Preschool children presenting with idiopathic childhood disease will usually experience remission of symptoms in several months to years. Recommendations are to suppress symptoms, usually with dapsone, as intensive immunosuppression therapy is seldom necessary.

Separation of drug-induced LABD from idiopathic disease on the basis of clinical exam alone is virtually impossible. A careful history of medication use must be taken with special attention to medications started within the last month. If a medication is implicated, termination of that medication is very likely to produce complete resolution within weeks using only suppressive therapy with dapsone. In severe or persistent cases prednisone may be used to achieve faster resolution. Therapy should be tapered early in the treatment course, within 4–6 weeks, to ascertain whether the disease is still active, warranting continuation of systemic therapy. A prolonged treatment course is rarely necessary.

The additional presence of IgG antibodies is probably associated with resistance to dapsone, and indicates the need for additional systemic treatment with corticosteroids and immunosuppressives.

Dapsone is the first-line medication therapy for LABD [28, 30]. Baseline glucose-6-phosphate dehydrogenase levels must be evaluated to ensure that the oxidative stress of dapsone will not induce a hemolytic crisis. Baseline complete blood count with auto-differential and liver function tests (LFTs) should be also evaluated. Dapsone is started at a low dose: 25–50 mg daily in adults and generally less than 0.5 mg/kg daily in children. This dose is gradually titrated upward over several weeks, depending on tolerance and treatment response. Complete blood counts (CBC) must be monitored every 2–4 weeks for the first 3 months to evaluate for leukopenia or severe hemolysis. Hemolysis to some degree occurs in all patients. Elderly patients or those with cardiac compromise need to be monitored closely as small decreases in the hematocrit or hemoglobin or minimal methemoglobinemia may produce symptoms [31]. Treatment response may occur in 24–48 hours with resolution of lesions within a few days of initiating therapy. If the disease is completely controlled with dapsone, a systematic approach at tapering is recommended. Dapsone should be tapered no more frequently than every 1 to 2 weeks by 12.5–25 mg. Development of an occasional small lesion is not an indication for increasing the dapsone dose as such lesions can be treated topically with potent corticosteroids. Tapering dapsone slowly will eventually allow discontinuation of treatment in cases that undergo spontaneous remission with time. Some patients with more extensive disease, particularly scarring mucosal disease and incomplete response to dapsone therapy may need oral corticosteroids or immediate treatment with rituximab to accelerate improvement of symptoms and effectively suppress the lesions [32, 33].

For patients who are intolerant of dapsone, there are other sulfa-based drugs available: sulfasalazine and sulfapyridine. Although there is no published verification of therapeutic efficacy, patients who are allergic to dapsone or sulfapyridine can be given a trial of the alternate medication at a low dose; and they are generally able to tolerate it. Sulfapyridine is not commercially available in the United States, but can be obtained through compounding pharmacies. Sulfapyridine dosing should be started at 0.5 g 3 times daily and increased up to 6 g daily for control of symptoms. Sulfasalazine is metabolized to sulfapyridine in the intestine; however, the active metabolite level is more predictable when sulfapyridine, itself, is given. Sulfasalazine should be dosed between 1 and 2 g daily [34]. Both medications have the potential adverse effects of agranulocytosis and hypersensitivity reactions, but not hemolysis. Adequate fluid intake and possible alkalinization of the urine with oral bicarbonate is also recommended to reduce the risk of drug-induced nephrolithiasis. As with dapsone, lab monitoring (CBC, LFTs and urinalysis) is recommended periodically.

As stated above, those patients with more extensive disease and incomplete response to dapsone may need oral corticosteroids (1 mg/kg daily) for faster resolution of symptoms and effective suppression of the lesions [32, 35, 36]. Corticosteroids may be particularly effective in patients who also have IgG BMZ antibodies on direct immunofluorescence or in the serum. Patients with lone IgA antibodies may not respond to corticosteroids at any dose.

Colchicine can be effective in children with LABD. Some case reports and case series have demonstrated it as a reasonable substitute therapy for dapsone [35, 37–39]. In a series of eight children with systemic glucocorticoid-refractory LABD, the addition of colchicine led to dramatic improvement in 5 patients within 4–6 weeks. Furthermore, these children were able to taper off steroid therapy. The typical dose in children is 0.6 mg twice daily. According to some case reports, adults have also responded to colchicine; however, other authors have not seen such reported results. The adult dosage is 0.6 mg taken 3 to 4 times daily. The dosage is most often limited by gastrointestinal side effects, (especially diarrhea), secondary to the higher dosages of colchicine.

This therapeutic combination has been effective for the treatment of bullous pemphigoid and has been applied to LABD. Three adult patients with LABD reported disease resolution within a few weeks of starting therapy [40–42]. The dosing range for tetracycline and nicotinamide are 1000–1500 mg daily and 900–2000 mg daily, respectively. Children under age 9 cannot take tetracycline due to the adverse effect on developing teeth.

Children with LABD may respond to systemic antibiotic therapy. The mechanism for efficacy is not known; whether it is due to anti-inflammatory or antibacterial properties, or another unknown action, remains to be clarified. One case series reported that in 7 children treated with flucloxacillin, all had complete resolution, but only 4 children stayed in remission off therapy [43]. Additional antibiotics reported to effectively treat LABD in children are oxacillin, dicloxacillin, erythromycin and trimethoprim-sulfamethoxazole [36, 44–48].

When patients with either prolonged disease who require further immunosuppressive therapy or with predominantly mucosal involvement need more aggressive therapy, steroid-sparing agents can be effective. In the authors’ estimate, these agents work in refractory disease. The order of preference is dictated by ease of use and severity of side effects [49–61].

This non-immunosuppressive agent is pooled purified plasma from blood donors that contains supraphysiologic quantities of IgG and trace other immunoglobulins [66]. Its immunomodulatory effects are still not fully elucidated; however a few of its mechanisms of action include: suppression of the complement activation pathway through inhibiton of the membrane attack complex formation and the enzymes C3 and C5 convertase, neutralization of circulating autoantibodies, and blockade of the Fc receptors on macrophages and Fas ligand receptors on keratinocytes [67]. IgA levels must be checked before use of this medication as it can precipitate anaphylaxis in patients with IgA deficiency. IVIg has been successfully used alone and in combination with corticosteroids in patients with chronic renal failure and LABD, treatment-refractory LABD, and in those with chronic ocular involvement [52–54].