion in incontinentia pigmenti: An unusual phenomenon and a fascinating pathologic mechanism. Arch Dermatol 2003; 139: 201-4.
2. Dupati A, et al. A case of incontinentia pigmenti reactivation after 12-month immunizations. JAAD Case Reports 2015; 1: 351-2.
3. Jefferson J, Grossberg A. Incontinentia pigmenti coxsackium. Pediatr Dermatol 2016; 33: e280-1.
4. Renert-Yuval, et al. Coxsackievirus A 6 polymorphic exanthem in Israeli children. Acta-Dermato-Venereologica 2016; 96: 564-9.

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