Transient Acantholytic Dermatosis 

Updated: Jun 07, 2018
Author: Edward J Zabawski, Jr, DO; Chief Editor: Dirk M Elston, MD 

Overview

Background

Transient acantholytic dermatosis (Grover disease) is not an uncommon condition, but, surprisingly, it was not thoroughly characterized until Grover did so in 1970.[1] While generally accepted to be a benign, self-limited disorder, it is often persistent and difficult to manage; hence, the description of transient is misleading.[2] The presentation can be subtle, or it may closely resemble 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 (Grover disease) closely resemble those of several other conditions that are clinically distinct, which may add to potential diagnostic confusion.

Pathophysiology

The etiology of transient acantholytic dermatosis (Grover disease) 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, although this association has been challenged, citing research that demonstrates that most patients with transient acantholytic dermatosis (Grover disease) present in winter, not summer.[3]

Many patients describe preceding exposure to sunlight, although exposure to artificial ultraviolet radiation has not been shown to reproduce the process. Transient acantholytic dermatosis (Grover disease) seems to occur more frequently in patients with atopic dermatitis and asteatotic dermatitis, although many individuals with these conditions never develop it. Viral, bacterial, and other pathogens have also been proposed, but no causative role has been established. A number of transient acantholytic dermatosis (Grover disease) case reports have described an association with lymphoma, but these seem to be in the extreme minority.[4, 5] The exact pathogenesis has not been elucidated. Melanoma therapy with CTLA-4 inhibition has been associated with the disease.[6, 7]

Epidemiology

Frequency

Exact numbers regarding the prevalence of transient acantholytic dermatosis (Grover disease) are not available. Because of the clinical similarities with other entities and variable histopathologic findings, the disease is underdiagnosed in nondermatologic settings and probably underdiagnosed overall.

Race

Transient acantholytic dermatosis (Grover disease) most commonly affects middle-aged white men, although it may be seen in other ethnic groups, such as Hispanics and blacks.

Sex

Men are affected three times more often than women.

Age

Transient acantholytic dermatosis (Grover disease) most commonly affects middle-aged men; however, it has been in reported in children.

Prognosis

Generally, transient acantholytic dermatosis (Grover disease) is a self-limited disorder that resolves over weeks to months, but it can be persistent and may repeatedly recur for years.

Patient Education

Transient acantholytic dermatosis (Grover disease) is not curable, and the cause is unknown. Although the symptoms can frequently be controlled, some cases are refractory to treatment and difficult to manage.

 

Presentation

History

One of the hallmarks of transient acantholytic dermatosis (Grover disease) is pruritus, and all individuals who are affected experience variable degrees of itching, sometimes severe in nature.

The clinical appearance does not always correlate to the degree of pruritus; for example, some patients with limited cutaneous disease complain of severe itching, whereas others with many lesions have few or no symptoms.

While lesions may resolve over weeks to months, they commonly recur.

No systemic symptoms are associated with transient acantholytic dermatosis (Grover disease), but oral lesions can develop that resemble aphthae and may be slightly painful.[8]

Physical Examination

The transient acantholytic dermatosis (Grover disease) process usually begins as an eruption of the skin on the anterior part of the chest, the upper part of the back, and the lower part of the rib cage (see the images below).[9]

A 54-year-old man with a pruritic eruption on the A 54-year-old man with a pruritic eruption on the trunk. Notice the slight lichenification and significant erythema from rubbing that is localized to the central part of the torso. Also note the red-brown papules in the abdominal region.
Close-up view of the abdominal area of a patient w Close-up view of the abdominal area of a patient with a pruritic eruption on the trunk. Multiple, small, discrete, red-brown papules characteristic of Grover disease are present.

Patients who are severely affected may have disseminated disease affecting the neck, the shoulders, the arms, and the legs. The scalp is usually not affected, and the palms and the soles are almost always spared.

Individual lesions are erythematous to red brown keratotic papules that remain discrete and do not usually tend to coalesce. Occasionally, lesions may be acneiform, vesicular, pustular, and rarely even bullous. Although the most common presentation is that of widespread scattered papules, unusual distributions, including zosteriform or unilateral, may occur.[10]

The utility of dermoscopy is limited, as no features specific for transient acantholytic dermatosis have been reported.

Complications

Lesions may resolve with postinflammatory pigmentary alteration or with no residual change. Scarring is usually minimal unless induced by excoriation.

 

DDx

Diagnostic Considerations

Clinical differential diagnoses and their key differentiating features are listed below:

  • Dermatitis herpetiformis - Vesicular; pruritus more severe; extensor distribution

  • Folliculitis - Follicular papules; pustules if lesions intact

  • Arthropod reaction - Tendency to cluster; extremities and exposed sites usually involved

  • Papular urticaria (prurigo simplex) - Primarily excoriations; unreachable areas tend to be spared

  • Miliaria rubra - History of exacerbation with heat; often more nodular lesions

  • Papular drug eruption - Papules tend to coalesce into plaques; no sparing of extremities

  • Disseminated herpes simplex or herpes zoster - Vesicular; painful; history of immunosuppression

  • Scabies - Intractable itching, worse at night; wrists, finger webs, and axillae affected

  • Papular pityriasis rosea - Herald patch, less severe or absent pruritus, collarette of scale; seasonal incidence

  • Secondary syphilis - Usually scaly, with palmar lesions; pruritus is mild or absent

  • Galli-Galli disease[11]

Differential Diagnoses

 

Workup

Laboratory Studies

A skin scraping with oil preparation to search for mites, ova, and scybala of scabies is commonly warranted in any patient with pruritus and a rash. However, the clinical features of transient acantholytic dermatosis (Grover disease) is substantially different from scabies. More uncommon parasite infections, such as bird mite or cat mite, could mimic transient acantholytic dermatosis clinically.[12]

Histologic Findings

The histology of transient acantholytic dermatosis (Grover disease) contains certain characteristic features, but for a precise diagnosis to be rendered, clinicopathologic correlation is needed (see the images below). Typically, focal acantholysis and dyskeratosis are seen. Spongiosis is also commonly observed, and the presence of spongiosis and acantholysis in the same specimen should raise the possibility of transient acantholytic dermatosis (Grover disease).[13, 14] Acrosyringeal acantholysis may be present,[15] and multinucleated cells may suggest herpetic infection.[16]

Histopathology of Darier-type Grover disease. A fo Histopathology of Darier-type Grover disease. A focus of acantholytic dyskeratosis is present in the epidermis with slight epithelial hyperplasia and hyperkeratosis, a sign of rubbing as a consequence of the pruritic nature of the disease (hematoxylin and eosin, original magnification X40).
Higher magnification reveals the acantholytic dysk Higher magnification reveals the acantholytic dyskeratosis to better advantage. Note the corps ronds and grains (hematoxylin and eosin, original magnification X400).

Five distinct histologic patterns of transient acantholytic dermatosis (Grover disease) have been described: (1) a pattern that simulates Hailey-Hailey disease; (2) a pattern that simulates Darier disease; (3) a pattern characterized mainly by spongiotic dermatitis; (4) a pattern that simulates pemphigus vulgaris; and (5) a pattern that simulates pemphigus foliaceus. Although one pattern may predominate, each pattern may be seen in different lesions from the same patient or, in some cases, within a single specimen. The key discriminating features are described below:

  • Darier disease - Virtually identical; greater tendency to involve follicles; clinical correlation essential

  • Linear acantholytic epidermal nevus - Virtually identical; clinical correlation essential

  • Hailey-Hailey disease - Epidermis usually more hyperplastic; more diffuse involvement

  • Pemphigus vulgaris - Broad zones of suprabasilar acantholysis; mucosal involvement; involvement of adnexal structures; often abundant eosinophils

  • Primary spongiotic dermatitis (allergic contact dermatitis, nummular dermatitis) - Involvement of entire epidermis; psoriasiform hyperplasia

  • Acantholytic solar keratosis - Atypical keratinocytic proliferation in lower portion of epidermis with cytologic atypia and mitoses; alternating orthokeratosis and parakeratosis; solar elastosis

  • Solitary acantholytic keratosis - Epidermal hyperplasia; slight papillomatosis or digitation of epidermis; clinical correlation required

  • Pemphigus foliaceus/erythematosus - Broad zone of subcorneal and subgranular acantholysis; involvement of adnexal structures; often eosinophils

  • Warty dyskeratoma - Cup-shaped exoendophytic cystlike lesion; acantholytic and dyskeratotic cells lining cyst wall; pseudopapillae with acantholytic dyskeratosis lined by a single layer of basal cells

  • Familial dyskeratotic comedones - Small cylindrical invagination with epithelial lining demonstrating acantholytic dyskeratosis

 

Treatment

Approach Considerations

Success in treatment relies heavily on correct identification of the disease early in its course and treatment of any features of underlying atopy. Recurrence is the rule, not the exception; the term "transient" should be dropped as it is inaccurate and confusing and replaced with "recurrent pruritic". The role of sweat antigen or high sweat metal concentrations in patients with refractory and/or severe disease has not be evaluated but should be considered in those patients.

Medical Care

Potent topical corticosteroids may be effective in diminishing inflammation and in controlling itching associated with transient acantholytic dermatosis (Grover disease). Menthol or pramoxine-containing lotions may also be helpful for itching.

For refractory disease, retinoids, such as vitamin A 50,000 U 3 times a day for 2 weeks then daily for up to 12 weeks or isotretinoin 40 mg/d for 2-12 weeks, may be effective.[17]

Oral corticosteroids, UV-B exposure, psoralen plus ultraviolet A light (PUVA), grenz radiation, and methotrexate (MTX) have all been reported to be effective in severely resistant cases. However, some cases are refractory to virtually all forms of therapy.

Activity

Excess heat and sweating are frequently associated with an increase in the symptoms of transient acantholytic dermatosis (Grover disease). Activities that cause these symptoms should be avoided.

Prevention

Patients should avoid activities that cause excessive heat, such as exercise and prolonged sun exposure. Patients should also avoid applying topical irritants.

Long-Term Monitoring

Initial care for transient acantholytic dermatosis (Grover disease) may be limited to midpotency topical corticosteroids and oral antihistamines. Atopic skin care measures should be recommended.

Acitretin, calcipotriol, and UVA-1 have been described as useful in patients with disease that is difficult to manage.[18]

 

Medication

Medication Summary

The goals of pharmacotherapy are to reduce morbidity and to prevent complications.

Fluocinonide gel 0.05% should be applied twice a day. Never apply to the face, the axillae, or the genital areas. Desoximetasone may be used in place of fluocinonide. High potency (class I) topical steroids, such as Temovate or Diprolene, are limited to 2 weeks' use. They can cause atrophy if used longer and, therefore, should be avoided.

Hydroxyzine 10-30 mg can be used every 6 hours as needed for itching. As a substitute, Benadryl 25-50 mg may be used every 6 hours as needed. Both may cause drowsiness.

Retinoid-like Agents

Class Summary

These agents decrease the cohesiveness of abnormal hyperproliferative keratinocytes, and they may reduce the potential for malignant degeneration. They also affect keratinocyte differentiation.

Isotretinoin (Amnesteem, Claravis, Myorisan, Sotret)

Isotretinoin is a synthetic 13-cis isomer of the naturally occurring tretinoin (trans- retinoic acid). Both agents are structurally related to vitamin A.

A US Food and Drug Administration–mandated registry is now in place for all individuals prescribing, dispensing, or taking isotretinoin. For more information on this registry, see iPLEDGE. This registry aims to further decrease the risk of pregnancy and other unwanted and potentially dangerous adverse effects during a course of isotretinoin therapy.

Corticosteroids

Class Summary

These agents have anti-inflammatory properties and cause profound and varied metabolic effects. In addition, these agents modify the body's immune response to diverse stimuli.

Prednisone

Prednisone is an immunosuppressant used for the treatment of autoimmune disorders; it may decrease inflammation by reversing increased capillary permeability and suppressing PMN activity.

Antineoplastics, Antimetabolite

Class Summary

These agents regulate cell growth and differentiation.

Methotrexate (Trexall, Rheumatrex)

Methotrexate is an antimetabolite that inhibits DNA synthesis and cell reproduction in malignant cells. It has an unknown mechanism of action in the treatment of inflammatory reactions; it may affect immune function. Methotrexate ameliorates symptoms of inflammation (eg, pain, swelling, stiffness).

Vitamins

Class Summary

Vitamins are are used to meet necessary dietary requirements and are used in metabolic pathways, as well as DNA and protein synthesis.

Vitamin A (Aquasol A, A-Natural-25, A-25)

Vitamin A is a cofactor in many biochemical processes. For refractory disease, vitamin A may be administered at 50,000 U 3 times a day for 2 weeks then daily for up to 12 weeks.

 

Questions & Answers

Overview

What is transient acantholytic dermatosis (Grover disease)?

What is the pathophysiology of transient acantholytic dermatosis (Grover disease)?

What is the prevalence of transient acantholytic dermatosis (Grover disease)?

What is the racial predilection of transient acantholytic dermatosis (Grover disease)?

What is the sexual predilection of transient acantholytic dermatosis (Grover disease)?

Which age groups are at highest risk for transient acantholytic dermatosis (Grover disease)?

What is the prognosis of transient acantholytic dermatosis (Grover disease)?

What should be included in the patient education about transient acantholytic dermatosis (Grover disease)?

Presentation

What are the signs and symptoms of transient acantholytic dermatosis (Grover disease)?

Which physical findings are characteristic of transient acantholytic dermatosis (Grover disease)?

What are the complications of transient acantholytic dermatosis (Grover disease)?

DDX

How is transient acantholytic dermatosis (Grover disease) differentiated from other skin conditions?

What are the differential diagnoses for Transient Acantholytic Dermatosis?

Workup

What is the role of skin scraping in the diagnosis of transient acantholytic dermatosis (Grover disease)?

Which histologic findings are characteristic of transient acantholytic dermatosis (Grover disease)?

What are key histologic patterns and features of transient acantholytic dermatosis (Grover disease)?

Treatment

How is transient acantholytic dermatosis (Grover disease) treated?

What is the role of corticosteroids in the treatment of transient acantholytic dermatosis (Grover disease)?

What is the role of activity modification in the treatment of transient acantholytic dermatosis (Grover disease)?

How is transient acantholytic dermatosis (Grover disease) prevented?

What is included in long-term monitoring of patients with transient acantholytic dermatosis (Grover disease)?

Medications

What is the role of drug treatment for transient acantholytic dermatosis (Grover disease)?

Which medications in the drug class Vitamins are used in the treatment of Transient Acantholytic Dermatosis?

Which medications in the drug class Antineoplastics, Antimetabolite are used in the treatment of Transient Acantholytic Dermatosis?

Which medications in the drug class Corticosteroids are used in the treatment of Transient Acantholytic Dermatosis?

Which medications in the drug class Retinoid-like Agents are used in the treatment of Transient Acantholytic Dermatosis?