An early-term female newborn presents with multiple blisters and erosions at birth over the acral area followed by lesions on the perianal, perioral, and chest regions (Figure 1).Born by elective cesarean delivery to a 25-year-old primigravida mother at 38 + 1/7 weeks’ gestationNo history of teratogens in this pregnancyNo family history of skin lesionsMaternal prenatal screening was negative including viral serology, hepatitis B, C, HIV, and toxoplasmosis, rubella, cytomegalovirus, and herpesFetal growth scans and level 2 antenatal ultrasonography at 20 weeks’ gestation were normalAt birth, the infant cried immediately and did not need any resuscitation. She was noted to have multiple flaccid, thin-walled bullae and erosions over distal extremities (hands and feet). Over the next few days, new lesions appeared on the perianal, perioral, and chest regions, while older superficial erosions healed with crusting (Figure 2). The perianal erosions had peeling margins. There were no lesions in the oral cavity. The infant was otherwise well, feeding normally and afebrile.Heart rate: 150 beats/minRespiratory rate: 48 breaths/minBlood pressure: 60/42 (mean 45) mm HgOxygen saturation: 98% (in room air)Temperature: 98.6 °F (36.9 °C)Birth weight = 2900 g (100th percentile), length = 50 cm (68th percentile), head circumference = 34 cm (54th percentile)Scalp: NormalSkin: Multiple blistering lesions over distal aspects of all limbsEyes (fundus): NormalHead: Normocephalic; normal, open, soft fontanelles; symmetric facies; patent nares; intact palate; no neck mass or crepitusOral cavity: Oral erosions present, intact palate, normal sucking and rooting reflexLungs: Clear, equal air entry and normal breath sounds; no respiratory distressCardiovascular: Normal S1, S2; regular rate and rhythm; no murmurs or gallopAbdomen: Not distended; no organomegalyGenitourinary: Normal female genitaliaSkeletal: Spine normal (no abnormal curvature, no tufts/dimple at the base of the spine)Neurological: consolable, symmetric Moro reflex, appropriate strength and tone (axial and appendicular)Hemoglobin: 16.6 g/dL (166 g/L)Platelet count: 340 × 103/μ1 (340 × 109/L)White blood cell count: 16.9 × 103/μ1 (16.9 × 109/L) with 64% neutrophils, 29% lymphocytesThyroid-stimulating hormone: 7.2 mIU/mL (normal range −1.7 to 9.1 mIU/mL)C-reactive protein: 12 mg/L (normal range <10 mg/L)Urine microscopy: no fungal hyphaeBlood culture: in processUrine culture: in processCongenital herpes simplex virusCandidiasisIncontinentia pigmentiEpidermolysis bullosaEpidermolytic ichthyosisBullous pemphigoidCongenital herpes simplex virus was excluded given the absence of fever, systemic illness, central nervous system involvement, or grouped vesicles. Candidiasis was ruled out due to absence of satellite pustules, flexural distribution, and negative fungal studies. Epidermolytic ichthyosis usually presents with widespread blistering and marked hyperkeratosis, whereas our patient had trauma-induced flaccid bullae without hyperkeratotic changes. Incontinentia pigmenti typically follows a staged evolution along Blaschko’s lines with associated ectodermal abnormalities, which were not present. Bullous pemphigoid, although reported rarely in neonates, usually shows tense blisters and urticarial plaques not observed here (Table 1). These considerations supported the diagnosis of epidermolysis bullosa, later confirmed by genetic testing.Epidermolysis bullosaNew blisters continued to appear in the postnatal period, while older lesions healed as superficial erosions without scarring. There was no granulation tissue, there were no contractures, and there was no involvement of scalp hair, eyes, genital mucosa, or oral mucosa. There were no feeding difficulties: baby was breastfeeding and taking expressed breast milk via cup (paladai feeds).Blistering was induced easily by minimal trauma. Given the onset at birth, recurrent trauma-induced lesions, and absence of systemic illness, an initial diagnosis of epidermolysis bullosa (suspected junctional type) was made. An abdominal radiograph was obtained to evaluate bowel gas pattern to screen for duodenal atresia given its association with epidermolysis bullosa. Renal ultrasonography was performed to screen for renal associations, revealing echogenic contents noted in the right kidney. Echocardiogram was also normal.The dermatology team advised cleaning the skin daily with a mild soap/cleanser and gentle application of moisturizer all over the body. Draining of blisters with a sterile needle with caution was advised. For dressing, mupirocin cream was applied, followed by nonadherent dressing (Mepitel/Mepilex), then a roller bandage. Use of soft seamless cloths was advised to avoid friction, which was accomplished by turning seams outward.On follow-up at 3 weeks (Figure 3), new lesions persisted, including perioral erosions causing feeding difficulty and poor weight gain. Genetic testing returned positive for epidermolysis bullosa dystrophica (homozygous COL7A1 mutation), which is an autosomal recessive skin disorder that presents at birth and is characterized by recurrent blisters at the level of the sublamina densa beneath the cutaneous basement membrane. It eventually results in scarring and contractures of hands, feet, and joints. Patients are even prone to develop strictures of the gastrointestinal tract from mucosal involvement, thereby leading to poor nutrition and failure to thrive. Affected individuals have an increased risk of developing aggressive squamous cell carcinoma.The same mutation (COL7A1) was detected in both parents.The clinical picture of flaccid acral blisters induced by minimal trauma, in the absence of systemic features, was most consistent with epidermolysis bullosa and confirmed by genetic testing. Epidermolysis bullosa is a group of rare genetic mechanobullous disorders caused by mutations in genes encoding structural proteins of the dermo-epidermal junction. Clinically, it manifests as blisters and erosions in response to minimal trauma.1 Incidence is estimated at 1 in 50 000 births for milder forms and 1 in 500 000 for severe forms.2 Neonatal blistering can arise from inherited disorders (epidermolysis bullosa, epidermolytic ichthyosis, incontinentia pigmenti), autoimmune conditions (neonatal pemphigoid, transient autoimmune blistering from maternal antibodies), infections (herpes simplex virus, staphylococcal scalded skin syndrome, candidiasis), or benign conditions (sucking blisters, neonatal pustular melanosis). Infections often present with systemic illness—fever, lethargy, or widespread lesions—features absent in this infant. Among inherited mimics, epidermolytic ichthyosis shows blistering with scaling and marked hyperkeratosis, while incontinentia pigmenti shows a staged evolution of lesions (vesicles → verrucae → pigmentary changes) along Blaschko’s lines, with hair, nails, and teeth. Bullous pemphigoid is rare in neonates and usually presents with tense blisters and urticarial plaques.Epidermolysis bullosa is classified according to the level of cleavage within the skin, the affected protein, and the inheritance pattern.3Epidermolysis bullosa simplex is predominantly an autosomal dominant disorder, with few recessive patterns in subtypes. Cleavage occurs within the basal keratinocytes. Blisters usually develop at friction-prone sites such as hands, feet, elbows, knees, and scalp.4 Most cases result due to mutated cytokeratin gene 5 or 14 (KRT 5) or (KRT 14). These genes code for proteins responsible for tissue integrity.Junctional epidermolysis bullosa involves separation at the dermo-epidermal junction, with the main proteins involved being laminin, type XVII collagen, and integrins. This can be severe, with blisters having an onset in the infantile period and frequent mucosal involvement.5Dystrophic epidermolysis bullosa involves protein collagen VII with separation beneath the lamina densa. The recessive form is severe, with scarring, contractures, gastrointestinal strictures, and extracutaneous features; dominant forms are generally milder.Kindler syndrome is caused by FERMT1 mutation with cleavage at multiple levels, blistering in infant age group, photosensitivity, and poikiloderma.Confirmatory diagnosis requires genetic testing, which helps confirm the exact subtype and also guides prognosis, genetic counseling, and planning for further pregnancies.Management is mainly supportive, with skin care aiming to prevent infections, gentle handling to avoid formation of blisters, and nutritional support for good weight gain.6 In addition, novel therapies—including gene therapy (eg, beremagene geperpavec), protein replacement, and stem cell–based therapies—offer hope for disease-modifying treatment in the future. Furthermore, cell-based methods, such as applying autologous genetically corrected keratinocyte grafts, have resulted in long-term skin regeneration in certain cases.7,8SummaryEpidermolysis bullosa is a rare but serious connective tissue genetic condition. Genetic heterogeneity makes prenatal diagnosis difficult. Affected neonates require precautions to minimize trauma during routine caregiving, as any minimal trauma can lead to formation of blisters. Death may occur due to secondary infection, sepsis, and poor weight gain due to poor nutrition. Hygienic care of blisters is extremely important.American Board of Pediatrics Neonatal-Perinatal Content SpecificationRecognize disorders of the skin, hair, and nails.Understand normal development of skin.
Kohli et al. (Wed,) studied this question.