Grover Disease Associated With Chemotherapy: Review of Potential Pathophysiology, Current Treatments, and Future Directions.

INTRODUCTION: Transient acantholytic dermatosis has been frequently reported in patients with malignancies. While paraneoplastic cases have rarely been reported, most eruptions occur in the setting of chemotherapeutic agents. Management is based on limited data and primarily with topical steroids and topical emollients. A subset of patients exhibits recalcitrant disease and require alternate therapeutic approachesMethods: This systematic review consisted of identifying records in PubMed using the medical subject headings (MeSH) terms “chemotherapy” AND “Grover”, “chemotherapy” AND “Grover’s”, “cancer” AND “Grover”, “cancer” AND “Grover’s”, “malignancy” AND “Grover”, “malignancy” AND “Grover’s”, as well as a free text search for “Grover” OR “Grover’s” OR “Grover disease” OR “Grovers disease” OR “Grover’s disease” OR “transient acantholytic dermatosis” OR “transient acantholytic” to identify case reports, case series, systematic reviews, review articles, meta-analyses, clinical trials, brief commentaries, and original articles. The titles and abstracts of all results were reviewed. Full texts of relevant results were then read in their entirety and applicability was determined. RESULTS: Overall, Grover disease has rarely been reported in the setting of malignancy. When it occurs, it is generally in the setting of chemotherapy use. Chemotherapy-associated Grover disease is reported most frequently in association with cytotoxic chemotherapies, followed by small molecule inhibitors. The first line treatment for this complication is the use of topical agents. When these provide inadequate relief, alternate therapies have been rarely reported, with novel treatments proposed based on the type of chemotherapy agent and its mechanism of action. CONCLUSIONS: Chemotherapy-associated Grover disease is an uncommon complication of cancer treatment. While most cases of chemotherapy-associated Grover disease can be treated with topical steroids and topical emollients, certain cases require a more specialized approach. This could include adjuvant adjuvant therapies, or novel treatments that are directly related to the mechanism of action of the chemotherapy involved. J Drugs Dermatol. 2020;19(11):1056-1064. doi:10.36849/JDD.2020.5648.

Identification of novel therapeutic targets for blocking acantholysis in pemphigus.

BACKGROUND AND PURPOSE: Pemphigus is caused by autoantibodies against desmoglein (Dsg) 1, Dsg3, and/or non-Dsg antigens. Pemphigus vulgaris (PV) is the most common manifestation of pemphigus, with painful erosions on mucous membranes. In most cases, blistering also occurs on the skin, leading to areas of extensive denudation. Despite improvements in pemphigus treatment, time to achieve remission is long, severe adverse events are frequent and 20% of patients do not respond adequately. Current clinical developments focus exclusively on modulating B cell function or autoantibody half-life. However, topical modulation of PV autoantibody-induced blistering is an attractive target because it could promptly relieve symptoms. EXPERIMENTAL APPROACH: To address this issue, we performed an unbiased screening in a complex biological system using 141 low MW inhibitors from a chemical library. Specifically, we evaluated PV IgG-induced Dsg3 internalization in HaCaT keratinocytes. Validation of the 20 identified compounds was performed using keratinocyte fragmentation assays, as well as a human skin organ culture (HSOC) model. KEY RESULTS: Overall, this approach led to the identification of four molecules involved in PV IgG-induced skin pathology: MEK1, TrkA, PI3Kα, and VEGFR2. CONCLUSION AND IMPLICATIONS: This unbiased screening revealed novel mechanisms by which PV autoantibodies induce blistering in keratinocytes and identified new treatment targets for this severe and potentially life-threatening skin disease.

Grover disease: review of subtypes with a focus on management options.

Grover disease (GD) is a benign eruption that causes a papulovesicular rash on the trunk and proximal extremities. It often resolves spontaneously but can follow a more chronic and fluctuating course that may last several years. Although the etiology remains unknown, several associated triggers have been identified including heat and sweating, cool and dry air, renal failure, malignancy, and the initiation of several drugs. Since the disease tends to resolve on its own, management is aimed at disease prevention and symptomatic relief. First-line therapy includes topical steroids and vitamin D analogues with adjuvant antihistamines. In more severe cases that are refractory to less aggressive therapy, systemic corticosteroids, retinoids, and phototherapy may lead to successful resolution. Novel therapies are few and have little evidence but involve innovative use of light therapy and immune modulators. Herein, we review the literature and new trends of GD with a focus on established and novel treatments.

Persistent generalized Grover disease: complete remission after treatment with oral acitretin.

Grover disease (GD) is a disorder of unknown origin, clinically characterized by the occurrence of pruritic, erythematous or brownish papules and papulovesicles, which histologically reveal four different patterns of acantholysis. Usually, the eruption is self-limited and spontaneously remit within a few weeks. In some cases, however, it may persist for months or even years and show a therapy-resistant course. We report a 56-year-old woman with recalcitrant, persistent, and generalized GD who showed complete remission after 6 weeks of treatment with oral acitretin (0.8mg/kg/day). The treatment was well-tolerated and laboratory parameters remained unchanged. The patient remains free of any recurrence at 26 months. To the best of our knowledge, this is the first report of a complete remission of the persistent form of GD as a result of oral acitretin monotherapy.

Pityriasis Rubra Pilaris With Extensive Follicular Acantholysis Resembling Pemphigus Vulgaris: A Case Report.

Pityriasis rubra pilaris (PRP) is a rare, chronic, heterogeneous, papulosquamous inflammatory dermatosis of unknown etiology. Although erythematous scaly patches characterize the classic presentation of PRP, a broad range of clinical presentations has been reported. Histologically, PRP is characterized by psoriasiform acanthosis with alternating orthokeratosis and parakeratosis and rarely small acantholytic foci. In this article, we report a patient who presented with diffuse erythroderma and extensive acantholysis mimicking pemphigus vulgaris histologically.

An unresponsive progressive pustular and crusting dermatitis with acantholysis in nine cats.

BACKGROUND: Between 2000 and 2012, nine cats were examined with a visually distinctive, progressive crusting dermatitis that was poorly responsive to all attempted therapies. OBJECTIVES: Documentation of clinical and histopathological findings of this disease. ANIMALS: Nine privately owned cats. METHODS: Retrospective study. RESULTS: Eight neutered males and one (presumably spayed) female ranging in age from two to eight years, presented for a progressive, well-demarcated, crusting dermatitis with variable pruritus of 1.5 months to five years duration. All cats lived in northern California, USA; seven lived within a 30 mile radius. Two males were littermates. Histopathological investigation showed both parakeratotic and orthokeratotic crusts, intraepidermal pustules and superficial folliculitis with rare to frequent acantholytic cells. Bacterial and fungal cultures were performed in six cats: meticillin-susceptible Staphylococcus pseudintermedius was isolated in three cats, two colonies of Trichophyton terrestre and three of Malassezia pachydermatis were isolated from one cat each. Treatment with various antibiotics, antifungal and a variety of immunosuppressive medications did not alter the progressive nature of the skin disease. CONCLUSIONS AND CLINICAL IMPORTANCE: The described disease shares some clinical and histopathological features with pemphigus foliaceus, but the lack of response to treatment, its progressive nature and the possible relatedness of some of the cats set it apart. The aetiology of this acantholytic dermatitis remains unknown.

Dermatosis papular acantolítica de la vulva con buena respuesta a tacrólimus tópico.

Papular acantholytic dermatosis of the vulva is a rare, chronic disorder and is an entity that remains to be fully understood. It shares clinical and histopathological overlap with Darier disease and Hailey-Hailey disease. We describe a 30-year-old woman with papular acantholytic dermatosis of the vulva. The lesions consisted of whitish papules and erosions on the labia majora. Histologically, there was hyperkeratosis and focal parakeratosis with acantholytic and dyskeratotic cells. She did not respond completely to topical steroids but clinical improvement occurred after the use of topical tacrolimus.

Paraneoplastic Itch Management.

Paraneoplastic itch occurs as the result of a systemic reaction to an underlying malignancy. Paraneoplastic itch is most commonly associated with lymphoproliferative malignancies and solid tumors that result in cholestasis. Paraneoplastic itch may occur in the absence of a primary rash or in association with dermatologic conditions such as erythroderma, acanthosis nigricans, dermatomyositis, Grover's disease, and eruptive seborrheic keratosis. Treatment of paraneoplastic itch is centered on targeting the underlying malignancy responsible for the systemic reaction. In cases of malignancy that are refractive to treatment, other therapies have been found to be effective for paraneoplastic itch, including selective serotonin reuptake inhibitors, mirtazapine, gabapentin, thalidomide, opioids, aprepitant, and histone deacetylase inhibitors.

Drug-related pityriasis rubra pilaris with acantholysis.

INTRODUCTION: Acantholysis is rarely reported histological feature of Pityriasis rubra pilaris (PRP), recently recognized as having diagnostic specificity for differentiating PRP from psoriasis. CASE REPORT: Adult male patient one week after the introduction of simvastatin had experienced pruritic erythemo-squamous eruption on head and upper trunk that in a month progressed to erythrodermia, with islands of sparing. Histological picture combined pemphigus-like acantholysis with alternating hyper- and parakeratosis, follicular plugs and dermal inflammation, and confirmed the clinical diagnosis of classic adult type 1 PRP. Acitretin therapy resulted in a resolution of skin disease. Patch test with simvastatin was negative, scratch test was positive, and it was estimated that potential risk of oral challenge with simvastatin outweighed actual need for it. Drug triggering PRP episode is the most likely explanation for temporal relation between the start of simvastatin treatment and skin eruption. CONCLUSION: In management of rare inflammatory skin disease, such as PRP, we have to carefully observe and evaluate not only diagnostic features but possible external influences on its course also.