Pemphigus

Definition

Pemphigus is a group of organ specific autoimmune diseases characterized by the production of autoantibodies to desmogleins (a). They are mucocutaneous blistering diseases that demonstrate a loss of cohesion of the epidermal cells (acantholysis) which result in the formation of clefts in the epidermis. Autoantibodies directed against adhesion molecules cause epidermal keratinocytes to separate, resulting in intraepidermal bullae.

Types

There are two histological types of pemphigus: deep (e.g., pemphigus vulgaris) and superficial (e.g., pemphigus foliaceus). They differ in the epidermal layers that are affected, in the clinical manifestations of the diseases, and in the associated immunologic abnormalities (b).

Pemphigus vulgaire

Pemphigus vulgaire (PV) is the most common form of pemphigus (up to 80% of all pemphigus (c)). It is an acquired autoimmune disease in which IgG antibodies target desmosomal proteins to produce intraepithelial, mucocutaneous blistering. Desmoglein (Dsg) 3 is the major antigen but 50–60% of patients have additional antibodies to Dsg1, the antigen in pemphigus foliaceus.

The underlying antibody profile is a major determinant of the clinical phenotype. Studies have shown a lower mortality in patients with predominantly mucosal PV (1–17%) compared with those with mucocutaneous PV (34–42%) (d).

The mortality of PV was 75% on average before the introduction of corticosteroids in the early 1950s, which may be an underestimate.

Pemphigus Foliaceus

Pemphigus Foliaceus (PF) is the second most common form of pemphigus (b), (5:1 aux États-Unis, but more common in Finland, Afrique du Sud, Mali (e)), and is endemic in some areas of Brazil and Columbia, where an insect vector is suspected but none yet identified. The prognosis of untreated pemphigus foliaceus is more favorable than that of pemphigus vulgaris, as the lesions of pemphigus foliaceus are not as deep, and there is less chance for infection, fluid loss, and metabolic disturbance. Although pemphigus foliaceus is often less severe, the doses of medications required for control are similar to those used for pemphigus vulgaris (although some patients may be treated with drugs like dapsone, and may not require corticosteroids or immunosuppressives).

Clinical Variants

Pemphigus erythematosus (also known as Senear-Usher syndrome) has features of lupus erythematosus.

Fogo selvagem (Portuguese for “wild fire”; also known as endemic pemphigus and Brazilian pemphigus) which may be triggered by exposure to one or more environmental antigens (b).

Drug-Related Pemphigus

Both pemphigus vulgaris and pemphigus foliaceus can be either induced or triggered (i.e., latent disease unmasked) by certain drugs. (Pemphigus that continues after a patient stops using a drug is referred to as triggered, whereas lesions that clear soon after withdrawal are referred to as induced). Although drug-related pemphigus is uncommon, its possibility must be excluded in all patients with newly diagnosed disease. The clinical, histological and immunofluorescence abnormalities of drug-induced pemphigus are similar to those of the idiopathic variety. For a list of drugs please see following a table with known implicated agents.

There are several conditions with the name ‘pemphigus’ that are not the same condition as these discussed. These include:

Paraneoplastic Pemphigus

Paraneoplastic pemphigus (also known as Paraneoplastic autoimmune multi-organ syndrome) shares clinical features of both pemphigus and severe erythema multiforme, and shows cutaneous and systemic involvement (f). It is an autoimmune disease of the skin and oral mucosa that develops in patients with an underlying neoplasm, most typically non-Hodgkins lymphoma. It is characterized by erosions of the oral cavity, and large, tense bullae. Unfortunately, standard treatments for autoimmune blistering diseases fail in most paraneoplastic cases, but may resolve with treatment of underlying neoplasm.

Hailey-Hailey Disease

Familial benign chronic pemphigus, or Hailey-Hailey disease, is a different condition from Pemphigus, and is not an autoimmune condition and therefore the IPPF does not provide support for it. It is instead a hereditary, autosomal dominant disorder marked by multiple vesicles on inflammatory bases, and erosions in skin subject to friction or pressure, such as intertriginous areas. In addition to pharmacologic treatment, therapy includes keeping involved areas dry and free of friction is helpful. For more information and support resources please visit www.haileyhailey.com

Epidemiology

  • PV shows has an approximately equal prevalence among men and women.
  • Peak incidence 30-60 years of age (i)
  • Mean onset of age is 50 À 60 ans (ranges on subtype and can affect persons at all ages)
  • Ethnicity: The disorder tends to affect persons of Mediterranean ancestry but can occur in persons of any ethnicity. Geographic variation is wide, with no special variation within the United States. High prevalence of subtype pemphigus foliaceus in Brazilian rain forest and Columbia.
  • Genetics:
    • The occurrence of the disease in first-degree relatives, although rare, suggests an inherited susceptibility transferred as a dominant trait.
    • Pemphigus is more common in persons with certain HLA allotypes
      • HLA DR4 and DR14 (DRB1*0402 and DRB1*0401 more specifically) crucial in susceptibility
      • HLA-DRB1*0402 is associated with the disease in Ashkenazi Jews and DRB1*1401/04 and DQB1*0503 in non-Jewish patients of European or Asian descent.
  • Socioeconomic features: none known as a risk factor or predictor
  • Incidence of 1-10 new cases per 1 million people worldwide, with variations in different regions and among different ethnic groups. Incidence is increased in patients of Ashkenazi Jewish descent and those of Mediterranean origin (ccc) (as high as 16 À 32 cases per million people)
  • Estimated prevalence of 30,000 40,000 cases in the U.S.
  • Pediatric Profile: Pediatric pemphigus is rare, but identical to adult in presentation

Histology

The basic abnormality in all forms of pemphigus is the separation of keratinocytes (acantholysis). This process leads to the formation of a cleft within the epidermis, which then enlarges into a bulla, which then breakdown into coalescing ulcers. All forms of pemphigus are associated with the presence of circulating and fixed autoantibodies—referred to as intercellular antibodies—against keratinocyte cell-surface antigens.

  • Circulating intercellular antibodies are present in about 80-90% of patients with active disease.
  • Tissue fixed intercellular antibodies are present in lesions and adjacent healthy skin in about 90% of patients.

Clinical Features

Pemphigus Vulgaris

La muqueuse buccale est souvent le premier site de participation. Généralement les patients aura eu plusieurs ulcères oraux (ampoules cassées) qui persistent pendant des semaines à un mois.

PV affecte la muqueuse orale dans presque tous les cas (>80%) et touche la muqueuse orale d'abord dans la majorité des cas (c), et peut en fait être le seul site chez des patients.

Une minorité présentera uniquement avec des érosions cutanées. Peau qui est généralement le haut du thorax, Précédent, cuir chevelu, et le visage, mais les lésions peuvent se produire sur une partie quelconque du corps. Notez que la forme dominante de la peau manifeste le profil d'auto-anticorps Dsg1 (comme dans les pemphigus foliacé Brésilien), alors que la forme dominante de mucosally manifeste le profil d'auto-anticorps Dsg3. Un modèle mixte de la peau et des muqueuses manifeste un profil mixte des auto-anticorps Dsg1 et Dsg3. Cours de condition au cours des semaines à un mois.

Sites souvent négligés notamment autour des clous (manifester comme douloureux, rouge, et gonflées), le pharynx et le larynx (douleur à la déglutition et la voix rauque), et la cavité nasale (la congestion nasale et un écoulement de mucus sanglant, particulièrement perceptible à souffler le nez le matin). Autant que 49% des patients se sont révélées avoir participation laryngée et nasale (a).

Cloquage peut être accompagnée par une douleur intense, démangeaisons, Burning, et picotements. If extensive, cloquage peut entraîner une perte de fluide menaçant le pronostic vital, infection, et défiguration. PV peut également causer des dommages importants à la peau, y compris la perte des ongles et des altérations pigmentaires, faire la rapidité d'intervention et de traitement essentiels à la prévention de l'invalidité.

Si non traitées, les érosions et les bulles de pemphigus vulgaire répandre progressivement, impliquant une augmentation de la surface, et peut devenir compliquée par des infections graves et de troubles métaboliques.

Avant l'avènement des corticostéroïdes, Pemphigus avait un taux de létalité élevé, avec environ 70+% des patients meurent dans l'année (q, p).

Avec le traitement, lesions can heal normally without scarring and the hyperpigmentation associated with pemphigus often resolves after several months (r). La plupart des patients traités pour pemphigus entrera une remise partielle au sein de 2 À 5 ans. (Dans une étude longitudinale des résultats dans 40 patients atteints de pemphigus vulgaire, 45% entré une rémission complète et à long terme après 5 ans et 71% après 10 ans (b).

Pemphigus vulgaire (or foliaceus) may present or worsen during pregnancy, especially in the first and second trimesters, and is associated with an increased risk of premature birth and fetal death (o).

Pemphigus Foliaceus

Pemphigus foliaceus usually begins with small (approximately 1 cm), pruritic, crusted lesions resembling corn flakes on the upper torso and face. The crusts are easily removed, leaving chronic, superficial erosions.

Over weeks to months, the condition progresses, with an increasing number of lesions appearing on the upper torso, face, and scalp. In extensive cases, lesions develop over the entire body, become confluent, and can progress to an ‘exfoliative erythroderma’.

In contrast to pemphigus vulgaris, oral involvement in pemphigus foliaceus does not occur.

(Note: 2 clinical variants: pemphigus erythematosus and fogo selvagem)