This is a relatively common skin rash that is probably underdiagnosed. Grover's disease is probably the better diagnostic term since not all cases are transient. It is characterized by an itchy (pruritic) eruption that may last an average of 10-12 months. It is characterized by papules and papulovesicles with excoriations occurring on the chest, back, lower sternum, arms, and thighs.
Epidemiology Disease Associations Pathogenesis Laboratory/Radiologic/
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EPIDEMIOLOGY CHARACTERIZATION SYNONYMS Transient Acantholytic Dyseratosis AGE RANGE-MEDIAN Usually >50 years SEX (M:F) Men
Persistent acantholytic dermatosis: sex-related differences in clinical presentation?
Mokni M, Aractingi S, Grossman R, Verola O, Letessier S, Civatte J, Dubertret L.
Clinics for skin diseases, Hopital Saint-Louis, Paris, France.
Acta Derm Venereol 1993 Feb;73(1):69-71 Abstract quote
We report the case of a 58-year-old man with a chronic papular eruption of 10 years' duration. Histopathology revealed focal acantholytic dyskeratosis. This condition is thought to represent a distinct entity which has been reported under several names and frequently referred to as persistent acantholytic dermatosis.
The relationship between this condition and transient acantholytic dermatosis (Grover's disease), emphasizing sex-related presentations, is discussed.
Incidence of transient acantholytic dermatosis (Grover's disease) in a hospital setting.
French LE, Piletta PA, Etienne A, Salomon D, Saurat JH.
Department of Dermatology/DHURDV, HCU, Geneva, Switzerland.
Dermatology 1999;198(4):410-1 Abstract quote
BACKGROUND: Grovers's disease may be triggered by bed rest.
METHODS: We have prospectively analyzed, over a 30-month period, all cases of transient acantholytic dermatosis (TAD) diagnosed in the context of a dermatological consultation for inpatients of a community hospital.
RESULTS: A total of 28 cases of TAD were diagnosed within a total of 3,750 patients examined (0.8%)/ The mean age of patients with TAD was 66.7 years, and the male-to-female ratio was 1.8. In 83% of cases the length of hospitalization preceding TAD was 66.7 years, and the male-to-female ratio was 1.8. In 83% of cases the length of hospitalization preceding TAD exceeded 2 weeks, and in all cases there was an association with strict bed rest. No association with malignant disease or other specific pathologies was observed.
CONCLUSION: Our results suggest that TAD, which is frequent in elderly patients within a hospital setting, is not paraneoplastic and favor the hypothesis of a sweat-related pathogenesis.
DISEASE ASSOCIATIONS CHARACTERIZATION Actinic damage Atopic dermatitis Asteatotic eczema Allergic contact dermatitis Chronic renal failure
Grover's disease in patients with chronic renal failure receiving hemodialysis: clinicopathologic review of 4 cases.
Casanova JM, Pujol RM, Taberner R, Egido R, Fernandez E, Alomar A.
Departments of Dermatology, Pathology, and Nephrology, Hospital Universitari Arnau de Vilanova, Facultat de Medicina de Lleida, Spain.
J Am Acad Dermatol 1999 Dec;41(6):1029-33 Abstract quote
In 4 patients undergoing hemodialysis for chronic renal failure, a transient or persistent, papular and keratotic eruption developed on the trunk and arms.
Histologic examination disclosed focal acantholysis with dyskeratosis. The lesions were clinically and histologically indistinguishable from those of Grover's disease. A possible association with Grover's disease and chronic renal failure and/or hemodialysis is postulated. Possible implicated pathogenic mechanisms are discussed.
We suggest that Grover's disease should be included in the differential diagnosis of cutaneous eruptions in patients with chronic renal failure.
Transient acantholytic dermatosis induced by recombinant human interleukin 4.
Mahler SJ, De Villez RL, Pulitzer DR.
Division of Dermatology, University of Texas Health Science Center, San Antonio 78284-7876.
J Am Acad Dermatol 1993 Aug;29(2 Pt 1):206-9 Abstract quote
BACKGROUND: Interleukin 4 is one of many cytokines under investigation about its possible role in the pathogenesis and treatment of disease. Transient acantholytic dermatosis is of uncertain origin. It has not previously been linked to drug ingestion and is generally not believed to have an immunologic basis.
OBJECTIVE: Our purpose was to describe the clinical characteristics and histologic features of a cutaneous eruption caused by interleukin 4.
METHODS: Three patients in whom an eruption developed after they received intravenous recombinant human interleukin 4 were examined and biopsy specimens were evaluated.
RESULTS: These patients had a pruritic papulovesicular eruption that was consistent, both clinically and histologically, with transient acantholytic dermatosis. None of the other conditions believed to precipitate transient acantholytic dermatosis was present in our patients.
CONCLUSIONS: This is the first report of a cutaneous side effect of interleukin 4. This may be antibody-mediated or related to increased production of tissue-type plasminogen activator.
Transient acantholytic dermatosis (Grover's disease). A skin disorder related to heat and sweating.
Hu CH, Michel B, Farber EM.
Arch Dermatol 1985 Nov;121(11):1439-41 Abstract quote
We report seven cases of transient acantholytic dermatosis (Grover's disease) to exemplify a causal association with heat and sweating.
The excessive heat and sweating was related to the use of a hot tub, a hot water bottle, a steam bath, an electric blanket, the prolonged wearing of a polyester suit, and postoperative bed confinement.
Immunocompromised states Ionizing radiation LEUKEMIA CUTIS
J Cutan Pathol. 2006 Jun;33(6):443-6. Abstract quote
Leukemia cutis used to be a late manifestation of leukemia. On the other hand, Grover's disease has been described in the setting of cancer.
Case Report: A patient diagnosed as having a chronic myelomonocytic leukemia presented with lichenoid, slightly infiltrated plaques on the anterior aspect of his thorax and abdomen and papulovesicles on his back. A skin biopsy showed the co-existence of leukemia cutis, Grover's disease, and syringoma-like features.
Discussion: We discuss and comment upon this unusual association.
Myelodysplastic syndrome and transient acantholytic dermatosis.
Rockley PF, Bergfeld WF, Tomecki KJ, Brydon JK.
Department of Dermatology, Cleveland Clinic Foundation, Ohio.
Cleve Clin J Med 1990 Sep;57(6):575-7 Abstract quote
Focal acantholytic dyskeratosis consistent with the clinical and histological features of Darier's type of transient acantholytic dermatosis occurred in a man with myelodysplasia.
Topical steroids and systemic antihistamines provided temporary and moderate relief from pruritus, but failed to control the dermatosis.
Grover disease (transient acantholytic dermatosis) and piebaldism.
Kiwan RA, Mutasim DF.
Department of Dermatology, University of Cincinnati College of Medicine, Ohio 45267-0592, USA.
Cutis 2002 Jun;69(6):451-3 Abstract quote
A 35-year-old white man with lifelong stable white lesions on the anterior trunk and extremities presented with a pruritic papular eruption limited to the white patches. Results of a histologic examination led to a diagnosis of Grover disease (transient acantholytic dermatosis).
To our knowledge, this article is the first to report an association between Grover disease and piebaldism or other depigmented disorders. We review the literature and speculate on the association between these conditions.
PATHOGENESIS CHARACTERIZATION DESMOSOMES
Junctional proteins of keratinocytes in Grover's disease, Hailey-Hailey's disease and Darier's disease.
Hashimoto K, Fujiwara K, Harada M, Setoyama M, Eto H.
Department of Dermatology & Syphilology, Wayne State University School of Medicine, Detroit, MI 48201, USA.
J Dermatol 1995 Mar;22(3):159-70 Abstract quote
Alterations of junctional structures in non-immune mediated acantholytic diseases (Grover's, Hailey-Hailey's and Darier's diseases) were examined using monoclonal antibodies against desmosomal attachment constituents (desmoplakin I & II and plakoglobin), desmosomal intercellular cement glycoprotein (desmoglein), protein of adherens junction (vinculin), and protein of gap junction (43Kd connexin).
Universal cell surface (transmembrane) glycoprotein CD44 was also studied. In acantholytic foci of these diseases, attachment plaque proteins had dissolved and diffused into the acantholytic cells. The normal dotted linear pattern of immunostaining on the cell membrane was totally lost. In contrast, CD44 was well preserved on the cell membranes of acantholytic cells. Adherens junction and gap junction proteins were mostly preserved. Acantholytic cells of pemphigus vulgaris were similarly studied. In these cells, desmosomal attachment plaque proteins were very well preserved, while intercellular cement substance (desmoglein), adherens junctional proteins (vinculin), and gap junction protein (connexin) were totally absent, either on the cell membrane or in the cytoplasm.
Electron microscopy confirmed an early dissolution of attachment plaque. Internalized desmosomal structures were seldom found in acantholytic cells of non-immune diseases. It was concluded that the primary event in acantholysis in these three diseases is the dissolution of desmosomal attachment plaque.
Desmosomal dissolution in Grover's disease, Hailey-Hailey's disease and Darier's disease.
Hashimoto K, Fujiwara K, Tada J, Harada M, Setoyama M, Eto H.
Department of Dermatology, Wayne State University School of Medicine, Detroit, MI 48201, USA.
J Cutan Pathol 1995 Dec;22(6):488-501 Abstract quote
Proteins involved in the formation of desmosomes and simpler adherens junctions were studied in three types of non-immune acantholytic diseases; specifically, four cases of Grover's disease (GD), one case of Hailey-Hailey's disease (HHD) and one case of Darier's disease (DD), and these were compared to two cases of immune-mediated acantholytic disease pemphigus vulgaris (PV).
The proteins studied included: 1. The intracellular desmosomal proteins, desmoplakin I and II and plakoglobin; 2. The intercellular desmosomal proteins, desmoglein and CD44; and 3. vinculin, which is a major intracellular protein of the simpler aherens junctions. In GD, HHD and DD, immunostaining showed a loss of desmoplakin I and II and plakoglobin from the desmosomes, and a diffuse staining in the cytoplasm. In contrast, in pemphigus vulgaris, these proteins seemed intact and were localized to dot-like spots on the cell surface. Also, desmoglein, and CD44 were slightly affected in GD, and moderately affected in HHD and DD. Absence of desmosomal attachment plaques, the lack of labeling with desmoglein in the affected desmosomes and a diffusion of the labels into cytoplasm were demonstrated with electron microscopy using an immunogold technique. In PV, desmoglein III is one of the target antigens for the autoantibodies in this disease and was only partially preserved in a small number of lesional cells, while CD44 was mostly preserved. Vinculin was intact in GD, HHD and DD, but was lost in PV.
This study, our previous work, and that of others, suggest that: 1. In GD, HHD and DD, the proteins of the desmosomal attachment plaque are primarily affected; 2. In PV, the intercellular glycoproteins are primarily involved; and 3. Simple adherens junctions are intact in GD, HHD and DD, but are damaged in PV.
Sudoriferous acrosyringeal acantholytic disease. A subset of Grover's disease.
Hashimoto K, Moiin A, Chang MW, Tada J.
Department of Dermatology & Syphilology, Wayne State University School of Medicine, Detroit, Michigan, USA.
J Cutan Pathol 1996 Apr;23(2):151-64 Abstract quote
Three selected cases of transient acantholytic dermatosis were studied because of their definitive correlation with sweating due to fever and/ or bed-ridden situations. Biopsy specimens were serially sectioned and acantholysis was found in the acrosyringium or traced to connect to the acrosyringium in all biopsy specimens.
Carcinoembryonic antigen (CEA) and eccrine gland-specific monoclonal antibody, IKH-4, were positive in acantholytic cells. Electron microscopy revealed electron dense material filling the lumen of intraepidermal eccrine ducts. This material leaked into lateral intercellular spaces of the luminal cells, passing tight junctions.
Marked edema and numerous lysosomes were reminiscent of those found when eccrine acrosyringium is formed in the embryo; this suggested that an occluded and damaged eccrine intraepidermal duct was being rebuilt via lysosomal digestion.
Grover's disease (transient acantholytic dermatosis): relationship of acantholysis to acrosyringia.
Antley CM, Carrington PR, Mrak RE, Smoller BR.
Department of Pathology, University of Arkansas for Medical Sciences, Little Rock, USA.
J Cutan Pathol 1998 Nov;25(10):545-9 Abstract quote
Transient acantholytic dermatosis is often associated with excessive sweating, fever, and bed confinement. The pathogenesis of this disease has been postulated to be poral occlusion of damaged eccrine intraepidermal ducts.
Histological and immunohistochemical and ultrastructural studies were performed on 10 biopsies from 10 patients with transient acantholytic dermatosis. Immunoreactions for carcinoembryonic antigen and cytokeratin-7 to identify eccrine duct epithelium were performed on all 11 biopsies. In addition, 5 of the biopsies were immunoreacted for cytokeratin 8.
All immunoreactions were reviewed independently by two observers to determine extent of reactivity and whether it correlated with areas of epidermal acantholysis. Among the 11 biopsies, 8 showed acantholysis not associated with eccrine duct outflow tracts. In 2 biopsies the acantholysis was consistently associated with acrosyringea; in one case acantholysis was inconsistently associated with eccrine outflow tracts.
Epidermal acantholysis in patients with Grover's disease is associated with the outflow tracts of eccrine ducts in a subgroup of patients. Although leakage of sweat from occluded sweat ducts in acrosyringia may be the mechanism operating in a subgroup of patients with Grover's disease, this does not appear to be the subgroup of patients in whom Grover's disease develops in the setting of being bedridden and/or sweating.
CLINICAL VARIANTS CHARACTERIZATION GENERAL
Grover's disease: clinicopathologic review of 72 cases.
Davis MD, Dinneen AM, Landa N, Gibson LE.
Department of Dermatology, Mayo Clinic Rochester, MN 55905, USA.
Mayo Clin Proc 1999 Mar;74(3):229-34 Abstract quote
OBJECTIVE: To report the clinicopathologic findings in patients with Grover's disease.
MATERIAL AND METHODS: We reviewed the medical records and biopsy specimens from 72 patients with transient acantholytic dermatosis (Grover's disease) examined at Mayo Clinic Rochester. Hematoxylin-eosin-stained biopsy specimens (from all patients) were assessed. Immunohistochemistry stains BRST-2, CAM 5.2, and CD44 were used to stain eight specimens. Direct immunofluorescence reports were reviewed. Selected specimens were stained by indirect immunofluorescence to detect major basic protein.
RESULTS: Of the 72 patients, 63 (88%) were men, and the mean age was 48 years (range, 31 to 85). Lesions were distributed mainly on the trunk (in 71 patients) and proximal extremities (in 25). Heat and sweating frequently were exacerbating factors. Fifteen patients (21%) were bedbound. Concurrent nondermatologic malignant disease was present in 18 patients (25%). Two patients (3%) had acquired immunodeficiency syndrome. Follow-up in 28 patients (mean, 38 months; range, 3 months to 7 years) revealed that the disease had recurred in 13, persisted in 3, and resolved in 12. Review of the biopsy specimens showed that acantholysis was pemphigus vulgaris-like in 40 patients (56%), Darier's disease-like in 16 (22%), spongiotic in 12 (17%), pemphigus foliaceus-like in 2 (3%), and Hailey-Hailey disease-like in 2 (3%). A perivascular lymphocytic infiltrate of varied intensity in 64 specimens (89%) was associated with eosinophils in 16 (22%). In nine biopsy specimens with dermal eosinophilia stained for major basic protein, varied dermal cellular and extracellular deposition of major basic protein was present. Results of direct immunofluorescence studies, performed in 17 cases, were negative or nonspecific. CD44 stained acantholytic areas in addition to sweat glands in two of eight specimens (25%).
CONCLUSION: Further studies of the pathogenesis of Grover's disease are needed. The predisposing conditions, site of involvement, and relapsing nature of this disorder may implicate acrosyringeal dysfunction as the cause.
VARIANTS MUCOUS MEMBRANE
Transient acantholytic dermatosis with involvement of oral mucosa.
Kanzaki T, Hashimoto K.
J Cutan Pathol 1978 Feb;5(1):23-30 Abstract quote
Histologic, immunologic and electron microscopic studies were performed in a patient with transient acantholytic dermatosis which involved oral mucosa.
Histologic and electron microscopic findings were almost identical in both cutaneous and mucous membrane lesions, and these were similar to pemphigus vulgaris; suprabasilar separation with acantholytic cells. Desmosome-desmosome complexes were separated without disruption of cell membranes and cytoplasmic structures were well-preserved without dyskeratosis. Lamina lucida, however, was often separated in mucous membrane lesions, in contrast to the normal lamina lucida in cutaneous lesions of such cases or in pemphigus vulgaris. Direct and indirect immunofluorescence studies for pemphigus were repeatedly negative.
This study shows that transient acantholytic dermatosis may involve mucous membrane and may resemble pemphigus vulgaris histologically and ultrastructurally except for the widened lamina lucida of the mucous membrane.
Persistent acantholytic dermatosis. A variant of transient acantholytic dermatosis (Grover disease).
Simon RS, Bloom D, Ackerman AB.
Arch Dermatol 1976 Oct;112(10):1429-31 Abstract quote
A patient with unusual manifestations of transient acantholytic dermatosis (Grover disease) has lesions that have persisted for more than three years. Biopsy specimen showed histologic changes previously unreported in Grover disease.
In order to emphasize that this condition is not always transient, we have titled this entity "persistent acantholytic dermatosis."
HISTOLOGICAL TYPES CHARACTERIZATION General
Arch Dermatol 1977;113:431-435
In general, the lesions are circumscribed and focal often with a mixed inflammatory pattern
Four main patterns have been described:
Darier-like Hailey-Hailey like Pemphigus like Spongiosis with acantholysis
CHARACTERIZATION DIRECT IMMUNO-FLUORESCENCE
Immunofluorescence studies in transient acantholytic dermatosis (Grover's disease).
Am J Dermatopathol 1979 Winter;1(4):325-7 Abstract quote
Abnormalities were found by immunofluorescence in five of 11 (45%) patients with transient acantholytic dermatosis. There was no consistent pattern to the abnormalities; for example, they were circulating antibodies to intercellular and basal cell antigens in a third.
Deposits of Ig and/or C3 were present in lesions of three patients and C3 was present in the intercellular substance in the lesions of a fourth patient.
These findings suggest that different immune mechanisms may be involved in the pathogenesis of transient acantholytic dermatosis.
PROGNOSIS AND TREATMENT CHARACTERIZATION TREATMENT Topical steroids CALCIPOTRIOL
- Grover's disease: successful treatment with acitretin and calcipotriol.
Miljkovic J, Marko PB.
Department of Dermatology, Maribor Teaching Hospital, Maribor, Slovenia.
Wien Klin Wochenschr. 2004;116 Suppl 2:81-3. Abstract quote
A 74-year-old man presented with a five-month history of highly pruritic keratotic papules on the trunk and extremities.
Laboratory data revealed mild eosinophilia, elevated IgE (483KE/I) and no other signs of atopy. Tests to exclude parasitic infestation were negative. Two biopsies showed non-specific changes. The third biopsy revealed small acantholytic clefts in the upper part of the epidermis and confirmed the diagnosis of Grover's disease.
Topical treatment with calcipotriol ointment and systemic treatment with acitretin in low doses successfully reduced the pruritus within one week, and brought about a complete remission within three weeks without any recurrence.
Successful treatment of Grover's disease with calcipotriol.
Mota AV, Correia TM, Lopes JM, Guimaraes JM.
Department of Dermatology, Hospital de Sao Joao, Alameda Prof. Hernani Monteiro, 4200 Porto, Portugal.
Eur J Dermatol 1998 Jan-Feb;8(1):33-5 Abstract quote
We report the case of an 84-year-old man with clinical, histological and electron-microscopic features of a Darier-like pattern of Grover's disease.
The lesions had a persistent course, with a 5-month history before diagnosis and a clinical onset 2 years after the surgical removal of a cholangiocarcinoma. A significant clinical improvement was observed after a three-week course of calcipotriol ointment applied as a monotherapy regimen.
Clinical uses of topical calcipotriol in dermatological conditions are reviewed with emphasis on dyskeratotic disorders.
Grover's disease treated with isotretinoin. Report of four cases.
J Am Acad Dermatol 1985 Jun;12(6):981-4 Abstract quote
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.
Successful treatment of transient acantholytic dermatosis with systemic steroids.
Eros N, Kovacs A, Karolyi Z.
Department of Dermatology, Semmelweis Hospital, Miskolc, Hungary.
J Dermatol 1998 Jul;25(7):469-75 Abstract quote
A sixty-year-old man, developed 2-5 mm sized, hyperemic, itchy papules, vesicles, erosions and crusts on hyperemic base on his chest, abdomen, back, gluteal region, and proximal sites of his upper and lower extremities. The direct and indirect immunoflurescence tests were negative.
Histology revealed extensive acantholysis in the epidermis in the following forms: pemphigus vulgaris-like suprabasal acantholysis, Darier-like acantholytic dyskeratosis with corps ronds, Hailey-Hailey-like suprabasal clefts, and pemphigus foliaceus-like superficial acantholysis with spongiosis. Using systemic steroids, topical drying, and reepithelising therapy, the patient was cured. He was symptom-free the first, fourth, and thirteenth months after finishing steroid therapy.
We review the literature and the new subdivision of the disease according to the histological and clinical features.
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