Epidermolysis bullosa can broadly be separated into 4 major types and numerous subtypes according to the plane of blistering within the skin, in addition to the pattern of involvement and clinical severity. Severe generalized RDEB (previously known as Hallopeau-Siemens) is one of the most severe forms with an overall mortality rate of 8% during childhood . The most common reported causes of death in childhood include sepsis and severe failure to thrive, while in the adolescent and adult population cutaneous squamous cell carcinoma accounts for the substantial majority of deaths, usually in the third to fifth decades. Other less common causes of death include renal failure and cardiomyopathy. Multidisciplinary care with early treatment of infections, optimizing nutrition and a wide variety of supporting services has improved the quality of life and survival rates over the past decade .
Nevertheless, clinical assessment and management of these patients remains challenging, especially as in our case additional nosological entities complicate the course of their illness. The presentation of persistent hip pain in a previously healthy child can pose a diagnostic dilemma with oligoarticular JIA being one of the possible diagnoses. In our patient there was a delay from initial onset of symptoms to establishing the diagnosis. Pain is also inevitable with this severe type of EB coupled with limitation of mobility from contractions and skin wounds. Additionally, the treatment with prednisolone and sulfasalazine for her IBD and regular use of NSAID for analgesia may have masked a more striking presentation. IBD arthropathy could be the cause of her joint symptoms; however the persistent oligoarticular pattern of presentation, the destructive form of arthritis, and the high ANA titers pointed towards a distinct diagnosis of JIA. Additionally, joint flare-ups persisted while bowel disease was in remission .
The routine approach to any patient presenting with monoarthritis of the hip would include synovial fluid aspiration +/- synovial biopsy. In this case the increased risk of secondary septic arthritis or sepsis in general precluded any intervention other than a therapeutic one; diagnosis was based on clinical and radiological findings alone.
With regards to treatment, although our patient had a common form of JIA, oral methotrexate failed to control her arthritis either because of innate disease resistance or inadequate gastrointestinal absorption. Oral instead of subcutaneous route was chosen based on family's preferences.
Introduction of anti-TNF-α biologics has altered the therapeutic approach to inflammatory conditions, over the last decade. The use of infliximab, a chimeric partly humanized monoclonal antibody, is well established in the treatment of both IBD and JIA in children. Placing a permanent intravenous catheter in a patient with DEB is very likely to have detrimental results given the high risk of secondary infection and sepsis. Adalimumab, a fully humanized IgG1 anti-TNF-α monoclonal antibody, is an approved drug for the treatment of JIA. Its use in IBD in adults is well documented and it has been recently reported as a safe and effective treatment for children with Crohn's disease . In our case, it was considered as a safe alternative given its benefit for subcutaneous administration.
The patient remains asymptomatic for over 12 months and both her IBD and arthritis are well controlled. Nevertheless, immunological long-term complications of anti-TNF-α biologics are yet to be determined. Additionally, the long term risk of developing skin cancer reported in adults on anti-TNF treatment needs to be kept in mind especially in this case since patients with RDEB are more prone to epithelial squamous cell carcinomas; hence closed surveillance with regular skin examination is required.
The occurrence in our patient of RDEB, IBD and JIA is difficult toexplain. Acquired EB has been linked with autoimmune conditions suchas IBD, rheumatoid arthritis, and Hashimoto's thyroiditis with the pathophysiological mechanism involving production of IgG antibodies against an epitope of collagen type VII, the main component of anchoring fibrils at the dermo-epidermal junction (DEJ), and the mutated protein in dystrophic forms of EB . Even in the absence of collagen VII in the joints, molecular mimicry might explain why these patients develop autoimmune arthritis. Similarly, in our case, it may be that fragility at the DEJ in RDEB leads to exposure of normally hidden autoantigens that subsequently trigger an immune reaction in other tissues including the joints.