Description

• Linear immunoglobulin A (IgA) dermatosis is a chronic autoimmune blistering skin disease that affects both adult and pediatric populations (1).
• Both adult and pediatric forms are characterized by subepidermal blisters, neutrophilic infiltrates, and linear deposition of IgA antibodies along the basement membrane zone (BMZ).
• Although the adult and pediatric forms of linear IgA disease share immunopathologic and immunogenetic characteristics, there are notable differences in their clinical presentations and disease courses.

Epidemiology

• Adult linear IgA disease is either idiopathic or drug-induced, with most patients are >60 years.
• Childhood linear IgA disease (also known as chronic bullous disease of childhood) appears in children between the ages of 6 months and 10 years and has an average age of onset between 3 and 5 years (2,3).
• Most childhood cases are idiopathic, benign, and self-limited in nature with spontaneous remission within 2 to 5 years.
• No gender predominance has been confirmed in either the adult or childhood form.

Incidence

• Linear IgA dermatosis is an uncommon disease; most studies cite an incidence of <1 person per 250,000 per year.
• Although rare, chronic bullous disease of childhood is the most common autoimmune blistering disorder in children.

Etiology and Pathophysiology

• The underlying mechanism is not known. Like other autoimmune blistering disorders, it is characterized by autoantibody formation against structural proteins in the epidermis or BMZ.
• Although a number of structural antigens have been implicated in linear IgA dermatosis, most cases involve the 180-kDa bullous pemphigoid antigen 2 (BPAg2), otherwise known as collagen XVII. Specifically, antibodies against the 97-kDa and 120-kDa degradation products of BPAg2 are seen.
• BPAg2 is a transmembrane protein of the lamina lucida layer of the BMZ. IgA antibody deposition in the lamina lucida with complement activation and inflammatory cell chemotaxis (primarily neutrophils) results in histologic division of the epidermis and dermis and subsequent subepidermal blister formation.

Genetics
Studies have demonstrated significantly increased frequencies of human leukocyte antigen (HLA) haplotypes Cw7, B8, DR3, and DQW2. Although frequencies are stronger in children with the disease, the HLA associations are similar in adults and children, supporting the hypothesis that adult linear IgA disease and chronic bullous disease of childhood are variant forms of the same autoimmune blistering disease.

Risk Factors

Many medications have been cited as agents known to induce adult linear IgA disease (4):

• Vancomycin is the most commonly associated medication.
• Angiotensin-converting enzyme (ACE) inhibitors, especially captopril; angiotensin receptor blockers
• Lithium
• Antibiotics, including penicillin, sulfamethoxazole/trimethoprim, and cephalosporins
• Furosemide
• Atorvastatin
• Amiodarone
• Diclofenac
• Carbamazepine; phenytoin
• Interleukin-2; interferon-γ
• Sulfasalazine
• Ustekinumab
• Piperacillin-tazobactam
• Infliximab

Commonly Associated Conditions

• Associations with malignancy has been reported:
  • Lymphoma, both Hodgkin and non-Hodgkin
  • Leukemia, such as chronic lymphocytic leukemia
  • Nonhematopoietic malignancies are less common but include cancers of the breast, bladder, and esophagus.
• Associations with inflammatory bowel disease, especially with ulcerative colitis
• Case reports suggest possible additional associations with autoimmune diseases, such as rheumatoid arthritis, systemic lupus erythematosus, dermatomyositis, multiple sclerosis, IgA nephropathy, and Sjögren syndrome.