Pemphigus erythematosus

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Pemphigus erythematosus
Other namesSenear–Usher syndrome [1]
Pronunciation
  • /ˈpɛmfɪɡəs ˌɛrɪθɪməˈtoʊsəs/
Specialty Dermatology
Symptoms Flaccid bullae (blisters), crusted plaques, photosensitivity
Usual onset40 - 60 years of age
DurationLong term
CausesUnclear
Diagnostic method Based on symptoms, blood tests, and skin biopsy
Differential diagnosis Pemphigus foliaceus, systemic lupus erythematosus
TreatmentCorticosteroids, mycophenolate mofetil, and anti-CD20 antibodies

Pemphigus erythematosus (Senear-Usher Syndrome) is a rare form of pemphigus with features of pemphigus foliaceus and lupus erythematosus. [1] [2] It was first described by Francis Senear and Barney Usher at the University of Illinois College of Medicine in 1926. [3] Patients with pemphigus erythematosus typically present with flaccid scaling blisters on the face, scalp, and trunk in sun-exposed areas. [1] Patients may also have a butterfly-shaped malar rash similar to systemic lupus erythematosus. [2]

Contents

Pemphigus is an autoimmune disease that involves antibodies targeting a protein called desmoglein 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. [4]

Patients with pemphigus erythematosus have antibodies against desmoglein-1 primarily, similar to pemphigus foliaceus. [1] Pemphigus erythematosus and pemphigus foliaceus both exhibit superficial blistering of the skin with minimal involvement on the mucosa (eg. mouth). This is in contrast to pemphigus vulgaris, which has antibodies against desmoglein-3 primarily. [2] Patients with pemphigus erythematosus will have positive ANA serology, a common feature of lupus. [5]

Signs and symptoms

Superficial erosions of pemphigus erythematosus may look similar to Grover's disease (pictured) Grover's disease, advanced case.JPG
Superficial erosions of pemphigus erythematosus may look similar to Grover's disease (pictured)

Patients with pemphigus erythematosus typically present with superficially eroded lesions, or vesiculobullae, that may ooze and crust. [5] This is especially common in areas of the body that are exposed to the sun, like the back, upper chest, and face. [5] The lesions are initially flaccid bullae that progress to crusted or scaly erosions with a red/pink base. [5] The early appearance of the lesions may be confused with other acantholytic processes like Grover's Disease, or cutaneous lupus. [3]

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. [5]

Patient with lupus showing malar erythema without blisters Lupusfoto.jpg
Patient with lupus showing malar erythema without blisters

The facial rash in pemphigus erythematosus is unique to the disease, as it is not seen in pemphigus foliaceus. [1] 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. [1] Although lupus patients may present with a rash in the same distribution, it does not present with blisters. [6]

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. [2] Pemphigus erythematosus targets desmoglein 1, which is primarily found in the skin. Desmoglein 3 is present in higher numbers in the mucosa. Pemphigus vulgaris targets desmoglein 3 and therefore produces mouth ulcers. [1]

Pathophysiology

Desmosomes between skin cells are the target of pemphigus antibodies. Desmosome cell junction en.svg
Desmosomes between skin cells are the target of pemphigus antibodies.

Pemphigus patients experience an autoimmune reaction that targets desmosomes, which are the structures that hold skin cells together. [7] Desmosomes are made of many different proteins, including proteins in the cadherin family like desmocollins and desmogleins. Patients with pemphigus have antibodies targeting their desmoglein proteins, triggering the immune system to destroy them. [1] Fewer numbers of functional desmoglein 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. The blisters often appear wet or crusted, which is caused by serous fluid leaking through the compromised skin barrier. [5]

The photosensitivity of pemphigus erythematosus is thought to occur by a similar mechanism to that of lupus. [6] Exposure to the sun's UV rays damages skin cells, leading to apoptosis (controlled cell death) and necrosis (uncontrolled cell death). In turn, cellular proteins including desmogleins are released from the cell, becoming exposed to pemphigus antibodies, causing an inflammatory reaction. [6]

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 use. [8] There has been one report of a new case of pemphigus erythematosus following topical ingenol mebutate treatment. [9]

Diagnosis

Like other forms of pemphigus, pemphigus erythematosus is diagnosed by physical symptoms, skin biopsies, and blood tests. [1]

Treatment

Rituximab (Anti-CD20 antibody) has been used to treat pemphigus erythematosus. Rituximab ( MabTas ).jpg
Rituximab (Anti-CD20 antibody) has been used to treat pemphigus erythematosus.

Immunosuppressant medication is the most common treatment for pemphigus erythematosus. [1] Corticosteroids such as oral prednisone pills are an established long-term therapy for pemphigus. However, their extensive side-effect profile may limit their use. [5] Alternative steroid-sparing therapies include methotrexate,azathioprine, mycophenolate mofetil, cyclophosphamide, and intravenous immunoglobulin. These may be used in combination with corticosteroids to manage disease symptoms. [2]

Rituximab is a monoclonal antibody therapy targeting CD20 that has been used to treat different forms of pemphigus reliably. In 2018, the FDA approved rituximab for the treatment of pemphigus vulgaris. [10] It has been shown effective in treating cases of pemphigus vulgaris that did not respond to corticosteroids. [11] Several recent case reports have shown its effectiveness in treating pemphigus erythematosus. Other anti-CD20 monoclonal antibodies such as ocrelizumab, veltuzumab, and ofatumumab have been suggested for the management of pemphigus. [12]

Immunoadsorption and plasmapheresis have also been shown to be useful treatments for pemphigus erythematosus. [13] [14]

See also

References

  1. 1 2 3 4 5 6 7 8 9 10 11 Rapini, Ronald P.; Bolognia, Jean L.; Jorizzo, Joseph L. (2007). Dermatology: 2-Volume Set. St. Louis: Mosby. ISBN   978-1-4160-2999-1.
  2. 1 2 3 4 5 6 Freedberg, et al. (2003). Fitzpatrick's Dermatology in General Medicine. (6th ed.). Page 562. McGraw-Hill. ISBN   0-07-138076-0.
  3. 1 2 3 Steffen, Charles; Thomas, David (October 2003). "The Men Behind the Eponym: Francis E. Senear, Barney Usher, and the Senear-Usher Syndrome". The American Journal of Dermatopathology. 25 (5): 432–436. doi:10.1097/00000372-200310000-00011. ISSN   0193-1091. PMID   14501294.
  4. "acantholysis", The Free Dictionary, retrieved 2025-01-24
  5. 1 2 3 4 5 6 7 8 9 10 11 Bharti, Rakesh (December 6, 2022). "Pemphigus Erythematosus: Practice Essentials, Etiology, Epidemiology". Medscape Reference. Retrieved February 4, 2024.
  6. 1 2 3 Lehmann, Percy; Homey, Bernhard (May 2009). "Clinic and pathophysiology of photosensitivity in lupus erythematosus". Autoimmunity Reviews. 8 (6): 456–461. doi:10.1016/j.autrev.2008.12.012. PMID   19167524.
  7. Oktarina, Dyah A. M.; Poot, Angelique M.; Kramer, Duco; Diercks, Gilles F. H.; Jonkman, Marcel F.; Pas, Hendri H. (October 1, 2012). "The IgG "Lupus-Band" Deposition Pattern of Pemphigus Erythematosus". Archives of Dermatology. 148 (10). American Medical Association (AMA): 1173–1178. doi:10.1001/archdermatol.2012.1896. ISSN   0003-987X. PMID   22801864.
  8. Lo Schiavo, Ada; Puca, Rosa Valentina; Romano, Francesca; Cozzi, Roberto (2014). "Pemphigus erythematosus relapse associated with atorvastatin intake". Drug Design, Development and Therapy. 8. Informa UK Limited: 1463–1465. doi: 10.2147/dddt.s66666 . ISSN   1177-8881. PMC   4173814 . PMID   25258514.
  9. Kim, YoungJae; Yang, HeeJoo; Lee, WooJin; Won, ChongHyun; Chang, SungEun; Lee, MiWoo; Choi, JeeHo (2021). "A case of new-onset pemphigus erythematosus after topical application of ingenol mebutate". Indian Journal of Dermatology. 66 (5). Medknow: 563–565. doi: 10.4103/ijd.ijd_820_20 . ISSN   0019-5154. PMC   8751704 . PMID   35068520.
  10. "Genentech: Press Releases | Thursday, Jun 7, 2018". www.gene.com. Retrieved 2025-01-24.
  11. Ahmed, A. Razzaque; Kaveri, Srini; Spigelman, Zachary (2015-12-31). "Long-Term Remissions in Recalcitrant Pemphigus Vulgaris". New England Journal of Medicine. 373 (27): 2693–2694. doi:10.1056/NEJMc1508234. ISSN   0028-4793. PMID   26716930.
  12. Klufas, Daniel M.; Amerson, Erin; Twu, Olivia; Clark, Leon; Shinkai, Kanade (August 2020). "Refractory pemphigus vulgaris successfully treated with ofatumumab". JAAD Case Reports. 6 (8): 734–736. doi:10.1016/j.jdcr.2020.05.034. PMC   7369462 . PMID   32715065.
  13. Ogata, Kimiko; Yasuda, Kayo; Matsushita, Mitsuji; Kodama, Hajime (1999). "Successful Treatment of Adolescent Pemphigus Vulgaris by Immunoadsorption Method". The Journal of Dermatology. 26 (4). Wiley: 236–239. doi:10.1111/j.1346-8138.1999.tb03463.x. ISSN   0385-2407. PMID   10343469. S2CID   22757265.
  14. Egan, Conleth A.; Meadows, Kappa P.; Zone, John J. (2000). "Plasmapheresis as a steroid saving procedure in bullous pemphigoid". International Journal of Dermatology. 39 (3). Wiley: 230–235. doi:10.1046/j.1365-4362.2000.00876.x. ISSN   0011-9059. PMID   10759969. S2CID   23582853.

Further reading