Anna L. Bruckner

Sildenafil for severe lymphatic malformations.

Lymphatic malformations are rare but can cause significant clinical problems in addition to cosmetic disfigurement. Sildenafil was used in a child whose pulmonary hypertension was caused by lymphatic malformation; the result was a marked decrease in the lymphatic malformation.

Collodion baby: An update with a focus on practical management

Collodion baby is an uncommon clinical presentation of several genetic conditions, primarily disorders of cornification. The severely compromised epidermal barrier presents the greatest challenge during the newborn period and advances in neonatal care have significantly improved the prognosis. This review summarizes the clinical characteristics, complications, outcomes, and differential diagnosis of the collodion baby. A practical approach to management based on the literature and clinical experience is presented.

Atopic Dermatitis: Skin-Directed Management

Atopic dermatitis is a common inflammatory skin condition characterized by relapsing eczematous lesions in a typical distribution. It can be frustrating for pediatric patients, parents, and health care providers alike. The pediatrician will treat the majority of children with atopic dermatitis as many patients will not have access to a pediatric medical subspecialist, such as a pediatric dermatologist or pediatric allergist. This report provides up-to-date information regarding the disease and its impact, pathogenesis, treatment options, and potential complications. The goal of this report is to assist pediatricians with accurate and useful information that will improve the care of patients with atopic dermatitis.

Adolescent hair loss.

Purpose of review Hair loss, or alopecia, may occur as a primary skin disorder or because of an underlying health problem. It may be upsetting to patients, particularly adolescents who are experiencing physical, emotional, and psychological transitions. Understanding the impact of alopecia is important for care providers who see adolescents. Recent findings The most common forms of alopecia in adolescence are telogen effluvium, androgenetic alopecia, and alopecia areata. Telogen effluvium may present suddenly or insidiously secondary to a variety of triggers. Androgenetic alopecia may begin in adolescence, and topical minoxidil is effective at retarding further hair loss. It may be a sign of underlying androgen excess, particularly polycystic ovary syndrome in women. Alopecia areata is less common, but may be distressing, especially if hair loss is extensive. Because treatments for alopecia are not curative, helping affected patients cope by offering support and nonpharmacologic techniques to help appear more like their peers should be part of care. Summary Physicians need to be skilled in evaluating the most common forms of alopecia presenting in adolescence and should be aware of potential treatments, including the value of psychosocial support.

Gene expression profiling in pachyonychia congenita skin

BACKGROUND Pachyonychia congenita (PC) is a skin disorder resulting from mutations in keratin (K) proteins including K6a, K6b, K16, and K17. One of the major symptoms is painful plantar keratoderma. The pathogenic sequelae resulting from the keratin mutations remain unclear. OBJECTIVE To better understand PC pathogenesis. METHODS RNA profiling was performed on biopsies taken from PC-involved and uninvolved plantar skin of seven genotyped PC patients (two K6a, one K6b, three K16, and one K17) as well as from control volunteers. Protein profiling was generated from tape-stripping samples. RESULTS A comparison of PC-involved skin biopsies to adjacent uninvolved plantar skin identified 112 differentially-expressed mRNAs common to patient groups harboring K6 (i.e., both K6a and K6b) and K16 mutations. Among these mRNAs, 25 encode structural proteins including keratins, small proline-rich and late cornified envelope proteins, 20 are related to metabolism and 16 encode proteases, peptidases, and their inhibitors including kallikrein-related peptidases (KLKs), and serine protease inhibitors (SERPINs). mRNAs were also identified to be differentially expressed only in K6 (81) or K16 (141) patient samples. Furthermore, 13 mRNAs were identified that may be involved in pain including nociception and neuropathy. Protein profiling, comparing three K6a plantar tape-stripping samples to non-PC controls, showed changes in the PC corneocytes similar, but not identical, to the mRNA analysis. CONCLUSION Many differentially-expressed genes identified in PC-involved skin encode components critical for skin barrier homeostasis including keratinocyte proliferation, differentiation, cornification, and desquamation. The profiling data provide a foundation for unraveling the pathogenesis of PC and identifying targets for developing effective PC therapeutics.

Reduced Toxicity Conditioning and Allogeneic Hematopoietic Progenitor Cell Transplantation for Recessive Dystrophic Epidermolysis Bullosa

Recessive dystrophic epidermolysis bullosa is a severe, incurable, inherited blistering disease caused by COL7A1 mutations. Emerging evidence suggests hematopoietic progenitor cells (HPCs) can be reprogrammed into skin; HPC-derived cells can restore COL7 expression in COL7-deficient mice. We report two children with recessive dystrophic epidermolysis bullosa treated with reduced-toxicity conditioning and HLA-matched HPC transplantation.

Symptomatic Congenital Hemangioma and Congenital Hemangiomatosis Associated With a Somatic Activating Mutation in GNA11.

IMPORTANCE Congenital hemangiomas are uncommon benign vascular tumors that present fully formed at birth. They are rarely associated with transient hematologic abnormalities, which are typically less severe than the Kasabach-Merritt phenomenon associated with kaposiform hemangioendotheliomas. Congenital hemangiomas are typically solitary and have not been reported to occur in a multifocal, generalized pattern. OBJECTIVE To describe a male infant born with an unusual, large vascular mass complicated by anemia, thrombocytopenia, and disseminated intravascular coagulopathy, as well as innumerable small vascular papules in a generalized cutaneous distribution. DESIGN, SETTING, AND PARTICIPANT This case report is a descriptive observation of the results of clinical, pathologic, and genetic studies performed in a single male infant observed for 2 years (May 2013 to June 2015) for vascular anomalies at a tertiary care referral center. MAIN OUTCOMES AND MEASURES Histopathologic, immunohistochemical, and genetic study results of tumor specimens and saliva. RESULTS Careful pathologic study of 3 tumor specimens revealed similar lobular proliferations of bland endothelial cells. Lesional vessels did not express GLUT1 or the lymphatic marker D2-40, whereas WT1 was expressed. A somatic c.A626C, p.Q209P mutation in the GNA11 gene was identified in tumoral tissue. CONCLUSIONS AND RELEVANCE These findings support a unifying diagnosis of congenital hemangioma for these vascular tumors. To date, this is the first-reported case of a hemangiomatosis presentation of congenital hemangioma. In addition to highlighting this novel phenotype, this case indicates the rare association of congenital hemangioma with hematologic abnormalities and verifies somatic activating mutations as the underlying cause of congenital hemangioma.

Instrument for scoring clinical outcome of research for epidermolysis bullosa: a consensus-generated clinical research tool.

Epidermolysis bullosa (EB) is a genetic condition characterized by skin fragility and blistering. There is no instrument available for clinical outcome research measurements. Our aim was to develop a comprehensive instrument that is easy to use in the context of interventional studies. Item collection was accomplished using a two‐step Delphi Internet survey process for practitioners and qualitative content analysis of patient and family interviews. Items were reduced based on frequency and importance using a 4‐point Likert scale and were subject to consensus (>80% agreement) using the nominal group technique. Pilot data testing was performed in 21 consecutive patients attending an EB clinic. The final score, Instrument for Scoring Clinical Outcome of Research for Epidermolysis Bullosa (iscorEB), is a combined score that contains clinician items grouped in five domains (skin, mucosa, organ involvement, laboratory abnormalities, and complications and procedures; maximum score 114) and patient‐derived items (pain, itch, functional limitations, sleep, mood, and effect on daily and leisurely activities; maximum score 120). Pilot testing revealed that combined (see below) and subscores were able to differentiate between EB subtypes and degrees of clinical severity (EB simplex 21.7 ± 16.5, junctional EB 28.0 ± 20.7, dystrophic EB 57.3 ± 24.6, p = 0.007; mild 17.3 ± 9.6, moderate 41.0 ± 19.4, and severe 64.5 ± 22.6, p < 0.001). There was high correlation between clinician and patient subscores (correlation coefficient = 0.79, p < 0.001). iscorEB seems to be a sensitive tool in differentiating between EB types and across the clinical spectrum of severity. Further validation studies are needed.

Patterns of oral mucosa lesions in patients with epidermolysis bullosa: comparison and agreement between oral medicine and dermatology

BACKGROUND The oral mucosa in patients with epidermolysis bullosa (EB) can be affected with different lesions and degrees of severity. However, patterns of oral lesions in distinct types of EB are still unclear. OBJECTIVES The purpose of this study was to determine the frequency and distribution of four types of lesions (erythema, erosion, atrophy, and blister) for each oral site and to calculate the interobserver reliability for each type of lesion in each site. METHODS Ninety-two patients with different EB types were assessed independently by an oral medicine specialist and a dermatologist. The degree of agreement was calculated by the intraclass correlation coefficient (ICC). RESULTS The most affected oral site was the tongue, with the most frequent lesion being erythema and atrophy [54(58.7%) patients] for the oral medicine specialist and erosion [54(58.7%) patients] for the dermatologist. Patients with recessive dystrophic EB-severe generalized (RDEB-sev gen) showed the highest mean of sites involved by each lesion for both oral medicine and dermatology. The interobserver reliability on the total of lesions was excellent on only 3 sites: lower lip (ICC: 0.89; 95%CI:0.83-0.92), hard palate (ICC:0.85; 95%CI:0.72-0.91), and tongue (ICC:0.89; 95%CI:0.84-0.92), whereas the interobserver reliability calculated for each single oral lesion showed a lower agreement. CONCLUSION Total distribution of sites involved by four types of lesions was higher in RDEB-sev gen than in the rest of EB types, with a predominance of erythema followed by erosion. The agreement on the type of lesion was found to be poor-moderate for many oral sites.

Expression of phosphodiesterase-5 in lymphatic malformation tissue.

Expression of Phosphodiesterase-5 in Lymphatic Malformation Tissue Lymphatic malformations (LMs) are uncommon and sometimes debilitating congenital vascular anomalies that presumably arise because of developmental dysplasia of the lymphatic network in utero. They comprise primitive lymphatic sacs surrounded by a thickened layer of connective tissue and interspersed muscle fibers.1 Current treatments for LM are palliative and only partially successful and include compression, surgical resection, laser ablation, and sclerotherapy. A recent report by Swetman and colleagues2 noted marked reductions in LM size in 3 children after starting treatment with oral sildenafil citrate, an inhibitor of phosphodiesterase isoform 5 (PDE5). The localization of PDE5 in LM tissue and the mechanism of the effect of sildenafil on LM is unknown. To further investigate PDE5 localization within LM tissue, we performed immunohistochemical studies to identify the presence and relative location of PDE5 expression in vascular smooth muscle, vascular endothelium, and lymphatic endothelium.