Chronic bullous disease of childhood (CBDC) is generally a self-limited disease of prepubescent children that resolves within months to years. However, as discussed in the previous issue of Dermatologic Clinics, the disease is associated with significant morbidity and usually requires systemic therapy. Treatment is aimed at controlling blistering while avoiding adverse reactions. There are several anecdotal reports of treatment options, but controlled or comparative studies are lacking.

Dapsone is considered the drug of choice and is begun at a low dose (<0.5 mg/kg) and slowly increased until blistering and symptoms are controlled (usually 2 mg/kg/day). Dose-related adverse effects include hemolysis (especially in the setting of glucose-6-phosphate dehydrogenase [G6PD] deficiency) and methemoglobinemia, which manifests as cyanosis, dyspnea, lethargy, and headache. A benign hemolysis is expected, and acompensatory reticulocytosis occurs. Idiosyncratic adverse reactions include agranulocytosis, peripheral neuropathy, hepatitis, gastrointestinal upset, cutaneous hypersensitivity reactions, and dapsone hypersensitivity syndrome. Initial laboratory evaluation should include a complete blood count (CBC) with differential; liver function tests; renal function tests, including urinalysis; and a G6PD level. A CBC should be monitored frequently during the first 3 months of treatment, and additional blood work must be done periodically thereafter.

Sulfapyridine (150 mg/kg although pediatric dosage is not well-established) is another first-line agent and is associated with adverse reactions similar to those of dapsone but generally less severe. This drug is no longer readily available in the United States but may be provided on a compassionate basis through Jacobus Pharmaceutical Company (telephone: 609-921-7447). Other sulfonamides may also be of benefit. Dapsone and sulfonamides may be combined for improved efficacy without additive side effects. The addition of systemic corticosteroids may be needed for symptomatic control at the onset of the disease and periodically during flares but long-term use is discouraged given the plethora of adverse effects. Topical corticosteroids may be used in combination with the systemic therapies described herein.

Children with G6PD deficiency in whom dapsone and sulfapyridine are contraindicated should be treated with an alternative agent. Colchicine, which exerts its antiinflammatory effects by inhibiting neutrophil motility, adhesiveness, and chemotaxis, has been shown to be an effective option. Systemic corticosteroids may be used in combination with colchicine initially but should be tapered over a few weeks such that patients are maintained on colchicine monotherapy, usually at a dosage of 0.5 mg twice daily. Side effects at this dosage are usually absent, but dosage-dependent gastrointestinal disturbances may occur at higher dosages. Colchicine should not be used in patients with blood dyscrasias or serious gastrointestinal, renal, hepatic, or cardiac disorders. Blood work should be monitored periodically during treatment.

Antibiotics may also be of benefit in patients who are not candidates for standard therapy. Successful treatment with erythromycin, presumably through its antiinflammatory actions, has been described. Erythromycin as a solo therapy is unlikely to provide sustained improvement in CBDC, but its administration on initial patient evaluation may lead to early improvement while awaiting further work-up. Gastrointestinal upset is a common side effect of erythromycin therapy, but serious adverse reactions are uncommon. Successful treatment with dicloxacillin and oxacillin, both at dosages of 50 mg/kg daily, has been described. Potential side effects include gastrointestinal intolerance, urticaria and other allergic reactions, and occasionally transient hepatic dysfunction. Improvement with trimethoprim-sulfamethoxazole has been reported in a single patient. Treatment with antibiotics does not require blood monitoring, which is particularly advantageous in the treatment of children.

CBDC has historically been treated with liquid arsenicals with variable response. Historical treatments also included a gluten-free diet because CBDC was initially thought to be a variant of dermatitis herpetiformis. Not unexpectedly, most patients found no improvement with this dietary restriction. Resection of the diseased rectal stump led to improvement in a child with CBDC associated with ulcerative colitis who failed prednisolone, cyclosporine, and thalidomide. Nicotinamide in combination with dapsone was effective in a child with CBDC. Nicotinamide and tetracycline have been effective in adults with linear immunoglobulin A (IgA) disease, but tetracycline antibiotics are contraindicated in young children. Intravenous immunoglobulin and immunoadsorption have led to favorable outcomes in adults with refractory linear IgA disease but have not been used in the treatment of CBDC.