What are the differences in skin manifestations between hemidesmosomes and desmosomes-related diseases?

From the Guidelines

Hemidesmosome defects are associated with subepidermal blistering diseases, such as bullous pemphigoid, whereas desmosome defects lead to intraepidermal blistering diseases, like pemphigus vulgaris. Hemidesmosomes and desmosomes are both cellular adhesion structures that, when disrupted, cause distinct skin diseases. Hemidesmosome defects typically lead to various forms of epidermolysis bullosa, particularly epidermolysis bullosa simplex and junctional epidermolysis bullosa, characterized by skin fragility and blister formation at the dermal-epidermal junction. These conditions result from mutations in genes encoding hemidesmosomal proteins like plectin, BP180, and integrin α6β4, which anchor basal keratinocytes to the basement membrane [ 1 ]. In contrast, desmosome defects cause pemphigus diseases, including pemphigus vulgaris and pemphigus foliaceus, where autoantibodies target desmosomal proteins like desmogleins, disrupting keratinocyte-to-keratinocyte adhesion and causing intraepidermal blistering [ 2 ].

Some key points to consider:

• Hemidesmosome defects are associated with subepidermal blistering, and treatment focuses on wound care and prevention of trauma.
• Desmosome defects lead to intraepidermal blistering and typically require immunosuppressive therapy with corticosteroids, rituximab, or other immunomodulators to suppress the autoimmune response targeting desmosomal components [ 2 ].
• The mortality rate for pemphigus vulgaris has decreased significantly since the introduction of corticosteroids, but still varies depending on the clinical phenotype, with mucocutaneous PV being more severe [ 3 ].
• The most recent guidelines for the management of pemphigus vulgaris, published in 2017, recommend immunosuppressive therapy as the primary treatment approach [ 2 ].

In terms of morbidity, mortality, and quality of life, it is essential to prioritize the treatment of pemphigus diseases, such as pemphigus vulgaris, with immunosuppressive therapy to suppress the autoimmune response and prevent intraepidermal blistering [ 2 ]. Additionally, wound care and prevention of trauma are crucial in managing hemidesmosome defects, such as epidermolysis bullosa, to improve quality of life and reduce morbidity [ 1 ].

From the Research

Hemidesmosomes vs Desmosomes Skin Manifestation Disease

• Hemidesmosomes and desmosomes are both important components of the skin's structure, but they are involved in different types of skin diseases.
• Hemidesmosomes are associated with autoimmune bullous diseases such as pemphigoid, which results from autoimmunity to hemidesmosomal proteins present in the basement membrane of stratified squamous epithelia 4.
• Desmosomes, on the other hand, are involved in paraneoplastic pemphigus, which results from autoimmunity to multiple antigens within the desmosomes 4.
• Epidermolysis bullosa acquisita (EBA) is a subepidermal autoimmune blistering disease that results from autoimmunity to type VII collagen in the anchoring fibrils of the basement membrane area, and can manifest with skin fragility, blisters, erosions, scars, milia, and nail loss 5.
• The treatment of these diseases varies, but may include systemic corticosteroids, immunosuppressants, and biologic agents such as rituximab 6, 7.
• In some cases, treatment may also involve topical corticosteroids, immunomodulators, or other therapies such as photopheresis or plasmapheresis 5, 7.

Clinical Manifestations

• Pemphigoid typically presents with tense blisters in flexural areas of the skin 4.
• Mucous membrane pemphigoid can affect one or more mucous membranes, resulting in lesions that may lead to scar formation and blindness 4.
• EBA can manifest with a range of clinical features, including skin fragility, blisters, erosions, scars, milia, and nail loss 5.
• Paraneoplastic pemphigus typically presents with severe stomatitis and polymorphous skin eruption 4.

Treatment Options

• Systemic corticosteroids are often used as a first-line treatment for autoimmune bullous diseases 6, 7.
• Immunossuppressants such as azathioprine, cyclophosphamide, and mycophenolate mofetil may be used as adjuvant therapies 6, 7.
• Biologic agents such as rituximab have been shown to be effective in the treatment of some autoimmune bullous diseases 6, 7.
• Topical corticosteroids and immunomodulators may be used for mild or localized disease 7.