A Rare Case of Bullous Pemphigoid Secondary to Checkpoint Inhibitor Immunotherapy: A Tense Situation

Abstract

Bullous pemphigoid is a serious and rare complication of immunotherapy. Here, we present a case of bullous pemphigoid secondary to ipilimumab/nivolumab checkpoint inhibitor therapy in a patient with metastatic melanoma. Immune checkpoint inhibitor therapy is more widely used now to treat cancer patients, bringing more challenging cases of adverse events associated with their use. Bullous pemphigoid can be a difficult diagnosis to make in the initial stages as the rash is similar to other red rashes before transforming into the typical appearance of a blister. As bullous pemphigoid can be a life-threatening adverse event, early identification is key to increasing patient survival.

Association of Bullous Pemphigoid With Immune Checkpoint Inhibitor Therapy in Patients With Cancer

“…The most common type of primary cancer for which ICI was initiated among 126 patients was melanoma (55 [43.6%]). Anti PD-1 therapy was the most frequently used immunotherapy (107 [84.7%]), although a few patients received combined anti-PD-1 and cytotoxic T lymphocyte-associated antigen 4 (CTLA-4) therapy (5 [3.9%]) 61,63,70,73,76 and CTLA-4 inhibitors (3 [2.4%]). 10,29,31 Of patients with ICI-BP, 24 (18.9%) had multiple irAEs.…”

“…78 Additional nonsteroid treatments were used in 50 patients (39.7%) and included antibiotics (eg, doxycycline, dapsone, minocycline, and niacinamide), antihistamines, and systemic immunomodulators, such as methotrexate, mycophenolate mofetil, and azathioprine. Biologic and targeted therapies, including infliximab (n = 1), 67 rituximab and intravenous immunoglobulin G (IVIG) (n = 2), 59,70 rituximab and plasma exchange (n = 1), 35 rituximab only (n = 7), 23,48,51,61,68,73,76 omalizumab (n = 3), 12,40 omalizumab and IVIG (n = 2), 78 IVIG only (1), 78 and dupilumab (n = 1) 65 were used by a small number of patients (18 of 127 [14.2%]), often in cases of ICI-BP that was refractory to systemic corticosteroids or those experiencing only partial symptomatic improvement.…”

“…Most patients experienced partial to complete improvement of BP with treatment (96 of 118 [81.4%]), although 4 patients (3.4%) 40,46,63 had ongoing pruritus despite resolution of their rash and 9 patients (7.6%) 18,24,34,37,41,42,53,61,72 required ongoing treatment with systemic steroids for effective symptomatic control. Among patients who received biologic therapy, 13 of 16 (81.3%) 12,23,35,40,48,51,65,67,68,70,73,78 had substantial improvement or resolution of their BP symptoms, whereas 3 (18.8%) had ongoing pruritus or continued skin involvement. 40,61,78 Although 1 previous study 80 found an association between the development of ICI-BP and improved cancer outcomes, there did not appear to be a marked pattern among published studies.…”

Skin manifestations associated with checkpoint inhibitors

“…BP presented later than the usual onset of classic lichenoid reactions (mean onset: 190 days vs. 88 days), with an average of 6.52 months after treatment initiation 53 . Fewer cases of BP in the context of anti‐CTLA‐4 therapy have been reported 54–56 …”

“…53 Fewer cases of BP in the context of anti-CTLA-4 therapy have been reported. [54][55][56] Clinically, a first phase characterised by pruritus and non-specific lesions, such as macules, papules and wheals, is typical. Later, vesiculobullous lesions develop on the trunk and extremities, often involving mucous surfaces (Figure 3).…”