Alerts and Notices
SynopsisImmunoglobulin A (IgA) pemphigus (nonclassic subcorneal pustular dermatosis) is a rare autoimmune blistering disorder. Unlike other forms of pemphigus that are mediated by immunoglobulin G (IgG) autoantibodies, IgA pemphigus is caused predominantly by IgA antibodies that are directed against various adhesion molecules expressed by keratinocytes.
There are 4 subtypes of IgA pemphigus: (1) subcorneal pustular dermatosis (SPD), (2) intraepidermal neutrophilic (IEN), although clinical overlap among subtypes as well as with other autoimmune bullous dermatoses (eg, pemphigus) has been reported, (3) IgA pemphigus foliaceus (PF), and (4) pemphigus vulgaris-like (PVe) IgA pemphigus. The PVe subtype is thought to be a type of pyodermatitis-pyostomatitis vegetans, which is associated with inflammatory bowel disease.
The SPD subtype is characterized by IgA autoantibodies directed against desmocollin 1 (not commercially available). The remaining 3 subtypes are characterized by a heterogeneous group of autoantigens (including desmoglein 1 or desmoglein 3), as well as desmocollin 1, 2, and 3.
Epidemiological data on IgA pemphigus is limited. Studies suggest a slight predominance among women, with an average age of onset in the fifth decade, although the condition has been reported in patients ranging in age from 1 month to 94 years. The clinical phenotype of IgA pemphigus is generally milder than other forms of pemphigus, although significant morbidity may be observed on occasion.
Malignancies have been reported in around 20% of patients. Reported associated malignancies include IgA gammopathy, IgA multiple myeloma, peripheral T-cell lymphoma, chronic myeloid leukemia, diffuse large B-cell lymphoma, and, less commonly, solid organ malignancies (ie, lung, pancreatic, laryngeal, and ovarian). Malignancy can be diagnosed simultaneously with, or after development of, IgA pemphigus. Other associated conditions include gastrointestinal disorders (ie, ulcerative colitis, Crohn disease, and celiac disease), autoimmune diseases (ie, Sjögren syndrome, myasthenia gravis, and rheumatoid arthritis), and HIV infection.
Related topic: subcorneal pustular dermatosis
L10.89 – Other pemphigus
402717008 – IgA Pemphigus
Differential Diagnosis & Pitfalls
- Classic subcorneal pustular dermatosis (Sneddon-Wilkinson disease) – Identical clinical and histologic features of IgA pemphigus, but the direct immunofluorescence (DIF) is negative.
- Pemphigus foliaceus – Look for superficial, fragile vesicles or bullae upon the scalp, face, and trunk in a seborrheic distribution. DIF is classically characterized by intercellular IgG.
- Mixed IgA / IgG pemphigus shows positivity on DIF to both intercellular IgG and IgA. Clinical features may parallel IgA pemphigus or pemphigus foliaceus.
- Bullous impetigo / pediatric bullous impetigo – Superficial, flaccid vesicles that progress to serous or yellow-filled bulla with minimal erythema. Secondary yellow crusting is common.
- Linear IgA bullous dermatosis of childhood – Look for grouped or annular papules, vesicles, or bullae on the extensor surfaces and buttocks. New lesions may present at the peripheral edge of a previous blister, giving it a "crown of jewels" appearance. DIF shows linear deposition of IgA along the basement membrane zone.
- Pustular psoriasis – Localized or widespread, erythematous, sterile pustules that may be distributed in "sheets" or in a more localized, annular pattern.
- Dermatitis herpetiformis – Classically presents as fragile, clustered vesicles commonly on the elbows, knees, and buttocks in the setting of an underlying gluten-sensitive enteropathy. DIF shows granular deposition of IgA at the dermal papillae, or, less commonly, continuous, granular, or fibrillar deposition of IgA along the basement membrane zone.