Human inborn errors of thymic T cell tolerance underlie the production of autoantibodies (auto-Abs) neutralizing type I IFNs, which predispose to severe viral diseases. We analyze 131 female patients with X-linked dominant incontinentia pigmenti (IP), heterozygous for loss-of-function (LOF) NEMO variants, from 99 kindreds in 10 countries. Forty-seven of these patients (36%) have auto-Abs neutralizing IFN-α and/or IFN-ω, a proportion 23 times higher than that for age-matched female controls. This proportion remains stable from the age of 6 years onward. On imaging, female patients with IP have a small, abnormally structured thymus. Auto-Abs against type I IFNs confer a predisposition to life-threatening viral diseases. By contrast, patients with IP lacking auto-Abs against type I IFNs are at no particular risk of viral disease. These results suggest that IP accelerates thymic involution, thereby underlying the production of auto-Abs neutralizing type I IFNs in at least a third of female patients with IP, predisposing them to life-threatening viral diseases.

Introduction: Incontinentia pigmenti (IP) is a rare X-linked geno-dermatosis characterized by numerous findings. Skin biopsy and histopathological analysis are considered as minor criteria for the diagnosis of IP. We assume that dermoscopy can assist the earlier diagnosis of IP. Objectives: To gain experience in earlier diagnosis of IP by observing dermoscopic findings of cutaneous changes. Methods: We revised confirmed cases of IP and examined them using dermoscopy, comparing histopathological and dermoscopic results. Results: Stage I presented solitary and grouped vesicles in linear arrangement on erythematous skin. Early stage II presented star-shaped verrucous lesions on erythematous or pigmented skin. In well-developed lesions, dotted vessels surround keratotic part, some with thrombosed capillaries, resembling a viral wart. Stage III presented linear brown dots on the pigmented areas. Dermoscopic image was uniform in all the examined pigmented Blaschko linear changes. Stage IV presented numerous dotted vessels on the hypopigmented skin. Terminal hair was scarce or absent in all four stages. The surrounding normal skin had perifollicular depigmentations in stages III and IV. Conclusions: Dermoscopy of all four stages is very specific compared to the dermoscopy of inflammatory dermatoses and pigmentations. Stage III has very close clinical, histological and dermoscopic mimickers and needs to be carefully examined with obligatory genetic testing. Dermoscopy of the stage IV closely corresponds to histopathological findings and may be crucial as a quick tool in revealing potential IP gene carriers. Dermoscopy should be used in addition to clinical examination since the two methods are complementary.

Incontinentia pigmenti (IP) is a rare skin disease combined with anomalies of the teeth, eyes, and central nervous system (CNS). Mutations of the IKBKG gene are responsible for IP. Among the most frequent CNS abnormalities found in IP using magnetic resonance imaging (MRI) are corpus callosum (CC) abnormalities. The aim of the study was to determine the presence of CC abnormalities, their relationship with the IKBKG mutations, and the possible presence of mutations of other genes. A group of seven IP patients was examined. Analyses of the IKBKG gene and the X-chromosome inactivation pattern were performed, as well as MRI and whole exome sequencing (WES) with the focus on the genes relevant for neurodegeneration. WES analysis showed IKBKG mutation in all examined patients. A patient who had a mutation of a gene other than IKBKG was excluded from further study. Four of the seven patients had clinically diagnosed CNS anomalies; two out of four had MRI-diagnosed CC anomalies. The simultaneous presence of IKBKG mutation and CC abnormalities and the absence of other mutations indicate that IKBKG may be the cause of CC abnormalities and should be included in the list of genes responsible for CC abnormalities.

Background: Acne vulgaris is one of the most frequent visits to primary care physicians and dermatologists alike. Isotretinoin is the backbone of acne treatment. In most countries, depending on the health care system, isotretinoin is prescribed by dermatologists but primary care physicians are a part of the follow-up and interpreting analysis. Adverse effects of isotretinoin on the kidney and urinary system are mostly limited to sparse case reports. Specifically, gross and microscopic haematuria is not mentioned to be associated with isotretinoin. Lack of data regarding these adverse effects can lead to doubt regarding further patient management not only with dermatologists but also primary care physicians. Objective: We report a 16-year-old male patient with isotretinoin-induced haematuria with multiple episodes and subsequent challenge and de-challenge. No personal or familial history of nephrological disease was present. Ultrasound imaging and nephrology workup was within normal limits. Other aetiologies were excluded. Nephrology consult stated there was no contraindication for isotretinoin use and was reinstated at 0.6 m/kg/day. More frequent observation was indicated until completion of isotretinoin. Conclusion: Our case raises awareness to other dermatologists and primary care physicians that haematuria can be secondary to isotretinoin but not a contraindication for further use if asymptomatic and microscopic. More extensive evaluation and monitoring should be done if the patient is symptomatic with other abnormalities and symptoms. Urinalysis should be a part of routine follow-up monitoring in patients on isotretinoin. Furthermore, delineating and differentiating when to refer to a nephrologist is essential for physicians, patients, and the health care system overall.

Rare diseases represent a diagnostic challenge due to their number, variety of clinical phenomena, and possibility of a simultaneous presence of two or more diseases. An illustration of this challenge is an occurrence of a late diagnosis of a proband initially diagnosed with West syndrome, later revealed to be caused by Incontinentia pigmenti (IP). Furthermore, 20 years later, it was discovered that the proband was also a carrier of a heterozygous GBA gene mutation. The methods used in diagnostics were as follows: IKBKG gene analysis, the X-chromosome inactivation assay, analyses of the genes relevant for neurodegeneration, WES analysis, analysis of biochemical parameters typical for Gaucher disease (GD), and autoantibodies including IFN-α2a and IFN-ω. To avoid overlooking IP and other possible rare disease diagnoses, carefully searching for dermatological signs in these conditions is recommended. It is important that the diagnostic criteria are based on quality and extensive data from multiple studies of each rare disease. Establishing precise diagnostic criteria for as many rare diseases as possible and establishing a publicly accessible database of rare diseases with a search possibility according to phenotypic abnormalities and genetic mutations would greatly facilitate and speed up the establishment of an accurate diagnosis.

Herpes simplex viruses (HSV) present one of the most frequent groups of viruses in the human population. Herpes simplex infections manifest through varying symptoms and lesions of the orofacial or genital tract. The peak of viral titers occurs within the first 24 h in both genital herpes and herpes labialis infections. Due to the rapid viral replication and subsequent progression of lesions in both Herpes labialis (HL) and Herpes genitalis (HG), the therapeutic window for treating HSV infections with antiviral drugs is narrow. It is important to recognize prodromal symptoms in patients and subsequently (self-)administer appropriate therapy. Clinical trials have shown that the shorter duration of higher doses of antiviral drugs, the more suitable and equally or even more effective results are obtained. According to the analysed literature, Acyclovir remains the most effective choice of treatment for the majority of patients. In some cases, other similar antiviral drugs could be effective when the treatment with Acyclovir fails to give the expected results.