Practice Essentials
Transient acantholytic dermatosis (also referred to as Grover disease) is a disorder characterized by papulovesicular eruptions on the trunk and proximal extremities. It is not uncommon, but surprisingly, it was not thoroughly characterized until Grover did so in 1970. [1] Transient acantholytic dermatosis is a reactive skin condition that may resolve over a period of weeks or months, but it is commonly persistent (chronic). Although this disorder is generally accepted as being benign and self-limited disorder, it can be difficult to manage; thus, the inclusion of the term transient in its name is misleading. [2]
Transient acantholytic dermatosis can be either idiopathic or acquired. The disease may erupt occur secondary to medications, malignancies, and external factors (eg, friction). A systematic review found that cancer therapeutics were the most common causative agents. [3]
The presentation can be subtle, or it may closely resemble those of other pruritic dermatoses. A high index of suspicion for this disease is necessary if the diagnosis is to be made correctly. Furthermore, the histologic features of transient acantholytic dermatosis closely resemble those of several other conditions that are clinically distinct, which may add to potential diagnostic confusion.
Transient acantholytic dermatosis is not curable. Although the symptoms can frequently be controlled, some cases are refractory to treatment and difficult to manage. Current methods of treating symptoms include topical steroids, retinoids, methotrexate, and 5-aminolevulinic acid photodynamic therapy (ALA-PDT).
Patients should avoid activities that cause excessive heat and sweating (eg, exercise and prolonged sun exposure). Patients should also avoid applying topical irritants.
Pathophysiology and Etiology
The etiology of transient acantholytic dermatosis is unknown. However, a number of factors have been suggested as being potentially causal or exacerbating. The most frequent association is with heat or sweating, and the obstruction of sweat ducts has been postulated to be responsible; however, this association has been challenged on the basis of research demonstrating that most patients with transient acantholytic dermatosis present in winter, not in summer. [4] This is particularly noteworthy, given that xerosis is a potential cause of transient acantholytic dermatosis and is exacerbated by cold weather.
Many patients describe preceding exposure to sunlight; however, exposure to artificial ultraviolet (UV) radiation has not been shown to reproduce the process. Transient acantholytic dermatosis seems to occur more frequently in patients with atopic dermatitis and asteatotic dermatitis, though many individuals with these conditions never develop it. A case of transient acantholytic dermatosis triggered by honeybee stings suggesting a hypersensitivity reaction. [5]
Viral, bacterial, and other pathogens have also been proposed as etiologic factors, but no causative role has been established. A number of case reports have described an association of transient acantholytic dermatosis with lymphoma, but these seem to be in the extreme minority. [6, 7] The exact pathogenesis has not been elucidated.
A systematic review found that cancer therapeutics were the most common agents reported in drug-induced transient acantholytic dermatosis. [3] For example, there have been reports of cases related to pembrolizumab and nivolumab (PD-1 inhibitors), [8] ipilimumab (CTLA-4 inhibitor), [9, 10] and letrozole (aromatase inhibitor). [11]
Similarly, a number of case reports have focused on describing a direct relation between autoimmune antibodies and transient acantholytic dermatosis. Although there is a positive correlation between the two, it is unclear whether the autoimmune antibodies cause transient acantholytic dermatosis or if they increase as a result of transient acantholytic dermatosis. [12, 13]
Seli et al conducted a retrospective study of sequencing data of 15 individuals with transient acantholytic dermatosis, in which damaging single-nucleotide variants in ATP2A2 were identified in 12 individuals (80%). [14] ATP2A2 defects are associated with Darier disease (keratosis follicularis). Because all variants identified were C>T or G>A substitutions, the researchers hypothesized that UV light–induced mutagenesis may contribute to the development of lesions. The importance of this is uncertain, given that Grover disease almost never manifests in sun-exposed areas.
Epidemiology
United States and international statistics
Exact numbers regarding the prevalence of transient acantholytic dermatosis are not available. Because of the clinical similarities to other entities and variability of the histopathologic findings, the disease is underdiagnosed in nondermatologic settings and is probably underdiagnosed overall. Given that transient acantholytic dermatosis has been linked to immobilization occlusion, it is likely that a growing number of cases have gone undetected in the hospital setting.
Age-, sex-, and race-related demographics
Transient acantholytic dermatosis most commonly affects adults older than 50 years. In rare instances, however, it has been reported in children. Men are affected three times more often than women. Whites are most commonly affected, though the condition may also be seen in other ethnic groups (eg, Hispanics and Blacks).
Prognosis
Generally, transient acantholytic dermatosis is a self-limited disorder that resolves over weeks to months, but it can be persistent and may repeatedly recur for years. Lesions may resolve with postinflammatory pigmentary alteration or with no residual change. Diagnosis can be complicated by the presence of dermatitis, which produces scattered, rounded crusted plaques that resemble those in transient acantholytic dermatosis. Scarring is usually minimal unless induced by excoriation.
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54-year-old man with pruritic eruption on trunk. Note slight lichenification and significant erythema from rubbing that is localized to central part of torso. Also note red-brown papules in abdominal region.
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Close-up view of abdominal area of patient with pruritic eruption on trunk. Multiple small, discrete, red-brown papules characteristic of Grover disease are present.
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Histopathology of Darier-type Grover disease. Focus of acantholytic dyskeratosis is present in epidermis with slight epithelial hyperplasia and hyperkeratosis, signaling rubbing as consequence of pruritic nature of disease (hematoxylin and eosin, original magnification X40).
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Higher magnification reveals acantholytic dyskeratosis to better advantage. Note corps ronds and grains (hematoxylin and eosin, original magnification X400).
