Severe RDEB
In severe RDEB, blisters are present at birth or become apparent in the neonatal period. Aplasia cutis congenita, especially of the extremities, may be found in the newborn period. Blisters can affect the whole body, including the skin, oral mucosa, esophageal mucosa, and corneas, as early as the newborn period. Chronic non-healing wounds and secondary infection are common, often with Staphylococcus, Pseudomonas, and Streptococcus. Many individuals develop large, irregular brown patches that histologically comprise collections of nevus cells and are called epidermolysis bullosa (EB) nevi [Lanschuetzer et al 2010]. No instances of melanoma arising in these nevi have been reported to date.
Squamous cell carcinoma (SCC). The lifetime risk of SCC is greater than 90% with significant metastatic potential [Fine et al 2009]. SCC usually appears in the third decade but can appear as early as the second decade [Ayman et al 2002]. Affected individuals often succumb to aggressive metastatic SCC [Mellerio et al 2016, Bonamonte et al 2022, Hwang et al 2024]. Satisfactory treatment is currently not available.
Oral involvement may lead to fusion of the tongue to the floor of the mouth (ankyloglossia), progressive diminution of the size of the oral cavity and mouth opening (microstomia), and poor dental hygiene and caries [Krämer et al 2012]. Individuals with RDEB lack lingual papillae [Krämer et al 2020].
Gastrointestinal. Esophageal blisters and erosions as well as webs and strictures can cause severe dysphagia [Azizkhan et al 2006, Mortell & Azizkhan 2010], and strictures can require dilation [Pope et al 2020]. Rarely, affected individuals can have esophageal disease with few or no skin manifestations. Gastroesophageal reflux disease is also common. Anal erosions, poor intake of fluid and fiber, and use of opioid analgesics contribute to frequent severe constipation.
Malnutrition caused by poor intake and an increased nutritional demand for tissue healing can result in growth restriction in young children and absent or delayed puberty in older children. Osteopenia/osteoporosis are not uncommon. Vitamin and mineral deficiencies can occur, especially with iron, zinc, carnitine, selenium, vitamin A, and vitamin D [Haynes 2010].
Anemia results from poor iron intake and/or absorption of iron as well as anemia of chronic disease with bone marrow suppression [Liy-Wong et al 2023, Tarango et al 2023].
Ocular. Corneal erosions can lead to scarring and loss of vision [Matsumoto et al 2005].
Cardiac. Dilated cardiomyopathy, sometimes associated with selenium and carnitine deficiency, has been reported in RDEB and can be fatal in some individuals [Lara-Corrales et al 2010, Ryan et al 2016].
Urologic / kidney function. Rarely, urethral erosions, strictures, bladder dysfunction, and glomerulonephritis can occur, sometimes leading to kidney failure [Fine et al 2004, Hughley et al 2020].
Orthopedic. Individuals with RDEB can develop contractures and pseudosyndactyly (fusion) of the fingers with consequent impairment of function and decreased quality of life [Eismann et al 2014]. Although fusion of the toes is not detrimental to function, painful blistering and progressive contractures of the foot and ankle as well as the larger joints (knees, hips, neck) can interfere with ambulation and function.
Endocrine. Delayed puberty is not uncommon and is often associated with osteopenia, osteoporosis, and vitamin D deficiency [Wasserman et al 2023]. Poor bone health results from poor nutrition, lack of exposure to adequate sunlight, and inactivity [Martinez & Mellerio 2010, Rodari et al 2017].
Psychosocial. Severe stress may affect the affected individual and family because of the complications of this disorder and the chronic pain endured by most individuals with EB. Quality of life can be decreased, and psychosocial disorders including anxiety, depression, and drug dependence/abuse may occur in older persons [Frew & Murrell 2010] – although a recent study showed that pain in individuals with DEB is not correlated with anxiety or depression [Fortuna et al 2016].