Blue-Gray Mucocutaneous Discoloration

Shkolnik, Tali Garin; Feuerman, Hana; Didkovsky, Elena; Kaplan, Ilana; Bergman, Reuven; Pavlovsky, Lev; Hodak, Emmilia

doi:10.1001/jamadermatol.2013.8895

Cited by 71 publications

(29 citation statements)

References 14 publications

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“…No patients were begun on treatment after the U.S. Food and Drug Administration published a warning and revised labeling indicating that EZO can cause retinal pigmentation abnormalities with potential risk of visual loss. 20–22 Parents of all patients under treatment at that time were informed of the warning and its detailed content, and the risks and benefits of continued treatment reassessed. Where treatment continued after this warning, the recommended visual monitoring was followed and included dilated funduscopic examinations and assessment of visual fields.…”

Section: Methodsmentioning

confidence: 99%

KCNQ2 encephalopathy

Millichap¹,

Park²,

Tsuchida³

et al. 2016

Neurol Genet

206

112

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Objective:To advance the understanding of KCNQ2 encephalopathy genotype–phenotype relationships and to begin to assess the potential of selective KCNQ channel openers as targeted treatments.Methods:We retrospectively studied 23 patients with KCNQ2 encephalopathy, including 11 treated with ezogabine (EZO). We analyzed the genotype–phenotype relationships in these and 70 previously described patients.Results:The mean seizure onset age was 1.8 ± 1.6 (SD) days. Of the 20 EEGs obtained within a week of birth, 11 showed burst suppression. When new seizure types appeared in infancy (15 patients), the most common were epileptic spasms (n = 8). At last follow-up, seizures persisted in 9 patients. Development was delayed in all, severely in 14. The KCNQ2 variants identified introduced amino acid missense changes or, in one instance, a single residue deletion. They were clustered in 4 protein subdomains predicted to poison tetrameric channel functions. EZO use (assessed by the treating physicians and parents) was associated with improvement in seizures and/or development in 3 of the 4 treated before 6 months of age, and 2 of the 7 treated later; no serious side effects were observed.Conclusions:KCNQ2 variants cause neonatal-onset epileptic encephalopathy of widely varying severity. Pathogenic variants in epileptic encephalopathy are clustered in “hot spots” known to be critical for channel activity. For variants causing KCNQ2 channel loss of function, EZO appeared well tolerated and potentially beneficial against refractory seizures when started early. Larger, prospective studies are needed to enable better definition of prognostic categories and more robust testing of novel interventions.Classification of evidence:This study provides Class IV evidence that EZO is effective for refractory seizures in patients with epilepsy due to KCNQ2 encephalopathy.

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Section: Methodsmentioning

confidence: 99%

KCNQ2 encephalopathy

Millichap¹,

Park²,

Tsuchida³

et al. 2016

Neurol Genet

206

112

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“…Histopathologically, the main finding was that dermal cells were heavily laden with coarse melanin granules, mainly in peri-vascular and peri-eccrine distribution. Biopsy of the hard palate showed coarse pigment in the submucosa, inside macrophages as well as in the extracellular matrix, positive for melanin [7]. Another case report that followed described bluish-purple discoloration of the fingernails and hard palate after 2 years of treatment with EZG/RTG [8].…”

Section: Discussionmentioning

confidence: 98%

“…The first report was of two patients with blue-gray skin dyspigmentation that was most pronounced on the face and lips [7]. There was also pigmentation on the nails, blue pigmentation on the hard palate, and black pigment deposits on the conjunctiva.…”

Section: Discussionmentioning

confidence: 99%

Ezogabine skin discoloration is reversible after discontinuation

Mathias

Abou‐Khalil

2017

Epilepsy & Behavior Case Reports

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There is concern that bluish skin discoloration associated with ezogabine treatment could be permanent. We present a case of ezogabine-induced skin discoloration that resolved completely after discontinuation. A 55-year-old woman started ezogabine 400 mg three times a day at age 41. Bluish pigmentation over the toe nails, finger nails, around eyes and over and around lips was first noted after 5 years of treatment. Ezogabine was discontinued eight years after initiation. Skin discoloration improved within 6 months and completely resolved within 6 years of discontinuation. This case suggests that ezogabine-induced discoloration is reversible after discontinuation of treatment.

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“…Unfortunately, ezogabine has been removed from prescription after a warning from the Food and Drug Administration due to retinal pigmentary changes and blue skin discoloration with chronic use 28. Interestingly, ezogabine and lithium share similar final pathways and could both trigger the opening of potassium voltage‐gated channels 23, 27.…”

Section: Discussionmentioning

confidence: 99%