Pemphigus erythematosus (Senear-Usher Syndrome) is a rare form of

pemphigus Pemphigus ( or ) 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". In pemphigus, autoantibody, autoantibodies form against de ...

with features of

pemphigus foliaceus Pemphigus foliaceus is an autoimmune blistering disease of the skin. Pemphigus foliaceus causes a characteristic inflammatory attack at the subcorneal layer of epidermis, which results in skin lesions that are scaly or crusted erosions with an ...

and

lupus erythematosus is a collection of autoimmune diseases in which the human immune system becomes hyperactive and attacks healthy tissues. Symptoms of these diseases can affect many different body systems, including joints, skin, kidneys, blood cells, heart, ...

.Freedberg, et al. (2003). ''Fitzpatrick's Dermatology in General Medicine''. (6th ed.). Page 562. McGraw-Hill. . It was first described by Francis Senear and Barney Usher at the

University of Illinois College of Medicine The University of Illinois College of Medicine offers a four-year program leading to the MD degree at four different sites in Illinois: Chicago, Peoria, Illinois, Peoria, Rockford, Illinois, Rockford, and formerly Champaign–Urbana metropolitan ...

in 1926. Patients with pemphigus erythematosus typically present with flaccid scaling

blisters A blister is a small pocket of body fluid (lymph, Serum (blood), serum, Plasma (blood), plasma, blood, or pus) within the Epidermis, upper layers of the skin, usually caused by forceful rubbing (friction), burning, freezing, chemical exposure o ...

on the face, scalp, and trunk in sun-exposed areas. Patients may also have a butterfly-shaped

malar rash A malar rash (), also called butterfly rash, is a medical sign consisting of a characteristic form of facial rash. It is often seen in lupus erythematosus. More rarely, it is also seen in other diseases, such as pellagra, dermatomyositis, and ...

similar to systemic lupus erythematosus.

Pemphigus Pemphigus ( or ) 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". In pemphigus, autoantibody, autoantibodies form against de ...

is an autoimmune disease that involves antibodies targeting a protein called

desmoglein The desmogleins are a family of desmosomal cadherins consisting of proteins DSG1, DSG2, DSG3, and DSG4. They play a role in the formation of desmosomes that join cells to one another. Pathology Desmogleins are targeted in the autoimmune disease ...

in the top layer of the skin that holds skin cells together. The proteins are destroyed or disabled by the immune system, leading to the separation of the skin layers, which causes the blisters. The separation itself is called

acantholysis Acantholysis is the loss of intercellular connections, such as desmosomes, resulting in loss of cohesion between keratinocytes,Kumar, Vinay; Fausto, Nelso; Abbas, Abul (2004) ''Robbins & Cotran Pathologic Basis of Disease'' (7th ed.). Saunders. ...

. Patients with pemphigus erythematosus have antibodies against

desmoglein-1 Desmoglein-1 is a protein that in humans is encoded by the ''DSG1'' gene. Desmoglein-1 is expressed everywhere in the skin epidermis, but mainly it is expressed in the superficial upper layers of the skin epidermis. Function Desmosomes are cel ...

primarily, similar to

. Pemphigus erythematosus and pemphigus foliaceus both exhibit superficial blistering of the skin with minimal involvement on the

mucosa A mucous membrane or mucosa is a membrane that lines various cavities in the body of an organism and covers the surface of internal organs. It consists of one or more layers of epithelial cells overlying a layer of loose connective tissue. It ...

(eg. mouth). This is in contrast to

pemphigus vulgaris 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 antibody, ...

, which has antibodies against

desmoglein-3 Desmoglein-3 is a protein that in humans is encoded by the ''DSG3'' gene. In the skin epidermis Desmoglein-3 is expressed in the basal lower layers of the epidermis, and dominates in terms of expression on mucosal surfaces compared to Desmoglein-1 ...

primarily. Patients with pemphigus erythematosus will have positive

ANA Ana or ANA may refer to: People * Ana (given name), a list of people with the name * Ana people or Atakpame people, an ethnic group of West Africa * ana (gamer), Anathan Pham, an Australian professional ''Dota 2'' player known as ana Places * A ...

serology, a common feature of

lupus Lupus, formally called systemic lupus erythematosus (SLE), is an autoimmune disease in which the body's immune system mistakenly attacks healthy tissue in many parts of the body. Symptoms vary among people and may be mild to severe. Common ...

Signs and symptoms

Patients with pemphigus erythematosus typically present with superficially eroded lesions, or vesiculobullae, that may ooze and crust. This is especially common in areas of the body that are exposed to the sun, like the back, upper chest, and face. The lesions are initially flaccid bullae that progress to crusted or scaly erosions with a red/pink base. The early appearance of the lesions may be confused with other acantholytic processes like Grover's Disease, or cutaneous lupus. The symptoms of pemphigus erythematosus usually appear slowly and progress slowly. The patient might not be aware that their condition is photosensitive, although the lesions frequently appear on sun-exposed areas and flare after prolonged exposure to the sun. Lupusfoto

The facial rash in pemphigus erythematosus is unique to the disease, as it is not seen in

. The appearance of crusted blisters on the cheeks and under the eyes that avoid the mouth and nasolabial folds is highly specific for pemphigus erythematosus. Although lupus patients may present with a rash in the same distribution, it does not present with blisters. Other forms of pemphigus present with oral blisters, which are often the first symptoms of the disease. Pemphigus erythematosus, however, does not produce oral ulcers, or any other mucosal lesions. Pemphigus erythematosus targets

desmoglein 1 Desmoglein-1 is a protein that in humans is encoded by the ''DSG1'' gene. Desmoglein-1 is expressed everywhere in the skin epidermis, but mainly it is expressed in the superficial upper layers of the skin epidermis. Function Desmosomes are cel ...

, which is primarily found in the skin.

Desmoglein 3 Desmoglein-3 is a protein that in humans is encoded by the ''DSG3'' gene. In the skin epidermis Desmoglein-3 is expressed in the basal lower layers of the epidermis, and dominates in terms of expression on mucosal surfaces compared to Desmoglein-1 ...

is present in higher numbers in the mucosa.

Pemphigus vulgaris 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 antibody, ...

targets

desmoglein 3 Desmoglein-3 is a protein that in humans is encoded by the ''DSG3'' gene. In the skin epidermis Desmoglein-3 is expressed in the basal lower layers of the epidermis, and dominates in terms of expression on mucosal surfaces compared to Desmoglein-1 ...

and therefore produces mouth ulcers.

Pathophysiology

Pemphigus patients experience an autoimmune reaction that targets

desmosomes A desmosome (; "binding body"), also known as a macula adherens (plural: maculae adherentes) (Latin for ''adhering spot''), is a cell structure specialized for cell-to-cell adhesion. A type of junctional complex, they are localized spot-like ad ...

, which are the structures that hold skin cells together.

Desmosomes A desmosome (; "binding body"), also known as a macula adherens (plural: maculae adherentes) (Latin for ''adhering spot''), is a cell structure specialized for cell-to-cell adhesion. A type of junctional complex, they are localized spot-like ad ...

are made of many different proteins, including proteins in the

cadherin Cadherins (named for "calcium-dependent adhesion") are cell adhesion molecules important in forming adherens junctions that let cells adhere to each other. Cadherins are a class of type-1 transmembrane proteins, and they depend on calcium (Ca2+) ...

family like desmocollins and desmogleins. Patients with

have antibodies targeting their

proteins, triggering the immune system to destroy them. Fewer numbers of functional

proteins lead to the separation of skin cells from one another. When a large number of skin cells separate in one area, this forms a

blister A blister is a small pocket of body fluid (lymph, serum, plasma, blood, or pus) within the upper layers of the skin, usually caused by forceful rubbing (friction), burning, freezing, chemical exposure or infection. Most blisters are filled ...

. The

often appear wet or crusted, which is caused by

serous fluid In physiology, serous fluid or serosal fluid (originating from the Medieval Latin word ''serosus'', from Latin ''serum'') is any of various body fluids resembling serum, that are typically pale yellow or transparent and of a benign nature. The fl ...

leaking through the compromised skin barrier. The

photosensitivity Photosensitivity is the amount to which an object reacts upon receiving photons, especially visible light. In medicine, the term is principally used for abnormal reactions of the skin, and two types are distinguished, photoallergy and phototoxicit ...

of pemphigus erythematosus is thought to occur by a similar mechanism to that of

. Exposure to the sun's

UV rays Ultraviolet radiation, also known as simply UV, is electromagnetic radiation of wavelengths of 10–400 nanometers, shorter than that of visible light, but longer than X-rays. UV radiation is present in sunlight and constitutes about 10% of th ...

damages skin cells, leading to

apoptosis Apoptosis (from ) is a form of programmed cell death that occurs in multicellular organisms and in some eukaryotic, single-celled microorganisms such as yeast. Biochemistry, Biochemical events lead to characteristic cell changes (Morphology (biol ...

(controlled cell death) and

necrosis Necrosis () is a form of cell injury which results in the premature death of cells in living tissue by autolysis. The term "necrosis" came about in the mid-19th century and is commonly attributed to German pathologist Rudolf Virchow, who i ...

(uncontrolled cell death). In turn, cellular proteins including desmogleins are released from the cell, becoming exposed to pemphigus antibodies, causing an inflammatory reaction. The cause of autoimmune pemphigus is generally unknown; however, certain medications have been linked to the development of pemphigus erythematosus. For example, pemphigus erythematosus flares have been linked to

atorvastatin Atorvastatin, sold under the brand name Lipitor among others, is a statin medication used to prevent cardiovascular disease in those at high risk and to treat abnormal lipid levels. For the prevention of cardiovascular disease, statins are a ...

use. There has been one report of a new case of pemphigus erythematosus following topical ingenol mebutate treatment.

Diagnosis

Like other forms of pemphigus, pemphigus erythematosus is diagnosed by physical symptoms, skin biopsies, and blood tests. * Punch biopsies are the primary type of

skin biopsy Skin biopsy is a biopsy technique in which a skin lesion is removed to be sent to a pathologist to render a microscopic diagnosis. It is usually done under local anesthetic in a physician's office, and results are often available in 4 to 10 day ...

performed to diagnose pemphigus erythematosus. Hematoxylin and Eosin staining is used to view the appearance of the lesion under the microscope; these biopsy samples are taken from inside the blister. * Direct immunofluorescence studies are used to view the presence of pemphigus

antibodies An antibody (Ab) or immunoglobulin (Ig) is a large, Y-shaped protein belonging to the immunoglobulin superfamily which is used by the immune system to identify and neutralize antigens such as bacteria and viruses, including those that caus ...

deposited between the skin cells; these biopsies are performed on perilesional skin (the skin next to the blister). This is the most specific diagnostic test for pemphigus erythematosus. * Indirect immunofluorescence studies can also be used to view the presence of pemphigus antibodies, however, this test involves taking a sample of the patient's blood and testing it on animal tissue (eg. monkey esophagus) and does not require a biopsy. * Anti-desmoglein antibody

serology Serology is the scientific study of Serum (blood), serum and other body fluids. In practice, the term usually refers to the medical diagnosis, diagnostic identification of Antibody, antibodies in the serum. Such antibodies are typically formed in r ...

may be used to find

in the blood that are unique to pemphigus erythematosus. Patients with the disease will have a positive

ELISA The enzyme-linked immunosorbent assay (ELISA) (, ) is a commonly used analytical biochemistry assay, first described by Eva Engvall and Peter Perlmann in 1971. The assay is a solid-phase type of enzyme immunoassay (EIA) to detect the presence of ...

result for anti-

antibody An antibody (Ab) or immunoglobulin (Ig) is a large, Y-shaped protein belonging to the immunoglobulin superfamily which is used by the immune system to identify and neutralize antigens such as pathogenic bacteria, bacteria and viruses, includin ...

and a negative result for anti-

antibodies. *

Antinuclear antibody Antinuclear antibodies (ANAs, also known as antinuclear factor or ANF) are autoantibodies that bind to contents of the cell nucleus. In normal individuals, the immune system produces antibodies to foreign proteins (antigens) but not to human pro ...

(ANA) serology can be used as a

screening test In medicine, screening is a strategy used to look for as-yet-unrecognised conditions or risk markers. This testing can be applied to individuals or to a whole population without symptoms or signs of the disease being screened. Screening interv ...

for pemphigus erythematosus. This test is not specific to the disease, but high titers of

and SSA in a patient with facial

on sun-exposed skin is highly suggestive of pemphigus erythematosus.

Treatment

Immunosuppressant Immunosuppressive drugs, also known as immunosuppressive agents, immunosuppressants and antirejection medications, are drugs that inhibit or prevent the activity of the immune system. Classification Immunosuppressive drugs can be classified ...

medication is the most common treatment for pemphigus erythematosus.

Corticosteroids Corticosteroids are a class of steroid hormones that are produced in the adrenal cortex of vertebrates, as well as the synthetic analogues of these hormones. Two main classes of corticosteroids, glucocorticoids and mineralocorticoids, are invol ...

such as oral

prednisone Prednisone is a glucocorticoid medication mostly used to immunosuppressive drug, suppress the immune system and decrease inflammation in conditions such as asthma, COPD, and rheumatologic diseases. It is also used to treat high blood calcium ...

pills are an established long-term therapy for pemphigus. However, their extensive side-effect profile may limit their use. Alternative steroid-sparing therapies include

methotrexate Methotrexate, formerly known as amethopterin, is a chemotherapy agent and immunosuppressive drug, immune-system suppressant. It is used to treat cancer, autoimmune diseases, and ectopic pregnancy, ectopic pregnancies. Types of cancers it is u ...

azathioprine Azathioprine, sold under the brand name Imuran, among others, is an immunosuppressive medication. It is used for the treatment of rheumatoid arthritis, granulomatosis with polyangiitis, Crohn's disease, ulcerative colitis, and systemic lupus er ...

mycophenolate mofetil Mycophenolic acid is an immunosuppressant medication used to prevent rejection following organ transplantation and to treat autoimmune conditions such as Crohn's disease and lupus. Specifically it is used following kidney, heart, and live ...

cyclophosphamide Cyclophosphamide (CP), also known as cytophosphane among other names, is a medication used as chemotherapy and to suppress the immune system. As chemotherapy it is used to treat lymphoma, multiple myeloma, leukemia, ovarian cancer, breast cancer ...

, and

intravenous immunoglobulin Immunoglobulin therapy is the use of a mixture of antibodies (normal human immunoglobulin) to treat several health conditions. These conditions include primary immunodeficiency, immune thrombocytopenic purpura, chronic inflammatory demyelinat ...

. These may be used in combination with

corticosteroids Corticosteroids are a class of steroid hormones that are produced in the adrenal cortex of vertebrates, as well as the synthetic analogues of these hormones. Two main classes of corticosteroids, glucocorticoids and mineralocorticoids, are invol ...

to manage disease symptoms.

Rituximab 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 (in children and ad ...

is a monoclonal antibody therapy targeting

CD20 B-lymphocyte antigen CD20 or CD20 is B lymphocyte cell-surface molecule. It is a 33-37 kDa non-glycosylated protein. CD20 is expressed on the surface of B-cells from the pre-B phase, the expression is lost in terminally differentiated plasm ...

that has been used to treat different forms of pemphigus reliably. In 2018, the FDA approved

rituximab 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 (in children and ad ...

for the treatment of

. It has been shown effective in treating cases of

that did not respond to

. Several recent

case reports In medicine, a case report is a detailed report of the symptoms, signs, diagnosis, treatment, and follow-up of an individual patient. Case reports may contain a demographic profile of the patient, but usually describe an unusual or novel occurrence ...

have shown its effectiveness in treating pemphigus erythematosus. Other anti-

monoclonal antibodies such as

ocrelizumab Ocrelizumab, sold under the brand name Ocrevus, is a medication used for the treatment of multiple sclerosis. It is a humanized anti-CD20 monoclonal antibody. It targets CD20 marker on B lymphocytes and is an immunosuppressive drug. Ocrelizu ...

veltuzumab Veltuzumab is a monoclonal antibody (targeted at CD20) which is being investigated for the treatment of non-Hodgkin's lymphoma. , it is undergoing Phase I/II clinical trials. When used with milatuzumab it showed activity. This drug was developed ...

, and

ofatumumab Ofatumumab is a fully human monoclonal antibody to CD20, which appears to provide rapid B-cell depletion. Under the brand name Kesimpta, it is approved for the treatment of multiple sclerosis in the United States as well as in the European Uni ...

have been suggested for the management of pemphigus. Immunoadsorption and

plasmapheresis Plasmapheresis (from the Greek language, Greek πλάσμα, ''plasma'', something molded, and ἀφαίρεσις ''aphairesis'', taking away) is the removal, treatment, and return or exchange of blood plasma or components thereof from and to the ...

have also been shown to be useful treatments for pemphigus erythematosus.

References

External links

Dermatology Advisor

VisualDx
{{Vesiculobullous disease Chronic blistering cutaneous conditions Syndromes