Validation of 3D skin imaging for objective repeatable quantification of severity of atrophic acne scarring.

BACKGROUND: One major sequelae of acne is atrophic scarring, yet objective tools to assess scars are lacking. Neither depth nor volume of atrophic scars is readily evaluable clinically and standard 2D photography is significantly affected by lighting and shadows. The aim of our study was to define and evaluate parameters of 3D imaging that can be used to assess severity of atrophic acne scarring. METHODS: Single center study of 31 patients with acne scarring. A target area of 3 × 3 cm was defined on the face. The global severity of atrophic acne scarring in the target area was evaluated by 5 dermatologists and scars were counted and categorized by size (scars < 2 mm, 2-4 mm, and > 4 mm in diameter). Three dimensional images of the target area were acquired with the LifeViz Micro® system and analysis was performed using MountainsMaps® software. An algorithm was developed to quantify the scar volume loss: shape removal step, with an order 5 polynomial, and to calculate the Valley void volume 80% (Vvv 80%) defined in the ISO-25178 standard for 3D surface texture. RESULTS: Correlation coefficient of the Vvv parameter to mean global severity at the target area rating was 0.77. The volume of scars evaluated with the Vvv parameter was mainly impacted by scars > 2 mm. The evaluations demonstrated good repeatability (with an intra-class correlation coefficient ICC = 0.98). CONCLUSIONS: We demonstrate convergent validation to clinical assessment and repeatability of 3D skin imaging in atrophic acne scarring. Image analysis is straightforward and can be integrated into an automated workflow.

Ehlers-Danlos syndrome with lethal cardiac valvular dystrophy in males carrying a novel splice mutation in FLNA.

Filamin A is an X-linked, ubiquitous actin-binding protein whose mutations are associated to multiple disorders with limited genotype-phenotype correlations. While gain-of-function mutations cause various bone dysplasias, loss-of-function variants are the most common cause of periventricular nodular heterotopias with variable soft connective tissue involvement, as well as X-linked cardiac valvular dystrophy (XCVD). The term "Ehlers-Danlos syndrome (EDS) with periventricular heterotopias" has been used in females with neurological, cardiovascular, integument and joint manifestations, but this nosology is still a matter of debate. We report the clinical and molecular update of an Italian family with an X-linked recessive soft connective tissue disorder and which was described, in 1975, as the first example of EDS type V of the Berlin nosology. The cutaneous phenotype of the index patient was close to classical EDS and all males died for a lethal cardiac valvular dystrophy. Whole exome sequencing identified the novel c.1829-1G>C splice variation in FLNA in two affected cousins. The nucleotide change was predicted to abolish the canonical splice acceptor site of exon 13 and to activate a cryptic acceptor site 15 bp downstream, leading to in frame deletion of five amino acid residues (p.Phe611_Gly615del). The predicted in frame deletion clusters with all the mutations previously identified in XCVD and falls within the N-terminus rod 1 domain of filamin A. Our findings expand the male-specific phenotype of FLNA mutations that now includes classical-like EDS with lethal cardiac valvular dystrophy, and offer further insights for the genotype-phenotype correlations within this spectrum. © 2016 Wiley Periodicals, Inc.

An Uncommon Presentation of Neonatal Lupus Erythematosus: A Case Report.

Neonatal lupus erythematosus (NLE) is a rare autoimmune disorder of newborns and infants, born to usually asymptomatic mothers with lupus erythematosus. Clinical manifestations include variable cutaneous findings, with possible cardiac or hepatic involvement. We present a case of a 3-month-old baby girl with NLE, born to an asymptomatic mother. Her atypical clinical presentation included hypopigmented atrophic scars on the temples. She improved with topical pimecrolimus cream, with almost complete resolution of the facial lesions and improvement in atrophy noted at the 4-month follow-up visit. Cutaneous findings of hypopigmentation and atrophic scarring are less commonly reported. To our knowledge, no similar cases have been published in the Middle East. We aim to share this interesting case, highlight the different clinical presentations of NLE and raise awareness among physicians about this variable phenotype of NLE for timely diagnosis of this uncommon entity.

Classification of Distinct Endotypes in Human Skin Scarring: S.C.A.R.-A Novel Perspective on Dermal Fibrosis.

Significance: Skin scarring is a permanent, irreversible end point of cutaneous injury. However, not everyone will acquire the same exact scar type. Skin scarring is generally recognized as complex with significant variability in individuals' scar type and response to treatment. Despite these tangible differences in treatment response, to date there has been no simplified approach in defining spectrum of skin scarring in relation to prediction and outcome post-treatment. Thus, in this study we propose that skin scarring consists of distinct endotypes, which is characterized by their specific pathology. Four distinct scar endotypes can be observed: (1) Stretched (flat), (2) Contracted, (3) Atrophic (depressed), and (4) Raised scarring, which can be abbreviated to S.C.A.R. endotypes. Each of these endotypes can certainly include subphenotypes and each phenotype can be present in more than one endotype. To define these endotypes, we also present a structured approach in assessment of all relevant parameters in skin scar evaluation including clinical (scar symptoms and signs) and nonclinical parameters (device measurements of structural, mechanical, and physiological properties of scars as well as gene and protein laboratory studies). Recent Advances: Scars can be phenotypically characterized based on a multitude of parameters assessed; however, not all scar types will share all the same characteristics. This leads to the question of whether skin scarring is a single disease entity with varying phenotypic characteristics or should be classed as several disease entities that have certain similar parameters. We suggest the latter and propose distinct scarring phenotypes arise mainly owing to genetic and environmental susceptibilities associated with the development of each specific scar endotype. Characteristic features of skin scarring, however, can be objectively and quantitively evaluated and used as an aid in the theranostic goal-directed management of scarring. Critical Issues: The concept of identifying different endotypes is key in formulating personalized treatments with improved outcomes beyond what is achieved with current nonspecific approaches in scar management. This approach has gained interest and significant traction in several other medical conditions including asthma, rheumatoid arthritis, and atopic dermatitis. Future Directions: To begin identifying distinct endotypic features in skin scarring, it is important to have a better understanding of underlying pathological mechanisms leading to further insight into the heterogeneous nature of skin scarring endotypes. This approach may lead to improved theranostic outcomes and further understanding of the pathophysiology of the complex nature of human skin scarring.

Dowling-Degos Disease Presenting Primarily with Comedones and Atrophic Scarring.

Dowling-Degos disease (DDD) is a rare genodermatosis primarily presenting with reticulated pigmentation of the flexures. Secondary features include comedones and atrophic scarring. We present a patient with histologically confirmed DDD whose predominant clinical finding was of comedones and scarring, with less prominent pigmentation, thus expanding the clinical spectrum of DDD.

Evaluating evidence for atrophic scarring treatment modalities.

INTRODUCTION: Atrophic scars cause significant patient morbidity. Whilst there is evidence to guide treatment, there does not appear to be a systematic review to analyse the efficacy of treatment options. OBJECTIVES: To retrieve all evidence relating to atrophic scar treatment and evaluate using the Clinical Evidence GRADE score in order to allow clinicians to make evidence-based treatment choices. METHOD: Searches were performed in Medline, EMBASE, CINHL and Cochrane to identify all English studies published evaluating treatment of atrophic scars on adults excluding journal letters. Each study was allocated a GRADE score based on type of study, quality, dose response, consistency of results and significance of results. The end score allowed categorisation of evidence into high, moderate, low or very low quality. RESULTS: A total of 41 studies were retrieved from searches including randomised controlled trials, observational studies, retrospective analyses and case reports of which 7% were allocated a high-quality score, 10% a moderate score, 7% a low score and 75% a very low score. Treatment modalities included ablative laser therapy, non-ablative laser therapy, autologous fat transfer, dermabrasion, chemical peels, injectables, subcision, tretinoin iontophoresis and combination therapy. CONCLUSION: There is a paucity of good-quality clinical evidence evaluating treatment modalities for atrophic scarring. Evidence supports efficacy of laser, surgery and peel therapy. Further biomolecular research is required to identify targeted treatment options and more randomised controlled trials would make the evidence base for atrophic scar treatment more robust.

Split Face Comparative Study of Microneedling with PRP Versus Microneedling with Vitamin C in Treating Atrophic Post Acne Scars.

INTRODUCTION: Acne scars are largely preventable complications of acne. 95% of the scars occur over the face thus impacting the quality of life. Correction of scars is the priority for acne patients. MATERIALS AND METHODS: Thirty patients with post acne atrophic facial scars attending the OPD during the period from April to October 2013 were offered four sittings of microneedling with PRP on one side and microneedling with vitamin C on other side of the face at an interval of 1 month. RESULTS: Twenty-seven out of the total 30 patients completed the treatment schedule. Two patients were lost to follow up and one dropped out of the study due to severe PIH. Mean age of the patients was 27.5 years. Out of 30 patients, 23 achieved reduction in scarring by one or two grades. Excellent response was seen in five (18.5%) patients with platelet-rich plasma (PRP) as compared to two (7%) patients who received treatment with vitamin C according to physician's assessment. As far as up gradation by 1 score is considered, i.e., good response, it was similar in both cases. Vitamin C did not prove to be as efficacious as PRP since 10 (37%) patients had poor response in vitamin C-treated area compared to only 6 (22.2%) patients who underwent PRP therapy, but vitamin C proved to be efficacious in dealing with post inflammatory hyper-pigmentation secondary to acne. Patients were more satisfied with PRP as compared to vitamin C. The results were evaluated and statistical analysis was done using SPSS 16.0.2. CONCLUSIONS: Overall results were better with microneedling and PRP. Vitamin C combined with microneedling also showed improvement with respect to firmness and smoothness of skin; as well as post inflammatory hyper-pigmentation. Microneedling combined with PRP proved to be good in treating boxcar and rolling scars but had limited efficacy in dealing with ice pick scars.

Leukocyte adhesion defect type 1 presenting with recurrent pyoderma gangrenosum.

Leukocyte adhesion deficiency 1 (LAD-1) is a rare autosomal recessive disorder of leukocyte function. LAD-1 affects about 1 per 10 million individuals and is characterized by recurrent bacterial and fungal infections and depressed inflammatory responses despite striking blood neutrophilia. Patients with the severe clinical form of LAD-1 express <0.3% of the normal amount of the ß2-integrin molecules, whereas patients with the moderate phenotype may express 2-7%. Skin infection may progress to large chronic ulcers with polymicrobial infection, including anaerobic organisms. The ulcers heal slowly, require months of antibiotic treatment, and often require plastic surgical grafting. The diagnosis of LAD-1 is established most readily by flow cytometric measurements of surface CD11b in stimulated and unstimulated neutrophils using monoclonal antibodies directed against CD11b. Pyoderma gangrenosum (PG) is an uncommon condition characterized by recurrent sterile, inflammatory skin ulcers. Commonly, PG occurs in the context of inflammatory bowel disease or rheumatic, hematologic, or immunologic disorders. Here, we present a 5-year-old female with a long history of PG, which healed with atrophic scarring, who was ultimately diagnosed with leukocyte adhesion deficiency type 1 (LAD1). She had a good response to high-dose prednisone therapy (2 mg/kg) and was discharged after 3 weeks of admission but only to be re-admitted 3 weeks later with severe pneumonia. During hospital stay, she developed pneumothorax and pneumomediastinum and later succumbed to her illness.

An Unusual Presentation of Chiari I Malformation.

The most typical symptom of Chiari malformation type I in children is headache. The authors describe a 14-year-old girl who presented with a 3-year history of gait decline and no headache, which is very unusual. After surgery to correct the Chiari I malformation, the patient's gait improved; however, she went on to develop decreased hand use with joint deformities. She was diagnosed with a probable connective tissue disorder. Patients with connective tissue disorders are at increased risk for developing Chiari I malformation. The authors discuss the possible reasons for the unusual presentation of the Chiari I malformation and possible mechanisms. The unusual presentation of Chiari I delayed this young patient's diagnosis and treatment.