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Dermatopathology (Basel, Switzerland) Feb 2024Galli-Galli disease (GGD) is a rare genodermatosis that exhibits autosomal dominant inheritance with variable penetrance. GGD typically manifests with erythematous... (Review)
Review
Galli-Galli disease (GGD) is a rare genodermatosis that exhibits autosomal dominant inheritance with variable penetrance. GGD typically manifests with erythematous macules, papules, and reticulate hyperpigmentation in flexural areas. A distinct atypical variant exists, which features brown macules predominantly on the trunk, lower limbs, and extremities, with a notable absence of the hallmark reticulated hyperpigmentation in flexural areas. This review includes a detailed literature search and examines cases since GGD's first description in 1982. It aims to synthesize the current knowledge on GGD, covering its etiology, clinical presentation, histopathology, diagnosis, and treatment. A significant aspect of this review is the exploration of the genetic, histopathological, and clinical parallels between GGD and Dowling-Degos disease (DDD), which is another rare autosomal dominant genodermatosis, particularly focusing on their shared mutations in the and genes. This supports the hypothesis that GGD and DDD may be different phenotypic expressions of the same pathological condition, although they have traditionally been recognized as separate entities, with suprabasal acantholysis being a distinctive feature of GGD. Lastly, this review discusses the existing treatment approaches, underscoring the absence of established guidelines and the limited effectiveness of various treatments.
PubMed: 38390850
DOI: 10.3390/dermatopathology11010008 -
JAMA Dermatology Jul 2023Grover disease (GD), a truncal eruption that typically occurs in older individuals, is exacerbated by sweating, irradiation, cancers, medications, kidney failure, and...
IMPORTANCE
Grover disease (GD), a truncal eruption that typically occurs in older individuals, is exacerbated by sweating, irradiation, cancers, medications, kidney failure, and organ transplantation. The pathobiology of GD remains unknown.
OBJECTIVE
To determine if damaging somatic single-nucleotide variants (SNVs) are associated with GD.
DESIGN, SETTING, AND PARTICIPANTS
In this retrospective case series, we identified consecutive patients from a dermatopathology archive over a 4-year period (January 2007 to December 2011) who had 1 biopsy with a clinical diagnosis of GD confirmed via histopathologic findings and another non-GD biopsy. Participant DNA was extracted from both biopsy tissues and sequenced to high depth with a 51-gene panel to screen for SNVs in genes previously associated with acantholysis and Mendelian disorders of cornification. Analysis took place between 2021 and 2023.
MAIN OUTCOMES AND MEASURES
Comparative analysis of sequencing data from paired GD and control tissue was employed to identify SNVs predicted to affect gene function, which were exclusive to, or highly enriched in, GD tissue.
RESULTS
Overall, 12 of 15 cases of GD (12 men and 3 women; mean [SD] age, 68.3 [10.0] years) were associated with C>T or G>A ATP2A2 SNVs in GD tissue; all were predicted to be highly damaging via combined annotation dependent depletion (CADD) scores, and 4 were previously associated with Darier disease. In 9 cases (75%), the GD-associated ATP2A2 SNV was absent from control tissue DNA, and in 3 cases (25%), ATP2A2 SNVs were enriched 4- to 22-fold in GD vs control tissue.
CONCLUSIONS AND RELEVANCE
In this case series study of 15 patients, damaging somatic ATP2A2 SNVs were associated with GD. This discovery expands the spectrum of acantholytic disorders associated with ATP2A2 SNVs and highlights the role of somatic variation in acquired disorders.
Topics: Aged; Female; Humans; Male; Acantholysis; Darier Disease; Ichthyosis; Retrospective Studies; Sarcoplasmic Reticulum Calcium-Transporting ATPases
PubMed: 37195706
DOI: 10.1001/jamadermatol.2023.1139 -
Indian Journal of Pathology &... Mar 2024Darier disease (DD) is a rare genodermatosis. Literature on this topic is overwhelmingly dominated by case reports with rare clinical presentations, which have mentioned...
Darier disease (DD) is a rare genodermatosis. Literature on this topic is overwhelmingly dominated by case reports with rare clinical presentations, which have mentioned the histopathologic features briefly. The aim of this study was to document the histopathology of DD. Skin biopsies diagnosed as Darier disease based on clinicopathologic correlation over 12 years were reviewed for various epidermal and dermal features. There were 16 patients included, who most commonly presented in the third decade, with slight female predilection. The most common clinical presentation was hyperpigmented, hyperkeratotic, papules and plaques (91%), with 69% affecting the trunk. In addition to the classic suprabasal acantholytic clefts, we noted some unusual features: absence of parakeratosis (19%), a cornoid lamella-like pattern (62%), follicular acantholysis (13%) and multiple foci of involvement within a single biopsy (63%). Features such as the presence of dyskeratotic cells and minimal dermal lymphocytic infiltrates were concordant with previous literature. The limitation of this study was the small sample size. To conclude, pathologists must be aware of the variations in histopathology of Darier's disease, especially when challenged with atypical clinical presentations. The Darier-like pattern is met within several acantholytic diseases, and clinicopathologic correlation has the last word in arriving at a diagnosis.
PubMed: 38563701
DOI: 10.4103/ijpm.ijpm_610_23 -
Transcriptional profiling of rare acantholytic disorders suggests common mechanisms of pathogenesis.JCI Insight Aug 2023Darier, Hailey-Hailey, and Grover diseases are rare acantholytic skin diseases. While these diseases have different underlying causes, they share defects in cell-cell...
Darier, Hailey-Hailey, and Grover diseases are rare acantholytic skin diseases. While these diseases have different underlying causes, they share defects in cell-cell adhesion in the epidermis and desmosome organization. To better understand the underlying mechanisms leading to disease in these conditions, we performed RNA-seq on lesional skin samples from patients. The transcriptomic profiles of Darier, Hailey-Hailey, and Grover diseases were found to share a remarkable overlap, which did not extend to other common inflammatory skin diseases. Analysis of enriched pathways showed a shared increase in keratinocyte differentiation, and a decrease in cell adhesion and actin organization pathways in Darier, Hailey-Hailey, and Grover diseases. Direct comparison to atopic dermatitis and psoriasis showed that the downregulation in actin organization pathways was a unique feature in the acantholytic skin diseases. Furthermore, upstream regulator analysis suggested that a decrease in SRF/MRTF activity was responsible for the downregulation of actin organization pathways. Staining for MRTFA in lesional skin samples showed a decrease in nuclear MRTFA in patient skin compared with normal skin. These findings highlight the significant level of similarity in the transcriptome of Darier, Hailey-Hailey, and Grover diseases, and identify decreases in actin organization pathways as a unique signature present in these conditions.
Topics: Humans; Actins; Skin; Acantholysis; Skin Diseases
PubMed: 37471166
DOI: 10.1172/jci.insight.168955 -
Drug Design, Development and Therapy 2023Thalidomide (Tha) can be used as a selective treatment for mild pemphigus vulgaris (PV). However, the specific mechanism of action remains unclear.
PURPOSE
Thalidomide (Tha) can be used as a selective treatment for mild pemphigus vulgaris (PV). However, the specific mechanism of action remains unclear.
PATIENTS AND METHODS
PV IgG extracted from patients' serum was cocultured with HaCaT cells to construct a PV cell model, and different concentrations of Tha were used to screen the drug effect. The expression level of MYD88 was assessed in skin lesions of PV patients. Intracellular Ca concentration, reactive oxygen species level, DSG3, PG, MYD88, apoptosis-related proteins (Caspase-3, Bcl-2, and Bax), NF-κB pathway-related proteins (IκBα, p-IκBα, p50, and p65), NLRP3, IFN-γ, TNF-α, IL-6, and IL-8 levels were measured. PV IgG was subcutaneously injected into C57BL/6 neonatal mice to construct the animal model. Immunofluorescence was used to detect IgG deposition in the mouse epidermis, whereas immunohistochemistry and TUNEL methods were used to detect the expression of MYD88 and NLRP3 as well as cell apoptosis level in the mouse epidermis.
RESULTS
Tha reversed the decrease in Dsg3 and PG caused by PV IgG. The expression of MyD88 increased in the patients' skin, PV cell model, and PV mouse model. The increase in MyD88 expression level in PV cell models and PV newborn mouse models was inhibited by Tha. Overexpression of MyD88 induced a decrease in the expression levels of Dsg3 and PG in Hacat cells. Overexpression of MyD88 inhibited Tha effects on Dsg3 and PG expressions and blocked Tha effects on Ca, apoptosis, Bax, Bcl-2, and Caspase-3 expressions, oxidative damage, and inflammatory response in HaCat cells. Tha alleviated acantholysis induced by PV IgG in model mice.
CONCLUSION
Through MYD88, Tha attenuated apoptosis of HaCat cells, modulated NF-κB to hamper the oxidative damage and inflammatory response in the PV cell models, and alleviated acantholysis, IgG deposition, and epidermal cell apoptosis induced by PV IgG in model mice.
Topics: Animals; Humans; Mice; Acantholysis; Animals, Newborn; Apoptosis; bcl-2-Associated X Protein; Caspase 3; HaCaT Cells; Immunoglobulin G; Inflammation; Mice, Inbred C57BL; Myeloid Differentiation Factor 88; NF-kappa B; NF-KappaB Inhibitor alpha; NLR Family, Pyrin Domain-Containing 3 Protein; Oxidative Stress; Pemphigus; Thalidomide
PubMed: 37719363
DOI: 10.2147/DDDT.S407242 -
Cureus Jun 2023Grover's disease (GD) is a rare skin condition that presents as a pruritic, erythematous papular, or papulovesicular rash. We report a unique case of GD triggered by...
Grover's disease (GD) is a rare skin condition that presents as a pruritic, erythematous papular, or papulovesicular rash. We report a unique case of GD triggered by honeybee stings. An 80-year-old Caucasian male presented with a pruritic papulovesicular rash on his trunk and arms after being stung by honeybees. He had a history of honeybee venom allergy and developed immediate erythema at the sting sites, which progressed over two days. His laboratory tests were unremarkable, including a complete blood count and comprehensive metabolic profile. Despite using oral antihistamines, emollients, and topical steroids, his rash continued to progress onto his neck, face, scalp, and back. A skin biopsy of the rash revealed suprabasilar and intraspinous acantholysis with focal corps ronds and upper dermis lymphocytic infiltrate -- the histopathologic finding of GD. He had failed first-line treatment for GD. However, after five months and significant morbidity, he was successfully treated with systemic steroids, high-potency topical steroids, emollients, and antihistamines for extensive and prolonged GD. This case report highlights honeybee venom as a possible trigger of GD and discusses a potential immune-mediated etiopathogenesis, which can be used to guide further research and management of this rare disease.
PubMed: 37476136
DOI: 10.7759/cureus.40648