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Bullous pemphigoid

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Bullous pemphigoid

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Bullous pemphigoid

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A 35-year-old man comes to the clinic because of painful severe blistering over his buttocks for the past week. About a year ago, he noticed a similar outbreak on his inner thighs, but it receded within a few days on its own. Physical examination shows that blisters are tense, and rubbing the affected skin does not result in “popping” of the blisters. A biopsy, shown below, shows extensive inflammatory infiltrates abundant with eosinophils. Which of the following cellular structures, if defective, is most likely involved in the formation of these blisters?

Transcript

Bullous pemphigoid is an autoimmune skin disease that causes the skin to form bullae or blisters.

Now, the skin is divided into three layers--the epidermis, dermis, and hypodermis.

The epidermis forms the thin outermost layer of skin.

Underneath, is the thicker dermis layer, and finally, there’s the hypodermis that anchors the skin to the underlying muscle.

The epidermis itself is made of multiple layers of developing keratinocytes - which are flat pancake-shaped cells that are named for the keratin protein that they’re filled with.

Keratinocytes start their life at the lowest layer of the epidermis called the stratum basale, or basal layer which is made of a single layer of stem cells, called basal cells that continually divide and produce new keratinocytes.

The stratum basale also contains another group of cells called melanocytes, which secrete melanin.

Melanin is a pigment protein, or coloring substance.

Below the epidermis is the basement membrane which is a thin layer of delicate tissue containing collagen, laminins, and other proteins.

Basal cells are attached to the basement membrane by hemidesmosomes, a protein complex that stems from the bottom of the basal cells.

Just like an anchor digs into the seafloor and holds a boat in place, hemidesmosomes dig into the basement membrane and hold basal cells in place.

The exact cause of bullous pemphigoid is unclear, but it’s thought that in a person with a genetic precondition, it can be triggered by medications like furosemide, captopril, penicillamine, non steroid anti-inflammatory drugs (or NSAIDs), and antibiotics.

Bullous pemphigoid is a type II hypersensitivity reaction, which is when the immune system produces antibodies that bind to the body’s own cells.

Immune cells called B cells produce IgG antibodies, which are Y shaped molecules with 2 regions, an antigen binding fragment region - or Fab region, and fragment crystallizable region or Fc region.

The Fab region of the antibody binds to pathogens which helps other immune cells destroy those pathogens.

The antibodies can also activate a part of the immune system called the complement system, which destroys the pathogen, or induces inflammation.

In bullous pemphigoid, the Fab region of IgG antibodies bind to proteins that make up the hemidesmosome: one of the proteins is called bullous pemphigoid antigen 1 or BPAG1, which is also called dystonin, and another protein is called bullous pemphigoid antigen 2 or BPAG2, which is also called BP 180 or type 17 collagen - lots of names for the same thing.

The Fc region activates the complement system.

The process gets started when C1, the first of the complement proteins, binds the Fc region of the antibody.

C1 then engages other members of the complement family - C2 through C9, some of which are activated by being cleaved or chopped by an enzyme.

Sources
  1. "Robbins Basic Pathology" Elsevier (2017)
  2. "Harrison's Principles of Internal Medicine, Twentieth Edition (Vol.1 & Vol.2)" McGraw-Hill Education / Medical (2018)
  3. "Pathophysiology of Disease: An Introduction to Clinical Medicine 8E" McGraw-Hill Education / Medical (2018)
  4. "CURRENT Medical Diagnosis and Treatment 2020" McGraw-Hill Education / Medical (2019)
  5. "Atypical presentations of bullous pemphigoid: Clinical and immunopathological aspects" Autoimmunity Reviews (2015)
  6. "Assessment of Diagnostic Strategy for Early Recognition of Bullous and Nonbullous Variants of Pemphigoid" JAMA Dermatology (2019)
  7. "Interventions for bullous pemphigoid" Cochrane Database of Systematic Reviews (2010)
  8. "Bullous pemphigoid: Etiology, pathogenesis, and inducing factors: Facts and controversies" Clinics in Dermatology (2013)