Bullous pemphigoid: associations and management guidelines: facts and controversies.

Bullous pemphigoid (BP) is an organ-specific human autoimmune disease typical of the elderly, which may be associated with many different disorders (immune, neurologic, psychiatric, hematologic, pulmonary, and cardiovascular), as well as with different types of tumors. The crucial question is whether these associations are casual or causal. In particular, the relationship between BP and malignancy is still a matter of debate. Although this association often has been emphasized, it is not clear whether the coexistent malignancy and BP are pathogenically connected or if their association is merely linked to aging. In our survey, the BP/neoplasm association ratios have not increased with age. Instead, significantly higher ratios have been found in younger patients; therefore, a meticulous investigation for a malignant neoplasm should always be pursued in young or middle-aged patients with BP, in particular regarding the severe forms of the disorder or those refractory to conventional treatment. The management of BP strictly depends on the multifactorial pathogenesis of this disorder. In fact, inflammation in BP seems to be more crucial for blister formation than in other autoimmune bullous disorders, such as pemphigus. Even if first-line treatments are typically immunosuppressants, newer therapeutic agents targeting specific pathogenic steps that are linked with inflammation have been proposed. Treatments selectively suppressing autoantibody formation, inflammation cascade, or both are available. Grouping therapies according to their mechanism of action may be useful to test new drug associations or to evaluate efficacy and tolerability of drugs with the same target.