Autoimmune dermatoses represent a complex and rare group of blister-forming skin conditions caused by the body’s immune system mistakenly targeting its own structural skin proteins. These diseases predominantly affect the outer layers of the skin and mucous membranes, resulting in significant patient discomfort and clinical challenges. Central to these conditions is the formation of autoantibodies against key proteins responsible for maintaining skin integrity.

What Are Bullous Autoimmune Dermatoses?

Bullous autoimmune dermatoses are characterised by the presence of blisters and erosions on the skin or mucosa due to autoantibody-mediated disruption of cell adhesion structures. The affected proteins play a critical role in maintaining the cohesion between skin cells (keratinocytes) and anchoring the epidermis to the dermis. Based on the specific target antigens and blister location, these conditions are categorised into four main groups:

• Pemphigus diseases – associated with autoantibodies against desmoglein 1 (Dsg1), desmoglein 3 (Dsg3) and plakins such as envoplakin.
• Pemphigoid diseases – characterised by autoantibodies targeting BP180, BP230, laminin 332 and P200.
• Epidermolysis bullosa acquisita (EBA) – marked by autoantibodies against collagen type VII.
• Dermatitis herpetiformis (DH) – linked to antibodies against endomysium (tissue/epidermal transglutaminase) and deamidated gliadin peptides (e.g., GAF-3X).

Each condition presents unique clinical and immunological features, requiring specific diagnostic approaches to ensure accurate identification and treatment.

Diagnostic Approach

Diagnosis of autoimmune blistering diseases relies on a combination of clinical assessment and serological testing. Two main types of autoantibodies are typically evaluated:

1. Tissue-bound autoantibodies – Detected through direct immunofluorescence (DIF), typically from a perilesional biopsy.
2. Circulating autoantibodies – Identified using indirect immunofluorescence testing (IIFT) and specific antigen assays.

IIFT is commonly performed using tissue sections of primate oesophagus or tongue to detect antibodies against prickle cell desmosomes and basement membrane antigens. For more detailed analysis, primate salt-split skin can be used to distinguish autoantibodies targeting different components of the basement membrane zone.

To pinpoint the specific target antigen, additional testing methods such as monospecific ELISA and immunoblot analyses are employed.

Disease-Specific Markers and Monitoring Tools

• Bullous Pemphigoid (BP)
  BP patients typically produce autoantibodies against BP180 and, less frequently, BP230. The Anti-BP180-NC16A-4X ELISA (IgG) and Anti-BP230-CF ELISA (IgG) serve dual roles: they confirm diagnosis and enable disease monitoring. Notably, BP180 autoantibody levels correlate with disease activity, while BP230 levels reflect disease duration.
• Pemphigus Vulgaris and Pemphigus Foliaceus
  These are identified through the presence of autoantibodies against desmoglein 1 and 3. Both IIFT and ELISA using recombinant Dsg1 and Dsg3 antigens offer reliable detection, with antibody titres often correlating with disease severity and treatment response.
• Paraneoplastic Pemphigus (PNP)
  Detection of autoantibodies against envoplakin supports the diagnosis of PNP and helps distinguish it from other pemphigus variants.
• Epidermolysis Bullosa Acquisita (EBA)
  Confirmed by detecting autoantibodies against collagen type VII, EBA can be differentiated from other subepidermal blistering diseases through targeted serological testing.

Conclusion

Autoimmune dermatoses, though rare, require timely and accurate diagnosis to guide effective patient care. Advances in immunodiagnostic testing – including IIFT, ELISA and immunoblotting – allow for detailed characterisation of the underlying autoantibody profile, enabling clinicians to distinguish between disease subtypes and monitor therapy progress. As our understanding of these complex conditions evolves, so too does our ability to offer targeted, patient-specific diagnostics and care.