Pemphigus vulgaris

Pemphigus vulgaris

Micrograph of pemphigus vulgaris with the characteristic "tombstoning". H&E stain.
Classification and external resources
ICD-10 L10.0
OMIM 169610
DiseasesDB 9764
MedlinePlus 000882


Pemphigus vulgaris is a chronic blistering skin disease with skin lesions that may initially be pruritic, but invariably become painful. It is classified as a type II hypersensitivity reaction, with the formation of anti-desmosome antibodies that lead to separation of the dermis from the epidermis. Over time, the clinical picture is one of inevitable progression of the disease, with lesions increasing in size and distribution throughout the body, behaving physiologically like a severe burn. Before the advent of modern treatments, mortality for the disease was close to 90%.

Pathophysiology

It is an autoimmune disease caused by antibodies directed against both desmoglein 1 and desmoglein 3 present in desmosomes resulting in the loss of desmosomes and therefore the loss of cohesion between keratinocytes in the epidermis, classified as a type II hypersensitivity reaction (in which antibodies bind to antigens on the body's own tissues). It is characterized by extensive flaccid blisters and mucocutaneous erosions. The severity of the disease, as well as the mucosal lesions, is believed to be directly proportional to the levels of desmoglein 3. Milder forms of pemphigus (like foliacious and erythematoses) are more desmoglein 1 heavy. It arises most often in middle-aged or older people, usually starting with a blister that ruptures easily. It can also start with blisters in the mouth. The lesions can become quite extensive. The pathogenesis of the disease involves autoantibodies against desmosome proteins, separating keratinocytes from the basal layer of the epidermis. On histology, the basal keratinocytes are usually still attached to the basement membrane leading to the appearance and thus the term, "tombstoning".

Transudative fluid accumulates in between the keratinocytes and basement membrane (suprabasal split), forming a blister and resulting in what is known as a positive Nikolsky's sign. This is a contrasting feature from bullous pemphigoid, which is thought to be due to anti-hemidesmosome antibodies, and where the detachment occurs between the epidermis and dermis (subepidermal bullae).

Diagnosis

On a physical exam, pemphigus vulgaris has flat bullae and a positive Nikolsky's sign. The gold standard for diagnosis is a punch biopsy from the area around the lesion that is examined by direct immunofluorescent staining, showing acantholytic cells. These can also be seen on a Tzanck smear. These cells are basically rounded, nucleated keratinocytes formed due to antibody mediated damage to cell adhesion protein: Desmoglein.

Pemphigus vulgaris is easily confused with impetigo and candidiasis. IgG4 is considered pathogenic. The diagnosis can be confirmed by testing for the infections that cause these other conditions, and by a lack of response to antibiotic treatment.[1] Eosinophils tend to be found within the blisters and provide an important clue supporting bullous pemphigoid as the diagnosis.

Treatment

Corticosteroids and other immunosuppressive drugs have historically been employed to reduce symptoms of pemphigus, yet steroids are associated with serious and long-lasting side effects and their use should be limited as much as possible. IVIg, mycophenolate mofetil, methotrexate, azathioprine, and cyclophosphamide have also been used with varying degrees of success.

An established alternative to steroids are monoclonal antibodies such as rituximab, which are increasingly being used as first line treatment. In numerous case series, a majority of patients achieve remission after one cycle of rituximab. Treatment is more successful if initiated early on in the course of disease, perhaps even at diagnosis. Rituximab treatment combined with monthly IV immune globulin infusion has resulted in long term remission with no recurrence of disease in 10 years after treatment was halted.[2] This was a small trial study of 11 patients with 10 patients followed to completion.

Patient Resources

Patients with pemphigus should be treated by a qualified dermatologist who is familiar with the disease. Contact the International Pemphigus Pemphigoid Foundation for pairing with a peer mentor.

See also

References

  1. ↑ Kaplan DL (2009). "Dermclinic". Consultant 49 (3).
  2. ↑ http://www.nejm.org/doi/full/10.1056/NEJMc1508234
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