A Neonate with Blisters

A newborn boy presented at 5 minutes of age with a large erosion on the sole of his left foot (Figs 1 and 2), which appeared after drying. He was a monochorionic diamniotic twin, delivered at 35 6/7 weeks by elective cesarean delivery after an uncomplicated pregnancy. Birth weight was 2,230 g (10th percentile) and he appeared very well at birth, with Apgar scores of 8 and 9. There was no family history of herpetic lesions or frequent blistering, and his twin brother was well, with no evidence of blisters.At 1 hour of age, 2 additional smaller blisters were noted on the sole of the right foot (Fig 2). There were no blisters elsewhere on the skin or mucosal membranes, and the remainder of the physical examination was unremarkable.Given the possibility of herpes simplex virus infection, a swab was taken from the blisters for viral polymerase chain reaction, and an evaluation for sepsis was performed. The patient was started on acyclovir and antibiotics and admitted to the NICU for further monitoring. In the NICU, he remained afebrile and well, with no further blistering. The results of all cultures were negative. The dermatology team performed a biopsy of the blister, which revealed the diagnosis.The biopsy revealed subepidermal blisters, with the absence of collagen VII protein expression on immunofluorescence mapping (IFM) and a significantly decreased number of anchoring fibrils on electron microscope (EM). These findings were consistent with a diagnosis of dystrophic epidermolysis bullosa (DEB).Epidermolysis bullosa (EB) is a genetically and clinically heterogeneous group of rare disorders characterized by fragility and blistering of the skin and mucosal membranes. (1) EB is caused by mutations in genes encoding structural proteins that make up the basement membrane zone (BMZ) of the skin and mucosa, which is critical for cell adhesion and barrier formation. (1) There are 4 major types of EB, classified by the level at which skin separation occurs: EB simplex (intraepidermal), junctional EB (within the skin BMZ), DEB (below the skin BMZ), and Kindler syndrome (mixed pattern with multiple cleavage planes). (1)(2)Hundreds of mutations have been described, leading to a wide phenotypic spectrum, from mild blister development with trauma to severe, spontaneous, generalized blistering and scarring. EB simplex is the most common form of EB and is typically characterized by blisters isolated to the skin that heal without scarring and are most often induced by trauma. (2) Junctional EB is characterized by blistering of the skin and mucosal membranes that heal with scarring. DEB is characterized by blistering of the skin and mucosal membranes that heal with scarring and milia. (2) In severe recessive DEB, the most severe form of DEB, blistering of the skin begins at birth, leading to extensive scarring, pseudosyndactyly, contractures, esophageal strictures, oral and ocular complications, and squamous cell carcinoma. (2) The dominant form of DEB is clinically much less severe. Kindler syndrome is characterized by blistering of the skin, photosensitivity, extensive skin atrophy, and poikiloderma. (2)The differential diagnosis of blisters, or vesiculopustular lesions, in the newborn is broad, ranging from benign conditions to serious, life-threatening infections, and congenital disorders. (3)(4)Benign conditions include congenital sucking blisters, and benign newborn rashes such as transient neonatal pustular melanosis, erythema toxicum neonatorum, and neonatal acne. (4) Sucking blisters are classically located on the wrists, hands, or fingers and contain sterile fluid. Benign newborn rashes occur in otherwise well newborns and are typically more pustular and less vesicular in appearance.Infections can be life-threatening and need to be treated promptly. Potential infectious agents can be viral, bacterial, or fungal. The most commonly implicated viruses are herpes simplex virus and varicella-zoster virus, but cytomegalovirus and coxsackieviruses have also been described. (3)(4) Bacterial infections include staphylococcal pustulosis, staphylococcus scalded skin syndrome, streptococcal infections, listeriosis, and congenital syphilis. (3)(4) Fungal infections include neonatal and congenital candidiasis. Scabies, caused by the mite Sarcoptes scabiei, although uncommon in the developed world, can be seen. (3)(4)Congenital bullous disorders include EB, epidermolytic ichthyosis (autosomal dominant; raw erosions present at birth and may be misdiagnosed as EB), aplasia cutis congenita (focal or widespread absence of skin, majority on the scalp; can be associated with underlying neurologic defect), incontinentia pigmenti (X-linked dominant, usually lethal to males in utero; neonates develop crops of vesicles in linear streaks, with other cutaneous manifestations later in life; abnormal teeth, hair, and nails; ocular and neurologic abnormalities), and cutaneous mastocytosis (reddish-brown macules caused by local mast cell proliferation, which can urticate and present with bullous lesions). (3)(4)All neonates presenting with blisters should have an evaluation for sepsis with cultures of the lesions, blood cultures, and consideration of a lumbar puncture. Patients should be started on antibiotics and antivirals pending results. If negative, a biopsy and dermatology consultation should be considered to assess for the rarer congenital disorders.The diagnosis of EB is made by skin biopsy, preferably of newly induced blisters, which is sent for EM and IFM. (2) This identifies the ultrastructural site of cleavage, and the specific structural proteins involved, which can be correlated to a suspected culprit gene. (2) Next, mutational analysis of suspected genes is sent, which allows for more precise classification. (2) Mutational analysis is also essential for genetic counseling and will become increasingly relevant as specific molecular treatments are developed. (2)Treatment of EB is largely supportive, with a focus on blister prevention and wound care management. (1) New blisters are drained with sterile large-bore needles to prevent extension. (1) The roof of the blister is left in place to act as a biologic dressing, reducing pain and minimizing the risk of infection. (1) Dressing options are individualized based on EB subtype, wound appearance, cost, and local availability. (1) In general, adhesive and compressive dressings should be avoided, as they can induce new blister formation. (1) Antibiotics should be used judiciously, as bacterial colonization is inevitable and often does not impede healing. Topical and oral antibiotics are reserved for wounds that fail to heal and those displaying signs of infection. (1) The most commonly implicated bacteria are Staphylococcus aureus, Streptococcus species, Pseudomonas aeruginosa, and anaerobes. (1) Pain and itch are commonly experienced and can be controlled with analgesics and nonsedating antihistamines. (1) Increased caloric intake is often required due to the increased energy expenditure from wound healing. (1) Patients with generalized severe recessive DEB often require surgical management for esophageal strictures, pseudosyndactyly, and squamous cell carcinoma. The overall prognosis is highly variable, depending on disease severity. Although there is currently no cure for EB, research on a number of more targeted approaches to therapy, including gene therapy, cell-based therapies (fibroblast therapy and bone marrow stem cell transplantation), gene editing/engineering, and protein replacement therapies, is currently underway and has the potential to significantly improve disease trajectory. (5) Family support is essential, and families can be directed to www.debra-international.org, a parental support and advocacy site dedicated to EB.Genetic testing was sent and was positive for a heterozygous mutation in COL7A1, which has been reported in cases of dominant DEB. The blisters on his bilateral feet healed nicely, and he has not developed any further blisters to date. He has been growing and developing normally.

Fetched live from OpenAlex and de-inverted. Abstracts are not stored in this database: the inverted indexes are 8.6 GB of the frame’s 9.3 GB of text, and the host has 13 GB free.