Risk factors for BP. Certain conditions linked to developing BP include neurologic disorders (dementia and Parkinson disease) and psychiatric disorders (unipolar and bipolar disorder).4 Further, it is important to note any medications that could be the cause of a patient’s BP, including dipeptidyl peptidase-4 (DPP-4) inhibitors, psychotropic medications, spironolactone, furosemide, beta-blockers, and antibiotics.3 This patient was taking a beta-blocker (metoprolol) and a DPP-4 inhibitor (linagliptin). Because he was most recently started on linagliptin, we suspected it may have had a causal role in the development of BP.
The association of DPP-4 inhibitors and BP
FPs are increasingly using DPP-4 inhibitors—including sitagliptin, vildagliptin, and linagliptin—as oral antihyperglycemic agents for type 2 diabetes mellitus. Therefore, it’s important to recognize this medication class’s association with BP.5 In a case-control study of 165 patients with BP, Benzaquen et al reported that 28 patients who were taking DPP-4 inhibitors had an associated increased risk for BP (adjusted odds ratio = 2.64; 95% confidence interval [CI], 1.19-5.85).3
The pathophysiology of BP associated with DPP-4 inhibitors remains unclear, but mechanisms have been proposed. The DPP-4 enzyme is expressed on many cells, including keratinocytes, T cells, and endothelial cells.3 It is possible that DPP-4 inhibition at these cells could stimulate activity of inflammatory cytokines, which can lead to enhanced local eosinophil activation and trigger bullous formation. DPP-4 enzymes are also involved in forming plasmin, which is a protease that cleaves BP180.3 Inhibition of this process can affect proper cleavage of BP180, impacting its function and antigenicity.3,6
Other conditions that also exhibit blisters
There are some skin conditions with similar presentations that need to be ruled out in the work-up.
Bullous diabeticorum is a rare, spontaneous, noninflammatory condition found in patients with diabetes.1 Blisters usually manifest as large, tense, asymmetrical, mildly tender lesions that commonly affect the feet and lower legs but can involve the trunk. These usually develop overnight without preceding trauma. Biopsy would show both intra-epidermal and subepidermal bulla with normal DIF findings.1 This condition usually has an excellent prognosis.
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