Search

Dermatological manifestations of hereditary fibrosing poikiloderma with tendon contractures, myopathy and pulmonary fibrosis (POIKTMP): a case series of 28 patients. Recently, the autosomal dominant hereditary fibrosing POIKiloderma with tendon contractures, myopathy and pulmonary fibrosis (POIKTMP; MIM 615704) has been described.1,2 POIKTMP is due to missense variations in the I FAM111B i gene. [Extracted from the article]

Background: Paediatric cutaneous granuloma with primary immunodeficiency (PID) is a rare condition. The physiopathology is unclear, and treatment is challenging. We report on 17 paediatric cases and review the literature. Objectives: To make dermatologists and dermatopathologists aware of the diagnostic value of skin granulomas in paediatric PID. Methods: We collected data on 17 patients with cutaneous granulomas and PID registered with us and also reviewed 33 cases from the literature. Results: Cutaneous granuloma was the presenting feature of the PID in 15 of the 50 collated cases. The lesions presented as red‐brownish nodules and infiltrated ulcerative plaques, predominantly on the face and limbs. Scleroderma‐like infiltration on a single limb was observed in 10% of the cases. The associated PID was ataxia‐telangiectasia (52%), combined immunodeficiency (24%), cartilage‐hair hypoplasia (6%) and other subtypes (18%). The granulomas were mostly sarcoidal, tuberculoid, palisaded or undefined subtypes. In some patients, several different histopathologic granulomatous patterns were found in the same biopsy. Some granulomas were associated with the presence of a vaccine strain of rubella virus. Conclusion: Cutaneous granulomas associated with a PID have a variable clinical presentation. A PID can be suspected when crusty, brownish lesions are found on the face or limbs. The concomitant presence of several histological subtypes in a single patient is suggestive of a PID. [ABSTRACT FROM AUTHOR]

A letter to the editor is presented which focuses on the study on ichthyosis as the dermatological phenotype associated with tetratricopeptide repeat domain 7A gene (Ttc7) mutations.

Background: Erythrodermas are often life-threatening conditions in infants. Determination of the underlying cause is crucial. Microscopic changes in adult erythroderma lack specificity. Objective: To determine if an early skin biopsy is helpful for the diagnosis of neonatal and infantile erythroderma. Methods: Seventy-two patients admitted for erythroderma in the first year of life were retrospectively included. One hundred and eleven skin biopsies (12-year period) were examined by 3 pathologists blinded to the clinical diagnosis, and classified into atopic dermatitis, immunodeficiency (ID), psoriasis, Netherton syndrome (NS), ichthyosis, other. From year 2000, LEKTI antibody was performed when NS was suspected. Pathological diagnosis was then compared with clinical diagnosis. Results: The final diagnosis was made in 69.3% of the cases. In 57.6%, pathological diagnosis was in accordance, and in 11.7%, it was in accordance, but other diagnosis had also been proposed. For ID, sensitivity and specificity were 58.5 and 98.5%, respectively. Before year 2000, NS was frequently misdiagnosed with psoriasis, but with the use of LEKTI antibody, sensitivity and specificity were 100%. Conclusion: Skin biopsy is helpful for etiologic diagnosis of early erythroderma of infancy, particularly in ID and NS, the most severe diseases. Consequently, these results justify an early systematic skin biopsy for a better and earlier management. Leclerc-Mercier S, Bodemer C, Bourdon-Lanoy E, Larousserie F, Hovnanian A, Brousse N, Fraitag S. Early skin biopsy is helpful for the diagnosis and management of Neonatal and Infantile Erythrodermas. [ABSTRACT FROM AUTHOR]

The article discusses research which assessed the specificity of histological skin abnormalities in Conradi-Hünermann-Happle (CHH) syndrome, an X-linked dominant disorder of cholesterol metabolism. Topics discussed include the association of the phenotype with skeletal defects, ocular anomalies and skin lesions and CHH caused by mutations in the emopamil-binding protein (EBP) gene.

Patient (F5-1) had a cirrhosis at the age of 34 years (after 12 years of OR), but liver blood parameters remained stable during the 31 years of follow-up. Before introducing OR, all also had liver anomalies, that consisted in either increased liver enzymes, hyper echogenic liver, hepatosplenomaly or cirrhosis for one patient (F6-1). In conclusion, awaiting future targeted therapy for DCS or prospective monitoring studies, there is no safety signal to contraindicate OR in CDS patients with disabling skin anomalies, on condition that a close monitoring is performed. [Extracted from the article]

A letter to the editor is presented in response to the article about a 32-year-old woman presenting with a bathing-trunk eruption associated with primary infection to human parvovirus B19 which was published in the previous issue.

Keratitis-ichthyosis-deafness (KID) syndrome (MIM: #148210) is a rare form of syndromic ichthyosis associated with heterozygous mutations in I GJB2 i encoding connexin 26, a member of the connexin family of transmembrane proteins, involved in cell-cell communication.[1] I GJB2 i mutations are also associated with non-syndromic deafness.[2] Mosaic I GJB2 i mutations were previously identified in porokeratotic eccrine ostial and dermal duct nevus (PEODDN).[3] Here, we report two patients with mosaic I GJB2 i mutations thus expanding the clinical spectrum of I GJB2 i -related disorders. Extending the phenotypic spectrum of keratitis-ichthyosis-deafness syndrome: report of a patient with GJB2 (G12R) Connexin 26 mutation and unusual clinical findings. [Extracted from the article]

Introduction: The distinction between epidermal necrolysis [EN; including Stevens–Johnson syndrome (SJS), toxic epidermal necrolysis (TEN) and overlap syndrome] and erythema multiforme major (EMM) in children is confusing. We aimed to better describe and compare these entities. Materials and methods: This French retrospective multicentre study included children ≤18 years old referred for EN or EMM between 1 January 2008 and 1 March 2019. According to pictures, children were reclassified into TEN/overlap, SJS or EMM/unclassified (SJS/EMM) groups and compared for epidemiological and clinical data, triggers, histology and follow‐up. Results: We included 62 children [43 boys, median age 10 years (range 3–18)]: 16 with TEN/overlap, 11 SJS and 35 EMM. The main aetiologies were drugs in EN and infections (especially Mycoplasma pneumoniae) in EMM (P < 0.001), but 35% of cases remained idiopathic (TEN/overlap, 47%; SJS, 24%; EMM, 34%). The typical target lesions predominated in EMM (P < 0.001), the trunk was more often affected in EN (P < 0.001), and the body surface area involved was more extensive in EN (P < 0.001). Mucosal involvement did not differ between the groups. Two patients with idiopathic TEN died. Histology of EMM and EN showed similar features. The recurrence rate was 42% with EMM, 7% with TEN/overlap and 0 with SJS (P < 0.001). Sequelae occurred in 75% of EN but involved 55% of EMM. Conclusion: Clinical features of EN and EMM appeared well demarcated, with few overlapping cases. Idiopathic forms were frequent, especially for EN, meaning that a wide and thorough infectious screening, repeated if needed, is indicated for all paediatric cases of EN/EMM without any trigger drug. We propose a comprehensive panel of investigations which could be a standard work‐up in such situation. Sequelae affected both EN and EMM. [ABSTRACT FROM AUTHOR]

Albinism is a worldwide genetic disorder caused by mutations in at least 20 genes, identified to date, that affect melanin production or transport in the skin, hair and eyes. Patients present with variable degrees of diffuse muco‐cutaneous and adnexal hypopigmentation, as well as ocular features including nystagmus, misrouting of optic nerves and foveal hypoplasia. Less often, albinism is associated with blood, immunological, pulmonary, digestive and/or neurological anomalies. Clinical and molecular characterizations are essential in preventing potential complications. Disease‐causing mutations remain unknown for about 25% of patients with albinism. These guidelines have been developed for the diagnosis and management of syndromic and non‐syndromic forms of albinism, based on a systematic review of the scientific literature. These guidelines comprise clinical and molecular characterization, diagnosis, therapeutic approach and management. [ABSTRACT FROM AUTHOR]

Summary: Background: Netherton syndrome (NS) is a rare disease caused by SPINK5 mutations, featuring variable skin and hair involvement and, in many cases, allergic manifestations with a risk of lethality, particularly in infants. The clinical management of NS is challenging. Objectives: To analyse the clinical manifestations of a cohort of infants with NS managed in a reference centre and to draw up recommendations for management. Methods: We conducted a monocentric analysis of patients with NS. The inclusion criteria were management in our reference centre, a histologically or molecularly confirmed diagnosis of NS and available epidemiological, clinical and laboratory data. Results: A total of 43 patients with NS were included. Hypernatraemia was reported in 23 cases (54%) and associated with a greater likelihood of enteral and/or parenteral nutritional support (P < 0.001). Moreover, hypernatraemia was more frequent in patients with skin manifestations at birth (P = 0.026) and in patients bearing the c.153delT mutation in SPINK5 exon 3 (P = 0.014). The need for enteral and/or parenteral nutritional support was associated with a history of hypernatraemic dehydration (P < 0.001). Several unexpected extracutaneous complications were recorded, and new mutations were reported. The death rate (9% overall) was higher among the subset of patients bearing the c.153delT deletion. Conclusions: Our data emphasize that neonatal NS is a severe and sometimes lethal multisystem disorder. Patients have a high risk of variable metabolic anomalies (i.e. lethal hypernatraemia) and therefore have major nutritional needs. Cases of NS associated with c.153delT are particularly severe. Unexpected clinical manifestations broadened the phenotypic spectrum of NS. We provide recommendations on the management of the life‐threatening manifestations of NS in neonates based on our multidisciplinary experience. What is already known about this topic? Netherton syndrome (NS) is a rare genetic disease characterized by dermatitis, skin fragility, hair involvement and (in most cases) severe allergic manifestations.Most previous clinical studies of NS have described older children. What does this study add? Our series of 43 infants with NS showed unexpected systemic manifestations and new mutations.Our findings prompted us to make several recommendations regarding multidisciplinary investigations and the management of life‐threatening manifestations in young children with NS.Infants with NS require specific care protocols and Netherton syndrome should be considered as a systemic lifelong disease. Plain language summary available online [ABSTRACT FROM AUTHOR]

Introduction: Severe epidermolysis bullosa simplex (EBS sev) is a rare genodermatosis characterized by congenital generalized blistering and mucosal involvement. Increased needs and decreased intake quickly lead to nutritional imbalance. Enteral nutrition support is proposed, but classical nasogastric tubes are not well tolerated in these patients and gastrostomy is preferred.Objective and Methods: To report the experience with EBS sev in neonatal units of French reference centers for gastrostomy. In this retrospective multicentric study, we included all patients with EBS sev who had gastrostomy placement before age 9 months during neonatal care hospitalization.Results: Nine infants (5 males/4 females) with severe skin and mucosal involvement were included. A gastrostomy was decided, at an early age (mean 3.7 months, range 1.4 to 8 months) in infants with mean weight 4426 g (range 3500 to 6000 g). Techniques used were endoscopy with the pull technique for 5 infants and surgery under general anesthesia for 4. Main complications were local but resolved after treatment. All infants gained weight after gastrostomy. The mean withdrawal time (n = 7) for the gastrostomy was 35.8 months (range 10.5 months to 6.5 years). Seven children had persistent oral disorders.Conclusions: Gastrostomy in infants with EBS sev can be necessary in neonatal intensive care units. Both surgical and endoscopic pull techniques seem efficient, with good tolerance. [ABSTRACT FROM AUTHOR]

Background: Autoimmune bullous dermatoses (AIBDs) in children are uncommon, and their long‐term evolution remains unknown. Objective: The aim of this retrospective study was to characterize the long‐term prognosis of AIBDs that started during childhood. Methods: We conducted a monocentric retrospective study, in the French dermatology centre, by including all children affected by AIBDs. The long‐term outcome was obtained through a phone call questionnaire. Results: Sixty‐three patients were included from January 1993 to December 2015, 34 female and 29 males: 27 Linear immunoglobulin A disease (LAD), 12 bullous pemphigoid (BP), 12 pemphigus, 8 herpetiform dermatitis (DH) and 4 epidermolysis bullosa aquisita (EBA). The mean age was 4.7 years old. Twenty‐five patients were lost during the follow‐up. For the 38 remaining patients, the mean follow‐up duration for all pathologies was 6.6 years. Twenty‐nine of them had at least one relapse. Late relapses were observed in two cases of DH and six cases of pemphigus (7–34 months). The mean treatment duration was 30.6 months with variability according to the AIBDs. Topical corticosteroids were used alone, effectively, for seven patients and in association with other treatment in 19 patients in complete remission. Complete remission was noted in 34/38 children with a follow‐up of 4.4 years (0.08–19.5). The mean duration to complete remission was 30.5 months (6–114 months). Late nasal synechiae were reported in one EBA only. There was no significant associated comorbidity, but an association with a primary immune deficiency (PID) was observed in two cases. Conclusion: Childhood AIBDs appear to be of good overall prognosis but a long‐term follow‐up is mandatory, as relapses can be late, except for BP. The use of topical corticosteroids is frequently effective alone or in association. The association with PID leads to think about the possibility of a possible underlying dysimmunity in the child. [ABSTRACT FROM AUTHOR]

Patients with putative missense mutations and, to a lesser degree, patients with splice-site mutations presented a milder phenotype. Patients 23 and 24, carrying the homozygous p.Cys458* mutation and the heterozygous c.3786 3789delCATT (p.Phe1262Leufs*49) and c.3579G>A (p.Trp1193*) mutations, respectively, did not display exon skipping and had a severe phenotype. The homozygous p.Tyr207* mutation causes in-frame skipping of exon 10, which results in a milder phenotype in the 5-year old patient 11 than in the 59-year old patient 20 who never benefited from specific management of her disease. [Extracted from the article]

Background Autosomal recessive congenital ichthyosis ( ARCI) is a genetically heterogeneous group of rare Mendelian skin disorders characterized by cornification and differentiation defects of keratinocytes. Mutations in nine genes including PNPLA1 are known to cause nonsyndromic forms of ARCI. To date, only 10 distinct pathogenic mutations in PNPLA1 have been reported. Objectives To identify new causative PNPLA1 mutations. Methods We screened genetically unresolved cases, including our ARCI collection, comprising more than 700 families. Screening for mutations was performed either by direct Sanger sequencing or in combination with a multigene panel, followed by sequence and mutation analysis. Results Here we report on 16 novel mutations present in patients from 17 families. While all previously reported mutations and most of our novel mutations are located within the core patatin domain, we report five novel PNPLA1 mutations that are downstream of this domain. Thus, as recently described for PNPLA2, we hypothesize that a region larger than the core domain is required for full enzymatic activity of PNPLA1 in human skin barrier formation. Conclusions We estimate the frequency of PNPLA1 mutations among patients with ARCI to be around 3%. Most of our patients were born as collodion babies and showed a relatively mild ichthyosis phenotype. In four unrelated patients we observed a cyclic scaling course, which seems to be a potential phenotypic variation in a small percentage of patients with PNPLA1 mutations. The variability of the clinical manifestations and the lack of typical clinical features are specific for patients with PNPLA1 mutations, and emphasize the importance of DNA sequencing for differential diagnosis of ARCIs. [ABSTRACT FROM AUTHOR]

Granulomas may develop as a response to a local antigenic trigger, leading to the activation of macrophages and T-lymphocytes. Primary immunodeficiency (PID) is associated with the development of extensive cutaneous granulomas, whose aetiology remains unknown. We performed high-throughput sequencing of the transcriptome of cutaneous granuloma lesions on two consecutive index cases, and RT-PCR in a third consecutive patient. The RA27/3 vaccine strain of rubella virus-the core component of a universally used paediatric vaccine-was present in the cutaneous granuloma of these three consecutive PID patients. Controls included the healthy skin of two patients, non-granulomatous cutaneous lesions of patients with immunodeficiency, and skin biopsy samples of healthy individuals, and were negative. Expression of viral antigens was confirmed by immunofluorescence. Persistence of the rubella vaccine virus was also demonstrated in granuloma lesions sampled 4-5 years earlier. The persistence of the rubella virus vaccine strain in all three consecutive cutaneous granuloma patients with PID strongly suggests a causal relationship between rubella virus and granuloma in this setting. [ABSTRACT FROM AUTHOR]

Linear immunoglobulin A dermatosis (LAD) is an autoimmune bullous dermatosis commonly reported in children over the age of 5. However, IB revealed IgA auto-antibodies against the 120 kD LAD-1 protein, thus confirming the diagnosis of neonatal LAD (Fig. Immunoblot on amniotic membrane extract (IB) highlighted IgA auto-antibodies against the 120 kD LAD-1 protein for the neonate (e). gl. [Extracted from the article]

They may be large or small, segmental or focal.[1] On immunohistochemistry, these lesions are positive for glucose transporter (GLUT)-1.[2] Ulcerations are the most frequent complication and occur mostly during the proliferative phase.[[3]] To our knowledge, ulcerations on IH sequelae are not reported. The remaining telangiectasia and venules observed in the area of the ulcer are consistent with a residual lesion of IH. These elements, in addition to the fact that there was no other aetiology, suggested that the ulcerations could be related to the pre-existing vascular lesion. [Extracted from the article]