Grover’s Disease (transient acantholytic dermatosis [TAD], persistent acantholytic dermatosis, transient acantholytic dyskeratosis)
Are You Confident of the Diagnosis?
What you should be alert for in the history
The history will include a variably pruritic eruption of variable duration, predominantly on the trunk. It may wax and wane, and may have seasonal variation.
Characteristic findings on physical examination
Characteristic findings include multiple 1-3mm monomorphous scaly papules on the trunk, occasionally papulovesicular or erythematous (
Grover’s disease. Small pink-red papules on the the back. (Courtesy of Bryan Anderson, MD)
Expected results of diagnostic studies
A skin biopsy for diffuse disease is usually not necessary, as the diagnosis of Grover’s disease (GD) may be made confidently on clinical grounds. Histopathology confirms acantholysis, with or without dyskeratosis (
Histology of Grover’s disease. Focal acantholytic dyskeratosis (H&E). (Courtesty of Bryan Anderson, MD)
Transient acantholytic dermatosis (TAD)-like eruptions may occur as a presentation of scabies. Scabies may be seen in all demographic groups and usually has other findings, such as burrows, acral lesions, and erythematous nodules (especially genital), as well as a positive skin prep.
Miliaria is similar in its distribution and heat-associated history; pathology is clear cut.
TAD lesions may occur after a recent insult such as an irritant contact dermatitis or superficial skin infection. This usually has a brief self-limited course.
GD may mimic a drug reaction (although it is not mentioned in Litt’s Drug Eruption Reference Manual). Dermatitis herpetiformis may resemble the truncal lesions of GD (may have superficial vesicles), but it is usually more prominent on the extremities and has distinctive pathologic and immunofluorescent features.
Solitary lesions—focal acantholytic dyskeratosis—may mimic a benign lichenoid keratosis or verruca, and may need to be biopsied to rule out an actinic keratosis/squamous cell carcinoma.
The Ackerman Academy of Dermatopathology reviewed all their specimens diagnosed as TAD. Interestingly, GD was listed as a possible clinical diagnosis in only half of the cases.
Who is at Risk for Developing this Disease?
Most patients are Caucasian adults over 50 years of age , with a mean age of 64 years and a male predominance. Younger patients tend to have shorter outbreaks. Common precipitating factors include heat or sweating, ultraviolet radiation, and winter xerosis. Ionizing radiation is an infrequent precipitant.
What is the Cause of the Disease?
The etiology of GD is not well elucidated. No familial/hereditary history or genetic mutation exists.
An insult to the skin produces epidermal demise, resulting in acanthosis and dyskeratosis.
Systemic Implications and Complications
GD is slightly more common in patients with a history of atopy or xerosis. While cases have been reported with the discovery of an internal malignancy, this association is generally believed to be coincidental.
Antipruritics (pramoxine, menthol)
Keratolytics (urea, lactic acid)
Mid-depth chemical peel
Narrow-band ultraviolet B
Psoralen and ultraviolet
Optimal Therapeutic Approach for this Disease
There is a paucity of dermatologic literature regarding the treatment of GD. Therapeutic triumphs may be overstated or over-believed due to the disease’s naturally transient nature. Treatments are often prescribed based on clinical appearance (e.g. corticosteroids for itchy red bumps) or known histology (e.g. retinoids for epidermal disarray).
Lead by the patient’s history, minimize precipitating environmental settings such as excessive heat, sunlight, irritants, or overly dry skin. Inquire about new medications; check for unusual distibution. Determine how severe the TAD is, and what effect it is having on the patient’s quality of life. Encourage the use of combination modalities for any potential synergistic effect. Optimizing the patient’s environs, and applying antipruritics and keratolytics/emollients, are the cornerstones of treatment. Bath oils may be used as a substitute for soap. Colloidal oatmeal may relieve pruritus.
As GD usually covers a broad area, the recommendation for all topical therapies is to use the lotion or solution vehicles when available. Antipruritics, such as pramoxine and camphor; and keratolytic lotions, such as lactic acid 10-12% or urea 20-40%; may be applied ad libidum. Topical calcipotriene twice daily for 1 month is a safe starting therapy. Topical corticosteroids, such as fluticasone lotion 0.05% twice daily, may be added for several weeks.
As calcipotriene is only avaliable in a cream or ointment, it is worth experimenting with a combination of calcipotriene 0.005% and betamethaxone diproprionate 0.0643% suspension daily.
Although their use is widespread, the efficacy of corticosteroids has not been thoroughly studied, which holds true for most modalities. Topical retinoids may work in theory, but their use is rarely reported in the dermatologic literature. Adapalene 0.1% is available as a lotion; warn the patient about possible irritation.
Patients that flare in the wintertime may benefit from ultraviolet B phototherapy. Results should be observed closely, as some patients may flare from ultraviolet radiation. This would be less of a concern with UVA1 cold light phototherapy, but this modality isn’t widely available. Likewise, Grenz ray treatments might be worthwhile, if available.
The use of psoralen and UVA (PUVA) therapy is nearly obsolete, given the improved efficacy of narrow-band UVB, and so this treatment should be reserved for the most severe cases, particularly given its potential side effects.
One successful case of mid-depth peeling suggests this is a tantalizing option before moving on to systemic treatment or phototherapy. The authors used 40% trichloracetic acid on the chest, but the article’s commentary suggests starting out at 20% and working up as needed to minimize the risk of scarring. As this case yielded long-term benefit, one wonders if nonablative fractional resurfacing could be enlisted (or avoided).
Moderate-to-severe cases recalcitrant to the above might benefit from systemic medications. As most patients are male or over 50, a trial of acetretin or isotretinoin may be tried. In four patients, 40mg daily of isotretinoin produced marked improvement in about 3 weeks. The authors then used a 10mg maintenance dose for about 2 months. Three of the four patients had a prolonged remission.
Acitretin has also shown success, and this would obviate the need for going through the iPledge program necessary for isotretinoin. Acitretin may be commenced at 0.3mg/kg per day for 2 weeks, then reduced over 4 weeks as the process settles.
In another study, oral vitamin A improved all eight patients in 2 weeks. Patients were treated with 50,000 units, three times a day for up to 2 weeks. They then received a maintenance dose of 50,000 units once a day for several more weeks. Seven of the eight patients were able to easily withdraw the medication. Patients should be monitored for signs of Vitamin A toxicity.
Recalcitrant cases may benefit from systemic corticosteroids such as prednisolone 25mg daily, tapered over 2 weeks. Methotrexate may be attempted as a treatment of last resort.
Explain the natural history of TAD to the patient. This condition may wax and wane, and may improve spontaneously. Most treatments need about 2-6 weeks to evaluate efficacy.
For mild disease on topical treatment(s), patients may be seen as needed, with the exception of monitoring for side effects of potent corticosteroids. Tell the patient that TAD is not dangerous, so that the risks of any potential systemic treatments or physical modality must be carefully weighed against potential benefit.
Many men over 50 may have dyslipoproteinemias, and thus may not be suitable candidates for oral retinoids. Warn patients particularly about hair thinning and skin peeling. Monitor the drug similarly to their usual indications.
Unusual Clinical Scenarios to Consider in Patient Management
Rare cases have been associated with renal failure/dialysis; while this association may be coincidental, one case resolved after kidney transplantation.
Particularly vesicular cases should be cultured for herpes simplex infection, as Kaposi’s varicelliform eruption in a patient with GD has been documented.
What is the Evidence?
Grover, RW. "Transient acantholytic dermatosis". Arch Dermatol. vol. 101. 1970. pp. 426-34.(The eponymous article is an eloquent soliloquy of this now common condition. Dr. Grover described six patients; three cases were precipitated by sunlight or sunlamp, and one by a contact dermatitis. While we usually think of GD as a truncal condition, Dr. Grover noted “discrete papules tended to spread distally on the extremities.” No treatment was mentioned in the article.)
Parsons, JM. "Transient acantholytic dermatosis (Grover’s disease): a global perspective". J Am Acad Dermatol. vol. 35. 1996. pp. 653-66.(A JAAD continuing medical education article with 149 references. One of the best reviews of treatment options as well as treatment failures. Not much has changed since.)
Scheinfeld, N, Mones, J. "Seasonal variation of transient acantholytic dyskeratosis (Grover’s disease)". J Am Acad Dermatol. vol. 55. 2006. pp. 263-8.(A pathologic review using biopsy data to analyze seasonal variation and demographics of GD. GD was diagnosed four times more commonly in winter than in summer. The authors suggest that sweating and heat probably do not play a major role in its origin.)
Helfman, RJ. "Grover’s disease treated with isotretinoin. Report of four cases". J Am Acad Dermatol. vol. 12. 1985. pp. 981-4.(Three of four patients with acute disease responded with remissions of at least 5 months. Two of the patients had previously failed systemic corticosteroids.)
Rohr, JB, Quirk, CJ. "Treatment of transient acantholytic dermatosis". Arch Dermatol. vol. 115. 1979. pp. 1033-4.(This letter to the editor may be the largest case series of GD ever reported. Eight patients improved with oral Vitamin A. Side effects of vitamin A toxicity are reviewed.)
Mota, AV, Correia, TM, Lopes, JM, Guimaraes, JM. "Successful treatment of Grover’s disease with calcipotriol". Eur J Dermatol. vol. 8. 1998. pp. 33-5.(Case report. A patient with GD of 5 month’s duration significantly improved after 3 weeks of twice daily calcipotriol ointment.)
Quirk, CJ, Heenan, PJ. Australasian J Dermatol. vol. 45. 2004. pp. 83-6.(A succinct review. This article summarizes the etiology, clinical variants, histologic subtypes, and treatment of GD. The authors made the specific treatment recommendations regarding acetretin and prednisolone.)
Kouba, DJ, Dasgeb, B, Deng, AC, Gaspari, AA. "Effective treatment of persistent Grover’s disease with trichloracetic peeling". Dermatol Surg. vol. 32. 2006. pp. 1083-8.(A case report of successful improvement with TCA peeling, including a detailed explanation of the peeling application. The authors opted for a relatively higher percentage of TCA, offset by a gentler application technique. Dr. Mark Rubin’s commentary suggests starting with the lowest concentration of acid possible to reduce the risk of scarring.)
Kosann, MK, Fogelman, JP, Stern, RL. "Kaposi’s varicelliform eruption in a patient with Grover’s disease". J Am Acad Dermatol. vol. 49. 2003. pp. 914-5.(Astute case report. The authors confirmed a case of GD by biopsy. The patient’s rash later vesiculated, and a culture confirmed herpes simplex.)
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