Laura Rodríguez-Pazos

Prevalence of autosomal recessive congenital ichthyosis: A population-based study using the capture-recapture method in Spain

BACKGROUND Previous reports on the prevalence of autosomal recessive congenital ichthyosis (ARCI) were based on single source data, such as lists of members in a patient association. These sources are likely to be incomplete. OBJECTIVES We sought to describe the prevalence of ARCI. METHODS We obtained data from 3 incomplete sources (dermatology departments, a genetic testing laboratory, and the Spanish ichthyosis association) and combined them using the capture-recapture method. RESULTS We identified 144 living patients with ARCI. Of these, 62.5% had classic lamellar ichthyosis and 30.6% had congenital ichthyosiform erythroderma. The age distribution included fewer elderly patients than expected. The prevalence of ARCI in patients younger than 10 years, the best estimate as less subject to bias, was 16.2 cases per million inhabitants (95% confidence interval 13.3-23.0). According to the capture-recapture model, 71% of the patients were not being followed up in reference units, 92% did not have a genetic diagnosis, and 78% were not members of the ichthyosis association. LIMITATIONS The prevalence of ARCI in Spain and findings related to the Spanish health care system might not be generalizable to other countries. CONCLUSIONS The prevalence of ARCI is higher than previously reported. Many patients are not being followed up in reference units, do not have a genetic diagnosis, and are not members of a patient association, indicating room for improvement in their care. Data suggesting a reduced number of older patients might imply a shorter life expectancy and this requires further study.

Onychomycosis observed in children over a 20‐year period

There are few reports studying the aetiology of onychomycosis in children in Spain. To study childhood dermatophyte onychomycosis, a retrospective study of children was carried out, who were <16 years of age with dermatophyte onychomycosis diagnosed between 1987 and 2007. Of 4622 nail samples from 3550 patients, 218 came from 181 children up to 16 years old. Onychomycosis caused by dermatophytes was demonstrated in 28 (15.5%) cases. Trichophyton rubrum (18 cases) was the most prevalent species, followed by Trichophyton tonsurans (five cases), Trichophyton mentagrophytes var. interdigitale (four cases) and Trichophyton mentagrophytes var. mentagrophytes (one case). Concomitant dermatophytosis at other locations was confirmed in seven cases (25%). Toenail onychomycosis was associated with tinea pedis in five cases. Distal and lateral subungual onychomycosis was the most common clinical pattern. The superficial white type was found in two cases of toenail onychomycosis caused by T. rubrum and T. tonsurans. During the period of study, only 5.1% of all investigated people were children up to 16 years. The prevalence of onychomycosis tended to increase over the years and represented 15.5% of all nail dystrophies in children. Therefore, dermatologists must consider onychomycosis in the differential diagnosis of nail alterations in children and always perform a mycological study to confirm the diagnosis.

Analysis of TGM1, ALOX12B, ALOXE3, NIPAL4 and CYP4F22 in autosomal recessive congenital ichthyosis from Galicia (NW Spain): evidence of founder effects.

Background  Mutations in six genes have been identified in autosomal recessive congenital ichthyosis (ARCI). To date, few studies have analysed the spectrum of these mutations in specific populations.

Autosomal Recessive Congenital Ichthyosis

The term autosomal recessive congenital ichthyosis (ARCI) refers to a group of rare disorders of keratinization classified as nonsyndromic forms of ichthyosis. This group was traditionally divided into lamellar ichthyosis (LI) and congenital ichthyosiform erythroderma (CIE) but today it also includes harlequin ichthyosis, self-healing collodion baby, acral self-healing collodion baby, and bathing suit ichthyosis. The combined prevalence of LI and CIE has been estimated at 1 case per 138 000 to 300 000 population. In some countries or regions, such as Norway and the coast of Galicia, the prevalence may be higher due to founder effects. ARCI is genetically highly heterogeneous and has been associated with 6 genes to date: TGM1, ALOXE3, ALOX12B, NIPAL4, CYP4F22, and ABCA12. In this article, we review the current knowledge on ARCI, with a focus on clinical, histological, ultrastructural, genetic, molecular, and treatment-related aspects.

Erythema multiforme photoinduced by statins

We report two cases of systemic photosensitivity induced by simvastatin and pravastatin that presented as photodistributed erythema multiforme. One of them occurred in a 75‐year‐old woman who had been suffering recurrent eruptions following sun exposures over a period of 12 years. The other patient was a 54‐year‐old man who had a 1‐week history of pruritic lesions on the face and the hands. They had no history of herpes simplex virus infection. In both cases, the close temporal relationship between drug ingestion and onset of the conditions suggested statin‐induced photosensitivity. The diagnosis was confirmed by the marked reduction of UVB‐MED or both UVA and UVB‐MED while taking the drug and its normalization after discontinuing the statin intake.

Identification of a novel PNPLA1 mutation in a Spanish family with autosomal recessive congenital ichthyosis

DEAR EDITOR, The term inherited ichthyosis subsumes numerous clinically and aetiologically heterogeneous cornification disorders with Mendelian inheritance patterns. Prior to January 2012, six genes had been identified as having loss-of-function mutations causing autosomal recessive congenital ichthyosis (ARCI): ABCA12, ALOX12B, ALOXE3, CYP4F22, NIPAL4 and TGM1. In a study of ALOX12B, ALOXE3, CYP4F22, NIPAL4 and TGM1 performed in 17 ARCI families in Galicia (NW

Erythema multiforme photoinduced by paroxetine and herpes simplex virus

Erythema multiforme (EM) is a self‐limited skin disease, characterized by the abrupt onset of symmetric red papules that may evolve into target lesions often precipitated by an infection. Photosensitive erythema multiforme (PEM) is a rare disorder characterized by the distribution of the lesions on sun‐exposed areas. It has been described at the sites of sunburn, following episodes of polymorphic light eruption or herpes labialis and in association with drugs. To our knowledge, PEM photoinduced by selective serotonin reuptake inhibitors has not been reported. We describe a patient who had two consecutive episodes of PEM related to two different triggers: paroxetine and HSV infection. In the first episode, systemic photosensitivity was confirmed with the photobiological study. UVB‐MED was decreased when the patient was taking paroxetine and did not change after its substitution for duloxetine. However, it became normal after the withdrawal of both drugs, suggesting a cross‐reactivity reaction. The UVB photopatch test with paroxetine was positive. The second episode occurred after a herpes labialis relapse. At that time, UVB‐MED was normal.

Disseminated eruptive clear cell acanthoma with spontaneous regression: further evidence of an inflammatory origin?

Clear cell acanthoma (CCA) is a benign epidermal lesion with distinctive clinicopathological features. Multiple disseminated eruptive CCA is an infrequent clinical variant that has been rarely reported. It is characterized by the presence of more than 30 lesions from 1 to 10 mm in diameter that appear progressively over the years. We report the case of a 65-year-old woman with multiple disseminated eruptive CCA affecting her lower extremities. In contrast to previous reports, most of the lesions appeared in a short period of time (less than a month) and, what is more interesting is that some of them have regressed spontaneously leaving residual hyperpigmentation. At present, the histogenesis and etiology of CCA remain unknown. Accumulating data suggest a reactive origin associated with a variety of different inflammatory conditions. The case presented in this report further substantiates that CCA is indeed a reactive epidermal reaction pattern with an inflammatory etiology.

Multiple Local and Recent Founder Effects of TGM1 in Spanish Families

Background Mutations in the TGM1 gene encoding transglutaminase 1 are a major cause of autosomal recessive congenital ichthyosis. In the Galician (NW Spain) population, three mutations, c.2278C>T, c.1223_1227delACAC and c.984+1G>A, were observed at high frequency, representing ∼46%, ∼21% and ∼13% of all TGM1 gene mutations, respectively. Moreover, these mutations were reported only once outside of Galicia, pointing to the existence of historical episodes of local severe genetic drift in this region. Methodology/Principal Findings In order to determine whether these mutations were inherited from a common ancestor in the Galician population, and to estimate the number of generations since their initial appearance, we carried out a haplotype-based analysis by way of genotyping 21 SNPs within and flanking the TGM1 gene and 10 flanking polymorphic microsatellite markers spanning a region of 12 Mb. Two linkage disequilibrium based methods were used to estimate the time to the most recent common ancestor (TMRCA), while a Bayesian-based procedure was used to estimate the age of the two mutations. Haplotype reconstruction from unphased genotypes of all members of the affected pedigrees indicated that all carriers for each of the two mutations harbored the same haplotypes, indicating common ancestry. Conclusions/Significance In good agreement with the documentation record and the census, both mutations arose between 2,800–2,900 years ago (y.a.), but their TMRCA was in the range 600–1,290 y.a., pointing to the existence of historical bottlenecks in the region followed by population growth. This demographic scenario finds further support on a Bayesian Coalescent Analysis based on TGM1 haplotypes that allowed estimating the occurrence of a dramatic reduction of effective population size around 900–4,500 y.a. (95% highest posterior density) followed by exponential growth.

Photosensitivity induced by naproxen

We present two cases of systemic photosensitivity due to naproxen that presented as photodistributed erythema multiforme (EM) and lichenoid photodermatitis (LP). Although naproxen is a commonly used nonsteroidal antinflammatory drug and has the capacity of causing systemic photosensitivity, there are very few reports about it in the literature. The diagnosis was suspected by the recent ingestion of the drug and the photodistribution of the lesions. A positive photopatch test in the first patient and the normalization of the MED‐UVB after discontinuing naproxen in the second patient supported the diagnosis.