Definition

Linear immunoglobulin A (IgA) disease is an acquired autoimmune blistering disease of the skin and mucous membranes that runs a chronic course over 3 to 6 years before remitting. It typically presents with papulovesicles and blisters configured in an arcuate pattern on an urticated base with 2 peaks in age of onset, although it can occur at any age. The first peak is in young prepubescent children, called chronic bullous disease of childhood, and the second peak affects patients older than 60 years of age.

The disease is characterized by subepidermal blistering and linear deposition of IgA along the dermoepidermal basement membrane zone. The clinical presentation, diagnosis, and pathogenesis have been covered in a recent issue of Dermatologic Clinics (Venning, 2011). In this article, the management of linear IgA in adults is considered, the management of children will be dealt with in the article by Mintz & Morel elsewhere in this issue.

Treatment

Linear IgA can be induced by drugs, including vancomycin; captopril; cephalosporins; nonsteroidal antiinflammatory drugs, such as diclofenac; as well as a wide range of other drugs reported in the literature. When drug-induced disease is considered, withdrawal of the suspect drug is essential.

The treatment of linear IgA disease should be tailored to the extent of involvement and the severity of the disease, with consideration being given to preexisting comorbidities that may influence treatment choice. Potent topical steroids in the form of clobetasol propionate can be an effective monotherapy for patients with mild disease. There have been case reports of successful control of this disease with antiinflammatory antibiotics, such as tetracyclines, and macrolide antibiotics alone or in combination with nicotinamide and topical steroids.

The majority of patients with cutaneous disease respond effectively to dapsone as a first-line therapy in dosages of 50 to 200 mg/d. This response is usually rapid, with a clinical response occurring within the first few days of starting therapy. Mucous membrane involvement is typically more resistant to single-agent treatment with dapsone.

Before commencing patients on dapsone, a glucose-6-phosphate dehydrogenase (G6PD) level should be obtained because a deficiency in this enzyme can lead to severe hemolysis. A reduction of 1 to 2 g/dL of hemoglobin is frequently observed in patients with normal G6PD levels and is usually well tolerated as long as the reduction is gradual and there are no significant comorbidities of anemia or ischemic heart disease.

Other well-established side effects associated with dapsone therapy are dose-related methemoglobinemia; bone marrow suppression, including agranulocytosis; and a motor peripheral neuropathy. Other less-common side effects include hepatitis, pneumonitis, nephritis, erythema multiforme, and dapsone hypersensitivity.

Sulfonamides, including sulfapyridine or sulfamethoxypyridazine (dosages range from 250 mg to 2 g/d), are alternatives to dapsone and can be used either as an alternative or in combination with dapsone. Both drugs have a similar side-effect profile to dapsone, but dapsone intolerance does not preclude their use.

For patients resistant or achieving only partial response to dapsone therapy, systemic corticosteroids/prednisolone in combination with dapsone can be trialed in dosages of up to 40 mg daily to achieve optimal control.

In patients who are resistant to the aforementioned therapies, azathioprine or cyclosporine has had favorable reports of achieving disease control. There have been isolated case reports of treatment with mycophenolate mofetil, nicotinamide/niacinamide, colchicines, intravenous immunoglobulins, and immunosorption.

It is postulated that patients who are more resistant to treatment have both IgG and IgA deposits on the basement membrane zone, which indicates multiple target antigens and possible prolonged antigenic stimulation.

Because this disease can spontaneously remit, there should be repeated attempts at tapering treatment once control has been achieved to ascertain whether remission has occurred.

Treatment

Linear IgA can be induced by drugs, including vancomycin; captopril; cephalosporins; nonsteroidal antiinflammatory drugs, such as diclofenac; as well as a wide range of other drugs reported in the literature. When drug-induced disease is considered, withdrawal of the suspect drug is essential.

The treatment of linear IgA disease should be tailored to the extent of involvement and the severity of the disease, with consideration being given to preexisting comorbidities that may influence treatment choice. Potent topical steroids in the form of clobetasol propionate can be an effective monotherapy for patients with mild disease. There have been case reports of successful control of this disease with antiinflammatory antibiotics, such as tetracyclines, and macrolide antibiotics alone or in combination with nicotinamide and topical steroids.

The majority of patients with cutaneous disease respond effectively to dapsone as a first-line therapy in dosages of 50 to 200 mg/d. This response is usually rapid, with a clinical response occurring within the first few days of starting therapy. Mucous membrane involvement is typically more resistant to single-agent treatment with dapsone.

Before commencing patients on dapsone, a glucose-6-phosphate dehydrogenase (G6PD) level should be obtained because a deficiency in this enzyme can lead to severe hemolysis. A reduction of 1 to 2 g/dL of hemoglobin is frequently observed in patients with normal G6PD levels and is usually well tolerated as long as the reduction is gradual and there are no significant comorbidities of anemia or ischemic heart disease.

Other well-established side effects associated with dapsone therapy are dose-related methemoglobinemia; bone marrow suppression, including agranulocytosis; and a motor peripheral neuropathy. Other less-common side effects include hepatitis, pneumonitis, nephritis, erythema multiforme, and dapsone hypersensitivity.

Sulfonamides, including sulfapyridine or sulfamethoxypyridazine (dosages range from 250 mg to 2 g/d), are alternatives to dapsone and can be used either as an alternative or in combination with dapsone. Both drugs have a similar side-effect profile to dapsone, but dapsone intolerance does not preclude their use.

For patients resistant or achieving only partial response to dapsone therapy, systemic corticosteroids/prednisolone in combination with dapsone can be trialed in dosages of up to 40 mg daily to achieve optimal control.

In patients who are resistant to the aforementioned therapies, azathioprine or cyclosporine has had favorable reports of achieving disease control. There have been isolated case reports of treatment with mycophenolate mofetil, nicotinamide/niacinamide, colchicines, intravenous immunoglobulins, and immunosorption.

It is postulated that patients who are more resistant to treatment have both IgG and IgA deposits on the basement membrane zone, which indicates multiple target antigens and possible prolonged antigenic stimulation.

Because this disease can spontaneously remit, there should be repeated attempts at tapering treatment once control has been achieved to ascertain whether remission has occurred.