Rare Case of Genetic and Autoimmune Subtypes of EB Described in Report

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by Alice Melao |

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genetic and autoimmune DEB

A rare case of autoimmune-driven epidermolysis bullosa (EB) was described in a patient who also had an undiagnosed mild genetic subtype of the disease.

The case study, “Epidermolysis Bullosa (EB) Acquisita in an Adult Patient with Previously Unrecognized Mild Dystrophic EB and Biallelic COL7A1 Mutations,” was published in the journal Acta Dermato-Venereologica.

A 33-year-old woman arrived at a clinic in Italy with a seven-year history of bullous skin mainly affecting the hands, feet, elbows, and knees.

A physical exam revealed that she had some blisters, erosions, and scars on her hands and knuckles, as well as painful erosions on her mouth.

She also reported progressive nail degeneration since early childhood that only affected her big toes. But this particular manifestation was diagnosed as a fungal infection at a different hospital and was not investigated further.

Based on the persistent clinical manifestations, physicians suspected she had mechanobullous epidermolysis bullosa acquisita (EBA) — a rare autoimmune disease characterized by the overproduction of antibodies that attack collagen VII molecules.

But the diagnosis of a mild form of dystrophic epidermolysis bullosa (DEB), a genetic form of the disease characterized by abnormal production of collagen type VII, could not be ruled out.

Skin biopsies revealed normally structured tissues, with collagen VII levels within the normal range. However, a reduced number of anchoring elements was detected, which could help explain the fragility of the skin. Also, tissue samples collected from skin regions close to lesions showed the accumulation of antibodies.

Blood tests revealed the patient had about 6.8 times higher levels of autoantibodies targeting collagen VII. This finding confirmed the final diagnosis of mechanobullous EBA.

Further analysis also revealed additional autoantibodies that were reactive against other structural elements of the skin, including laminin chains and collagen type XVII.

At the same time, the team conducted a genetic study focused on the genes known to be linked to epidermolysis bullosa. They found that the patient had two genetic mutations on the COL7A1 gene — one inherited from the father and the other from the mother.

The paternal COL7A1 variant had been previously reported and linked to the disease, but the maternal genetic variant had never been identified.

The team then conducted several experiments to assess the potential damaging effect of these mutations. They found that the maternal COL7A1 variant might have no effect on the production of collagen VII protein, but could lead to a shorter version of the protein, meaning the genetic mutation had a “leaky” effect.

Considering all the data, clinicians concluded the patient had the “nails-only” subtype of recessive DEB during childhood and developed EBA in adulthood.

The team believes that regular antibody analysis in patients who present worsening skin fragility “may reveal additional examples of DEB and EBA overlap.” Recognizing such coincidences may have important therapeutic implications, they added.