P/P Clinical Information

Key features: Mucosal or mucosal and cutaneous involvement, blisters on the upper skin layer, autoantibodies attack desmoglein 3 or both desmoglein 1 and desmoglein 3

Clinical variants: Pemphigus vegetans, pemphigus herpetiformis

• The pain associated with mucosal involvement of pemphigus vulgaris can be severe.
• Oral pain is often augmented by chewing and swallowing, which may result in poor alimentation, weight loss, and malnutrition.

Pemphigus vulgaris is the most common form of pemphigus. However, in certain areas, particularly in locations where an endemic form of pemphigus foliaceus occurs, pemphigus foliaceus is more prevalent.

Almost all patients with pemphigus vulgaris develop mucosal involvement. The oral cavity is the most common site of mucosal lesions and often represents the initial site of disease. Mucous membranes at other sites are also often affected, including the conjunctiva, nose, esophagus, vulva, vagina, cervix, and anus. In women with cervical involvement, the histological findings of pemphigus vulgaris may be mistaken for cervical dysplasia in Papanicolaou (Pap) smears.

Since mucosal blisters erode quickly, erosions are often the only clinical findings. The buccal mucosa and palatine mucosa are the most common sites for lesion development in the oral cavity.

Most patients also develop cutaneous involvement manifesting as flaccid blisters on normal-appearing or erythematous skin. The blisters rupture easily, resulting in painful erosions that bleed easily. Pruritus usually is absent. Although any cutaneous site may be affected, the palms and soles are usually spared. The Nikolsky sign (induction of blistering via mechanical pressure at the edge of a blister or on normal skin) often can be elicited.

Key features: Cutaneous (skin) involvement only, subcorneal acantholytic blisters, autoantibodies against desmoglein 1

Clinical variants: Endemic pemphigus foliaceus (fogo selvagem), pemphigus erythematosus (Senear-Usher syndrome), pemphigus herpetiformis

• Pain or burning sensations frequently accompany the cutaneous lesions. Systemic symptoms are usually absent.
• The clinical manifestations of drug-induced pemphigus foliaceus are similar to idiopathic disease.

Pemphigus foliaceus is a superficial variant of pemphigus that presents with cutaneous lesions. The mucous membranes are typically spared.

Pemphigus foliaceus usually develops in a seborrheic distribution. The scalp, face, and trunk are common sites of involvement. The skin lesions usually consist of small, scattered superficial blisters that rapidly evolve into scaly, crusted erosions. The Nikolsky sign often is present. The skin lesions may remain localized or may coalesce to cover large areas of skin. Occasionally, pemphigus foliaceus progresses to involve the entire skin surface as an exfoliative erythroderma.

Key features: Grouped vesicles or pustules and erythematous plaques with crusts, subcorneal or intraepidermal blisters, autoantibodies against desmocollin 1

Subtypes: Subcorneal pustular dermatosis-type IgA pemphigus (Sneddon-Wilkinson disease), intraepidermal neutrophilic IgA dermatosis

• The subcorneal pustular dermatosis type of IgA pemphigus is clinically similar to classic subcorneal pustular dermatosis (Sneddon-Wilkinson disease).
• Immunofluorescence studies are necessary to distinguish these diseases.

Both the subcorneal pustular dermatosis and intraepidermal neutrophilic IgA dermatosis types of IgA pemphigus are characterized by the subacute development of vesicles that evolve into pustules. The vesicles and pustules are usually, but not always, accompanied by erythematous plaques. A herpetiform, annular, or circinate pattern may be present.

The trunk and proximal extremities are common sites for involvement. The scalp, postauricular skin, and intertriginous areas are less common sites for lesion development. Pruritus may or may not be present. Mucous membranes are usually spared.

Key features: Extensive, intractable stomatitis and variable cutaneous findings; associated neoplastic disease; suprabasal acantholytic blisters; autoantibodies against desmoplakins or other desmosomal antigens

• Life-threatening pulmonary involvement consistent with bronchiolitis obliterans also may be seen.
• Paraneoplastic pemphigus is the rarest form of the pemphigus types.

Paraneoplastic pemphigus (also known as paraneoplastic autoimmune multiorgan syndrome) is an autoimmune multi-organ syndrome associated with neoplastic disease. Typically, patients suffer from severe and acute mucosal involvement with extensive, intractable stomatitis. The cutaneous manifestations are variable, and include blisters, erosions, and lichenoid lesions that may resemble other autoimmune blistering diseases, erythema multiforme, graft versus host disease, or lichen planus.

Mucous membrane pemphigoid (MMP) is a chronic autoimmune disorder characterized by blistering lesions that primarily affect the various mucous membranes of the body, but also affects the skin (MMP is now the preferred term for lesions only involving the mucosa). It is also known as Cicatricial Pemphigoid (CP), as it is often scarring.

The mucous membranes of the mouth and eyes are most often affected, but those of the nose, throat, genitalia, and anus may also be affected. The symptoms of MMP vary among affected individuals depending upon the specific site(s) involved and the progression of the disease. Disease onset is usually between 40 and 70 years and oral lesions are seen as the initial manifestation of the disease in about two thirds of the cases. Blistering lesions eventually heal, sometimes with scarring. Progressive scarring may potentially lead to serious complications affecting the eyes and throat.

There is no racial or ethnic predilection although most studies have demonstrated a female to male ratio of approximately 2:1. The diagnosis of MMP is mainly based on history, clinical examination and biopsy of the lesions.

Bullous Pemphigoid (BP) is a subepidermal blistering autoimmune disease that primarily affects the skin, especially the lower abdomen, groin, and flexor surfaces of the extremities. Mucous membrane involvement is seen in 10%-40% of patients. The disease tends to persist for months or years with periods of exacerbation and remission.

The spectrum of presentations is extremely broad, but typically there is an itchy eruption with widespread blistering, and tense vesicles and bulla (blisters), with clear fluid (can be hemorrhagic) on apparently normal or slightly erythematous skin.

Lesions normally appear on the torso and flexures, particularly on the inner thighs. Blisters can range in size from a few millimeters to several centimeters, and although pruritic, typically heal without scarring.

Sometimes erosions and crusting is seen. Also itchy bumps (papules) and crusts (plaques) can be seen with an annular or figurate pattern. A characteristic feature is that multiple bullae usually arise from large (palm-sized or larger), irregular, urticarial plaques. Mucosal (oral, ocular, genital) involvement is also sometimes present, but ocular involvement, is rare. BP can be difficult to diagnose in its ‘non-blistering’ stage, when just itchy, red, elevated patches are visible. Erosions are much less common than in pemphigus, and the Nikolsky sign is negative.

BP is characterized by spontaneous remissions followed by flares in disease activity that can persist for years. Even without therapy, BP is often self-limited, resolving after a period of many months to years, but may become very extensive.

Localized variants of the disease have been reported, most often limited to the lower extremities and usually affecting women. One such variant, localized vulvar pemphigoid, reported in girls aged 6 months to 8 years, presents with recurrent vulvar vesicles and ulcerations that do not result in scarring.

Bullous pemphigoid is distinguished from other blistering skin diseases, such as linear IgA dermatosis, epidermolysis bullosa acquisita, and MMP/cicatricial pemphigoid, by the following clinical items (it can also be distinguished by biopsy and certain immunological tests):

• Absence of atrophic scars;
• Absence of head and neck involvement;
• Relative absence of mucosal involvement.

Pemphigoid gestationis (PG) is a rare autoimmune bullous dermatosis of pregnancy. The disease was originally named herpes gestationis on the basis of the morphological herpetiform feature of the blisters, but this term is a misnomer because PG is not related to or associated with any active or prior herpes virus infection. PG typically manifests during late pregnancy, with an abrupt onset of extremely pruritic urticarial papules and blisters on the abdomen and trunk, but lesions may appear any time during pregnancy, and dramatic flares can occur at or immediately after delivery. PG usually resolves spontaneously within weeks to months after delivery.