Transient Acantholytic Dermatosis (Grover Disease) Associated With Chemotherapy: Review of Potential Pathophysiology, Current Treatments and Future Directions for Treatment

October 2020 | Volume 19 | Issue 10 | Original Article | 11 | Copyright © October 2020


Published online September 25, 2020

Jacob Beer BAa, Misha Rosenbach MDb

aPerelman School of Medicine, University of Pennsylvania, Philadelphia, PA bDepartment of Dermatology, University of Pennsylvania, Philadelphia, PA

Abstract
Introduction: Transient acantholytic dermatosis has been frequently reported in patients with malignancies. While paraneoplastic cases have been reported, most eruptions occur in the setting of chemotherapeutic agents. Management is based on limited data and primarily with topical steroids and topical emollients. A subset of patients exhibits recalcitrant disease and require alternate therapeutic approaches
Methods: This systematic review consisted of identifying records in PubMed using the medical subject headings (MeSH) terms “chemotherapy” AND “Grover”, “chemotherapy” AND “Grover’s”, “cancer” AND “Grover”, “cancer” AND “Grover’s”, “malignancy” AND “Grover”, “malignancy” AND “Grover’s”, as well as a free text search for “Grover” OR “Grover’s” OR “Grover disease” OR “Grovers disease” OR “Grover’s disease” OR “transient acantholytic dermatosis” OR “transient acantholytic” to identify case reports, case series, systematic reviews, review articles, meta-analyses, clinical trials, brief commentaries, and original articles. The titles and abstracts of all results were reviewed. Full texts of relevant results were then read in their entirety and applicability was determined.
Results: Overall, Grover disease is reported most frequently in association with cytotoxic chemotherapies, followed by small molecule inhibitors. The first line treatment for this complication is the use of topical agents. When these provide inadequate relief, different therapies are proposed with certain treatments suggested based on the chemotherapy agent used.
Conclusions: While most cases of chemotherapy associated Grover disease can be treated with topical steroids and topical emollients, certain cases require a more specialized approach. This could include adjuvant therapies or treatments that are directly related to the mechanism of action for the chemotherapy involved.

J Drugs Dermatol. 2020;19(10): doi:10.36849/JDD.2020.5648

INTRODUCTION

History of Transient Acantholytic Dermatosis (Grover Disease)
Transient acantholytic dermatosis, or Grover disease, is a rare acantholytic skin disorder that was first described by Dr. Ralph Weir Grover.1 Over the course of five years he observed six patients who presented with unusual transient truncal rashes. In 1970, he published a case series of these six patients and observed that the histology indicated an acantholytic process that seemed consistent with Hailey-Hailey disease or Darier disease. However, the clinical presentations, including the age of onset, temporal transience, and distribution of lesions, were not consistent with either entity. As such, he termed the disease “transient acantholytic dermatosis” in order to note the transient nature of this acantholytic eruption. Over time, more patients were described as having a similar condition.2-7 In many cases, their eruptions were not transient, prompting a shift toward the name “Grover’s disease” initially, and with a shift in medical literature away from possessive, eponymous disease names, it is more commonly known as “Grover disease” or “transient acantholytic dermatosis”.8 The disease was later categorized by subtypes based on histological patterns, with four main subtypes: Hailey-Hailey-like , Darier-like, Pemphigus vulgaris-like, and Spongiotic.9 Chalet et al. described histopathological diagnosis principles that remain relevant in the diagnosis of Grover disease, despite changing clinical criteria (Table 1).9 They note a clinical picture that consists of discrete lesions that do not demonstrate confluence and that can range from papulovesicular to keratotic. The lesions are frequently pruritic, and the primary locations include the upper chest, lumbar area, or the back. Although previously disputed, the consensus from the available literature is that Grover disease is more commonly diagnosed in the winter than in the summer.8,10-12 Scheinfeld et al. found a 4-fold increase of Grover disease diagnosis in winter months (January–March) than in summer months (June–August).10 Grover disease is typically diagnosed in older, male patients with a mean age of 61 years when diagnosed and a male to female ratio of 2.4:1.4,13,14

Discussion of Pathophysiology and Immunology
The exact pathogenesis of Grover disease is not entirely known. One theory suggests occlusion of the eccrine ducts leads to leakage, or “internal sweating.”13 This process in which sweat molecules leak from the ducts to the epidermis is proposed to lead