Assessment of Blue Light Phototherapy for Grover Disease: A Nonrandomized Controlled Trial.

This nonrandomized clinical trial assesses treatment of patients diagnosed with Grover disease with blue light phytotherapy for several weeks.

Grover's Disease in a Kidney Transplant Recipient.

Dear Editor, It is not unusual for patients with renal insufficiency to develop skin pathologies. There are reports in the literature of increased incidence of calciphylaxis, pruritus, perforating dermatoses, and porphyria cutanea tarda in this patient population (1). Although it is quite rare, Grover's disease (GD) has been reported in several patients with renal insufficiency, but only once in a renal transplant recipient (2). The disease follows three patterns: persistently pruritic, transient eruptive, or a chronic asymptomatic course (3). Common risk factors concomitant with disease prevalence are immunosuppression, HIV, hemodialysis, viral and bacterial infections, malignancies, and other skin pathologies like contact and atopic dermatitis (4). A 60-year-old woman had a family history of polycystic kidney disease and was subsequently diagnosed in 1997. The patient had concomitant hepatic involvement and a stable aneurysm of the anterior cerebral artery. Consequently, the patient preemptively received a kidney transplant in 2015. The immunosuppressive therapy consisted of tacrolimus, mycophenolate mofetil, and prednisone with basiliximab induction. In 2017, a biopsy of the right thigh demonstrated squamous cell carcinoma in situ measuring 1×1cm in size. The lesion was treated with surgical excision. The patient also exhibited an erythematous brown macule with undefined borders on the left side of the nose with a size of 12 mm; it was later determined to be actinic keratosis. The lesion was treated successfully with cryotherapy. During this period, a fever prompted a PCR for BK virus DNA which showed a substantial amount of copies, measuring 28,850 copies/mL in urine and 98 copies/mL in blood. The mycophenolate dose was reduced, and tacrolimus trough concentration was maintained at between 3 and 5 µg/L. In 2018 the patient presented with multiple pruritic erythematous papules located on the trunk. Upon histological biopsy, there was dominant suprabasal acantholysis with numerous cells separating from the epithelium. Furthermore, there was a moderate amount of mononuclear infiltrate in the upper portion of the dermis and sparse suprabasal clefts (Figure 1). Clinical presentation and histologic examination were consistent with Grover's disease. The patient was treated topically with betamethasone cream twice daily for four weeks. The skin changes persisted for only a few weeks. The pathophysiological mechanism causing GD is still unknown. It is usually only a transient skin condition that lasts no more than a few weeks, but there have been more chronic cases lasting for years, particularly in patients on hemodialysis (5). The lesions commonly affect the chest area but may spread to diffusely envelope the body as erythematous papules, pustules, lichenoid lesions, or vesicles (2). Grover characterized 4 different subtypes based on the pathohistological findings as Darier-like (the most common), pemphigus vulgaris-like, Hailey-Hailey-like, or spongiotic subtype (3). The histological patterns are not exclusive to one patient and may even be found concomitantly in a single lesion. The condition is definitively diagnosed through histology, showing distinctive acantholysis along the epidermis with dyskeratosis that is described as "corps ronds" and "grains" (3). Grover's disease is more prevalent in middle-aged Caucasian men than any other group, with a 1.6-2.1 gender ratio (6). It was originally thought that the disease was caused by dysfunctional eccrine sweat glands, as the ailment was more common in patients that had increased perspiration either due to environmental heat, fever, or extensive bedrest. This idea was reinforced by histological evidence of atrophied sweat glands in uremic patients with renal insufficiency (7). Moreover, a case series and case report described remissions of GD in their patients on hemodialysis that received a renal transplant (5,8). However, subsequent studies have not supported an association with sweat dysfunction and disease development, while others have only managed to attribute sweat gland dysfunction as the primary trigger in 20-30% of cases (9). Conversely, cold dry air and xerosis cutis is thought to trigger the disease because it is four times more likely to be diagnosed in the winter months (10). Ultraviolet radiation has been identified as an exacerbating factor for GD, which could have been the trigger for onset of disease in our patient as demonstrated by her squamous cell carcinoma and actinic keratosis (11). Despite immunosuppression being a risk factor for GD, as shown by its association in patients with HIV, bone marrow transplantation, hemodialysis, and hematological malignancies, GD has been reported only once in the literature after a renal transplant (2,4). As our case, that patient developed GD a few years after transplant without an obvious trigger and the lesions appeared as red papules that were disseminated over the anterior thorax. Their patient's cutaneous lesion resolved spontaneously after 2 weeks and never returned in the 2.5-year follow-up period. Their patient has had two renal allografts over a 20 year timespan, while ours had had her graft for only two years. The immunosuppressive regimen was slightly different: cyclosporine, azathioprine, and methylprednisolone versus our combination of tacrolimus, mycophenolate mofetil, and prednisone. Grover's disease can be treated conservatively by avoiding risk factors such as UV light and sweating as well as and applying moisturizing emollients which may cause the lesion to resolve spontaneously. Medical therapy consists of topic corticosteroids, topical vitamin D analogues, oral retinoids, and oral corticosteroids, PUVA, and methotrexate for resistant cases (6,12). When a patient exhibits pruritic papules of the skin, GD should be considered in differential diagnosis, especially in kidney transplant patients and those on hemodialysis. While the condition is rare, increased recognition in this patient population will allow for studies to further characterize this poorly understood disease.

Enfermedad de Grover, una patología ampollar poco frecuente: a propósito de 2 casos / Grover's disease, a pathology blistering unusual: About 2 cases

Grover's disease (GD) or transient acantholytic dermatosis, is a papulovesicular pruritic disease of unknown etiology. It´s most important histopathological finding is the presence of focal acantholysis. The incidence has not been firmly established. Case report: We report two cases of papulovesicular rashes, the first one in a 79 year old man with good response to second line treatment and the second one, in a 30 year old woman. Both with different suspected triggering factors. Comment: GD predominates in white men with an average age of presentation of 61. Clinically, it presents as erythematous papules, crusted-papule and is usually pruritic. The etiopathology is still unknown, but it is associated with triggers such as: ultraviolet radiation (UVR), ionizing radiation, heat, sweat, friction and chemotherapy. Acantholysis is the classic histological finding. Management includes general measures, topical corticosteroids, calcineurin inhibitors, tretinoin, calcipotriene and antihistamines. In refractory cases, second-line treatment is used: oral isotretinoin, systemic corticosteroids and phototherapy. Paradoxically, phototherapy can also trigger GD. Conclusions: Due to the low prevalence of GD in Chile, 2 new cases are provided to the literature. In both cases, the diagnostic presumption was based on an exhaustive clinical history, confirmed by histopathological findings. (AU)

[PEMPHIGUS ACANTHOLYTICUS PARANEOPLASTIC: LITERATURE REVIEW AND CASE REPORT].

The article describes the clinical observation of a rare severe dermatosis, paraneoplastic acantholyticus pemphigus, associated with colon cancer with reference to pathogenesis, clinical variations and difficulties of diagnostics of this condition.

Monolateral Grover's Disease with Blaschkoid Distribution.

Dear Editor, Grover's disease, also known as transient acantholytic dermatosis, is an idiopathic and acquired pruritic eruption of small vesicles and erythematous papules, classically on the central chest. The pathogenesis is not clearly defined, although heat sweating and occlusion have been interpreted as predisposing factors. We describe a case of monolateral acantholytic eruption with blaschkoid distribution in a patient treated with an orthopedic bandage for a shoulder injury. A 53-years-old man was referred to the dermatologic department because of an acute eruption of pruritic, discrete, pinkish grey papulovesicles, developed on the right side of the trunk 14 days after the positioning of an orthopedic bandage for a shoulder injury. This skin eruption followed a multilinear distribution along Blaschko lines (Figure 1, a, b). The medical history was unremarkable. The patient's family history was negative for similar dermatosis. Histopathological analysis showed acantholytic dyskeratosis with suprabasal cleft. A basket weave epidermic pattern with hyperkeratosis was observed, with a perivascular lymphocytic infiltration in the upper dermis (Figure 1, c, d). Given the clinical and histopathological features, a diagnosis of monolateral Grover's disease was established. The patient was treated with topical mometasone furoate 0.1% cream for 3 weeks with clinical improvement. Monolateral blaschkoid distribution in Grover's disease is extremely rare, with only 1 case reported in the literature (1). Two cases of zosteriform distribution have been described (2,3). The exact pathogenesis and the differential diagnosis with linear Darier's disease were the main topics of discussion, while the pathogenesis is still in debate. In our case, it appears that a shoulder bandage can cause an occlusive environment that can elicit the disease (4). Similar conditions were present in a previously described cases of bedridden patients (1). Some authors have postulated that such conditions may act as precipitating factors on a genetically predisposed epidermis (1). In monolateral and localized cases, postzygotic somatic mutations along Blasckho's lines or in dermatomes could be present. It is also important to distinguish this monolateral and blasckhoid Grover's disease from other acantholytic dermatoses. In this case, the differential diagnosis with an eruptive linear Darier's disease is very difficult (5). Histopathological analysis is not useful. Both monolateral and ordinary variants of Darier's disease can be elicited by environmental factors such as heat, sweating, or occlusion. The diagnosis of monolateral blaschkoid Grover's disease was preferred due to the patient's anamnesis (late-onset and no familiar history of similar dermatosis) and the clinical features (sparing of the head, extremities, and flexures). Since only additional genetic analysis could definitively resolve this question, it was performed. No mutation in genes coding the Ca2+ pump using genomic DNA from the patient's white blood cells or from a skin biopsy was found. A clinical anamnestic and genetic correlation is always crucial in these rare and unique acantholytic dermatoses.

Pruritic eruption on the chest.

The fact that this patient's rash was limited to his chest provided an important diagnostic clue.

Pemphigus vulgaris: a multidisciplinary approach to management.

Pemphigus vulgaris (PV) is a rare but potentially life-threatening autoimmune disease affecting the mucosa and the skin. The disease is caused by circulating antibodies to desmosomes (important adhesion proteins linking cells together). Disruption of these intercellular connections results in a loss of cohesion between cells (acantholysis). The clinical result of this process is the development of multiple blisters that easily rupture, leaving behind painful sloughing eroded areas of mucosa and/or skin. We report a case of severe PV in a 56-year-old man presenting with widespread, painful, eroded mucocutaneous lesions. The severity of the disease demanded a range of medical and surgical specialties to successfully manage the problem. This paper highlights the importance of an early multidisciplinary team approach to improve the outcome of patients suffering with this disease.

Cutaneous toxicities of RAF inhibitors.

The RAF inhibitors vemurafenib and dabrafenib are emerging as the standard of care for Val600 BRAF-mutant metastatic melanoma. These drugs have shown clinical benefit over the standard care (dacarbazine); however, they are associated with frequent cutaneous adverse events, which can be concerning to the patient and their physician. Herein, we review the range of cutaneous disorders that seem to be induced by RAF inhibitors, including cutaneous squamous-cell carcinoma, hyperkeratotic lesions, Grover's disease, keratosis pilaris-like reactions, and photosensitivity. These disorders often affect patients' quality of life; therefore, dermatological assessment and timely management is essential to ensure that patients continue to use RAF inhibitors.

Dermatosis acantolíticas: a propósito de un caso / Acantholytic dermatosis: a case report

Se presenta el caso de una paciente de 64 años que ha tenido episodios recurrentes de lesiones vesiculosas en su extremidad inferior derecha, diagnosticándose una dermatosis acantolítica. Existe un espectro de enfermedades acantolíticas que histopatológicamente presentan acantolisis, pero que no comparten factores genéticos. El diagnóstico clínico puede ser extremadamente difícil y es la suma de herencia, clínica, histopatología y evolución, la que permite llegar a un diagnóstico. Se realiza una reseña de todas estas enfermedades.

We present the case of 64-year-old female patient with recurrent episodes of vesicles in her lower right limb. Histopathological study revealed acantholytic dermatosis. There is a large spectrum of acantholytic dermatosis that histopathologically presents acantholysis but does not share genetic factors. Clinical diagnosis may be extremely difficult and results in the sum of genetics, clinical findings, histopathological studies and evolution. We also present a review of these diseases.

[Grover's disease following hemodialysis in a patient with renal failure]. / Morbus Grover unter Hämodialy--setherapie bei Niereninsuffizienz.

A 54-year-old woman with polycystic renal disease and renal failure developed Grover's disease while undergoing renal dialysis. Grover's disease or transitory acantholytic dermatosis is characterized by intensely pruritic, hyperkeratotic, succulent papules and plaques located on the trunk. The pathogenesis is unknown; genetic factors and actinic damage have been implicated. Medications, heat or immunosuppression can worsen the disease. Associations with atopic dermatitis, contact dermatitis and asteatotic dermatitis have also been described. Differential diagnostic considerations include folliculitis, scabies and dermatitis herpetiformis. Therapeutic options include moisturizing agents and phototherapy, as well as topical and systemic retinoids. There are only few case reports in the literature describing Grover's disease occurring during hemodialysis treatment. All such previous patients have been men; ours is the first woman.

[Papular acantholytic dyskeratosis]. / Papulöse akantholytische Dyskeratose.

Papular acantholytic dyskeratosis is a very rare skin disease, which shows a suprabasilar cleft with acantholytic and dyskeratotic cells, simulating the light microscopic picture of Darier disease. In this condition, the lesions are acquired without a genetic basis. We observed a 40-year-old woman with about 200 papules on the lower aspects of her legs; histological examination showed changes similar to Darier disease. Transmission electron microscopy showed a reduced number of desmosomes and perinuclear distribution of tonofilaments. The lesions were successfully treated with cryotherapy with spray technique.

A case report: persistent acantholytic dermatosis in chronic renal failure.

INTRODUCTION: This is the second case of persistent acantholytic dermatosis in a patient with chronic renal failure, seen at the same institution in 2 years. CLINICAL PICTURE: A 70-year-old Chinese man with end-stage renal failure on continuous ambulatory peritoneal dialysis for 6 months presented with pruritic rashes over the scalp and chest for 3 months. Histologically, the lesions resembled Darier's disease. Differential diagnoses include Darier's disease, Grover's disease and perforating dermatosis in chronic renal failure. TREATMENT: The patient was treated with anti-histamines, topical steroids and emollients. OUTCOME: Resolution of pruritus was documented. However, the extensive hyperkeratotic papules remained persistent. CONCLUSION: A chronic non-remitting course is to be expected for this dermatoses in which the aetiology is unknown.

A rare presentation of acantholytic dyskeratosis.

We describe an elderly woman who presented with numerous papular, keratotic lesions on the scalp. Histology of a biopsy specimen revealed epidermal invaginations, with large keratotic plugs, at the sites of hair follicles. In addition, there was acantholytic epidermal cell separation at a suprabasal level, and a large number of corps ronds were present above the split. It is likely that this case represents a rare presentation of acantholytic dyskeratosis. The relationship to other conditions which show acantholysis and dyskeratosis histologically is discussed.

High doses of antigen-nonspecific IgG do not inhibit pemphigus acantholysis in skin organ cultures.

A patient suffering from severe pemphigus vulgaris was treated using large-volume plasma exchange in combination with an immunosuppressive regimen. As some recent reports have shown evidence that polyclonal, polyspecific human IgG in high doses through the i.v. route (IGIV) protect target platelets in idiopathic thrombocytopenic purpura from attack by antiplatelet autoantibodies and/or immune complexes, we also administered IGIV to this pemphigus-vulgaris patient. In order to test the hypothesis that IGIV might protect in vitro-cultured human skin from acantholysis induced by pemphigus antibodies, studies with skin organ cultures were carried out using plasma from another pemphigus-vulgaris patient who had undergone plasma exchange. The preincubation of either the skin explants or the pemphigus plasma with various concentrations of IGIV (ranging from 0.15 to 15 mg/ml in the culture medium) did not prevent acantholysis induced by the pemphigus plasma nor did it inhibit the binding of the specific antibodies visualized by direct immunofluorescence. Thus, the assumption that IGIV may coat the pemphigus antigens on epidermal cells making them inaccessible to pathogenic autoantibodies was not substantiated by our tests in vitro; likewise, the hypothesis of functionally blocking autoantibody activity by means of anti-idiotype effects of IGIV cannot be supported.