Clinical Pathologic Mismatch in a TNF-α Inhibitor-Associated Drug Reaction

August 2019 | Volume 18 | Issue 8 | Case Reports | 218 | Copyright © August 2019

Kathleen F. O’Brien MS,ª Rachel E. Maiman MD,B Christine A. DeWitt MDB

aGeorgetown University School of Medicine, Washington, DC, bMedstar Georgetown University Hospital, Department of Dermatology, Washington, DC

Case in point, our patient had a long-standing history of psoriasis, a plausible psoriasis rebound reaction after systemic steroids, and a clinical course consistent with an erythrodermic flare, however, none of the biopsies showed psoriasiform hyperplasia; rather, they consistently showed LID. While anecdotes exist, this histologic finding of LID among patients with clinically psoriasiform eruptions has scarcely been reported.3,4

The pathophysiology underlying LID in the setting of TNF-α blockade is poorly understood, but is thought to be T-cellmediated.8 It is speculated that suppression of TNF-α increases opposing inflammatory cytokines, creating a relative cytokine imbalance.9 This results in a paradoxical autoimmune attack by T cells on the epidermis, which manifests as LID on histopathology.9

This clinicopathologic disconnect highlights an important barrier to proper diagnosis and management. For our patient, we suspect that titration to the maximum dose of infliximab created the precise inflammatory milieu to provoke his psoriasiform drug eruption and the LID seen on biopsy. This is supported by the finding that patients on high doses of TNF-α blockade experience the highest rate of presumably dose-dependent cutaneous side effects.6 This phenomenon appears to be more common in patients with underlying psoriasis.3 Unlike prior reports on this phenomenon, our patient failed to improve after discontinuation of the inciting agent, which we believe is due to steroid dependency stemming from multiple systemic steroid tapers throughout his course.3,4 It is well-known that withdrawal of systemic steroids is a frequent precipitant of psoriasis flares; consequently, the most appropriate treatment for psoriasiform drug eruptions are steroid-sparing systemic anti-inflammatory agents.

The importance of this case is to highlight that LID should not be an unexpected histologic finding in patients on TNF-α inhibitors.3,4 The paucity of literature on this phenomenon makes it particularly difficult to recognize, which risks improper diagnosis and a detrimental impact on patient care. Thus, we strongly recommend selecting treatment based on clinical presentation, rather than histopathologic findings.


The authors have no conflicts.


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Rachel E. Maiman MD Rachel E. Maiman MD