Grover’s Disease Abstracts 1


A new cutaneous sign of mercury poisoning. (Ann Intern Med)
            (Dantzig, 2003b) Download
Background: Long-term mercury poisoning is becoming a major health problem because of the extreme toxicity of mercury and its extensive pollution in the environment. However, mercury poisoning is difficult to diagnose. I report on 11 patients who contracted mercury poisoning by eating seafood. In these patients, poisoning manifested with a specific eruption characterized by nonpruritic, discrete, flesh-colored or slightly erythematous papules and papulovesicles. These lesions were small ( 1 mm in diameter) and correlated with serum mercury levels; they resolved when mercury levels decreased.

A new cutaneous sign of mercury poisoning. (J Am Acad Dermatol)
            (Dantzig, 2003a) Download
Chronic mercury poisoning is becoming a health concern because of extensive pollution of water and fish, and the increasing consumption of fish in the human diet. Mercury is extremely toxic to the body, especially the central nervous system, but diagnosis is difficult because of the lack of specific signs. A total of 11 patients were observed to have a nonpruritic or mildly pruritic discreet papular and papulovesicular eruption that correlated with high blood mercury levels. The mercury evidently came from increased seafood consumption. All of the patients improved when they were placed on either a seafood-free diet or chelation therapy. Physicians should suspect mercury poisoning in patients who eat a high-seafood diet who present with an asymptomatic or mildly pruritic papular or papulovesicular eruption.

Age related macular degeneration and cutaneous signs of mercury toxicity
            (Dantzig, 2005) Download
Objective. The objective of this study is to determine the relationship between age-related macular disease, and cutaneous signs of mercury toxicity. Methods. Fourteen patients with macular degeneration, 14 patients with Grover’s disease, 14 control patients over the age of 52 with no signs of Grover’s disease, and nine control patients over age 57 with measurable blood mercury levels but no evidence of macular degeneration were randomly selected. All patients had physical exam, skin biopsies where applicable, and blood mercury levels checked. Results. Of the 14 patients with macular degeneration, 11 patients had Grover’s disease, two had spongiotic papules as reported by Dantzig, and 13 had measurable blood mercury levels. Of the 14 patients with Grover’s disease, all 14 patients had measur- able blood mercury levels and three of the patients were treated with diet and chelation with excellent response. Conclusions. Grover’s disease may represent a cutaneous marker for age-related macular degeneration, and low levels of mercury may represent an etiology for both age-related macular degeneration and Grover’s disease. If these findings are corro- borated and proven to be true, then both diseases could potentially be drastically reduced or eradicated through strict environment controls.

Parkinson's disease, macular degeneration and cutaneous signs of mercury toxicity.
            (Dantzig, 2006) Download
OBJECTIVE:  The objective of this study was to determined if there was a relationship between Grover's disease and Parkinson disease. METHODS:  Fourteen patients with Parkinson disease and 14 control patients were randomly selected and examined for cutaneous eruptions and blood mercury levels. RESULTS:  Of the 14 patients with Parkinson's disease, 13 had Grover's disease and detectable blood mercury. None of the patients in the control group had a cutaneous eruption and only 2of the 14 had detectable blood mercury. CONCLUSION:  Mercury may play a role in the etiology of Parkinson disease and Grover's disease.

Grover's disease and mercury.
            (Dantzig, 2010) Download
An article was published in the Cutaneous and Ocular Toxicology Volume 24, Number1 entitled “Age related macular degeneration and cutaneous signs of mercury toxicity” which showed that Grover’s disease (transient acantholytic dermatitis) correlates very well with blood mercury levels and can be successfully treated with chelation and avoidance of exposure to mercury, especially seafood (1). This is important because Grover’s disease is increasing in incidence and present treatments are ineffective. This is also important because Grover’s disease coexists with other diseases, especially neurologic diseases, and may give some insight into the etiology of those diseases. The environment is becoming increasingly recognized as a cause of human diseases and it is important to identify these to help erradicate them.


Pruritic papules on the chest and back. Grover's disease.
            (Hanson and Hsu, 2006) Download
Photo Quiz. A 60-year-old man presented with a pruritic eruption on his back and chest that had begun several months earlier. He was otherwise healthy and was not taking any medications. His physical examination was normal except for numerous erythematous papules on his back and chest. Some of the lesions were excoriated. A biopsy specimen revealed focal acantholysis. Based on the patient’s history and physical examination, which one of the following is the correct diagnosis? A. Candidiasis. B. Drug eruption. C. Folliculitis. D. Grover’s disease. E. Darier’s disease.

Grover's disease treated with isotretinoin. Report of four cases.
            (Helfman, 1985) Download
Grover's disease (transient acantholytic dermatosis; TAD), a disorder of unknown etiology, may resemble Darier's disease and frequently resists conventional therapies. The lesions can be extensive and pruritus can be a prominent feature. Four patients with Grover's disease were treated with isotretinoin. Three patients with relatively acute disease responded with remissions of up to 10 months after treatment. One patient with disease of 8 months' duration obtained partial relief but experienced a relapse when medication was stopped.

Grover's disease associated with pregnancy.
            (Lee et al., 2010) Download
Grover’s disease (GD) was first described by Grover in 1970 as a pruritic papular or papulovesicular acan- tholytic dermatosis.1 Clinically, GD is characterized by disseminated erythematous papules or papu- lovesicles with erosions and crusts. In addition, the lesions tend to be extremely pruritic. GD primarily involves the upper and mid-trunk areas, although the lower trunk and proximal extremities are occasionally affected. GD can spontaneously resolve after weeks to months or it can follow a chronic relapsing course over a period of several years. The typical histological features of GD are focal acantholysis and dyskerato- sis. GD occurs most commonly in white men over 40 years of age. GD occurring during pregnancy is extremely rare. It was reported once in 1985.2 Herein, we describe a case of GD associated with pregnancy.


Is Grover's disease an autoimmune dermatosis
            (Phillips et al., 2013) Download
Grover's disease (GD) is a transient or persistent, monomorphous, papulovesicular, asymptomatic or pruritic eruption classified as non-familial acantholytic disorder. Contribution of autoimmune mechanisms to GD pathogenesis remains controversial. The purpose of this study was to investigate antibody-mediated autoimmunity in 11 patients with GD, 4 of which were positive for IgA and/or IgG antikeratinocyte antibodies by indirect immunofluorescence. We used the most sensitive proteomic technique for an unbiased analysis of IgA- and IgG-autoantibody reactivities. Multiplex analysis of autoantibody responses revealed autoreactivity of all 11 GD patients with cellular proteins involved in the signal transduction events regulating cell development, activation, growth, death, adhesion and motility. Semiquantitative fluorescence analysis of cultured keratinocytes pretreated with sera from each patient demonstrated decreased intensity of staining for desmoglein 1 and/or 3 and PCNA, whereas 4 of 10 GD sera induced BAD expression, indicating that binding of autoantibodies to keratinocytes alters expression/function of their adhesion molecules and activates apoptosis. We also tested the ability of GD sera to induce visible alterations of keratinocyte shape and motility in vitro but found no specific changes. Thus, our results demonstrated that humoral autoimmunity in GD can be mediated by both IgA and IgG autoantibodies. At this point, however, it is impossible to conclude whether these autoantibodies cause or are caused by the disease. Antidesmoglein antibodies may be triggered by exposure to immune system of sequestered antigens due to disintegration of desmosomes during primary acantholysis. Clarifying aetiology of GD will help improve treatment, which currently is symptomatic and of marginal effectiveness.

Grover's disease: 34 years on.
            (Quirk and Heenan, 2004) Download
Grover's disease is an entity reported worldwide and recognized as a common disease since Grover first described it in 1970. Its cause remains obscure, but hospitalized, febrile and sun-damaged patients are particularly prone. It is frequently associated with some other skin diseases, including eczemas, psoriasis and solar keratoses. Acantholysis is the universal histological finding in all the varying clinical presentations. Treatment in the past has been ad hoc, but topical therapy, acitretin and phototherapy can suppress symptoms.


Grover disease (transient acantholytic dermatosis).
            (Weaver and Bergfeld, 2009) Download
Grover disease, also known as transient acantholytic dermatosis, is a papulovesicular rash of the upper trunk, generally among older white males; it is usually pruritic but temporary. Grover disease is characterized by 4 different acantholytic histologic patterns, and it has been associated with numerous disorders, including hematologic malignancies. Follow-up and treatment are often difficult to evaluate secondary to the spontaneous remittance and occasional fluctuant course of the disease. Our objective will be to discuss the diagnostic considerations of Grover disease and focus on the postulated pathogenesis, including concurrent disorders and the role of the pathologist in examining skin biopsies of this nonhereditary vesicobullous disorder. Although recognized as a common condition, Grover disease's pathogenesis still remains unknown. Because Grover disease has been associated frequently with other dermatologic and nondermatologic skin conditions, inspection for other pathologic processes within the skin biopsy is essential to rule out other concomitant disorders, including hematopoietic malignancies.

Chronic inflammatory acantholytic dermatosis: a previously under-recognized or emerging variant of Grover disease.
            (Wong et al., 2017) Download
Grover disease (GD) is characterized histologically by acantholysis, with or without dyskeratosis. Four classic histopathological patterns are recognized: Darier-like, pemphigus vulgaris-like, Hailey–Hailey-like and spongi- otic.1 However, a recent study has identified five new patterns of GD (porokeratotic, lentiginous, vesicular, lichenoid and dysmaturative), which expand the histopathological diagnostic criteria of GD.2 We describe two patients with GD.



Dantzig, P (2005), ‘Age related macular degeneration and cutaneous signs of mercury toxicity’, Cutan Ocul Toxicol, 24 3-9. PubMed:
——— (2010), ‘Grover’s disease and mercury.’, Cutan Ocul Toxicol, 29 (1), 73. PubMed: 19827971
Dantzig, PI (2003a), ‘A new cutaneous sign of mercury poisoning’, J Am Acad Dermatol, 49 (6), 1109-11. PubMed: 14639393
——— (2003b), ‘A new cutaneous sign of mercury poisoning.’, Ann Intern Med, 139 (1), 78-80. PubMed: 12834329
——— (2006), ‘Parkinson’s disease, macular degeneration and cutaneous signs of mercury toxicity.’, J Occup Environ Med, 48 (7), 656. PubMed: 16832218
Hanson, M and S Hsu (2006), ‘Pruritic papules on the chest and back. Grover’s disease.’, Am Fam Physician, 74 (4), 641-42. PubMed: 16939188
Helfman, RJ (1985), ‘Grover’s disease treated with isotretinoin. Report of four cases.’, J Am Acad Dermatol, 12 (6), 981-84. PubMed: 3859501
Lee, EH, et al. (2010), ‘Grover’s disease associated with pregnancy.’, J Dermatol, 37 (4), 381-83. PubMed: 20507412
Phillips, C, et al. (2013), ‘Is Grover’s disease an autoimmune dermatosis’, Exp Dermatol, 22 (12), 781-84. PubMed: 24131368
Quirk, CJ and PJ Heenan (2004), ‘Grover’s disease: 34 years on.’, Australas J Dermatol, 45 (2), 83-6; quiz 87. PubMed: 15068451
Weaver, J and WF Bergfeld (2009), ‘Grover disease (transient acantholytic dermatosis).’, Arch Pathol Lab Med, 133 (9), 1490-94. PubMed: 19722762
Wong, JLC, et al. (2017), ‘Chronic inflammatory acantholytic dermatosis: a previously under-recognized or emerging variant of Grover disease.’, Clin Exp Dermatol, PubMed: 28636090