Linear IgA dermatosis (ORPHA:46488)
A rare, acquired autoimmune bullous skin disease characterized by annular, grouped blisters on the skin and, frequently, mucous membranes with linear deposition of immunoglobulin A along the basement membrane zone (BMZ).
Epidemiology
The estimated incidence varies worldwide, ranging between 0.2-1/1000,000.
Clinical description
Linear IgA dermatosis (LAD) has two forms: the infantile/childhood form and the adult form. In children, presentation is characterized by annular, tense blisters with new lesions appearing at the periphery of older lesions, giving the ''string of pearls'' appearance. Sites of predilection include the face, lower trunk, perineum, and perioral region. Childhood onset is typically before 5 years of age, rarely affects neonates, and tends to resolve spontaneously before puberty. The adult form typically involves severe pruritus with variable lesions, which may consist of annular papules, vesicles, tense bullae, erythema, urticarial plaques, and/or erosions. Scarring is possible. Sites of predilection include the face, extension faces of the limbs, large body folds, buttocks and trunk. LAD can occur at any age, however there is an increased risk of chronic disease in those less than 70 years of age. Mucous membrane involvement occurs in up to 80% of affected children and 70% of affected adults and can affect oral, nasal, pharyngeal, or esophageal mucosa. Drug induced LAD tends to be more severe than the spontaneous form. Lesions occur between 1 and 30 days after treatment and can result in toxic epidermal necrolysis that can be fatal. The disease is associated with ulcerative colitis prior to LAD onset, and with an increased risk of developing lymphoproliferative diseases.
Etiology
Spontaneous LAD is mediated by IgA autoimmunity which targets heterogeneous antigens of either the lamina lucida or sublamina densa of the BMZ. LAD can also be triggered by various drugs including vancomycin, beta lactam antibiotics, captopril, or non-steroidal anti-inflammatory drugs. Infections and malignancies have also been suspected as possible factors triggers in LAD.
Diagnostic methods
Histology analysis on skin biopsy typically demonstrates features of subepidermal blisters with a prominent neutrophilic infiltrate and linear and positive direct immunofluorescence microscopy demonstrates continuous deposition of IgA in the BMZ and/or IgG and C3. Indirect immunofluorescence microscopy on patients's sera demonstrates that circulating IgA anti-basement membrane binds the epidermal side of 1 M NACL split human skin.
Differential diagnosis
Differential diagnosis includes bullous pemphigoid, dermatitis herpetiformis, mucous membrane pemphigoid, lichen planus, lichenoid drug reaction, contact allergy, and other causes of toxic epidermal necrolysis.
Management and treatment
Dapsone and sulfapyridine (or sulfasalazine) as are the preferred therapeutics in combination with topical corticosteroids and general supportive care for skin lesions. Systemic corticosteroids may be used in severe cases. Erythromycin, colchicine, flucloxacillin, intravenous immunoglobulin, azathioprine, mycophenolic acid, and immunoadsorption have been also used in unresponsive patients. Some severe cases have been treated with rituximab. In case of drug induced LAD, the culprit drug is withdrawn and a short course of corticosteroids may be considered.
Prognosis
Prognosis is generally better for children, who frequently have spontaneous resolution and long-term remission. The prognosis is variable in adults who may have complete remission or suffer chronic disease either with permanent lesions or relapse.

                            Last update: 
                            April 2020


                            - Expert reviewer(s): 
                            Dr Marion CASTEL | ERN-Skin* - Pr Pascal JOLY | ERN-Skin*


                                * European Reference Network