Blistering eruptions are rare cutaneous manifestations of SLE that can result from two distinct mechanisms, as illustrated by the two patients described here. In the first case, vesicles resulted from a subepidermal blistering disease with an acute neutrophil-predominant infiltrate in the upper dermis, known as bullous SLE [1, 13]. In the second case, blisters developed from hydropic degeneration of the basal layer and severe edema in the upper dermis, also referred to as SLE with blisters [1, 14].
Bullous SLE is a rare, transient autoimmune bullous disease that occurs in established cases of SLE . It appears in less than 5% of patients with SLE, either in isolation or in addition to other cutaneous manifestations . This condition usually affects young females, with only eleven cases reported in children [3–13] until now.
The association of bullous SLE with lupus nephritis has been reported in adults [15–17]. It appears that the close relationship between bullous SLE and lupus nephritis is also important in children, as demonstrated by Sirka et al , Vijayalakshmi and Jayavardhana , Kumar and Agarwal , and the first of the two cases presented here.
The relationship between lupus nephritis and bullous SLE does not appear to be casual. Onetti Muda et. al  demonstrated that type VII collagen, which is usually not present in normal glomeruli, is actively synthesized and incorporated in areas of glomerular and/or tubular scarring, irrespective of the underlying disease (including SLE nephritis). These findings confirm the de novo expression of fibrillary collagens in the diseased renal extracellular matrix.
Systemic lupus erythematosus is a multisystem heterogeneous autoimmune disease and auto-antibodies directed against several components of the cell have been described. It can be hypothesized that bullous SLE develops in patients with lupus nephritis once type VII collagen deposition has occurred in an abnormal location (e.g., the kidney) and antibody production towards this abnormally located protein has been initiated. Type VII collagen is the major component of anchoring fibrils at the dermal-epidermal junction, and is the target of autoimmunity in patients with bullous SLE . There has been at least one report of bullous eruption as the first clinical sign of SLE relapse  suggesting that skin damage can be a marker of disease activity.
The second patient described in this report developed SLE with blisters, which is also a rare manifestation of SLE both in adults and children. The actual incidence of this condition is difficult to ascertain, especially because some cases are reported under the term 'bullous SLE', even when the patients do not have the typical autoimmune blistering disease with acute neutrophilic upper dermal infiltrate and subepidermal separation, as well as positive direct immunofluorescence tests. However, of the 148 pediatric SLE cases that have been examined in our lupus clinic over the last 8 years, this is our first incidence of SLE with blisters.
As opposed to bullous SLE, SLE with blisters has not been associated with specific systemic lupus manifestations and therefore does not necessarily imply a worse prognosis. This LE-specific lesion represents a severe dermo-epidermal edema, which is not directed towards specific antigens.
The differential diagnosis of blistering eruptions in patients with SLE includes dermatitis herpetiformis and bullous pemphigoid which are clinically similar but can be differentiated by direct immunofluorescence. Bullous lesions in SLE due to photosensitivity, acute lupus or drugs can be differentiated by both histopathology and immunopathology. Epidermolysis bullosa acquisita (EBA) is histopathologically and immunopathologically identical since both are mediated by circulating antibodies against type VII collagen. However, a dramatic therapeutic response to dapsone in bullous SLE differentiates it from EBA . When in a linear disposition, herpes zoster can be considered in the differential, but it can be easily differentiated by histopathology .
It seems contradictory that the patient with bullous SLE continued to thrive, whereas the patient with SLE with blisters, which are apparently not associated with any further risk, had a fatal clinical course. However, the cause of death in the latter case could be related to an APS relapse when the patient developed what has been called "catastrophic APS" after low-dose aspirin was inadvertently withdrawn. There were no other signs or symptoms of SLE disease activity, cyclophosphamide had been stopped, and the prednisone dose was low. Therefore, the patient had a low risk of developing a septic event due to the immunosuppressive effects of medical treatment.