emedicine.medscape.com eMedicine Specialties > Dermatology > Bullous Diseases Pemphigus, IgA Lawrence Chan, MD, Department Head and Director of Skin Immunology Research, Professor, Departments of Dermatology and Microbiology/Immunology, University of Illinois College of Medicine Updated: Sep 24, 2008 Introduction Background Immunoglobulin A (IgA) pemphigus is a group of newly characterized immune-mediated intraepidermal blistering skin diseases. Unlike typical immunoglobulin G (IgG)–mediated pemphigus, IgA pemphigus is characterized by tissue- bound and circulating IgA autoantibodies that target the desmosomal proteins of the epidermis. Histopathologically, epidermal acantholysis and neutrophil infiltration predominate, hence the synonyms intraepidermal neutrophilic IgA dermatosis, intraepidermal IgA pustulosis, IgA herpetiform pemphigus, and intercellular IgA vesiculopustular dermatosis have been used to describe this group of diseases. No consensus has been reached concerning the nomenclature. IgA pemphigus has not been described in animals. Although the term IgA pemphigus has not been established in the veterinary literature, IgA deposition around epidermal cells has been detected by direct immunofluorescence in animals affected with pemphigus foliaceus. The following eMedicine articles on other types of pemphigus may be of interest: • Pemphigus Erythematosus • Pemphigus Foliaceus • Pemphigus Herpetiformis • Pemphigus Vulgaris • Pemphigus, Drug-Induced • Pemphigus, Paraneoplastic Pathophysiology The exact pathomechanism of IgA pemphigus is not well defined. According to currently available data, IgA autoantibodies clearly bind to desmosomal components of the epidermis, desmogleins, or desmocollins. Since the IgA autoantibodies possess specific binding sites for the monocyte/granulocyte IgA-Fc receptor (CD89), hypothesis indicates that neutrophils accumulate intraepidermally, causing the blistering process to occur.1,2,3 The direct pathogenic effects of the IgA autoantibodies have not been established. Frequency United States IgA pemphigus is a group of newly characterized diseases, and its frequency is unknown, although IgA pemphigus has been reported in the United States. International IgA pemphigus is a group of newly characterized diseases, and its frequency is not yet defined. IgA pemphigus has been reported in Asia (including Japan), South America, and Europe (including Scandinavian countries4 ). A 2004 article surveying patients affected by autoimmune blistering diseases in Kuwait suggested that IgA pemphigus may be extremely rare in that part of the world.5 Mortality/Morbidity Mortality directly resulting from IgA pemphigus is not reported. In general, the clinical course of IgA pemphigus is less severe than that of IgG-mediated pemphigus, and no significant morbidity exists. In some patients with IgA pemphigus, pruritus is a significant symptom and may interfere with the patient's daily life. Race IgA pemphigus is a rare disease and is newly characterized; therefore, the race distribution is unknown. IgA pemphigus has been reported in American, European, South American, and Asian patients. Sex The sex distribution is unknown. A review of 28 cases reported from 1982-1997 revealed a male-to-female ratio of 1:1.33. Age IgA pemphigus has been reported to occur in persons aged 1 month6 to 85 years. A review of 28 cases reported from 1982-1997 determined the average age of onset to be alvato da Windows Internet Explorer 8> Subject: Pemphigus, IgA: [Print] - eMedicine Dermatology Date: Fri, 4 Sep 2009 00:44:54 +0200 MIME-Version: 1.0 Content-Type: multipart/related; type="text/html"; boundary="----=_NextPart_000_0147_01CA2CF8.EB600310" X-MimeOLE: Produced By Microsoft MimeOLE V6.00.2900.5579 This is a multi-part message in MIME format. ------ =_NextPart_000_0147_01CA2CF8.EB600310 Content-Type: text/html; charset="Windows-1252" Content-Transfer- Encoding: quoted-printable Content-Location: http://emedicine.medscape.com/article/1063776-print emedicine.medscape.com eMedicine Specialties > Dermatology > Bullous Diseases Pemphigus, IgA Lawrence Chan, MD, Department Head and Director of Skin Immunology Research, Professor, Departments of Dermatology and Microbiology/Immunology, University of Illinois College of Medicine Updated: Sep 24, 2008 Introduction Background Immunoglobulin A (IgA) pemphigus is a group of newly characterized immune-mediated intraepidermal blistering skin diseases. Unlike typical immunoglobulin G (IgG)–mediated pemphigus, IgA pemphigus is characterized by tissue-bound and circulating IgA autoantibodies that target the desmosomal proteins of the epidermis. Histopathologically, epidermal acantholysis and neutrophil infiltration predominate, hence the synonyms intraepidermal neutrophilic IgA dermatosis, intraepidermal IgA pustulosis, IgA herpetiform pemphigus, and intercellular IgA vesiculopustular dermatosis have been used to describe this group of diseases. No consensus has been reached concerning the nomenclature. IgA pemphigus has not been described in animals. Although the term IgA pemphigus has not been established in the veterinary literature, IgA deposition around epidermal cells has been detected by direct immunofluorescence in animals affected with pemphigus foliaceus. The following eMedicine articles on other types of pemphigus may be of interest: • Pemphigus Erythematosus • Pemphigus Foliaceus • Pemphigus Herpetiformis • Pemphigus Vulgaris • Pemphigus, Drug-Induced • Pemphigus, Paraneoplastic Pathophysiology The exact pathomechanism of IgA pemphigus is not well defined. According to currently available data, IgA autoantibodies clearly bind to desmosomal components of the epidermis, desmogleins, or desmocollins. Since the IgA autoantibodies possess specific binding sites for the monocyte/granulocyte IgA-Fc receptor (CD89), hypothesis indicates that neutrophils accumulate intraepidermally, causing the blistering process to occur.1,2,3 The direct pathogenic effects of the IgA autoantibodies have not been established. Frequency United States IgA pemphigus is a group of newly characterized diseases, and its frequency is unknown, although IgA pemphigus has been reported in the United States. International IgA pemphigus is a group of newly characterized diseases, and its frequency is not yet defined. IgA pemphigus has been reported in Asia (including Japan), South America, and Europe (including Scandinavian countries4 ). A 2004 article surveying patients affected by autoimmune blistering diseases in Kuwait suggested that IgA pemphigus may be extremely rare in that part of the world.5 Mortality/Morbidity Mortality directly resulting from IgA pemphigus is not reported. In general, the clinical course of IgA pemphigus is less severe than that of IgG- mediated pemphigus, and no significant morbidity exists. In some patients with IgA pemphigus, pruritus is a significant symptom and may interfere with the patient's daily life. Race IgA pemphigus is a rare disease and is newly characterized; therefore, the race distribution is unknown. IgA pemphigus has been reported in American, European, South American, and Asian patients. Sex The sex distribution is unknown. A review of 28 cases reported from 1982-1997 revealed a male-to-female ratio of 1:1.33. Age IgA pemphigus has been reported to occur in persons aged 1 month6 to 85 years. A review of 28 cases reported from 1982-1997 determined the average age of onset to be 53 years. Clinical History Patients affected with IgA pemphigus usually have subacute onset of disease. In more than one half of reported patients, pruritus is present. Physical 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 fill with neutrophils and transform into pustules. • In some patients, neutrophils settle at the lower part of the blister, forming a hypopyon pattern. • In most patients, the trunk and proximal extremities primarily are involved. • In some patients, scalp and postauricular areas are involved extensively. • In some patients, intertriginous areas (axillary and inframammary areas) are involved. • Mucous membranes, palms, and soles usually are spared. • Lesions usually became flaccid after an initial tense appearance. Some lesions become crusted and form a herpetiform pattern.7 • In one patient, involvement of perianal skin and oral mucosa was observed.8 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 mechanism for such initiation 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.9,10,11,12,13,14,15 Other unidentified target antigens also may be involved. • Possible role of a specific cytokine: 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. • Possible role of specific T-cell receptors (TCRs): 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.16 • Possible role of the binding site for monocyte/granulocyte IgA-Fc receptor (CD89) in human