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A case is presented of a patient who was referred to the rheumatology department with symptoms of systemic lupus erythematosus and bullous disease. A 55-year-old woman with 2 year history of blistering involving the hands and face, presented with new lesions on the thorax, feet, toes, inferior lip, and tongue accompanied by pruritus. The patient also had joint pain without inflammation of the knees, ankles, and hands. After the investigations the patient was diagnosed with a blistering disorder, specifically epidermolysis bullosa acquisita. The patient completely recovered following treatment with topical and oral corticosteroids, and colchicine.
This case shows the difficulties that clinicians sometimes encounter when differentiating between two autoimmune diseases that present with skin lesions, especially when it comes to ruling out the possibility of SLE. The patient was referred to the rheumatology department with symptoms of systemic lupus erythematosus (SLE) and bullous disease. Although the patient did not fulfil the criteria for SLE, and a diagnosis of epidermolysis bullosa acquisita (EBA) was made, the possible future development of SLE in this patient should not be excluded.
A 55-year-old woman, with a 2 year history of blistering involving the hands and face, presented with new lesions on the thorax, feet, toes, inferior lip, and tongue accompanied by pruritus (fig 1). The patient also had joint pain without inflammation of the knees, ankles, and hands. Laboratory tests were as follows: haemoglobin 8.5 g/dl; white cell count 1.7–3.7×103/mm3; erythrocyte sedimentation rate (ESR) 100 mm/h. Antinuclear antibody (ANA) was 3+ with a speckled pattern; the rheumatic factor test was negative. The complement components C3 and C4 were slightly low; anti-Sm, anti-DNA, and anti-La antibodies were negative, but anti-RNP and anti-Ro antibodies were 2+. After the investigations the patient was diagnosed with a blistering disorder, specifically epidermolysis bullosa acquisita (EBA).
Routine histologic examination of a lesion on the right arm showed subepidermal blister formation with underlying dermal fibrosis and a sparse perivascular and interstitial lymphocytic infiltrate. Direct immunofluorescence of perilesional skin revealed linear homogenous deposition of C3 and IgG on the dermoepidermal junction. At that time, the split skin examinations were not available. Ultrasonography of the abdomen, computed tomography scan of the thorax, and bone marrow biopsy were normal.
Differential diagnoses include bullous pemphigoid (BP), bullous SLE, and the combination of EBA and SLE. EBA associated with SLE is characterised by the presence of the criteria for EBA and American Rheumatism Association (ARA) criteria for SLE. Bullous SLE presents with blisters in the skin in patients with SLE, typically young adults in the second and fourth decade of life. Finally, BP patients show tense blisters with cutaneous involvement without mucosal involvement. There are several presenting forms, including vesicular, vegetative, generalised erythroderma, urticarial, and nodular variants. The histology shows subepidermal bulla with inflammatory eosinophil predominant infiltrate, also containing lymphocytes and neutrophils.
The patient was treated with topical and oral corticosteroids, and colchicine.
The patient recovered completely and did not return for follow-up after she left the hospital.
There are five clinical presentations of EBA: “classical”; BP-like presentation; cicatricial pemphigoid (CP)-like presentation; Brunsting–Perry pemphigoid-like presentation; and linear IgA bullous dermatosis (LIA)-like disease.1,2 The case presented here might correspond to the classical form of EBA, which presents as a mechanobullous non-inflammatory disease. This is characterised by skin fragility over trauma prone surfaces with blisters, erosions, scars, and milia formation occurring over the back of the hands, knuckles, elbows, knees, sacral area, and toes.2 The patient presented with blisters, erosion, scars and milia on the back of her hands and knuckles (fig 1).
EBA is also characterised by the presence of autoantibodies to type VII collagen, which is a 290 kDa collagenous protein within the dermal–epidermal junction.1,2 This protein represents the α chain of type VII collagen.1
Current immunopathologic criteria of bullous SLE are similar to those of EBA and include: immunoglobulin and complement deposition at the basement membrane zone (BMZ) on direct immunofluorescence (DIF), and immune deposits ultrastructurally localised on or beneath the lamina densa.3 Although both EBA and bullous SLE are autoimmune diseases, and often have a common human leucocyte antigen (HLA) major histocompatibility (MHC) class II cell surface protein, HLA-DR2, the extent of the relationship between them is not known, although patients with both diseases have been reported.4 In these cases is important for the clinician to differentiate between the classical presentation of EBA alone or associated with SLE and bullous SLE. The bullous SLE patient must fulfil the ARA criteria for SLE. Although bullous SLE typically affects young adults in the second and fourth decade of life, some cases have been observed in older patients, and could be the initial manifestation of SLE.5,6 Bullous SLE was initially defined as a non-scarring bullous disease, as in the vast majority of patients, skin fragility, mechanobullous lesions, scarring, and milia—characteristic of the classical variant of EBA—are absent; however, several cases of bullous SLE have been reported presenting with features of classical EBA.5
The first diagnostic criterion for bullous SLE was proposed in 1983 and more than 70 cases with bullous SLE have been reported in the literature. The incidence of bullous SLE among SLE patients has been reported at between 1.5–3%.5,6
There are several possible mechanisms for autoantibody induced blister formation in bullous SLE: (1) autoantibodies bound to type VII collagen may interfere with the normal interactions between type VII collagen and its extracellular matrix ligands in the BMZ or the papillary dermis, resulting in defective lamina densa–dermal adhesion; (2) autoantibodies bound to the NC2 domain may destabilise anchoring fibrils leading to epidermal–dermal disadherence; and (3) autoantibodies may produce complement dependent inflammatory tissue damage.5
Another possible diagnosis was BP. BP is a chronic, autoimmune blistering disease that primarily affects the skin.7,8 The incidence of BP has been reported to be 6–10 cases per million.1 The mean age of onset is 65 years and it affects both genders equally. Patients with BP present with tense blisters with cutaneous involvement. Mucosal involvement is rare. These blisters are usually distributed in the upper and lower extremities, groin, axilla, and abdomen. Bullous pemphigoid may present in several forms, including vesicular, vegetative, generalised erythroderma, urticarial, and nodular variants.7,8
The treatment of EBA either alone or in association with other diseases can be challenging and difficult. Patients with EBA have been treated initially with high dose systemic corticosteroids in combination with dapsone, phenytoin, gold, or colchicine. Immunosuppressive agents, including methotrexate, azathioprine, cyclophosphamide, and cyclosporine, have been used with minimal success, especially in EBA patients with the classical mechanobullous form.9 Other treatment modalities include plasmapheresis, extracorporeal photochemotherapy, cyclosporine at high doses (>6 mg/kg), and intravenous immunoglobulins.1,9 However, the most important treatment is wound care and antibiotics for skin infection, and avoidance of exacerbating factors such as trauma and sun exposure.9
Competing interests: None.
Patient consent: Patient/guardian consent was obtained for publication.