Validation of an Optical Pencil Method to Estimate the Affected Body Surface Area in Psoriasis. / Validación del método de cuantificación del área corporal afectada por la psoriasis mediante lápiz óptico.

INTRODUCTION: Body surface area (BSA) affected by psoriasis is one of the most often used measures for assessing severity, but this method has shortcomings. OBJECTIVE: To validate a new way to estimate BSA. MATERIAL AND METHOD: Prospective, multicenter study in 56 patients with psoriasis. Each patient was evaluated by 2 dermatologists in 2 visits to the same hospital. Each dermatologist used 2 methods for estimating BSA: the traditional visual estimation in which the area of the palm equals 1% of the total body surface and an optical pencil (OP) method in which the affected area is drawn on a touch screen. Software in the application then calculates the BSA. RESULTS: Overall concordance between the 2 methods was acceptable according to an intraclass correlation coefficient (ICC) of 0.87. However, the limits of agreement were unacceptably large and there was systematic bias: traditional estimates were consistently greater than OP calculations. Concordance between the methods was better (ICC>0.8) on the trunk and lower extremities. Intraobserver reliability was excellent with both methods (ICCs, 0.97 and 0.98 for the traditional and OP estimates, respectively). Interobserver reliability was also high (ICCs, 0.91 and 0.94 for the traditional and OP methods), although the mean BSA differed significantly between observers. The ICCs were much lower for BSA estimates on the head. CONCLUSIONS: This study to validate the OP method for estimating the affected BSA in patients with psoriasis shows good agreement between the OP and traditional approaches. The OP calculations also showed less variance and better interobserver reliability.

Biogeographical origin and timing of the founder ichthyosis TGM1 c.1187G > A mutation in an isolated Ecuadorian population.

An unusually high frequency of the lamellar ichthyosis TGM1 mutation, c.1187G > A, has been observed in the Ecuadorian province of Manabí. Recently, the same mutation has been detected in a Galician patient (Northwest of Spain). By analyzing patterns of genetic variation around this mutation in Ecuadorian patients and population matched controls, we were able to estimate the age of c.1187G > A and the time to their most recent common ancestor (TMRCA) of c.1187G > A Ecuadorian carriers. While the estimated mutation age is 41 generations ago (~1,025 years ago [ya]), the TMRCA of Ecuadorian c.1187G > A carrier haplotypes dates to just 17 generations (~425 ya). Probabilistic-based inferences of local ancestry allowed us to infer a most likely European origin of a few (16% to 30%) Ecuadorian haplotypes carrying this mutation. In addition, inferences on demographic historical changes based on c.1187G > A Ecuadorian carrier haplotypes estimated an exponential population growth starting ~20 generations, compatible with a recent founder effect occurring in Manabí. Two main hypotheses can be considered for the origin of c.1187G > A: (i) the mutation could have arisen in Spain >1,000 ya (being Galicia the possible homeland) and then carried to Ecuador by Spaniards in colonial times ~400 ya, and (ii) two independent mutational events originated this mutation in Ecuador and Galicia. The geographic and cultural characteristics of Manabí could have favored a founder effect that explains the high prevalence of TGM1 c.1187G > A in this region.

Prevalence of dystrophic epidermolysis bullosa in Spain: a population-based study using the 3-source capture-recapture method. Evidence of a need for improvement in care.

BACKGROUND: Dystrophic epidermolysis bullosa (DEB) is a rare disease that represents a heavy burden for both the patient and the health care system. There are currently no data on the prevalence of DEB in Spain. OBJECTIVE: To determine the prevalence of DEB in Spain. METHODS: We used data from 3 incomplete population-based sources (hospital dermatology departments, diagnostic laboratories performing antigenic mapping, genetic testing or both, and the Spanish Association of Epidermolysis Bullosa Patients [DEBRA]) and combined them using the 3-source capture-recapture methodology. RESULTS: We identified 152 living DEB patients. The estimated prevalence of DEB was 6.0 cases per million (95% CI, 4.2-11.8) in adults and 15.3 (95% CI, 10.4-40.8) in children under 18 years of age. The data indicated that 77% of the patients were not being followed up in specialized centers of reference; 65% had not had a genetic diagnosis, and 76% were not members of DEBRA. CONCLUSIONS: The prevalence of DEB in Spain is 6.0 patients per million (95% CI, 4.2-11.8), a figure higher than previous estimates in many areas, but similar to those found in other southern Europe countries. The north-south difference may represent real geographic differences in prevalence, but it might be due to the fact that most of the data come from registries with a lower than expected catchment. Many patients are not being followed up in centers of reference, do not have genetic diagnosis, and are not members of patients' associations, suggesting that there is room for considerable improvement in their care.

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.

Scleroderma-like syndrome due to hydroxyurea.

Scleroderma-like cutaneous changes have been reported in association with several drugs, but not with hydroxyurea (HU), to our knowledge. We report the case of a 67-year-old man who was treated with HU (hydroxycarbamide) for 12 years for a myeloproliferative disorder, and presented a progressive pruritic woody induration, symmetrically affecting both legs. He also had Gottron-like papules on the back of the metacarpophalangeal joints, and a retroauricular undifferentiated squamous cell carcinoma. On histological examination of a skin biopsy taken from the leg, massive dermal fibrosis was seen, with thickening of collagen bundles throughout the entire dermis. Six months after HU withdrawal, the skin induration resolved without scarring. Scleroderma-like syndrome has not been previously considered one of the secondary effects of HU. The evolution of our patient's condition supports a causal relationship between the HU treatment and the sclerodermiform changes of the skin.

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. OBJECTIVES: We have studied the characteristics of patients with ARCI in Galicia (NW Spain). Methods We recruited patients by contacting all dermatology departments of Galicia and the Spanish patient organization for ichthyosis. TGM1, ALOX12B, ALOXE3, NIPAL4 and CYP4F22 were analysed in the patients and their relatives. RESULTS: We identified 23 patients with ARCI and estimated a prevalence of 1 : 122 000. Twenty of the patients were studied. Seventeen of them were clinically categorized as having lamellar ichthyosis (LI) and three as having congenital ichthyosiform erythroderma (CIE). TGM1 and ALOXE3 mutations were identified in 12/16 (75%) probands whereas no ALOX12B, NIPAL4 and CYP4F22 mutations were found. TGM1 mutations were found in 11/13 (85%) of LI probands. ALOXE3 mutations were identified in a single patient with CIE. Remarkably, mutations p.Arg760X, p.Asp408ValfsX21 and c.984+1G>A of TGM1 were present in six, four and two families, accounting for 41%, 23% and 14% of all TGM1 mutant alleles, respectively. CONCLUSIONS: The high percentage of patients with the same TGM1 mutations, together with the high number of homozygous probands (64%), indicates the existence of a strong founder effect in our population.

Clinical diagnosis of toenail onychomycosis is possible in some patients: cross-sectional diagnostic study and development of a diagnostic rule.

BACKGROUND: Suspected toenail onychomycosis is a frequent problem. Clinical diagnosis has been considered inadequate. OBJECTIVES: To assess the diagnostic accuracy of clinical findings for detecting fungi in toenails, and to develop and validate a clinical diagnostic rule aimed at improving dermatologists' diagnosis of onychomycosis. METHODS: A cross-sectional diagnostic study was performed including a total of 277 patients seen by 12 dermatologists. The gold standard was the presence of dermatophytes on culture or a positive nail plate biopsy. For each sign we described prevalence, sensitivity, specificity, positive and negative predictive values, and likelihood ratios for positive and negative results. We developed a diagnostic clinical rule and validated it in a subsample. RESULTS: Helpful findings to predict the presence of fungi are: previous diagnosis of fungal disease; abnormal plantar desquamation (affecting > 25% of the sole); onychomycosis considered the most probable diagnosis by a dermatologist; and presence of interdigital tinea. When dermatologists considered onychomycosis the most probable diagnosis and plantar desquamation was present (13% of patients), the positive predictive value for presence of fungi was 81%. When both signs were absent (34% of patients), the positive predictive value for absence of fungi was 71%. In other situations, clinical diagnosis might not give enough information to decide on therapy. CONCLUSIONS: In 13% of the patients (a large number in absolute terms), when dermatologists consider onychomycosis the most probable diagnosis and plantar desquamation is present, therapy should be started without any further test, as clinical diagnosis is at least as accurate as laboratory tests. In other situations, an optimal management strategy should be defined.

[Molluscum contagiosum: descriptive study]. / Molusco contagioso: estudio descriptivo.

INTRODUCTION: Molluscum contagiosum is a cutaneous viral infection that often requires assistance. The aim of our study is to review the cases admitted in our clinic, evaluate the epidemiological features and the treatment prescribed. PATIENTS AND METHODS: We conducted a descriptive survey of the patients diagnosed of molluscum contagiosum in our clinic (Complexo Hospitalario Arquitecto Marcide-Novoa Santos, Ferrol, Spain) between June 16th 2008 and January 15th 2009. The following dates were recorded in all cases: age, sex, personal history of atopy, swimming pool attendance, number of lesions and treatment prescribed. RESULTS: 140 cases of molluscum contagiosum were included in the study. Average age was 10.7 years. 51.43% of patients had a personal history of atopy and 72.1% used to attendance swimming-pool. Average number of lesions was 13.3, with a higher number of them in males, atopic and swimming-pool attendants. Curettage was the treatment performed in 86.4% of cases. CONCLUSIONS: Atopic dermatitis and swimming-pool attendance were associated in our study with a higher frequency and number of molluscum contagiosum. Although different therapeutic options must be evaluated depending on the patient and clinical skills, curettage is the most frequent treatment performed by dermatologists.

Observer agreement in toenail disorders: implications for diagnosis and clinical research.

BACKGROUND: Toenail disorders are frequent, especially onychomycosis. The interobserver variability of nail signs needs to be known before these signs can be confidently applied for diagnosis. OBJECTIVES: To describe observer agreement in toenail findings as described by dermatologists in standard clinical practice, focusing on signs that could be useful for diagnosis of onychomycosis. METHODS: Prospective cross-sectional study in five dermatology departments. Eighty-six patients with abnormal toenails that could have onychomycosis as a differential diagnosis were independently examined by a pair of dermatologists using a predefined questionnaire, to describe the presence of 10 findings on previous history and 14 physical signs. RESULTS: Agreement was fine for previous history findings: it was very good (kappa > 0.81) for previous diagnosis of diabetes, smoking and use of public dressing rooms or swimming pools. Agreement was good (kappa 0.61-0.80) for immune suppression (drugs or cancer), previous diagnosis of fungal disease and worsening in the last year. It was moderate (kappa 0.41-0.60) for previous diagnosis of arterial disease, trauma induced by work or sports, and distal vs. proximal or lateral vs. central start of the lesion. Agreement was worse for physical signs: we found good agreement for the presence of the same disease in fingernails, abnormal plantar desquamation, deformity causing nail trauma, and subungual hyperkeratosis. It was moderate for the presence of nail destruction, tinea interdigitalis, onycholysis, and the type of material obtained by subungual curettage (dust vs. hard). Agreement was fair (kappa 0.21-0.40) for the presence of longitudinal or transverse striae, trachyonychia, pachyonychia, and change in colour of the nail plate. Pitting was too infrequent to allow for kappa calculation. Chance expected agreement was between 51% and 84% for all signs except pitting. CONCLUSIONS: Agreement is adequate for most signs. It is low for the presence of longitudinal or transverse striae, trachyonychia, and change in colour of the nail plate. Pitting is rare in toenails.