Case Presentation: This patient is an 81 year old female with a history of chronic lymphocytic leukemia and small lymphocytic lymphoma who presented to the hospital’s emergency department 5 to 6 months after the initiation of ibrutinib with a diffuse, highly pruritic, erythematous, blanchable papular rash distributed across her trunk and upper right extremity. Initially based on her presentation, we believed the rash was either a cutaneous manifestation of her leukemia or a reaction to the ibrutinib. Therefore the medication was held. Although her rash improved (Figure 1), the patient still endorsed severe pruritus. Punch biopsy was subsequently taken and showed focal, basally located keratinocyte necrosis and detachment of the epidermis ( Figure 2). This was reviewed by two dermatopathologists and confirmed to be consistent with acantholytic dyskeratosis. On follow up, the patient was found to have a flare of her rash, without resumption of her ibrutinib. She was subsequently given a trial of topical triamcinolone cream which improved her symptoms significantly.
Discussion: The classic presentation of the Grover Disease is of pruritic papulovesicles on the trunk of older white men. Extensive disease typically includes at least 1 area of the body in addition to the trunk. Some association of this condition with solid tumors, hematological malignancies and other malignancies has been thoroughly established, as well as a connection with certain classes of immunomodulating agents. While the mechanism through which such malignancies and drugs induce transient acantholytic dermatosis has not been well established, it has been speculated to be related to concentration of drug metabolites and/or elimination via sweating, or possibly via paraneoplastic process (Gantz et al). A systematic review in 2015 determined an incidence of 15-28% of ibrutinib associated rash. It showed a wide range of rash presentation from non-palpable petechial rash, rashes with palpable purpura, maculopapular rash and pityriasis rosea-type rash. Typically, rashes which are grade 1 or 2 resolve spontaneously, however there are more severe rashes that require dose interruption (McFarlane et al). To the best of our knowledge, there has not previously been a documented correlation of Bruton’s tyrosine kinase inhibitors with the condition.
Conclusions: Grover disease has infrequently been described in the setting of malignancy but can be associated with chemotherapy. Although the rash is benign and has been described as self – limited with spontaneous resolution, there are various atypical presentations including appearance, symptomatology, inciting or associated factors that need to be identified. In our case, the inciting event was ibrutinib which was discontinued, and over time the patient’s symptomatology demonstrated steady improvement.
