Table of Contents
Definition / general | Essential features | Epidemiology | Sites | Etiology | Clinical features | Case reports | Treatment | Clinical images | Microscopic (histologic) description | Microscopic (histologic) images | Negative stains | Immunofluorescence description | Molecular / cytogenetics description | Differential diagnosis | Board review style question #1 | Board review style answer #1 | Board review style question #2 | Board review style answer #2Cite this page: Aljarbou O, Sangueza OP. Transient acantholytic dermatosis. PathologyOutlines.com website. https://www.pathologyoutlines.com/topic/skinnontumorGrover.html. Accessed December 27th, 2024.
Definition / general
- Transient papulovesicular eruption on the trunk
- Sporadic, reactive condition
- Initially characterized by Grover in 1970 (Arch Dermatol 1970;101:426)
Essential features
- Middle aged to elderly, white, mostly male patients
- Multiple pruritic papulovesicular eruption
- Pathologically can mimic other vesiculobullous disease and epithelial neoplasms
- Correlation with clinical findings is essential
Epidemiology
- Incidence of 0.1% of skin biopsy specimens (J Am Acad Dermatol 2006;55:263)
- M:F = 2:1 (Am J Dermatopathol 2010;32:541)
- Mean age 62 years
Sites
- Most common location is the trunk (93%)
- Lower percentage from the upper and lower limbs (12%) (Patterson: Weedon's Skin Pathology, 4th Edition, 2015)
Etiology
- Unknown, multifactorial
- Dry skin, excessive heat, sun exposure or chemotherapy
- Associated with atopic disease, steatosis, psoriasis or neoplasms among other triggers (Am J Dermatopathol 2010;32:541)
- Diagnosed 4x more frequently in winter compared to summer (J Am Acad Dermatol 2006;55:263)
Clinical features
- Pruritic papules, papulovesicles, plaques and bullae lesions
- Lesions distributed mainly on the trunk and proximal extremities but rarely can appear on the scalp, on the face and in the mouth (these lesions resembled aphthae)
- No systemic symptoms
Case reports
- 38 year old man, 52 year old woman and 54 year old man with Grover disease after bone marrow transplant (Australas J Dermatol 2016;57:e120)
- 53 year old man with pruritic papulovesicular eruption followed a multilinear distribution along Blaschko lines (Acta Dermatovenerol Croat 2017;25:31)
- 58 year old man with pemphigus vulgaris and nodules on the back and abdomen (Int J Dermatol 2017;56:1052)
- 68 year old man with syringoma-like features and leukemia cutis and a 71 year old man with Grover disease induced by cetuximab (J Cutan Pathol 2006;33:443)
- 72 year old man with Grover disease in association with leukemia cutis (Am J Dermatopathol 2011;33:e41)
- 73 year old man with extensive erythematous, papular rash after ipilimumab (J Immunother Cancer 2016;4:55)
Treatment
- Treatment options include topical steroids, retinoids and vitamin D analogues and systemic steroids, retinoids and methotrexate
- 5-aminolevulinic acid photodynamic therapy (ALA-PDT) shows rapid, dramatic improvement in symptoms, allowing for significant improvement in quality of life (Dermatol Surg 2013;39:960)
Clinical images
Microscopic (histologic) description
- Suprabasal acantholysis with vesicle formation is the principal microscopic finding
- Elongation of rete ridges with focal acantholysis and eosinophils may be the only early changes in Grover disease
- Main 4 histopathological patterns are:
- Pemphigus vulgaris / foliaceous-like: predominantly limited to suprabasal acantholysis, with basal keratinocytes attached to basement membrane forming a characteristic tombstone appearance
- Darier-like: suprabasal acantholysis of keratinocytes with scattered apoptotic or dyskeratotic cells within various levels of the epidermis
- Spongiotic: edema within epidermis, causing separation of keratinocytes and prominent intracellular bridges
- Hailey-Hailey-like: suprabasal acantholysis of all levels of the epidermis without significant dyskeratosis (dilapidated brick wall appearance)
- More than one pattern can be seen in the same setting
- Other newly described histopathological pattern include: (Am J Dermatopathol 2010;32:541)
- Porokeratotic: presence of oblique columns of parakeratosis over areas of epidermis devoid of granular layer, with occasional dyskeratotic cells in the upper epidermal layers and a tendency to basal vacuolization
- Lentiginous: elongation of the rete ridges with some basal hyperpigmentation resembling a solar lentigo or Dowling-Degos disease
- Vesicular: intraepidermal vesicles with minimal spongiosis or acantholysis on their sides
- Lichenoid: vacuolar damage and slight lymphocytic infiltrate at the dermoepidermal junction, with occasional dyskeratosis and barely identifiable acantholysis
- Dysmaturative: disordered keratinocyte maturation with nuclear pleomorphism and slight hyperchromasia (Am J Dermatopathol 2018;40:642)
- Epidermolytic hyperkeratosis-like pattern (Am J Dermatopathol 2014;36:358)
Microscopic (histologic) images
Negative stains
- HSV1, HSV2, VZV (J Cutan Pathol 2017;44:486)
Immunofluorescence description
- Negative (Am J Dermatopathol 1979;1:325)
Molecular / cytogenetics description
- No molecular changes identified (Br J Dermatol 2000;143:658)
Differential diagnosis
- Darier disease:
- Abnormality in the ATP2A2 gene
- Greater tendency to involve follicles
- No eosinophilic infiltrate
- Pemphigus vulgaris:
- Broad zones of suprabasal acantholysis
- Mucosal involvement, involvement of adnexal structures
- Often abundant eosinophils
- Net pattern of IgG and C3 on direct immunofluorescence
- Pemphigus foliaceus:
- Broad zone of subcorneal and subgranular acantholysis
- Involvement of adnexal structures, often eosinophils
- Net pattern of IgG and C3 on direct immunofluorescence
- Hailey-Hailey disease: broad zone of suprabasal acantholysis with few dyskeratotic keratinocytes
- Actinic keratosis / squamous cell carcinoma in situ: reduced or absent granular cell layer
- Herpes: multinucleation, chromatin margination and molding which constitute the viral cytopathic changes (Am J Dermatopathol 2018;40:445, J Cutan Pathol 2017;44:486)
Board review style question #1
A white, elderly male presented with multiple pruritic papule involving the trunk. Which of the following is true regarding the diagnosis of this lesion?
- Associated mucosal lesion is diagnostic
- ATP2A2 gene abnormality is a common finding
- Net pattern of IgG and C3 on direct immunofluorescence
- Sparing of acrosyringium can be a helpful feature
Board review style answer #1
D. Sparing of acrosyringium can be a helpful feature. Transient acantholytic dermatosis (Grover disease) can mimic variable vesiculobullous entities, especially pemphigus vulgaris, Darier and Hailey-Hailey. Differentiation depends on clinical presentation, microscopic findings and direct immunofluorescence findings. One microscopic finding that can help to differentiate between pemphigus vulgaris and Grover disease is adnexal structure and acrosyringium involvement in the former.
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Board review style question #2
Which of the following case scenarios is typical for transient acantholytic dermatosis (Grover disease)?
- 17 year old man with crusted popular lesions involving head and neck
- 20 year old woman with flaccid blisters involving the axillae and inframammary region
- 40 year old woman with oral blisters and flaccid bullae involving the trunk
- 60 year old man with erythematous papule involving the trunk
Board review style answer #2
D. 60 year old man with erythematous papule involving the trunk. Transient acantholytic dermatosis (Grover disease) is most common in middle aged to elderly, Caucasian men. It most commonly manifest as a vesicular eruption of the trunk.
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