Multidisciplinary consensus recommendations from a European network for the diagnosis and practical management of patients with incontinentia pigmenti

Abstract

Background Incontinentia pigmenti (IP) is a rare multisystemic X-linked dominant genetic disorder characterized by highly diagnostic skin lesions. The disease can be misdiagnosed in infants, and complications affecting the eyes and/or the brain can be severe. Our objective was to highlight the urgency of an appropriate diagnosis and management strategy, as soon as the first symptoms appear, and the need for a well-codified monitoring strategy for each child.Methods An in-depth literature review using a large number of databases was conducted. The selection criteria for articles were literature review articles on the disease, case series and retrospective studies based on the disease, clinical studies (randomized or not) on treatment, articles discussing patient care and management (treatment, diagnosis, care pathways), and recommendations. The research period was from 2000 until 2018. A group of multidisciplinary experts in IP management was involved, issued from different healthcare providers of the European Network for Rare Skin Diseases (ERN-Skin). The final recommendations have been submitted to two patient representative associations and to a general practitioner and a neonatal specialist prior to their finalization. Results and conclusionThe diagnosis of IP must be promptly performed to detect potential extracutaneous manifestations, thus allowing the timely implementation of specific therapeutic and monitoring strategies. Eye involvement can be a therapeutic urgency, and central nervous system (CNS) involvement requires a very rigorous long-term follow-up.Assessments and patient support should take into account the possible co-occurrence of various symptoms (including motor, visual and cognitive symptoms).

Importance of extracutaneous organ involvement in determining the clinical severity and prognosis of incontinentia pigmenti caused by mutations in the IKBKG gene

“…In this study, all 25 females with genetically confirmed IP developed cutaneous symptoms at the time of birth or during the neonatal period similar to that reported in previous studies, 1‐3,16 suggesting the important role of paediatricians and dermatologists in the early diagnosis of IP. Cutaneous defects occur in patients with IP because the NF‐kB mutant cells are killed by the wild‐type NF‐kB cells along the Blaschko lines of the skin 17 .…”

“…Cutaneous defects occur in patients with IP because the NF‐kB mutant cells are killed by the wild‐type NF‐kB cells along the Blaschko lines of the skin 17 . Although molecular genetic testing is currently available with high sensitivity, histologic examination can help in the diagnosis of affected individuals with borderline findings in whom molecular genetic testing has not identified an IKBKG pathogenic variant 16,18 . Besides dermatological findings, hair, nail, dental and mammary gland anomalies can be accompanied in IP and constitute minor diagnostic criteria 2,3 .…”

“…For histopathologic abnormalities, vaso‐occlusions usually begin on the arterial side of the vascular tree, 33‐35 which cause irreversible ischaemic infarctions leading to preretinal neovascularization, haemorrhages and retinal detachment 36,37 . The ocular anomalies in patients with IP may be serious, leading to vision‐threatening manifestations or even blindness caused by retinal disease 1,16 . In the present study, all of the probands who had ocular anomalies underwent early treatment and showed favourable outcomes without retinal detachment and blindness, although three showed amblyopia in the involved eye.…”

How to Deal with Skin Biopsy in an Infant with Blisters?

“…IP is a rare X-linked dominant genodermatosis caused by mutations in the inhibitor of the kappa B kinase gamma (IKBKG) (previously known as NEMO or nuclear factor kappa B essential modulator) gene. IP affects mostly female patients and is usually lethal in utero for males, but cases in boys are reported [ 15 , 16 ]. The phenotype in females is variable, manifestations being dependent on the effects of mosaicism resulting from X-chromosome lyonization.…”

Retinal Neovascularization in Two Patients with Incontinentia Pigmenti

“… 7 , 9 CNS and ocular manifestations can remain undetected until infancy or early childhood, leading to severe functional nervous system abnormalities such as convulsion, mental retardation, 3 , 12 and muscle spasticity, 3 as well as visual impairments ranging from mild to severe, even blindness. 2 , 7 , 13 , 14 …”