Granulomatous and lichenoid dermatitis after IgG4 anti‐PD‐1 monoclonal antibody therapy for advanced cancer

Abstract

Nivolumab is a fully human IgG4 monoclonal antibody directed against programmed cell death protein 1 (PD-1). PD-1 inhibition allows T-cell activation and recruitment to destroy cancer cells. Checkpoint inhibitors have shown significant survival advantage and relatively low side-effects in comparison with conventional chemotherapy in several types of advanced cancer. Granulomatous cutaneous reactions have been reported showing sarcoidal and panniculitic morphology. Here we present a case of drug-induced lichenoid and granulomatous dermatitis after checkpoint inhibitor therapy observed in a 63-year-old male treated with nivolumab for advanced glioblastoma. This morphology has not been previously reported. We documented a high number of CD8+ T-cells within the lesions. Additionally, we review the side-effects observed with the use of checkpoint inhibitors, with special focus on cutaneous manifestations.

Postherpes zoster programmed death-1 inhibitor−associated zosteriform granulomatous reactions

“…Although the reported cases of ICPI-induced GD are mainly mild (grade 1, low body surface area involvement, and little to no impact on quality of life), a severe reaction (grade 3, [50% body surface area involvement, and impact on quality of life) has been reported. 5 Histopathology revealed dermal histiocytic infiltrate with sparing of the epidermis. Similar to that for GA, the mainstays of treatment are topical and oral steroids; however, several cases of GD did not resolve fully until an average period of 21 weeks after the cessation of immunotherapy.…”

Interstitial granulomatous dermatitis and granulomatous arteritis in the setting of PD‐1 inhibitor therapy for metastatic melanoma

“…Numerous sarcoidal granulomatous reactions have been reported with both ipilimumab and some with nivolumab therapy . Another pattern of inflammation within the scope of IRAEs is the mixed lichenoid and granulomatous pattern after nivolumab therapy for advanced glioblastoma . Lastly, a case of steroid‐responsive granulomatous panniculitis 6 months after nivolumab and ipilimumab therapy has been described as well.…”

“…Cutaneous toxicities due to checkpoint inhibition have a diverse clinical spectrum. Cutaneous damage is generally observed within 1 to 2 months of treatment onset . Morbilliform, pustular, vesicular, and acneiform eruptions have been reported .…”

The new differential diagnostic test for the lichenoid drug eruption

“…The negative reaction showed on photograph is an absence of bulla formation on the surface of the lesion after injection T A B L E 2 Calculation of sensitivity, specificity, positive predictive value, and negative predictive value of the proposed skin test to differentiate lichenoid drug reaction and lichen planus The cause of the disease can be different medications ranging from "home kit" medicines to molecular biology preparations. [5][6][7][8][9][10][11][12][13][14][15][16][17][18][19][20] Several authors described cases of development of a LDE reaction after vaccination. 28,29 In our study, ACE inhibitors and NSAIDs were the drugs that caused the LDE reaction, usually with delayed onset.…”

“…Medications involved in the development of an LDE include amplodepine, 5 captopril, enalapril, 6,7 propranalol, oxprenalol, labetolol, [8][9][10] gold salts 11 , immunoglobulin, 12note levamisole, 13 NSAIDs, 14 penicillamine, 15 imatinib mesylate, 16 streptomycin 14 simvastatin, 17 suramin, 18 rifampicin, 19 molecularly-biological [Correction added on 20 July, after first online publication: Dr. Shalaeva name has been corrected to Evgeniya V. Shalaeva. ] drugs, 20 antimalarial drugs, thiazide diuretics, furosemide, spironolactone, antituberculous drugs, 14 ketoconazole, and so forth.…”