Diagnosis Of Epidermolysis Bullosa Acquisita Research Articles

U-serrated immunodeposition pattern differentiates type VII collagen targeting bullous diseases from other subepidermal bullous autoimmune diseases.

Epidermolysis bullosa acquisita (EBA) can be differentiated from other subepidermal bullous diseases by sophisticated techniques such as immunoelectron microscopy, salt-split skin antigen mapping, fluorescence overlay antigen mapping, immunoblot and enzyme-linked immunosorbent assay. To determine whether the diagnosis can also be made by routine direct immunofluorescence microscopy. We studied frozen skin biopsies from 157 patients with various subepidermal immunobullous diseases. We found three distinct 'linear' fluorescence patterns at the basement membrane zone: true linear, n-serrated and u-serrated. The true linear pattern, often seen in conjunction with either the n- or the u-serrated pattern, was found in any subepidermal immunobullous disease with nongranular depositions. In bullous pemphigoid, mucous membrane pemphigoid, antiepiligrin cicatricial pemphigoid, p200 pemphigoid and linear IgA disease the n-serrated pattern was found, corresponding with depositions located in hemidesmosomes, lamina lucida or lamina densa. However, in EBA and bullous systemic lupus erythematosus the u-serrated staining pattern was seen, corresponding with the ultralocalization of type VII collagen in the sublamina densa zone. The diagnosis of EBA with IgG or IgA autoantibodies directed against type VII collagen was confirmed by immunoelectron microscopy, salt-split skin antigen mapping, fluorescence overlay antigen mapping or immunoblotting. Using this pattern recognition by direct immunofluorescence microscopy we discovered several cases of EBA which would otherwise have been erroneously diagnosed as a form of pemphigoid or linear IgA disease.

Epidermolysis bullosa acquisita–like reaction associated with penicillamine therapy for sclerodermatous graft-versus-host disease

A case of a bullous eruption occurred in a patient being treated with penicillamine for sclerodermatous graft-versus-host disease following bone marrow transplantation. After 7 days of treatment with 150 mg penicillamine, a painful bullous eruption with accompanying purpuric lesions suddenly developed in previous sclerodermatous infiltrations. A diagnosis of epidermolysis bullosa acquisita–like eruption was made, and the patient was treated with drug withdrawal and administration of cyclosporine and methylprednisolone. Epidermolysis bullosa acquisita–like reaction is an extremely rare cutaneous side effect of penicillamine. The surprisingly early onset of this eruption in lesions of sclerodermatous graft-versus-host disease might have been due to severe immune alteration.

Management of epidermolysis bullosa acquisita

By all accounts, epidermolysis bullosa acquisita (EBA) is a very rare chronic subepidermal blistering disease which involves the skin and mucous membranes. The disease can appear in childhood, but has a wide age range with no sex, racial or ethnic group predilection. There is an absence of family or personal history of any blistering diseases. There is a developing association of the HLA-DR2 allele and some of these cases can have enhanced susceptibility to bullous SLE. Other disease associations with EBA include inflammatory bowel disease, amyloidosis, myeloma, thyroiditis, diabetes and multiple endocrinopathy syndrome. EBA often presents with skin fragility and blistering that is usually trauma induced, so that the elbows, knees, knuckles, fingers and fingernails tend to be affected. The lesions heal with scarring and milia formation. However, some cases of EBA can have a clinical phenotype, similar to bullous pemphigoid, with widespread inflammatory vesicles and bullae. Other cases may present similarly to cicatricial pemphigoid with involvement of the eyes, mouth and genital areas. The severity of EBA varies, indicating a rather heterogenous nature. Milder cases undoubtedly occur and some of these go into spontaneous remission, but very severe cases can lead to blindness, oesophageal strictures and anal stenosis and be very incapacitating. The diagnosis of EBA can be confirmed by salt-split immunofluoresence procedures where the BMZ antibodies bind to the dermal side of the split. Ideally, one wishes to identify type 7 collagen by Western blot analysis, ELISA or immunoelectron microscopy. EBA can be a very frustrating and difficult disease to treat. In our experience, EBA can show great heterogeneity in the response to therapy. Some cases appear mild and respond to low dose prednisolone with dapsone, 50–100 mg daily. More moderately severe cases require prednisolone, azathioprine or cyclosporin. There are, undoubtedly, very severe cases which appear to be resistant to all of the above therapies. It is not advised that very high dose oral corticosteroids he administered in EBA, as often this is ineffective and leads to crippling steroid side-effects. For very resistant or severe cases, the use of oral mycophenolate mofetil can be recommended. Some cases may respond to IV pulses of prednisolone and cyclophosphamide and others, to IVIG infusions. Unfortunately, because of the rarity of the disease, no exact therapeutic policy has been established and each case requires consideration on its merits. Management of cases with severe ocular, oesophageal or genital involvement is best done within a specialized centre which includes facilities for endoscopic techniques for strictures.

Diagnostic Value of Indirect Immunofluorescence on Sodium Chloride-Split Skin in Differential Diagnosis of Subepidermal Autoimmune Bullous Dermatoses

To determine the diagnostic value of indirect immunofluorescence on sodium chloride-split skin (SSS) in differentiating the pemphigoid group of subepidermal autoimmune bullous dermatoses, including bullous pemphigoid (BP), cicatricial pemphigoid, and pemphigoid gestationis, from epidermolysis bullosa acquisita (EBA). Serum samples were tested using immunofluorescence on SSS and immunoblot assay on epidermal and dermal extracts, a recombinant protein corresponding to the C-terminal end of the 230-kd BP antigen, and purified laminin-5. An immunodermatology laboratory. One hundred forty-two serum samples from patients with BP (n = 98), cicatricial pemphigoid (n = 23), pemphigoid gestationis (n = 10), EBA (n = 10), and anti-type IV collagen (n = 1). Binding sites of serum to the epidermal and/or dermal sides of SSS were correlated with their antigenic specificities. Epidermal staining on SSS was highly specific for pemphigoid. Alternatively, a poor correlation was found for the dermal-reacting serum samples and the diagnosis of EBA; of the 19 serum samples with dermal staining on SSS, only 10 reacted with the EBA antigen. The remaining serum samples were from patients with cicatricial pemphigoid having antibodies to the alpha 3 or beta 3 chains of laminin-5 (n = 5) or patients with BP having antibodies to the 180-kd BP antigen (n = 2). One sample recognized exclusively a 185-kd dermal antigen corresponding to type IV collagen. One more BP serum sample with dermal staining did not recognize any dermal or epidermal antigen. In case of immunofluorescent dermal staining, the precise diagnosis should be confirmed by identification of the involved antigen, since it may reveal antibodies to laminin-5 or type XVII or IV collagen, in addition to the EBA antigen.

Epidermolysis bullosa acquisita: Efficacy of high-dose intravenous immunoglobulins

A 16-year-old boy had a 6-year history of a generalized bullous eruption that was resistant to multiple therapies. Findings of immunofluorescent split-skin studies and electron microscopy were consistent with a diagnosis of epidermolysis bullosa acquisita. Treatment with cyclosporine and prednisolone decreased new blister formation. Additional therapy with high-dose intravenous immunoglobulins was successful in controlling the patient's disease.

Epidermolysis bullosa acquisita: Efficacy of high-dose intravenous immunoglobulins

A 16-year-old boy had a 6-year history of a generalized bullous eruption that was resistant to multiple therapies. Findings of immunofluorescent split-skin studies and electron microscopy were consistent with a diagnosis of epidermolysis bullosa acquisita. Treatment with cyclosporine and prednisolone decreased new blister formation. Additional therapy with high-dose intravenous immunoglobulins was successful in controlling the patient's disease.

Location of basement membrane Type IV collagen beneath subepidermal bullous diseases

Using standard immunohistochemical methods, routinely processed sections, and a polyclonal antibody to Type IV collagen, we have determined the location of Type IV collagen, a substance located in the lamina densa of basement membrane, in a spectrum of acquired subepidermal bullous diseases. Type IV collagen was attached to the blister roof in five cases of well-established epidermolysis bullosa acquisita and to the blister base in 25 cases of bullous pemphigoid, four cases of dermatitis herpetiformis and 12 cases of porphyria cutanea tarda. Immunohistochemical localization of Type IV collagen in epidermal-dermal basement membrane is a simple, rapid and reliable technique which can be utilized to exclude and possibly to confirm the diagnosis of epidermolysis bullosa acquisita in routinely fixed paraffin-embedded tissues.

Immunofluorescence on salt-split skin for the diagnosis of epidermolysis bullosa acquisita

Immunofluorescence on salt-split skin for the diagnosis of epidermolysis bullosa acquisita

Epidermolysis Bullosa Acquisita and Crohn's Disease

A review of the literature shows that the association of epidermolysis bullosa acquisita and Crohn's disease is rare. A 27-year-old man developed cutaneous blisters on the trauma-prone areas that were consistent with the diagnosis of epidermolysis bullosa acquisita. Immunological and electron-microscopic studies of the skin showed intense IgG deposits located beneath the basal lamina. Three years later, Crohn's colitis was diagnosed. Prednisolone and sulfasalazine treatment resulted in an improvement of the bowel disease but without appreciable effect on the skin lesions.

Localization of bullous pemphigoid antibody--an indirect immunofluorescence study of 228 cases using a split-skin technique.

We have re-examined the site of deposition of IgG anti-basement membrane zone antibodies in 228 sera from suspected cases of bullous pemphigoid (BP), using 1.0 M sodium chloride split-skin as substrate for indirect immunofluorescence. Nine sera (4%) produced fluorescence on the floor of the split suggesting sub-basal lamina antibody deposition compatible with a diagnosis of epidermolysis bullosa acquisita (EBA). This ultrastructural localization was confirmed in only three of these nine by immuno-electron microscopy. Clinical details were available on six of these nine cases, and none had clinical features suggesting EBA. We have found the split-skin immunofluorescence technique unhelpful in identifying 'missed' cases of EBA. The prevalence of EBA presenting as BP would appear to be very low indeed in the U.K.

Childhood Epidermolysis Bullosa Acquisita

A 5 1/2-year-old girl with a blistering disease involving the skin and the oral, ocular, and anogenital mucosa is described. The initial clinical, histologic, and immunofluorescence findings suggested a diagnosis of cicatricial pemphigoid. However, immunoelectron microscopy demonstrated linear deposits of several immunoreactants within the sub-lamina densa region of the dermoepidermal junction, consistent with the diagnosis of epidermolysis bullosa acquisita. Although epidermolysis bullosa acquisita is considered a disease of adult onset, it should be included in the differential diagnosis of blistering diseases in children.

The Spectrum of Epidermolysis Bullosa Acquisita

A patient has an acquired, scarring, bullous eruption. The severity of the cutaneous, ocular, esophageal, and laryngeal scarring was suggestive of cicatricial pemphigoid or the severely dystrophic forms of epidermolysis bullosa. Clinical features and histologic and immunofluorescence and electron microscopic study led to the diagnosis of epidermolysis bullosa acquisita. The spectrum of epidermolysis bullosa acquisita includes cases that closely approximate the severity of disease previously recognized only for the recessive form of epidermolysis bullosa dystrophica.