Linear IgA Bullous Dermatosis
- Linear IgA bullous dermatosis is an autoimmune, mucocutaneous blistering disorder in adults and children, characterized by linear IgA deposition on direct immunofluorescence of the skin.
- Cases may be idiopathic or drug-induced. Many other disease associations have been reported, though further studies are needed to determine their strength and significance.
- First-line treatment is oral dapsone. Systemic corticosteroids and other immunomodulators are sometimes necessary for severe or refractory cases.
Linear IgA bullous dermatosis (LABD) is an acquired, immune-mediated mucocutaneous blistering disorder. It is characterized by the linear deposition of immunoglobulin A (IgA) along the basement membrane zone on direct immunofluorescence of the skin. LABD occurs in both adults and children and can be idiopathic or drug-induced. In adults, disease tends to occur in two peaks; young adults and patients over 60 years of age.
In adults, the clinical manifestations of LABD can be varied. The classic morphology is blisters arranged in an annular or herpetiform pattern on normal, erythematous, or urticarial skin. Other less common variants include non-bullous (morbilliform or eczematous), targetoid, and a severe, toxic epidermal necrolysis (TEN)-like variant characterized by a positive Nikolsky’s sign and extensive skin denudation. Lesions are often pruritic, though they can rarely be asymptomatic. The face (especially periorally), trunk, and extensor extremities are the most commonly affected areas in adults.
Oral mucosal involvement including vesicles, erosions, and ulcerations occurs in approximately 30-45% of patients. Oral lesions are frequently located on the palate or buccal mucosa. About 10% of patients have conjunctival involvement (conjunctival injection, discharge, or a gritty sensation) that can lead to significant scarring complications including symblepharon and ectropion. Nasopharyngeal, esophageal and rarely tracheobronchial mucosal involvement have also been reported. In most patients, the disease is limited to mucocutaneous involvement, though there are rare reports of associated IgA nephropathy.
Childhood LABD, also known as chronic bullous disease of childhood (CBDC) typically presents around 4.5 years and resolves prior to puberty. Like classic adult LABD, childhood LABD typically presents with annular or arciform bullae. Crusts form over old lesions and new bullae can develop at the edge leading to an annular configuration that can resemble a “string of pearls” or “crown of jewels.” In children, bullae favor flexural areas including the lower abdomen, buttocks, genitalia, and upper thighs.
Linear IgA dermatosis is commonly a drug-induced disease. Clinical manifestations do not usually differ from idiopathic disease. Onset is typically within two weeks of drug exposure.
Culprit drugs include:
- Antibiotics: vancomycin* (most common), penicillins, cephalosporins, moxifloxacin, sulfonamide antibiotics
- Anticonvulsants: phenytoin*, carbamazepine
- Anti-hypertensives: ACE inhibitors (especially captopril), angiotensin receptor antagonists
- Others: NSAIDs, furosemide, interleukin-2, interferon-alpha, PUVA, cyclosporine, statins, amiodarone, lithium
LABD has also been reported in association with inflammatory bowel disease, especially ulcerative colitis, and gluten sensitive enteropathy (though some authors argue that these cases are actually cases of dermatitis herpetiformis). Other reported associations include internal malignancies, paraproteinemia, autoimmune diseases, and infections (upper respiratory tract infections [URIs]) and varicella zoster virus). In children, the most common associations are URIs and the use of penicillins.
Further studies are needed to confirm the strength and significance of these reported associations. In contrast to dermatitis herpetiformis, gluten-free diets do not typically improve LABD and should not be routinely recommended. In addition, in the absence of any concerning signs or symptoms, additional malignancy screening beyond an age-appropriate evaluation is not routinely recommended in LABD patients.
The natural course of disease is persistence for several years with eventual spontaneous remission in as many as two-thirds of patients. Childhood LABD typically remits prior to puberty but rarely can recur. Thus, therapeutic medications should be tapered periodically to see if spontaneous remission has occurred. In drug-induced disease, resolution typically occurs within two to six weeks of stopping the offending medication.
* Most commonly associated with TEN-like variant