Bullous pemphigoid

Last updated
Bullous pemphigoid
Legs Bullous Pemphigoid.jpg
A patient present with legs covered in popped blisters caused by bullous pemphigoid. The blisters cover his entire body.
Specialty Dermatology   OOjs UI icon edit-ltr-progressive.svg

Bullous pemphigoid (a type of pemphigoid) is an autoimmune pruritic skin disease that typically occurs in people aged over 60, that may involve the formation of blisters (bullae) in the space between the epidermal and dermal skin layers. It is classified as a type II hypersensitivity reaction, which involves formation of anti-hemidesmosome antibodies, causing a loss of keratinocytes to basement membrane adhesion.

Contents

Signs and symptoms

Clinically, the earliest lesions may appear as a hives-like red raised rash, but could also appear dermatitic, targetoid, lichenoid, nodular, or even without a rash (essential pruritus). [1] Tense bullae eventually erupt, most commonly at the inner thighs and upper arms, but the trunk and extremities are frequently both involved. Any part of the skin surface can be involved. Oral lesions are present in a minority of cases. [2] The disease may be acute, but can last from months to years with periods of exacerbation and remission. [3]

Several other skin diseases may have similar symptoms. However, milia are more common with epidermolysis bullosa acquisita, because of the deeper antigenic targets. A more ring-like configuration with a central depression or centrally collapsed bullae may indicate linear IgA disease. Nikolsky's sign is negative, unlike pemphigus vulgaris, where it is positive. [4]

Causes

In most cases of bullous pemphigoid, no clear precipitating factors are identified. [2] Potential precipitating events that have been reported include exposure to ultraviolet light and radiation therapy. [2] [5] Onset of pemphigoid has also been associated with certain drugs, including furosemide, nonsteroidal anti-inflammatory agents, DPP-4 inhibitors, captopril, penicillamine, and antibiotics. [5]

Pathophysiology

The bullae are formed by an immune reaction, initiated by the formation of IgG [ citation needed ] autoantibodies targeting dystonin, also called bullous pemphigoid antigen 1, [6] and/or type XVII collagen, also called bullous pemphigoid antigen 2, [7] which is a component of hemidesmosomes. A different form of dystonin is associated with neuropathy. [6] Following antibody targeting, a cascade of immunomodulators results in a variable surge of immune cells, including neutrophils, lymphocytes and eosinophils coming to the affected area. Unclear events subsequently result in a separation along the dermoepidermal junction and eventually stretch bullae.[ citation needed ]

Diagnosis

Micrograph of bullous pemphigoid. Subepidermal blistering [solid arrows in (A,B)] and influx of inflammatory cells including eosinophils and neutrophils in thedermis [solid arrow (C)] and blister cavity [dashed arrows (C)]. In (C) also deposition of fibrin is noted (asterisks). Micrograph of bullous pemphigoid.jpg
Micrograph of bullous pemphigoid. Subepidermal blistering [solid arrows in (A,B)] and influx of inflammatory cells including eosinophils and neutrophils in thedermis [solid arrow (C)] and blister cavity [dashed arrows (C)]. In (C) also deposition of fibrin is noted (asterisks).

Diagnosis consist of at least 2 positive results out of 3 criteria (2-out-of-3 rule): (1) pruritus and/or predominant cutaneous blisters, (2) linear IgG and/or C3c deposits (in an n- serrated pattern) by direct immunofluorescence microscopy (DIF) on a skin biopsy specimen, and (3) positive epidermal side staining by indirect immunofluorescence microscopy on human salt-split skin (IIF SSS) on a serum sample. [9] Routine H&E staining or ELISA tests do not add value to initial diagnosis.[ citation needed ]

Treatment

Treatments include topical steroids such as clobetasol, and halobetasol which in some studies have proven to be equally effective as systemic, or pill, therapy and somewhat safer. [2] However, in difficult-to-manage or widespread cases, systemic prednisone and powerful steroid-free immunosuppressant medications, such as methotrexate, azathioprine or mycophenolate mofetil, may be appropriate. [2] Some of these medications have the potential for severe adverse effects such as kidney and liver damage, increased susceptibility to infections, and bone marrow suppression. [10] Antibiotics such as tetracycline or erythromycin may also control the disease, particularly in patients who cannot use corticosteroids.[ citation needed ]

The anti-CD20 monoclonal antibody rituximab has been found to be effective in treating some otherwise refractory cases of pemphigoid. [11] A 2010 (updated in 2023) meta-analysis of 14 randomized controlled trials showed that oral steroids and potent topical steroids are effective treatments, although their use may be limited by side-effects, while lower doses of topical steroids are safe and effective for treatment of moderate bullous pemphigoid. [10]

IgA-mediated pemphigoid can often be difficult to treat even with usually effective medications such as rituximab. [12]

Prognosis

Bulbous pemphigoid may be self-resolving in a period ranging from several months to many years even without treatment. [2] Poor general health related to old age is associated with a poorer prognosis. [2]

Epidemiology

Very rarely seen in children, bullous and non-bullous pemphigoid most commonly occurs in people 70 years of age and older. [2] Its estimated frequency is seven to 14 cases per million per year, but has been reported to be as high as 472 cases per million per year in Scottish men older than 85. [2] At least one study indicates the incidence might be increasing in the United Kingdom. [13] Some sources report it affects men twice as frequently as women,[ citation needed ] while others report no difference between the sexes. [2]

Many mammals can be affected, including dogs, cats, pigs, and horses, as well as humans. It is very rare in dogs; on average, three cases are diagnosed around the world each year.[ citation needed ]

Research

Animal models of bullous pemphigoid have been developed using transgenic techniques to produce mice lacking the genes for the two known autoantigens, dystonin and collagen XVII. [6] [7]

See also

Related Research Articles

<span class="mw-page-title-main">Hemidesmosome</span> Structures connecting keratinocyte cells to the extracellular matrix

Hemidesmosomes are very small stud-like structures found in keratinocytes of the epidermis of skin that attach to the extracellular matrix. They are similar in form to desmosomes when visualized by electron microscopy; however, desmosomes attach to adjacent cells. Hemidesmosomes are also comparable to focal adhesions, as they both attach cells to the extracellular matrix. Instead of desmogleins and desmocollins in the extracellular space, hemidesmosomes utilize integrins. Hemidesmosomes are found in epithelial cells connecting the basal epithelial cells to the lamina lucida, which is part of the basal lamina. Hemidesmosomes are also involved in signaling pathways, such as keratinocyte migration or carcinoma cell intrusion.

<span class="mw-page-title-main">Pemphigus</span> Blistering autoimmune diseases

Pemphigus is a rare group of blistering autoimmune diseases that affect the skin and mucous membranes. The name is derived from the Greek root pemphix, meaning "blister".

<span class="mw-page-title-main">Rituximab</span> Biopharmaceutical drug

Rituximab, sold under the brand name Rituxan among others, is a monoclonal antibody medication used to treat certain autoimmune diseases and types of cancer. It is used for non-Hodgkin lymphoma, chronic lymphocytic leukemia, rheumatoid arthritis, granulomatosis with polyangiitis, idiopathic thrombocytopenic purpura, pemphigus vulgaris, myasthenia gravis and Epstein–Barr virus-positive mucocutaneous ulcers. It is given by slow intravenous infusion.

<span class="mw-page-title-main">Pemphigus vulgaris</span> Chronic blistering skin disease

Pemphigus vulgaris is a rare chronic blistering skin disease and the most common form of pemphigus. Pemphigus was derived from the Greek word pemphix, meaning blister. It is classified as a type II hypersensitivity reaction in which antibodies are formed against desmosomes, components of the skin that function to keep certain layers of skin bound to each other. As desmosomes are attacked, the layers of skin separate and the clinical picture resembles a blister. These blisters are due to acantholysis, or breaking apart of intercellular connections through an autoantibody-mediated response. Over time the condition inevitably progresses without treatment: lesions increase in size and distribution throughout the body, behaving physiologically like a severe burn.

<span class="mw-page-title-main">Pemphigoid</span> Autoimmune blistering diseases

Pemphigoid is a group of rare autoimmune blistering diseases of the skin and mucous membranes. As its name indicates, pemphigoid is similar in general appearance to pemphigus, however unlike pemphigus, pemphigoid does not feature acantholysis, a loss of connections between skin cells.

<span class="mw-page-title-main">Gestational pemphigoid</span> Medical condition

Gestational pemphigoid (GP) is a rare autoimmune variant of the skin disease bullous pemphigoid, and first appears in pregnancy. It presents with tense blisters, small bumps, hives and intense itching, usually starting around the navel before spreading to limbs in mid-pregnancy or shortly after delivery. The head, face and mouth are not usually affected.

<span class="mw-page-title-main">Collagen, type XVII, alpha 1</span> Mammalian protein found in humans

Collagen XVII, previously called BP180, is a transmembrane protein which plays a critical role in maintaining the linkage between the intracellular and the extracellular structural elements involved in epidermal adhesion, identified by Diaz and colleagues in 1990.

<span class="mw-page-title-main">Dystonin</span> Neurologically significant human protein

Dystonin(DST), also known as bullous pemphigoid antigen 1 (BPAG1), isoforms 1/2/3/4/5/8, is a protein that in humans is encoded by the DST gene.

<span class="mw-page-title-main">Dermatitis herpetiformis</span> Chronic autoimmune disorder leading to blistering skin

Dermatitis herpetiformis (DH) is a chronic autoimmune blistering skin condition, characterised by intensely itchy blisters filled with a watery fluid. DH is a cutaneous manifestation of coeliac disease, although the exact causal mechanism is not known. DH is neither related to nor caused by herpes virus; the name means that it is a skin inflammation having an appearance similar to herpes.

Pemphigus erythematosus is simply a localized form of pemphigus foliaceus with features of lupus erythematosus.

Epidermolysis bullosa acquisita, also known as acquired epidermolysis bullosa, is a longterm autoimmune blistering skin disease. It generally presents with fragile skin that blisters and becomes red with or without trauma. Marked scarring is left with thin skin, milia and nail changes. It typically begins around age 50.

Paraneoplastic pemphigus (PNP) is an autoimmune disorder stemming from an underlying tumor. It is hypothesized that antigens associated with the tumor trigger an immune response resulting in blistering of the skin and mucous membranes.

<span class="mw-page-title-main">Linear IgA bullous dermatosis</span> Medical condition

Linear IgA bullous dermatosis is a rare immune-mediated blistering skin disease frequently associated with medication exposure, especially vancomycin, with men and women being equally affected. It was first described by Tadeusz Chorzelski in 1979 and may be divided into two types:

<span class="mw-page-title-main">IgA pemphigus</span> Medical condition

IgA pemphigus is a subtype of pemphigus with two distinct forms:

<span class="mw-page-title-main">Vesiculobullous disease</span> Presence of fluid-filled lesions in the skin or mucous membranes

A vesiculobullous disease is a type of mucocutaneous disease characterized by vesicles and bullae. Both vesicles and bullae are fluid-filled lesions, and they are distinguished by size. In the case of vesiculobullous diseases which are also immune disorders, the term immunobullous is sometimes used. Examples of vesiculobullous diseases include:

A coma blister, or coma bullae, is a skin lesion or blister that typically arises due to pressure in an individual with impaired consciousness. They vary in size, ranging from 4 to 5 centimeters in diameter, and may appear hemorrhagic or blood filled. Coma blisters are usually found in the extremities and trunk. These types of blisters have been associated with the overdose of central nervous system (CNS) depressants especially barbiturates, but also tricyclic antidepressants, hypnotics, benzodiazepines, opiates, antipsychotics, and alcohol. However, studies have found that coma blisters are not caused by the toxicity of these drugs, but due to hypoxia and external pressure on the comatose individual's skin from being immobilized. Coma blisters have been frequently found on individuals who have overdosed on drugs, but have also been found on individuals with chronic kidney failure, hypercalcemia, diabetic ketoacidosis, and a variety of neurologic conditions. Coma blisters are more frequent in adults and less common among children as demonstrated by the few cases published in literature.

Mucous membrane pemphigoid is a rare chronic autoimmune subepithelial blistering disease characterized by erosive lesions of the mucous membranes and skin. It is one of the pemphigoid diseases that can result in scarring.

References

  1. ↑ Cozzani E, Gasparini G, Burlando M, Drago F, Parodi A (May 2015). "Atypical presentations of bullous pemphigoid: Clinical and immunopathological aspects". Autoimmunity Reviews. 14 (5): 438–45. doi:10.1016/j.autrev.2015.01.006. PMID   25617817.
  2. 1 2 3 4 5 6 7 8 9 10 Culton, Donna A; Liu, Zhi; Diaz, Luis A (2019). "Bullous Pemphigoid". In Kang, Sewon; Amagai, Masayuki; Bruckner, Anna L; Enk, Alexander H; Margolis, David J; McMichael, Amy J; Orringer, Jeffrey S (eds.). Fitzpatrick's Dermatology (9th ed.). McGraw-Hill Education. ISBN   978-0-07-183779-8.
  3. ↑ Yancey, Kim B.; Chong, Benjamin F.; Lawley, Thomas J. (2022). "Immunologically Mediated Skin Diseases". In Loscalzo, Joseph; Fauci, Anthony; Kasper, Dennis; Hauser, Stephen; Longo, Dan; Jameson, J. Larry (eds.). Harrison's Principles of Internal Medicine (21st ed.). McGraw-Hill Education. ISBN   978-1-264-26850-4.
  4. ↑ Kumaran, MSendhil; Kanwar, AmrinderJ; Seshadri, Divya (2013). "Acantholysis revisited: Back to basics". Indian Journal of Dermatology, Venereology and Leprology. 79 (1): 120–126. doi: 10.4103/0378-6323.104688 . PMID   23254748.
  5. 1 2 Bullous Pemphigoid~clinical at eMedicine
  6. 1 2 3 Online Mendelian Inheritance in Man (OMIM): DYSTONIN; DST - 113810
  7. 1 2 Online Mendelian Inheritance in Man (OMIM): COLLAGEN, TYPE XVII, ALPHA-1; COL17A1 - 113811
  8. ↑ Giang, Jenny; Seelen, Marc A. J.; van Doorn, Martijn B. A.; Rissmann, Robert; Prens, Errol P.; Damman, Jeffrey (16 April 2018). "Complement Activation in Inflammatory Skin Diseases". Frontiers in Immunology. 9: 639. doi: 10.3389/fimmu.2018.00639 . PMC   5911619 . PMID   29713318.
  9. ↑ Meijer, Joost M.; Diercks, Gilles F. H.; de Lang, Emma W. G.; Pas, Hendri H.; Jonkman, Marcel F. (February 2019). "Assessment of Diagnostic Strategy for Early Recognition of Bullous and Nonbullous Variants of Pemphigoid". JAMA Dermatology. 155 (2): 158–165. doi:10.1001/jamadermatol.2018.4390. PMC   6439538 . PMID   30624575.
  10. 1 2 Singh, Sanjay; Kirtschig, Gudula; Anchan, Vinayak N; Chi, Ching-Chi; Taghipour, Kathy; Boyle, Robert J; Murrell, Dedee F (11 August 2023). "Interventions for bullous pemphigoid". Cochrane Database of Systematic Reviews. 2023 (11): CD002292. doi:10.1002/14651858.CD002292.pub4. PMC   10421473 . PMID   37572360.
  11. ↑ Lamberts A, Euverman HI, Terra JB, Jonkman MF, Horváth B (2018). "Effectiveness and Safety of Rituximab in Recalcitrant Pemphigoid Diseases". Frontiers in Immunology. 9: 248. doi: 10.3389/fimmu.2018.00248 . PMC   5827539 . PMID   29520266.
  12. ↑ He Y, Shimoda M, Ono Y, Villalobos IB, Mitra A, Konia T, Grando SA, Zone JJ, Maverakis E (June 2015). "Persistence of Autoreactive IgA-Secreting B Cells Despite Multiple Immunosuppressive Medications Including Rituximab". JAMA Dermatology. 151 (6): 646–50. doi:10.1001/jamadermatol.2015.59. PMID   25901938.
  13. ↑ Langan SM, Smeeth L, Hubbard R, Fleming KM, Smith CJ, West J (July 2008). "Bullous pemphigoid and pemphigus vulgaris--incidence and mortality in the UK: population based cohort study". BMJ. 337 (7662): a180. doi:10.1136/bmj.a180. PMC   2483869 . PMID   18614511.

Further reading

This page is based on this Wikipedia article
Text is available under the CC BY-SA 4.0 license; additional terms may apply.
Images, videos and audio are available under their respective licenses.