Hyperbaric oxygen management of recurrent cellulitis in poikiloderma with neutropenia.

Poikiloderma with neutropenia (PN), is a rare autosomal recessive condition with many associated complications and manifestations. Here we present a patient with confirmed PN who is of one-quarter Chucktaw or Cherokee heritage with no known descent from the Navajo tribe. The patient's condition was complicated by chronic bilateral lower limb cellulitis and associated osteomyelitis which was unresponsive to extensive antibiotic regimens. Subsequent treatment with hyperbaric oxygen therapy (HBOT) was successful. To date, no author has reported on the treatment of recurrent cellulitis using HBOT in this patient population. Based on our experience, HBOT should be considered in patients with PN.

Self-improving dystrophic epidermolysis bullosa: First report of clinical, molecular, and genetic characterization of five patients from Southeast Asia.

Self-improving dystrophic epidermolysis bullosa is a rare subtype of dystrophic epidermolysis bullosa (DEB) characterized by significant improvement in skin fragility within the first few years of life. Genetic inheritance has previously been reported as autosomal dominant or recessive with both forms harboring mutations in COL7A1. To date, there have been no reports of this rare clinical entity from various Southeast Asian ethnicities. Here, we describe the clinical and molecular features of five patients from the Southeast Asia region who presented with predominantly acral-distributed blisters and erosions in the first few days of life. Blistering resolved over several months, without appearance of new blisters. By immunofluorescence, intraepidermal retention of Type VII collagen was observed in all patient skin biopsies when investigated with antibody staining. Genetic analysis of four patients revealed pathogenic variants in COL7A1 which have not been previously reported. The clinical diagnosis in these rare patients is confirmed with molecular histology and genetic characterization.

Skin Fragility: Perspectives on Evidence-based Therapies.

The term skin fragility disorders describes a group of conditions in which the structural integrity of the skin is compromised and its resistance to external shear forces diminished. Skin fragility can have different causes, ranging from genetic variations to inflammatory or physical phenomena. The genetic skin fragility disorders, collectively called epidermolysis bullosa, serve as a paradigm for the study of causes and mechanisms of skin fragility. Recent biomedical research has revealed substantial genetic heterogeneity of the epidermolysis bullosa group, delivered ample new knowledge on its pathophysiology, and facilitated the design of evidence-based therapeutic strategies. The therapy development process extends from in vitro testing to preclinical validation in animal models, and clinical trials. This article reviews different approaches to curative and symptom-relief therapies, and appraises their status and perspectives for clinical implementation.

Laser for vascular anomalies: successful outcomes in children.

Vascular anomalies can cause both emotional and physical distress to patients, particularly children. The paediatric laser service at Great Ormond Street Hospital (GOSH) treats a range of dermatological conditions including a variety of vascular anomalies, excess hair growth and disfiguring scars. The laser team at GOSH has 25 years of experience in treating a wide variety of paediatric dermatological conditions using various laser therapies. With over 600 new referrals for laser therapy and over 1000 laser procedures each year the GOSH laser team has vast amounts of experience with both common and rare conditions. Excellent clinical outcomes continue to be delivered, and new treatment therapies are constantly being developed to treat more recalcitrant lesions. The adverse effect rates experienced by the GOSH laser patients have been decreasing over the past two decades, reaching the low rate of 0.8% per treated patients per year. This remarkable achievement has been continuously improved by integrating specific and standardized laser protocols for each patient treated, to ensure efficacious and safe laser treatment delivery. Treating vascular anomalies with laser therapy creates significant positive results among the paediatric population, thus laser therapy at GOSH makes a significant impact upon children's lives with both rare and common vascular anomalies.

CHRNG-related nonlethal multiple pterygium syndrome: Muscle imaging pattern and clinical, histopathological, and molecular genetic findings.

Mutations in the CHRNG gene cause autosomal recessive multiple pterygium syndrome (MPS). Herein we present a long-term follow-up of seven patients with CHRNG-related nonlethal MPS and we compare them with the 57 previously published patients. The objective is defining not only the clinical, histopathological, and molecular genetic characteristics, but also the type and degree of muscle involvement on whole-body magnetic resonance imaging (WBMRI). CHRNG mutations lead to a distinctive phenotype characterized by multiple congenital contractures, pterygium, and facial dysmorphism, with a stable clinical course over the years. Postnatal abnormalities at the neuromuscular junction were observed in the muscle biopsy of these patients. WBMRI showed distinctive features different from other arthrogryposis multiple congenita. A marked muscle bulk reduction is the predominant finding, mostly affecting the spinal erector muscles and gluteus maximus. Fatty infiltration was only observed in deep paravertebral muscles and distal lower limbs. Mutations in CHRNG are mainly located at the extracellular domain of the protein. Our study contributes to further define the phenotypic spectrum of CHRNG-related nonlethal MPS, including muscle imaging features, which may be useful in distinguishing it from other diffuse arthrogryposis entities.

Brittle cornea syndrome: a case report and review of the literature.

BACKGROUND: To report a patient who presented with bluish scleral discoloration, keratoconus, and progressive high myopia. CASE PRESENTATION: A 6-year-old Chinese female patient presented with a significant bluish discoloration of the sclera in both eyes and extreme corneal thinning with anterior corneal protrusion. General pediatric physical examination was normal for all systems and no genetic disorders known were observed. CONCLUSIONS: We aim to highlight the importance of diagnosis and treatment of patients suffering from Brittle cornea syndrome. Timely diagnosis and early provision of protective glasses seem to be the most important step in treating BCS. To our knowledge, this is the first case of BCS being reported in the Asia area.

Restrictive Dermopathy: A Rare Disease with Unusual Radiographic Findings.

The patient is a unique case presenting with presumed Restrictive Dermopathy (RD) and intracranial and adrenal calcifications, an association not previously described in the literature. This case postulates the possibility of additional radiographic features that can be included in the spectrum of RD or as secondary events from the underlying pathophysiology of RD.

Tropism-modified AAV vectors overcome barriers to successful cutaneous therapy.

Autologous human keratinocytes (HK) forming sheet grafts are approved as skin substitutes. Genetic engineering of HK represents a promising technique to improve engraftment and survival of transplants. Although efficacious in keratinocyte-directed gene transfer, retro-/lentiviral vectors may raise safety concerns when applied in regenerative medicine. We therefore optimized adeno-associated viral (AAV) vectors of the serotype 2, characterized by an excellent safety profile, but lacking natural tropism for HK, through capsid engineering. Peptides, selected by AAV peptide display, engaged novel receptors that increased cell entry efficiency by up to 2,500-fold. The novel targeting vectors transduced HK with high efficiency and a remarkable specificity even in mixed cultures of HK and feeder cells. Moreover, differentiated keratinocytes in organotypic airlifted three-dimensional cultures were transduced following topical vector application. By exploiting comparative gene analysis we further succeeded in identifying αvß8 integrin as a target receptor thus solving a major challenge of directed evolution approaches and describing a promising candidate receptor for cutaneous gene therapy.

Strengthening the skin with topical delivery of keratinocyte growth factor-1 using a novel DNA plasmid.

Fragile skin, susceptible to decubitus ulcers and incidental trauma, is a problem particularly for the elderly and for those with spinal cord injury. Here, we present a simple approach to strengthen the skin by the topical delivery of keratinocyte growth factor-1 (KGF-1) DNA. In initial feasibility studies with the novel minimalized, antibiotic-free DNA expression vector, NTC8385-VA1, the reporter genes luciferase and enhanced green fluorescent protein were delivered. Transfection was documented when luciferase expression significantly increased after transfection. Microscopic imaging of enhanced green fluorescent protein-transfected skin showed green fluorescence in hair follicles, hair shafts, and dermal and superficial epithelial cells. With KGF-1 transfection, KGF-1 mRNA level and protein production were documented with quantitative reverse transcriptase-polymerase chain reaction and immunohistochemistry, respectively. Epithelial thickness of the transfected skin in the KGF group was significantly increased compared with the control vector group (26 ± 2 versus 16 ± 4 µm) at 48 hours (P = 0.045). Dermal thickness tended to be increased in the KGF group (255 ± 36 versus 162 ± 16 µm) at 120 hours (P = 0.057). Biomechanical assessment showed that the KGF-1-treated skin was significantly stronger than control vector-transfected skin. These findings indicate that topically delivered KGF-1 DNA plasmid can increase epithelial thickness and strength, demonstrating the potential of this approach to restore compromised skin.

[Hyaline-vascular Multicentric Castleman's Disease in an immunocompetent patient]. / Enfermedad de Castleman Multicéntrica tipo hialino-vascular en paciente inmunocompetente.

A previously healthy, immunocompetent 67-year-old female presented with a one-month history of general symptoms, weight loss, night fevers, and bilateral lower extremity edema. On admission she had severe anemia, acute kidney injury, and multiple lymphadenopathies. An excisional biopsy of one of the axillary lymphadenopathies confirmed hyaline-vascular Castleman's disease. This rare disease is a polyclonal lymphoproliferative disorder that affects the normal lymph node architecture. According to its location it can be divided in unicentric (localized) or multicentric disease; it can be further divided according to histopathology in hyaline-vascular or plasmatic cells variety. Clinical presentation relates more to histopathological variety than to centricity. Human herpes virus 8 is ubiquitous in this disease and, along with interleukin 6, plays an important role in pathogenesis and symptoms presentation. Surgery is the go-to treatment of localized disease, while systemic chemotherapy is the option in multicentric disease. Communication between the clinical and anatomopathological teams is crucial; lag in diagnosis can lead to futile investigations in search of other diseases and delay in treatment.

[Cutaneous vascular anomalies in children]. / Les anomalies vasculaires cutanées chez l'enfant.

INTRODUCTION: Vascular anomalies, which are erroneously categorized under the term angiomas, are a highly heterogeneous group of lesions that are poorly understood and affect a mean of 5 to 10 % of children. The fortuitous discovery of propranolol's efficacy in one of these entities has made them a topical issue. OBJECTIVES: The paper's main objective is to inform family doctors of the various types of vascular anomalies, clarify their classification, and provide a common terminology. Its secondary objective is to provide a decision tree that enables primary care doctors to avoid diagnostic pitfalls, successfully detect cases, and optimize management. METHODS: Systematic review. CONCLUSIONS: According to a recent study, 71,3 % of publications use the term hemangioma erroneously, regardless of the authors' field. The key for family doctors is to use one international classification only, that of the International Society for the Study of Vascular Anomalies (ISSVA), in order to facilitate management and comprehension between the different healthcare levels. The diagnosis of vascular anomalies is clinical in 90 % of cases, so all family doctors can, whilst using a decision tree, diagnose a vascular anomaly and refer only those that are complex for specialist care. The most common vascular anomaly is infantile hemangioma in infants, which spontaneously regresses around the age of 5-7 years in 90 % of cases. Watchful waiting and regular follow-up suffice, therefore, in such settings.

[Developmental abnormalities and nevi of the scalp]. / Fehlbildungen und Nävi des behaarten Kopfes.

Unusual congenital or early-onset skin lesions on the scalp often pose a diagnostic challenge particularly as the clinical evaluation may be hampered by dense hair growth. Thus, this paper provides a concise review on developmental abnormalities and nevi with exclusive or predominant scalp localization. Aplasia cutis congenita occurs as an isolated finding, in association with genetic syndromes, nevi and anomalies or as a consequence of intrauterine trauma and teratogens. A hairless area with a narrow surrounding rim of hypertrichosis (hair collar sign) may point to occult cranial dysraphism, especially if accompanied by further suggestive signs as port-wine stains, large hemangiomas, dimples, congenital dermoid cysts, and sinuses. Many diverse entities may hide behind cutis verticis gyrata with the primary essential form being rare and representing a diagnosis of exclusion. In contrast to former belief, benign adnexal tumors arise in a nevus sebaceus considerably more often than basal cell carcinomas and other malignant epithelial tumors. Provided that tumor development is not suspected, excision of a nevus sebaceus nevus is indicated primarily for aesthetic-psychosocial reasons. However, surgical treatment is considerably easier in small children. Nevus sebaceus may be a cutaneous marker for several complex syndromes whereas nevus psiloliparus presents almost always in connection with encephalocraniocutaneous lipomatosis. Congenital melanocytic nevi of the scalp tend toward clinical regression, so that surgical intervention in large lesions should be carefully considered. In contrast, the threshold for excision of blue nevi and other conspicuous melanocytic nevi on the scalp should be low, especially since they are difficult to monitor.

Vascular anomalies - a practical approach.

Vascular anomalies are common clinical problems (around 4.5% of all patients) in pediatric dermatology. A correct diagnosis is possible on clinical grounds in around 90% of cases; the remaining patients may require radiologic evaluations (duplex ultrasonography, MRI scan) and, rarely, histology. Vascular anomalies are divided into tumors and vascular malformations. This clear division reflects the different biological behaviors of these two groups. The infantile hemangioma represents by far the most common vascular tumor and is characterized by a typical growth cycle consisting of rapid proliferation, plateau phase, and finally slow regression. The discovery in 2008 of the efficacy of beta blockers in this disease is a therapeutic milestone. Vascular malformations can affect all types of vessels (capillaries, veins, arteries and lymphatic vessels). They usually manifest at birth and grow proportionally with the affected child. Some show marked progression especially during puberty. Considerable progress has been made with innovative interventional therapies in recent years, but surgery remains an important option. Basic knowledge of these diseases is important to every dermatologist in order to be able to counsel and manage affected patients correctly.

Nuclear medicine in the management of superficial skin abnormalities and institutional experience.

Keloid, hypertrophic scars and basal cell carcinoma (BCC) falls under the category of non-melanoma skin cancer. Intralesional steroids, external beam radiation therapy, 5-Fluorouracil, cryotherapy, laser, etc are the available treatment options. However, recurrence has been reported with each type of treatment mode. In the present article, various treatment modes have been discussed and institutional experience of Rhenium-188 skin patches for the treatment of keloids and BCC has been discussed.

Diagnosis and management of extensive vascular malformations of the lower limb: part I. Clinical diagnosis.

There is significant confusion in the literature when describing vascular anomalies, and vascular malformations are often misnamed or incorrectly classified. Part I of this two-part series on the diagnosis and management of extensive vascular malformations of the lower limbs will discuss the dermatologist's role in the diagnosis of these lesions. At least nine types of vascular malformations with specific clinical and radiologic characteristics must be distinguished in the lower limbs: Klippel-Trénaunay syndrome, port-wine stain with or without hypertrophy, cutis marmorata telangiectatica congenita, macrocephaly-capillary malformation, Parkes Weber syndrome, Stewart-Bluefarb syndrome, venous malformation, glomuvenous malformation, and lymphatic malformation. This article highlights the differences in clinical appearance and discusses the differential diagnosis of extensive vascular malformations in an attempt to ensure earlier diagnosis and better outcomes for these patients.

Diagnosis and management of extensive vascular malformations of the lower limb: part II. Systemic repercussions [corrected], diagnosis, and treatment.

At least nine types of vascular malformations with specific clinical and radiologic characteristics must be distinguished in the lower limbs: Klippel-Trénaunay syndrome, port-wine stain with or without hypertrophy, cutis marmorata telangiectatica congenita, macrocephaly-capillary malformation, Parkes Weber syndrome, Stewart-Bluefarb syndrome, venous malformation, glomuvenous malformation, and lymphatic malformation. Extensive vascular malformations are often more complex than they appear and require a multidisciplinary therapeutic approach. Vascular malformations may be associated with underlying disease or systemic anomalies. Part II of this two-part series on the diagnosis and management of extensive vascular malformations of the lower limb highlights the systemic repercussions [corrected] (bone, articular, visceral, and hematologic involvement), diagnosis, and treatment of these lesions.

Vascular birthmarks.

Vascular birthmarks can be classified into hemangioma and vascular malformations. Hemangioma are frequent tumours of early infancy demonstrating endothelial hyperplasia, a history of rapid neonatal growth and slow involution during later childhood. Treatment of hemangioma is dependent of stage and type of the lesion. Given the current availability of drugs, lasers, and other techniques to treat hemangioma safely, philosophy of "benign neglect" should not be considered anymore. Vascular malformations show a normal endothelial turnover, being present at birth and growing commensurately with the child. Exact diagnosis by employing modern diagnostic means,which are able to differentiate low-flow from high flow lesions is important for further therapeutic management. Beside conservative treatment strategies, use of laser, sclerotherapy, interventional embolization and surgical treatment are possible management options. Patients should receive multidisciplinary care in qualified vascular centres.

Anaesthetic management of a patient with multiple pterygium syndrome for elective caesarean section.

We report a case of a pregnant woman with multiple pterygium syndrome who presented for elective caesarean section. Neuraxial anaesthesia failed and the backup plan of awake intubation was extremely difficult.

Escobar (multiple pterygium) syndrome: Multidisciplinary approach to a very rare syndrome.

Escobar (multiple pterygium) syndrome is progressive and a very rare syndrome. It is generally characterized by multiple pterygia that are found in the cervical, antecubital and popliteal regions. In this report, we present the treatment management of a 14-year-old case with late stage Escobar syndrome who was admitted due to multiple pterygia and bilateral knee contractures. The treatment of this case was conducted in collaboration with the department of orthopedics and the department of physical therapy. The treatment of the case was done in three stages: soft tissue procedures, femoral recurvatum osteotomy and triple arthrodesis, respectively. In addition to all these, the patient did intensive physical therapy for one year. As a result of the operations and physical therapy, adequate muscle strength was obtained.