Epidermolysis bullosa and inherited blistering disorders — short-answer questions

Question 1 (10 marks)

Outline the differential diagnosis of blistering at birth, state the most likely inherited epidermolysis bullosa subtype suggested by the hoarse cry and periorificial pattern, and describe how you would confirm the diagnosis and classify the disease. [1]

Question 1 — model answer

The neonatal blistering differential is wide and dangerous, and a structured approach avoids missing a treatable mimic while securing the inherited diagnosis. Staphylococcal scalded skin syndrome causes widespread tender superficial peeling around flexures and orifices driven by a staphylococcal exotoxin, rather than the friction-localised erosions of this infant. Neonatal herpes simplex produces grouped vesicles on an erythematous base with systemic illness. Incontinentia pigmenti is an X-linked dominant disorder, lethal in males, with a vesicular blaschkoid stage along the lines of Blaschko. Bullous impetigo is culture-positive and pustular, and aplasia cutis congenita is a localised area of absent skin at the scalp vertex without ongoing friction blistering. [5]

The combination of blistering at birth that tracks friction, periorificial granulation tissue and a hoarse cry points to junctional EB generalised severe, formerly Herlitz. The hoarse cry signals laryngeal granulation tissue, which can obstruct the airway, and the periorificial granulation around the mouth, nose, eyes and nail folds is characteristic. The lack of family history is typical because junctional EB is autosomal recessive, so each unaffected parent carries one silent copy. [5]

Confirmation rests on a skin biopsy taken correctly, because the wrong specimen invalidates the result. The clinician induces a fresh blister by gentle rotation or rubbing of unaffected skin, biopsies across the edge of the new lesion within twenty-four hours, and sends it in Michel's medium for immunofluorescence antigen mapping and in glutaraldehyde for electron microscopy. Immunofluorescence mapping with antibodies against laminin-332, type IV collagen, type VII collagen and type XVII collagen localises the cleavage level to the lamina lucida and reveals whether the protein is reduced or absent. Genetic testing with an EB gene panel then confirms the responsible mutation in LAMA3, LAMB3, LAMC2 or COL17A1, anchours genetic counselling and supports prenatal diagnosis in future pregnancies. [1]

Question 2 (10 marks)

A separate 16-year-old with severe generalised recessive dystrophic EB presents with a chronic wound on the right lower leg that has enlarged and become nodular over three months despite meticulous atraumatic dressings. Discuss the likely diagnosis, the surveillance strategy in recessive dystrophic EB, and the principles of lifelong multidisciplinary management. [10]

Question 2 — model answer

The likely diagnosis is cutaneous squamous cell carcinoma arising in a chronic wound of recessive dystrophic EB. National EB Registry data established that squamous cell carcinoma arises at a young age in this subtype, recurs after excision, metastasises early, and is the leading cause of death. A chronic wound that enlarges, becomes nodular or simply fails to heal on schedule is squamous cell carcinoma until biopsy proves otherwise, so the immediate action is a prompt tissue biopsy rather than continued empirical dressings. [10]

The surveillance strategy is systematic and lifelong. From early adolescence, every patient with severe generalised recessive dystrophic EB undergoes full-skin examination by a clinician experienced in EB every three to six months, with a low threshold to biopsy any suspicious, non-healing, ulcerated or nodular lesion. Early detection allows wide local excision, which remains the mainstay because the tumours are radioresistant and metastasise early. The clinician also screens for recurrence after excision and for metastatic disease, and counsels the young person about the warning signs so that delay is minimised. [10]

Lifelong management is built on atraumatic handling as its foundation. Every contact avoids adhesive tape, slides nothing across the skin, secures lines with soft silicone or no tape, and dresses wounds with non-adherent contact layers, an absorbent secondary layer and a soft conforming bandage. Pain is treated multimodally before every dressing change. Nutrition is supported with a high-calorie high-protein diet, iron and zinc, and gastrostomy feeding when oesophageal stricturing defeats oral intake. Hand surgery releases pseudosyndactyly, balloon dilation relieves oesophageal strictures, and for eligible patients the topical COL7A1 gene therapy beremagene geperpavec improves wound healing. The whole plan is coordinated by a multidisciplinary team spanning dermatology, surgery, genetics, nutrition, pain, dentistry and psychology, with a structured transition into adult EB services. [7]