Linear IgA Bullous Dermatosis

Linear IgA bullous dermatosis (LABD), also known as linear IgA dermatosis, is a rare immune-mediated disease that results in blistering of the skin, in the subepidermal layers. It is commonly associated with the use of certain drugs.

LABD targets proteins that are found in the basement membrane, which functions as an anchor connecting the epidermis to the dermis, thereby stabilizing the skin structure.

The autoimmune destruction of basement membrane proteins found in layers such as the sublamina densa and the lamina lucida by IgA results in the formation of the typical tense blisters.

LABD may be divided into childhood and adult forms. Chronic bullous disease of childhood is an acquired, self-limited LABD that may present during the first 2 to 3 years of life. It usually goes into remission by the age of 13. It is the most common blistering autoimmune disease of childhood.

Clinically, it may mimic bullous pemphigoid; however, the blisters of LABD have a more ring-like arrangement. A prodromal itch heralds the formation of tense blisters in clusters (the “cluster of jewels”) or a string (“string of beads”). Lesions in children are located in the perioral or anogenital region, or in the perineum.

LABD in adults is an acquired, blistering autoimmune disease that is often very difficult to treat. It is likewise a challenge to distinguish it clinically from other vesicular forms of dermatitis, such as dermatitis herpetiformis (an intensely itchy, blistering disease associated with an autoantigen called epidermal transglutaminase (eTG)).

Like children, adults experience prodromal itching before the onset of blisters. The distribution of the lesions over the body occurs over the trunk, the gluteal region, extensor surfaces, and face.

However, the frequency of the lesions in these areas is less than in children. Both children and adults may develop lesions on the mucous membranes and the eyes.

Pathophysiology of LABD

The exact mechanism involved in the loss of self-tolerance to target antigens in the basement membrane is unknown. However, proteins in the basement membrane bind the IgA antibodies, leading to a linear pattern of IgA deposition. This leads to the activation of the immune system via the complement pathway.

This sequentially causes neutrophils (the most abundant type of white blood cells) to migrate to the site, inducing damage. Blister formation is a consequence of the loss of the adhesive properties of the epithelium at the dermal-epidermal junction.

The pathophysiology underlying drug-induced LABD is not entirely understood. However, it is believed to be as a result of an immune response towards a drug-derived hapten-protein antigen. The drug most frequently implicated is vancomycin, a glycopeptide antibiotic.

Other causes of LABD remain unknown, accounting for the majority of cases of idiopathic disease. When the disease presents in childhood, it tends to go into remission over a few years.

In adults, it has a much more protracted course, and may be linked with other conditions such as infections, malignancies, and other autoimmune diseases.

Treatment and prognosis of LABD

The diagnosis is based upon the typical clinical features and direct immunofluorescence of the skin biopsy sample to identify the autoantibodies. These are followed by serological assays for circulating autoantibodies, such as ELISA or Western blotting techniques.

The treatment of drug-induced LABD begins with the cessation of exposure to the offending agent. Treatment of idiopathic LABD is more complex. It depends on the degree of mucocutaneous involvement, and the identification of any exacerbating factors.

The first-line treatment for LABD is dapsone, which inhibits the local immune response in the skin, suppressing neutrophil activation.

LABD has also been demonstrated to respond to other pharmaceuticals such as colchicine,  sulfonamides, tetracyclines, mycophenolate and intravenous immunoglobulins (IVIG). In addition to these, corticosteroids may also be administered to help reduce inflammation.

For patients with more extensive disease or those who do not respond to any of the conventional treatments, newer therapies include immunoadsorption, rituximab and high-dose IVIG, alone or in combination.

Most cutaneous lesions heal within a few weeks; however, there may be some scarring associated with mucous and ocular lesions.

References

1. http://www.aocd.org/?page=LinearIgABullousD
2. http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3123771/
3. http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3702236/