IgA Pemphigus Clinical Presentation

Updated: Apr 18, 2017
  • Author: Blanca Anais Estupiñan; Chief Editor: Dirk M Elston, MD  more...
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Presentation

History

Patients affected with IgA pemphigus usually have subacute onset of disease. In more than one half of reported patients, pruritus is present.

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Physical Examination

IgA pemphigus is a vesiculopustular skin disease. In general, lesions form within erythematous plaques but also can form in skin without plaques. The initial, clear, fluid-filled blisters associated with IgA pemphigus fill with neutrophils and transform into pustules. Note the following:

In some IgA pemphigus patients, neutrophils settle at the lower part of the blister, forming a hypopyon pattern. Lesions usually became flaccid after an initial tense appearance. Some lesions become crusted and form a herpetiform pattern. [28]

In most IgA pemphigus patients, the trunk and proximal extremities primarily are involved. In some IgA pemphigus patients, scalp and postauricular areas are involved extensively. In some IgA pemphigus patients, intertriginous areas (axillary and inframammary areas) are involved. Mucous membranes, palms, and soles usually are spared. In one patient with IgA pemphigus, involvement of perianal skin and oral mucosa was observed. [29]

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Causes

The exact pathomechanism of IgA pemphigus is not well defined at the present time. Clearly, IgA autoantibodies are initiated to target desmosomal components, although the initiating mechanism is unknown. At least 3 desmosomal components, including desmoglein 3 (in intraepidermal neutrophilic–type [IEN-type] IgA pemphigus), desmoglein 1, and desmocollin 1 (in subcorneal pustular dermatosis–type [SPD-type] IgA pemphigus foliaceus), have been identified as target antigens in IgA pemphigus. [15, 16, 17, 18, 6, 19, 20] Other unidentified target antigens also may be involved.

A possible role for a specific cytokine has been postulated in IgA pemphigus. Interleukin 5, a TH 2-secreted cytokine that preferentially induces B cells to produce IgA class antibodies, may be activated preferentially in patients with IgA pemphigus.

A possible role for specific T-cell receptors (TCRs) has also been suggested in IgA pemphigus. Gamma/delta TCR-containing T cells, which have been found to be important in influencing mucosal IgA production, may be involved in the IgA pemphigus process. [21]

Additionally, a possible role for the binding site for monocyte/granulocyte IgA-Fc receptor (CD89) in human IgA subclass 1 (IgA1) has been suggested for IgA pemphigus. Human IgA1 antibody has a binding site for the monocyte/granulocyte IgA-Fc receptor (CD89) that is located distally to the hinge region, thus providing a stronger resistance to protease digestion. The protease-resistant property of IgA1 may provide efficient binding of neutrophils, thus allowing the intraepidermal neutrophil infiltration that may contribute to the blistering process. [9]

Postembedding immunoelectron microscopy has localized the target antigen of the SPD-type IgA pemphigus to the extracellular domain of desmocollin, whereas the target antigen of the IEN-type IgA pemphigus was found to be in an intercellular space outside the desmosomal areas. These findings suggest that the pathomechanism of IgA pemphigus involves the weakening of extracellular components of cell-to-cell adhesion molecules.

An association of IgA pemphigus and IgA gammopathy and lung cancer has been reported. [22] Additionally, an association of peripheral T-cell lymphoma complicated by IgA pemphigus has been reported. [23]

The 2005 report of cases of pemphigus characterized by the presence of both IgA and IgG classes of autoantibodies raises the question of whether this IgA/IgG pemphigus is a subset of IgA pemphigus or a novel disease entity. [24]

In some cases of IgA pemphigus, IgA autoantibodies from a single patient were detected against all 3 desmocollin proteins (desmocollins 1, 2, and 3), [25] and, in some patients, IgA autoantibodies from an individual patient were found to recognize both desmocollin and desmoglein proteins. [26] These cases of multiple target antigens identified by patient IgA autoantibodies support the occurrence of epitope spreading, an interesting autoimmune phenomenon in which the inflammatory event "releases" a new target antigen (or antigens) to be recognized by the immune system, leading to a subsequent autoimmunity to the new target antigen (or antigens). [27]

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