August 2025
INTRODUCTION —
Linear IgA (immunoglobulin A) bullous dermatosis (LABD) is a rare autoimmune blistering disease characterized by the linear deposition of IgA at the dermoepidermal junction. LABD occurs in both adults and children and can be idiopathic or drug induced.
The treatment of LABD will be reviewed here. The clinical features and diagnosis of LABD and the approach to the diagnosis of blistering disorders are reviewed separately.
●(See "Linear IgA bullous dermatosis: Pathogenesis, clinical features, and diagnosis".)
●(See "Approach to the patient with cutaneous blisters".)
TREATMENT OF IDIOPATHIC DISEASE —
Data on the treatment options for LABD are limited. The approach to treatment is primarily based upon case reports and case series [1].
Initial therapy — Oral dapsone is the preferred initial treatment for idiopathic LABD [2-7].
Oral dapsone — Dapsone is an immunomodulatory sulfone used for the treatment of multiple dermatologic disorders characterized by neutrophilic infiltrates.
●Administration and precautions – Dapsone therapy begins at a low dose. The dose is titrated upward over several weeks in accordance with tolerance and treatment response [8].
Typical dose ranges for dapsone therapy are:
•Children – Starting dose <0.5 mg/kg per day, titrated up to 0.5 to 3 mg/kg per day [9-11]
•Adults – Starting dose 25 or 50 mg per day, titrated up to 1 to 2 mg/kg per day [6,7]
Our usual maximum dose is 200 mg per day.
The response to treatment can be dramatic, with signs of improvement noted within a few days.
Although most patients tolerate dapsone, potential serious adverse effects, such as hemolysis, methemoglobinemia, agranulocytosis, hypersensitivity syndrome, and peripheral motor neuropathy, may occur. Hemolysis occurs to some degree in all patients, supporting frequent hematologic monitoring during the early stages of treatment. (See "Drug-induced hemolytic anemia" and "Methemoglobinemia".)
If dapsone is not tolerated or the response is inadequate after four to eight weeks at the maximum dose, proceeding to alternative treatments is reasonable. The disease severity, rate of disease progression, and patient comorbidities often influence the timing of the introduction of other treatments.
●Laboratory monitoring – A complete blood count (CBC) with differential, liver function tests and glucose-6-phosphate dehydrogenase (G6PD) level should be obtained prior to the initiation of dapsone. Patients with G6PD deficiency have an elevated risk for severe hemolytic anemia from dapsone therapy. Dapsone therapy should be avoided in this population. (See "Glucose-6-phosphate dehydrogenase (G6PD) deficiency", section on 'Acute hemolytic anemia' and "Glucose-6-phosphate dehydrogenase (G6PD) deficiency", section on 'Screening tests'.)
Approaches to subsequent dapsone monitoring vary. In general, patients require frequent laboratory monitoring for hematologic toxicity early during dapsone therapy.
One approach consists of a CBC with differential obtained once weekly for one month, and then every two weeks for an additional eight weeks. Liver function tests are monitored monthly for the first three months.
Long-term monitoring consists of a CBC with differential, renal function tests, and liver function tests every three to four months.
Other approaches with less frequent monitoring after the first month have been utilized. (See "Dapsone (systemic): Drug information".)
●Efficacy – Case series, case reports, and clinical observations support the efficacy of dapsone [9,12-18]. In one retrospective study in which 19 children received dapsone (1 to 2 mg/kg per day) as monotherapy, 11 patients (61 percent) had lesion regression within 8 to 15 days [9].
Adjunctive topical corticosteroids — Topical corticosteroids are primarily used as adjunctive therapy. Although some authors suggest that topical corticosteroid therapy may be sufficient for mild or localized LABD, most patients require systemic therapy for adequate disease control [7,19,20].
●Administration and precautions – Lesions on nonintertriginous areas of the trunk and extremities can be treated with high-potency or superpotent (group 1 or 2 (table 1)) topical corticosteroids applied once or twice daily.
Lower-potency topical corticosteroids (eg, group 6 or 7) are preferred for lesions on the face, genital, or intertriginous regions due to an increased risk for corticosteroid-induced cutaneous atrophy in these areas. (See "Topical corticosteroids: Use and adverse effects", section on 'Adverse effects'.)
●Efficacy – The efficacy of topical corticosteroids for LABD has not been evaluated in formal studies. Clinical experience suggests a benefit of this therapy [20,21].
Patients with dapsone intolerance — Adults and children who cannot tolerate oral dapsone may benefit from treatment with other oral sulfonamides (eg, sulfapyridine, sulfamethoxypyridazine). Colchicine is an additional therapeutic option.
Other sulfonamides — Sulfonamide alternatives to dapsone include sulfapyridine, sulfamethoxypyridazine, and sulfasalazine. Sulfapyridine and sulfamethoxypyridazine have structural similarities with dapsone [5]. Sulfasalazine is a prodrug composed of 5-aminosalicylic acid and sulfapyridine.
The availability of sulfapyridine and sulfamethoxypyridazine is limited in some countries. In the United States, sulfapyridine can be obtained through compounding pharmacies, and sulfamethoxypyridazine is not available.
●Administration and precautions – Adults with LABD may be treated with 1000 to 1500 mg per day of sulfapyridine or sulfamethoxypyridazine [6]. Children have been treated with 15 to 60 mg/kg per day of sulfapyridine [2,5]. An appropriate dose range has not been established for sulfamethoxypyridazine treatment in children [2].
It is difficult to predict the resulting sulfapyridine levels from a sulfasalazine dose [22]. Patients at least 17 years of age have improved with sulfasalazine doses of 1 g given twice daily or three times daily, or as 40 to 60 mg/kg per day [23-25].
The adverse effect profile of sulfapyridine is similar to dapsone, but the toxicity is less, a feature that makes sulfapyridine therapy possible in patients with dapsone intolerance [26]. Alveolitis has been reported in patients treated with sulfamethoxypyridazine [27,28].
Examples of adverse effects of sulfasalazine include hepatotoxicity, hematologic abnormalities, and reduced male fertility. (See "Sulfasalazine: Pharmacology, administration, and adverse effects in the treatment of rheumatoid arthritis", section on 'Adverse effects'.)
Monitoring guidelines for sulfapyridine and sulfamethoxypyridazine have not been established. During treatment with sulfapyridine, we typically obtain a CBC every three to six months to evaluate for leukopenia.
Monitoring recommendations for sulfasalazine include CBC, liver function tests, and renal function tests, and are reviewed separately. (See "Sulfasalazine: Drug information".)
●Efficacy – Efficacy data for sulfapyridine, sulfamethoxypyridazine, and sulfasalazine are primarily limited to reports of clinical experience [2,5,6,8,23-25,27]. In one series, sulfamethoxypyridazine monotherapy (at a dose of 1000 mg per day) was associated with disease control in three patients with LABD who discontinued dapsone due to poor tolerance [27]. None of these patients were young children.
Colchicine — Colchicine may be another reasonable alternative for patients who cannot tolerate dapsone.
●Administration and precautions – The typical dose for colchicine is 0.6 mg twice daily in children and 0.6 to 1 mg two to three times daily in adults [2,4,29,30].
Gastrointestinal distress is a common adverse effect. Examples of other adverse effects include bone marrow suppression, hepatotoxicity, neuromyopathy, and drug interactions. Caution is indicated for colchicine in patients with kidney or liver disease. (See "Gout: Treatment of flares", section on 'Colchicine'.)
●Efficacy – Efficacy data for colchicine are limited, particularly for adults. Successful treatment of childhood LABD with colchicine has been documented in case reports and small case series [15,29-32]. In a series of eight children with systemic glucocorticoid-refractory LABD, five patients experienced dramatic responses within four to six weeks after the addition of colchicine to glucocorticoid therapy. In addition, these patients tolerated tapering and discontinuation of glucocorticoid therapy.
Colchicine has appeared to be effective in a few adults with generalized or localized LABD [33,34]. However, the clinical experiences of some authors with adult patients have been less favorable [6].
Severe or refractory disease — Other immunomodulatory drugs have been used for severe disease (eg, widespread, disabling, or rapidly progressive disease) or refractory disease.
Systemic glucocorticoids — In patients with severe disease, systemic glucocorticoids may help to accelerate improvement while awaiting the response to dapsone (eg, 0.5 to 1 mg/kg of prednisone tapered over two to four weeks) [6,7,9,15]. Appropriate regimens may vary based on the severity of the disease and patient comorbidities.
In addition, LABD that responds insufficiently to dapsone may improve with the addition of systemic glucocorticoids to dapsone therapy [6,8,16-18,35]. Long-term treatment with systemic glucocorticoids is not advised due to the potential for severe adverse effects. (See "Major adverse effects of systemic glucocorticoids".)
Other interventions for severe or refractory disease — Limited data suggest other therapies may be helpful for severe or refractory LABD:
●Conventional immunosuppressants – Conventional immunosuppressants, such as mycophenolate mofetil [36-40], and cyclosporine [41], have been reported as effective in small numbers of patients. Cyclophosphamide has been used to treat patients with severe mucosal involvement [42].
●Biologic agents – Biologic agents, such as rituximab, intravenous immunoglobulin, anti-tumor necrosis factor (TNF)-alpha inhibitors, dupilumab, omalizumab, and tocilizumab, have appeared effective in individual patients [20,42-52].
●Combined sulfonamide therapies – Sulfapyridine and sulfamethoxypyridazine have been used in combination with dapsone for LABD [5,27,53]. In one series, three children given sulfapyridine as an adjunct to dapsone improved after having insufficient responses to dapsone [53].
●Other – Immunoadsorption, tofacitinib, and apremilast have each appeared effective in a few patients with LABD [54-56].
Additional treatments
Antibiotics — Case reports and small case series suggest that some systemic antibiotics are beneficial for LABD. Whether anti-inflammatory, antibacterial, or other properties contribute to benefit is unknown.
We tend to consider antibiotic therapy for patients with limited disease or with contraindications to dapsone or sulfonamides.
●Tetracyclines – Tetracyclines (eg, doxycycline, minocycline, tetracycline) in combination with nicotinamide may improve LABD. Tetracycline (at a dose of 1000 to 1500 mg per day) plus nicotinamide (at a dose of 900 to 2000 mg per day) has appeared to induce disease clearance within a few weeks in adult patients with LABD [57-59].
In general, children under the age of eight with LABD are not treated with tetracyclines because of the potential adverse effects of long-term treatment on developing teeth. (See "Tetracyclines", section on 'Teeth and bone'.)
●Other antibiotics – Responses of LABD to penicillins, macrolides, and trimethoprim-sulfamethoxazole have also been reported.
In a series of seven children with LABD treated with flucloxacillin, disease clearance occurred in all patients, but only four patients who received treatment early in the course of the disease (within one month of disease onset) had long-lasting remission off of therapy [60].
Oxacillin [9], dicloxacillin [61], erythromycin [16], and miocamycin [62], all given at doses of 50 mg/kg per day, have seemed beneficial in individual children [63]. Erythromycin may also have been effective in an adult [64]. Trimethoprim-sulfamethoxazole has been associated with both the induction and remission of LABD [65-68].
Other — LABD resolved in a child on dapsone therapy two weeks after changing the adjunctive topical therapy from betamethasone dipropionate 0.05% to tacrolimus 0.03% ointment [69]. However, spontaneous resolution may have also led to improvement.
Duration of therapy — The necessary treatment duration for idiopathic LABD varies. We typically start to gradually taper dapsone or other treatments after 8 to 12 weeks of sustained clinical remission. Treatment can be resumed if the disease relapses [35].
Tapering dapsone by 50 mg every 12 weeks is a reasonable approach. However, we adjust the speed of tapering based on patient comorbidities, the disease severity, and how difficult it was to attain disease control. A cautious approach to treatment tapering and cessation is also prudent for patients who may be at increased risk for a chronic course or who have a history of disease recurrence. (See 'Prognosis' below.)
Although further study is necessary to validate this approach, it has been proposed that serial serum IgA autoantibodies measured by indirect immunofluorescence (IIF) or enzyme-linked immunosorbent assay (ELISA) and direct immunofluorescence (DIF) microscopy may be helpful supplementary tools for guiding treatment cessation, particularly for patients with recurrent disease. Clearance of serum IgA autoantibodies and a negative DIF study of skin in a site of prior involvement may provide further support that gradual tapering towards treatment cessation is reasonable [6,35,42].
DRUG-INDUCED DISEASE —
LABD may be drug induced. Vancomycin is the most common cause of drug-induced LABD. (See "Linear IgA bullous dermatosis: Pathogenesis, clinical features, and diagnosis", section on 'Drug exposure'.)
●General approach – Prompt withdrawal of the inciting drug is the primary intervention for drug-induced LABD.
Drug-induced LABD typically resolves with withdrawal of the offending agent. Cessation of new lesion formation typically occurs within three days of removal of the inciting agent, and disease resolution usually occurs within several weeks [70].
●Severe or persistent drug-induced LABD – In our experience, in addition to cessation of the inciting drug, treatment with prednisone and/or dapsone may be beneficial for severe or persistent cases. (See 'Oral dapsone' above and 'Systemic glucocorticoids' above.)
In a case report, severe drug-induced LABD with toxic epidermal necrolysis (TEN)-like presentation resolved after withdrawal of the causative drug and etanercept therapy [71].
In general, drug therapy for drug-induced LABD should be tapered or discontinued early in the course of treatment (eg, within the first four to six weeks) to confirm the presence of active disease that necessitates the continuation of systemic treatment. Prolonged systemic treatment is rarely needed.
PROGNOSIS —
Idiopathic LABD typically persists for months to several years prior to spontaneous resolution and resolves in most children prior to puberty [4,35,72]. However, disease may persist for a decade or longer, and relapses may occur after long periods of remission [35]. In a retrospective study of 72 patients with idiopathic LABD (ages 17 to 88 years) followed for a median of 39 months (range 0 to 22 years), 24 (36 percent) of the 66 patients with follow-up data had sustained complete remission, while 42 (64 percent) had a chronic course or disease recurrence [42].
Drug-induced LABD typically resolves relatively quickly after removal of the inciting agent. (See 'Drug-induced disease' above and "Linear IgA bullous dermatosis: Pathogenesis, clinical features, and diagnosis", section on 'Drug exposure'.)
Among adults with idiopathic LABD, age and mucosal involvement may be relevant prognostic factors. In the retrospective study of 72 patients, age greater than 70 years and mucous membrane involvement were associated with a greater likelihood of complete remission (hazard ratio [HR] 2.0, 95% CI 1.06-3.91 and HR 2.18, 95% CI 1.16-4.10, respectively) [42].
Cutaneous and oral lesions usually heal without permanent scars. Consequences related to poor oral hygiene and alimentation may occur in patients with oral disease. (See "Linear IgA bullous dermatosis: Pathogenesis, clinical features, and diagnosis", section on 'Mucosal involvement'.)
INDICATIONS FOR REFERRAL —
A dermatologist or another clinician familiar with the management of LABD should be involved in the care of these patients.
Patients with signs or symptoms of ocular disease should be referred to an ophthalmologist. In addition, consultation with an otolaryngologist or gastroenterologist is appropriate for patients with symptoms suggestive of pharyngeal, laryngeal, or esophageal disease.
SUMMARY AND RECOMMENDATIONS
●Disease overview – Linear IgA bullous dermatosis (LABD) is a rare autoimmune blistering disorder that usually presents with the abrupt onset of tense bullae and inflammatory lesions on the skin (picture 1A-D). LABD may be idiopathic or drug induced. (See "Linear IgA bullous dermatosis: Pathogenesis, clinical features, and diagnosis".)
●Treatment of idiopathic LABD
•Most patients – For the initial treatment of most children and adults with idiopathic LABD, we suggest oral dapsone rather than other therapies (Grade 2C). Initial signs of response to dapsone are usually evident within days. Adjunctive topical corticosteroid therapy may help to accelerate the improvement of skin lesions. (See 'Initial therapy' above.)
Sulfapyridine, sulfamethoxypyridazine, sulfasalazine, and colchicine are alternative initial treatments for patients who cannot tolerate oral dapsone. (See 'Patients with dapsone intolerance' above.)
•Patients with severe disease – For the initial treatment of patients with severe LABD (eg, widespread, disabling, or rapidly progressing disease), we suggest adding a systemic glucocorticoid to dapsone therapy rather than dapsone therapy alone (Grade 2C). The systemic glucocorticoid may help to accelerate improvement. Our typical regimen consists of a prednisone taper given over two to four weeks. (See 'Severe or refractory disease' above.)
Immunomodulatory therapies, such as conventional immunosuppressants and biologic agents, may be beneficial for patients with refractory LABD. (See 'Other interventions for severe or refractory disease' above.)
●Drug-induced LABD – Prompt discontinuation of the offending agent is the primary intervention for drug-induced LABD. Drug-induced LABD typically improves within days and resolves within several weeks after withdrawal of the offending agent. Patients with severe presentations may benefit from oral prednisone and/or dapsone to accelerate improvement. (See 'Drug-induced disease' above and 'Oral dapsone' above and 'Systemic glucocorticoids' above.)
●Prognosis – Idiopathic LABD typically persists for months to several years prior to spontaneous resolution. Disease relapses are common. LABD in children often resolves prior to puberty. Drug-induced LABD typically resolves with withdrawal of the offending agent. (See 'Prognosis' above.)
ACKNOWLEDGMENTS —
The UpToDate editorial staff acknowledges Russell P Hall, III, MD, and Caroline L Rao, MD, who contributed to earlier versions of this topic review.
آیا می خواهید مدیلیب را به صفحه اصلی خود اضافه کنید؟
