Linear IgA bullous dermatosis

Management Strategy

A detailed medical history should be obtained because there are some reports of linear IgA bullous dermatosis occurring after vaccinations, infections, or use of drugs. Moreover, associated diseases such as ulcerative colitis, Crohn disease, and lymphoproliferative malignancies have been rarely reported but should be detected. In case of ocular or ear, nose, and throat (ENT) functional signs, patients should be evaluated by an ophthalmologist or otolaryngologist to delineate mucosal lesions, which may influence the treatment. In patients with mucosal involvement who are at risk of chronic evolution, immunologic investigations (BP180 ELISA, BP230 ELISA, type VII collagen ELISA, immunoblotting) must be performed.

Even if spontaneous remission of linear IgA bullous dermatosis may occur, treatment is required to control flare of blisters. If drug-induced disease is considered, the suspect trigger drug must be withdrawn. Treatment of linear IgA bullous dermatosis is dictated by the severity of disease and the areas of involvement. No therapeutic recommendations exist, and all drugs are used off-label. Because linear IgA bullous dermatosis tends to be chronic, it is important to be aware of the potential, not only for short-term but also for long-term, toxicities in any treatment used.

Despite the absence of controlled trials evaluating dapsone in linear IgA bullous dermatosis, this is the first-line therapy. The majority of patients with disease limited to the skin will respond well, with the mucous membrane lesions being more resistant. Dapsone generally works quite rapidly, with responses often occurring in the first few days of starting the drug. Prior to prescribing dapsone, patients should be screened for glucose-6-phosphate dehydrogenase (G6PD) deficiency because those with a deficiency in this enzyme can develop severe hemolysis and should avoid this drug.

The dosage of dapsone should be individually titrated to determine the best dose that effectively controls the disease. Typically, initial dosage is low (< 0.5 mg/kg) and slowly increased (25 mg per month while monitoring full blood count and liver function tests) until control of blistering is achieved. A dose of 2.5–3.0 mg/kg is usually considered maximal. After disease control is attained, the dosage can then be slowly reduced to the minimum that maintains appropriate control.

All patients treated with dapsone will experience some degree of hemolysis that is usually dose dependent. A reduction of approximately 2–3 g of hemoglobin is often observed. As long as this decrease is relatively gradual and patients have no history of cardiovascular disease or anemia, this is usually well tolerated. Methemoglobinemia, which is also dosage dependent, occurs in most patients but is usually asymptomatic. More worrisome toxicities include bone marrow suppression and even agranulocytosis, which usually happens early in the course of therapy, and a dapsone-induced neuropathy, which appears more commonly in patients treated for several years with more than 200 mg of dapsone daily. Less commonly, hepatitis, nephritis, pneumonitis, erythema multiforme, and dapsone hypersensitivity syndrome have all been reported.

For those patients who fail to achieve satisfactory control of their disease with dapsone as first-line therapy, it is often of value to add corticosteroids . This combination is considered second-line therapy. Topical corticosteroids could be added in mild disease and can even be effective as a sole agent. Systemic corticosteroids may be associated in moderate-to-severe disease; the dosage of prednisone required is often in the 20–40-mg daily range but may be higher. The benefit–risk balance for systemic corticosteroids in children has to be evaluated since these patients are more prone to develop complications arising from the use of steroids.

Alternatives to dapsone are the sulfonamides: salazosulfapyridine (a.k.a. sulfasalazine) and sulfapyridine . Salazosulfapyridine, which is also effective in treating ulcerative colitis and Crohn disease, may be successful given at a dose of 15–60 mg/kg/day. The side effects are similar to dapsone. If the patient is intolerant to dapsone, it is not recommended to use sulfonamides even if some experts mention it is possible. Similarly it is not advised to use dapsone in case of sulfa allergy.

Other applicable second-line therapies include erythromycin at doses of approximately 1.5–3 g daily in adults and 50 mg/kg/day in children, and colchicine , which has been reported to be beneficial at doses of 1.0–1.5 mg daily. Often, erythromycin is used while awaiting confirmation of the diagnosis of linear IgA bullous dermatosis as this drug may have a beneficial effect in the first few months of treatment.

Third-line therapies include sulfamethoxypyridazine , which is available in the UK; antibiotics ( dicloxacillin , oxacillin , flucloxacillin , trimethoprim-sulfamethoxazole , and tetracycline combined with niacinamide ); immunosuppressants ( mycophenolate mofetil , methotrexate , azathioprine , cyclophosphamide , ciclosporin ); and biologic agents ( intravenous immunoglobulin (IVIG) , rituximab , omalizumab ). Toxicity profiles and financial considerations favor using antibiotics before treatment with the immunosuppressive agents or IVIG. However, in the case of life-threatening mucous membrane involvement or blindness risks (ocular, pharyngeal, esophageal, and laryngeal mucosae), immunosuppressive agents may be necessary. In severe or recalcitrant linear IgA bullous dermatosis, rituximab has been reported to be beneficial but necessitating several infusions and having a longer delay of action than in pemphigus.

The efficacy of treatments such as thalidomide, miocamycin, interferon-α, infliximab, tacrolimus ointment, botulinum toxin A, and immunoabsorption has been reported in solitary case reports, making it difficult to draw a conclusion on their therapeutic effect.