**6. Linear IgA bullous dermatosis**

Linear IgA bullous dermatosis (LABD) is a rare autoimmune subepidermal vesiculobullous disease, characterized by linear deposition of IgA along the basement membrane zone [57]. The disease is caused by IgA autoantibodies directed against different antigens of the basement membrane zone (BMZ) which are extracellular polypeptides of BP180 or collagen VII [58]. LABD may be idiopathic or due to different triggering factors including drugs and systemic autoimmune diseases (rheumatoid

arthritis, psoriasis, systemic lupus erythematosus, Crohn's disease, and ulcerative colitis), infections (upper respiratory tract, gynecological infections, typhoid, brucellosis, varicella zoster, and tetanus), malignancies(bladder cancer) or less frequently, traumatic events such as burns and exposure to ultraviolet light [59–61].

The relationship between disease with drugs is well known. Vancomycin is the drug that most commonly causes LABD, followed by phenytoin and trimethoprim/ sulfamethoxazole. The other commonly responsible drugs are antibiotics, non-steroidal anti-inflammatory agents, antiepileptic agents, or antihypertensives [60, 62].

The disease can occur in both adults and children. In children, the disease is known as "chronic bullous disease of childhood", that occurs in prepubertal children and has a self-healing course until adulthood [63].

LABD lesions, as in other subepidermal bullous diseases present as vesicles and tense bullae located on erythematous or normal skin and usually involve the trunk, extensor surfaces, buttocks, and face [61]. The typical clinical manifestation of LABD is an annular erythematous lesion with a ring of vesicles, a so-called "string of pearl, cluster of jewels, or rosette pattern" configuration [63, 64]. This configuration is more common in children and common locations are the trunk, the limbs, the perineum, and the perioral areas [65].

Mucous membrane involvement is common in both adults and children. The mucosa is involved more often in children than in adults [63]. While skin lesions heal without scarring, mucosal lesions may result in significant scarring. The disease is most commonly seen in the oral mucosa and conjunctiva. Mucosal strictures and corneal and conjunctival scars are the most important causes of morbidity [53, 66].

LABD clinical findings may be similar to toxic epidermal necrolysis (TEN), and even Nikolsky positivity may be seen. This situation should be kept in mind when making a differential diagnosis and a direct immunofluorescence examination should be performed [60].

Histopathological examination reveals the presence of subepidermal blisters associated with a dermal infiltrate of neutrophils and eventually eosinophils and mononuclear cells [64]. Neutrophil microabscesses at the tip of the dermal papillae may be seen [61]. In DIF examination, there is a linear accumulation of IgA along the basement membrane. IgG, IgM, and C3 accumulation may also be observed [67].

When the diagnosis of LABD is made, first of all, the patient's drug history should be well questioned. In drug-related diseases, first of all, the responsible drug should be discontinued [59]. Because drug-induced LABD has a good prognosis and most cases resolve within 2–6 weeks after discontinuation of the causative drug [66].

Topical potent corticosteroids can be used as the first choice in mild and localized diseases. In severe diseases, they are preferred in addition to systemic treatment [61].

Dapsone is considered the first-line therapy for LABD. The disease shows improvement within 2–3 days after dapsone therapy is started [66]. The dosage is 0.5–3 mg/kg/day for children and 25–150 mg/day for adults. The treatment should be started with a low dose, and the dose should be increased at intervals of 1–2 weeks until the disease is under control. Before starting treatment, the patient's glucose 6 phosphate dehydrogenase (G6PD) enzyme levels should be checked. This treatment should not be started for those with low enzyme levels. Due to the side effects of dapsone such as hemolytic anemia, agranulocytosis, dapsone hypersensitivity syndrome, leukopenia, methemoglobinemia, peripheral neuropathy, nephrotic syndrome, and abnormalities of liver function tests, patients should be followed closely during

treatment and laboratory tests should be repeated at regular intervals. Hemogram and liver tests should be checked weekly for the first 1 month, then monthly for 6 months. In long-term treatment, controls can be made every 6 months [61, 66, 67].

Sulfonamides, including sulfapyridine and sulfamethoxy-pyridazine, oral corticosteroids, tetracycline and nicotinamide, colchicine, and trimethoprim-sulfamethoxazole can be used in the treatment of cases that do not response or partial response to dapsone [59, 61, 66].
